julilili42/papers huggingface dataset:
Clonal Hematopoiesis–Associated Gene Mutations in a Clinical Cohort of 448 Patients With Ovarian Cancer
2021-12-27

Abstract Background Cancer patients are at risk of secondary therapy–related myeloid neoplasms (t-MNs). Acquired blood-specific mutations in clonal hematopoiesis (CH)–associated genes are t-MN risk factors, and their occurrence associated with cancer therapy and age. Patients with ovarian cancer (OC) showed a particularly high prevalence of CH–associated gene mutations, which may additionally be explained by the high proportion of a hereditary disease cause in this cancer entity. Methods We performed a retrospective analysis of 448 OC patients enrolled in the AGO-TR1 study; 249 were enrolled at primary diagnosis and 199 at platinum-sensitive recurrence. Analyses included the most frequently altered CH–associated genes (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, TP53). Results were analyzed according to the BRCA1/2 germline (gBRCA1/2) mutation status. All statistical tests were 2-sided. Results Advanced age at blood draw and a high number of prior platinum-based chemotherapy lines were risk factors to acquire CH–associated gene mutations, with gene-specific effects observed. Binomial logistic regression suggested increased probabilities for gBRCA1/2 mutation carriers to acquire CH-associated PPM1D and TP53 gene mutations (PPM1D: odds ratio = 4.30, 95% confidence interval = 1.48 to 12.46, P = .007; TP53: odds ratio = 6.20, 95% confidence interval = 0.98 to 53.9, P = .06). This observation was due to a statistically significantly increased number of platinum-based chemotherapy lines in gBRCA1/2 mutation carriers vs noncarriers (PPM1D: mean [SD] = 2.04 [1.27] vs 1.04 [0.99], P &amp;lt; .001; TP53: mean [SD] = 2.83 [1.33] vs 1.07 [1.01], P &amp;lt; .001). No interaction between platinum-based chemotherapy and gBRCA1/2 mutation status with the occurrence of CH–associated gene mutations was observed. Conclusions A positive gBRCA1/2 mutation status is not a risk factor to acquire CH–associated gene mutations. OC patients may benefit from monitoring CH–associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.
A CNN-based Human Activity Recognition System Combining a Laser Feedback Interferometry Eye Movement Sensor and an IMU for Context-aware Smart Glasses
2021-12-27

Smart glasses are considered the next breakthrough in wearables. As the successor of smart watches and smart ear wear, they promise to extend reality by immersive embedding of content in the user's field of view. While advancements in display technology seems to fulfill this promises, interaction concepts are derived from established wearable concepts like touch interaction or voice interaction, preventing full immersion as they require the user to frequently interact with the glasses. To minimize interactions, we propose to add context-awareness to smart glasses through human activity recognition (HAR) by combining head- and eye movement features to recognize a wide range of activities. To measure eye movements in unobtrusive way, we propose laser feedback interferometry (LFI) sensors. These tiny low power sensors are highly robust to ambient light. We combine LFI sensors and an IMU to collect eye and head movement features from 15 participants performing 7 cognitive and physical activities, leading to a unique data set. To recognize activities we propose a 1D-CNN model and apply transfer learning to personalize the classification, leading to an outstanding macro-F1 score of 88.15 % which outperforms state of the art methods. Finally, we discuss the applicability of the proposed system in a smart glasses setup.
The evolution of quantitative sensitivity
2021-12-27

The ability to represent approximate quantities appears to be phylogenetically widespread, but the selective pressures and proximate mechanisms favouring this ability remain unknown. We analysed quantity discrimination data from 672 subjects across 33 bird and mammal species, using a novel Bayesian model that combined phylogenetic regression with a model of number psychophysics and random effect components. This allowed us to combine data from 49 studies and calculate the Weber fraction (a measure of quantity representation precision) for each species. We then examined which cognitive, socioecological and biological factors were related to variance in Weber fraction. We found contributions of phylogeny to quantity discrimination performance across taxa. Of the neural, socioecological and general cognitive factors we tested, cortical neuron density and domain-general cognition were the strongest predictors of Weber fraction, controlling for phylogeny. Our study is a new demonstration of evolutionary constraints on cognition, as well as of a relation between species-specific neuron density and a particular cognitive ability. This article is part of the theme issue ‘Systems neuroscience through the lens of evolutionary theory’.
Probing the timescale dependency of local and global variations in surface air temperature from climate simulations and reconstructions of the last millennia
2021-12-27

Earth's climate can be understood as a dynamical system that changes due to external forcing and internal couplings. Essential climate variables, such as surface air temperature, describe this dynamics. Our current interglacial, the Holocene (11 700 yr ago to today), has been characterized by small variations in global mean temperature prior to anthropogenic warming. However, the mechanisms and spatiotemporal patterns of fluctuations around this mean, called temperature variability, are poorly understood despite their socioeconomic relevance for climate change mitigation and adaptation. Here we examine discrepancies between temperature variability from model simulations and paleoclimate reconstructions by categorizing the scaling behavior of local and global surface air temperature on the timescale of years to centuries. To this end, we contrast power spectral densities (PSD) and their power-law scaling using simulated and observation-based temperature series of the last 6000 yr. We further introduce the spectral gain to disentangle the externally forced and internally generated variability as a function of timescale. It is based on our estimate of the joint PSD of radiative forcing, which exhibits a scale break around the period of 7 yr. We find that local temperature series from paleoclimate reconstructions show a different scaling behavior than simulated ones, with a tendency towards stronger persistence (i.e., correlation between successive values within a time series) on periods of 10 to 200 yr. Conversely, the PSD and spectral gain of global mean temperature are consistent across data sets. Our results point to the limitation of climate models to fully represent local temperature statistics over decades to centuries. By highlighting the key characteristics of temperature variability, we pave a way to better constrain possible changes in temperature variability with global warming and assess future climate risks.
New insights on hip bone sexual dimorphism in adolescents and adults using deformation-based geometric morphometrics.
2021-12-27

Morphological variation of the human pelvis, and particularly the hip bone, mainly results from both female-specific selective pressure related to the give birth of large-headed newborns, and constraints in both sexes for efficient bipedal locomotion, abdominal stability, and adaptation to climate. Hip bone morphology has thus been extensively investigated using several approaches, although the nuances of inter-individual and sex-related variation are still underappreciated, and the effect of sex on ontogenetic patterns is debated. Here, we employ a landmark-free, deformation-based morphometric approach to explore variation in modern human hip bone shape and size from middle adolescence to adulthood. Virtual surface models of the hip bone were obtained from 147 modern human individuals (70 females and 77 males) including adolescents, and young and mature adults. The 3D meshes were registered by rotation, translation, and uniform scaling prior to analysis in Deformetrica. The orientation and amplitude of deviations of individual specimens relative to a global mean were assessed using Principal Component Analysis, while colour maps and vectors were employed for visualisation purposes. Deformation-based morphometrics is a time-efficient and objective method free of observer-dependent biases that allows accurate shape characterisation of general and more subtle morphological variation. Here, we captured nuanced hip bone morphology revealing ontogenetic trends and sex-based variation in arcuate line curvature, greater sciatic notch shape, pubic body and rami length, acetabular expansion, and height-to-width proportions of the ilium. The observed ontogenetic trends showed a higher degree of bone modelling of the lesser pelvis of adolescent females, while male variation was mainly confined to the greater pelvis.
Rapid Diagnosis of Central Nervous System Scedosporiosis by Specific Quantitative Polymerase Chain Reaction Applied to Formalin-Fixed, Paraffin-Embedded Tissue
2021-12-27

Scedosporium (S.) apiospermum is a typical mold causing cerebral abscesses, often after near-drowning. Infections are associated with high morbidity and mortality due to diagnostic challenges including the need for prolonged incubation of cultures. In addition, histopathological differentiation from other filamentous fungi, including Aspergillus fumigatus, may not be possible, excluding early specific diagnosis and targeted therapy. Polymerase chain reaction (PCR) on tissue samples can rapidly identify fungi, leading to an earlier adequate treatment. Due to an extensive spectrum of causative fungi, broad-range PCRs with amplicon sequencing have been endorsed as the best DNA amplification strategy. We herein describe a case with brain abscesses due to S. apiospermum in a 66-year-old immunocompromised female patient. While broad-range PCR failed to identify a fungal pathogen from a cerebral biopsy demonstrating hyaline mold hyphae, specific quantitative PCR (qPCR) identified Scedosporium and ruled out Aspergillus, the most prevalent agent of central nervous system mold infection. A panel of specific qPCR assays, guided by the morphology of fungal elements in tissue or as a multiplex assay, may be a successful molecular approach to identify fungal agents of brain abscesses. This also applies in the presence of negative broad-range fungal PCR, therefore providing diagnostic and therapeutic potential for early specific management and improvement of patient clinical outcome.
Local Tumor Infiltration and Locoregional Recurrence in Desmoplastic Cutaneous Squamous Cell Carcinoma
2021-12-27

BACKGROUND Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective. OBJECTIVE The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure. METHODS AND MATERIALS Between 2005 and 2015, 320 SCCs were analyzed and histological sections of all tumors were examined. Data collection included locoregional recurrence, metastasis rate, and tumor-specific death. The median follow-up was 36.5 months. RESULTS The desmoplastic subtype required significant more re-excisions (70.0% vs 23.9%, p &lt; .001), more interventions until tumor-free margins were achieved (maximal 6 vs 2; p &lt; .001), showed more widespread tumor infiltration with larger excisional margins (median 9 mm, 2–51 mm vs median 4 mm, 1–10 mm; p &lt; .001), and a 5-fold higher local recurrence rate (26.7% vs 5.0%, p &lt; .001). The metastasis rate (16.6% vs 2.3%, p &lt; .001) was increased. CONCLUSION The desmoplastic subtype is characterized by a widespread local infiltration associated with perineural infiltration. It seems to be a marker for decreased histological detectability with a high rate of locoregional recurrence and metastasis.
Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with increased protection
2021-12-27

Abstract The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum parasite. Using protein microarrays, levels of IgG to 1,000 P. falciparum antigens were measured in 2,138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase 3 trial, sampled before and at four longitudinal visits after vaccination. One month post-vaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no pre-vaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (∼11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and re-increasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site and post-vaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.
Low-altitude periglacial activity in southeastern Australia during the late Pleistocene
2021-12-28

Abstract Only a small area of the Australian mainland was glaciated during the Pleistocene, whereas periglacial deposits are far more common, indicating that cold environments were extensive and a major influence on landscape evolution. Here we identify representative low-elevation examples of scree slopes and frost action, together with fans and valley fills, indicating pronounced erosion cycles during the Pleistocene. To date the deposits, we explore approaches using radiocarbon, optically stimulated luminescence, and profile dating using the cosmogenic nuclide 10 Be. The radiocarbon and optical ages show that screes, alluvial valley fill, and fans were deposited between 66–13 ka during the coldest part of the last glacial cycle, and within the previous glacial cycle. Exposure dating indicates further landscape erosion cycles back to the mid Pleistocene. Together, the deposits indicate the frost cracking limit was ~1300 m lower at 680 ± 10 m and mean winter temperature was 8.2 ± 0.5°C colder than present. Periglacial conditions probably affected much of southeastern Australia. The treeless and dry conditions resulted in widespread erosion and increased run off. Combined with increased snow storage within catchments, rivers were paradoxically larger, with high seasonal discharge and sediment loads.
Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles
2021-12-28

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargos to the retina. The new formulation, based on a gel core and composite shell, allowed up to two-fold increase in the encapsulation efficiency. The type of hydrophobic polyester used in the composite shell mixture affected the particle surface charge, colloidal stability, and cell internalization profile. We validated SLNs as a drug delivery system by performing the encapsulation of a hydrophilic neuroprotective cyclic guanosine monophosphate analog, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with a size of ±250 nm, anionic charge &gt; −20 mV, and an encapsulation efficiency of ±60%, criteria that are suitable for retinal delivery. In vitro studies using the ARPE-19 and 661W retinal cell lines revealed the relatively low toxicity of SLNs, even when a high particle concentration was used. More importantly, SLN could be taken up by the cells and the release of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings suggest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all the characteristics suitable for the drug delivery of small hydrophilic active molecules into retinal cells.
BRCA2 Haploinsufficiency in Telomere Maintenance
2021-12-28

Our previous studies showed an association between monoallelic BRCA2 germline mutations and dysfunctional telomeres in epithelial mammary cell lines and increased risk of breast cancer diagnosis for women with BRCA2 999del5 germline mutation and short telomeres in blood cells. In the current study, we analyzed telomere dysfunction in lymphoid cell lines from five BRCA2 999del5 mutation carriers and three Fanconi Anemia D1 patients by fluorescence in situ hybridization (FISH). Metaphase chromosomes were harvested from ten lymphoid cell lines of different BRCA2 genotype origin and analyzed for telomere loss (TL), multitelomeric signals (MTS), interstitial telomere signals (ITS) and extra chromosomal telomere signals (ECTS). TL, ITS and ECTS were separately found to be significantly increased gradually between the BRCA2+/+, BRCA2+/- and BRCA2-/- lymphoid cell lines. MTS were found to be significantly increased between the BRCA2+/+ and the BRCA2+/- heterozygous (p &lt; 0.0001) and the BRCA2-/- lymphoid cell lines (p &lt; 0.0001) but not between the BRCA2 mutated genotypes. Dysfunctional telomeres were found to be significantly increased in a stepwise manner between the BRCA2 genotypes indicating an effect of BRCA2 haploinsufficiency on telomere maintenance.
Inhomogeneous defect distribution of triangular WS2 monolayer revealed by surface-enhanced and tip-enhanced Raman and photoluminescence spectroscopy
2021-12-28

Confocal optical microscopy and tip-enhanced optical microscopy are applied to characterize the defect distributions in chemical vapor deposition-grown WS2 monolayer triangles qualitatively and quantitatively. The presence of defects in individual monolayer WS2 triangles is revealed with diffraction-limited spatial resolution in their photoluminescence (PL) images, from which the inhomogeneous defect density distribution is calculated, showing an inverse relationship to the PL intensity. The defect-related surface-enhanced Raman spectroscopy (SERS) effect is investigated by depositing a thin copper phthalocyanine layer (5 nm) as the probe molecule on the monolayer WS2 triangles surface. Higher SERS enhancement effects are observed at the defect-rich areas. Furthermore, tip-enhanced optical measurements are performed, which can reveal morphologically defected areas invisible in the confocal optical measurements. Furthermore, the area with high defect density appears brighter than the low-defected area in the tip-enhanced optical measurements, which are different from the observation in the confocal optical measurements. The underlying reasons are attributed to the near-field enhancement of the defect exciton emission induced by the optically excited tip and to an improved coupling efficiency between the tip-generated near-field with the altered dipole moment orientation at the local defect.
31P Transversal Relaxation Times and Metabolite Concentrations in the Human Brain at 9.4T
2021-12-28

Abstract A method to estimate phosphorus ( 31 P) transversal relaxation times (T 2 ) of coupled spin systems is demonstrated. Additionally, intracellular and extracellular pH (pH ext , pH int ) and relaxation corrected metabolite concentrations are reported. Echo time (TE) series of 31 P metabolite spectra were acquired using STEAM localization. Spectra were fitted using LCModel with accurately modeled Vespa basis sets accounting for J-evolution of the coupled spin systems. T 2 s were estimated by fitting a single exponential two-parameter model across the TE series. Fitted inorganic phosphate frequencies were used to calculate pH, and relaxation times were used to determine the brain metabolite concentrations. The method was demonstrated in the healthy human brain at a field strength of 9.4T. T 2 relaxation times of ATP and NAD are the shortest between 8 ms and 20 ms, followed by T 2 s of inorganic phosphate between 25 ms and 50 ms, and PCr with a T 2 of 100 ms. Phosphomonoesters and –diesters have the longest T 2 s of about 130 ms. Measured T 2 s are comparable to literature values and fit in a decreasing trend with increasing field strengths. Calculated pHs and metabolite concentrations are also comparable to literature values.
Quality of Life After Deep Brain Stimulation of Pediatric Patients with Dyskinetic Cerebral Palsy: A Prospective, Single‐Arm, Multicenter Study with a Subsequent Randomized Double‐Blind Crossover (STIM‐CP)
2021-12-29

Abstract Background Patients with dyskinetic cerebral palsy are often severely impaired with limited treatment options. The effects of deep brain stimulation (DBS) are less pronounced than those in inherited dystonia but can be associated with favorable quality of life outcomes even in patients without changes in dystonia severity. Objective The aim is to assess DBS effects in pediatric patients with pharmacorefractory dyskinetic cerebral palsy with focus on quality of life. Methods The method used is a prospective, single‐arm, multicenter study. The primary endpoint is improvement in quality of life (CPCHILD [Caregiver Priorities &amp; Child Health Index of Life with Disabilities]) from baseline to 12 months under therapeutic stimulation. The main key secondary outcomes are changes in Burke‐Fahn‐Marsden Dystonia Rating Scale, Dyskinesia Impairment Scale, Gross Motor Function Measure‐66, Canadian Occupational Performance Measure (COPM), and Short‐Form (SF)‐36. After 12 months, patients were randomly assigned to a blinded crossover to receive active or sham stimulation for 24 hours each. Severity of dystonia and chorea were blindly rated. Safety was assessed throughout. The trial was registered at ClinicalTrials.gov, number NCT02097693. Results Sixteen patients (age: 13.4 ± 2.9 years) were recruited by seven clinical sites. Primary outcome at 12‐month follow‐up is as follows: mean CPCHILD increased by 4.2 ± 10.4 points (95% CI [confidence interval] –1.3 to 9.7; P = 0.125); among secondary outcomes: improvement in COPM performance measure of 1.1 ± 1.5 points (95% CI 0.2 to 1.9; P = 0.02) and in the SF‐36 physical health component by 5.1 ± 6.2 points (95% CI 0.7 to 9.6; P = 0.028). Otherwise, there are no significant changes. Conclusion Evidence to recommend DBS as routine treatment to improve quality of life in pediatric patients with dyskinetic cerebral palsy is not yet sufficient. Extended follow‐up in larger cohorts will determine the impact of DBS further to guide treatment decisions in these often severely disabled patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society