julilili42/papers huggingface dataset:
Patient‐derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib
2023-06-25

Summary Anaplastic large‐cell lymphoma (ALCL) is a T‐cell malignancy predominantly driven by the oncogenic anaplastic lymphoma kinase (ALK), accounting for approximately 15% of all paediatric non‐Hodgkin lymphoma. Patients with central nervous system (CNS) relapse are particularly difficult to treat with a 3‐year overall survival of 49% and a median survival of 23.5 months. The second‐generation ALK inhibitor brigatinib shows superior penetration of the blood–brain barrier unlike the first‐generation drug crizotinib and has shown promising results in ALK+ non‐small‐cell lung cancer. However, the benefits of brigatinib in treating aggressive paediatric ALK+ ALCL are largely unknown. We established a patient‐derived xenograft (PDX) resource from ALK+ ALCL patients at or before CNS relapse serving as models to facilitate the development of future therapies. We show in vivo that brigatinib is effective in inducing the remission of PDX models of crizotinib‐resistant (ALK C1156Y, TP53 loss) ALCL and furthermore that it is superior to crizotinib as a second‐line approach to the treatment of a standard chemotherapy relapsed/refractory ALCL PDX pointing to brigatinib as a future therapeutic option.
Revealing the ionising star of evolved planetary nebulae
2023-06-25

Context. Planetary nebulae represent a late stage of the evolution of stars of ordinary mass. The nucleus of a planetary nebula, a stellar remnant, is a faint star for which it is usually difficult to gather spectroscopic data. The spectral types of these stars cover a wide range, mainly separated into two large groups, those rich in hydrogen and those that are not. In this complex scenery it is of great importance to increase the number of stars with defined spectral types and physical parameters. In this way, we can improve our actual models of stellar evolution. Aims. Our main objective is to increase the number of known white dwarfs that are the ionisation sources of planetary nebulae. Our aim is to obtain the spectral type and physical parameters of these stars, which are to be confronted with models of stellar evolution. In this way, we want to increase our knowledge of the final stages of stellar evolution. Methods. We present Gemini spectra of nine nuclei of faint and extended southern planetary nebulae. The spectra were fitted with models of stellar atmospheres, which allowed the derivation of their atmospheric parameters. In addition, stellar evolution models were used to infer the stars’ mass. Results. We discovered six hydrogen-rich white dwarfs (spectral types DA and DAO; effective temperatures in the range T eff = 60 000–80 000 K). One of the DAO white dwarfs is probably a new member of only a few known post-red-giant-branch central stars. In addition, we found two hot hydrogen-deficient PG 1159 stars ( T eff = 120 000 and 160 000 K). Taken together, this represents a significant increase in the number of known white dwarf central stars. We also discovered an early O(H) star ( T eff = 90 000 K).
Functional trait trade-offs define plant population stability across different biomes
2023-06-26

Ecological theory posits that temporal stability patterns in plant populations are associated with differences in species' ecological strategies. However, empirical evidence is lacking about which traits, or trade-offs, underlie species stability, especially across different biomes. We compiled a worldwide collection of long-term permanent vegetation records (greater than 7000 plots from 78 datasets) from a large range of habitats which we combined with existing trait databases. We tested whether the observed inter-annual variability in species abundance (coefficient of variation) was related to multiple individual traits. We found that populations with greater leaf dry matter content and seed mass were more stable over time. Despite the variability explained by these traits being low, their effect was consistent across different datasets. Other traits played a significant, albeit weaker, role in species stability, and the inclusion of multi-variate axes or phylogeny did not substantially modify nor improve predictions. These results provide empirical evidence and highlight the relevance of specific ecological trade-offs, i.e. in different resource-use and dispersal strategies, for plant populations stability across multiple biomes. Further research is, however, necessary to integrate and evaluate the role of other specific traits, often not available in databases, and intraspecific trait variability in modulating species stability.
Long‐Term Follow‐Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation
2023-06-26

ABSTRACT Background Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long‐term effects and the safety profile are rare. Objectives We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. Methods The STIM‐CP trial was a prospective, single‐arm, multicenter study in which patients from the parental trial agreed to be followed‐up for up to 36 months. Assessments included motor and non‐motor domains. Results Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. Conclusion DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
The Exploitation of Toxic Fish from the Terminal Pleistocene in Maritime Southeast Asia: A Case Study from the Mindoro Archaeological Sites, Philippines
2023-06-26

Representatives of the Diodontidae family (porcupinefish) are known to have been fished by prehistoric Indo-Pacific populations; however, the antiquity of the use of this family is thus far unknown. We report here on the presence of Diodontidae in the archaeological sites of Bubog I, II, and Bilat in Mindoro, Philippines, dating back to c. 13,000 BP (Before Present). This evidence demonstrates the early exploitation by islanders of poisonous fish. Every part of porcupinefish can be toxic, but the toxicity is mostly concentrated in some organs, while other parts are edible. The continuous presence of Diodontidae remains throughout the stratigraphic record of these Philippines shell middens suggests that porcupinefish were prepared by human inhabitants of the sites to render them safe for consumption, indicating an advanced cultural knowledge of the preparation needed to separate the toxic principle from the edible parts. This constitutes one of the rare examples of poison processing by humans, aside from the contentious wooden stick poison applicator from Border Cave (South Africa).
Surgical management of syringomyelia associated with spinal arachnoid web: strategies and outcomes
2023-06-26

Abstract Spinal arachnoid web (SAW) is a rare disease entity characterized as band-like arachnoid tissue that can cause spinal cord compression and syringomyelia. This study aimed to analyze the surgical management of the spinal arachnoid web in patients with syringomyelia, focusing on surgical strategies and outcomes. A total of 135 patients with syringomyelia underwent surgery at our department between November 2003 and December 2022. All patients underwent magnetic resonance imaging (MRI), with a special syringomyelia protocol (including TrueFISP and CINE), and electrophysiology. Among these patients, we searched for patients with SAW with syringomyelia following careful analysis of neuroradiological data and surgical reports. The criteria for SAW were as follows: displacement of the spinal cord, disturbed but preserved CSF flow, and intraoperative arachnoid web. Patients were evaluated for initial symptoms, surgical strategies, and complications by reviewing surgical reports, patient documents, neuroradiological data, and follow-up data. Of the 135 patients, 3 (2.22%) fulfilled the SAW criteria. The mean patient age was 51.67 ± 8.33 years. Two patients were male, and one was female. The affected levels were T2/3, T6, and T8. Excision of the arachnoid web was performed in all cases. No significant change in intraoperative monitoring was noted. Postoperatively, none of the patients presented new neurological symptoms. The MRI 3 months after surgery revealed that the syringomyelia improved in all cases, and caliber variation of the spinal cord could not be detected anymore. All clinical symptoms improved. In summary, SAW can be safely treated by surgery. Even though syringomyelia usually improves on MRI and symptoms also improve, residual symptoms might be observed. We advocate for clear criteria for the diagnosis of SAW and a standardized diagnostic (MRI including TrueFISP and CINE).
Trading mental and physical health in vestibular schwannoma treatment decision
2023-06-26

Objective Observation, radiotherapy and surgery are treatment options in vestibular schwannomas (VS). Decision making differs between centers and is usually based on tumor characteristics (e.g., size) and the expected physical health (PH) outcome (i.e., hearing and facial function). However, mental health (MH) is often under-reported. The objective of the present study was to ascertain the impact of VS treatment on PH and MH. Methods PH and MH were assessed in a prospective cross-sectional study including 226 patients with unilateral sporadic VS before and after surgical removal (SURG). Quality-of-life (QoL) was estimated by self-rating questionnaires: general Short-Form Health Survey (SF-36), Penn Acoustic Neuroma Quality-of-Life Scale (PANQOL), Dizziness Handicap Inventory (DHI), Hearing Handicap Inventory (HHI), Tinnitus Handicap Inventory (THI), and Facial Disability Index (FDI). QoL changes over time as well as predictive factors were accessed by multivariate analyses of covariance (MANCOVA). Results In total, 173 preoperative and 80 postoperative questionnaires were analyzed. There was a significant PH deterioration related to facial function (FDI, PANQOL-face) after surgery. In line with facial rehabilitation, however, FDI improved within the first five years after surgery and did not differ compared to the preoperative patient cohort, eventually. In contrast, MH (i.e., PANQOL-anxiety) and general health (i.e., PANQOL-GH) improved with surgery and correlated with the extent-of-resection. Conclusion Physical and mental health is significantly influenced by VS surgery. While PH might decrease after surgery, MH potentially increases when patient is cured. Practitioners should take MH into account before advising an incompletely VS treatment (e.g., subtotal resection, observation or radiosurgery).
Interventional SHAP Values and Interaction Values for Piecewise Linear Regression Trees
2023-06-26

In recent years, game-theoretic Shapley values have gained increasing attention with respect to local model explanation by feature attributions. While the approach using Shapley values is model-independent, their (exact) computation is usually intractable, so efficient model-specific algorithms have been devised including approaches for decision trees or their ensembles in general. Our work goes further in this direction by extending the interventional TreeSHAP algorithm to piecewise linear regression trees, which gained more attention in the past few years. To this end, we introduce a decomposition of the contribution function based on decision paths, which allows a more comprehensible formulation of SHAP algorithms for tree-based models. Our algorithm can also be readily applied to computing SHAP interaction values of these models. In particular, as the main contribution of this paper, we provide a more efficient approach of interventional SHAP for tree-based models by precomputing statistics of the background data based on the tree structure.
Surrogate‐Model Assisted Plausibility‐Check, Calibration, and Posterior‐Distribution Evaluation of Subsurface‐Flow Models
2023-06-26

Abstract Modern physics‐based subsurface‐flow models often require many parameters and computationally costly simulations. This prohibits traditional ensemble‐based conditioning. We expedite the calibration of such models by using surrogate/proxy models based on Gaussian Process Regression (GPR). In an iterative procedure, we use the proxy models to (a) estimate the direction of steepest descent, (b) propose only parameter combinations for full‐model runs that are likely to lead to plausible results, and (c) preselect proposed parameter combinations by their predicted performance. This method yields an ensemble of full‐model runs covering the full plausible parameter space, but at higher resolution close to the optimum. This is the basis for Markov‐Chain Monte Carlo (MCMC) simulations using GPR to estimate the posterior parameter distribution. We tested several variants of the scheme on a 3‐D variably‐saturated steady‐state subsurface‐flow model and compared it to a Neural Posterior Estimation (NPE) scheme, which requires samples of the prior distribution only. While the estimated posterior distributions of the two approaches were similar, the GPR‐based MCMC approach reproduced the data better than samples from the NPE‐based posterior distributions.
The VA-CAL Test Quantifies Improvement of Visual Acuity in Achromatopsia by Means of Short-Wave Cutoff Filter Glasses in Daily Living Conditions
2023-06-26

The VA-CAL test discovers losses of spatial resolution in the visual acuity space not seen in standardized BCVA assessment. Filter glasses improve the patients' daily visual performance, rendering them a strongly recommended visual aid in achromatopsia.
Optimizing Methodology of Sleep and Memory Research in Humans
2023-06-26

Understanding the complex relationship between sleep and memory is a major challenge in neuroscience. Many studies on memory consolidation in humans suggest that sleep triggers offline memory processes, resulting in less forgetting of declarative memory and performance stabilization in non-declarative memory. However, issues related to non-optimal experimental designs, task characteristics and measurements, and inappropriate data analysis practices can significantly affect the interpretation of the effect of sleep on memory. In this article, we discuss these issues and suggest constructive solutions to address them. We believe that implementing these solutions in future sleep and memory research will significantly advance this field by improving the understanding of the specific role of sleep in memory consolidation.
Extensible benchmarking of methods that identify and quantify polyadenylation sites from RNA-seq data
2023-06-26

ABSTRACT The tremendous rate with which data is generated and analysis methods emerge makes it increasingly difficult to keep track of their domain of applicability, assumptions, and limitations and consequently, of the efficacy and precision with which they solve specific tasks. Therefore, there is an increasing need for benchmarks, and for the provision of infrastructure for continuous method evaluation. APAeval is an international community effort, organized by the RNA Society in 2021, to benchmark tools for the identification and quantification of the usage of alternative polyadenylation (APA) sites from short-read, bulk RNA-sequencing (RNA-seq) data. Here, we reviewed 17 tools and benchmarked eight on their ability to perform APA identification and quantification, using a comprehensive set of RNA-seq experiments comprising real, synthetic, and matched 3′-end sequencing data. To support continuous benchmarking, we have incorporated the results into the OpenEBench online platform, which allows for seamless extension of the set of methods, metrics, and challenges. We envisage that our analyses will assist researchers in selecting the appropriate tools for their studies. Furthermore, the containers and reproducible workflows generated in the course of this project can be seamlessly deployed and extended in the future to evaluate new methods or datasets.
The largest record of the minute beaver Euroxenomys minutus (Mammalia, Castoridae) from the early Late Miocene hominid locality Hammerschmiede (Bavaria, Southern Germany) and palaeoecological considerations
2023-06-26

In this study, we describe the dental remains of a very minute beaver from the early Late Miocene locality Hammerschmiede (MN 7/8) located at the Northern Alpine Foreland Basin (Southern Germany, Bavaria). The finds represent the so far most comprehensive (>1.000 dental specimens) collection of the trogontheriine castorid Euroxenomys minutus. Metrically and morphologically, the large data set demonstrates an extensive intraspecific variability of this beaver from Hammerschmiede that covers most finds of other European localities and confirms previous species assignments. The subspecies Euroxenomys minutus rhenanus from Dorn-Dürkheim (Germany), clearly isolates from this range of variation and can thus be validated. The performed age-frequency distributions for Euroxenomys minutus from the local stratigraphic levels HAM 5 (rivulet) and HAM 4 (river) correspond roughly and also resemble Euroxenomys from the swamp deposit Rudabánya (Hungary). Since previous mortality studies on the also occurring larger beaver Steneofiber depereti from Hammerschmiede demonstrated dominance of behavioural or internal factors, this cross-ecosystem similarity in mortality for the small beaver species is likely explained by external factors, such as predation. Supported by a taphonomic bone analysis, a multitude of predators are finally considered to prey on Euroxenomys minutus and indicate a predatory bone assemblage.
The first European woolly rhinoceros mitogenomes retrieved from within cave hyena coprolites suggest long-lasting phylogeographic differentiation
2023-06-26

Summary The woolly rhinoceros ( Coelodonta antiquitatis ) is an iconic species of the Eurasian Pleistocene megafauna, which was abundant in Eurasia in the Pleistocene until its demise beginning approximately 10,000 years ago. Despite the early recovery of several specimens from well-known European archaeological sites, including its type specimen (Blumenbach 1799), no genomes of European populations were available so far, and all available genomic data originated exclusively from the Siberian population 1 . Using coprolites of cave hyenas ( Crocuta crocuta spelea ) recovered from Middle Palaeolithic layers of two caves in Germany (Bockstein-Loch and Hohlenstein-Stadel), we isolated and enriched predator and prey DNA to assemble the first European woolly rhinoceros mitogenomes, in addition to cave hyena mitogenomes. These mitogenomes of European woolly rhinoceros are genetically distinct from the Siberian woolly rhinoceros, and analyses of the more complete mitogenome suggests a split of the populations potentially coinciding with the earliest fossil records of wooly rhinoceros in Europe.
Unnatural endo type-B PPAPs as novel compounds with activity against Mycobacterium tuberculosis.
2023-06-26

Before the emergence of SARS-CoV-2, tuberculosis (TB) was the leading cause of infectious disease mortality worldwide. Like all antibiotic-exposed bacteria Mycobacterium tuberculosis (Mtb) developed multidrug-resistant (MDR) and exten-sively drug-resistant (XDR) strains which require new antibiotics with novel mechanism of actions. Hyperforin, a natural type-A polyprenylated polycyclic acylphloroglucinol (PPAP) isolated from St. John’s wort, is known for its antibacterial, antidepressant and antimycobacterial activity. However, hyperforin is not stable and easily degradable in light, heat it and oxidizes. Here we report photo- and benchstable type-B PPAPs with structural similarity to hyperforin and enhanced an-timycobacterial activity. We tested a panel of PPAPs and identified our previously reported molecule PPAP22 as lead compound. Converting PPAP22 into the corresponding sodium salt, PPAP53, enhanced the solubility dramatically. We show that PPAP53 inhibits the growth of virulent, extracellular Mtb. Strikingly, the activity is more pronounced intracel-lular Mtb residing in human primary macrophages without damaging the host cell or lung cells. Importantly PPAP53 was also highly active against drug-resistant Mtb. Additionally, we analysed the in vitro properties of PPAP53 in terms of CYP-induction and PXR interaction. Taken together we introduce type-B PPAPs are a new class of antimycobacterial com-pounds, with remarkable activity and favorouble physical properties.
110: Tapering enteroplasty or bowel lengthening? – A surgical algorithm for pediatric intestinal rehabilitation patients with bowel dilatation
2023-06-26

Introduction: Bowel dilatation regularly occurs in children with short bowel syndrome (SBS). Despite the common nature of this finding, there is no standardized approach for dilated bowel in affected patients with regard to surgical indications and techniques. This is mainly due to the highly individualized conditions of the patients. Several surgical techniques have been proposed for the management of bowel dilatation in pediatric SBS patients including bowel lengthening procedures. However, certain limitations for the different approaches have meanwhile been identified. Aim of this study was to systematically analyze indications and decision making for surgery of children with SBS and bowel dilatation, and to establish an algorithm for the decision making process. Methods: We retrospectively evaluated all patients of our intestinal rehabilitation program that underwent surgery for bowel dilatation between 11/2010 and 12/2020. We registered indications and techniques of the surgical procedures and analyzed their outcome with special regard to surgical and functional outcome. Based on these retrospective data we formulated an algorithm for the surgical decision making process, which we then prospectively analyzed for the subsequent operations until 09/2022. Success of surgery was evaluated by matching the individual indication/aim of surgery with the actual postoperative patient condition. Results: Of the 203 children treated in our intestinal rehabilitation program, 55 underwent surgery for dilated bowel and were evaluated for this study. Indications for surgery were established in our multidisciplinary treatment board. Most common surgical procedures were resection of stenosis with primary anastomosis (n=28), stoma revision (n=11), bowel tapering (n=10), and Serial Transverse Enteroplasty (STEP, n=9). With focus on the surgical decision making process, the main factors for establishing our algorithm were presence of mechanical obstruction, bowel length, and motility. After retrospective evaluation of patients’ data, this formulated algorithm was successfully used prospectively, resulting in a surgical success rate of 89%. Conclusion: We successfully established a surgical algorithm for decision making in children with SBS and bowel dilatation. This algorithm is now being evaluated prospectively in our intestinal rehabilitation program. Further analyses are necessary to evaluate the application of our algorithm in a broader fashion.