julilili42/papers huggingface dataset:
MASH Native: a unified solution for native top-down proteomics data processing
2023-06-01

Abstract Motivation Native top-down proteomics (nTDP) integrates native mass spectrometry (nMS) with top-down proteomics (TDP) to provide comprehensive analysis of protein complexes together with proteoform identification and characterization. Despite significant advances in nMS and TDP software developments, a unified and user-friendly software package for analysis of nTDP data remains lacking. Results We have developed MASH Native to provide a unified solution for nTDP to process complex datasets with database searching capabilities in a user-friendly interface. MASH Native supports various data formats and incorporates multiple options for deconvolution, database searching, and spectral summing to provide a “one-stop shop” for characterizing both native protein complexes and proteoforms. Availability and implementation The MASH Native app, video tutorials, written tutorials, and additional documentation are freely available for download at https://labs.wisc.edu/gelab/MASH_Explorer/MASHSoftware.php. All data files shown in user tutorials are included with the MASH Native software in the download .zip file.
Advance Progress on Luminescent Sensing of Nitroaromatics by Crystalline Lanthanide–Organic Complexes
2023-06-01

Water environment pollution is becoming an increasingly serious issue due to industrial pollutants with the rapid development of modern industry. Among many pollutants, the toxic and explosive nitroaromatics are used extensively in the chemical industry, resulting in environmental pollution of soil and groundwater. Therefore, the detection of nitroaromatics is of great significance to environmental monitoring, citizen life and homeland security. Lanthanide–organic complexes with controllable structural features and excellent optical performance have been rationally designed and successfully prepared and used as lanthanide-based sensors for the detection of nitroaromatics. This review will focus on crystalline luminescent lanthanide–organic sensing materials with different dimensional structures, including the 0D discrete structure, 1D and 2D coordination polymers and the 3D framework. Large numbers of studies have shown that several nitroaromatics could be detected by crystalline lanthanide–organic-complex-based sensors, for instance, nitrobenzene (NB), nitrophenol (4-NP or 2-NP), trinitrophenol (TNP) and so on. The various fluorescence detection mechanisms were summarized and sorted out in the review, which might help researchers or readers to comprehensively understand the mechanism of the fluorescence detection of nitroaromatics and provide a theoretical basis for the rational design of new crystalline lanthanide–organic complex-based sensors.
Clinical Pathobiochemistry of Vitamin B12 Deficiency: Improving Our Understanding by Exploring Novel Mechanisms with a Focus on Diabetic Neuropathy
2023-06-01

Vitamin B12 (B12) is an essential cofactor of two important biochemical pathways, the degradation of methylmalonic acid and the synthesis of methionine from homocysteine. Methionine is an important donor of methyl groups for numerous biochemical reactions, including DNA synthesis and gene regulation. Besides hematological abnormalities (megaloblastic anemia or even pancytopenia), a deficiency in B12 may cause neurological symptoms, including symptoms resembling diabetic neuropathy. Although extensively studied, the underlining molecular mechanism for the development of diabetic peripheral neuropathy (DPN) is still unclear. Most studies have found a contribution of oxidative stress in the development of DPN. Detailed immunohistochemical investigations in sural nerve biopsies obtained from diabetic patients with DPN point to an activation of inflammatory pathways induced via elevated advanced glycation end products (AGE), ultimately resulting in increased oxidative stress. Similar results have been found in patients with B12 deficiency, indicating that the observed neural changes in patients with DPN might be caused by cellular B12 deficiency. Since novel results show that B12 exerts intrinsic antioxidative activity in vitro and in vivo, B12 may act as an intracellular, particularly as an intramitochondrial, antioxidant, independent from its classical, well-known cofactor function. These novel findings may provide a rationale for the use of B12 for the treatment of DPN, even in subclinical early states.
Turtle body size evolution is determined by lineage‐specific specializations rather than global trends
2023-06-01

Abstract Organisms display a considerable variety of body sizes and shapes, and macroevolutionary investigations help to understand the evolutionary dynamics behind such variations. Turtles (Testudinata) show great body size disparity, especially when their rich fossil record is accounted for. We explored body size evolution in turtles, testing which factors might influence the observed patterns and evaluating the existence of long‐term directional trends. We constructed the most comprehensive body size dataset for the group to date, tested for correlation with paleotemperature, estimated ancestral body sizes, and performed macroevolutionary model‐fitting analyses. We found no evidence for directional body size evolution, even when using very flexible models, thereby rejecting the occurrence of Cope's rule. We also found no significant effect of paleotemperature on overall through‐time body size patterns. In contrast, we found a significant influence of habitat preference on turtle body size. Freshwater turtles display a rather homogeneous body size distribution through time. In contrast, terrestrial and marine turtles show more pronounced variation, with terrestrial forms being restricted to larger body sizes, up to the origin of testudinids in the Cenozoic, and marine turtles undergoing a reduction in body size disparity after the extinctions of many groups in the mid‐Cenozoic. Our results, therefore, suggest that long‐term, generalized patterns are probably explained by factors specific to certain groups and related at least partly to habitat use.
Eradicating Pulmonary Mycobacterium abscessus: The Promise of Dual β-Lactam Therapy
2023-06-01

Abstract Macrolide resistance has rendered the treatment of Mycobacterium abscessus extremely difficult and is fueling a crisis. Recently, there has been dramatically increased incidence of infections by M abscessus. Select dual β-lactam combinations have shown promising in vitro results. Herein, we present a patient whose M abscessus infection cured using dual β-lactams as part of multidrug regimen.
First‐trimester screening strategies: A balance between costs, efficiency and diagnostic yield
2023-06-01

Key points What's already known about this topic? An early scan at 11–13 + 6 weeks offers the ideal opportunity for a first detailed anatomical assessment of the fetus. Non‐invasive prenatal testing (NIPT) is superior to the combined test to screen for common trisomies, especially trisomy 21, in both singleton and twin pregnancies. What does this study add? In first‐trimester screening strategies based on NIPT and ultrasound, many factors must be considered when choosing how to combine the two methods. We propose four screening strategies with different pro‐ and contra arguments. The article may help choose the strategy that best fits local needs and health economic considerations.
Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
2023-06-01

Background The need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patterns and quantification of peripheral myeloid-derived suppressor cells (MDSC), but none has yet achieved sufficient accuracy for clinical utility. Methods Here, we investigated potential cellular biomarkers from clinical routine blood counts as well as several myeloid and T cell subsets, using flow cytometry, in two independent cohorts of a total of 141 patients with stage IV M1c melanoma before and during ICB. Results Elevated baseline frequencies of monocytic MDSCs (M-MDSC) in the blood were confirmed to predict shorter overall survival (OS) (HR 2.086, p=0.030) and progression-free survival (HR 2.425, p=0.001) in the whole patient cohort. However, we identified a subgroup of patients with highly elevated baseline M-MDSC frequencies that fell below a defined cut-off during therapy and found that these patients had a longer OS that was similar to that of patients with low baseline M-MDSC frequencies. Importantly, patients with high M-MDSC frequencies exhibited a skewed baseline distribution of certain other immune cells but these did not influence patient survival, illustrating the paramount utility of MDSC assessment. Conclusion We confirmed that in general, highly elevated frequencies of peripheral M-MDSC are associated with poorer outcomes of ICB in metastatic melanoma. However, one reason for an imperfect correlation between high baseline MDSCs and outcome for individual patients may be the subgroup of patients identified here, with rapidly decreasing M-MDSCs on therapy, in whom the negative effect of high M-MDSC frequencies was lost. These findings might contribute to developing more reliable predictors of late-stage melanoma response to ICB at the individual patient level. A multifactorial model seeking such markers yielded only MDSC behavior and serum lactate dehydrogenase as predictors of treatment outcome.
quantms: A cloud-based pipeline for proteomics reanalysis enables the quantification of 17521 proteins in 9,502 human samples.
2023-06-01

<title>Abstract</title> Public proteomics data is rapidly increasing, creating a computational challenge for large-scale reanalysis. Here, we introduce quantms, an open-source cloud-based pipeline for massively parallel proteomics data analysis. We used quantms to reanalyze 56 of the largest datasets, comprising 26801 instrument files from 9502 human samples, to quantify 17521 based on 1.02 million unique peptides. Based on standard file formats improves the reproducibility and deposition of the data to ProteomeXchange.
Inferred pyrite growth via the particle attachment pathway in the presence of trace metals
2023-06-01

The morphology of pyrite has been used to infer ancient redox states and biogenicity.However, the influence of trace metals on pyrite morphology is poorly understood.Through batch synthesis experiments, we demonstrate that bioessential trace metals (Co, Cu, Mo, Ni, Zn) accelerate pyrite formation.The first precipitate, FeS am , transformed to an intermediate greigite phase and to pyrite with increasing time and temperature.Trace metals either facilitated polysulphide formation or precipitated as nanoparticles that can serve as nuclei for pyrite growth, depending on the initial metal concentration.Despite varying precipitation rates, the final pyrite morphologies were unaffected.Various morphologies including tabular precipitates (<150 nm), aggregates resembling microframboids (100-250 nm), octahedral (300-1500 nm) and rose-like particles (1000-3000 nm) were observed.This size-shape particle continuum was interpreted as stages of pyrite growth via particle attachment.This process could be important in explaining variations in the mineral's reactivity (e.g., defects), isotopic and trace metal distributions, and morphologies (e.g., framboids) for applications in paleo-proxies, environmental research and biosignatures.
A discriminative lexicon approach to word comprehension, production, and processing: Maltese plurals
2023-06-01

Comprehending and producing words is a natural process for human speakers.In linguistic theory, investigating this process formally and computationally is often done by focusing on forms only.By moving beyond the world of forms, we show in this study that the Discriminative Lexicon (DL) model operating with word comprehension as a mapping of form onto meaning and word production as a mapping of meaning onto form generates accurate predictions about what meanings listeners understand and what forms speakers produce.Furthermore, we show that measures derived from the computational model are predictive for human reaction times.Although mathematically very simple, the linear mappings between form and meaning posited by our model are powerful enough to capture the complexity and productivity of a Semitic language with a complex hybrid morphological system.
β Band Rhythms Influence Reaction Times
2023-06-01

Abstract Despite their involvement in many cognitive functions, β oscillations are among the least understood brain rhythms. Reports on whether the functional role of β is primarily inhibitory or excitatory have been contradictory. Our framework attempts to reconcile these findings and proposes that several β rhythms co-exist at different frequencies. β Frequency shifts and their potential influence on behavior have thus far received little attention. In this human magnetoencephalography (MEG) experiment, we asked whether changes in β power or frequency in auditory cortex and motor cortex influence behavior (reaction times) during an auditory sweep discrimination task. We found that in motor cortex, increased β power slowed down responses, while in auditory cortex, increased β frequency slowed down responses. We further characterized β as transient burst events with distinct spectro-temporal profiles influencing reaction times. Finally, we found that increased motor-to-auditory β connectivity also slowed down responses. In sum, β power, frequency, bursting properties, cortical focus, and connectivity profile all influenced behavioral outcomes. Our results imply that the study of β oscillations requires caution as β dynamics are multifaceted phenomena, and that several dynamics must be taken into account to reconcile mixed findings in the literature.
Efficacy of adjuvant therapy in patients (pts) with AJCC v8 stage IIIA cutaneous melanoma.
2023-06-01

9518 Background: Pts with resected AJCC v8 stage IIIA melanoma have been under-represented in clinical trials of adjuvant drug therapy. The benefit of adjuvant targeted and immunotherapy in this population is unclear. Methods: In this multicenter, retrospective study, pts with stage IIIA melanoma (AJCC v8) who received adjuvant pembrolizumab or nivolumab (PD1), BRAF/MEK-targeted therapy dabrafenib + trametinib (TT), or no adjuvant treatment (OBS) were included. Recurrence free survival (RFS), distant metastasis free survival (DMFS), and toxicity rates were examined. Results: 613 pts from 34 centers across Australia, Europe and USA were included. The median follow-up was 2.6 yrs (IQR, 1.6-3.4 yrs). Pt characteristics and follow-up were similar across the cohorts (Table). Completion rates of 12-month PD1 and TT therapy were 57.0% and 69.2% respectively. 1-yr RFS was 93.3% (95% CI, 90.3-96.4) in PD1, 100% in TT and 91.3% (95% CI, 88.1-94.7) in OBS cohorts. 2-yr RFS was 79.3% (95% CI, 74.1-84.8) for PD1, 100% for TT and 84.3% (95% CI, 79.9-89.0) in OBS cohorts. 2-yr DMFS was 88.4% (95% CI, 84.3-92.8) in PD1, 100% in TT and 91.1% (95% CI, 87.7-94.7) in OBS cohorts. Risk of recurrence was associated with higher breslow thickness (HR 1.73, 95% CI 1.36-2.20), higher mitotic rate (HR 1.07, 95% CI 1.02-1.12) and neck as the site of nodal metastases (HR 2.71, 95% CI 1.45-5.06) in the overall cohort (p&lt;0.05). Neck nodal metastases were associated with higher risk of recurrence in OBS cohort (HR 3.82, 95% CI 1.91-7.66; p&lt;0.05) but not in the PD1 cohort. Rates of ≥ Grade 3 toxicities were 10.9% with PD1 and 20.0% with TT; discontinuation due to toxicity occurred in 25.0% and 30.0%, respectively. No new safety signals were observed. Rates of unresolved toxicity at last follow-up were 26.9% in PD1 and 7.7% in TT cohorts. Conclusions: In this large international study, adjuvant PD1 or TT did not significantly improve RFS or DMFS compared to OBS in pts with resected stage IIIA melanoma. Prognosis in stage IIIA melanoma is favourable and outcomes after adjuvant therapy in this population needs further study in prospective randomised trials. [Table: see text]
Structure-Based Discovery of Thiosemicarbazones As SARS-CoV-2 Main Protease Inhibitors
2023-06-01

<b>Aim:</b> Discovery of novel SARS-CoV-2 main protease (M<sup>pro</sup>) inhibitors using a structure-based drug discovery strategy. <b>Materials & methods:</b> Virtual screening employing covalent and noncovalent docking was performed to discover M<sup>pro</sup> inhibitors, which were subsequently evaluated in biochemical and cellular assays. <b>Results:</b> 91 virtual hits were selected for biochemical assays, and four were confirmed as reversible inhibitors of SARS CoV-2 M<sup>pro</sup> with IC<sub>50</sub> values of 0.4-3 μM. They were also shown to inhibit SARS-CoV-1 M<sup>pro</sup> and human cathepsin L. Molecular dynamics simulations indicated the stability of the M<sup>pro</sup> inhibitor complexes and the interaction of ligands at the subsites. <b>Conclusion:</b> This approach led to the discovery of novel thiosemicarbazones as potent SARS-CoV-2 M<sup>pro</sup> inhibitors.
Easy to get, difficult to avoid: Behavioral tendencies toward high-calorie and low-calorie food during a mobile approach-avoidance task interact with body mass index and hunger in a community sample
2023-06-01

In recent years, different studies highlighted the importance of assessing behavioral tendencies toward different food stimuli in healthy and pathological samples. However, heterogeneities in experimental approaches and small sample sizes make this literature rather inconsistent. In this study, we used a mobile approach-avoidance task to investigate the behavioral tendencies toward healthy and unhealthy foods compared to neutral objects in a large community sample. The role of some contextual and stable subjective variables was also explored. The sample included 204 participants. The stimuli comprised 15 pictures of unhealthy foods, 15 pictures of healthy foods, and 15 pictures of neutral objects. Participants were required to approach or avoid stimuli by respectively pull or push the smartphone toward or away from themselves. Accuracy and reaction time of each movement were calculated. The analyses were conducted using a generalized linear mixed-effect model (GLMMs), testing the two-way interaction between the type of movement and the stimulus category and the three-way interactions between type of movement, stimulus, and specific variables (BMI, time passed since the last meal, level of perceived hunger). Our results evidenced faster approaching movement toward food stimuli but not toward neutrals. An effect of BMI was also documented: as the BMI increased, participants became slower in avoiding unhealthy compared to healthy foods, and in approaching healthy compared to unhealthy stimuli. Moreover, as hunger increased, participants became faster in approaching and slower in avoiding healthy compared to unhealthy stimuli. In conclusion, our results show an approach tendency toward food stimuli, independent from caloric content, in the general population. Furthermore, approach tendencies to healthy foods decreased with increasing BMI and increased with perceived hunger, indicating the possible influence of different mechanisms on eating-related behavioral tendencies.
Neurosurgical morbidity in pediatric supratentorial midline low‐grade glioma: Results from the German LGG studies
2023-06-01

Abstract Surgical resection is a mainstay of treatment for pediatric low‐grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Records were retrospectively analyzed from 318 patients with SML‐LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Exactly 537 operations (230 resections, 167 biopsies, 140 nontumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed following 254/537 (47.3%) and medical morbidity following 97/537 (18.1%) patients with a 40.1% 30‐day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age &lt;3 years at operation, tumor volume ≥80 cm 3 , presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor‐related procedures and during the earlier study period between 1998 and 2006, while the neurosurgical approach, tumor location, NF1 status or previous nonsurgical treatment were not. Neurosurgery‐associated morbidity was frequent in pediatric patients with SML‐LGG undergoing surgery in the German LGG‐studies. We identified patient‐ and institution‐associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills.
Agreement and accuracy of fully automated morphometric femorotibial cartilage analysis in radiographic knee osteoarthritis
2023-06-01

To examine the performance of automated convolutional neuronal network cartilage segmentation in knees with radiographic osteoarthritis (ROA), and its dependence on the OA status of the training set and MRI sequences. We studied 122 ROA and 92 healthy reference cohort (HRC) knees from the Osteoarthritis Initiative. All knees had expert manual segmentation of the femorotibial cartilages based on coronal FLASH and sagittal DESS MRI. Two U-net convolutional neural networks were trained on 86/50 ROA/HRC knees, validated on 18/21, and tested on 18/21. Of 122 ROA knees, 43 (35%) were KLG2, 41 (34%) KLG3, and 38 (31%) KLG4. In the ROA test set, Dice Similarity Coefficients (DSCs) were 0.86/0.86 (FLASH/DESS) for the algorithm trained on ROA, and 0.82/0.82 for that trained on HRC knees. In the HRC test set, mean DSCs of 0.91/0.90 were observed with FLASH/DESS, both with the HRC- and with the ROA-trained algorithm. Cartilage thickness computation from automated segmentation in the FLASH ROA test set showed a correlation of r = 0.94 with manual segmentation for the ROA-trained, and of r = 0.89 for the HRC-trained algorithm. In the FLASH HRC test set, it exhibited a correlation of r = 0.96 for the HRC-trained and r = 0.88 for the ROA-trained algorithm. Results were similar between the DESS and FLASH, but were less accurate for KLG4 than for KLG2/3 knees. An automated algorithm trained on ROA knees was able to accurately segment and compute cartilage thickness on FLASH and DESS MRI, in both ROA and healthy knees, whereas an algorithm trained on healthy knees did not perform as well in ROA knees.