julilili42/papers huggingface dataset:
Neural Adaptation at Stimulus Onset and Speed of Neural Processing as Critical Contributors to Speech Comprehension Independent of Hearing Threshold or Age
2024-05-06

Background: It is assumed that speech comprehension deficits in background noise are caused by age-related or acquired hearing loss. Methods: We examined young, middle-aged, and older individuals with and without hearing threshold loss using pure-tone (PT) audiometry, short-pulsed distortion-product otoacoustic emissions (pDPOAEs), auditory brainstem responses (ABRs), auditory steady-state responses (ASSRs), speech comprehension (OLSA), and syllable discrimination in quiet and noise. Results: A noticeable decline of hearing sensitivity in extended high-frequency regions and its influence on low-frequency-induced ABRs was striking. When testing for differences in OLSA thresholds normalized for PT thresholds (PTTs), marked differences in speech comprehension ability exist not only in noise, but also in quiet, and they exist throughout the whole age range investigated. Listeners with poor speech comprehension in quiet exhibited a relatively lower pDPOAE and, thus, cochlear amplifier performance independent of PTT, smaller and delayed ABRs, and lower performance in vowel-phoneme discrimination below phase-locking limits (/o/-/u/). When OLSA was tested in noise, listeners with poor speech comprehension independent of PTT had larger pDPOAEs and, thus, cochlear amplifier performance, larger ASSR amplitudes, and higher uncomfortable loudness levels, all linked with lower performance of vowel-phoneme discrimination above the phase-locking limit (/i/-/y/). Conslusions: This study indicates that listening in noise in humans has a sizable disadvantage in envelope coding when basilar-membrane compression is compromised. Clearly, and in contrast to previous assumptions, both good and poor speech comprehension can exist independently of differences in PTTs and age, a phenomenon that urgently requires improved techniques to diagnose sound processing at stimulus onset in the clinical routine.
Working memory processes and intrinsic motivation: An EEG study
2024-05-06

Processes typically encompassed by working memory (WM) include encoding, retention, and retrieval of information. Previous research has demonstrated that motivation can influence WM performance, although the specific WM processes affected by motivation are not yet fully understood. In this study, we investigated the effects of motivation on different WM processes, examining how task difficulty modulates these effects. We hypothesized that motivation level and personality traits of the participants (N = 48, 32 females; mean age = 21) would modulate the parietal alpha and frontal theta electroencephalography (EEG) correlates of WM encoding, retention, and retrieval phases of the Sternberg task. This effect was expected to be more pronounced under conditions of very high task difficulty. We found that increasing difficulty led to reduced accuracy and increased response time, but no significant relationship was found between motivation and accuracy. However, EEG data revealed that motivation influenced WM processes, as indicated by changes in alpha and theta oscillations. Specifically, higher levels of the Resilience trait-associated with mental toughness, hardiness, self-efficacy, achievement motivation, and low anxiety-were related to increased alpha desynchronization during encoding and retrieval. Increased scores of Subjective Motivation to perform well in the task were related to enhanced frontal midline theta during retention. Additionally, these effects were significantly stronger under conditions of high difficulty. These findings provide insights into the specific WM processes that are influenced by motivation, and underscore the importance of considering both task difficulty and intrinsic motivation in WM research.
Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study
2024-05-06

Abstract Purpose The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. Methods This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels &lt; 20 ng/ml and ≥ one PI-RADS lesion (grades 3–5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3–5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. Results Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p &lt; 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p &gt; 0.05). Conclusion We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.
Topology-dependent coalescence controls scaling exponents in finite networks
2024-05-06

Studies of neural avalanches across different data modalities led to the prominent hypothesis that the brain operates near a critical point. The observed exponents often indicate the mean-field directed-percolation universality class, leading to the fully connected or random network models to study the avalanche dynamics. However, cortical networks have distinct nonrandom features and spatial organization that is known to affect critical exponents. Here we show that distinct empirical exponents arise in networks with different topology and depend on the network size. In particular, we find apparent scale-free behavior with mean-field exponents appearing as quasicritical dynamics in structured networks. This quasicritical dynamics cannot be easily discriminated from an actual critical point in small networks. We find that the local coalescence in activity dynamics can explain the distinct exponents. Therefore, both topology and system size should be considered when assessing criticality from empirical observables. Published by the American Physical Society 2024
Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update
2024-05-07

Covalent inhibitors and other types of covalent modalities have seen a revival in the past two decades, with a variety of new targeted covalent drugs having been approved in recent years. A key feature of such molecules is an intrinsically reactive group, typically a weak electrophile, which enables the irreversible or reversible formation of a covalent bond with a specific amino acid of the target protein. This reactive group, often called the "warhead", is a critical determinant of the ligand's activity, selectivity, and general biological properties. In 2019, we summarized emerging and re-emerging warhead chemistries to target cysteine and other amino acids (Gehringer, M.; Laufer, S. A. <i>J. Med. Chem.</i> 2019, 62, 5673-5724; DOI: 10.1021/acs.jmedchem.8b01153). Since then, the field has rapidly evolved. Here we discuss the progress on covalent warheads made since our last Perspective and their application in medicinal chemistry and chemical biology.
A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1
2024-05-07

The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1 alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer.
Assessing AI Awareness and Identifying Essential Competencies: Insights From Key Stakeholders in Integrating AI Into Medical Education
2024-05-07

Abstract Background The increasing importance of artificial intelligence (AI) in health care has generated a growing need for health care professionals to possess a comprehensive understanding of AI technologies, requiring an adaptation in medical education. Objective This paper explores stakeholder perceptions and expectations regarding AI in medicine and examines their potential impact on the medical curriculum. This study project aims to assess the AI experiences and awareness of different stakeholders and identify essential AI-related topics in medical education to define necessary competencies for students. Methods The empirical data were collected as part of the TüKITZMed project between August 2022 and March 2023, using a semistructured qualitative interview. These interviews were administered to a diverse group of stakeholders to explore their experiences and perspectives of AI in medicine. A qualitative content analysis of the collected data was conducted using MAXQDA software. Results Semistructured interviews were conducted with 38 participants (6 lecturers, 9 clinicians, 10 students, 6 AI experts, and 7 institutional stakeholders). The qualitative content analysis revealed 6 primary categories with a total of 24 subcategories to answer the research questions. The evaluation of the stakeholders’ statements revealed several commonalities and differences regarding their understanding of AI. Crucial identified AI themes based on the main categories were as follows: possible curriculum contents, skills, and competencies; programming skills; curriculum scope; and curriculum structure. Conclusions The analysis emphasizes integrating AI into medical curricula to ensure students’ proficiency in clinical applications. Standardized AI comprehension is crucial for defining and teaching relevant content. Considering diverse perspectives in implementation is essential to comprehensively define AI in the medical context, addressing gaps and facilitating effective solutions for future AI use in medical studies. The results provide insights into potential curriculum content and structure, including aspects of AI in medicine.
Content Validity of the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) Instrument in Spinocerebellar Ataxia
2024-05-07

Abstract The functional Scale for the Assessment and Rating of Ataxia (f-SARA) assesses Gait, Stance, Sitting, and Speech. It was developed as a potentially clinically meaningful measure of spinocerebellar ataxia (SCA) progression for clinical trial use. Here, we evaluated content validity of the f-SARA. Qualitative interviews were conducted among individuals with SCA1 ( n = 1) and SCA3 ( n = 6) and healthcare professionals (HCPs) with SCA expertise (USA, n = 5; Europe, n = 3). Interviews evaluated symptoms and signs of SCA and relevance of f-SARA concepts for SCA. HCP cognitive debriefing was conducted. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.TI software. Individuals with SCA1 and 3 reported 85 symptoms, signs, and impacts of SCA. All indicated difficulties with walking, stance, balance, speech, fatigue, emotions, and work. All individuals with SCA1 and 3 considered Gait, Stance, and Speech relevant f-SARA concepts; 3 considered Sitting relevant (42.9%). All HCPs considered Gait and Speech relevant; 5 (62.5%) indicated Stance was relevant. Sitting was considered a late-stage disease indicator. Most HCPs suggested inclusion of appendicular items would enhance clinical relevance. Cognitive debriefing supported clarity and comprehension of f-SARA. Maintaining current abilities on f-SARA items for 1 year was considered meaningful for most individuals with SCA1 and 3. All HCPs considered meaningful changes as stability in f-SARA score over 1–2 years, 1–2-point change in total f-SARA score, and deviation from natural history. These results support content validity of f-SARA for assessing SCA disease progression in clinical trials.
Profiling Teachers’ Motivation for Professional Development: A Nationwide Study
2024-05-07

Situated in the context of advanced placement (AP) reform in the United States, we investigated profiles of teachers’ motivation for participating in professional development (PD) courses in a two-cohort sample of n t1 = 2,369 and n t2 = 2,170 chemistry teachers via multilevel latent class analysis. In addition, the study investigated to what extent profile membership was related to factors at the teacher, school, and PD levels. Participation in PD courses was associated with one of three profiles, labeled “reform-motivated,” “convenience-motivated,” and “interaction-motivated.” Participation in PD courses was more likely to be reform-motivated if a teacher had a major in chemistry, more experience teaching AP, more positive attitudes toward PD, or higher enactment of AP redesign in the classroom, or if the PD course was formal and face-to-face. The results show that teachers have different motivations for participating in PD courses and provide insight into how to engage teachers in professional learning.
Toward Gigahertz Photodetection with Transition Metal Dichalcogenides
2024-05-07

ConspectusTransition metal dichalcogenides (TMDCs) exhibit favorable properties for optical communication in the gigahertz (GHz) regime, such as large mobilities, high extinction coefficients, cheap fabrication, and silicon compatibility. While impressive improvements in their sensitivity have been realized over the past decade, the bandwidths of these devices have been mostly limited to a few megahertz. We argue that this shortcoming originates in the relatively large RC constants of TMDC-based photodetectors, which suffer from high surface defect densities, inefficient charge carrier injection at the electrode/TMDC interface, and long charging times. However, we show in a series of papers that rather simple adjustments in the device architecture afford TMDC-based photodetectors with bandwidths of several hundreds of megahertz. We rationalize the success of these adjustments in terms of the specific physical-chemical properties of TMDCs, namely their anisotropic in-plane/out-of-plane carrier behavior, large optical absorption, and chalcogenide-dependent surface chemistry. Just one surprisingly simple yet effective pathway to fast TMDC photodetection is the reduction of the photoresistance by using light-focusing optics, which enables bandwidths of 0.23 GHz with an energy consumption of only 27 fJ/bit.By reflecting on the ultrafast intrinsic photoresponse times of a few picoseconds in TMDC heterostructures, we motivate the application of more demanding chemical strategies to exploit such ultrafast intrinsic properties for true GHz operation in real devices. A key aspect in this regard is the management of surface defects, which we discuss in terms of its dependence on the layer thickness, its tunability by molecular adlayers, and the prospects of replacing thermally evaporated metal contacts by laser-printed electrodes fabricated with inks of metalloid clusters. We highlight the benefits of combining TMDCs with graphene to heterostructures that exhibit the ultrafast photoresponse and large spectral range of Dirac materials with the low dark currents and high responsivities of semiconductors. We introduce the bulk photovoltaic effect in TMDC-based materials with broken inversion symmetry as well as a combination of TMDCs with plasmonic nanostructures as means for increasing the bandwidth and responsivity simultaneously. Finally, we describe the prospects of embedding TMDC photodetectors into optical cavities with the objective of tuning the lifetime of the photoexcited state and increasing the carrier mobility in the photoactive layer.The findings and concepts detailed in this Account demonstrate that GHz photodetection with TMDCs is feasible, and we hope that these bright prospects for their application as next-generation optoelectronic materials motivate more chemists and material scientists to actively pursue the development of the more complicated material combinations outlined here.
Leaf fluctuating asymmetry is not a reliable indicator of stress
2024-05-07

Abstract Stress experienced during development in organisms with bilateral structures could result in developmental instability, which is expressed as subtle non‐directional deviations from perfect symmetry, known as fluctuating asymmetry (FA). As such, FA has been proposed, and extensively used, as a trait indicating stress for many organisms with bilateral structures and many types of stress. However, while this concept may apply to animals, the evidence for plants' main vegetative structures, that is, leaves, remains equivocal, and a comprehensive synthesis on this topic is still missing. We designed observational field and controlled greenhouse studies, combining different growth and leaf forms across multiple stress gradients, comprising 21 species and 80 populations. We measured FA as the difference between the left and right area of the leaf, an approach that accommodates diverse leaf forms. We used high‐precision, blind, single‐person measurements and tested for other forms of symmetry and the effect of leaf size. We further complemented our study with a systematic literature review of FA in plant leaves, compiling 51 studies comprising 72 species, 23 stress types and 131 unique entries (species × stress type). We consistently found no effect of stress on leaf FA in any of the studied species in both our field and experimental gradients. In the systematic literature review, only 39% of the unique entries showed the expected increase in FA with stress, 53% showed no effect, 9% showed an opposite trend of a decrease in FA with stress and 1% showed a unimodal relationship. Importantly, only 40% of all entries fulfilled the crucial step of controlling for a high‐precision measurement, and of these 49% reported the expected increase in FA with stress. Both the results of our observational and experimental approaches and the systematic literature review failed to support a clear relationship between stress and FA in plant leaves. These results clearly show that FA in plant leaves cannot be used as a reliable trait indicating stress during development. Read the free Plain Language Summary for this article on the Journal blog.
Radiation Exposure and Safety Considerations in Interventional Radiology: Comparison of a Twin Robotic X-ray System to a Conventional Angiography System
2024-05-07

Background/Objectives: To evaluate radiation exposure in standard interventional radiology procedures using a twin robotic X-ray system compared to a state-of-the-art conventional angiography system. Methods: Standard interventional radiology procedures (port implantation, SIRT, and pelvic angiography) were simulated using an anthropomorphic Alderson RANDO phantom (Alderson Research Laboratories Inc. Stamford, CT, USA) on an above-the-table twin robotic X-ray scanner (Multitom Rax, Siemens Healthineers, Forchheim, Germany) and a conventional below-the-table angiography system (Artis Zeego, Siemens Healthineers, Forchheim, Germany). The phantom’s radiation exposure (representing the potential patient on the procedure table) was measured with thermoluminescent dosimeters. Height-dependent dose curves were generated for examiners and radiation technologists in representative positions using a RaySafe X2 system (RaySafe, Billdal, Sweden). Results: For all scenarios, the device-specific dose distribution differs depending on the imaging chain, with specific advantages and disadvantages. Radiation exposure for the patient is significantly increased when using the Multitom Rax for pelvic angiography compared to the Artis Zeego, which is evident in the dose progression through the phantom’s body as well as in the organ-related radiation exposure. In line with these findings, there is an increased radiation exposure for the performing proceduralist, especially at eye level, which can be significantly minimized by using protective equipment (p &lt; 0.001). Conclusions: In this study, the state-of-the-art conventional below-the-table angiography system is associated with lower radiation dose exposures for both the patient and the interventional radiology physician compared to an above-the-table twin robotic X-ray system for pelvic angiographies. However, in other clinical scenarios (port implantation or SIRT), both devices are suitable options with acceptable radiation exposure.
Immune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans
2024-05-07

Vaccination of malaria-naive volunteers with a high dose of Plasmodium falciparum sporozoites chemoattenuated by chloroquine (CQ) (PfSPZ-CVac [CQ]) has previously demonstrated full protection against controlled human malaria infection (CHMI). However, lower doses of PfSPZ-CVac [CQ] resulted in incomplete protection. This provides the opportunity to understand the immune mechanisms needed for better vaccine-induced protection by comparing individuals who were protected with those not protected. Using mass cytometry, we characterized immune cell composition and responses of malaria-naive European volunteers who received either lower doses of PfSPZ-CVac [CQ], resulting in 50% protection irrespective of the dose, or a placebo vaccination, with everyone becoming infected following CHMI. Clusters of CD4+ and γδ T cells associated with protection were identified, consistent with their known role in malaria immunity. Additionally, EMRA CD8+ T cells and CD56+CD8+ T cell clusters were associated with protection. In a cohort from a malaria-endemic area in Gabon, these CD8+ T cell clusters were also associated with parasitemia control in individuals with lifelong exposure to malaria. Upon stimulation with P. falciparum-infected erythrocytes, CD4+, γδ, and EMRA CD8+ T cells produced IFN-γ and/or TNF, indicating their ability to mediate responses that eliminate malaria parasites.