julilili42/papers huggingface dataset:
Capture of an In Situ Formed Distanna-S-heterocyclic Carbene
2025-04-01

The planar, non-twisted distannene Sn<sub>2</sub>(TIPS)<sub>4</sub> (<b>1</b>, TIPS = Si<sup><i>i</i></sup>Pr<sub>3</sub>) reacts with CS<sub>2</sub> to form a tetrathiaethylene derivative via the dimerization of two S-heterocyclic carbenes (SHCs). These intermediary-formed SHCs can be transferred to palladium as ligands or captured with B(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub> (BCF) and, furthermore, facilitate a new pathway for formation of the stannaethene SHC═Sn(TIPS)<sub>2</sub> by the reaction of <b>1</b> with (PPh<sub>3</sub>)<sub>2</sub>Pd-CS<sub>2</sub>. In addition to the characterization of the new complexes, theoretical calculations of the frontier orbitals were performed, which indicate a high π-acceptor character of the SHC.
A 125 million-year-old freshwater isopod shines new light on the origin of subterranean freshwater species
2025-04-01

Here, we report fossil isopods preserved in laminated oil-shale mudstone (dysodile) from the Lower Cretaceous of Lebanon (Lower Barremian, 125 Ma, Grès du Liban Alloformation, Jezzine District). Based on a variety of proxies, their palaeoenvironments are determined to have been a shallow freshwater lake. The fossil isopods were studied using modern imaging techniques, such as multispectral imaging and photometric stereo, allowing for a detailed comparison of these specimens with comparable extant and fossil taxa. The conspecific fossils are herein recognized as remains of a new species — † Dysopodus gezei gen. et sp. nov.—of uncertain affinity within Cymothoida and bearing a strong resemblance to its non-parasitic lineages (Cirolanidae). A conspicuous pleotelson and uropod morphology set it apart from most species, with the notable exception of † Pseudoplakolana chiapaneca gen. nov. et comb. nov. from the Cretaceous of Mexico, originally attributed to an Australasian lineage (herein disputed). So far, the biogeographical distribution of the peri-Mediterranean underground fauna has predominantly been explained through a passive isolation process of former marine species, driven by regressing coastlines. Stemming from a freshwater lake environment, the 125 million-year-old fossils from Lebanon provide an unconventional perspective on the evolutionary origin of extant cave- and groundwater-dwelling cymothoidans.
Does Covariation Between Cranial and Pelvic Shapes Alleviate the Obstetric Dilemma? Insights From a Brazilian Sample
2025-04-01

ABSTRACT Cranial and pelvic bones could have evolved in response to each other during human evolutionary history due to the increasingly tight fit between the baby's head and the mother's pelvis during delivery. A recently identified covariation pattern between these sets of bones and stature has shown important evidence of such an evolutionary trade‐off, alleviating the chances of obstructed labor. Here, we tested the validity of this covariation pattern in a different sample, from a population with known high rates of C‐section. 98 computed tomographies were used to perform statistical covariation tests (two‐block partial least squares and ANOVA Procrustes) between pelvic and cranial shape, as well as other anthropometric variables, like stature, body mass, and BMI. Additionally, measurements were taken from cranial and pelvic bones for classic morphometric analyses. The results have shown an important sexual dimorphism in pelvic bones' shape but no correlation between them and stature or cranial size or shape. In terms of size, the sexual dimorphism on the true pelvis was also noticeable. The fact that the results obtained from this sample do not corroborate previous findings suggests the absence of this pattern in some populations. It also suggests that the current ideal rates of C‐sections proposed by the World Health Organization might not be considering the existing diversity among human populations that may account for variable levels of difficulties in birth.
Water Communities in the Plain of Palermo. A Neglected Islamic Document from Norman Sicily
2025-04-01

Abstract The Archivio Storico Diocesano di Palermo conserves a unique Arabic-Islamic document dating to 526/1132 that allows for insights into the legal practices of small-scale water management in the fertile countryside of Sicily’s capital city Palermo. Almost entirely neglected by previous scholarship, this article offers the first analysis of the document’s legal content and situates it within the wider context of Mālikī law, landscape engineering, and Muslim communal practices in medieval Sicily at a time when Latin-Christian elites came to dominate the possession of resources in Palermo’s hinterland.
Global existence and asymptotic behavior of strong solutions to three dimensional modified primitive equations with Caputo fractional time derivatives
2025-04-01

A three dimensional system of globally modified fractional viscous primitive equations with Caputo fractional time derivatives, is developed and analyzed. To investigate the asymptotic behavior of strong solutions, the modifying factors FN(‖v‖W1,2(1+2ε)1+2ε) and FN(‖v‖W1,2(1+2ε)1+2ε+‖T‖W1,2(1+2ε)1+2ε) are introduced into the time fractional primitive equations. The global existence of strong solutions is established for the globally modified time fractional primitive equations. Subsequently, the existence and uniqueness of local (or global) strong solutions to the time fractional primitive equations are presented for any (or small) initial data and external force, in which we do not add any modifying factor on the nonlinear terms. Then after constructing a positively invariant absorbing set, we show the existence of a global attracting set for the globally modified time fractional primitive equations.
US FDA–accelerated approvals and subsequent withdrawals: influence on Japanese clinical oncology practice guidelines
2025-04-01

Summary The US (US) Food and Drug Administration (FDA)-accelerated approval pathway facilitates early access to oncology drugs based on surrogate endpoints, with required confirmatory post-marketing trials. However, regulatory decisions vary globally, with some drugs withdrawn in the US remaining approved in Japan. We conducted a cross-sectional analysis of Japanese professional society guidelines, evaluating recommendations for seven accelerated approval cancer drugs withdrawn from the US market but retained in Japan. We assessed for level of evidence and level of treatment preference ratings with consensus across guidelines issued by the corresponding Japanese professional societies. Four of the seven drugs (57%) were recommended as highly or moderately preferred treatment options in Japanese guidelines: gemtuzumab ozogamicin for acute myeloid leukemia, gefitinib for EGFR-positive non-small cell lung cancer, bevacizumab for HER2-negative metastatic breast cancer, and atezolizumab with nab-paclitaxel for PD-L1-positive triple-negative breast cancer. Detailed analysis of regulatory history and background of guideline recommendation revealed discrepancies in the assessment of clinical benefits: gemtuzumab ozogamicin failed to demonstrate benefits amid safety concerns, while gefitinib, bevacizumab, and atezolizumab were more controversial, although they did not demonstrate improved overall survival in post-marketing trials. Despite regulatory withdrawal in the US due to unproven clinical benefits, drugs retained in Japan received positive guideline recommendations. This finding highlights regional variations in regulatory decisions and different approaches to benefit-risk assessments, suggesting a need for improved transparency in Japan’s regulatory decisions and guideline recommendations, with clearer justifications for endorsing drugs that are considered to have unproven clinical benefits in the US.
Efficacy of deep brain stimulation in treating monogenic dystonia symptoms: protocol for a systematic review
2025-04-01

Introduction Complexity leads to some dystonias being considered as rare diseases with scarce synthesised evidence. Despite the deficit of scientific evidence, deep brain stimulation (DBS) is currently an effective treatment for dystonias using different brain targets, providing significant improvement of dystonic symptoms regardless of their cause. However, there is considerable variability and non-response rate due to factors such as classification, semiology, duration, aetiology and genetic cause of the disease. This protocol presents the methodology of a planned systematic review to assess the efficacy of DBS as a treatment for monogenic dystonia symptoms, a broad spectrum of pathogenic dystonias due to variants in single genes not yet explored. Methods and analysis This protocol follows the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols guidelines. With the aim to test the efficacy of DBS in monogenic dystonias, the research question in population, intervention, comparator and outcomes format will cover patients with monogenic dystonia treated with DBS with a minimum of 3 months' follow-up after surgery. The outcomes will be assessed using generic and specific scales to measure the efficacy and safety of the intervention. The search will be performed in generic and specific databases and bibliographic resources from 2000. We will include systematic reviews, randomised controlled trials and primary studies in English. In this protocol, the initial search strategy in MEDLINE is presented. Additionally, the protocol provides a description of the prospective assessment of the risk of bias in the selected studies. If studies appear homogeneous and the sample of patients is sufficiently large, a meta-analysis and a subgroup analysis are planned. Ethics and dissemination Ethics committee approval is not required. The results of the review will be published through an open access journal. PROSPERO registration number CRD42023448145
Peripheral Iridotomy-Less Approach in Descemet’s Membrane Endothelial Keratoplasty Using Pupil-Dilating Eye Drops, a Retrospective Case–Control Study
2025-04-01

Patients may benefit from the promising results of the study regarding postoperative IOP developments and graft viability after DMEK using mydriatic eye drops (phenylephrine 25 mg/mL, tropicamide 5 mg/mL). PI-less triple DMEK in particular might improve accessibility, reduce surgical complexity, or lower costs, making it attractive in resource-limited settings. Close postoperative IOP monitoring is advised in PI-less DMEKs.
An Investigation of Corticospinal Tract Microstructural Integrity in ARSACS Using a Profilometry MRI Analysis: Results From the PROSPAX Study
2025-04-01

ABSTRACT Background Spasticity represents a core clinical feature of Autosomal Recessive Spastic Ataxia of Charlevoix‐Saguenay (ARSACS) patients. Nonetheless, its pathophysiological substrate is poorly investigated. We assessed the microstructural integrity of the corticospinal tract (CST) using diffusion MRI (dMRI) via profilometry analysis to understand its possible role in the development of spasticity in ARSACS. Materials and Methods In this multi‐center prospective study, data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years) and 29 controls (M/F = 13/16; 42.1 ± 17.2 years) acquired within the PROSPAX consortium were collected from January 2021 to October 2022 and analyzed. Differences in terms of global CST microstructural integrity were probed, as well as a possible spatial distribution of the damage along the tract via profilometry analysis. Possible correlations between clinical severity, including the Spastic Paraplegia Rating Scale (SPRS), were also tested. Results A significant global involvement of the CST was found in ARSACS compared to controls (all tests with p &lt; 0.001), with a spatially defined pattern of more pronounced microstructural integrity loss occurring right below and above the pons, a structure that was also confirmed to be thickened in these patients ( p &lt; 0.001). A bilateral negative correlation emerged between the microstructural integrity of the CST and clinical indices of spasticity expressed via SPRS ( p = 0.02 for both CSTs). Conclusion A clinically meaningful microstructural involvement of CST is present in ARSACS patients, with a spatially defined pattern of damage occurring right below and above a thickened pons. An evaluation of the microstructure of this bundle might serve as a possible biomarker in this condition.
Bite force production and the origin of Homo
2025-04-01

The divergence of Homo from gracile australopiths has been described as a trend of decreasing dentognathic size and robusticity, precipitated by stone tool use and/or a shift to softer foods, including meat. Yet, mechanical evidence supporting this narrative is sparse, and isotopic and archaeological data have led to the suggestion that a shift away from a gracile australopith-like diet would not have occurred in the most basal members of Homo but rather only with the appearance of Homo erectus, implying that the origin of our genus is not rooted in dietary change. Here, we provide mechanical evidence that Homo habilis exhibits an australopith-like pattern of facial strain during biting but, unlike most australopiths, was not suited for a diet that required forceful processing by the molar teeth. Homo habilis was at elevated risk of distractive jaw joint forces during those bites, constraining muscle recruitment so as to avoid generating uncomfortable/dangerous levels of tension in the joint. Modern humans have similar limitations. This suggests that selection on skeletal traits favouring forceful postcanine processing was relaxed by the earliest stages in the evolution of our genus, implying that dietary or food processing changes played an important role in the emergence of Homo .
Inhibition of cGMP‐Signalling Rescues Retinal Ganglion Cells From Axotomy‐Induced Degeneration
2025-04-01

ABSTRACT The axons of retinal ganglion cells (RGCs) form the optic nerve, which relays visual information to the brain. RGC degeneration is the root cause of a variety of blinding diseases linked to optic nerve damage, including glaucoma, the second leading cause of blindness worldwide. The underlying cellular mechanisms of RGC degeneration are largely unclear; yet, they have been connected to excessive production of the signalling molecule nitric oxide (NO) by nitric oxide synthase (NOS). NO activates soluble guanylate cyclase (sGC), which subsequently produces the second messenger cyclic guanosine monophosphate (cGMP). This, in turn, activates protein kinase G (PKG), which can phosphorylate downstream protein targets. To study the role of NO/cGMP/PKG signalling in RGC degeneration, we used organotypic retinal explant cultures in which the optic nerve had been severed. We assessed the activity of NOS, RGC death and survival at different times after optic nerve transection. While NOS activity was high right after optic nerve transection, significant RGC loss occurred with a 24–48‐h delay. We then treated retinal explants with inhibitors selectively targeting either NOS, sGC, PKG, or Kv1.3 and Kv1.6 voltage‐gated potassium channels. While all four treatments reduced RGC death, the PKG inhibitor CN238 and the Kv‐channel blocker Margatoxin (MrgX) showed the most pronounced rescue effects. Our results confirm an involvement of NO/cGMP/PKG signalling in RGC degeneration, highlight the potential of PKG and Kv1‐channel targeting drugs for treatment development, and further suggest organotypic retinal explant cultures as a useful model for investigations into optic nerve damage. image
Rapid assessment of direct oral anticoagulants in acute stroke—An educational systematic review
2025-04-01

Purpose: To provide an overview on commercially available point-of-care tests (POCT) for rapid assessment of direct oral anticoagulant (DOAC) activity, their diagnostic accuracy in identifying blood samples containing clinically relevant DOAC concentrations, and guidance on selecting the appropriate POCT system/assay for decision-making in emergencies. Methods: Systematic review with PubMed and Cochrane library search for published studies until September 6, 2024. Papers were included if in English, original research using blood samples from DOAC patients and POCT was implemented. Two reviewers assessed studies for eligibility and quality. Data from studies were aggregated and diagnostic accuracy at DOAC plasma thresholds of 30/50/100 ng/ml was recalculated. Findings: 16 studies involving four commercially available POCT systems/assays were identified. Eleven studies evaluated blood-based POCT and five used urine for indirect estimation of DOAC plasma levels. Discussion: DOAC Dipsticks do not require knowledge about the taken DOAC, but measure urine and, due to low specificity, require blood testing in case of positive results. Hemochron Signature Elite (HSE) and CoaguChek use global coagulation assays and provide high sensitivity for edoxaban and rivaroxaban, HSE additionally for dabigatran. Due to insufficient correlation, both POCT are not recommended for apixaban, CoaguChek also not for dabigatran. The thromboelastometric ClotPro performs well for all DOAC, does not require knowledge about the DOAC, but was taken off the market recently. Conclusion: Studies have shown feasibility of POCT in identifying blood samples containing clinically relevant DOAC plasma concentrations. Each POCT device has its own unique limitations. Knowledge about the POCT assays, time since last intake and type of DOAC enhances confidence in making appropriate therapeutic decisions. We propose an algorithm that could help guiding physicians in selecting an appropriate POCT system/assay in DOAC-related emergencies.
The longitudinal impact of health behaviours on mental health, diabetes distress, and quality of life in people with type 1, type 2, and gestational diabetes: A scoping review
2025-04-01

Introduction There can be a considerable mental health burden to living with diabetes. Health behaviours are modifiable factors that influence mental health in the general population. However, despite the centrality of health behaviours to diabetes management, there are significant gaps in our understanding of their longitudinal impact on mental health in people with diabetes. Objectives This scoping review aimed to synthesise the longitudinal evidence from observational and intervention research on the impact of health behaviours on mental health and related psychological factors in people with type 1, type 2, and gestational diabetes. Methods PubMed, PsychINFO, Embase, CINAHL, and PsycArticles were searched for intervention and observational studies examining the effect of health-promoting, health-risk, or diabetes-specific health behaviours on aspects of mental health, diabetes distress, and quality of life, in people with all types of diabetes. Abstracts, titles, and full texts were screened by two independent reviewers. Results In total, 100 relevant studies were identified, including 29 observational studies and 71 intervention studies. Studies had a mean follow-up time of 12.9 ± 17.8 months. The health behaviours investigated in the included studies were adherence, alcohol, carbohydrate-counting, diet, diet and exercise combined, exercise, fasting, medical visits, sleep, self-monitoring blood glucose, smoking, and weight. The review identified knowledge gaps surrounding diabetes-specific behaviours, behaviour interactions/clusters, sleep, sedentary behaviour, screen-time, gestational diabetes, mood and ecologically valid and objective measurements. Exercise was the most freqently investigated health behaviour and also the most likely to be found to have a mental health promoting impact. Conclusions Findings suggest that health-promoting behaviours influence mental health in people with diabetes. There is less conclusive evidence regarding the impact of health-risk or diabetes-specific health behaviours. In particular, a broad range of physical activities may improve mental health and wellbeing in people with diabetes. Disclosure of Interest None Declared
A Phase 3 Trial of Upadacitinib for Giant-Cell Arteritis
2025-04-02

In patients with giant-cell arteritis, upadacitinib at a dose of 15 mg - but not 7.5 mg - with a 26-week glucocorticoid taper showed efficacy superior to that of placebo with a 52-week glucocorticoid taper. (Funded by AbbVie; SELECT-GCA ClinicalTrials.gov number, NCT03725202.).
Opportunities and Challenges of Population Pharmacogenomics
2025-04-02

ABSTRACT Pharmacological responses can vary significantly among patients from different ethnogeographic backgrounds. This variability can, at least in part, be attributed to population‐specific genetic patterns in genes involved in drug absorption, distribution, metabolism, and excretion, as well as in genes associated with drug‐induced toxicity. Identification of such ethnogeographic variability is thus crucial for the optimization of precise population‐specific drug treatments. In this review, we summarize the current knowledge about the clinically actionable pharmacogenetic diversity of genes involved in drug metabolism ( CYP2B6 , CYP2C8 , CYP2C9 , CYP2C19 , CYP2D6 , CYP3A5 , DPYD , TPMT , NUDT15 , UGT1A1 , and NAT2 ), drug‐induced hypersensitivity reactions ( HLA‐A and HLA‐B ), and drug‐induced acute hemolytic anemia ( G6PD ). We highlight risk populations with distinct allele frequencies and discuss implications for the customization of treatment. Subsequently, we discuss key challenges and opportunities in population pharmacogenomics, including the importance of considering distinct allele frequency patterns in indigenous or founder populations, interpreting pharmacogenomic response in admixed populations, addressing the investigation bias of the pharmacogenomic literature, and difficulties in including rare and population‐specific variants into drug response predictions. The information provided here underscores the critical role of population pharmacogenomics in refining pharmacological treatment strategies and aspires to provide further guidance to maximize the benefits of precision medicine across populations.
Individual-level deviations from normative brain morphology in violence, psychosis, and psychopathy
2025-04-02

Abstract Neuroimaging research has shown brain morphological abnormalities associated with violence and psychosis, but individual differences are substantial and results not consistent across studies. Normative modeling of brain MRI-features facilitates a systematic mapping of individual brain characteristics of complex phenotypes also in small samples but has not yet been applied to forensic psychiatry populations. We explored brain heterogeneity in persons with a history of severe violence with a comorbid schizophrenia spectrum disorder (SSD-V; n = 38), non-violent persons with schizophrenia spectrum disorders (SSD-NV; n = 138), persons with a history of severe violence without comorbid schizophrenia spectrum disorder (nonSSD-V; n = 20), and healthy non-violent participants (HC; n = 196) from lifetime normative trajectories of cortical thickness, surface area, and subcortical volumes. Normative models based on Freesurfer derived regions of interest from 58,836 individuals were used to investigate individual deviances, group differences, and associations to psychopathy traits. We found overall heterogeneous patterns of individual deviations from the norm, which were most prominent for regions within the collateral transverse sulcus, lingual gyrus, and cerebellum among SSD-V, a pattern that differed from SSD-NV (parieto-occipital and suborbital sulci), and nonSSD-V (paracentral and middle frontal regions). We found no significant associations to psychopathy traits. By applying normative modeling, we demonstrate heterogeneous patterns of brain morphometry deviations associated with violence and psychosis. While the results warrant replication, studies addressing individual brain deviations may contribute to improved understanding of the neurobiological underpinnings of comorbid violence and psychosis, which ultimately may have clinical impact on treatment and forensic psychiatric evaluations.