julilili42/papers huggingface dataset:
Systemic and SARS-CoV-2 specific Immune Disturbances in Individuals With Post–COVID Syndrome
2025-04-24

Abstract Background Post–coronavirus disease 2019 syndrome (PCS) is characterized by persistent symptoms lasting &amp;gt;12 weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The underlying pathological mechanisms remain poorly understood. Methods We conducted detailed immunological analyses in 47 individuals with PCS, assessed &amp;gt;12 weeks after acute SARS-CoV-2 infection, and we compared them with 25 convalescent controls without symptoms. We performed immune phenotyping of T- and B-cell subsets, assessed SARS-CoV-2–specific responses using activation-induced marker (AIM) flow cytometry for T cells, and tetramer staining of spike-specific B cells. Cytokine levels in peptide-stimulated cell supernatants and plasma were quantified using a Luminex platform. Results Individuals with PCS exhibited reduced frequencies of AIM-positive SARS-CoV-2–specific T cells (OX40+PDL1+) and CD8 T cells (CD137+CD69+) following peptide stimulation with spike or nucleocapsid antigen, accompanied by diminished interferon γ and interleukin 2, as measured in the cell culture supernatants. In contrast, non–virus-specific T-cell populations, including memory differentiation, activation and helper cell differentiation status, did not differ between the groups. Individuals with PCS showed a significant increase in total (CD19+) and activated (CD86+HLA-DR+) B cells but not in SARS-CoV-2 spike–specific B cells (approximately 0.2% of total B cells). Plasma cytokine analysis revealed elevated markers associated with vascular damage and inflammation in those with PCS. Conclusions Persistent immune disturbances in individuals with PCS are characterized by reduced SARS-CoV-2–specific T-cell responses, increased B-cell activation, and altered inflammatory and vascular biomarkers. These findings provide insights into the underlying mechanisms of PCS and may contribute to biomarker discovery and therapeutic development. Trial no DRKS00030974 (registry: https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html).
Automated derivatization with 6-aminoquinolyl-N-hydroxysccinimidyl carbamate for the enantioselective amino acid analysis of neurotensin synthesized by liquid phase peptide synthesis
2025-04-24

This study presents an automated derivatization protocol utilizing 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) for enantioselective amino acid analysis of peptides synthesized via liquid phase peptide synthesis, as exemplified by neurotensin. The primary aim was to enhance operational efficiency to manage the derivatization of large sample sets and reduce human error in routine enantioselective amino acid analysis of peptide therapeutics. The chromatographic method based on Chiralpak QN-AX demonstrated enantio- and chemoselectivity for all proteinogenic amino acids (except D-Leu/D-Ile and Glu/pGlu), with quantitative analysis achieved by HPLC-ESI-MS/MS with MRM acquisition through external calibration using stable isotope-labeled internal standards. The goal was to test for racemization of amino acids during peptide synthesis and process optimization, respectively. The results confirmed varying susceptibility to racemization among amino acids during peptide synthesis and cleavage of protection groups, with specific amino acids exhibiting higher levels of D-enantiomer formation. The developed protocol effectively assessed the amino acid composition and stereointegrity of the liquid phase synthesized neurotensin. This research and application highlights the critical role of automation in optimizing peptide analysis workflows and sets the foundation for future improvements in peptide synthesis and chromatographic conditions to enhance specificity, particularly for challenging amino acid pairs. Ultimately, the findings contribute to advancing laboratory practices in peptide chemistry, ensuring the quality and efficacy of peptide-based therapeutics.
Metathetical Exchange, Synthesis, and Carbon Dioxide Addition of Higher Homologues of Group 9 Metal Carbynes
2025-04-24

Abstract A one‐pot synthesis for previously unknown heavy homologues of Group 9 metal carbynes [(Me 3 P) 3 Co≡GeAr*] ( 1 ), [(Me 3 P) 3 Rh≡GeAr*] ( 2 ), [(Me 3 P) 3 Ir≡GeAr*] ( 3 ), [(Me 3 P) 3 Ir≡SnAr*] ( 5 ), and [(Et 3 P) 3 Ir≡PbAr*] ( 7 ) is presented [Ar* = C 6 H 3 ‐2,6‐(Trip) 2 , Trip = 2,4,6‐C 6 H 2 i Pr 3 ]. During these preparations, the tetrylidynes [(Me 3 P) 3 Rh≡SnAr*] ( 4 ), and [(Me 3 P) 3 Rh≡PbAr*] ( 6 ), were also prepared in a one‐pot procedure. In a hitherto unknown metathetical exchange reaction, the transition metal plumbylidynes were converted into the respective stannylidynes in reaction with terphenyl stannylene chloride, and the germylidynes were formed from the corresponding stannylidynes in reaction with terphenyl germylene chloride. These metathesis reactions were tracked by 31 P{ 1 H} NMR spectroscopy, which shows complete exchange of the tetrel [EAr]‐fragment and the formation of an intermediate in the rhodium plumbylidyne reaction with stannylene chloride (Ar = Ar*, Tbb). Reactions of the tetrylidynes ( 2 – 5 ) with carbon dioxide yield the products of a redox reaction [(Me 3 P) 3 (CO)M‐E( η 2 ‐O 2 CO‐ κ 2 O )Ar*] [E = Ge, M = Rh ( 11 ); M = Ir ( 12 ); E = Sn, M = Rh ( 14 ), M = Ir ( 16 )] with a carbon monoxide coordinated at the transition metal and a carbonate coordinated at the Group 14 element. For tin the intermediates formed by mono CO 2 addition [(Me 3 P) 3 M( μ , η 2 ‐CO 2 ‐ κC : κO )SnAr*] [M = Rh ( 13 ), M = Ir ( 15 )] have been isolated.
Metathetischer Austausch, Synthese und Addition von Kohlenstoffdioxid an schweren Gruppe‐9‐Metall‐Carbinen
2025-04-24

Zusammenfassung In einer One‐Pot‐ Synthese wurden die bislang unbekannten schweren Homologe der Gruppe‐9‐Metall‐Carbine [(Me 3 P) 3 Co≡GeAr*] ( 1 ), [(Me 3 P) 3 Rh≡GeAr*] ( 2 ), [(Me 3 P) 3 Ir≡GeAr*] ( 3 ), [(Me 3 P) 3 Ir≡SnAr*] ( 5 ) und [(Et 3 P) 3 Ir≡PbAr*] ( 7 ) synthetisiert. [Ar* = C 6 H 3 ‐2,6‐(Trip) 2 , Trip = 2,4,6‐C 6 H 2 i Pr 3 ]. Auch die Tetrylidine [(Me 3 P) 3 Rh≡SnAr*] ( 4 ) und [(Me 3 P) 3 Rh≡PbAr*] ( 6 ) wurden in einer One‐Pot‐ Reaktion dargestellt. In einer neuartigen metathetischen Austauschreaktion reagieren die Übergangsmetallplumbylidine mit Terphenylstannylenchlorid zu den entsprechenden Stannylidinen, während diese in der Umsetzung mit Terphenylgermylenchlorid die entsprechenden Germylidine bilden. 31 P{ 1 H}‐NMR‐spektroskopische Untersuchungen der Metathesen zeigen den vollständigen Austausch des Tetrel‐[EAr]‐Fragments und, in der Reaktion des Rhodiumplumbylidins mit Stannylenchlorid, die Bildung eines Zwischenprodukts (Ar = Ar*, Tbb). Die Umsetzungen der Tetrylidine ( 2 – 5 ) mit Kohlenstoffdioxid ergeben die Produkte einer Redoxreaktion [(Me 3 P) 3 (CO)M‐E( η 2 ‐O 2 CO‐ κ 2 O )Ar*] [E = Ge, M = Rh ( 11 ), M = Ir ( 12 ); E = Sn, M = Rh ( 14 ), M = Ir ( 16 )] mit einem am Übergangsmetall koordinierten Kohlenstoffmonoxidliganden und einem am Gruppe‐14‐Element koordinierten Carbonat. Für das Zinn wurden die durch die einfache CO 2 ‐Addition gebildeten Intermediate [(Me 3 P) 3 M( μ , η 2 ‐CO 2 ‐ κC : κO )SnAr*] [M = Rh ( 13 ), M = Ir ( 15 )] isoliert.
antiSMASH 8.0: extended gene cluster detection capabilities and analyses of chemistry, enzymology, and regulation
2025-04-25

Abstract Microorganisms synthesize small bioactive compounds through their secondary or specialized metabolism. Those compounds play an important role in microbial interactions and soil health, but are also crucial for the development of pharmaceuticals or agrochemicals. Over the past decades, advancements in genome sequencing have enabled the identification of large numbers of biosynthetic gene clusters directly from microbial genomes. Since its inception in 2011, antiSMASH (https://antismash.secondarymetabolites.org/), has become the leading tool for detecting and characterizing these gene clusters in bacteria and fungi. This paper introduces version 8 of antiSMASH, which has increased the number of detectable cluster types from 81 to 101, and has improved analysis support for terpenoids and tailoring enzymes, as well as improvements in the analysis of modular enzymes like polyketide synthases and nonribosomal peptide synthetases. These modifications keep antiSMASH up-to-date with developments in the field and extend its overall predictive capabilities for natural product genome mining.
Lipoprotein(a) as a Stroke Biomarker: Pathophysiological Pathways and Therapeutic Implications
2025-04-25

Lipoprotein(a) [Lp(a)] has attracted widespread interest as a potential biomarker for cerebrovascular diseases due to its genetically determined and stable plasma concentration throughout life. Lp(a) exhibits pro-atherogenic and pro-thrombotic properties that contribute to vascular pathology in both extracranial and intracranial vessels. Elevated Lp(a) levels are strongly associated with large-artery atherosclerotic stroke, while data on its role in other ischemic subtypes and hemorrhagic stroke remains limited and inconsistent. Recent advances in Lp(a)-lowering therapies, such as antisense oligonucleotides and RNA-based agents, have demonstrated significant efficacy in reducing plasma Lp(a) levels. These advances have prompted increasing research into their potential application in the prevention and treatment of cerebrovascular diseases, aiming to determine whether Lp(a) reduction may translate into a reduced risk of stroke and large-artery atherosclerosis. This narrative review summarizes the current evidence on the association between Lp(a) and stroke, focusing on its utility in patient risk stratification. It also highlights existing knowledge gaps and outlines directions for future research, particularly in understanding subtype-specific effects and evaluating the clinical benefits of Lp(a)-targeted therapies.
Inner Branch Off the Shelf Technology for Chronic Post-dissection Thoraco-Abdominal Aneurysm with Narrow True Lumen: Results of a European Multicentre Study
2025-04-25

Endovascular treatment of AD with an off the shelf, inner branched endograft is feasible, with acceptable short and midterm outcomes. The results showed good technical implantation safety and efficacy. Long term follow up results are needed to better define the clinical role of this novel endograft.
The Bombina hybrid zone: a review of the legacy and future research directions
2025-04-25

Abstract Hybrid zones present a unique framework to study the genetic basis of reproductive isolation and speciation. The European fire-bellied toad ( Bombina bombina ) and yellow-bellied toad ( B. variegata ) hybridize in a zone across several thousand kilometres in Central Europe. The Bombina system has been examined for more than a century and its scientific legacy comprises the development of the ‘multilocus cline theory’ and the ‘maintenance of hybrid zones theory’. To set the scene for future genomic research we review the scientific literature on the Bombina hybrid zone, with emphasis on studies that provided insights into genetic processes. Our review emphasises that the two species are highly genetically diverged and reduced hybrid fitness prevents unrestricted gene flow between the two parental species (endogenous selection). However, environmental variables influence the location of hybrid populations (exogenous selection). Depending on region, the transects are described as clinal, tension, mosaic, and residual hybrid zones. The era of genomics has opened a plethora of yet unutilized analytical possibilities in Bombina research, including high resolution population genomics, understanding the genetic basis of reproductive isolation, phenotype-genotype associations, and elucidating the roles of endo- and exogenous selection in maintaining the hybrid zone. Because the hybrid zone occurs across many different environmental settings and genetic backgrounds, it should be possible to distinguish common genetic barriers to gene flow from those arising due to local adaptation. We argue that the Bombina zone offers an excellent opportunity to gain deep genomic insights into the selection processes that maintain the species boundary.
Exploring the Impact of Dyskinetic Crises in GNAO1‐Related Disorders: A Survey for Parents and Caregivers
2025-04-25

Abstract Background GNAO1 ‐related disorders ( GNAO1 ‐RD) encompass developmental delay, epilepsy and movement disorders, including dyskinetic crises. Objectives To explore the characteristics of dyskinetic crises in GNAO1 ‐RD, their impact and the challenges parents face. Methods A cross‐sectional EU survey of 26 parents of children with GNAO1 ‐RD collected demographic, clinical, and management‐related data. Results Dyskinetic crises were experienced by 80% of children. They began at a mean age of 4.17 ± 2.61 years and varied widely in frequency and duration, with triggers including infections and emotions. Dyskinetic crises significantly impacted quality of life (QoL), motor function, and emotional well‐being. Medications were variably effective, and 10 children underwent deep brain stimulation with mixed outcomes. Parents reported challenges in managing crises and accessing support services, with financial burdens. Conclusions Dyskinetic crises in GNAO1 ‐RD significantly impact QoL and present complex management challenges. Variability in outcomes underscores the need for optimized treatment protocols, better coordination, and accessible resources for affected families.
Physical inactivity linked to depressive symptoms in people with and without diabetes: A longitudinal network analysis of health risk behaviours and individual depressive symptoms from the Survey of Health, Ageing and Retirement in Europe
2025-04-25

This study examined cross-sectional (Ising) and longitudinal (cross-lagged panel) networks of depressive symptoms and health risk behaviours in people with diabetes, compared to those without. Participants ( N = 22,510) from the Survey of Health, Ageing and Retirement in Europe with ( n = 1781) and without ( n = 20,729) diabetes with full data on smoking, high alcohol consumption, low fruit and vegetable consumption, physical inactivity and depressive symptoms (EURO-D) were included. Network models indicated that physical inactivity was by far the most closely connected behaviour to depressive symptoms for both groups. Networks were more densely connected for people without diabetes. Differences in whether sleep problems and physical inactivity activated or were activated by depressive symptoms were observed between people with and without diabetes. Identifying structural, symptom-level differences between health risk behaviours and depressive symptoms associated with the presence of diabetes holds potential for informing precision medicine.
Investigation and Kinetic Analysis of Rare Earth Elements Leaching: Case Study of the Weathering Crust of the Kundybay Deposit (Northern Kazakhstan)
2025-04-25

The study investigates the process of intensifying rare earth elements (REEs) group uncovering from the Kundybay deposit (Northern Kazakhstan). Currently, there is no interest in extracting REEs because the ore lying beneath is significantly richer in both rare elements and REEs. However, this type of raw material is a potential source of REEs. The total content of all REEs in the weathering crust is 372.7 ppm; of these, 82.6% are Sc, Y, La, Ce, and Nd, which are present in the form of complex salts and native minerals. In order to find the optimal REE group leaching mode, the influence of the L/S ratio, temperature, acid concentration in the leaching solution, leaching kinetics, and the influence of adding HF and Na2S2O5 on process efficiency were studied. The optimal conditions for REE leaching are as follows: L/S-20, T = 70 °C, t = 180 min. The maximum REE extraction yields, %: Sc-70.84; Y-90.2; La-99.8; Ce-99.24; Nd-97.98. The leaching process kinetic study results show that the process is managed by two steps. The activation energy differences for Sc, Y, La, Ce, and Nd, kJ/mol: 26.19, 23.83, 29.18, 11.15, and 15.13 allow to conclude that REEs in the Kundybay deposit weathering crust are in different forms.
The epidemiology of snakebites, treatment-seeking behaviour, and snakebite management in the department of Ogooué et des Lacs, Gabon, Central Africa: a cross-sectional community and health facility-based survey
2025-04-25

This study provides the first robust epidemiological estimates of the burden of snakebites in Gabon and highlights the importance of community-based surveys in accurately assessing this high burden. Training health care workers, developing treatment guidelines, and ensuring the availability of effective and affordable antivenom are important steps to improving the outcome for snakebite victims.
Full‐Length Cryptochrome 1 in the Outer Segments of the Retinal Blue Cone Photoreceptors in Humans and Great Apes Suggests a Role Beyond Transcriptional Repression
2025-04-25

ABSTRACT Mammalian cryptochrome 1 (CRY1) is a central player in the circadian transcription‐translation feedback loop, crucial for maintaining a roughly 24‐h rhythm. CRY1 was suggested to also function as a blue‐light photoreceptor in humans and has been found to be expressed at the mRNA level in various cell types of the inner retina. However, attempts to detect CRY1 at the protein level in the human retina have remained unsuccessful so far. Using various C‐terminal specific antibodies recognizing full‐length CRY1 protein, we consistently detected selective labeling in the outer segments of short wavelength‐sensitive (SWS1, “blue”) cone photoreceptor cells across human, bonobo, and gorilla retinae. No other retinal cell types were stained, which is in contrast to what would be expected of a ubiquitous clock protein. Subcellular fractionation experiments in transfected HEK cells using a C‐terminal specific antibody located full‐length CRY1 in the cytosol and membrane fractions. Our findings indicate that human CRY1 has several different functions including at least one nonclock function. Our results also raise the likely possibility that several different versions of CRY1 exist in humans. We suggest that truncation of the C‐terminal tail, maybe to different degrees, may affect the localization and function of human CRY1.
Abstract LB024: CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency
2025-04-25

Abstract Chimeric antigen receptor (CAR) T cell therapy has demonstrated promising outcomes in patients with certain refractory hematological malignancies. However, insufficient functional T cell persistence impedes therapeutic success of CAR therapies in a significant number of patients. Here, we performed a CAR-adapted screen of base-edited PIK3CD alleles to optimally calibrate PI3K/AKT signaling in T cells given its critical role in T cell function, metabolism, and fate. Our screen comprised both, prototypic 4-1BBz and CD28z CAR T cells to account for the distinct effector and memory functions imparted to T cells through incorporation of different costimulatory domains in CARs. We identified individual point mutations that induce beneficial CAR T cell profiles through precise balancing of endogenous PI3Kδ signaling strength in 4-1BBz and CD28z CAR T cells, respectively. Remarkably, point mutations with differing effects on PI3Kδ signaling activity were advantageous within the distinct CAR contexts: While 28z CAR T cells profited from attenuated signaling, the PI3Kδ-activating mutation E81K enhanced proliferative capacity, metabolic fitness and effector function in 4-1BBz but not in 28z CAR T cells. E81K-modified BBz CARs ameliorated long-term functional T cell persistence and enhanced therapeutic efficacy in established in vivo models of hematological and solid tumors without evidence of malignant transformation. Together, these data illustrate the importance of tailoring intrinsic T cell signaling capacities to the specific requirements of different CAR designs and demonstrate the potential of base editing to precisely optimize T cell function for bespoke cellular therapies. Citation Format: Josef Leibold, Philip Bucher, Judith Feucht, Nadine Brückner, Jule Kortendieck, Melanie Grimm, Karlotta Bartels, Steffen Hardy, Hannah Wurzer, Meike Thiemann, Celina May, Julia Quach, Nayan Jain, Letizia Quintanilla de Fend, Yu-Jui Ho, Francisco J. Sanchez-Rivera, Jie Sun, Bettina Weigelin, Martina Rausch, Mara Mitstorfer, Irene Gonzalez-Menendez, Michel Sadelain. CAR-adapted PIK3CD base editing enhances T cell anti-tumor potency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB024.
Biotic resistance predictably shifts microbial invasion regimes
2025-04-27

Abstract Invading new territory is a central aspect of the microbial lifestyle. However, invading microbes rarely find novel territories uninhabited; resident microbes can interact with the newcomers and, in many cases, impede their invasion – an effect known as ‘biotic resistance’. Accordingly, invasions are shaped by the interplay between dispersal and resistance. However, these two factors are difficult to disentangle or manipulate in natural systems, making their interplay challenging to understand. To address this challenge, we track microbial invasions in the lab over space and time – first in a model system of two interacting microbes, then in a multi-strain system involving a pathogen invading resident communities. In the presence of biotic resistance, we observe three qualitatively different invasion regimes: ‘consistent’, ‘pulsed’, and ‘pinned’, where, in the third regime, strong biotic resistance stalls the invasion entirely despite ongoing invader dispersal. These rich invasion dynamics could be qualitatively predicted with a simple, parameter-free framework that ignores individual species interactions, even for rather complex communities. Moreover, we show that this simple framework could accurately predict simulated invasions from different mechanistic models, indicating its broad applicability. Our work offers an understanding of how biotic resistance impacts invasions and introduces a predictive tool to identify invasion-resistant communities.
Cognitive Impairment-Associated Risk Factors of Parkinson’s Disease: A Hospital-Based Study in a Cohort of Upper Egypt Parkinson’s Patients
2025-04-27

Background/Objectives: Cognitive impairment (CI) in Parkinson’s disease (PD) is a major burden and significantly affects patients’ quality of life. Previous studies found that older age at onset and presence of the akinetic–rigid (AR) subtype are associated with an increased likelihood of CI in PD. The present study aimed to assess factors that are related to the development of CI in PD. Methods: Eighty-three PD patients were consecutively recruited. Demographic information, clinical details, Montreal cognitive assessment (MoCA), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), walking speed, and instrumental activity of daily living (IADL) were assessed. Resting motor threshold (rMT), was also assessed for subgroup of patients with versus without cognitive impairment. Results: According to the MoCA cut-off score of 26, 45 had PD without CI (PD-NCI) (54.22%) and 38 cases (45.78%) had PD with CI (PD-CI). The age and age at onset were significantly older in the PD-CI group (p = 0.006 and 0.018, respectively). The patients were reclassified into AR and tremor-dominant (TR) phenotype. PD-CI patients were more likely to have the AR (81.6%). Walking speed, MDS-UPDRS score, and IADL scores were significantly worse in PD-CI than in PD-NCI. Stepwise linear regression analysis of risk factors associated CI revealed that higher MDS-UPDRS scores, later age of onset, and higher rMT values were considered risk factors for developing CI. Conclusions: Higher UPDRS score, later age of onset, and higher rMT values were considered as risk factors associated CI in PD patients and provide valuable insights for further investigation and potential clinical considerations.