bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-Himalayan tectono-metamorphic impresses in the Baijnath klippe, Kumaun Himalaya, NW India: Implications on a veiled saga of Paleoproterozoic–Neoproterozoic crustal evolution and thermal history of the northern Indian cratonic margin
Authors: Mukherjee Sneha , Ghosh Gautam , Sorcar Nilanjana , Dev J. Amal , Tomson J.K. , Bose Sankar 
Published: August 2024

Abstract
Rocks of the Lesser Himalayan Sequence are important from a global tectonic perspective as they represent a crucial evolutionary chronicle of the Indian continent from the Paleoproterozoic to the Cenozoic Himalayan orogeny. Eroded remnants of tectonically transported crystalline thrust sheets overlying the Lesser Himalayan metasedimentary zone along the Main Central thrust are represented by the Almora, Baijnath, Askot, and Chiplakot klippen belts in the Kumaun Himalaya, India. In this work, we present the deformation history, geochemistry, and U-Pb zircon-apatite geochronology of the Baijnath klippe rocks and its footwall. Our age and tectonic setting results for the klippe rocks help to illustrate the continental accretion processes that prevailed during Paleoproterozoic–Neoproterozoic time along the northern Indian cratonic margin.
Granitoids within the Baijnath klippen yield crystallization ages varying from ca. 1870 Ma to ca. 1850 Ma, while the supracrustal sequence preserves a prominent age signature of ca. 1855 Ma. The metasediments of the Berinag Formation at the klippe footwall yield a detrital age of ca. 1810 Ma. Based on these results and the geochemistry, we infer that the Baijnath klippe rocks bear an affinity with the inner Lesser Himalayan Sequence, and the granitoid magmatism took place within a span of ~20 m.y. (1870–1850 Ma) in an arc setting linked to active subduction along the north Indian continental margin, possibly due to the formation of the Columbia supercontinent during the Paleoproterozoic. Textural and mineralogical data from the amphibolite-facies supracrustals of the Baijnath klippe suggest that the progressive metamorphism (M1) reached peak at ~580 °C and ~8.6 kbar followed by a decompression-dominated retrogression (M1R) down to ~450 °C and ~5.8 kbar, possibly through a clockwise pressure-temperature (P-T) trajectory that was overprinted by the Cenozoic reworking (M2 metamorphism?) and deformation (D2) related to the Himalayan orogeny. Texturally constrained apatite grains from M1 metamorphic domains preserve traces of a Neoproterozoic-age tectonothermal imprint that affected the Lesser Himalayan Sequence rocks, possibly during the assembly of the Gondwana supercontinent.
Quantitative spectral micro-CT of a CA4+ loaded osteochondral sample with a tabletop system
Authors: Fantoni Simone , Brun Francesco , Cardarelli Paolo , Baruffaldi Fabio , Cristofori Virginia , Taibi Angelo , Trapella Claudio , Brombal Luca 
Published: August 2024

AbstractMicro-computed tomography ($$\upmu$$
μ
CT) is the gold standard for nondestructive 3D imaging of biomedical samples in the centimeter scale, but it has limited effectiveness in revealing intricate soft tissue details due to the limited attenuation contrast. Radiopaque contrast agents that accumulate in the structures of interest are employed to enhance their visibility. However, the increased attenuation provided by the contrast agents does not guarantee discrimination among tissues. This issue can be solved by spectral $$\upmu$$
μ
CT (S$$\upmu$$
μ
CT) systems employing small-pixel chromatic photon-counting detectors. These detectors, combined with material decomposition algorithms, allow the generation of high-resolution material-specific 3D maps. This work aims to demonstrate the potential of photon-counting X-ray S$$\upmu$$
μ
CT on osteochondral samples loaded with a cationic iodinated contrast agent (CA4+) at a spatial resolution below 50 $$\upmu$$
μ
m, and to compare the results against a conventional $$\upmu$$
μ
CT system. An osteochondral sample extracted from a bovine stifle joint was loaded with CA4+ and imaged with a novel multimodal X-ray imaging system, featuring a 62 $$\upmu$$
μ
m pixel CdTe spectral detector (Pixirad1-PixieIII). After material decomposition, quantitative 3D density maps of iodine and hydroxyapatite were reconstructed. The same sample was also scanned with a commercial $$\upmu$$
μ
CT scanner with matched spectrum and exposure time. SCT$$\upmu$$
μ
images at a (measured) spatial resolution comparable with the commercial scanner ($$\sim$$
∼
45 $$\upmu$$
μ
m) were obtained. Spectral images allowed for a fully automatic segmentation of cartilage and subchondral bone. The unambiguous discrimination between iodine and hydroxyapatite revealed a more realistic representation of proteoglycan distribution compared to conventional imaging.
Transcriptomic Heterogeneity of EGFR-Mutant Non–Small Cell Lung Cancer Evolution Toward Small-Cell Lung Cancer
Authors: Oh Songji , Koh Jaemoon , Kim Tae Min , Kim Soyeon , Youk Jeonghwan , Kim Miso , Keam Bhumsuk , Jeon Yoon Kyung , Ku Ja-Lok , Kim Dong-Wan , Chung Doo Hyun , Heo Dae Seog 
Published: August 2024

Abstract

Purpose:
Histologic transformation from EGFR-mutant non–small cell lung cancer (NSCLC) to small-cell lung cancer (SCLC) is a key mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI). However, transcriptomic changes between NSCLC and transformed SCLC (t-SCLC) remain unexplored.

Experimental Design:
We conducted whole-transcriptome analysis of 59 regions of interest through the spatial profiling of formalin-fixed, paraffin-embedded tissues obtained from 10 patients (lung adenocarcinoma, 22; combined SCLC/NSCLC, 7; and t-SCLC, 30 regions of interests). Transcriptomic profiles and differentially expressed genes were compared between pre- and post-transformed tumors.

Results:
Following EGFR-TKI treatment, 93.7% (15/16) of t-SCLC components evolved into neuroendocrine-high subtypes (SCLC-A or SCLC-N). The transition to t-SCLC occurred regardless of EGFR-TKI treatment and EGFR mutational status, with a notable decrease in EGFR expression (P &lt; 0.001) at both mRNA and protein levels. Pathway analysis revealed that gene overexpression was related to epigenetic alterations in t-SCLC. Interestingly, histone deacetylase inhibitors restored EGFR expression in SNU-2962A cells and their organoid model. The synergistic effects of third-generation EGFR-TKI osimertinib and the histone deacetylase inhibitor fimepinostat were validated in both in vitro and in vivo models.

Conclusions:
Our study demonstrated that most t-SCLC cases showed neuronal subtypes with low EGFR expression. Differentially expressed gene analysis and t-SCLC preclinical models identified an epigenetic modifier as a promising treatment strategy for t-SCLC.
YAP1 Status Defines Two Intrinsic Subtypes of LCNEC with Distinct Molecular Features and Therapeutic Vulnerabilities
Authors: Stewart C. Allison , Diao Lixia , Xi Yuanxin , Wang Runsheng , Ramkumar Kavya , Serrano Alejandra G. , Tanimoto Azusa , Rodriguez B. Leticia , Morris Benjamin B. , Shen Li , Zhang Bingnan , Yang Yan , Hamad Samera H. , Cardnell Robert J. , Duarte Alberto , Sahu Moushumi , Novegil Veronica Y. , Weissman Bernard E. , Frumovitz Michael , Kalhor Neda , Solis Soto Luisa , da Rocha Pedro , Vokes Natalie , Gibbons Don L. , Wang Jing , Heymach John V. , Glisson Bonnie , Byers Lauren Averett , Gay Carl M. 
Published: August 2024

Abstract

Purpose:
Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with the absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies, which are often adapted from SCLC and non–small cell lung cancer approaches.

Experimental Design:
To better define the biology of LCNEC, we analyzed cell line and patient genomic data and performed IHC and single-cell RNA sequencing of core needle biopsies from patients with LCNEC and preclinical models.

Results:
In this study, we demonstrate that the presence or absence of YAP1 distinguishes two subsets of LCNEC. The YAP1-high subset is mesenchymal and inflamed and is characterized, alongside TP53 mutations, by co-occurring alterations in CDKN2A/B and SMARCA4. Therapeutically, the YAP1-high subset demonstrates vulnerability to MEK- and AXL-targeting strategies, including a novel preclinical AXL chimeric antigen receptor–expressing T cell. Meanwhile, the YAP1-low subset is epithelial and immune-cold and more commonly features TP53 and RB1 co-mutations, similar to those observed in pure SCLC. Notably, the YAP1-low subset is also characterized by the expression of SCLC subtype–defining transcription factors, especially ASCL1 and NEUROD1, and as expected, given its transcriptional similarities to SCLC, exhibits putative vulnerabilities reminiscent of SCLC, including delta-like ligand 3 and CD56 targeting, as is with novel preclinical delta-like ligand 3 and CD56 chimeric antigen receptor–expressing T cells, and DNA damage repair inhibition.

Conclusions:
YAP1 defines distinct subsets of LCNEC with unique biology. These findings highlight the potential for YAP1 to guide personalized treatment strategies for LCNEC.
Harnessing the Potential of FAP-IL12mut TMEkine for Targeted and Enhanced Antitumor Responses
Authors: Lee Dahea , Kim Dongsu , Kim Donggeon , Kang Jisu , Lee Kiram , Lee Hyunji , Yoon Yujin , Lee Youngin , Kim Nahmju , Cho Byoung Chul , Chang Jihoon , Lee Byoung Chul 
Published: August 2024

Abstract
Although cancer immunotherapy has yielded encouraging outcomes in hematologic malignancies, it has faced challenges in achieving the same level of effectiveness in numerous solid tumors, primarily because of the presence of immunosuppressive tumor microenvironments (TME). The immunosuppressive qualities of the TME have generated considerable interest, making it a focal point for treatments aimed at enhancing immune responses and inhibiting tumor progression. Fibroblast activation protein (FAP), an attractive candidate for targeted immunotherapy, is prominently expressed in the TME of various solid tumors. IL12, recognized as a key mediator of immune responses, has been explored as a potential candidate for cancer treatment. Nevertheless, initial efforts to administer IL12 systemically demonstrated limited efficacy and notable side effects, emphasizing the necessity for innovation. To address these concerns, our molecules incorporated specific IL12 mutations, called IL12mut, which reduced toxicity. This study explored the therapeutic potential of the FAP-IL12mut TMEkine—a novel immunotherapeutic agent selectively engineered to target FAP-expressing cells in preclinical cancer models. Our preclinical results, conducted across diverse murine cancer models, demonstrated that FAP-IL12mut significantly inhibits tumor growth, enhances immune cell infiltration, and promotes a shift toward a cytotoxic immune activation profile. These findings suggest that FAP-IL12mut could offer effective cancer treatment strategies.
Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models
Authors: Wu Jin , Wang Jianxin , O’Connor Thomas N. , Tzetzo Stephanie L. , Gurova Katerina V. , Knudsen Erik S. , Witkiewicz Agnieszka K. 
Published: August 2024

Abstract
The combination of CDK4/6 and MEK inhibition as a therapeutic strategy has shown promise in various cancer models, particularly in those harboring RAS mutations. An initial high-throughput drug screen identified high synergy between the CDK4/6 inhibitor palbociclib and the MEK inhibitor trametinib when used in combination in soft tissue sarcomas. In RAS mutant models, combination treatment with palbociclib and trametinib induced significant G1 cell cycle arrest, resulting in a marked reduction in cell proliferation and growth. CRISPR-mediated RB1 depletion resulted in a decreased response to CDK4/6 and MEK inhibition, which was validated in both cell culture and xenograft models. Beyond its cell cycle inhibitory effects, pathway enrichment analysis revealed the robust activation of interferon pathways upon CDK4/6 and MEK inhibition. This induction of gene expression was associated with the upregulation of retroviral elements. The TANK-binding kinase 1 inhibitor GSK8612 selectively blocked the induction of interferon-related genes induced by palbociclib and trametinib treatment and highlighted the separable epigenetic responses elicited by combined CDK4/6 and MEK inhibition. Together, these findings provide key mechanistic insights into the therapeutic potential of CDK4/6 and MEK inhibition in soft tissue sarcomas.
How Perception, Actuation, and Communication Impact the Emergence of Collective Intelligence in Simulated Modular Robots
Authors: Rusin Francesco , Medvet Eric 
Published: August 2024

Abstract
Modular robots are collections of simple embodied agents, the modules, that interact with each other to achieve complex behaviors. Each module may have a limited capability of perceiving the environment and performing actions; nevertheless, by behaving coordinately, and possibly by sharing information, modules can collectively perform complex actions. In principle, the greater the actuation, perception, and communication abilities of the single module are the more effective is the collection of modules. However, improved abilities also correspond to more complex controllers and, hence, larger search spaces when designing them by means of optimization. In this article, we analyze the impact of perception, actuation, and communication abilities on the possibility of obtaining good controllers for simulated modular robots, that is, controllers that allow the robots to exhibit collective intelligence. We consider the case of modular soft robots, where modules can contract, expand, attach, and detach from each other, and make them face two tasks (locomotion and piling), optimizing their controllers with evolutionary computation. We observe that limited abilities often do not prevent the robots from succeeding in the task, a finding that we explain with (a) the smaller search space corresponding to limited actuation, perception, and communication abilities, which makes the optimization easier, and (b) the fact that, for this kind of robot, morphological computation plays a significant role. Moreover, we discover that what matters more is the degree of collectivity the robots are required to exhibit when facing the task.
Evidence for a sustained cerebrovascular response following motor practice
Authors: Patitucci Eleonora , Di Censo Davide , Chiarelli Antonio M. , Germuska Michael , Tomassini Valentina , Wise Richard G. 
Published: August 2024

Abstract
Motor tasks have been extensively used to probe neuroplasticity and the changes in MRI signals are often associated with changes in performance. Changes in performance have been linked to alterations in resting-state fluctuations of BOLD signal after the end of the task. We hypothesize that motor learning will induce localized changes in cerebral blood flow (CBF) sustained even after the execution of a motor learning task. We implemented a new motor task to probe neuroplasticity and mapped the associated cerebrovascular responses. Twenty healthy volunteers underwent two MRI sessions 1-week apart: a task session with a sequence learning task performed with a data glove and a control session. During each session, CBF and BOLD signals were acquired during the task and during two periods of rest, each lasting 8 min, before and after execution of the task. Evoked BOLD and CBF responses to the motor task were seen to decrease in a regionally specific manner as the task proceeded and performance accuracy improved. We observed a localized increase in resting CBF in the right extra-striate visual area that was sustained during the 8-min rest period after the completion of the motor learning task. CBF increase in the area was accompanied by a regional increase in local BOLD signal synchronization. Our observation suggests an important connection between neuroplastic changes induced by learning and sustained perfusion in the apparently resting brain followed task completion.
FAST functional connectivity implicates P300 connectivity in working memory deficits in Alzheimer’s disease
Authors: Roy Om , Moshfeghi Yashar , Ibanez Agustin , Lopera Francisco , Parra Mario A. , Smith Keith M. 
Published: August 2024

Abstract
Measuring transient functional connectivity is an important challenge in electroencephalogram (EEG) research. Here, the rich potential for insightful, discriminative information of brain activity offered by high-temporal resolution is confounded by the inherent noise of the medium and the spurious nature of correlations computed over short temporal windows. We propose a methodology to overcome these problems called filter average short-term (FAST) functional connectivity. First, a long-term, stable, functional connectivity is averaged across an entire study cohort for a given pair of visual short-term memory (VSTM) tasks. The resulting average connectivity matrix, containing information on the strongest general connections for the tasks, is used as a filter to analyze the transient high-temporal resolution functional connectivity of individual subjects. In simulations, we show that this method accurately discriminates differences in noisy event-related potentials (ERPs) between two conditions where standard connectivity and other comparable methods fail. We then apply this to analyze an activity related to visual short-term memory binding deficits in two cohorts of familial and sporadic Alzheimer’s disease (AD)-related mild cognitive impairment (MCI). Reproducible significant differences were found in the binding task with no significant difference in the shape task in the P300 ERP range. This allows new sensitive measurements of transient functional connectivity, which can be implemented to obtain results of clinical significance.
Generative dynamical models for classification of rsfMRI data
Authors: Huckins Grace , Poldrack Russell A. 
Published: August 2024

Abstract
The growing availability of large-scale neuroimaging datasets and user-friendly machine learning tools has led to a recent surge in studies that use fMRI data to predict psychological or behavioral variables. Many such studies classify fMRI data on the basis of static features, but fewer try to leverage brain dynamics for classification. Here, we pilot a generative, dynamical approach for classifying resting-state fMRI (rsfMRI) data. By fitting separate hidden Markov models to the classes in our training data and assigning class labels to test data based on their likelihood under those models, we are able to take advantage of dynamical patterns in the data without confronting the statistical limitations of some other dynamical approaches. Moreover, we demonstrate that hidden Markov models are able to successfully perform within-subject classification on the MyConnectome dataset solely on the basis of transition probabilities among their hidden states. On the other hand, individual Human Connectome Project subjects cannot be identified on the basis of hidden state transition probabilities alone—although a vector autoregressive model does achieve high performance. These results demonstrate a dynamical classification approach for rsfMRI data that shows promising performance, particularly for within-subject classification, and has the potential to afford greater interpretability than other approaches.
Freshwater crabs from Crete: a unique key for the reconstruction of the biogeographical history of Potamon Savigny, 1816 (Brachyura, Potamidae) in the Aegean region
Authors: Gruetzke Svetlana , Ewers Christine , Klaus Sebastian , Brandis Dirk 
Published: August 2024

Abstract
The Aegean region is biogeographically complex for freshwater crabs of the genus Potamon Savigny, 1816. Especially Potamon kretaion Giavarini, 1943 has a remarkably different distribution pattern compared to its congeners: With its exclusive occurrence on the island of Crete, it is the only Potamon species that is endemic to an Aegean island, and its range is geographically disjunct from its sister group, including Potamon ibericum (Bieberstein, 1809) and Potamon bilobatum Brandis, Storch and Türkay, 2000, with a Ponto-Caspian distribution. In addition, the morphology of the first gonopods differs substantially from that of closely related species. Therefore, the aim of this study was to (1) develop a new plausible hypothesis for the dispersal history of the genus Potamon into the Aegean area based on a re-analysis of gonopodal characters and existing phylogenetic data, and under consideration of recent palaeogeographical hypotheses, and (2) test whether the first gonopods of P. kretaion — being substantially different from its closest relatives — represent the ancestral or derived character state within Aegean Potamon. The results revealed a close link between the distribution of freshwater crabs and the biogeographical history of the Aegean region and that P. kretaion shows plesiomorphic characteristics of the first gonopods. These findings indicate that the original population of Pontipotamon (including P. kretaion) was isolated on Crete about 9 Mya, spread northwards during the Messinian salinity crisis and was separated in the original populations of P. kretaion and P. ibericum by the flooding of the Mediterranean Sea 5.33 Mya.
Evolutionary transitions of decapod crustaceans to non-marine, polar, and deep-sea environments: developmental, physiological and biochemical adaptations
Authors: Anger Klaus , Urzúa Ángel 
Published: August 2024

Abstract
In this brief, non-exhaustive essay, we review major adaptive changes in reproductive and developmental traits of decapod crustaceans, which have passed through evolutionary transitions from ancestral life in coastal marine environments to brackish, limnic, polar, or deep-sea habitats. Two major approaches can be recognised in studies of life-history evolution, focussing on: (1) developmental changes in adaptive physiological or biochemical traits of successive ontogenetic stages, comparing, for instance, osmoregulatory capabilities in larvae, juveniles, and adults (“ontogeny of adaptations” perspective); (2) adaptive changes in the modes of reproduction and development, e.g., enhanced maternal energy investment in egg production, abbreviated, non-feeding larval development (“adaptations in ontogeny”). Using both scientific approaches, Christoph D. Schubart has significantly contributed to our understanding of evolutionary transitions in crustaceans. In our essay, we pay particular attention to the significance of nutritional selection factors in relation to presumably adaptive developmental, physiological, and biochemical traits in different life-history stages. In this context, we highlight the key roles of lipids and carotenoid pigments, in particular of essential polyunsaturated fatty acids (PUFAs) and astaxanthin. While PUFAs and other lipid compounds have received wide scientific attention, we propose that future studies should further analyse also the potential role of astaxanthin and other essential carotenoids.