bluuebunny/crossref_metadata_2025 huggingface dataset:
Cis Feminist Moves to Innocence
Authors: Berenstain Nora
Published: January 2024

Cis feminist theorists sometimes employ rhetorical moves to claim innocence while abdicating responsibility for engaging with trans scholarship and theory as well as structural transmisogyny. I suggest that it is helpful to understand this phenomenon using a conception of cis feminist moves to innocence. These rhetorical moves enable cisgender feminists to falsely position their failure to engage with both trans scholarship and structures of transmisogyny as epistemically virtuous.
High-Prandtl-number thermocapillary liquid bridges with dynamically deformed interface: effect of an axial gas flow on the linear stability
Authors: Stojanović Mario , Romanò Francesco , Kuhlmann Hendrik C.
Published: January 2024

The linear stability of the axisymmetric steady flow in a thermocapillary liquid bridge made from 2-cSt silicone oil

$({Pr}=28)$

is investigated numerically. The liquid bridge is heated either from above or below and exposed to an axial air flow which is confined to a concentric tube surrounding the bridge. At the annular inlet, the air flow is fully developed and has the same temperature as the adjacent support rod. Using an extended Oberbeck–Boussinesq approximation in which the density of both fluids depends linearly on the temperature in all equations, critical thermocapillary Reynolds numbers are obtained depending on the strength of the imposed axial air flow. The critical conditions are sensitive with respect to the direction of a weak air flow, because the air flow changes the plateau value of the interfacial temperature midway between the hot and cold ends. For stronger air flow the critical thermocapillary Reynolds number almost saturates at moderate values. Throughout, the instability arises as a hydrothermal wave with the gas phase being passive. The dynamic interface deformations for axisymmetric flow caused by the thermocapillarity flow in the liquid and by the stresses from the air flow are considered separately. Apart from turning points of the critical curve, the impact of dynamic surface deformations on the critical thermocapillary Reynolds number is moderate.
THE BAIRE CLOSURE AND ITS LOGIC
Authors: BEZHANISHVILI G. , FERNÁNDEZ-DUQUE D.
Published: January 2024

The Baire algebra of a topological space X is the quotient of the algebra of all subsets of X modulo the meager sets. We show that this Boolean algebra can be endowed with a natural closure operator, resulting in a closure algebra which we denote
$\mathbf {Baire}(X)$
. We identify the modal logic of such algebras to be the well-known system
$\mathsf {S5}$
, and prove soundness and strong completeness for the cases where X is crowded and either completely metrizable and continuum-sized or locally compact Hausdorff. We also show that every extension of
$\mathsf {S5}$
is the modal logic of a subalgebra of
$\mathbf {Baire}(X)$
, and that soundness and strong completeness also holds in the language with the universal modality.
Evaluation of suitable reference genes for expression profile analyses of target genes in the coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae)
Authors: Zhang Shaohua , Zhu Enhang , Wang Zheng , Zhong Yaofeng , Zha Xuezong , Ji Hengqing , Meng Qianqian
Published: January 2024

The coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae), is a major destructive insect pest of coffee, which impacts the coffee crops negatively. As a draft genome has been completed for this insect, most molecular studies on gene transcriptional levels under different experimental conditions will be conducted using real-time reverse-transcription quantitative polymerase chain reactions (RT-qPCR). However, the lack of suitable internal reference genes will affect the accuracy of RT-qPCR results. In this study, the expression stability of nine candidate reference genes was evaluated under different developmental stages, temperature stress, and Beauveria bassiana infection. Data analyses were completed by four commonly used programs, BestKeeper, NormFinder, geNorm, and RefFinder. The result showed that RPL3 and EF1α combination were recommended as the most stable reference genes for developmental stages. EF1α and RPS3a combination were the top two stable reference genes for B. bassiana infection. RPS3a and RPL3 combination performed as the optimal reference genes both in temperature stress and all samples. Our results should provide a good foundation for the expression profile analyses of target genes in the future, especially for molecular studies on insect genetic development, temperature adaptability, and immune mechanism to entomogenous fungi in H. hampei.
Colonialism and Nationalism in Hong Kong: Towards True Decolonization
Authors: Tam Gina Anne
Published: January 2024

In June of 2019, millions of Hong Kongers took to the streets. What began as a protest against an extradition bill quickly evolved into a broader movement to safeguard Hong Kong’s autonomy from the People’s Republic of China (PRC). Protesters pointed with increasing alarm to the fast disappearance of Hong Kong’s distinct legal system, political system, and civic culture as well as the erosion of the borders, both physical and abstract, that separated the territory from the mainland. The 1997 handover was designed to safeguard Hong Kong’s local autonomy after the end of British colonialism, these demonstrators claimed, and Beijing’s government was threatening that promise.
Global Maoism and the Decolonization of China’s History
Authors: Evans James Gethyn
Published: January 2024

Charu Mazumdar seemed like an unlikely leader for a violent guerilla organization. Born into a family of landlords in India’s West Bengal in 1918, his slender frame gave him the look of someone more used to studying than directing armed insurgency. Yet, Mazumdar justified his violent leadership in West Bengal during the 1960s and 1970s by referencing the writings of Mao Zedong – known collectively as Mao Zedong Thought or Maoism – as inspiration for his revolutionary actions. Mazumdar declared that ‘the foremost duty of [Indian] revolutionaries is to spread and propagate the thought of Chairman Mao’, and that ‘China’s path is our path, China’s chairman is our chairman.’ While Mazumdar had no claim to Chinese ethnic or linguistic belonging, his activities – along with the actions of thousands of others – manifested as a result of the transnational connections and entanglements between Maoism, its translation and propagation by the Chinese Communist Party (CCP), and its reception by revolutionaries across the world.
Characterization of the violence between Türkiye and the PKK
Authors: Kurtuluş Şehmus
Published: January 2024

This article addresses the question of whether the violence between Türkiye and the Kurdistan Worker’s Party (PKK) constitutes an armed conflict within the meaning of international humanitarian law. The article first explains the different non-international armed conflict descriptions provided by (i) the ICTY’s famous Tadić decision, (ii) Additional Protocol II, and (iii) the Rome Statute of the ICC and discusses the different applicability thresholds set by these sources. After noting that the terrorist nature of the acts of violence in a situation will not prevent them from being characterized as an armed conflict and that the application of the international humanitarian law norms would not in fact affect the legal status of the PKK, this article examines whether Türkiye’s struggle against the PKK could be classified as an armed conflict subject to international humanitarian law norms.
A year’s a long time in generative AI
Authors: Dale Robert
Published: January 2024

A lot has happened since OpenAI released ChatGPT to the public in November 2022. We review how things unfolded over the course of the year, tracking significant events and announcements from the tech giants leading the generative AI race and from other players of note; along the way we note the wider impacts of the technology’s progress.
Is rape a crime in Japan?
Authors: Johnson David T.
Published: January 2024

Japan is often said to have one of the lowest rape rates in the world, and Japanese police claim to solve 97 percent of rape cases. But in reality, only 5–10 percent of rape victims report it to police, and police record half or less of reported cases while prosecutors charge about one-third of recorded cases. The result of this process of caseload attrition is that for every 1,000 rapes in Japan, only 10–20 result in a criminal conviction – and fewer than half of convicted rapists are incarcerated. Similar patterns characterize Japan's criminal justice response to other sex crimes. This article shows that impunity for sex offenders is extremely common in Japan, and it argues that patriarchal social and legal norms help explain this pattern.
Wideband design and modeling of efficient multi-resonance reflective linear-to-circular polarization converter
Authors: Zaker Reza , Jolani Farid
Published: January 2024

A reflective linear-to-circular polarization converter based on dual frequency-selective structures (FSSs) is proposed and modeled to exhibit efficient wideband performance. The design utilizes a diagonal array of two connected circular patches as an effective anisotropy with regular current distribution in several successive resonances, resulting in orthogonal reflections with a 90° phase difference. The relevant upper-part characteristic is improved by using two separate square patches as a high-frequency resonator. This design with distinct key parameters leads to high overlapping and then excellent bandwidth and efficiency over 105% and 96%, respectively, with an axial ratio below 1.7 dB. A sophisticated equivalent circuit-admittance model including effective mutual coupling between two FSSs is extracted, featuring closed-form equations for the physical design. Different dielectric constants are studied on the converter, which offer controllable coverage in the range of 3–24 GHz (S, C, X, Ku, and K bands), variably. For actual validation, a very thin (0.04λ0 at 3.65 GHz) 8 × 8 array prototype was built and measured at different incident angles, showing angular stability up to 45° in 78% (6–14 GHz) bandwidth. This converter has potential applications in communication, spectroscopy, detection, and imaging in micro-, mm-, and THz-wave regions.
A Hybrid Gain Analog Offline EnKF for Paleoclimate Data Assimilation
Authors: Sun Haohao , Lei Lili , Liu Zhengyu , Ning Liang , Tan Zhe‐Min
Published: January 2024

For Paleoclimate data assimilation (PDA), a hybrid gain analog offline ensemble Kalman filter (HGAOEnKF) is proposed. It keeps the benefits of the analog offline ensemble Kalman filter (AOEnKF) that constructs analog ensembles from existing climate simulations with joint information of the proxies. The analog ensembles can provide more accurate prior ensemble mean and “flow‐dependent” error covariances than randomly sampled ensembles. HGAOEnKF further incorporates the benefits of static prior error covariances that better capture large‐scale error correlations and mitigate sampling errors than the sample prior error covariances, through a hybrid gain approach within an ensemble framework. Observing system simulation experiments are conducted for various data assimilation methods, using ensemble simulations from the Community Earth System Model‐Last Millennium Ensemble Project. Results show that using the static prior error covariances estimated from a sufficiently large sample set is beneficial for the traditional offline ensemble Kalman filter (OEnKF) and AOEnKF. HGAOEnKF method is superior to the OEnKF and AOEnKF with and without static prior error covariances, especially for the reconstruction of extreme events. The advantages of HGAOEnKF over OEnKF and AOEnKF with and without static prior error covariances are persistent with varying sample sizes and presence of model errors.
Tradeoffs Between Temporal and Spatial Pattern Calibration and Their Impacts on Robustness and Transferability of Hydrologic Model Parameters to Ungauged Basins
Authors: Demirel M. C. , Koch J. , Rakovec O. , Kumar R. , Mai J. , Müller S. , Thober S. , Samaniego L. , Stisen S.
Published: January 2024

Optimization of spatially consistent parameter fields is believed to increase the robustness of parameter estimation and its transferability to ungauged basins. The current paper extends previous multi‐objective and transferability studies by exploring the value of both multi‐basin and spatial pattern calibration of distributed hydrologic models as compared to single‐basin and single‐objective model calibrations, with respect to tradeoffs, performance and transferability. The mesoscale Hydrological Model (mHM) is used across six large central European basins. Model simulations are evaluated against streamflow observations at the basin outlets and remotely sensed evapotranspiration patterns. Several model validation experiments are performed through combinations of single‐ (temporal evaluation through discharge) and multi‐objective (temporal and spatial evaluation through discharge and spatial evapotranspiration patterns) calibrations with holdout experiments saving alternating basins for model evaluation. The study shows that there are very minimal tradeoffs between spatial and temporal performance objectives and that a joint calibration of multiple basins using multiple objective functions provides the most robust estimations of parameter fields that perform better when transferred to ungauged basins. The study indicates that particularly the multi‐basin calibration approach is key for robust parametrizations, and that the addition of an objective function tailored for matching spatial patterns of ET fields alters the spatial parameter fields while significantly improving the spatial pattern performance without any tradeoffs with discharge performance. In light of model equifinality, the minimal tradeoff between spatial and temporal performance shows that adding spatial pattern evaluation to the traditional temporal evaluation of hydrological models can assist in identifying optimal parameter sets.
Downslope Weakening of Soil Revealed by a Rapid Robotic Rheometer
Authors: Ruck John G. , Wilson Cristina G. , Shipley Thomas , Koditschek Daniel , Qian Feifei , Jerolmack Douglas
Published: January 2024

Moving down a hillslope from ridge to valley, soil develops and becomes increasingly weathered. Downslope variation in clay content, organic matter, and porosity should produce concomitant changes in soil strength that influence slope stability and erosion. This has yet to be demonstrated, however, because in situ measurements of soil rheology are challenging and rare. Here we employ a robotic leg as a mechanically sensitive and time‐efficient penetrometer to map soil strength along a canonical temperate hillslope profile. We observe a systematic downslope weakening, and increasing heterogeneity, of soil strength associated with a transition from sand‐rich ridge materials to cohesive valley bottom soil aggregates. Weathering‐induced changes in soil composition lead to physically distinct mechanical behaviors in cohesive soils that depart from the behavior observed for sand. We also demonstrate the promise that legged robots may use their limbs to sense and improve mobility in complex environments, with implications for planetary exploration.
Spatial Patterns and Controls on Wind Erosion in the Great Basin
Authors: Treminio Ronald S. , Webb Nicholas P. , Edwards Brandon L. , Faist Akasha , Newingham Beth , Kachergis Emily
Published: January 2024

The Great Basin of the western United States is experiencing dramatic increases in wildfire and Bromus species invasion that potentially accelerate wind erosion and plant community change. We used a wind erosion model parameterized for rangelands and standard ecological monitoring data sets collected at 10,779 locations from 2011 to 2019 to characterize potential wind erosion in the Great Basin, assess relationships between factors affecting wind erosion, and quantify effects of wildfire and invasive Bromus species on aeolian horizontal sediment flux, Q. There were 403 monitoring plots (∼3.7% of plots) with Q > 100 g m−1 d−1. Median values for the highest Q category (>100) ranged from 196.5 to 308.5 g m−1 d−1. Locations with Q > 100 g m−1 d−1 were associated with dry, low elevation areas of the Great Basin with low perennial grass and perennial forb cover, and with large bare gaps between plants. Areas with high perennial grass, perennial forb, and shrub cover had small Q (≤10 g m−1 d−1). Substantial wind erosion was predicted in areas that have experienced wildfires, but areas with multiple wildfires had a lower predicted probability of Q particularly as invasive Bromus species cover increased. Modeled Q was up to two orders of magnitude higher post‐wildfire (median 44.2 g m−1 d−1) than in intact or annual grass‐invaded regions of the Great Basin (median 0.4 g m−1 d−1). Our results reveal the complex interplay among plant community composition, wildfire, and the amount of bare ground controlling wind erosion on Great Basin rangelands.
Harnessing upregulated E-selectin while enhancing SDF-1α sensing redirects infused NK cells to the AML-perturbed bone marrow
Authors: Sanz-Ortega Laura , Andersson Agneta , Carlsten Mattias
Published: January 2024

Increased bone marrow (BM) homing of NK cells is associated with positive outcome in patients with acute myeloid leukemia (AML) treated within adoptive NK cell transfer trials. While most efforts to further improve the efficacy focus on augmenting NK cell persistence and cytotoxicity, few address their ability to home to the tumor. Here, we decipher how AML growth alters the BM niche to impair NK cell infiltration and how insights can be utilized to resolve this issue. We show that AML development gradually impairs the BM homing capacity of infused NK cells, which was tightly linked to loss of SDF-1α in this environment. AML development also triggered up-regulation of E-selectin on BM endothelial cells. Given the poor E-selectin-binding capacity of NK cells, introduction of fucosyltransferase-7 (FUT7) to the NK cells per mRNA transfection resulted in potent E-selectin binding and stronger adhesion to E-selectin+ endothelial cells. Co-introduction of FUT7 and gain-of-function CXCR4 (CXCR4R334X) redirected NK cell homing to the BM of AML-bearing mice nearly to the levels in AML-free mice. This work shows how impaired NK cell homing caused by AML-induced microenvironmental changes can be overcome by genetic engineering. We speculate our insights can help further advance future NK cell immunotherapies.
Ultrahigh-fidelity spatial mode quantum gates in high-dimensional space by diffractive deep neural networks
Authors: Wang Qianke , Liu Jun , Lyu Dawei , Wang Jian
Published: January 2024

While the spatial mode of photons is widely used in quantum cryptography, its potential for quantum computation remains largely unexplored. Here, we showcase the use of the multi-dimensional spatial mode of photons to construct a series of high-dimensional quantum gates, achieved through the use of diffractive deep neural networks (D2NNs). Notably, our gates demonstrate high fidelity of up to 99.6(2)%, as characterized by quantum process tomography. Our experimental implementation of these gates involves a programmable array of phase layers in a compact and scalable device, capable of performing complex operations or even quantum circuits. We also demonstrate the efficacy of the D2NN gates by successfully implementing the Deutsch algorithm and propose an intelligent deployment protocol that involves self-configuration and self-optimization. Moreover, we conduct a comparative analysis of the D2NN gate’s performance to the wave-front matching approach. Overall, our work opens a door for designing specific quantum gates using deep learning, with the potential for reliable execution of quantum computation.
Highly efficient and aberration-free off-plane grating spectrometer and monochromator for EUV—soft X-ray applications
Authors: Li Jie , Li Kui , Zhang Xiaoshi , Popmintchev Dimitar , Xu Hao , Wang Yutong , Li Ruixuan , Zhang Guangyin , Tang Jiyue , Niu Jin , Ma Yongjun , Meng Runyu , Ke Changjun , Qiu Jisi , Ma Yunfeng , Popmintchev Tenio , Fan Zhongwei
Published: January 2024

We demonstrate a novel flat-field, dual-optic imaging EUV—soft X-ray spectrometer and monochromator that attains an unprecedented throughput efficiency exceeding 60% by design, along with a superb spectral resolution of λ/Δλ > 200 accomplished without employing variable line spacing gratings. Exploiting the benefits of the conical diffraction geometry, the optical system is globally optimized in multidimensional parameter space to guarantee optimal imaging performance over a broad spectral range while maintaining circular and elliptical polarization states at the first, second, and third diffraction orders. Moreover, our analysis indicates minimal temporal dispersion, with pulse broadening confined within 80 fs tail-to-tail and an FWHM value of 29 fs, which enables ultrafast spectroscopic and pump-probe studies with femtosecond accuracy. Furthermore, the spectrometer can be effortlessly transformed into a monochromator spanning the EUV—soft X-ray spectral region using a single grating with an aberration-free spatial profile. Such capability allows coherent diffractive imaging applications to be conducted with highly monochromatic light in a broad spectral range and extended to the soft X-ray region with minimal photon loss, thus facilitating state-of-the-art imaging of intricate nano- and bio-systems, with a significantly enhanced spatiotemporal resolution, down to the nanometer–femtosecond level.
Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer
Authors: Zhang Yu , Liu Liang , Pei Jinpeng , Ren Zhiqiang , Deng Yan , Yu Ker
Published: January 2024

The recently approved KRASG12C mutation-specific inhibitors sotorasib and adagrasib (KRASG12C-I) represent a promising therapy for KRASG12C-driven non-small cell lung cancer (NSCLC). However, many eligible patients do not benefit due to intrinsic or acquired drug resistance. Tissue factor (TF) is overexpressed in KRAS-mutated (KRASmut) NSCLC and is the target of the FDA-approved ADC Tivdak. Here, we employed HuSC1-39, the parent antibody of a clinical stage TF-ADC (NCT04843709), to investigate the role of TF in KRASmut NSCLC. We found that patients with TF-overexpression had poor survival, elevated P-ERK/P-AKT activity levels and low immune effector cell infiltration in the tumor. In a panel of KRASG12C cell lines, KRASG12C-I response correlated with suppression of TF mRNA, which was not observed in resistant cells. In the drug resistant cells, TF-overexpression relied on an mTORC2-mediated and proteasome-dependent pathway. Combination treatment of HuSC1-39 or mTORC1/2 inhibitor MTI-31 with KRASG12C-I each produced synergistic antitumor efficacy in cell culture and in an orthotopic lung tumor model. TF-depletion in the resistant cells diminished epithelial mesenchymal transition, reduced tumor growth and greatly sensitized KRASG12C-I response. Moreover, employing immunohistochemistry and coculture studies, we demonstrated that HuSC1-39 or MTI-31 reset the tumor microenvironment and restore KRASG12C-I sensitivity by reshaping an M1-like macrophage profile with greatly enhanced phagocytic capacity toward tumor cell killing. Thus, we have identified the TF/mTORC2 axis as a critical new mechanism for triggering immunosuppression and KRASG12C-I resistance. We propose that targeting this axis with HuSC1-39 or MTI-31 will improve KRASG12C-I response in KRAS-driven NSCLC.
HPV-associated oropharyngeal cancer: in search of surrogate biomarkers for early lesions
Authors: Lim Yvonne X. , D’Silva Nisha J.
Published: January 2024

The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early cancer screening is needed for timely clinical intervention and may reduce mortality and morbidity, but the lack of knowledge about premalignant lesions for OPSCC poses a significant challenge to early detection. Biomarkers that identify individuals at high risk for OPSCC may act as surrogate markers for precancer but these are limited as only a few studies decipher the multistep progression from HPV infection to OPSCC development. Here, we summarize the current literature describing the multistep progression from oral HPV infection, persistence, and tumor development in the oropharynx. We also examine key challenges that hinder the identification of premalignant lesions in the oropharynx and discuss potential biomarkers for oropharyngeal precancer. Finally, we evaluate novel strategies to improve investigations of the biological process that drives oral HPV persistence and OPSCC, highlighting new developments in the establishment of a genetic progression model for HPV + OPSCC and in vivo models that mimic HPV + OPSCC pathogenesis.
SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair
Authors: Huang Yujia , Tang Ming , Hu Zhiyi , Cai Bailian , Chen Guofang , Jiang Lijun , Xia Yan , Guan Pujun , Li Xiaoqi , Mao Zhiyong , Wan Xiaoping , Lu Wen
Published: January 2024

Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression. Through meticulous in vivo and in vitro experiments, we reveal that depletion of SMYD3 curtails cell proliferation, migration, and invasion capabilities, leading to compromised non-homologous end joining repair (NHEJ) and heightened sensitivity of EC cells to radiation. Furthermore, our pathway enrichment analysis underscores the pivotal involvement of the DNA damage repair pathway in regulating EC progression. Mechanistically, in response to DNA damage, SMYD3 is recruited to these sites in a PARP1-dependent manner, specifically methylating LIG4. This methylation sets off a sequential assembly of the LIG4/XRCC4/XLF complex, actively participating in the NHEJ pathway and thereby fostering EC progression. Notably, our findings highlight the promise of SMYD3 as a crucial player in NHEJ repair and its direct correlation with EC progression. Intriguingly, pharmacological intervention targeting SMYD3 with its specific inhibitor, BCI-121, emerges as a potent strategy, markedly suppressing the tumorigenicity of EC cells and significantly enhancing the efficacy of radiotherapy. Collectively, our comprehensive data position SMYD3 as a central factor in NHEJ repair and underscore its potential as a promising pharmacological target for endometrial cancer therapy, validated through both in vitro and in vivo systems.
Identifying misdiagnosed bipolar disorder using support vector machine: feature selection based on fMRI of follow-up confirmed affective disorders
Authors: Jiang Xiaowei , Cao Bo , Li Chao , Jia Linna , Jing Yi , Cai Wei , Zhao Wenhui , Sun Qikun , Wu Feng , Kong Lingtao , Tang Yanqing
Published: January 2024

Nearly a quarter of bipolar disorder (BD) patients were misdiagnosed as major depressive disorder (MDD) patients, which cannot be corrected until mania/hypomania develops. It is important to recognize these obstacles so that the appropriate treatment can be initiated. Thus, we sought to distinguish patients with BD from MDD, especially to identify misdiagnosed BD before mania/hypomania, and further explore potential trait features that allow accurate differential diagnosis independent of state matters. Functional magnetic resonance imaging scans were performed at baseline on 92 MDD patients and 48 BD patients. The MDD patients were then followed up for more than two years. After follow-up, 23 patients transformed into BD (tBD), and 69 patients whose diagnoses remained unchanged were eligible for unipolar depression (UD). A support vector machine classifier was trained on the amygdala-based functional connectivity (FC) of 48 BD and 50 UD patients using a novel region-based feature selection. Then, the classifier was tested on the dataset, encompassing tBD and the remaining UD. It performed well for known BD and UD and can also distinguish tBD from UD with an accuracy of 81%, sensitivity of 82.6%, specificity of 79%, and AUC of 74.6%, respectively. Feature selection results revealed that ten regions within the cortico-limbic neural circuit contributed most to classification. Furthermore, in the FC comparisons among diseases, BD and tBD shared almost overlapped FC patterns in the cortico-limbic neural circuit, and both of them presented pronounced differences in most regions within the circuit compared with UD. The FC values of the most discriminating brain regions had no prominent correlations with the severity of depression, anxiety, and mania/hypomania (FDR correction). It suggests that BD possesses some trait features in the cortico-limbic neural circuit, rendering it dichotomized by the classifier based on known-diagnosis data.
Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex
Authors: Sartori Simone B. , Keil Thomas M. V. , Kummer Kai K. , Murphy Conor P. , Gunduz-Cinar Ozge , Kress Michaela , Ebner Karl , Holmes Andrew , Singewald Nicolas
Published: January 2024

The ventromedial prefrontal cortex (vmPFC; rodent infralimbic cortex (IL)), is posited to be an important locus of fear extinction-facilitating effects of the dopamine (DA) bio-precursor, L-DOPA, but this hypothesis remains to be formally tested. Here, in a model of impaired fear extinction (the 129S1/SvImJ inbred mouse strain; S1), we monitored extracellular DA dynamics via in vivo microdialysis in IL during fear extinction and following L-DOPA administration. Systemic L-DOPA caused sustained elevation of extracellular DA levels in IL and increased neuronal activation in a subpopulation of IL neurons. Systemic L-DOPA enabled extinction learning and promoted extinction retention at one but not ten days after training. Conversely, direct microinfusion of DA into IL produced long-term fear extinction (an effect that was insensitive to ɑ-/ß-adrenoreceptor antagonism). However, intra-IL delivery of a D1-like or D2 receptor agonist did not facilitate extinction. Using ex vivo multi-electrode array IL neuronal recordings, along with ex vivo quantification of immediate early genes and DA receptor signalling markers in mPFC, we found evidence of reduced DA-evoked mPFC network responses in S1 as compared with extinction-competent C57BL/6J mice that were partially driven by D1 receptor activation. Together, our data demonstrate that locally increasing DA in IL is sufficient to produce lasting rescue of impaired extinction. The finding that systemic L-DOPA increased IL DA levels, but had only transient effects on extinction, suggests L-DOPA failed to reach a threshold level of IL DA or produced opposing behavioural effects in other brain regions. Collectively, our findings provide further insight into the neural basis of the extinction-promoting effects of DA and L-DOPA in a clinically relevant animal model, with possible implications for therapeutically targeting the DA system in anxiety and trauma-related disorders.
Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study
Authors: Zapparoli Laura , Devoto Francantonio , Mariano Marika , Seghezzi Silvia , Servello Domenico , Porta Mauro , Paulesu Eraldo
Published: January 2024

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of “relaxed situations” and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient’s unique needs.
Exploring the steps of learning: computational modeling of initiatory-actions among individuals with attention-deficit/hyperactivity disorder
Authors: Katabi Gili , Shahar Nitzan
Published: January 2024

Attention-deficit/hyperactivity disorder (ADHD) is characterized by difficulty in acting in a goal-directed manner. While most environments require a sequence of actions for goal attainment, ADHD was never studied in the context of value-based sequence learning. Here, we made use of current advancements in hierarchical reinforcement-learning algorithms to track the internal value and choice policy of individuals with ADHD performing a three-stage sequence learning task. Specifically, 54 participants (28 ADHD, 26 controls) completed a value-based reinforcement-learning task that allowed us to estimate internal action values for each trial and stage using computational modeling. We found attenuated sensitivity to action values in ADHD compared to controls, both in choice and reaction-time variability estimates. Remarkably, this was found only for first-stage actions (i.e., initiatory actions), while for actions performed just before outcome delivery the two groups were strikingly indistinguishable. These results suggest a difficulty in following value estimation for initiatory actions in ADHD.
Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy
Authors: Babamohamadi Mehregan , Mohammadi Nastaran , Faryadi Elham , Haddadi Maryam , Merati Amirhossein , Ghobadinezhad Farbod , Amirian Roshanak , Izadi Zhila , Hadjati Jamshid
Published: January 2024

Cancer is one of the most common diseases and causes of death worldwide. Since common treatment approaches do not yield acceptable results in many patients, developing innovative strategies for effective treatment is necessary. Immunotherapy is one of the promising approaches that has been highly regarded for preventing tumor recurrence and new metastases. Meanwhile, inhibiting immune checkpoints is one of the most attractive methods of cancer immunotherapy. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) is an essential immune molecule that plays a vital role in cell cycle modulation, regulation of T cell proliferation, and cytokine production. This molecule is classically expressed by stimulated T cells. Inhibition of overexpression of immune checkpoints such as CTLA-4 receptors has been confirmed as an effective strategy. In cancer immunotherapy, immune checkpoint-blocking drugs can be enhanced with nanobodies that target immune checkpoint molecules. Nanobodies are derived from the variable domain of heavy antibody chains. These small protein fragments have evolved entirely without a light chain and can be used as a powerful tool in imaging and treating diseases with their unique structure. They have a low molecular weight, which makes them smaller than conventional antibodies while still being able to bind to specific antigens. In addition to low molecular weight, specific binding to targets, resistance to temperature, pH, and enzymes, high ability to penetrate tumor tissues, and low toxicity make nanobodies an ideal approach to overcome the disadvantages of monoclonal antibody-based immunotherapy. In this article, while reviewing the cellular and molecular functions of CTLA-4, the structure and mechanisms of nanobodies’ activity, and their delivery methods, we will explain the advantages and challenges of using nanobodies, emphasizing immunotherapy treatments based on anti-CTLA-4 nanobodies.
Informing disaster-risk management policies for education infrastructure using scenario-based recovery analyses
Authors: Opabola Eyitayo A. , Galasso Carmine
Published: January 2024

Recent natural-hazard events have shown that post-disaster education continuity is still a significant global challenge. Here, we propose a methodology to support various stakeholders in quantifying the impact of disaster management policies on education continuity in low- and lower-middle-income countries. We then apply the proposed methodology to a hypothetical earthquake scenario impacting a testbed education infrastructure in Central Sulawesi, Indonesia. This case study accounts for local practice influencing recovery through interviews with stakeholders involved in post-disaster management in the region. The analyses reveal that early response financing mechanisms can help speed up education recovery by a factor of three. Also, community-managed school reconstruction projects are likely to be completed up to three to five times faster than agency-managed projects. Furthermore, we demonstrate how the framework can be used to prioritize school reconstruction projects to ensure inclusive education continuity at the community level.
Interfacial self-healing polymer electrolytes for long-cycle solid-state lithium-sulfur batteries
Authors: Pei Fei , Wu Lin , Zhang Yi , Liao Yaqi , Kang Qi , Han Yan , Zhang Huangwei , Shen Yue , Xu Henghui , Li Zhen , Huang Yunhui
Published: January 2024

Coupling high-capacity cathode and Li-anode with solid-state electrolyte has been demonstrated as an effective strategy for increasing the energy densities and safety of rechargeable batteries. However, the limited ion conductivity, the large interfacial resistance, and unconstrained Li-dendrite growth hinder the application of solid-state Li-metal batteries. Here, a poly(ether-urethane)-based solid-state polymer electrolyte with self-healing capability is designed to reduce the interfacial resistance and provides a high-performance solid-state Li-metal battery. With its dynamic covalent disulfide bonds and hydrogen bonds, the proposed solid-state polymer electrolyte exhibits excellent interfacial self-healing ability and maintains good interfacial contact. Full cells are assembled with the two integrated electrodes/electrolytes. As a result, the Li||Li symmetric cells exhibit stable long-term cycling for more than 6000 h, and the solid-state Li-S battery shows a prolonged cycling life of 700 cycles at 0.3 C. The use of ultrasound imaging technology shows that the interfacial contact of the integrated structure is much better than those of traditional laminated structure. This work provides an interesting interfacial dual-integrated strategy for designing high-performance solid-state Li-metal batteries.
Enhancing geometric representations for molecules with equivariant vector-scalar interactive message passing
Authors: Wang Yusong , Wang Tong , Li Shaoning , He Xinheng , Li Mingyu , Wang Zun , Zheng Nanning , Shao Bin , Liu Tie-Yan
Published: January 2024

Geometric deep learning has been revolutionizing the molecular modeling field. Despite the state-of-the-art neural network models are approaching ab initio accuracy for molecular property prediction, their applications, such as drug discovery and molecular dynamics (MD) simulation, have been hindered by insufficient utilization of geometric information and high computational costs. Here we propose an equivariant geometry-enhanced graph neural network called ViSNet, which elegantly extracts geometric features and efficiently models molecular structures with low computational costs. Our proposed ViSNet outperforms state-of-the-art approaches on multiple MD benchmarks, including MD17, revised MD17 and MD22, and achieves excellent chemical property prediction on QM9 and Molecule3D datasets. Furthermore, through a series of simulations and case studies, ViSNet can efficiently explore the conformational space and provide reasonable interpretability to map geometric representations to molecular structures.
Compartments in medulloblastoma with extensive nodularity are connected through differentiation along the granular precursor lineage
Authors: Ghasemi David R. , Okonechnikov Konstantin , Rademacher Anne , Tirier Stephan , Maass Kendra K. , Schumacher Hanna , Joshi Piyush , Gold Maxwell P. , Sundheimer Julia , Statz Britta , Rifaioglu Ahmet S. , Bauer Katharina , Schumacher Sabrina , Bortolomeazzi Michele , Giangaspero Felice , Ernst Kati J. , Clifford Steven C. , Saez-Rodriguez Julio , Jones David T. W. , Kawauchi Daisuke , Fraenkel Ernest , Mallm Jan-Philipp , Rippe Karsten , Korshunov Andrey , Pfister Stefan M. , Pajtler Kristian W.
Published: January 2024

Medulloblastomas with extensive nodularity are cerebellar tumors characterized by two distinct compartments and variable disease progression. The mechanisms governing the balance between proliferation and differentiation in MBEN remain poorly understood. Here, we employ a multi-modal single cell transcriptome analysis to dissect this process. In the internodular compartment, we identify proliferating cerebellar granular neuronal precursor-like malignant cells, along with stromal, vascular, and immune cells. In contrast, the nodular compartment comprises postmitotic, neuronally differentiated malignant cells. Both compartments are connected through an intermediate cell stage resembling actively migrating CGNPs. Notably, we also discover astrocytic-like malignant cells, found in proximity to migrating and differentiated cells at the transition zone between the two compartments. Our study sheds light on the spatial tissue organization and its link to the developmental trajectory, resulting in a more benign tumor phenotype. This integrative approach holds promise to explore intercompartmental interactions in other cancers with varying histology.
Quick model-based viscoelastic clot strength predictions from blood protein concentrations for cybermedical coagulation control
Authors: Ghetmiri Damon E. , Venturi Alessia J. , Cohen Mitchell J. , Menezes Amor A.
Published: January 2024

Cybermedical systems that regulate patient clotting in real time with personalized blood product delivery will improve treatment outcomes. These systems will harness popular viscoelastic assays of clot strength such as thromboelastography (TEG), which help evaluate coagulation status in numerous conditions: major surgery (e.g., heart, vascular, hip fracture, and trauma); liver cirrhosis and transplants; COVID-19; ICU stays; sepsis; obstetrics; diabetes; and coagulopathies like hemophilia. But these measurements are time-consuming, and thus impractical for urgent care and automated coagulation control. Because protein concentrations in a blood sample can be measured in about five minutes, we develop personalized, phenomenological, quick, control-oriented models that predict TEG curve outputs from input blood protein concentrations, to facilitate treatment decisions based on TEG curves. Here, we accurately predict, experimentally validate, and mechanistically justify curves and parameters for common TEG assays (Functional Fibrinogen, Citrated Native, Platelet Mapping, and Rapid TEG), and verify results with trauma patient clotting data.
Selective knowledge sharing for privacy-preserving federated distillation without a good teacher
Authors: Shao Jiawei , Wu Fangzhao , Zhang Jun
Published: January 2024

While federated learning (FL) is promising for efficient collaborative learning without revealing local data, it remains vulnerable to white-box privacy attacks, suffers from high communication overhead, and struggles to adapt to heterogeneous models. Federated distillation (FD) emerges as an alternative paradigm to tackle these challenges, which transfers knowledge among clients instead of model parameters. Nevertheless, challenges arise due to variations in local data distributions and the absence of a well-trained teacher model, which leads to misleading and ambiguous knowledge sharing that significantly degrades model performance. To address these issues, this paper proposes aselective knowledge sharingmechanism for FD, termedSelective-FD, to identify accurate and precise knowledge from local and ensemble predictions, respectively. Empirical studies, backed by theoretical insights, demonstrate that our approach enhances the generalization capabilities of the FD framework and consistently outperforms baseline methods. We anticipate our study to enable a privacy-preserving, communication-efficient, and heterogeneity-adaptive federated training framework.
Mesozoic evolution of cicadas and their origins of vocalization and root feeding
Authors: Jiang Hui , Szwedo Jacek , Labandeira Conrad C. , Chen Jun , Moulds Maxwell S. , Mähler Bastian , Muscente A. Drew , Zhuo De , Nyunt Thet Tin , Zhang Haichun , Wei Cong , Rust Jes , Wang Bo
Published: January 2024

Extant cicada (Hemiptera: Cicadoidea) includes widely distributed Cicadidae and relictual Tettigarctidae, with fossils ascribed to these two groups based on several distinct, minimally varying morphological differences that define their extant counterparts. However, directly assigning Mesozoic fossils to modern taxa may overlook the role of unique and transitional features provided by fossils in tracking their early evolutionary paths. Here, based on adult and nymphal fossils from mid-Cretaceous Kachin amber of Myanmar, we explore the phylogenetic relationships and morphological disparities of fossil and extant cicadoids. Our results suggest that Cicadidae and Tettigarctidae might have diverged at or by the Middle Jurassic, with morphological evolution possibly shaped by host plant changes. The discovery of tymbal structures and anatomical analysis of adult fossils indicate that mid-Cretaceous cicadas were silent as modern Tettigarctidae or could have produced faint tymbal-related sounds. The discovery of final-instar nymphal and exuviae cicadoid fossils with fossorial forelegs and piercing-sucking mouthparts indicates that they had most likely adopted a subterranean lifestyle by the mid-Cretaceous, occupying the ecological niche of underground feeding on root. Our study traces the morphological, behavioral, and ecological evolution of Cicadoidea from the Mesozoic, emphasizing their adaptive traits and interactions with their living environments.