Miracle-dz/UniFAR-FTUs huggingface dataset:
Formal Tests for Resistance-Resilience in Archaeological Time Series

The study of resilience is a common pathway for scientific data to inform policy and practice towards impending climate change. Consequently, understanding the mechanisms and features that contribute towards building resilience is a key goal of much research on coupled socio-environmental systems. In parallel, archaeology has developed the ambition to contribute to this agenda through its unique focus on cultural dynamics that occur over the very long term. This paper argues that archaeological studies of resilience are limited in scope and potential impact by incomplete operational definitions of resilience, itself a multifaceted and contested concept. This lack of interdisciplinary engagement fundamentally limits archaeology’s ability to contribute meaningfully to understanding factors behind the emergence and maintenance of long-term societal resilience, a topic of significant interest that the field is in theory ideally positioned to address. Here, we introduce resilience metrics drawn from ecology and develop case studies to illustrate their potential utility for archaeological studies. We achieve this by extending methods for formally measuring resistance, the capacity of a system to absorb disturbances; and resilience, its capacity to recover from disturbances, with a novel significance test for palaeodemographic data. Building on statistical permutation and post-hoc tests available in the rcarbon package in the R statistical environment, we apply our adapted resilience-resistance framework to summed probability distributions of calibrated radiocarbon dates drawn from the Atlantic Forest of eastern Brazil. We deploy these methods to investigate cross-sectional trends across three recognised biogeographical zones of the Atlantic Forest domain, against the backdrop of prehistoric phases of heightened hydroclimatic variability. Our analysis uncovers novel centennial-scale spatial structure in the resilience of palaeodemographic growth rates. In addition to the case-specific findings, we suggest that adapting formal metrics can help archaeology create impact and engagement beyond relatively narrow disciplinary concerns. To this end, we supply code and data to replicate our palaeodemographic analyses to enable their use and adaptation to other archaeological problems.
Multiplex-Heterogeneous Network-Based Capturing Potential SNP “Switches” of Pathways Associating With Diverse Disease Characteristics of Asthma

Asthma is a complex heterogeneous respiratory disorder. In recent years nubbly regions of the role of genetic variants and transcriptome including mRNAs, microRNAs, and long non-coding RNAs in the pathogenesis of asthma have been separately excavated and reported. However, how to systematically integrate and decode this scattered information remains unclear. Further exploration would improve understanding of the internal communication of asthma. To excavate new insights into the pathogenesis of asthma, we ascertained three asthma characteristics according to reviews, airway inflammation, airway hyperresponsiveness, and airway remodeling. We manually created a contemporary catalog of corresponding risk transcriptome, including mRNAs, miRNAs, and lncRNAs. MIMP is a multiplex-heterogeneous networks-based approach, measuring the relevance of disease characteristics to the pathway by examining the similarity between the determined vectors of risk transcriptome and pathways in the same low-dimensional vector space. It was developed to enable a more concentrated and in-depth exploration of potential pathways. We integrated experimentally validated competing endogenous RNA regulatory information and the SNPs with significant pathways into the ceRNA-mediated SNP switching pathway network (CSSPN) to analyze ceRNA regulation of pathways and the role of SNP in these dysfunctions. We discovered 11 crucial ceRNA regulations concerning asthma disease feature pathway and propose a potential mechanism of ceRNA regulatory SNP → gene → pathway → disease feature effecting asthma pathogenesis, especially for MALAT1 (rs765499057/rs764699354/rs189435941) → hsa-miR-155 → IL13 (rs201185816/rs1000978586/rs202101165) → Interleukin-4 and Interleukin-13 signaling → inflammation/airway remodeling and MALAT1 (rs765499057/rs764699354/rs189435941) → hsa-miR-155 → IL17RB (rs948046241) → Interleukin-17 signaling (airway remodeling)/Cytokine-cytokine receptor interaction (inflammation). This study showed a systematic and propagable workflow for capturing the potential SNP “switch” of asthma through text and database mining and provides further information on the pathogenesis of asthma.
The Associations of Caesarean Delivery With Risk of Wheezing Diseases and Changes of T Cells in Children

Objectives This study aimed to assess the associations of caesarean delivery (CD) with risk of wheezing diseases and changes of immune cells in children. Design The cross-sectional study was conducted between May, 2020 and April, 2021. Setting and participants The study was conducted in Shanghai Children’s Medical Center, Shanghai, China. A total of 2079 children with a mean age of 36.97 ± 40.27 months and their guardians were included in the present study via face-to-face inquiry and physical examination by clinicians. Methods Logistic regression was applied to estimate odds ratio (ORs) and 95% confidence intervals (CIs) for the association between CD and first episode of wheezing (FEW) or asthma. Models were adjusted for premature or full-term delivery, exclusive breastfeeding (at least 4 months) or not. Results Among the 2079 children, 987 children (47.47%) were born by CD and 1092 (52.53%) by vaginal delivery (VD). Children delivered by caesarean had significantly lower gestational age (P<0.01) compared with those who delivered vaginally. Our results also showed that CD was related to increased risk of FEW by the age of 3(adjusted OR 1.50, 95%CI 1.06, 2.12) and increased tendency to develop asthma by the age of 4 (adjusted OR 3.16, 95%CI 1.25, 9.01). The subgroup analysis revealed that the negative effects of CD on asthma were more obvious in children without exclusive breastfeeding (adjusted OR 4.93, 95%CI 1.53, 21.96) or without postnatal smoking exposure (adjusted OR 3.58, 95%CI 1.20, 13.13). Furthermore, compared with children born through VD, a significant change of the T cells (increased proportion of CD4+ T cells and decreased number and proportion of CD8+ T cells) were observed before the age of one in the CD group. However, the changes were insignificant in children over 1 year old. Conclusions This study showed age-dependent associations of CD with asthma and FEW in offspring. Moreover, CD appeared to have an effect on the cellular immunity in infants, the disorder of which may contribute to the development of asthma in children.
Rapidly Learning Generalizable and Robot-Agnostic Tool-Use Skills for a Wide Range of Tasks

Many real-world applications require robots to use tools. However, robots lack the skills necessary to learn and perform many essential tool-use tasks. To this end, we present the TRansferrIng Skilled Tool Use Acquired Rapidly (TRI-STAR) framework for task-general robot tool use. TRI-STAR has three primary components: 1) the ability to learn and apply tool-use skills to a wide variety of tasks from a minimal number of training demonstrations, 2) the ability to generalize learned skills to other tools and manipulated objects, and 3) the ability to transfer learned skills to other robots. These capabilities are enabled by TRI-STAR’s task-oriented approach, which identifies and leverages structural task knowledge through the use of our goal-based task taxonomy. We demonstrate this framework with seven tasks that impose distinct requirements on the usages of the tools, six of which were each performed on three physical robots with varying kinematic configurations. Our results demonstrate that TRI-STAR can learn effective tool-use skills from only 20 training demonstrations. In addition, our framework generalizes tool-use skills to morphologically distinct objects and transfers them to new platforms, with minor performance degradation.
Transcriptome Dynamics of Human Neuronal Differentiation From iPSC

The generation and use of induced pluripotent stem cells (iPSCs) in order to obtain all differentiated adult cell morphologies without requiring embryonic stem cells is one of the most important discoveries in molecular biology. Among the uses of iPSCs is the generation of neuron cells and organoids to study the biological cues underlying neuronal and brain development, in addition to neurological diseases. These iPSC-derived neuronal differentiation models allow us to examine the gene regulatory factors involved in such processes. Among these regulatory factors are long non-coding RNAs (lncRNAs), genes that are transcribed from the genome and have key biological functions in establishing phenotypes, but are frequently not included in studies focusing on protein coding genes. Here, we provide a comprehensive analysis and overview of the coding and non-coding transcriptome during multiple stages of the iPSC-derived neuronal differentiation process using RNA-seq. We identify previously unannotated lncRNAs via genome-guided de novo transcriptome assembly, and the distinct characteristics of the transcriptome during each stage, including differentially expressed and stage specific genes. We further identify key genes of the human neuronal differentiation network, representing novel candidates likely to have critical roles in neurogenesis using coexpression network analysis. Our findings provide a valuable resource for future studies on neuronal differentiation.
Survival of Patients Following First Diagnosis of Diabetic Foot Complications: A Nationwide 15-Year Longitudinal Analysis

Background and Aims The long-term survival in people with type 2 diabetes following first diagnosis of diabetic foot complications (FDDFC) is unclear. The object is to evaluate the mortality rate in subjects with type 2 diabetes following FDDFC and the impacts of the major cardiovascular comorbidities. Methods Nationwide data were analyzed for subjects with T2D and DFC between 2003 and 2017 according to ICD-9 coding. DFC was defined with the codes of ulcers, infections, or severe peripheral artery disease that required intervention (PAD) to mimic the real world diagnosis. Criteria of FDDFC were preceded by a period without any DFC for at least 5 years. Major cardiovascular comorbidities: established PAD and cardiovascular diseases (CVD: including coronary heart disease (CHD), stroke, or heart failure) before the index date as well as lower-extremity amputations (LEA) at the index episode were analyzed. Results Among 300,115 subjects with DFC, a total of 103,396 patients had FDDFC. The mean 5-year survival rate of these subjects was 81.05%. Using subjects without associated major cardiovascular comorbidity as baseline, the adjusted hazard ratios (aHR) were1.43 (95% confidence interval 1.38–1.49) in group PAD-/CVD+, followed by 1.70 (1.59–1.80) in PAD+/CVD- and 1.98 (1.89–2.08) in PAD+/CVD+. The aHR was further increased in patients with PAD who additionally had heart failure (3.77, 3.50–4.05), stroke (2.06, 1.95–2.18), or CHD (1.89, 1.79–2.00). Subjects with PAD rather than other CVD were associated with LEA at FDDFC. Patients with major LEA (above the ankle) at FDDFC episode had lower 5-year survival rate (65.01%) followed by those with minor LEA (72.24%) and without LEA (81.61%). Conclusions Cardiovascular comorbidity as well as LEA status at the event of FDDFCs were both associated with patient survival outcomes. Earlier identification of this large population could lead to higher survival rates.
Tides and Volcanoes: A Historical Perspective

In this paper, we examine the origins and the history of the hypothesis for an influence of tidal forces on volcanic activity. We believe that exploring this subject through a historical perspective may help geoscientists gain new insights in a field of research so closely connected with the contemporary scientific debate and often erroneously considered as a totally separated niche topic. The idea of an influence of the Moon and Sun on magmatic processes dates back to the Hellenistic world. However, it was only since the late 19th century, with the establishment of volcano observatories at Mt. Etna and Vesuvius allowing a systematic collection of observations with modern methods, that the “tidal controversy” opened one of the longest and most important debates in Earth Science. At the beginning of the 20th century, the controversy assumed a much more general significance, as the debate around the tidal influence on volcanism developed around the formulation of the first modern theories on the origins of volcanism, the structure of the Earth’s interior and the mechanisms for continental drift. During the same period, the first experimental evidence for the existence of the Earth tides by Hecker (Beobachtungen an Horizontalpendeln über die Deformation des Erdkörpers unter dem Einfluss von Sonne und MondVeröffentlichung des Königl, 1907, 32), and the Chamberlin–Moulton planetesimal hypothesis (proposed in 1905 by geologist Thomas Chrowder Chamberlin and astronomer Forest Ray Moulton) about the “tidal” origin of the Solar System, influenced and stimulated new researches on volcano-tides interactions, such as the first description of the “lava tide” at the Kilauea volcano by Thomas Augustus Jaggar in 1924. Surprisingly, this phase of gradual acceptance of the tidal hypothesis was followed by a period of lapse between 1930 to late 1960. A new era of stimulating and interesting speculations opened at the beginning of the seventies of the 20th century thanks to the discovery of the moonquakes revealed by the Apollo Lunar Surface Experiment Package. A few years later, in 1979, the intense volcanism on the Jupiter’s moon Io, discovered by the Voyager 1 mission, was explained by the tidal heating produced by the Io’s orbital eccentricity. In the last part of the paper, we discuss the major advances over the last decades and the new frontiers of this research topic, which traditionally bears on interdisciplinary contributions (e.g., from geosciences, physics, astronomy). We conclude that the present-day debate around the environmental crisis, characterized by a large collection of interconnected variables, stimulated a new field of research around the complex mechanisms of mutual interactions among orbital factors, Milankovitch Cycles, climate changes and volcanism.
Characterizing the Access of Cholinergic Antagonists to Efferent Synapses in the Inner Ear

Stimulation of cholinergic efferent neurons innervating the inner ear has profound, well-characterized effects on vestibular and auditory physiology, after activating distinct ACh receptors (AChRs) on afferents and hair cells in peripheral endorgans. Efferent-mediated fast and slow excitation of vestibular afferents are mediated by α4β2*-containing nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs), respectively. On the auditory side, efferent-mediated suppression of distortion product otoacoustic emissions (DPOAEs) is mediated by α9α10nAChRs. Previous characterization of these synaptic mechanisms utilized cholinergic drugs, that when systemically administered, also reach the CNS, which may limit their utility in probing efferent function without also considering central effects. Use of peripherally-acting cholinergic drugs with local application strategies may be useful, but this approach has remained relatively unexplored. Using multiple administration routes, we performed a combination of vestibular afferent and DPOAE recordings during efferent stimulation in mouse and turtle to determine whether charged mAChR or α9α10nAChR antagonists, with little CNS entry, can still engage efferent synaptic targets in the inner ear. The charged mAChR antagonists glycopyrrolate and methscopolamine blocked efferent-mediated slow excitation of mouse vestibular afferents following intraperitoneal, middle ear, or direct perilymphatic administration. Both mAChR antagonists were effective when delivered to the middle ear, contralateral to the side of afferent recordings, suggesting they gain vascular access after first entering the perilymphatic compartment. In contrast, charged α9α10nAChR antagonists blocked efferent-mediated suppression of DPOAEs only upon direct perilymphatic application, but failed to reach efferent synapses when systemically administered. These data show that efferent mechanisms are viable targets for further characterizing drug access in the inner ear.
Reducing Addiction in Bipolar Disorder via Hacking the Dopaminergic System

The dopaminergic system plays a central and decisive role in substance use disorder (SUD), bipolar disorder (BD), and possibly in a subgroup of patients with refractory depression. Common genetic markers and underlying cellular processes, such as kindling, support the close link between these disorders, which is also expressed by the high rate of comorbidity. Although partial dopamine agonists/antagonists acting on D2 and D3 receptors have an established role in treating BD, their usefulness in SUD is less clear. However, dopamine D3 receptors were shown to play a central role in SUD and BD, making D2/D3 partial agonists/antagonists a potential target for both disorders. This narrative review examines whether these substances bear the promise of a future therapeutic approach especially in patients with comorbid BD and SUD.
Seasonal and Inter-Annual Variations of Stable Isotopic Characteristics of Rainfall and Cave Water in Shennong Cave, Southeast China, and Its Paleoclimatic Implication

Speleothem calcite stable oxygen isotope (δ18OC) is one of the most widely used proxies in paleoclimate research, and understanding its seasonal-annual variability is very significant for palaeoclimate reconstruction. Five-year precipitation and karst cave water from 2016 to 2021 were monitored in Shennong cave, Jiangxi Province, Southeast China. The local meteoric water line (LMWL) is δD = 8.20 × δ18O + 13.34, which is similar to the global meteoric water line. The stable hydrogen and oxygen isotope (δD and δ18O) characteristics of precipitation and cave water were studied. δ18O and δD of precipitation and cave water show obvious seasonal variations. Lower precipitation δ18O and δD generally occur during summer and autumn compared with higher δ18O and δD values during winter and spring. Meanwhile, low precipitation δ18O values do not only appear in June–July when precipitation is the highest of the year but also appear in August–September when precipitation is limited. The back-trajectory analysis of monsoon precipitation moisture sources shows that the moisture uptake regions vary little on inter-annual scales; the water vapor of rainfall in June–July comes from the South China Sea and the Bay of Bengal, while the moisture source in August–September is mainly from the West Pacific and local area. The El Niño-Southern Oscillation is an important factor affecting the value of δ18O by modulating the percentage of summer monsoon precipitation in the annual precipitation and moisture source. The relationship between amount-weighted monthly mean precipitation δ18O and Niño-3.4 index shows that the East Asian summer monsoon (EASM) intensifies during La Niña phases, resulting in more precipitation in monsoon season (May to September, MJJAS) and lower δ18O values, and vice versa during El Niño phases.
Antibacterial Activity and Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections Caused by Carbapenem-Resistant Klebsiella pneumoniae

Objectives: This work was to investigate the activity and optimal treatments of ceftazidime-avibactam (CZA) and aztreonam-avibactam (AZA) against bloodstream infections caused by carbapenem resistant Klebsiella pneumoniae (BSIs-CRKP). Methods: A total of 318 nonduplicate BSIs-CRKP isolates were collected from Blood Bacterial Resistant Investigation Collaborative System (BRICS) program. The minimum inhibitory concentration (MIC) of CZA and AZA were determined by agar dilution method. Carbapenemase genes and multilocus sequence typing were amplified by PCR. Monte Carlo simulation (MCS) was conducted to calculate cumulative fraction of response (CFR) of different CZA or AZA administrations. Results: The MIC90 of CZA and AZA were 128/4 and 1/4 mg/L, respectively. There are 87.4 and 3.5% isolates carried bla KPC-2 and bla NDM-1. A total of 68 ST types were identified and 29 novel ST types. ST11 accounted for 66.6%. Further MCS showed CFR of CZA using two-step infusion therapy (rapid first-step 0.5 h infusion and slow second-step 3 h infusion, TSIT) (2.5 g 0.5 h, 3.75 g every 8 h with 3 h infusion and 3.75 g 0.5 h, 2.5 g every 8 h with 3 h infusion) was above 89%. The CFR of AZA with TSIT was above 96%. Conclusion: TSIT with sufficient pharmacokinetic conditions could be useful for enhancing the therapeutic efficacy of CZA and AZA against BSIs-CRKP.
Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma

Glutamine metabolism (GM) plays a critical role in hepatocellular carcinoma (HCC); however, a comprehensive methodology to quantify GM activity is still lacking. We developed a transcriptome-based GMScore to evaluate GM activity and investigated the association of GMScore with prognosis and therapeutic resistance. Two independent HCC cohorts with transcriptome data were selected from The Cancer Genome Atlas (TCGA, n = 365) and the International Cancer Genome Consortium (ICGC, n = 231). The expression of 41 GM-associated genes were used to construct and validate GMScore. Several genomic or transcriptomic biomarkers were also estimated. Tumor response to immune checkpoint inhibitors (ICIs) was predicted using the tumor immune dysfunction and exclusion algorithm. GMScore was closely correlated with patient characteristics, including stage, histology grade, alpha-fetoprotein level, and vascular invasion. High GMScore was an independent risk factor for overall survival (OS) in both cohorts (HR = 4.2 and 3.91, both p < 0.001), superior to clinical indices and other biomarkers. High GMScore presented transcriptome features to indicate cell growth advantages and genetic stability, which was associated with poor OS of patients who received transcatheter arterial chemoembolization (TACE). High GMScore was also related to high expression of immune checkpoint genes, increased infiltration of regulatory T cells, and decreased infiltration of M1 macrophages. More importantly, high GMScore indicated poor predicted responses to ICIs, which could be verified in an ICI-treated melanoma cohort. In conclusion, GMScore is a strong prognostic index that may be integrated into existing clinical algorithms. A high GMScore may indicate resistance to TACE and ICIs based on its transcriptome and immune features. Validations using other HCC cohorts, especially ICI-treated HCC cohorts, are necessary.
Integration of Networks of Sensors and Electronics for Structural Health Monitoring of Composite Materials

The low-cost, widespread availability and robust nature of current electronic devices suggest the feasibility of creating a composite structure with integrated networked sensors to monitor in real time the life of civil and aerospace structures while in service conditions. For structures that need to survive to high number of life cycles under varying load-environmental conditions, it is of crucial importance that the strength, stiffness, endurance, and general load-bearing capabilities of the composite not to be severely degraded by the integrated networked components. Therefore, design tools must be developed to achieve optimized, safe, and reliable structures. High values of stress concentrations due to the presence of a rigid device within a highly anisotropic material can trigger the initiation of microcracks in the resin matrix. To quantify these effects, the acoustic emission technique is used to characterize the initiation of microfailures within laminated composites with integrated electronics.