Reconstructing the Genetic Relationship between Ancient and Present-Day Siberian Populations.

Human populations across a vast area in northern Eurasia, from Fennoscandia to Chukotka, share a distinct genetic component often referred to as the Siberian ancestry. Most enriched in present-day Samoyedic-speaking populations such as Nganasans, its origins and history still remain elusive despite the growing list of ancient and present-day genomes from Siberia. Here, we reanalyze published ancient and present-day Siberian genomes focusing on the Baikal and Yakutia, resolving key questions regarding their genetic history. First, we show a long-term presence of a unique genetic profile in southern Siberia, up to 6,000 yr ago, which distinctly shares a deep ancestral connection with Native Americans. Second, we provide plausible historical models tracing genetic changes in West Baikal and Yakutia in fine resolution. Third, the Middle Neolithic individual from Yakutia, belonging to the Belkachi culture, serves as the best source so far available for the spread of the Siberian ancestry into Fennoscandia and Greenland. These findings shed light on the genetic legacy of the Siberian ancestry and provide insights into the complex interplay between different populations in northern Eurasia throughout history.

Effect of the Interaction between Transition Metal Redox Center and Cyanide Ligand on Structural Evolution in Prussian White Cathodes.

Transition metal (TM) based Prussian whites, comprising a cyanide anion ((C≡N)-) and TM cations in an alternative manner, have been widely adopted as cathode materials for rechargeable batteries. Prussian whites are characterized by the TM electronic states that exclusively adopt low spin (LS) toward the C atom and high spin (HS) toward the N atom through the hybridized covalent bonding in the TM─C≡N─TM unit with the average oxidation states of the TM ions being 2+, considerably affecting the phase transition behavior upon the release and storage of carrier ions; however, there have been only a few studies on their associated features. Herein, Prussian whites with different HS TM ions were synthesized via coprecipitation and the phase transition behavior controlled by the π electron interaction between the cyanide anions and TM ions during battery operations was investigated. In situ X-ray characterizations reveal that the combined effect of π backdonation in the LS Fe-C unit and π donation in the HS TM-N unit effectively controls the bond length of the TM─C≡N─TM building unit, thus markedly influencing the lattice volume of a series of Prussian white cathodes during the charge/discharge process. This study presents a comprehensive understanding of the structure-property relationship of the Prussian white cathodes involving π electron interactions during battery operations.

Discovering individual fingerprints in resting-state functional connectivity using deep neural networks.

Non-negligible idiosyncrasy due to interindividual differences is an ongoing issue in resting-state functional MRI (rfMRI) analysis. We show that a deep neural network (DNN) can be employed for individual identification by learning important features from the time-varying functional connectivity (FC) of rfMRI in the Human Connectome Project. We employed the trained DNN to identify individuals from an independent dataset acquired at our institution. The results revealed that the DNN could successfully identify 300 individuals with an error rate of 2.9% using 15 s time-window and 870 individuals with an error rate of 6.7%. A trained DNN with nonlinear hidden layers led to the proposal of the "fingerprint of FC" (fpFC) as representative edges of individual FC. The fpFCs for individuals exhibited commonly important and individual-specific edges across time-window lengths (from 5 min to 15 s). Furthermore, the utility of our model for another group of subjects was validated, supporting the feasibility of our technique in the context of transfer learning. In conclusion, our study offers an insight into the discovery of the intrinsic mode of the human brain using whole-brain resting-state FC and DNNs.

Survival analysis of breast cancer patients after diagnosis of second primary malignancies, focusing on the second primary hematologic malignancy.

Purpose: Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). Methods: We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. Results: Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856-2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045-3.654; P = 0.036). Conclusion: Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

Can chemotherapy be omitted for patients with N0 or N1 endocrine-sensitive breast cancer treated with gonadotropin-releasing hormone agonist and tamoxifen?

Purpose: Whether administering chemotherapy followed by tamoxifen plus a gonadotropin-releasing hormone (GnRH) agonist to treat patients with lower-risk hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer provides a greater benefit than administering tamoxifen plus GnRH agonist alone remains unclear. This study aimed to compare the outcomes of propensity score-matched (PSM) patients who underwent these 2 types of treatment plans. Methods: This retrospective study included patients treated at our institution between 2009 and 2019. Eligible patients had HR-positive, HER2-negative, invasive breast cancer who had undergone surgery. There were 579 patients with HR-positive, HER2-negative breast cancer who were treated with a GnRH agonist and tamoxifen; patients with pathologic N2 and those who received neoadjuvant chemotherapy were excluded. After 1:1 PSM of patients who underwent GnRH agonist treatment and tamoxifen with versus without chemotherapy, 122 patients from these 2 groups were analyzed. Survival rates were calculated using the Kaplan-Meier method and compared via the log-rank test. Results: After PSM, there were no significant differences in several baseline characteristics between the 2 groups. After a median follow-up of 62.8 months, the patients in both groups demonstrated similar outcomes with no significant difference in disease-free survival (P = 0.596). Conclusion: Patients derived no significant survival benefit from undergoing a chemotherapy regimen before receiving tamoxifen and GnRH agonist therapy compared to forgoing such chemotherapy.

InZnTiON Channel Layer for Highly Stable Thin-Film Transistors and Light-Emitting Transistors.

In this study, we incorporated TiN as a carrier suppressor into an amorphous InZnO channel to achieve stable channels for thin-film transistors (TFTs) and light-emitting transistors (LETs). The low electronegativity and standard electrode potential of the Ti dopant led to a reduction in the number of oxygen vacancies in the InZnO channel. Moreover, the substitution of nitrogen into the oxygen sites of InZnO effectively decreased the excess electrons. As a result, the cosputtering of the TiN dopant resulted in a decrease in the carrier concentration of the InZnO channel, serving as an effective carrier suppressor. Due to the distinct structures of TiN and InZnO, the TiN-doped InZnO channel exhibited a completely amorphous structure and a featureless surface morphology. The presence of oxygen vacancies in the InZnO channel creates trap states for electrons and holes. Consequently, the TFT with the InZnTiON channel demonstrated an improved subthreshold swing and enhanced stability during the gate bias stress test. Furthermore, the threshold voltage shift (ΔVth) changed from 3.29 to 0.86 V in the positive bias stress test and from -0.92 to -0.09 V in the negative bias stress test. Additionally, we employed an InZnTiON channel in LETs as a substitute for organic semiconductors. The reduction in the number of oxygen vacancies effectively prevented exciton quenching caused by hole traps within the vacancies. Consequently, appropriate TiN doping in the InZnO channel enhanced the intensity of the LET devices.

Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that MELK mRNA levels were higher in TNBC tumors [8.11 (3.79-10.95)] than in HR+HER2- tumors [6.54 (2.90-9.26)]; P < 0.001]. In univariate analysis, patients with breast cancer with high-MELK-expressing tumors had worse overall survival (P < 0.001) and distant metastasis-free survival (P < 0.01) than patients with low-MELK-expressing tumors. In a multicovariate Cox regression model, high MELK expression was associated with shorter overall survival after adjusting for other baseline risk factors. MELK knockdown using siRNA or MELK inhibition using the MELK inhibitor MELK-In-17 significantly reduced invasiveness, reversed epithelial-to-mesenchymal transition, and reduced CSC self-renewal and maintenance in TNBC cells. Nude mice injected with CRISPR MELK-knockout MDA-MB-231 cells exhibited suppression of lung metastasis and improved overall survival compared with mice injected with control cells (P < 0.05). Furthermore, MELK-In-17 suppressed 4T1 tumor growth in syngeneic BALB/c mice (P < 0.001). Our findings indicate that MELK supports metastasis by promoting epithelial-to-mesenchymal transition and the CSC phenotype in TNBC. Significance: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

Reliability of self-reported dispositional mindfulness scales and their association with working memory performance and functional connectivity.

We systematically investigated the link between trait mindfulness scores and functional connectivity (FC) features or behavioral data, to emphasize the importance of the reliability of self-report mindfulness scores. Sixty healthy young male participants underwent two functional MRI runs with three mindfulness or mind-wandering task blocks with an N-back task (NBT) block. The data from 49 participants (age: 23.3 ± 2.8) for whom two sets of the self-reported Mindfulness Attention Awareness Scale (MAAS) and NBT performance were available were analyzed. We divided participants into two groups based on the consistency level of their MAAS scores (i.e., a "consistent" and an "inconsistent" group). Then, the association between the MAAS scores and FC features or NBT performance was investigated using linear regression analysis with p-value correction and bootstrapping. Meaningful associations (a) between MAAS and NBT accuracy (slope = 0.41, CI = [0.10, 0.73], corrected p < 0.05), (b) between MAAS and the FC edges in the frontoparietal network, and (c) between the FC edges and NBT performance were only observed in the consistent group (n = 26). Our findings demonstrate the importance of appropriate screening mechanisms for self-report-based dispositional mindfulness scores when trait mindfulness scores are combined with neuronal features and behavioral data.

Genetic population structure of the Xiongnu Empire at imperial and local scales.

The Xiongnu established the first nomadic imperial power, controlling the Eastern Eurasian steppe from ca. 200 BCE to 100 CE. Recent archaeogenetic studies identified extreme levels of genetic diversity across the empire, corroborating historical records of the Xiongnu Empire being multiethnic. However, it has remained unknown how this diversity was structured at the local community level or by sociopolitical status. To address this, we investigated aristocratic and local elite cemeteries at the western frontier of the empire. Analyzing genome-wide data from 18 individuals, we show that genetic diversity within these communities was comparable to the empire as a whole, and that high diversity was also observed within extended families. Genetic heterogeneity was highest among the lowest-status individuals, implying diverse origins, while higher-status individuals harbored less genetic diversity, suggesting that elite status and power was concentrated within specific subsets of the broader Xiongnu population.

Overcoming the imatinib-resistant BCR-ABL mutants with new ureidobenzothiazole chemotypes endowed with potent and broad-spectrum anticancer activity.

The design of kinase inhibitors targeting the oncogenic kinase BCR-ABL constitutes a promising paradigm for treating chronic myeloid leukaemia (CML). Nevertheless, the efficacy of imatinib, the first FDA-approved targeted therapy for CML, is curbed by the emergence of resistance. Herein, we report the identification of the 2-methoxyphenyl ureidobenzothiazole AK-HW-90 (2b) as a potent pan-BCR-ABL inhibitor against imatinib-resistant mutants, particularly T315I. A concise array of six compounds 2a-f was designed based on our previously reported benzothiazole lead AKE-5l to improve its BCR-ABLT315I inhibitory activity. Replacing the 6-oxypicolinamide moiety of AKE-5l with o-methoxyphenyl and changing the propyl spacer with phenyl afforded 2a and AK-HW-90 (2b) with IC50 values of 2.0 and 0.65 nM against BCR-ABLT315I, respectively. AK-HW-90 showed superior anticancer potency to imatinib against multiple cancer cells (NCI), including leukaemia K-562. The obtained outcomes offer AK-HW-90 as a promising candidate for the treatment of CML and other types of cancer.

Structural Evolution of Mg-Doped Single-Crystal LiCoO2 Cathodes: Importance of Morphology and Mg-Doping Sites.

Layered lithium cobalt oxide (LiCoO2, LCO), which serves as a structural motif for the widely adopted layered cathodes in lithium-ion batteries, has a long history, and its unstable phase transition during high-voltage operation (∼4.5 V) remains an intractable problem. Many research strategies, such as surface coating and immobile ion doping, have been proposed to address this issue, but a clear understanding of the effects has not been demonstrated because of various potential parameters (e.g., particle size, shape, and dopant content). Herein, we report a molten salt synthesis method that produces sphere-like single-crystal magnesium (Mg)-doped LCO. In situ X-ray diffraction and X-ray absorption fine structure analyses confirmed that the lattice strain was effectively alleviated by the effects of both the particle shape and Mg doping compared to the plate-like and sphere-like single-crystal LCO samples. Furthermore, the preference for Mg doping in the Co site (3b) rather than in the Li site (3a) in the LCO framework is systematically revealed, and a clear understanding of Mg doping that suppresses the monoclinic phase transition is discussed in detail.

Microplastic remediation technologies in water and wastewater treatment processes: Current status and future perspectives.

Microplastics (MPs) are a type of contaminants produced during the use and disposal of plastic products, which are ubiquitous in our lives. With the high specific surface area and strong hydrophobicity, MPs can adsorb various hazardous microorganisms and chemical contaminants from the environment, causing irreversible damage to our humans. It is reported that the MPs have been detected in infant feces and human blood. Therefore, the presence of MPs has posed a significant threat to human health. It is critically essential to develop efficient, scalable and environmentally-friendly methods to remove MPs. Herein, recent advances in the MPs remediation technologies in water and wastewater treatment processes are overviewed. Several approaches, including membrane filtration, adsorption, chemically induced coagulation-flocculation-sedimentation, bioremediation, and advanced oxidation processes are systematically documented. The characteristics, mechanisms, advantages, and disadvantages of these methods are well discussed and highlighted. Finally, the current challenges and future trends of these methods are proposed, with the aim of facilitating the remediation of MPs in water and wastewater treatment processes in a more efficient, scalable, and environmentally-friendly way.

Neural representations of the perception of handwritten digits and visual objects from a convolutional neural network compared to humans.

We investigated neural representations for visual perception of 10 handwritten digits and six visual objects from a convolutional neural network (CNN) and humans using functional magnetic resonance imaging (fMRI). Once our CNN model was fine-tuned using a pre-trained VGG16 model to recognize the visual stimuli from the digit and object categories, representational similarity analysis (RSA) was conducted using neural activations from fMRI and feature representations from the CNN model across all 16 classes. The encoded neural representation of the CNN model exhibited the hierarchical topography mapping of the human visual system. The feature representations in the lower convolutional (Conv) layers showed greater similarity with the neural representations in the early visual areas and parietal cortices, including the posterior cingulate cortex. The feature representations in the higher Conv layers were encoded in the higher-order visual areas, including the ventral/medial/dorsal stream and middle temporal complex. The neural representations in the classification layers were observed mainly in the ventral stream visual cortex (including the inferior temporal cortex), superior parietal cortex, and prefrontal cortex. There was a surprising similarity between the neural representations from the CNN model and the neural representations for human visual perception in the context of the perception of digits versus objects, particularly in the primary visual and associated areas. This study also illustrates the uniqueness of human visual perception. Unlike the CNN model, the neural representation of digits and objects for humans is more widely distributed across the whole brain, including the frontal and temporal areas.

Dynamic landscape of long noncoding RNAs during leaf aging in Arabidopsis.

Leaf senescence, the last stage of leaf development, is essential for whole-plant fitness as it marks the relocation of nutrients from senescing leaves to reproductive or other developing organs. Temporally coordinated physiological and functional changes along leaf aging are fine-tuned by a highly regulated genetic program involving multi-layered regulatory mechanisms. Long noncoding RNAs (lncRNAs) are newly emerging as hidden players in many biological processes; however, their contribution to leaf senescence has been largely unknown. Here, we performed comprehensive analyses of RNA-seq data representing all developmental stages of leaves to determine the genome-wide lncRNA landscape along leaf aging. A total of 771 lncRNAs, including 232 unannotated lncRNAs, were identified. Time-course analysis revealed 446 among 771 developmental age-related lncRNAs (AR-lncRNAs). Intriguingly, the expression of AR-lncRNAs was regulated more dynamically in senescing leaves than in growing leaves, revealing the relevant contribution of these lncRNAs to leaf senescence. Further analyses enabled us to infer the function of lncRNAs, based on their interacting miRNA or mRNA partners. We considered functionally diverse lncRNAs including antisense lncRNAs (which regulate overlapping protein-coding genes), competitive endogenous RNAs (ceRNAs; which regulate paired mRNAs using miRNAs as anchors), and mRNA-interacting lncRNAs (which affect the stability of mRNAs). Furthermore, we experimentally validated the senescence regulatory function of three novel AR-lncRNAs including one antisense lncRNA and two mRNA-interacting lncRNAs through molecular and phenotypic analyses. Our study provides a valuable resource of AR-lncRNAs and potential regulatory networks that link the function of coding mRNA and AR-lncRNAs. Together, our results reveal AR-lncRNAs as important elements in the leaf senescence process.

Envisioning the use of in-situ arm movement data in stroke rehabilitation: Stroke survivors' and occupational therapists' perspectives.

BACKGROUND: The key for successful stroke upper-limb rehabilitation includes the personalization of therapeutic interventions based on patients' functional ability and performance level. However, therapists often encounter challenges in supporting personalized rehabilitation due to the lack of information about how stroke survivors use their stroke-affected arm outside the clinic. Wearable technologies have been considered as an effective, objective solution to monitor patients' arm use patterns in their naturalistic environments. However, these technologies have remained a proof of concept and have not been adopted as mainstream therapeutic products, and we lack understanding of how key stakeholders perceive the use of wearable technologies in their practice. OBJECTIVE: We aim to understand how stroke survivors and therapists perceive and envision the use of wearable sensors and arm activity data in practical settings and how we could design a wearable-based performance monitoring system to better support the needs of the stakeholders. METHODS: We conducted semi-structured interviews with four stroke survivors and 15 occupational therapists (OTs) based on real-world arm use data that we collected for contextualization. To situate our participants, we leveraged a pair of finger-worn accelerometers to collect stroke survivors' arm use data in real-world settings, which we used to create study probes for stroke survivors and OTs, respectively. The interview data was analyzed using the thematic approach. RESULTS: Our study unveiled a detailed account of (1) the receptiveness of stroke survivors and OTs for using wearable sensors in clinical practice, (2) OTs' envisioned strategies to utilize patient-generated sensor data in the light of providing patients with personalized therapy programs, and (3) practical challenges and design considerations to address for the accelerated integration of wearable systems into their practice. CONCLUSIONS: These findings offer promising directions for the design of a wearable solution that supports OTs to develop individually-tailored therapy programs for stroke survivors to improve their affected arm use.

Metal-Coordinated Phthalocyanines as Platform Molecules for Understanding Isolated Metal Sites in the Electrochemical Reduction of CO2.

Single-atom catalysts (SACs) of non-precious transition metals (TMs) often show unique electrochemical performance, including the electrochemical carbon dioxide reduction reaction (CO2RR). However, the inhomogeneity in their structures makes it difficult to directly compare SACs of different TM for their CO2RR activity, selectivity, and reaction mechanisms. In this study, the comparison of isolated TMs (Fe, Co, Ni, Cu, and Zn) is systematically investigated using a series of crystalline molecular catalysts, namely TM-coordinated phthalocyanines (TM-Pcs), to directly compare the intrinsic role of the TMs with identical local coordination environments on the CO2RR performance. The combined experimental measurements, in situ characterization, and density functional theory calculations of TM-Pc catalysts reveal a TM-dependent CO2RR activity and selectivity, with the free energy difference of ΔG(*HOCO) - ΔG(*CO) being identified as a descriptor for predicting the CO2RR performance.

Quantitative Study of Enantiomer-Specific State Transfer.

We here report on a quantitative study of enantiomer-specific state transfer, performed in a pulsed, supersonic molecular beam. The chiral molecule 1-indanol is cooled to low rotational temperatures (1-2 K) and a selected rotational level in the electronic and vibrational ground state of the most abundant conformer is depleted via optical pumping on the S_{1}←S_{0} transition. Further downstream, three consecutive microwave pulses with mutually perpendicular polarizations and with a well-defined duration and phase are applied. The population in the originally depleted rotational level is subsequently monitored via laser-induced fluorescence detection. This scheme enables a quantitative comparison of experiment and theory for the transfer efficiency in what is the simplest enantiomer-specific state transfer triangle for any chiral molecule, that is, the one involving the absolute ground state level, |J_{K_{a}K_{c}}⟩=|0_{00}⟩. Moreover, this scheme improves the enantiomer enrichment by over an order of magnitude compared to previous works. Starting with a racemic mixture, a straightforward extension of this scheme allows one to create a molecular beam with an enantiomer-pure rotational level, holding great prospects for future spectroscopic and scattering studies.

Highly stretchable transparent bar coated Ag NW/PEDOT:PSS hybrid electrode for wearable and stretchable devices.

In this study, we demonstrated poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT:PSS) as a composite with Ag nanowire (Ag NW) to enhance the stretchability of the Ag NW network electrode. The composite Ag NW/PEDOT:PSS hybrid ink (AP ink) was prepared at a ratio of 1 : 10, 1 : 20, and 1 : 30, respectively and bar coated on polyurethane substrate. The different ink ratios were studied and optimized with a sheet resistance of 14.93 Ω sq-1. and a transmittance of 88.6% showing a high performance in mechanical stress tests such as bending, folding, rolling, twisting, and stretching. It also showed a conductive bridge effect where the PEDOT:PSS acted as an anchor or support to Ag NW during mechanical strain and PEDOT:PSS also enhanced the electrical conductivity of the Ag NW. Therefore, to prove the real time performance of the electrode as a wearable device, we fabricated transparent electroluminescence devices and thin film heater devices which are highly flexible and demonstrated excellent performance proving that the AP electrode is more suitable candidate for future wearable transparent devices.