Miracle-dz/UniFAR-FTUs huggingface dataset:
Different Proteins Mediate Step-Wise Chromosome Architectures in Thermoplasma acidophilum and Pyrobaculum calidifontis

Archaeal species encode a variety of distinct lineage-specific chromosomal proteins. We have previously shown that in Thermococcus kodakarensis, histone, Alba, and TrmBL2 play distinct roles in chromosome organization. Although our understanding of individual archaeal chromosomal proteins has been advancing, how archaeal chromosomes are folded into higher-order structures and how they are regulated are largely unknown. Here, we investigated the primary and higher-order structures of archaeal chromosomes from different archaeal lineages. Atomic force microscopy of chromosome spreads out of Thermoplasma acidophilum and Pyrobaculum calidifontis cells revealed 10-nm fibers and 30–40-nm globular structures, suggesting the occurrence of higher-order chromosomal folding. Our results also indicated that chromosome compaction occurs toward the stationary phase. Micrococcal nuclease digestion indicated that fundamental structural units of the chromosome exist in T. acidophilum and T. kodakarensis but not in P. calidifontis or Sulfolobus solfataricus. In vitro reconstitution showed that, in T. acidophilum, the bacterial HU protein homolog HTa formed a 6-nm fiber by wrapping DNA, and that Alba was responsible for the formation of the 10-nm fiber by binding along the DNA without wrapping. Remarkably, Alba could form different higher-order complexes with histone or HTa on DNA in vitro. Mass spectrometry detected HTa in the T. acidophilum chromosome but not in other species. A putative transcriptional regulator of the AsnC/Lrp family (Pcal_1183) was detected on the P. calidifontis chromosome, but not on that of other species studied. Putative membrane-associated proteins were detected in the chromosomes of the three archaeal species studied, including T. acidophilum, P. calidifontis, and T. kodakarensis. Collectively, our data show that Archaea use different combinations of proteins to achieve chromosomal architecture and functional regulation.
SICD6mA: Identifying 6mA Sites using Deep Memory Network

Background DNA N6-methyladenine (6mA) is a kind of epigenetic modification in prokaryotes and eukaryotes, which involves multiple biological processes, such as gene regulation and tumorigenesis. Identifying 6mA contributes to understand its regulatory role. Therefore, to satisfy the needs of large-scale preliminary screening, it is necessary to develop the high-quality computational models for the rapid identification of 6mA sites. However, the existing calculation approaches are mostly specific to rice, and they have not been extensively applied to human genome. Results This study proposed a classification method of deep learning based on the memory mechanism named SICD6mA. In addition, the large benchmark datasets were constructed for human and rice, respectively, which integrated the recently reported 6mA sites. According to the evaluation results, SICD6mA displayed favorable robustness during cross-validations, which achieved the area under the curve (AUC) values of 0.9824 and 0.9903 for Human and Rice’s genomes in independent test evaluations, separately. Conclusions The successful prediction rate of 6mA sites on cross-species genomes exhibited higher accuracy than that of the state-of-the-art methods. For the convenience of experimental scientists, the user-friendly tool SICD6mA was developed to predict the cross-species 6mA sites, thereby accelerating and facilitating future cross-species genome research.
Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation

Re-activation and clonal expansion of tumor specific antigen (TSA)-reactive T cells are critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL) based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. Here we introduce FucoID as a general platform to detect endogenous antigen-specific T cells and study their biology. Through this interaction dependent labeling approach, TSA-reactive T cells can be detected and separated from bystander T cells in primary tumor digests based on their cell-surface enzymatic fucosyl-biotinylation. Compared to bystander TILs, TSA-reactive TILs possess a distinct TCR repertoire and unique gene features. Though exhibiting a dysfunctional phenotype, this subset of TILs possesses substantial capabilities of proliferation and tumor specific killing. FucoID features genetic manipulation-free procedures and a quick turnover cycle, and therefore should have the potential of accelerating the pace of personalized cancer treatment. Highlights Interaction dependent fucosylation enables the detection and isolation of bona fide intratumoral tumor specific antigen-reactive T cells Tumor specific antigen-reactive CD8+ T cells possess capabilities to be expanded and adoptively transferred for tumor control Tumor specific antigen-reactive CD8+ T cells feature oligoclonal expansion and upregulate genes for the steroid biosynthesis and metabolic process Intratumoral bystander CD8+ T cells can be separated into two groups based on PD-1 expression that feature distinct gene modules
Association between intentional ingestion of foreign objects and psychiatric disease among prisoners: A retrospective study

Introduction: Intentional ingestion of foreign objects (IIFO) is prevalent among U.S. prisoners. IIFOs often require surgical or endoscopic interventions, extended hospital stays, and may result in significant morbidity or even mortality. Although psychiatric illness is prevalent among prisoners engaging in IIFO, this association remains poorly defined. The aim of this study is to describe the psychiatric illness profile among prisoners diagnosed with IIFO. We hypothesized that repeated episodes of IIFO are associated with an escalating pattern of documented psychiatric illness. Methods: After approvals were obtained from our Institutional Review Board and the Ohio Department of Rehabilitation and Correction, a retrospective study was conducted of prisoners presenting to our facility with IIFO between 2004 and 2011. All historical and concurrent psychiatric diagnoses were abstracted from the medical record and classified into Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition based categories. In addition, medical history, alcohol/drug use, and prior episodes of IIFO were recorded. Statistical analyses included Chi-square and Kruskal–Wallis tests for categorical and continuous data, respectively. Results: We analyzed 136 IIFO episodes involving 27 patients. Repeat IIFO episodes were associated with an increasing number of psychiatric diagnoses. Patients with their fifth or later IIFO had a larger number of psychiatric diagnoses and the number of objects ingested as compared to patients presenting with a first episode (P < 0.01). Similarly, patients who went on to present with additional episodes of IIFO during the study had more psychiatric diagnoses identified throughout their visits (P < 0.01). The proportion of patients with mood and anxiety disorders (including post-traumatic stress) was progressively greater among prisoners with recurrent episodes of IIFO (P < 0.05). Other psychiatric disorders were not significantly associated with IIFO escalation. Conclusions: We observed a significant association between IIFO recurrences and increases in both the quantity of ingested items and the number of documented psychiatric diagnoses. Of note, psychiatric diagnoses of malingering or secondary gain were not identified in the current patient sample. Consideration of early psychiatric evaluation and intervention in the setting of IIFO, especially recurrent IIFO, is strongly encouraged. The following core competencies are addressed in this article: Medical knowledge, Patient care, Systems-based practice.
Krüppel-Like Factor 14 Improves Cardiac Function After Myocardial Infarction

Background Reversal of heart failure after myocardial infarction (MI) remains a global challenge. The goal of a clinical physician is to prevent heart failure immediately following the infarct. Since traditional strategies are only partially helpful for improving cardiac function, there is an urgency to identify novel approaches to maintain cardiac function. Objectives The aim of this study was to determine the role of Krüppel-Like Factor 14 (KLF14) in the heart post-MI. Methods and Results Wild-type and KLF14 overexpression mice were subjected to MI. At four weeks following MI, the infarct size was significantly reduced, left ventricular fraction shortening was significantly preserved, and left ventricular chamber dilation was attenuated in the KLF14 overexpression group. Transmission electron microscopy studies revealed striking evidence of decreased mitochondrial damage in the KLF14 overexpression myocardium following MI. To gain insight into the underlying relationship between KLF14 and mitochondria, we examined a broad array of genes involved in mitochondrial function and found that KLF14 overexpression was involved in the decreased apoptosis of mitochondria induced by H2O2. This beneficial effect was associated with increased levels of PGC-1α. Conclusions These results demonstrate that KLF14 plays a critical protective role in the heart after MI by regulating mitochondrial function, which may be achieved by regulating PGC-1α.
Presynaptically silent synapses are modulated by the density of surrounding astrocytes

The astrocyte, a major glial cell type, is involved in formation and maturation of synapses, and thus contributes to sustainable synaptic transmission between neurons. Given that the animals in the higher phylogenetic tree have brains with higher density of glial cells with respect to neurons, there is a possibility that the relative astrocytic density directly influences synaptic transmission. However, the notion has not been tested thoroughly. Here we addressed it, by using a primary culture preparation where single hippocampal neurons are surrounded by a variable but countable number of cortical astrocytes in dot-patterned microislands, and recording synaptic transmission by patch-clamp electrophysiology. Neurons with a higher astrocytic density showed a higher amplitude of evoked excitatory postsynaptic current (EPSC) than that of neurons with a lower astrocytic density. The size of readily releasable pool of synaptic vesicles per neuron was significantly higher. The frequency of spontaneous synaptic transmission (miniature EPSC) was higher, but the amplitude was unchanged. The number of morphologically identified glutamatergic synapses was unchanged, but the number of functional ones was increased, indicating a lower ratio of presynaptically silent synapses. Taken together, the higher astrocytic density enhanced excitatory synaptic transmission by increasing the number of functional synapses through presynaptic un-silencing.
COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning

To ultimately combat the emerging COVID-19 pandemic, it is desired to develop an effective and safe vaccine against this highly contagious disease caused by the SARS-CoV-2 coronavirus. Our literature and clinical trial survey showed that the whole virus, as well as the spike (S) protein, nucleocapsid (N) protein, and membrane protein, have been tested for vaccine development against SARS and MERS. We further used the Vaxign reverse vaccinology tool and the newly developed Vaxign-ML machine learning tool to predict COVID-19 vaccine candidates. The N protein was found to be conserved in the more pathogenic strains (SARS/MERS/COVID-19), but not in the other human coronaviruses that mostly cause mild symptoms. By investigating the entire proteome of SARS-CoV-2, six proteins, including the S protein and five non-structural proteins (nsp3, 3CL-pro, and nsp8-10) were predicted to be adhesins, which are crucial to the viral adhering and host invasion. The S, nsp3, and nsp8 proteins were also predicted by Vaxign-ML to induce high protective antigenicity. Besides the commonly used S protein, the nsp3 protein has not been tested in any coronavirus vaccine studies and was selected for further investigation. The nsp3 was found to be more conserved among SARS-CoV-2, SARS-CoV, and MERS-CoV than among 15 coronaviruses infecting human and other animals. The protein was also predicted to contain promiscuous MHC-I and MHC-II T-cell epitopes, and linear B-cell epitopes localized in specific locations and functional domains of the protein. Our predicted vaccine targets provide new strategies for effective and safe COVID-19 vaccine development.
Surgery and Radioactive Iodine Therapeutic Strategy for Patients Greater Than 60 Years of Age with Differentiated Thyroid Cancer

Purpose The purpose of the current study was to determine whether older patients with differentiated thyroid cancer (DTC) who received surgical treatment had a better cause-specific survival (CSS) than patients who were recommended surgery, but declined, and whether patients who underwent post-operative RAI-131 therapy had an impact on CSS based on TNM staging and number of lymph node metastases for all total or near-total thyroidectomy patients. Patients and Methods All DTC patients information were obtained from the SEER*Stat 8.3. 6 program, and only patients ≥ 60 years or older were considered. The patients were divided into two groups (underwent surgery and surgery recommend, but not performed). Furthermore, patients were grouped as follows: T4; N1b; M1; T1-3N0-1a; specific number of lymph node metastases; and total or near-total thyroidectomy. Results The 120-month cause-specific survival (CSS) rate of females and males showed a gradual declining trend from 60-64 to ≥80 years of age in the group that underwent surgery. The CSS rate of females and males showed a marked downward and irregular trend with an increase in age in the recommended, but no surgery group. Univariate analysis indicated that the surgery group had a higher 120-month CSS in females in most stages and males, compared with the no surgery group. RAI-131 therapy was associated with an improved 80-month CSS in T4/N1b/M1 females (P<0.0183) and males (P<0.0011). There was no CSS difference in females or males between the T1-3N0 and T1-3N1a patients. There was no statistical difference between the two subgroups. Conclusions Surgical treatment should be recommended for elderly DTC patients because surgery can lead to a better CSS. High-risk patients achieve a higher benefit-to-risk ratio with RAI-131 therapy. To avoid the adverse effects associated with RAI-131 therapy, a multidisciplinary discussion should be arranged for intermediate- and low-risk patients.
Acute renal infarction complicated by a sentinel loop in a patient with atrial fibrillation

A sentinel loop observed on plain radiography is a known sign of localized paralytic ileus that is primarily associated with acute pancreatitis, acute cholecystitis, and acute appendicitis. Here, we report a case of acute renal infarction (RI) complicated by a sentinel loop. A 58-year-old man with atrial fibrillation (AF) was hospitalized for paralytic ileus and was subsequently diagnosed with acute RI caused by embolism from the heart. Reports of sentinel loop signs on radiographs as a complication of acute RI are not available in previous English literature. For early diagnosis of acute RI and initiation of therapy to recover the function of the affected kidney and to prevent repeated thromboembolic events, it is important to recognize that a sentinel loop can be seen in acute RI as well as in other intra-abdominal inflammatory diseases.
Unsupervised manifold learning of collective behavior

Collective behavior is an emergent property of numerous complex systems, from financial markets to cancer cells to predator-prey ecological systems. Characterizing modes of collective behavior is often done through human observation, training generative models, or other supervised learning techniques. Each of these cases requires knowledge of and a method for characterizing the macro-state(s) of the system. This presents a challenge for studying novel systems where there may be little prior knowledge. Here, we present a new unsupervised method of detecting emergent behavior in complex systems, and discerning between distinct collective behaviors. We require only metrics, d(1), d(2), defined on the set of agents, X, which measure agents’ nearness in variables of interest. We apply the method of diffusion maps to the systems (X, d(i)) to recover efficient embeddings of their interaction networks. Comparing these geometries, we formulate a measure of similarity between two networks, called the map alignment statistic (MAS). A large MAS is evidence that the two networks are codetermined in some fashion, indicating an emergent relationship between the metrics d(1) and d(2). Additionally, the form of the macro-scale organization is encoded in the covariances among the two sets of diffusion map components. Using these covariances we discern between different modes of collective behavior in a data-driven, unsupervised manner. This method is demonstrated on empirical fish schooling data. We show that our state classification subdivides the known behaviors of the school in a meaningful manner, leading to a finer description of the system’s behavior. Author summary Many complex systems in society and nature exhibit collective behavior where individuals’ local interactions lead to system-wide organization. One challenge we face today is to identify and characterize these emergent behaviors, and here we have developed a new method for analyzing data from individuals, to detect when a given complex system is exhibiting system-wide organization. Importantly, our approach requires no prior knowledge of the fashion in which the collective behavior arises, or the macro-scale variables in which it manifests. We apply the new method to an agent-based model and empirical observations of fish schooling. While we have demonstrated the utility of our approach to biological systems, it can be applied widely to financial, medical, and technological systems for example.
The Drosophila Amyloid Precursor Protein homologue mediates neuronal survival and neuro-glial interactions

The amyloid precursor protein (APP) is a structurally and functionally conserved transmembrane protein whose physiological role in adult brain function and health is still unclear. Because mutations in APP cause familial Alzheimer’s disease, most research focuses on this aspect of APP biology. We investigated the physiological function of APP in the adult brain using the fruit fly Drosophila melanogaster, which harbors a single APP homologue called APP Like (APPL). Previous studies have provided evidence for the implication of APPL in neuronal wiring and axonal growth through the Wnt signaling pathway. However, like APP, APPL continues to be expressed in all neurons of the adult brain where its functions and their molecular and cellular underpinnings are unknown. We report that APPL loss of function results in the dysregulation of endolysosomal function, in both neurons and glia, with a notable enlargement of early endosomal compartment in neurons followed by neuronal cell death, the accumulation of dead neurons in the brain during a critical period at a young age and subsequent reduction in lifespan. These defects can be rescued by reduction in the levels of the early endosomal regulator Rab5, indicating a causal role of endosomal function for cell death. Finally, we show that the secreted extracellular domain of APPL is taken up by glia, regulates their endosomal morphology and this is necessary and sufficient for the clearance of neuronal debris in an axotomy model. We propose that the APP proteins represent a novel family of neuro-glial signaling proteins required for adult brain homeostasis.
EEG signal diversity reflects capability for behavioral responsiveness during propofol sedation

Background Transitions between wakefulness and anesthesia are accompanied by profound changes in brain functioning. A key challenge is to disentangle neuronal mechanisms specific to loss and recovery of consciousness, from more general effects that are not directly related to the capacity for conscious experience. Measures of neuronal diversity have been recently proposed to constitute a robust correlate of the global states of consciousness. In the present study we investigated whether EEG signal diversity is indeed related to behavioral responsiveness during propofol sedation, or rather to the general drug-related effects. Methods We reanalyzed data collected from 20 subjects sedated with propofol. Based on the responsiveness to auditory stimuli all subjects were subdivided into two subgroups - responsive (n = 13), who remains awake throughout the experiment, and drowsy (n = 7), who becomes unresponsive during moderate sedation. Resting state EEG recorded during wakefulness and sedation was characterized by the Mean Information Gain - an information-theory measure estimating signal diversity. Results In line with our hypothesis, the drowsy group exhibited a decrease in diversity during sedation but, unexpectedly, the responsive group exhibited a robust increase in diversity (ANOVA group x state interaction: F(3) = 7.81, p < 0.001; BF10 > 100). Conclusions We revealed that propofol sedation is initially related to an increase in EEG signal diversity, and that only upon loss of responsiveness EEG diversity decreases. The qualitatively different pattern of changes in the responsive and drowsy groups makes EEG diversity a robust indirect index of responsiveness and, presumably, consciousness.
Age at surgery and outcomes of an undescended testis: A single center experience

Objective - To evaluate age at surgery and outcomes of undescended testis (UDT) of boys who underwent surgical treatment at our institution. Methods - The retrospective study was conducted from December 2006 until December 2016 analysing the medical documentation of boys with UDT who were treated with orchidopexy. Age of boys at the time of diagnosis, age at which orchidopexy was performed, results of intraoperative observations and treatment complications were analysed. Results - Orchidopexy was performed in 562 boys with UDT. The median age at the time of orchidopexy was 50.5 months (IQR 22 – 117); orchidopexy was most frequently performed between the ages of 4 and 6 in 35.2% (198/562) boys, while the least number of boys 3.5% (20/562) underwent orchidopexy during the first year of life. The most common form was unilateral UDT with the prevalence of 93% (523/562), out of which 67.6% (380/562) of cases had UDT located in the inguinal canal. The rarest location of UDT was intraabdominal with the prevalence of 3.9% (22/562). Complications such as retraction of testis out of scrotum, testicular atrophy, postoperative hernia and wound infection were observed in 1.7% (10/562), 0.53% (3/562), 1.2% (7/562) and 0.88% (5/562), respectively. The efficacy of orchidopexy was 96.6%. Conclusion - Although the most boys included in the study had surgery at a later age than recommended, the success rate of orhidopexy was significant with the small number of complications. Our findings support that orhidopexy is both the standard and the option for the successful management of UDT.