Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced respiration prevents drug tolerance and drug resistance in Mycobacterium tuberculosis

Significance Tuberculosis (TB) patients would greatly benefit from shorter treatment options. The treatment of drug-susceptible TB, a disease caused by the bacillus Mycobacterium tuberculosis, is a lengthy and strenuous process. This long therapy is because of the ability of a small population of cells to become drug-tolerant. Here, we demonstrate that the addition of small thiols to drug-treated M. tuberculosis prevents the emergence of drug-tolerant but also drug-resistant cells leading to sterilization of the cultures in vitro. The thiols potentiate drug activity by preventing the cells from entering a persister state and shutting down their metabolism while generating an oxidative burst. This dual mechanism of killing could lead to novel approaches to shorten TB chemotherapy. Persistence, manifested as drug tolerance, represents a significant obstacle to global tuberculosis control. The bactericidal drugs isoniazid and rifampicin kill greater than 99% of exponentially growing Mycobacterium tuberculosis (Mtb) cells, but the remaining cells are persisters, cells with decreased metabolic rate, refractory to killing by these drugs, and able to generate drug-resistant mutants. We discovered that the combination of cysteine or other small thiols with either isoniazid or rifampicin prevents the formation of drug-tolerant and drug-resistant cells in Mtb cultures. This effect was concentration- and time-dependent, relying on increased oxygen consumption that triggered enhanced production of reactive oxygen species. In infected murine macrophages, the addition of N-acetylcysteine to isoniazid treatment potentiated the killing of Mtb. Furthermore, we demonstrate that the addition of small thiols to Mtb drug treatment shifted the menaquinol/menaquinone balance toward a reduced state that stimulates Mtb respiration and converts persister cells to metabolically active cells. This prevention of both persister cell formation and drug resistance leads ultimately to mycobacterial cell death. Strategies to enhance respiration and initiate oxidative damage should improve tuberculosis chemotherapies.
Diversity Arrays Technology (DArT) Marker Platforms for Diversity Analysis and Linkage Mapping in a Complex Crop, the Octoploid Cultivated Strawberry (Fragaria × ananassa)

Cultivated strawberry (Fragaria × ananassa) is a genetically complex allo-octoploid crop with 28 pairs of chromosomes (2n = 8x = 56) for which a genome sequence is not yet available. The diploid Fragaria vesca is considered the donor species of one of the octoploid sub-genomes and its available genome sequence can be used as a reference for genomic studies. A wide number of strawberry cultivars are stored in ex situ germplasm collections world-wide but a number of previous studies have addressed the genetic diversity present within a limited number of these collections. Here, we report the development and application of two platforms based on the implementation of Diversity Array Technology (DArT) markers for high-throughput genotyping in strawberry. The first DArT microarray was used to evaluate the genetic diversity of 62 strawberry cultivars that represent a wide range of variation based on phenotype, geographical and temporal origin and pedigrees. A total of 603 DArT markers were used to evaluate the diversity and structure of the population and their cluster analyses revealed that these markers were highly efficient in classifying the accessions in groups based on historical, geographical and pedigree-based cues. The second DArTseq platform took benefit of the complexity reduction method optimized for strawberry and the development of next generation sequencing technologies. The strawberry DArTseq was used to generate a total of 9,386 SNP markers in the previously developed ‘232’ × ‘1392’ mapping population, of which, 4,242 high quality markers were further selected to saturate this map after several filtering steps. The high-throughput platforms here developed for genotyping strawberry will facilitate genome-wide characterizations of large accessions sets and complement other available options.
Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer

Background: Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib. To determine whether ALK-positive NSCLC is also sensitive to pemetrexed, we retrospectively evaluated progression-free survival (PFS) of ALK-positive versus ALK-negative patients who had been treated with pemetrexed-based chemotherapy for advanced NSCLC. Patients and methods: We identi ﬁ ed 121 patients with advanced, ALK-positive NSCLC in the USA, Australia, and Italy. For comparison, we evaluated 266 patients with advanced, ALK-negative, epidermal growth factor receptor (EGFR)-wild-type NSCLC, including 79 with KRAS mutations and 187 with wild-type KRAS (WT/WT/WT). We determined PFS on different pemetrexed regimens. Results: Among 70 ALK-positive patients treated with a platinum/pemetrexed regimen, the median PFS (mPFS) was 7.3 months (95% con ﬁ dence interval (CI) 5.5 – 9.5). The mPFS of 51 ALK-positive patients treated with single-agent pemetrexed or nonplatinum/pemetrexed combinations was 5.5 months (2.8 – 9.0). For ALK-negative patients, PFS on all pemetrexed-based regimens was similar to that of ALK-positive patients, except in the speci ﬁ c setting of ﬁ rst-line platinum/pemetrexed where the mPFS was only 4.2 and 5.4 months in KRAS and WT/WT/WT patients, respectively. However, among patients with a never/light-smoking history (0 – 10 pack-year smoking history) treated with ﬁ rst-line platinum/pemetrexed, there was no difference in PFS between ALK-positive and ALK-negative patients. Conclusions: PFS on pemetrexed or nonplatinum/pemetrexed combinations was similar in ALK-positive and ALK-negative patients. PFS on ﬁ rst-line platinum/pemetrexed may be prolonged in never/light-smoking patients regardless of ALK status.
De novo variants in KLF7 are a potential novel cause of developmental delay/intellectual disability, neuromuscular and psychiatric symptoms

Due to small numbers of reported patients with pathogenic variants in single genes, the phenotypic spectrum associated with genes causing neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder is expanding. Among these genes is KLF7 (Krüppel‐like factor 7), which is located at 2q33.3 and has been implicated in several developmental processes. KLF7 has been proposed to be a candidate gene for the phenotype of autism features seen in patients with a 2q33.3q34 deletion. Herein, we report 4 unrelated individuals with de novo KLF7 missense variants who share similar clinical features of developmental delay/ID, hypotonia, feeding/swallowing issues, psychiatric features and neuromuscular symptoms, and add to the knowledge about the phenotypic spectrum associated with KLF7 haploinsufficiency.
Acute Effects of Aerobic Exercise on Affect and Smoking Craving in the Weeks Before and After a Cessation Attempt

Introduction Aerobic exercise may improve smoking abstinence via reductions in craving and negative affect and increases in positive moods. Acute changes in craving and affect before and after structured exercise sessions have not been examined during the weeks prior to and following quit attempts nor has smoking status been examined in relation to these effects. Given that regular cigarette smoking can be perceived as affect enhancing and craving reducing, it is not known whether exercise could contribute additional affective benefit beyond these effects. Method Participants (N = 57; 68.4% women) were low-active daily smokers randomized to cessation treatments plus either group-based aerobic exercise (AE) or a health-education control (HEC). Mood, anxiety, and craving were assessed before and after each intervention session for each of the 12 weeks. Carbon monoxide (CO) breath samples ≤ 5ppm indicated smoking abstinence. Results During the prequit sessions, significantly greater decreases in anxiety following AE sessions relative to HEC sessions were observed. Changes in mood and craving were similar after AE and HEC sessions prior to quitting. Postquit attempt, significant reductions in craving and anxiety were observed after AE sessions but not following HEC. During the postquit period, positive mood increased following AE sessions relative to HEC only among individuals who were abstinence on that day. Conclusions AE may be effective in acutely reducing anxiety prior to a quit attempt and both anxiety and craving following the quit attempt regardless of abstinence status. The mood-enhancing effects of AE may occur only in the context of smoking abstinence. Implications The current findings underscore the importance of examining the acute effects of aerobic exercise prior to and after a cessation attempt and as a function of smoking status. Given the equivocal results from previous studies on the efficacy of exercise for smoking cessation, increasing our understanding of how aerobic exercise produces its reinforcing benefits for smokers attempting to quit could potentially inform the refinement (e.g., timing/sequencing) of exercise interventions within smoking cessation programs.
Trends and Patterns of Corticosteroid Use During Coronary Artery Bypass Grafting Surgery in the United States

Background: Several clinical trials have documented clinical benefits associated with prophylactic corticosteroid administration at the time of coronary artery bypass graft (CABG) surgery, including a reduction in the risk of atrial fibrillation and hospital length of stay. Despite the published data, the extent to which providers have adopted the perioperative use of corticosteroids remains unknown. Objectives: To assess temporal trends, between-hospital variation, and determinants of perioperative intravenous corticosteroid use during CABG surgery. Methods: We identified all patients admitted for CABG surgery in the Premier Healthcare Database (2003-2014), a large US-based inpatient database. We determined the proportion of patients administered prophylactic corticosteroids on the day of CABG surgery. Linear time-series models were used to estimate the rate and trend of corticosteroid use over time. Separate multivariable generalized estimating equation models were used to quantify the variation in and determinants of perioperative corticosteroid use. Results: Of 401 788 eligible patients who underwent a CABG surgery between 2003 and 2014, 20% (n = 80 681) were administered intravenous prophylactic perioperative corticosteroids (methylprednisolone, dexamethasone, or hydrocortisone). Corticosteroid use increased from 17.5% in 2003 to 22.6% in 2014 (annual rate = 0.42%; P < .001). Individual hospitals accounted for >50% of variation in corticosteroid use. High between-hospital variation was also observed, and the probability of utilization was ≥32.4% in the upper versus ≤3.4% in the bottom quartiles of hospitals. Conclusion: Prophylactic corticosteroid administration during CABG has increased gradually since 2003. To further evaluate the risk–benefit trade-off associated with their use, we believe a large-scale outcomes study is warranted to assess this highly variable practice.
Comparative evaluation of machine learning-based malware detection on Android

The Android platform is known as the market leader for mobile devices, but it also has gained much attention among malware authors in recent years. The widespread of malware, a consequence of its popularity and the design features of the Android ecosystem, constitutes a major security threat currently targeted by the research community. Among all counter methods proposed in previous publications, many rely on machine learning algorithms based on statically extracted attributes from an app. Machine learning, which is also inspired by the developed field of desktop malware detection, has proven to be a promising approach for fighting Android malware. Many publications, however, rely on different data sets for different application attributes, rendering the comparison of them difficult. Furthermore, there exist attribute sets known from the desktop world which have not been ported to Android yet. In this paper, we aim to step towards filling this gap by assessing the effectiveness of the total number of 11 attribute sets, including those never evaluated on Android before, using a consistent data set of 10,000 apps. Our comparative evaluation provides a ranking for the single attribute sets according the detection performance they can reach, and suggests the most effective combination of all attributes.
Half-Duplex Relay-Help Transmission with Dirty Paper Coding

In this paper, we consider a half-duplex relay channel where the relay node cannot transmit and receive simul- taneously. The information to be transmitted at the source node is composed of relayed information and non-relayed information. They interfere with each other in the existing scheme when the relay node forwards the relayed information and simultaneously the source node transmits the non-relayed information. In order to improve the transmission reliability, we propose two schemes where the source node chooses the non-relayed information codeword in terms of dirty paper coding (DPC). In Scheme 1, DPC technique is applied during the listening phase; and in Scheme 2, DPC technique is applied during the cooperative phase. Specially, we discuss the capacity behaviors of the proposed schemes and compare them with the baseline, namely the capacity behaviors of the existing scheme without the application of DPC technique. The corresponding numerical results prove that both proposed schemes outperform the existing scheme in the sense of capacity performance.
On the limits of computational functional genomics for bacterial lifestyle prediction

We review the level of genomic specificity regarding actinobacterial pathogenicity. As they occupy various niches in diverse habitats, one may assume the existence of lifestyle-specific genomic features. We include 240 actinobacteria classified into four pathogenicity classes: human pathogens (HPs), broad-spectrum pathogens (BPs), opportunistic pathogens (OPs) and non-pathogenic (NP). We hypothesize: (H1) Pathogens (HPs and BPs) possess specific pathogenicity signature genes. (H2) The same holds for OPs. (H3) Broad-spectrum and exclusively HPs cannot be distinguished from each other because of an observation bias, i.e. many HPs might yet be unclassified BPs. (H4) There is no intrinsic genomic characteristic of OPs compared with pathogens, as small mutations are likely to play a more dominant role to survive the immune system. To study these hypotheses, we implemented a bioinformatics pipeline that combines evolutionary sequence analysis with statistical learning methods (Random Forest with feature selection, model tuning and robustness analysis). Essentially, we present orthologous gene sets that computationally distinguish pathogens from NPs (H1). We further show a clear limit in differentiating OPs from both NPs (H2) and pathogens (H4). HPs may also not be distinguished from bacteria annotated as BPs based only on a small set of orthologous genes (H3), as many HPs might as well target a broad range of mammals but have not been annotated accordingly. In conclusion, we illustrate that even in the post-genome era and despite next-generation sequencing technology, our ability to efficiently deduce real-world conclusions, such as pathogenicity classification, remains quite limited.
Beyond rigidity: obtain localisability with noisy ranging measurement

Location awareness is crucial for wireless networks, attracting many research efforts in recent years. One of the fundamental problems of localisation is to determine whether or not a network is uniquely localisable. To address this problem, existing approaches often adopt the rigidity theory, which assumes accurate inter-node distance measurements. Considering the measurement errors, we introduce the concept of strong localisability and propose an algorithm, called LAS, to identify and locate a kind of strongly localisable networks. Besides, we further conduct extensive simulations to show the performance of LAS design.
Judged and Remembered Trustworthiness of Faces Is Enhanced by Experiencing Multisensory Synchrony and Asynchrony in the Right Order

This work builds on the enfacement effect. This effect occurs when experiencing a rhythmic stimulation on one’s cheek while seeing someone else’s face being touched in a synchronous way. This typically leads to cognitive and social-cognitive effects similar to self-other merging. In two studies, we demonstrate that this multisensory stimulation can change the evaluation of the other’s face. In the first study, participants judged the stranger’s face and similar faces as being more trustworthy after synchrony, but not after asynchrony. Synchrony interacted with the order of the stroking; hence trustworthiness only changed when the synchronous stimulation occurred before the asynchronous one. In the second study, a synchronous stimulation caused participants to remember the stranger’s face as more trustworthy, but again only when the synchronous stimulation came before the asynchronous one. The results of both studies show that order of stroking creates a context in which multisensory synchrony can affect the trustworthiness of faces.
Induced Förster resonance energy transfer by encapsulation of DNA-scaffold based probes inside a plant virus based protein cage

Insight into the assembly and disassembly of viruses can play a crucial role in developing cures for viral diseases. Specialized fluorescent probes can benefit the study of interactions within viruses, especially during cell studies. In this work, we developed a strategy based on Förster resonance energy transfer (FRET) to study the assembly of viruses without labeling the exterior of viruses. Instead, we exploit their encapsulation of nucleic cargo, using three different fluorescent ATTO dyes linked to single-stranded DNA oligomers, which are hybridised to a longer DNA strand. FRET is induced upon assembly of the cowpea chlorotic mottle virus, which forms monodisperse icosahedral particles of about 22 nm, thereby increasing the FRET efficiency by a factor of 8. Additionally, encapsulation of the dyes in virus-like particles induces a two-step FRET. When the formed constructs are disassembled, this FRET signal is fully reduced to the value before encapsulation. This reversible behavior makes the system a good probe for studying viral assembly and disassembly. It, furthermore, shows that multi-component supramolecular materials are stabilized in the confinement of a protein cage.
Integrating Diverse Types of Genomic Data to Identify Genes that Underlie Adverse Pregnancy Phenotypes

Progress in understanding complex genetic diseases has been bolstered by synthetic approaches that overlay diverse data types and analyses to identify functionally important genes. Pre-term birth (PTB), a major complication of pregnancy, is a leading cause of infant mortality worldwide. A major obstacle in addressing PTB is that the mechanisms controlling parturition and birth timing remain poorly understood. Integrative approaches that overlay datasets derived from comparative genomics with function-derived ones have potential to advance our understanding of the genetics of birth timing, and thus provide insights into the genes that may contribute to PTB. We intersected data from fast evolving coding and non-coding gene regions in the human and primate lineage with data from genes expressed in the placenta, from genes that show enriched expression only in the placenta, as well as from genes that are differentially expressed in four distinct PTB clinical subtypes. A large fraction of genes that are expressed in placenta, and differentially expressed in PTB clinical subtypes (23–34%) are fast evolving, and are associated with functions that include adhesion neurodevelopmental and immune processes. Functional categories of genes that express fast evolution in coding regions differ from those linked to fast evolution in non-coding regions. Finally, there is a surprising lack of overlap between fast evolving genes that are differentially expressed in four PTB clinical subtypes. Integrative approaches, especially those that incorporate evolutionary perspectives, can be successful in identifying potential genetic contributions to complex genetic diseases, such as PTB.
Preserved Error-Monitoring in Borderline Personality Disorder Patients with and without Non-Suicidal Self-Injury Behaviors

Background The presence of non-suicidal self-injury acts in Borderline Personality Disorder (BPD) is very prevalent. These behaviors are a public health concern and have become a poorly understood phenomenon in the community. It has been proposed that the commission of non-suicidal self-injury might be related to a failure in the brain network regulating executive functions. Previous studies have shown that BPD patients present an impairment in their capacity to monitor actions and conflicts associated with the performance of certain actions, which suppose an important aspect of cognitive control. Method We used Event Related Potentials to examine the behavioral and electrophysiological indexes associated with the error monitoring in two BPD outpatients groups (17 patients each) differentiated according to the presence or absence of non-suicidal self-injury behaviors. We also examined 17 age- and intelligence- matched healthy control participants. Results The three groups did not show significant differences in event-related potentials associated with errors (Error-Related Negativity and Pe) nor in theta power increase following errors. Conclusions This is the first study investigating the behavioral and electrophysiological error monitoring indexes in BPD patients characterized by their history of non-suicidal self-injury behaviors. Our results show that error monitoring is preserved in BPD patients and suggest that non-suicidal self-injury acts are not related to a dysfunction in the cognitive control mechanisms.
GCH1 attenuates cardiac autonomic nervous remodeling in canines with atrial‐tachypacing via tetrahydrobiopterin pathway regulated by microRNA‐206

Cardiac autonomic nerve remodeling (ANR) is an important mechanism of atrial fibrillation (AF). GTP cyclohydrolase I, encoded by GCH1, is the rate‐limiting enzyme in de novo synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthesis. Previous studies reported that increased BH4 and NO content negatively regulated nerve regeneration. This study investigated the effects of GCH1 on ANR via BH4 pathway, regulated by microRNA‐206 (miR‐206).