Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies

Abstract Background Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Materials and methods Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided. Results Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125). Conclusion The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted. Trial registration (Clinicaltrials.gov) PRIME (NCT00364013), PEAK (NCT00819780).
A framework for the etiology of running‐related injuries

The etiology of running‐related injury is important to consider as the effectiveness of a given running‐related injury prevention intervention is dependent on whether etiologic factors are readily modifiable and consistent with a biologically plausible causal mechanism. Therefore, the purpose of the present article was to present an evidence‐informed conceptual framework outlining the multifactorial nature of running‐related injury etiology. In the framework, four mutually exclusive parts are presented: (a) Structure‐specific capacity when entering a running session; (b) structure‐specific cumulative load per running session; (c) reduction in the structure‐specific capacity during a running session; and (d) exceeding the structure‐specific capacity. The framework can then be used to inform the design of future running‐related injury prevention studies, including the formation of research questions and hypotheses, as well as the monitoring of participation‐related and non‐participation‐related exposures. In addition, future research applications should focus on addressing how changes in one or more exposures influence the risk of running‐related injury. This necessitates the investigation of how different factors affect the structure‐specific load and/or the load capacity, and the dose‐response relationship between running participation and injury risk. Ultimately, this direction allows researchers to move beyond traditional risk factor identification to produce research findings that are not only reliably reported in terms of the observed cause‐effect association, but also translatable in practice.
Fine-Tuning of Photosynthesis Requires CURVATURE THYLAKOID1-Mediated Thylakoid Plasticity1

The CURT1A component of the CURT1 protein complex mediates thylakoid membrane curvature and modulates photosynthesis to maintain plant fitness during fluctuating environmental conditions. The thylakoid membrane system of higher plant chloroplasts consists of interconnected subdomains of appressed and nonappressed membrane bilayers, known as grana and stroma lamellae, respectively. CURVATURE THYLAKOID1 (CURT1) protein complexes mediate the shape of grana stacks in a dosage-dependent manner and facilitate membrane curvature at the grana margins, the interface between grana and stroma lamellae. Although grana stacks are highly conserved among land plants, the functional relevance of grana stacking remains unclear. Here, we show that inhibiting CURT1-mediated alteration of thylakoid ultrastructure in Arabidopsis (Arabidopsis thaliana) reduces photosynthetic efficiency and plant fitness under adverse, controlled, and natural light conditions. Plants that lack CURT1 show less adjustment of grana diameter, which compromises regulatory mechanisms like the photosystem II repair cycle and state transitions. Interestingly, CURT1A suffices to induce thylakoid membrane curvature in planta and thylakoid hyperbending in plants overexpressing CURT1A. We suggest that CURT1 oligomerization is regulated at the posttranslational level in a light-dependent fashion and that CURT1-mediated thylakoid plasticity plays an important role in fine-tuning photosynthesis and plant fitness during challenging growth conditions.
Dependability of modular software in a multiuser operational environment

Effects of shared use on the dependability of modular software are evaluated in terms of a generally defined stochastic model. The total system in question consists of a community of n users who share a software system with m modules. The input aspect of the operational environment, reflecting user demands at the module level, is represented by a continuous-time, finite-state Markov process, called the operational profile. The profile's construction is based on the isolated profiles of individual users which, in the case of heterogeneous use, are pairwise-distinct processes. Moreover, in the presence of other users, an individual profile can differ from its isolated version due to "slowdowns" caused by sharing. This multiuser profile is then combined with a failure model which, among other things, captures "stress" due to shared use. A number of basic issues are then addressed and resolved in terms of closed-form dependability solutions obtained for elementary 2-user, 1-module systems. Specifically, three measures are investigated in this manner, providing considerable insight into how dependability, as perceived by a subject user, is affected by the profile of an interfering user.
Channel sparse representation based authentication for reconciliation of key generation

We propose a novel authentication method based on sparse representation for the reconciliation in physical layer key Generation. In order to protect the legitimation of the channel, sparse representation is considered to enhance wireless security by using the unique channel location information. In contrast to traditional approaches, in this paper, we consider that this reconciliation channel is unauthentic, and we formulate this problem as one of improved sparse representation. In this scheme, the position of the primary decomposition coefficients is adopted to ascertain whether the signal comes from legitimate devices or not. The effectiveness of this new process model is validated through experiments and simulations. These results shown that the proposed scheme can achieve desired identification performance even at lower signal-to-noise ratio (SNR).
Systematic Transcreation of Self-Help Smoking Cessation Materials for Hispanic/Latino Smokers: Improving Cultural Relevance and Acceptability

Smoking-related illnesses are the leading causes of death among Hispanics/Latinos. Yet, there are few smoking cessation interventions targeted for this population. The goal of this study was to “transcreate” an existing, previously validated, English language self-help smoking cessation intervention, titled Forever Free®: Stop Smoking for Good, for Spanish-speaking smokers. Rather than simply translating the materials, our transcreation process involved culturally adapting the intervention to enhance acceptability and receptivity of the information. We utilized a multiphase qualitative approach (focus groups and learner verification interviews) to develop a linguistically and culturally relevant intervention for the diverse sub-ethnic groups of Hispanic/Latino smokers. Focus group findings indicated a need to underscore several additional cultural characteristics and themes such as the need to address familism and unique stressors faced by immigrants and to provide information regarding nicotine replacement therapy. Learner verification findings indicated a need to further emphasize financial and social benefits of quitting smoking and to discuss how family and friends can support the quit attempt. These steps led to the development of a Spanish-language smoking cessation intervention titled, Libre del cigarillo, por mi familia y por mí: Guía para dejar de fumar, that is currently being tested in a national randomized controlled trial.
Endoplasmic reticulum stress, the unfolded protein response, and gene network modeling in antiestrogen resistant breast cancer

Abstract Lack of understanding of endocrine resistance remains one of the major challenges for breast cancer researchers, clinicians, and patients. Current reductionist approaches to understanding the molecular signaling driving resistance have offered mostly incremental progress over the past 10 years. As the field of systems biology has begun to mature, the approaches and network modeling tools being developed and applied therein offer a different way to think about how molecular signaling and the regulation of crucial cellular functions are integrated. To gain novel insights, we first describe some of the key challenges facing network modeling of endocrine resistance, many of which arise from the properties of the data spaces being studied. We then use activation of the unfolded protein response (UPR) following induction of endoplasmic reticulum stress in breast cancer cells by antiestrogens, to illustrate our approaches to computational modeling. Activation of UPR is a key determinant of cell fate decision-making and regulation of autophagy and apoptosis. These initial studies provide insight into a small subnetwork topology obtained using differential dependency network analysis and focused on the UPR gene XBP1. The XBP1 subnetwork topology incorporates BCAR3, BCL2, BIK, NF-κB, and other genes as nodes; the connecting edges represent the dependency structures among these nodes. As data from ongoing cellular and molecular studies become available, we will build detailed mathematical models of this XBP1-UPR network.
Annotation of Two Large Contiguous Regions from the Haemonchus contortus Genome Using RNA-seq and Comparative Analysis with Caenorhabditis elegans

The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes.
A Comparison of Computational Methods to Determine Intrastroke Velocity in Swimming Using IMUs

Sacrum located IMU sensors were used to monitor three-axis acceleration and three-axis rotation from elite swimmers in competition conditions. The intrastroke velocity was determined for each swimmer using their preferred swim stroke (freestyle, backstroke, and breaststroke) using three different calculation techniquesdual-axis acceleration, dual-axis acceleration eliminating the static gravity constant, and altitude and heading reference system. The mean intrastroke velocity variation (averaged over one 50-m lap) in freestyle swimming was less than 0.6 in all cases. This resulted in a timing under-estimate of less than 0.60ms for freestyle, 4.0ms for breaststroke, and a timing overestimate of less than 6.2ms for backstroke. The difference was less than 5 over the complete stroke (one way ANOVA p > 0.05), indicating no significant difference in the velocity profiles. These simple, robust analysis techniques can be used to quantify variations in every stroke as the swimmer fatigues, providing significant information to coaching staff and athletes.
A prospective, randomized, open label, controlled study investigating the efficiency and safety of 3 different methods of rectus sheath block analgesia following midline laparotomy

Background: There is a controversy regarding the efficacy of rectus sheath block (RSB). The aim of the present study was to evaluate analgesic efficacy and safety of three different methods of RSB in postoperative pain management after midline laparotomy. Methods: A prospective, randomized, controlled, open-label clinical trial with 4 parallel groups was conducted in a tertiary care hospital in Finland. A total of 57 patients undergoing midline laparotomy were randomized to the control group (n = 12) or to 1 of the 3 active RSB analgesia groups: single-dose (n = 16), repeated-doses (n = 12), or continuous infusion (n = 17). Opioid consumption with iv-patient-controlled analgesia pump was recorded, and pain scores and patients’ satisfaction were surveyed on an 11-point numeric rating scale for the first 48 postoperative h. Plasma concentrations of oxycodone and levobupivacaine were analyzed. All adverse events during the hospital stay were recorded. Results: Oxycodone consumption was less during the first 12 h in the repeated-doses and in the continuous infusion groups (P = .07) and in numerical values up to 48 h in the repeated-doses group. Plasma oxycodone concentrations were similar in all 4 groups. Pain scores were lower in the repeated-doses group when coughing during the first 4 h (P = .048 vs. control group), and at rest on the first postoperative morning (P = .034 vs. the other 3 groups) and at 24 h (P = .006 vs. the single-dose group). All plasma concentrations of levobupivacaine were safe. The patients’ satisfaction was better in the repeated-doses group compared with the control group (P = .025). No serious or unexpected adverse events were reported. Conclusions: RSB analgesia with repeated-doses seems to have opioid sparing efficacy, and it may enhance pain relief and patients’ satisfaction after midline laparotomy.
Overexpression of endoplasmic reticulum-resident chaperone attenuates cardiomyocyte death induced by proteasome inhibition.

AIMS Proteasome inhibitors are a novel class of anticancer agents that induce tumour cell death via endoplasmic reticulum (ER) stress. Since ER stress is involved in the development of heart failure, we investigated the role of ER-initiated cardiomyocyte death by proteasome inhibition. METHODS AND RESULTS Rat neonatal cardiomyocytes were used in this study. Proteasome activity was assayed using proteasome peptidase substrates. Cell viability and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide and flow cytometry, respectively. Western blot analysis, real-time polymerase chain reaction (PCR) and reverse transcriptional PCR were used to detect the expression of protein and messenger ribonucleic acid (RNA). The location of overexpressed glucose-regulated protein (GRP) 78 was observed by confocal fluorescence microscopy. Proteasome inhibition induced cardiomyocyte death and activated ER stress-induced transcriptional factor ATF6, but not XBP1 (X-box binding protein 1), without up-regulating ER chaperones. ER-initiated apoptosis signalling, including cytosine-cytosine-adenine-adenine-thymine enhancer-binding protein (C/EBP) homologous protein (CHOP), c-Jun-N-terminal kinase (JNK), and caspase-12, was activated by proteasome inhibition. Short interference RNA targeting CHOP, but not the blockage of caspase-12 or JNK pathway, attenuated cardiomyocyte death. Overexpression of GRP78 suppressed both CHOP expression and cardiomyocyte death by proteasome inhibition. CONCLUSION These findings demonstrate that proteasome inhibition induces ER-initiated cardiomyocyte death via CHOP-dependent pathways without compensatory up-regulation of ER chaperones. Supplement and/or pharmacological induction of GRP78 can attenuate cardiac damage by proteasome inhibition.
Real-Time System Modeling and Verification Through Labeled Transition System Analyzer

Model checking as a computer-assisted verification method is widely used in many fields to verify whether a design model satisfies the requirements specifications of the target system. In practice, it is difficult to design a system without the sophisticated requirements analysis. Unlike other model checking tools, the labeled transition system analyzer (LTSA) not only can specify the property specifications of the target system but also provides a structure diagram to specify the system architecture of the requirements model, which can be further used to design the target system. In this paper, we demonstrate the abilities of LTSA shipped with the classic case study of the steam boiler system. In the requirements analysis, the LTSA can specify the cyber and physical components of the target system and interactions between the components and the safety properties of the target system. In system design, the LTSA can automatically generate a start-up design model as the finite state process from the requirements model, and then a design model can be further accomplished by system architects and developers. Finally, the LTSA can automatically verify whether the design model meets the requirements specifications. Our work demonstrates the potential power of model checking tools can be applied and useful in software engineering for requirements analysis, system design, and verification.
Multimodal Mood Classification Framework for Hindi Songs

Music information retrieval is currently an active domain of research. An interesting aspect of music information retrieval involves mood classification. While the Western music captured much attention, research on Indian music was limited and mostly based on audio data. In this work, the authors propose a mood taxonomy and describe the framework for developing a multimodal dataset (audio and lyrics) for Hindi songs. We observed differences in mood for several instances of Hindi songs while annotating the audio of such songs in contrast to their corresponding lyrics. Finally, the mood classification frameworks were developed for Hindi songs and they consist of three different systems based on the features of audio, lyrics and both. The mood classification systems based on audio and lyrics achieved F-measures of 58.2% and 55.1%, respectively whereas the multimodal system (combination of both audio and lyrics) achieved the maximum F-measure of 68.6%.
Boolean approximation of a phase-coded aperture diffraction pattern system for X-ray crystallography

The phase retrieval problem involves recovering the phase of a signal from the amplitude of its Fourier transform. Recently, a phase recovery approach for a coded aperture-based acquisition system was proposed. The modulation is realized before the signal being diffracted, such that the underlying signal is recovered from coded diffraction patterns. Moreover, the modulation effect before diffraction can be obtained by using a phase coded aperture located after the sample under study. However, the practical implementation of a phase coded aperture in an X-ray application is not feasible, since it results in a matrix with complex entries and it requires changing the phase of the diffracted beams. Hence, this paper describes a coded X-ray diffraction pattern system based on block-unblock (Boolean) coded apertures that, unlike the phase coded apertures are easily implementable. The proposed system approximates the phase coded aperture by a block-unblock coded aperture by using the detour-phase method. This work used the SAXS/WAXS X-ray crystallography software to simulate the diffraction patterns of a real crystal structure called Rhombic Dodecahedron. Several simulations were realized to obtain the performance of some Boolean approximations in recovering the phase using the simulated diffraction pattern images. The quality of the reconstructions attain up to 22dB in terms of the Peak-Signal-to-Noise-Ratio.
2-Aminoacrylate Stress Induces a Context-Dependent Glycine Requirement in ridA Strains of Salmonella enterica

ABSTRACT The reactive enamine 2-aminoacrylate (2AA) is a metabolic stressor capable of damaging cellular components. Members of the broadly conserved Rid (RidA/YER057c/UK114) protein family mitigate 2AA stress in vivo by facilitating enamine and/or imine hydrolysis. Previous work showed that 2AA accumulation in ridA strains of Salmonella enterica led to the inactivation of multiple target enzymes, including serine hydroxymethyltransferase (GlyA). However, the specific cause of a ridA strain's inability to grow during periods of 2AA stress had yet to be determined. Work presented here shows that glycine supplementation suppressed all 2AA-dependent ridA strain growth defects described to date. Depending on the metabolic context, glycine appeared to suppress ridA strain growth defects by eliciting a GcvB small RNA-dependent regulatory response or by serving as a precursor to one-carbon units produced by the glycine cleavage complex (GCV). In either case, the data suggest that GlyA is the most physiologically sensitive target of 2AA inactivation in S. enterica. The universally conserved nature of GlyA among free-living organisms highlights the importance of RidA in mitigating 2AA stress. IMPORTANCE The RidA stress response prevents 2-aminoacrylate (2AA) damage from occurring in prokaryotes and eukaryotes alike. 2AA inactivation of serine hydroxymethyltransferase (GlyA) from Salmonella enterica restricts glycine and one-carbon production, ultimately reducing fitness of the organism. The cooccurrence of genes encoding 2AA production enzymes and serine hydroxy-methyltransferase (SHMT) in many genomes may in part underlie the evolutionary selection for Rid proteins to maintain appropriate glycine and one-carbon metabolism throughout life.