Miracle-dz/UniFAR-FTUs huggingface dataset:
Testing of the therapist to reduce maladaptive interactional patterns: Categorizing patients’ tests

ABSTRACT Objective This empirical study undertakes a categorization of the core concept of Control Mastery Theory: mostly unconscious testing of pathogenic beliefs that patients exhibit in relating to their therapist to work on their problems. The focus lays on latent meanings of manifest tests. Method We qualitatively analyze transcripts of 172 psychotherapy sessions with 23 patients for sequences in which significant patient-therapist interactions occur, and systematize identified tests into thematic categories based on what tests intent to achieve (ICC = .68). Guided by theory, the analysis is attending to complexity, individuality, and the unconscious. Results Tests circle around striving for independence, deserving/self-worth, acceptance, and entitlement. Individual tests have various underlying meanings, are interrelated, and may be multidimensional. Conclusion Meanings of tests must be confirmed within the psychotherapeutic process. Incorporating the treating clinician thus seems important.
A technical note on emerging combination approach involved in the onconanotherapeutics

Abstract Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made to formulate nanocarrier fabricated combinatorial drugs (NFCDs) to effectively manage and treat cancer. This approach offers several advantages, such as improved stability, lower drug exposure, targeted drug delivery, low side effects, and improved clinical outcome. Hence, in this review, first time, we have discussed the recent advancement and various types of nano carrier-based combinatorial drug delivery systems in a different type of cancer and highlighted the personalized combinatorial theranostic medicine as a futuristic anticancer treatment approach.
VIOLATION OF CHANDRASEKHAR MASS LIMIT: THE EXCITING POTENTIAL OF STRONGLY MAGNETIZED WHITE DWARFS

We consider a relativistic, degenerate, electron gas under the influence of a strong magnetic field, which describes magnetized white dwarfs. Landau quantization changes the density of states available to the electrons, thus modifying the underlying equation of state. In the presence of very strong magnetic fields a maximum of either one, two or three Landau level(s) is/are occupied. We obtain the mass–radius relations for such white dwarfs and their detailed investigation leads us to propose the existence of white dwarfs having a mass ~2.3M⊙, which overwhelmingly exceeds the Chandrasekhar mass limit.
Occupational Experience Effects on Physiological and Perceptual Responses of Common Soldiering Tasks

Supplemental Digital Content is Available in the Text. Abstract Cohen BS, Redmond JE, Haven CC, Foulis SA, Canino MC, Frykman PN, Sharp MA. Occupational Experience Effects on Physiological and Perceptual Responses of Common Soldiering Tasks. J Strength Cond Res 37(4): 894–901, 2023—This study measured the impact of occupational experience (i.e., time spent deployed, in military service, and in job and task performance frequency in training, deployment, and study practice) on the physiological (heart rate [HR] and oxygen consumption [VO2]) and perceptual (rate of perceived exertion [RPE]) responses to performance of critical physically demanding tasks (CPDTs). Five CPDTs (road march, build a fighting position, move under fire, evacuate a casualty, and drag a casualty to safety), common to all soldiers, were performed by 237 active duty soldiers. Linear regression models examined the association between measures of experience and physiological and perceptual performance responses to task demands. The level of significance was adjusted for multiple comparisons and set at ρ ≤ 0.0125 for this study. Significant and notable effect sizes included the impact of time spent deployed on the physiological measures of the road march (PostHR F = 24.84, p < 0.0001, β=-9.65), sandbag fill (PostHR F = 8.26, p = 0.005, β = −2.83), and sandbag carry (MeanHR F = 7.51, p = 0.007, β = −1.12; PostHR F = 7.35, p = 0.007, β = −0.87). For the road march task, there was a nearly 10 bpm decrease in postperformance HR for every year spent deployed. Road march, sandbag fill, and sandbag carry tasks PostHRs were also notably negatively associated with the experience measures of time in their MOS (job and time in military service but not for other physiological and perceptual responses, including VO2 and RPE. Frequency of task performance in training, deployment, and study practice was not meaningfully associated with experience. The results suggest that increasing task familiarization through on-the-job occupational operational experience may result in greater proficiency and reduced physiological effort.
Blood–Brain Barrier Disruption in Preclinical Mouse Models of Stroke Can Be an Experimental Artifact Caused by Craniectomy

Abstract The pathophysiological features of ischemia-related blood–brain barrier (BBB) disruption are widely studied using preclinical stroke models. However, in many of these models, craniectomy is required to confirm arterial occlusion via laser Doppler flowmetry or to enable direct ligation of the cerebral artery. In the present study, mice were used to construct a distal middle cerebral artery occlusion (dMCAO) model, a preclinical stroke model that requires craniectomy to enable direct ligation of the cerebral artery, or were subjected to craniectomy alone. dMCAO but not craniectomy caused neurodegeneration and cerebral infarction, but both procedures induced an appreciable increase in BBB permeability to Evans blue dye, fluorescein, and endogenous albumin but not to 10 kDa dextran-FITC, leading to cerebral edema. Using rats, we further showed that BBB disruption induced by craniectomy with no evidence of dural tearing was comparable to that induced by craniectomy involving tearing of the dura. In conclusion, our data demonstrated that craniectomy can be a major contributor to BBB disruption and cerebral edema in preclinical stroke models. The implications of this experimental artifact for translational stroke research and preclinical data interpretation are discussed.
Generation of platicons and frequency combs in optical microresonators with normal GVD by modulated pump

We demonstrate that flat-topped dissipative solitonic pulses, “platicons”, and corresponding frequency combs can be excited in optical microresonators with normal group velocity dispersion using either the amplitude modulation of the pump or the bichromatic pump. Soft excitation may occur in a particular frequency range if the modulation depth is large enough and the modulation frequency is close to the free spectral range of the microresonator.
Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns

Cancer cells undergo substantial metabolic alterations to sustain increased energy supply and uncontrolled proliferation. As an essential trace element, iron is vital for many biological processes. Evidence has revealed that cancer cells deploy various mechanisms to elevate the cellular iron concentration to accelerate proliferation. Ferroptosis, a form of cell death caused by iron-catalyzed excessive peroxidation of polyunsaturated fatty acids (PUFAs), is a promising therapeutic target for therapy-resistant cancers. Previous studies have reported that long noncoding RNA (lncRNA) is a group of critical regulators involved in modulating cell metabolism, proliferation, apoptosis, and ferroptosis. In this review, we summarize the associations among iron metabolism, ferroptosis, and ferroptosis-related lncRNA in tumorigenesis. This information will help deepen understanding of the role of lncRNA in iron metabolism and raise the possibility of targeting lncRNA and ferroptosis in cancer combination therapy.
Genetically Encoded Whole Cell Biosensor for Drug Discovery of HIF-1 Interaction Inhibitors

The heterodimeric transcription factor, hypoxia inducible factor-1 (HIF-1), is an important anticancer target as it supports the adaptation and response of tumors to hypoxia. Here, we optimized the repressed transactivator yeast two-hybrid system to further develop it as part of a versatile yeast-based drug discovery platform and validated it using HIF-1. We demonstrate both fluorescence-based and auxotrophy-based selections that could detect HIF-1α/HIF-1β dimerization inhibition. The engineered genetic selection is tunable and able to differentiate between strong and weak interactions, shows a large dynamic range, and is stable over different growth phases. Furthermore, we engineered mechanisms to control for cellular activity and off-target drug effects. We thoroughly characterized all parts of the biosensor system and argue this tool will be generally applicable to a wide array of protein–protein interaction targets. We anticipate this biosensor will be useful as part of a drug discovery platform, particularly when screening DNA-encoded new modality drugs.
A reinforcement learning‐based hybrid modeling framework for bioprocess kinetics identification

Constructing predictive models to simulate complex bioprocess dynamics, particularly time‐varying (i.e., parameters varying over time) and history‐dependent (i.e., current kinetics dependent on historical culture conditions) behavior, has been a longstanding research challenge. Current advances in hybrid modeling offer a solution to this by integrating kinetic models with data‐driven techniques. This article proposes a novel two‐step framework: first (i) speculate and combine several possible kinetic model structures sourced from process and phenomenological knowledge, then (ii) identify the most likely kinetic model structure and its parameter values using model‐free Reinforcement Learning (RL). Specifically, Step 1 collates feasible history‐dependent model structures, then Step 2 uses RL to simultaneously identify the correct model structure and the time‐varying parameter trajectories. To demonstrate the performance of this framework, a range of in‐silico case studies were carried out. The results show that the proposed framework can efficiently construct high‐fidelity models to quantify both time‐varying and history‐dependent kinetic behaviors while minimizing the risks of over‐parametrization and over‐fitting. Finally, the primary advantages of the proposed framework and its limitation were thoroughly discussed in comparison to other existing hybrid modeling and model structure identification techniques, highlighting the potential of this framework for general bioprocess modeling.
UPF1 increases amino acid levels and promotes cell proliferation in lung adenocarcinoma via the eIF2α-ATF4 axis

Up-frameshift 1 (UPF1), as the most critical factor in nonsense-mediated messenger RNA (mRNA) decay (NMD), regulates tumor-associated molecular pathways in many cancers. However, the role of UPF1 in lung adenocarcinoma (LUAD) amino acid metabolism remains largely unknown. In this study, we found that UPF1 was significantly correlated with a portion of amino acid metabolic pathways in LUAD by integrating bioinformatics and metabolomics. We further confirmed that UPF1 knockdown inhibited activating transcription factor 4 (ATF4) and Ser51 phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), the core proteins in amino acid metabolism reprogramming. In addition, UPF1 promotes cell proliferation by increasing the amino-acid levels of LUAD cells, which depends on the function of ATF4. Clinically, UPF1 mRNA expression is abnormal in LUAD tissues, and higher expression of UPF1 and ATF4 was significantly correlated with poor overall survival (OS) in LUAD patients. Our findings reveal that UPF1 is a potential regulator of tumor-associated amino acid metabolism and may be a therapeutic target for LUAD.
Interactions between host epithelial cells and Acinetobacter baumannii promote the emergence of highly antibiotic resistant and highly mucoid strains

ABSTRACT Acinetobacter baumannii is an important nosocomial pathogen. Upon colonizing a host, A. baumannii are subjected to selective pressure by immune defenses as they adapt to the host environment. However, the mechanism of this pathoadaptation is unknown. Here, we established an in vitro system to evolve A. baumannii driven by the continuous selective pressure exerted by epithelial cells, and we used a combination of experimental evolution, phenotypic characterization and multi-omics analysis to address the underlying mechanism. When continuously exposed to selective pressure by pulmonary epithelial cells, A. baumannii showed ptk mutation-mediated mucoid conversion (reduced adhesion and increased anti-phagocytic ability) by enhancement of capsular exopolysaccharide chain length; rsmG mutation-mediated deficiency of 7-methylguanosine modification in the 524th nucleotide of 16S rRNA, which increased ribosome translation efficiency; and rnaseI mutation-mediated changes in outer membrane permeability and efflux pump expression. Together, these mutations altered susceptibility to a variety of antimicrobial agents, including the novel antibiotic cefiderocol, by regulating siderophore and siderophore-receptor biosynthesis. In conclusion, pulmonary epithelial cells modulate A. baumannii pathoadaptation, implicating the host–microbe interaction in the survival and persistence of A. baumannii.
Physical exercise during neoadjuvant chemotherapy for breast cancer as a mean to increase pathological complete response rates: Trial protocol of the randomized Neo-ACT trial

Introduction In early breast cancer, neoadjuvant chemotherapy (NACT) is increasingly used. The proof of efficacy is pathologically complete response (pCR), i.e. the absence of invasive tumour in breast and lymph nodes at surgery. Today, pCR is a common endpoint in pharmaceutical trials since it is significantly associated with survival especially in triple-negative and HER2-positive subtypes. Apart from the mitigation of treatment-related toxicity and symptoms, physical exercise mediates anti-tumoral systemic effects associated with tumour regression in preclinical and clinical models. The aim of Neo-ACT is to test the hypothesis that physical exercise can improve pCR rates in breast cancer patients receiving NACT. Method The Neo-ACT trial is a prospective clinical trial, randomising T1-3N0-2 breast cancer patients planned for NACT to either a home-based physical exercise intervention supported by a mobile application or routine care. The primary endpoint is pCR; secondary endpoints are patient-reported quality of life, toxicity-related outcomes, and oncological outcomes such as Residual Cancer Burden, objective radiological tumour response, as well as overall, breast cancer-specific and disease-free survival at 2, 5 and 10 years. The intervention consists of a combination of high-intensity interval and resistance training of progressing intensity, and includes at least 150 min of moderate to vigorous physical activity per week, inclusive of two weekly 60-min exercise sessions. In order to show an improvement in pCR of 10%, a total of 712 participants need to be included in the analysis. The Neo-ACT has been registered at clinicaltrials.gov on January 11, 2022 (NCT05184582). Expected results If Neo-ACT can prove the oncological efficacy of physical exercise, implementation of training programmes into NACT schedules will be pursued. The use of a digitally led exercise intervention aims to test the potential of such a strategy for use in rural areas and areas of limited resources.
An analytic model for interacting dark energy and its observational constraints

The paper deals with a theoretical model for interacting dark energy. The interaction between the cold dark matter (dust) and the dark energy has been assumed to be non-gravitational in nature. Exact analytic cosmological solutions are obtained both for constant and variable equation of state for dark energy. It is found that, for very small value of the coupling parameter (in the interaction term), the model asymptotically extends up to $\Lambda$CDM, while the model can enter into the phantom domain asymptotically, if the coupling parameter is not so small. Both the solutions are then analyzed with 194 Supernovae Type Ia data. The best fit parameters are shown with 1$\sigma$ and 2$\sigma$ confidence intervals. Finally, we have discussed the cosmographic parameters for both the cases.
On topological modifications of Newton's law

Recent cosmological data for very large distances challenge the validity of the standard cosmological model. Motivated by the observed spatial flatness the accelerating expansion and the various anisotropies with preferred axes in the universe we examine the consequences of the simple hypothesis that the three-dimensional space has a global 2 ? 1 topology. We take the radius of the compactification to be the observed cosmological scale beyond which the accelerated expansion starts. We derive the induced corrections to the Newton's gravitational potential and we find that for distances smaller than the 1 radius the leading 1/r-term is corrected by convergent power series of multipole form in the polar angle making explicit the induced anisotropy by the compactified third dimension. On the other hand, for distances larger than the compactification scale the asymptotic behavior of the potential exhibits a logarithmic dependence with exponentially small corrections. The change of Newton's force from 1/r2 to 1/r behavior implies a weakening of the deceleration for the expanding universe. Such topologies can also be created locally by standard Newtonian axially symmetric mass distributions with periodicity along the symmetry axis. In such cases we can use our results to obtain measurable modifications of Newtonian orbits for small distances and flat rotation spectra, for large distances at the galactic level.
Discovering Asymmetric Dark Matter with Anti-Neutrinos

We discuss possible signatures of Asymmetric Dark Matter (ADM) through dark matter decays to neutrinos. We specifically focus on scenarios in which the Standard Model (SM) baryon asymmetry is transferred to the dark sector (DS) through higher dimensional operators in chemical equilibrium. In such cases, the dark matter (DM) carries lepton and/or baryon number, and we point out that for a wide range of quantum number assignments, by far the strongest constraints on dark matter decays come from decays to neutrinos through the "neutrino portal" operator HL. Together with the facts that ADM favors lighter DM masses ~ a few GeV and that the decays would lead only to anti-neutrinos and no neutrinos (or vice versa), the detection of such decays at neutrino telescopes would provide compelling evidence for ADM. We discuss current and future bounds on models where the DM decays to neutrinos through operators of dimension ~ 10^12 - 10^13 GeV.
Validating the short gambling harm screen against external benchmarks

Abstract Background and aims The Short Gambling Harm Screen (SGHS) is currently the most frequently applied dedicated measure of gambling-related harm (GRH), though concerns relating to scale validity have been expressed. The current study aimed to address criticisms that several SGHS items do not depict genuine harms that may occur as a result of gambling, causing the scale to overestimate harm. Specifically, we aimed to test convergence between the SGHS and its constituent items with: (1) wellbeing, and (2) psychological distress. Methods To test criterion validity of both the scale and the items, retrospective analyses of survey data from 2,704 Australian adults (36% non-gamblers; 64% gamblers) were conducted. Subjective wellbeing and psychological distress scores, captured using the Personal Wellbeing Index (PWI) and the Kessler-6 Psychological Distress Scale (K6), respectively, were used as external (non-gambling) benchmarks. A total of 428 (16%) respondents scored at least 1 on the SGHS. Results Monotonic decreases and increases, corresponding to poorer personal wellbeing and higher psychological distress, were found with each additional SGHS score increase. Gamblers endorsing a single SGHS item reported lower wellbeing and higher psychological distress than both non-gamblers and gamblers who scored zero on the SGHS. Discussion and conclusion These results show that the SGHS is a valid measure of GRH and contradict suggestions that low scores on the SGHS do not indicate true harm. The SGHS represents a valid and innovative short screening tool to measure GRH in population prevalence studies.
Korean guidelines for postpolypectomy colonoscopic surveillance: 2022 revised edition

Colonoscopic polypectomy is effective in decreasing the incidence and mortality of colorectal cancer (CRC). Premalignant polyps discovered during colonoscopy are associated with the risk of metachronous advanced neoplasia. Postpolypectomy surveillance is the most important method for the management of advanced metachronous neoplasia. A more efficient and evidence-based guideline for postpolypectomy surveillance is required because of limited medical resources and concerns regarding colonoscopy complications. In these consensus guidelines, an analytic approach was used to address all reliable evidence to interpret the predictors of CRC or advanced neoplasia during surveillance colonoscopy. The key recommendations state that the high-risk findings for metachronous CRC following polypectomy are as follows: (1) adenoma ≥10 mm in size; (2) 3 to 5 (or more) adenomas; (3) tubulovillous or villous adenoma; (4) adenoma containing high-grade dysplasia; (5) traditional serrated adenoma; (6) sessile serrated lesion (SSL) containing any grade of dysplasia; (7) serrated polyp of at least 10 mm in size; and (8) 3 to 5 (or more) SSLs. More studies are needed to fully comprehend the patients most likely to benefit from surveillance colonoscopy and the ideal surveillance interval to prevent metachronous CRC.
Development of a particle flux detection system for the MERIT high intensity target experiment at CERN

The construction of a high intensity neutrino source requires multi megawatt beams and challenges the targets in use. MERIT is a proof-of-principle test for a novel kind of neutrino factory target, employing a 24 GeV/c proton beam and a 1 cm in diameter free mercury jet as beam target. This thesis describes the design and implementation of a secondary particle flux production detection system. Employed detectors are polycrystalline diamond detectors and electron multipliers. Simulations of the secondary particle production have been made using FLUKA. The detection system is remotely controlled by a LabView interface and experimental observations from the initial analysis are presented.