Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced carbonyl stress induces irreversible multimerization of CRMP2 in schizophrenia pathogenesis

Enhanced carbonyl stress results in neurodevelopmental deficits by affecting microtubule function through the formation of irreversible dysfunctional multimer of carbonylated CRMP2. Enhanced carbonyl stress underlies a subset of schizophrenia, but its causal effects remain elusive. Here, we elucidated the molecular mechanism underlying the effects of carbonyl stress in iPS cells in which the gene encoding zinc metalloenzyme glyoxalase I (GLO1), a crucial enzyme for the clearance of carbonyl stress, was disrupted. The iPS cells exhibited significant cellular and developmental deficits, and hyper-carbonylation of collapsing response mediator protein 2 (CRMP2). Structural and biochemical analyses revealed an array of multiple carbonylation sites in the functional motifs of CRMP2, particularly D-hook (for dimerization) and T-site (for tetramerization), which are critical for the activity of the CRMP2 tetramer. Interestingly, carbonylated CRMP2 was stacked in the multimer conformation by irreversible cross-linking, resulting in loss of its unique function to bundle microtubules. Thus, the present study revealed that the enhanced carbonyl stress stemmed from the genetic aberrations results in neurodevelopmental deficits through the formation of irreversible dysfunctional multimer of carbonylated CRMP2.
Targeting DNA repair in gliomas.

PURPOSE OF REVIEW Gliomas represent a disparate group of malignancies with varying clinical outcomes despite a tremendous amount of time, effort, and resources dedicated to their management and understanding. The most aggressive entity, glioblastoma, has a dismal prognosis with poor local control despite intense local and systemic treatment, including radiation therapy. RECENT FINDINGS Given the heterogeneity in genotype, phenotype, and patient outcomes, researchers and clinicians have turned their attention toward attacking DNA damage response and repair mechanisms in gliomas in an effort to develop novel chemo and radiosensitizers. However, despite extensive work in both the laboratory and the clinic, no sensitizers have yet to emerge as clear options in the treatment of glioma, often because of meager preclinical data or an inability to penetrate the blood-brain barrier. SUMMARY This review will examine current understanding of molecular DNA repair targets in glioma and their potential exploitation to improve local control and, ultimately, overall survival of patients afflicted with these diseases.
Prognostic value of neutrophil-to-lymphocyte ratio in locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

Purpose This study aimed to investigate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with locally advanced non-small cell lung cancer (NSCLC) who received concurrent chemoradiotherapy (CCRT). Materials and Methods We retrospectively analyzed 66 patients with locally advanced NSCLC treated with definitive CCRT. Among these patients, 95% received paclitaxel/carboplatin or docetaxel/cisplatin. The median radiation dose was 66 Gy in 33 fractions. The NLR and PLR before/after CCRT were evaluated. The maximally selected log-rank test was used to obtain the cutoff values related to the overall survival (OS). Results Patients with high post-CCRT NLR (>3.12) showed worse OS, locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) than those with low NLR (2-year OS: 25.8% vs. 68.2%, p < 0.001; 2-year LRPFS: 12.9% vs. 33.8%, p = 0.010; 2-year DMFS: 22.6% vs. 38.2%, p = 0.030). Patients with high post-CCRT PLR (>141) showed worse OS and LRPFS than those with low PLR (2-year OS: 37.5% vs. 71.1%, p = 0.004; 2-year LRPFS: 16.5% vs. 40.3%, p = 0.040). Patients with high NLR change (>1.61) showed worse OS and LRPFS than those with low NLR change (2-year OS: 26.0% vs. 59.0%, p < 0.001; 2-year LRPFS: 6.8% vs. 31.8%, p = 0.004). The planning target volume (hazard ration [HR] = 2.05, p = 0.028) and NLR change (HR = 3.17, p = 0.025) were the significant factors for OS in the multivariate analysis. Conclusion NLR change after CCRT was associated with poor prognosis of survival in patients with locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased treatment failure risk.
Why Are You Running and Does It Hurt? Pain, Motivations and Beliefs about Injury Prevention among Participants of a Large-Scale Public Running Event

Organized running events have gained substantial popularity. This study aimed to elucidate the prevalence of musculoskeletal pain, knowledge about injury prevention as well as the attitudes and motivations of individuals participating in the JP Morgan Corporate Challenge in Frankfurt (Germany). A total of 720 recreational runners completed a digital questionnaire immediately prior to the start. The majority of them displayed low to moderate physical activity levels and were rather unambitious regarding targeted finishing time. One quarter (25.3%) participated for the first time in an organized race. The most stated reasons to register were team building (76.4%) and experiencing the run’s atmosphere (50.6%). In contrast, improving health played a minor role (19.4%). More than one in five individuals (n = 159 runners) reported pain, with the most common locations being the knee and lower back. Both at rest (3.2/10 on a numerical rating scale) and during activity (4.7/10), average pain intensity was clinically relevant. Almost three thirds of the participants believed that stretching and wearing appropriate shoes would be effective for injury prevention while other methods such as resistance training, balance exercise or wearing of orthoses were rarely named. Musculoskeletal pain is a significant burden in runners participating in an urban mass event. In view of the poor knowledge about injury prevention, organizers and coaches may consider offering structured preparation programs as well as tailored running-related health education.
Financial Burdens of Cancer Treatment: A Systematic Review of Risk Factors and Outcomes.

BACKGROUND Patients with cancer experience financial toxicity from the costs of treatment, as well as material and psychologic stress related to this burden. A synthesized understanding of predictors and outcomes of the financial burdens associated with cancer care is needed to underpin strategic responses in oncology care. This study systematically reviewed risk factors and outcomes associated with financial burdens related to cancer treatment. METHODS MEDLINE, Embase, PubMed, PsychINFO, and the Cochrane Library were searched from study inception through June 2018, and reference lists were scanned from studies of patient-level predictors and outcomes of financial burdens in US patients with cancer (aged ≥18 years). Two reviewers conducted screening, abstraction, and quality assessment. Variables associated with financial burdens were synthesized. When possible, pooled estimates of associations were calculated using random-effects models. RESULTS A total of 74 observational studies of financial burdens in 598,751 patients with cancer were identified, among which 49% of patients reported material or psychologic financial burdens (95% CI, 41%-56%). Socioeconomic predictors of worse financial burdens with treatment were lack of health insurance, lower income, unemployment, and younger age at cancer diagnosis. Compared with patients with health insurance, those who were uninsured demonstrated twice the odds of financial burdens (pooled odds ratio [OR], 2.09; 95% CI, 1.33-3.30). Financial burdens were most severe early in cancer treatment, did not differ by disease site, and were associated with worse health-related quality of life (HRQoL) and nearly twice the odds of cancer medication nonadherence (pooled OR, 1.70; 95% CI, 1.13-2.56). Only a single study demonstrated an association with increased mortality. Studies assessing the comparative effectiveness of interventions to mitigate financial burdens in patients with cancer were lacking. CONCLUSIONS Evidence showed that financial burdens are common, disproportionately impacting younger and socioeconomically disadvantaged patients with cancer, across disease sites, and are associated with worse treatment adherence and HRQoL. Available evidence helped identify vulnerable patients needing oncology provider engagement and response, but evidence is critically needed on the effectiveness of interventions designed to mitigate financial burden and impact.
Recent developments in deep learning applied to protein structure prediction

Although many structural bioinformatics tools have been using neural network models for a long time, deep neural network (DNN) models have attracted considerable interest in recent years. Methods employing DNNs have had a significant impact in recent CASP experiments, notably in CASP12 and especially CASP13. In this article, we offer a brief introduction to some of the key principles and properties of DNN models and discuss why they are naturally suited to certain problems in structural bioinformatics. We also briefly discuss methodological improvements that have enabled these successes. Using the contact prediction task as an example, we also speculate why DNN models are able to produce reasonably accurate predictions even in the absence of many homologues for a given target sequence, a result that can at first glance appear surprising given the lack of input information. We end on some thoughts about how and why these types of models can be so effective, as well as a discussion on potential pitfalls.
Variability of Multiangle Isometric Force-Time Characteristics in Trained Men

Abstract Oranchuk, DJ, Storey, AG, Nelson, AR, Neville, JG, and Cronin, JB. Variability of multiangle isometric force-time characteristics in trained men. J Strength Cond Res 36(1): 284–288, 2022—Measurements of isometric force, rate of force development (RFD), and impulse are widely reported. However, little is known about the variability and reliability of these measurements at multiple angles, over repeated testing occasions in a homogenous, resistance-trained population. Thus, understanding the intersession variability of multiangle isometric force-time characteristics provides the purpose of this article. Three sessions of isometric knee extensions at 40°, 70°, and 100° of flexion were performed by 26 subjects across 51 limbs. All assessments were repeated on 3 occasions separated by 5–8 days. Variability was qualified by doubling the typical error of measurement (TEM), with thresholds of 0.2–0.6 (small), 0.6–1.2 (moderate), 1.2–2.0 (large), 2.0–4.0 (very large), and >4.0 (extremely large). In addition, variability was deemed large when the intraclass correlation coefficient (ICC) was <0.67 and coefficient of variation (CV) >10%; moderate when ICC >0.67 or CV <10% (but not both); and small when both ICC >0.67 and CV <10%. Small to moderate between-session variability (ICC = 0.68–0.95, CV = 5.2–18.7%, TEM = 0.24–0.49) was associated with isometric peak force, regardless of angle. Moderate to large variability was seen in early-stage (0–50 ms) RFD and impulse (ICC = 0.60–0.80, CV = 22.4–63.1%, TEM = 0.62–0.74). Impulse and RFD at 0–100 ms, 0–200 ms, and 100–200 ms were moderately variable (ICC = 0.71–0.89, CV = 11.8–42.1%, TEM = 0.38–0.60) at all joint angles. Isometric peak force and late-stage isometric RFD and impulse measurements were found to have low intersession variability regardless of joint angle. However, practitioners need to exercise caution when making inferences about early-stage RFD and impulse measures due to moderate-large variability.
Isolation and growth characterization of novel full length and deletion mutant human MERS-CoV strains from clinical specimens collected during 2015

Middle East respiratory syndrome (MERS) is a viral respiratory illness first reported in Saudi Arabia in September 2012 caused by the human coronavirus (CoV), MERS-CoV. Using full-genome sequencing and phylogenetic analysis, scientists have identified three clades and multiple lineages of MERS-CoV in humans and the zoonotic host, dromedary camels. In this study, we have characterized eight MERS-CoV isolates collected from patients in Saudi Arabia in 2015. We have performed full-genome sequencing on the viral isolates, and compared them to the corresponding clinical specimens. All isolates were clade B, lineages 4 and 5. Three of the isolates carry deletions located on three independent regions of the genome in the 5′UTR, ORF1a and ORF3. All novel MERS-CoV strains replicated efficiently in Vero and Huh7 cells. Viruses with deletions in the 5′UTR and ORF1a exhibited impaired viral release in Vero cells. These data emphasize the plasticity of the MERS-CoV genome during human infection.
The Impact of HeartMath Resiliency Training on Health Care Providers.

BACKGROUND Health care providers must think clearly and make critical decisions under stressful circumstances. Providing effective strategies for managing stress in the moment helps mitigate the physical, emotional, and psychological impacts associated with caring for others and promotes resiliency. Staff may also utilize these techniques with patients and their families to help alleviate the symptoms of stress that may be experienced as the result of illness. AIM The purpose of this study was to measure whether HeartMath techniques reduce stress and improve resiliency in health care providers. METHODS Study participants were asked to complete the Personal and Organizational Quality Assessment-Revised 4 Scale (2016) immediately before the start of training and then again 4 to 6 weeks after completion of the class. Participants were also asked to voluntarily share their experiences using HeartMath techniques personally or with family, friends, and patients. RESULTS Significant improvements were found in 3 of 4 primary scales (organizational stress, emotional stress, and physical stress) and in 6 of 9 subscales on the Personal and Organizational Quality Assessment-Revised 4 Scale indicating a positive impact on employee health, well-being, and performance. Stories shared by participants posttraining indicated that HeartMath techniques were being used personally and with patients as an adjunct in the management of pain, anxiety, and insomnia. CONCLUSIONS This study supports existing evidence that HeartMath techniques are effective in managing stress and increasing resiliency. These techniques are also valuable tools for health care providers to use with patients and their families in the management of symptoms such as pain, anxiety, and sleeplessness related to hospitalization and illness.
Bridging Distances with Life Reviews: A Study on Intergenerational Learning in the History Alive Program

This study employed six senior citizens from the Chaoyang Changching Day Care Center, 53 first-year students from the Chaoyang University Department of Business Administration Class A taking the Corporate Social Responsibility and Service Learning course, and 6 fourth-year student volunteers from the Department of Golden-Ager Industry Management as research targets. The study discussed the physical, psychological, and spiritual benefits of the History Alive program for senior citizens and the changes between the relationship of senior citizens and college students after their interactions and mutual learning process. This study adopted qualitative and quantitative research methods to collect data and conduct analysis on recordings of course activity observations, the activity feedback of college students, and the researchers' reflection. Study results revealed that the History Alive program improved the physical, psychological, and spiritual aspects of senior citizens and promoted intergenerational interaction, understanding, communication, and learning. Most importantly, the History Alive program changed the stereotypical image that college students had of senior citizens. It is suggested that technology assistance, such as webpages, website presentations, videotapes, etc. can be stored on the Internet in the future, which helps circulation sharing and digitizes life reviews. Let the life story of the senior citizens be preserved for a long time. At the same time, it is also possible to combine the social network platform, such as Facebook and social software to display the life story of the senior citizens, and enhance the sense of accomplishment and self-worth of the senior citizens through the praise rate of netizens.
pH-Responsive Carboxymethylcellulose Nanoparticles for 68Ga-WBC Labeling in PET Imaging

Carboxymethylcellulose (CMC) is a well-known pharmaceutical polymer, recently gaining attention in the field of nanomedicine, especially as a polyelectrolyte agent for the formation of complexes with oppositely charged macromolecules. Here, we report on the application of pH-sensitive pharmaceutical grade CMC-based nanoparticles (NP) for white blood cells (WBC) PET imaging. In this context and as an alternative to 99mTc-HMPAO SPECT labeling, the use of 68Ga3+ as PET radionuclide was investigated since, at early time points, it could provide the greater spatial resolution and patient convenience of PET tomography over SPECT clinical practices. Two operator-friendly kit-type formulations were compared, with the intention of radiolabeling within a short time (10 min), under mild conditions (physiological pH, room temperature) and in agreement with the actual clinically applied guidelines. NP were labeled by directly using 68Ga3+ eluted in HCL 0.05 N, from hospital suited 68Ge/68Ga generator and in absence of chelator. The first kit type approach involved the application of 68Ga3+ as an ionotropic gelation agent for in-situ forming NP. The second kit type approach concerned the re-hydration of a proper freeze-dried injectable NP powder. pH-sensitive NP with 250 nm average diameter and 80% labeling efficacy were obtained. The NP dispersant medium, including a cryoprotective agent, was modulated in order to optimize the Zeta potential value (−18 mV), minimize the NP interaction with serum proteins and guarantee a physiological environment for WBC during NP incubation. Time-dependent WBC radiolabeling was correlated to NP uptake by using both confocal and FT-IR microscopies. The ready to use lyophilized NP formulation approach appears promising as a straightforward 68Ga-WBC labeling tool for PET imaging applications.
All‐atom molecular dynamics simulations reveal how kinesin transits from one‐head‐bound to two‐heads‐bound state

Kinesin dimer walks processively along a microtubule (MT) protofilament in a hand‐over‐hand manner, transiting alternately between one‐head‐bound (1HB) and two‐heads‐bound (2HB) states. In 1HB state, one head bound by adenosine diphosphate (ADP) is detached from MT and the other head is bound to MT. Here, using all‐atom molecular dynamics simulations we determined the position and orientation of the detached ADP‐head relative to the MT‐bound head in 1HB state. We showed that in 1HB state when the MT‐bound head is in ADP or nucleotide‐free state, with its neck linker being undocked, the detached ADP‐head and the MT‐bound head have the high binding energy, and after adenosine triphosphate (ATP) binds to the MT‐bound head, with its neck linker being docked, the binding energy between the two heads is reduced greatly. These results reveal how the kinesin dimer retains 1HB state before ATP binding and how the dimer transits from 1HB to 2HB state after ATP binding. Key residues involved in the head‐head interaction in 1HB state were identified.
Pretectal neurons control hunting behaviour

For many species, hunting is an innate behaviour that is crucial for survival, yet the circuits that control predatory action sequences are poorly understood. We used larval zebrafish to identify a population of pretectal neurons that control hunting. By combining calcium imaging with a virtual hunting assay, we identified a discrete pretectal region that is selectively active when animals initiate hunting. Targeted genetic labelling allowed us to examine the function and morphology of individual cells and identify two classes of pretectal neuron that project to ipsilateral optic tectum or the contralateral tegmentum. Optogenetic stimulation of single neurons of either class was able to induce sustained hunting sequences, in the absence of prey. Furthermore, laser ablation of these neurons impaired prey-catching and prevented induction of hunting by optogenetic stimulation of the anterior-ventral tectum. We propose that this specific population of pretectal neurons functions as a command system to induce predatory behaviour.
Detection of Candida auris Antifungal Drug Resistance Markers Directly from Clinical Skin Swabs

Accurate and rapid assessment of Candida auris antifungal drug resistance is crucial for effective infection prevention and control actions, as well as for patient management. Here, performance of a molecular diagnostic platform, enabling rapid identification of FKS1 and ERG11 mutations conferring echinocandin and azole resistance, respectively, was evaluated on a panel of clinical skin swabs. Gene sequencing and antifungal susceptibility testing were used as the gold standard. ABSTRACT Accurate and rapid assessment of Candida auris antifungal drug resistance is crucial for effective infection prevention and control actions, as well as for patient management. Here, performance of a molecular diagnostic platform, enabling rapid identification of FKS1 and ERG11 mutations conferring echinocandin and azole resistance, respectively, was evaluated on a panel of clinical skin swabs. Gene sequencing and antifungal susceptibility testing were used as the gold standard. All swabs were correctly categorized as harboring wild-type or mutant C. auris.