Miracle-dz/UniFAR-FTUs huggingface dataset:
Telomere length is maternally inherited and associated with lipid metabolism in Chinese population

Telomere is a unique DNA-protein complex which covers the ends of chromosomes to avoid end fusion and maintain the stability and integrity of chromosomes. Telomere length (TL) shortening has been linked to aging and various age-related diseases in humans. Here we recruited a total of 1031 Chinese individuals aged between 12 and 111 years, including 108 families with parents and their offspring. DNA was extracted from peripheral white blood cells and TL was measured by quantitative PCR (qPCR). We explored the associations of TL with age, gender and clinical variables, and tested the parental effects on TL variation. First, we found that TL was shortened with age, however, TL was better maintained in females than males. Second, there was a robust association of TL between mother and offspring, but not between father and their offspring. In addition, TL was inversely associated with visceral fat index in females, and positively associated with apolipoprotein A levels. Knockdown of the key genes for lipid metabolism (PNPLA2 and CPT1) shortened the TL in HepG2 cells. These findings indicate that TL is maternally inherited, and impairment of lipid metabolism may contribute to the TL shortening in the Chinese population.
Evidence attack in public health: Diverse actors’ experiences with translating controversial or misrepresented evidence in health policy and systems research

ABSTRACT Bringing evidence into policy and practice discussions is political; more so when evidence from health studies or programme data are deemed controversial or unexpected, or when results are manipulated and misrepresented. Furthermore, opinion and misinformation in recent years has challenged our notions about how to achieve evidence-informed decision-making (EIDM). Health policy and systems (HPS) researchers and practitioners are battling misrepresentation that only serves to detract from important health issues or, worse, benefit powerful interests. This paper describes cases of politically and socially controversial evidence presented by researchers, practitioners and journalists during the Health Systems Research Symposium 2020. These cases cut across global contexts and range from public debates on vaccination, comprehensive sexual education, and tobacco to more inward debates around performance-based financing and EIDM in refugee policy. The consequences of engaging in controversial research include threats to commercial profit, perceived assaults on moral beliefs, censorship, fear of reprisal, and infodemics. Consequences for public health include research(er) hesitancy, contribution to corruption and leakage, researcher reflexivity, and ethical concerns within the HPS research and EIDM fields. Recommendations for supporting researchers, practitioners and advocates include better training and support structures for responding to controversy, safe spaces for sharing experiences, and modifying incentive structures.
Chance-Constrained H∞ State Estimation for Recursive Neural Networks Under Deception Attacks and Energy Constraints: The Finite-Horizon Case

In this article, the chance-constrained <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> state estimation problem is investigated for a class of time-varying neural networks subject to measurements degradation and randomly occurring deception attacks. A novel energy-constrained deception attack model is proposed, in which both the occurrence of the attack and the selection of released faked packet are random and the energy of the deception attack is introduced, calculated, and analyzed quantitatively. The main purpose of the addressed problem is to design an <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> estimator such that the prefixed probabilistic constraints of the system error dynamics are satisfied and the <inline-formula> <tex-math notation="LaTeX">$H_{\infty }$ </tex-math></inline-formula> performance is also ensured. Subsequently, the explicit expression of the estimator gains is derived by solving a minimization problem subjected to certain recursive inequality constraints. Finally, a numerical example and a practical three-tank system are utilized to demonstrate the correctness and effectiveness of the proposed estimation scheme.
Lipoprotein-associated phospholipase A2: A paradigm for allosteric regulation by membranes

Significance Lp-PLA2 is a physiologically important human enzyme and an inflammatory biomarker for assessing risk factors associated with cardiovascular diseases. It is associated with low- and high-density lipoproteins in human plasma and acts on the outside of the phospholipid monolayer that coats these particles, in stark contrast to traditional PLA2 enzymes that act on bilayer membranes. This study addresses the allosteric activation of Lp-PLA2 by phospholipid monolayers and membranes, its precise selectivity and specificity for particular oxidized and short acyl-chain phospholipid substrates not previously possible. Of particular importance, this work identifies and confirms by site-directed mutagenesis a phospholipid head-group binding pocket distinct from known drug inhibitor binding pockets that informs us about Lp-PLA2’s mechanism of action and creates opportunities for additional therapeutic approaches. Lipoprotein-associated phospholipase A2 (Lp-PLA2) associates with low- and high-density lipoproteins in human plasma and specifically hydrolyzes circulating oxidized phospholipids involved in oxidative stress. The association of this enzyme with the lipoprotein’s phospholipid monolayer to access its substrate is the most crucial first step in its catalytic cycle. The current study demonstrates unequivocally that a significant movement of a major helical peptide region occurs upon membrane binding, resulting in a large conformational change upon Lp-PLA2 binding to a phospholipid surface. This allosteric regulation of an enzyme’s activity by a large membrane-like interface inducing a conformational change in the catalytic site defines a unique dimension of allosterism. The mechanism by which this enzyme associates with phospholipid interfaces to select and extract a single phospholipid substrate molecule and carry out catalysis is key to understanding its physiological functioning. A lipidomics platform was employed to determine the precise substrate specificity of human recombinant Lp-PLA2 and mutants. This study uniquely elucidates the association mechanism of this enzyme with membranes and its resulting conformational change as well as the extraction and binding of specific oxidized and short acyl-chain phospholipid substrates. Deuterium exchange mass spectrometry coupled with molecular dynamics simulations was used to define the precise specificity of the subsite for the oxidized fatty acid at the sn-2 position of the phospholipid backbone. Despite the existence of several crystal structures of this enzyme cocrystallized with inhibitors, little was understood about Lp-PLA2‘s specificity toward oxidized phospholipids.
Factors affecting chiropractor requests for full‐length spinal radiography: A scoping review

Chiropractors often refer their patients for full‐length (three‐ to four‐region) radiographs of the spine as part of their clinical assessment, which are frequently completed by radiographers in medical imaging practices. Overuse of spinal radiography by chiropractors has previously been reported and remains a contentious issue. The purpose of this scoping review was to explore the issues surrounding the utilisation of full‐length spinal radiography by chiropractors and examine the alignment of this practice with current evidence. A search of four databases (AMED, EMBASE, MedLine and Scopus) and a hand search of Google was conducted using keywords. Articles were screened against an inclusion/exclusion criterion for relevance. Themes and findings were extracted from eligible articles, and evidence was synthesised using a narrative approach. In total, 25 articles were identified, five major themes were extracted, and subsequent conclusions drawn by authors were charted to identify confluent findings. This review identified a paucity of literature addressing this issue and an underrepresentation of relevant perspectives from radiographers. Several issues surrounding the use of full‐length spinal radiography by chiropractors were identified and examined, including barriers to the adherence of published guidelines for spinal imaging, an absence of a reporting mechanism for the utilisation of spinal radiography in chiropractic and the existence of a spectrum of beliefs amongst chiropractors about the clinical utility and limitations of full‐length spinal radiography. Further investigation is required to further understand the scope of this issue and its impacts for radiation protection and patient safety.
4‐PBA Treatment Improves Bone Phenotypes in the Aga2 Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a genetically heterogenous disorder most often due to heterozygosity for mutations in the type I procollagen genes, COL1A1 or COL1A2. The disorder is characterized by bone fragility leading to increased fracture incidence and long‐bone deformities. Although multiple mechanisms underlie OI, endoplasmic reticulum (ER) stress as a cellular response to defective collagen trafficking is emerging as a contributor to OI pathogenesis. Herein, we used 4‐phenylbutiric acid (4‐PBA), an established chemical chaperone, to determine if treatment of Aga2+/− mice, a model for moderately severe OI due to a Col1a1 structural mutation, could attenuate the phenotype. In vitro, Aga2+/− osteoblasts show increased protein kinase RNA‐like endoplasmic reticulum kinase (PERK) activation protein levels, which improved upon treatment with 4‐PBA. The in vivo data demonstrate that a postweaning 5‐week 4‐PBA treatment increased total body length and weight, decreased fracture incidence, increased femoral bone volume fraction (BV/TV), and increased cortical thickness. These findings were associated with in vivo evidence of decreased bone‐derived protein levels of the ER stress markers binding immunoglobulin protein (BiP), CCAAT/−enhancer‐binding protein homologous protein (CHOP), and activating transcription factor 4 (ATF4) as well as increased levels of the autophagosome marker light chain 3A/B (LC3A/B). Genetic ablation of CHOP in Aga2+/− mice resulted in increased severity of the Aga2+/− phenotype, suggesting that the reduction in CHOP observed in vitro after treatment is a consequence rather than a cause of reduced ER stress. These findings suggest the potential use of chemical chaperones as an adjunct treatment for forms of OI associated with ER stress. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Encapsulation of Zanthoxylum bungeanum essential oil to enhance flavor stability and inhibit lipid oxidation of Chinese-style sausage.

BACKGROUND Z. bungeanum essential oil (ZBEO) is a popular seasoning and commonly applied in food industries. ZBEO contains many easily degraded bioactive substances with high volatility. Therefore, control of the stability of the bioactive substances in ZBEO is a very important in the food industry. RESULTS In this study, microencapsulation was applied to improve ZBEO stability. The key parameters for microcapsule preparation were optimized by the Box-Behnken Design method, and the optimum conditions were as follows: ratio of core to wall, 1:8; ratio of hydroxypropyl-α-cyclodextrin (HPCD) to soy protein isolate (SPI), 4; total solids content, 12%; and homogenization rate, 12000 rpm. Antioxidants experiments indicated that tea polyphenols (TPPs) effectively inhibited hydroxy-ɑ-sanshool degradation in ZBEO microcapsules. Further application of ZBEO microcapsules in Chinese-style sausage showed that the encapsulation of ZBEO effectively inhibited lipid oxidation in sausages and protected hydroxy-ɑ-sanshool and typical volatiles from volatilization and degradation during sausage storage. CONCLUSION The results suggested that ZBEO microencapsulation is an effective strategy for improving the stability of its bioactive components and flavor ingredients during food processing. This article is protected by copyright. All rights reserved.
The Effect of Allergen Immunotherapy on the Development of New Sensitization in Children

Aim: The protective effect of allergen immunotherapy against a new allergic sensitization is controversial. This study aimed to investigate the effect of allergen immunotherapy on new allergic sensitization in children. Materials and Methods: The study included 50 patients who received immunotherapy for at least 3 years, and whose skin prick tests were repeated at intervals of at least 3 years (31 patients for house dust mite immunotherapy, 19 patients for pollen immunotherapy), and 69 controls with similar characteristics. Results: The number of patients who developed a new sensitization was similar both in the groups of patients who received house dust mite and pollen immunotherapy, and the control group. There was no significant difference between the first and last skin prick tests of the patients who received house dust mite and pollen immunotherapy; however, in the control groups, a significant increase in sensitivity to tree pollens (n = 2, 5.4%; n = 8, 21.6%) and weed pollens (n = 7, 26.9%; n = 14, 53.8%) was detected (P = .031 and P = .039). While allergen sensitivities in the first tests of the pollen immunotherapy group and the control group were similar, weed pollen sensitivity was significantly higher in the last tests of the control group (n = 14, 53.8%; n = 4, 21.1%, P = .027). It was determined that the presence of weed pollen sensitization (OR: 8.1, 95% CI: 1.5-42.4) and having asthma (OR: 3.5, 95% CI: 1.3-10.8) increases the risk of new sensitization in all groups. Conclusion: Allergen immunotherapy has been found to protect against new sensitization to tree and weed pollens. However, this effect was insignificant in the multivariate analysis. Weed pollen sensitization and the presence of asthma are related to the development of new sensitization.
Comorbidity as a moderator of the differential efficacy of transdiagnostic behavior therapy and behavioral activation for affective disorders

Abstract Objective Transdiagnostic psychotherapies have been proposed as an effective means for addressing the needs of patients with multiple, comorbid disorders. Yet, it remains unknown whether transdiagnostic approaches empirically outperform disorder-specific psychotherapies for patients with comorbid disorders. Thus, this study tested whether comorbidity moderated the efficacy of transdiagnostic behavior therapy (TBT) and behavioral activation (BA) for patients with various affective disorders. Methods Data derived from a randomized controlled trial in which 93 treatment-seeking veterans received 12 sessions of TBT (n = 46) or BA (n = 47). Baseline comorbidity was assessed with a diagnostic interview. Patients rated their symptoms and functioning throughout treatment, and therapists recorded premature treatment discontinuation. Results Multilevel models revealed significant interactive effects on changes in symptoms and functioning, but not on the posttreatment levels of these outcomes; whereas patients with more comorbidity experienced greater reductions in distress and symptom interference in TBT compared to BA, those with one disorder had better outcomes in BA. Similarly, whereas patients with more comorbidity were less likely to prematurely discontinue TBT compared to BA, those with one disorder were less likely to prematurely discontinue BA. Conclusions The results lend empirical support to previously untested hypotheses for potential benefits of transdiagnostic psychotherapies. Trial registration: ClinicalTrials.gov identifier: NCT01947647.
Pathobiology, Diagnosis, and Current Biomarkers in Neuromyelitis Optica Spectrum Disorders.

BACKGROUND Neuromyelitis optica spectrum disorder (NMOSD) is characterized by chronic inflammation of the central nervous system (CNS), particularly the optic nerves and spinal cord. Although it displays some clinical features similar to multiple sclerosis (MS), the etiology and treatment are distinct, and therefore accurate diagnosis is essential. Autoantibodies targeting the water channel protein aquaporin-4 (AQP4) and the myelin sheath protein myelin oligodendrocyte glycoprotein are the major antigen-specific serological biomarkers known to date, with destruction of astrocytes as the primary mode of CNS damage in AQP4-positive disease. CONTENT This mini-review summarizes the pathobiology, clinical features, and current methods of serological testing used to assess NMOSD and differentiate this disorder from MS. A brief summary of emerging therapies is also presented. SUMMARY NMOSD can be distinguished from MS through a combination of clinical findings, imaging investigations, and serological analysis. Seronegative cases are particularly difficult to diagnose and can pose a challenge to clinicians. As knowledge deepens, new therapies and biomarkers are expected to improve treatment of this rare debilitating disease.
Contralateral Limb Specificity for Movement Preparation in the Parietal Reach Region

The canonical view of motor control is that distal musculature is controlled primarily by the contralateral cerebral hemisphere; unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. To distinguish between these possibilities, we serially inactivated the parietal reach region, comprising the posterior portion of medial intraparietal area, the anterior portion of V6a, and portions of the lateral occipital parietal area, in each hemisphere of 2 monkeys (23 experimental sessions, 46 injections total) to evaluate parietal reach region's contribution to the contralateral reaching deficits observed following lateralized brain lesions. Following unilateral inactivation, reach reaction times with the contralesional limb were slowed compared with matched blocks of control behavioral data; there was no effect of unilateral inactivation on the reaction time of either ipsilesional limb reaches or saccadic eye movements. Following bilateral inactivation, reaching was slowed in both limbs, with an effect size in each no different from that produced by unilateral inactivation. These findings indicate contralateral organization of reach preparation in posterior parietal cortex. SIGNIFICANCE STATEMENT Unilateral brain lesions typically affect contralateral but not ipsilateral musculature. Contralateral-only limb deficits following a unilateral lesion suggest but do not prove that control is strictly contralateral: the loss of a contribution of the lesioned hemisphere to the control of the ipsilesional limb could be masked by the intact contralateral drive from the nonlesioned hemisphere. Unilateral lesions cannot distinguish between contralateral and bilateral control, but bilateral lesions can. Here we show similar movement initiation deficits after combined unilateral and bilateral inactivation of the parietal reach region, indicating contralateral organization of reach preparation.
Does the Internal Carotid Artery Attenuate Blood‐Flow Pulsatility in Small Vessel Disease? A 7 T 4D‐Flow MRI Study

Increased cerebral blood‐flow pulsatility is associated with cerebral small vessel disease (cSVD). Reduced pulsatility attenuation over the internal carotid artery (ICA) could be a contributing factor to the development of cSVD and could be associated with intracranial ICA calcification (iICAC).
Translational findings for odronextamab: From preclinical research to a first‐in‐human study in patients with CD20+ B‐cell malignancies

Odronextamab is a fully‐human IgG4‐based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T‐cell‐mediated cytotoxicity independent of T‐cell‐receptor recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first‐in‐human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B‐cell non‐Hodgkin lymphoma (B‐NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half‐maximal effective concentration values from in vitro cytokine release assays (range: 0.05–0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1–10 mg/L) were useful to predict efficacious concentrations in patients and inform dose‐escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step‐up dosing, the highest‐tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step‐up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B‐NHL.
Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: A Multicenter Randomized Controlled Trial

PURPOSE We aimed to evaluate the efficacy and feasibility of patient-reported outcome (PRO)-based symptom management in the early period after lung cancer surgery. METHODS Before surgery, patients with clinically diagnosed lung cancer were randomly assigned 1:1 to receive postoperative PRO-based symptom management or usual care. All patients reported symptoms on MD Anderson Symptom Inventory-Lung Cancer presurgery, daily postsurgery, and twice a week after discharge for up to 4 weeks via an electronic PRO system. In the intervention group, treating surgeons responded to overthreshold electronic alerts driven by any of the five target symptom scores (score ≥ 4 on a 0-10 scale for pain, fatigue, disturbed sleep, shortness of breath, and coughing). The control group patients received usual care and no alerts were generated. The primary outcome was the number of symptom threshold events (any target symptom with a score of ≥ 4) at discharge. Per-protocol analyses were conducted. RESULTS Of the 166 participants, 83 were randomly allocated to each group. At discharge, the intervention group reported fewer symptom threshold events than the control group (median [interquartile range], 0 [0-2] v 2 [0-3]; P = .007). At 4 weeks postdischarge, this difference was maintained between the intervention and control groups (median [interquartile range], 0 [0-0] v 0 [0-1]; P = .018). The intervention group had a lower complication rate than the control group (21.5% v 40.6%; P = .019). Surgeons spent a median of 3 minutes managing an alert. CONCLUSION PRO-based symptom management after lung cancer surgery showed lower symptom burden and fewer complications than usual care for up to 4 weeks postdischarge. PRO-based symptom management may be the preferred patient care approach following lung cancer surgery.