Miracle-dz/UniFAR-FTUs huggingface dataset:
One Health WASH: an AMR-smart integrative approach to preventing and controlling infection in farming communities

Correspondence to Dr Chris E Pinto Jimenez; cpintoj@ gmail. com © Author(s) (or their employer(s)) 2023. Reuse permitted under CC BYNC. No commercial reuse. See rights and permissions. Published by BMJ. INTRODUCTION Prevention is a critical, yet neglected, cornerstone for the response to antimicrobial resistance (AMR). The importance of a multitude of preventative measures is recognised across the One Health spectrum, with attention drawn to the issue by multilateral institutions. The 2022 World Antimicrobial Awareness Week saw the World Health Organization, the Food and Agriculture Organization, the United Nations Environment Programme and the World Organisation for Animal Health focused their campaign on the theme ‘Preventing AMR together’ to improve awareness and understanding of AMR and encourage best practices. While a One Health framework is now promoted for conceptualising the complex problem of AMR, the evidence base of interventions designed within this rubric is thin. Outstanding questions remain, for example, about how best to prevent and control infection across humans, animals, and the environment. In public health, measures such as hygiene practices, biosecurity, vaccinations and other means to strengthen immunity, are commonly used to prevent and control infections. Highlighting the potential contribution of such measures to reducing AMR, the World Bank introduced the terms ‘AMRsensitive’ and ‘AMRspecific’ to describe interventions that indirectly or directly contribute to reducing AMR, respectively. For example, measures to reduce the burden of infections in human health, such as water, sanitation, and hygiene (WASH), are recognised as essential to support AMR strategies due to their potential to indirectly combat AMR and produce cobenefits. Thus, investments in these interventions would be ‘AMRSmart. ’ Currently, measures to prevent and control infections in human health are most obvious for infections acquired in healthcare settings. Infection Prevention and Control (IPC) in human health is considered fundamental for AMR, defined as measures ‘that prevent patients and health workers from being harmed by avoidable infections and as a result of AMR’. In animal health, the prevention and control of infections commonly focus on measures to reduce the risk of introduction and/or spread of diseases between animals on farms and from and to farm workers. While the acronym IPC most commonly refers to healthcare settings in the human health sector, the general principle of infection prevention and control has a wider resonance. The subtle but important differences in the terminology for prevention and control of infections between health sectors have the potential to create misunderstandings across the wider One Health SUMMARY BOX
The integrated brain network that controls respiration

Respiration is a brain function on which our lives essentially depend. Control of respiration ensures that the frequency and depth of breathing adapt continuously to metabolic needs. In addition, the respiratory control network of the brain has to organize muscular synergies that integrate ventilation with posture and body movement. Finally, respiration is coupled to cardiovascular function and emotion. Here, we argue that the brain can handle this all by integrating a brainstem central pattern generator circuit in a larger network that also comprises the cerebellum. Although currently not generally recognized as a respiratory control center, the cerebellum is well known for its coordinating and modulating role in motor behavior, as well as for its role in the autonomic nervous system. In this review, we discuss the role of brain regions involved in the control of respiration, and their anatomical and functional interactions. We discuss how sensory feedback can result in adaptation of respiration, and how these mechanisms can be compromised by various neurological and psychological disorders. Finally, we demonstrate how the respiratory pattern generators are part of a larger and integrated network of respiratory brain regions.
Intraindividual change in pain tolerance and negative affect over 20 years: findings from the MIDUS study

ABSTRACT Pain tolerance, defined as the ability to withstand physical pain states, is a clinically important psychobiological process associated with several deleterious outcomes, including increased pain experience, mental health problems, physical health problems, and substance use. A significant body of experimental work indicates that negative affect is associated with pain tolerance, such that increased negative affect is associated with decreased pain tolerance. Although research has documented the associations between pain tolerance and negative affect, little work has examined these associations over time, and how change in pain tolerance is related to changes in negative affect. Therefore, the current study examined the relationship between intraindividual change in self-reported pain tolerance and intraindividual change in negative affect over 20 years in a large, longitudinal, observation-based national sample of adults (n = 4,665, M age = 46.78, SD =12.50, 53.8% female). Results from parallel process latent growth curve models indicated that slope of pain tolerance and negative affect were associated with each other over time (r = .272, 95% CI [.08, .46] p = .006). Cohen’s d effect size estimates provide initial, correlational evidence that changes in pain tolerance may precede changes in negative affect. Given the relevance of pain tolerance to deleterious health outcomes, better understanding how individual difference factors, including negative affect, influence pain tolerance over time, are clinically important to reduce disease-related burden.
The coral microbiome: towards an understanding of the molecular mechanisms of coral–microbiota interactions

Abstract Corals live in a complex, multipartite symbiosis with diverse microbes across kingdoms, some of which are implicated in vital functions, such as those related to resilience against climate change. However, knowledge gaps and technical challenges limit our understanding of the nature and functional significance of complex symbiotic relationships within corals. Here, we provide an overview of the complexity of the coral microbiome focusing on taxonomic diversity and functions of well-studied and cryptic microbes. Mining the coral literature indicate that while corals collectively harbour a third of all marine bacterial phyla, known bacterial symbionts and antagonists of corals represent a minute fraction of this diversity and that these taxa cluster into select genera, suggesting selective evolutionary mechanisms enabled these bacteria to gain a niche within the holobiont. Recent advances in coral microbiome research aimed at leveraging microbiome manipulation to increase coral’s fitness to help mitigate heat stress-related mortality are discussed. Then, insights into the potential mechanisms through which microbiota can communicate with and modify host responses are examined by describing known recognition patterns, potential microbially derived coral epigenome effector proteins and coral gene regulation. Finally, the power of omics tools used to study corals are highlighted with emphasis on an integrated host–microbiota multiomics framework to understand the underlying mechanisms during symbiosis and climate change-driven dysbiosis.
Observation and measurement of the Higgs boson in the WW* decay channel with ATLAS at the LHC

A measurement of the Higgs boson production has been performed with the ATLAS detector at the Large Hadron Collider. Proton-proton collision data was used, corresponding to an integrated luminosity of 25 fb−1, obtained at center-of-mass energies of 7 and 8 TeV, during 2011 and 2012. The H → WW ∗ → `ν`ν decay channel was analyzed, with particular emphasis on events with two electrons or two muons in the final state. New analysis techniques were developed to deal with the overwhelming contamination from Drell-Yan background processes. An overall excess of events was observed over the predicted background, with a significance of 6. 1σ, conclusively establishing the observation of the Higgs boson in the H → WW ∗ → `ν`ν channel. The observed rate of events is compatible with the expectation for a Standard Model Higgs boson with a mass of 125.36 GeV, as shown by the ratio between the observed and expected cross section times branching ratio, measured at 1.08 +0.16 −0.15 (stat.) +0.08 −0.07 (expt.) +0.13 −0.11 (theo.) ±0.03 (lumi.) = 1.08 +0.22 −0.20.
The interaction between a pair of circular cylinders normal to a stream

This paper describes how the flows around two circular cylinders, displaced in a plane normal to the free stream, interact as the two bodies are brought close together. Surface pressure measurements at a Reynolds number of 2·5 × 104, based on the diameter of a single cylinder, show the presence of a mean repulsive force between the cylinders. An instability of the flow was found when the gap between the cylinders was in the range between one diameter and about 0·1 of a diameter. Correlation measurements of hot-wire outputs indicate how mutual interference influences the formation of vortex streets from the two cylinders. Spanwise correlation measurements show that the correlation length doubles as the cylinders are brought into contact.
Prevalence and distribution of ultrasound-detected hand synovial abnormalities in a middle-aged and older population

Abstract Objective Synovial abnormalities are modifiable targets for hand pain and osteoarthritis. We examined the prevalence and distribution of ultrasound-detected hand synovial abnormalities in a community-derived sample of older people in China. Methods Within the Xiangya Osteoarthritis Study, a community-based study, we assessed synovial hypertrophy (SH), joint effusion, and Power Doppler signal (PDS) on all fingers and thumbs of both hands using standardized ultrasound examinations (score: 0–3). We assessed distribution patterns of SH and effusion using χ2-test and interrelationships of SH and effusion in different joints and hands by generalized estimating equations. Results Among 3,623 participants (mean age: 64.4 years; women: 58.1%), prevalence of SH, effusion and PDS were 85.5%, 87.3% and 1.5%, respectively. Prevalence of SH, effusion and PDS increased with age, was higher in the right hand than in the left hand and was more common in proximal than in distal hand joints. SH and effusion often occurred in multiple joints (P < 0.001). SH in one joint was strongly associated with presence of SH in the same joint of the opposite hand (odds ratio [OR]= 6.60, 95% confidence interval [CI]: 6.19–7.03) followed by SH in other joints in the same row, (OR=5.70, 95%CI: 5.32–6.11), and then other joints in the same ray of the same hand (OR=1.49, 95%CI: 1.39–1.60). Similar patterns were observed for effusion. Conclusion Hand synovial abnormalities are common among older people, often affect multiple hand joints and present a unique pattern. These findings suggest both systemic and mechanical factors play roles in their occurrence.
Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma: Results from a German real‐world cohort

Phase III trials have established atezolizumab plus bevacizumab as the novel standard of care for patients with unresectable hepatocellular carcinoma (HCC). However, these trials raised concerns regarding treatment efficacy in non‐viral HCC, and it remains unclear whether combination immunotherapy is safe and effective in patients with advanced cirrhosis.
Scarcity mindset reduces empathic responses to others’ pain: the behavioral and neural evidence

Abstract Resource scarcity pervades our life. A scarcity mindset triggered by perceiving insufficient resources has been proven to influence our cognition and behaviors, yet it remains unknown whether this mindset specifically influences empathy. The present study induced feelings of scarcity or abundance in separate groups of participants through experimental manipulation and examined the effects of both mindsets on the behavioral and neural responses to others’ pain. Behaviorally, pain intensity ratings of others’ pain were lower in the scarcity group than in the abundance group. The analysis of event-related potentials revealed that N1 amplitudes for painful and nonpainful stimuli were comparable in the scarcity group but differed significantly in the abundance group. Additionally, while both groups showed larger late positive potential amplitudes for painful stimuli than for nonpainful stimuli, this amplitude differential was significantly smaller in the scarcity group than in the abundance group. Thus, behavioral and neural evidence suggests that inducing a scarcity mindset significantly dampens the ability to empathize with others’ pain during both the early and late stages of empathic processing. These findings shed light on our understanding of how a scarcity mindset may influence social emotions and behaviors.
Short-chain acyl-CoA dehydrogenase is a potential target for the treatment of vascular remodelling

Objectives: Short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme in the fatty acid oxidation process, is not only involved in ATP synthesis but also regulates the production of mitochondrial reactive oxygen species (ROS) and nitric oxide synthesis. The purpose of this study was to investigate the possible role of SCAD in hypertension-associated vascular remodelling. Methods: In-vivo experiments were performed on spontaneously hypertensive rats (SHRs, ages of 4 weeks to 20 months) and SCAD knockout mice. The aorta sections of hypertensive patients were used for measurement of SCAD expression. In-vitro experiments with t-butylhydroperoxide (tBHP), SCAD siRNA, adenovirus-SCAD (MOI 90) or shear stress (4, 15 dynes/cm2) were performed using human umbilical vein endothelial cells (HUVECs). Results: Compared with age-matched Wistar rats, aortic SCAD expression decreased gradually in SHRs with age. In addition, aerobic exercise training for 8 weeks could significantly increase SCAD expression and enzyme activity in the aortas of SHRs while decreasing vascular remodelling in SHRs. SCAD knockout mice also exhibited aggravated vascular remodelling and cardiovascular dysfunction. Likewise, SCAD expression was also decreased in tBHP-induced endothelial cell apoptosis models and the aortas of hypertensive patients. SCAD siRNA caused HUVEC apoptosis in vitro, whereas adenovirus-mediated SCAD overexpression (Ad-SCAD) protected against HUVEC apoptosis. Furthermore, SCAD expression was decreased in HUVECs exposed to low shear stress (4 dynes/cm2) and increased in HUVECs exposed to 15 dynes/cm2 compared with those under static conditions. Conclusion: SCAD is a negative regulator of vascular remodelling and may represent a novel therapeutic target for vascular remodelling.
Xanthohumol inhibits non‐small cell lung cancer via directly targeting T‐lymphokine‐activated killer cell‐originated protein kinase

Xanthohumol is a principal prenylated chalcone isolated from hops. Previous studies have shown that xanthohumol was effective against various types of cancer, but the mechanisms, especially the direct targets for xanthohumol to exert an anticancer effect, remain elusive. Overexpression of T‐lymphokine‐activated killer cell‐originated protein kinase (TOPK) promotes tumorigenesis, invasion and metastasis, implying the likely potential for targeting TOPK in cancer prevention and treatment. In the present study, we found that xanthohumol significantly inhibited the cell proliferation, migration and invasion of non‐small cell lung cancer (NSCLC) in vitro and suppressed tumor growth in vivo, which is well correlated with inactivating TOPK, evidenced by reduced phosphorylation of TOPK and its downstream signaling histone H3 and Akt, and decreased its kinase activity. Moreover, molecular docking and biomolecular interaction analysis showed that xanthohumol was able to directly bind to the TOPK protein, suggesting that TOPK inactivation by xanthohumol is attributed to its ability to directly interact with TOPK. The findings of the present study identified TOPK as a direct target for xanthohumol to exert its anticancer activity, revealing novel insight into the mechanisms underlying the anticancer activity of xanthohumol.
Co‐administration of curcumin with other phytochemicals improves anticancer activity by regulating multiple molecular targets

Natural plant phytochemicals are effective against different types of diseases, including cancer. Curcumin, a powerful herbal polyphenol, exerts inhibitory effects on cancer cell proliferation, angiogenesis, invasion, and metastasis through interaction with different molecular targets. However, the clinical use of curcumin is limited due to poor solubility in water and metabolism in the liver and intestine. The synergistic effects of curcumin with some phytochemicals such as resveratrol, quercetin, epigallocatechin‐3‐gallate, and piperine can improve its clinical efficacy in cancer treatment. The present review specifically focuses on anticancer mechanisms related to the co‐administration of curcumin with other phytochemicals, including resveratrol, quercetin, epigallocatechin‐3‐gallate, and piperine. According to the molecular evidence, the phytochemical combinations exert synergistic effects on suppressing cell proliferation, reducing cellular invasion, and inducing apoptosis and cell cycle arrest. This review also emphasizes the significance of the co‐delivery vehicles‐based nanoparticles of such bioactive phytochemicals that could improve their bioavailability and reduce their systemic dose. Further high‐quality studies are needed to firmly establish the clinical efficacy of the phytochemical combinations.
Differential Cue Weighting in Mandarin Sibilant Production

Individual talkers vary in their relative use of different cues to signal phonological contrast. Previous work provides limited and conflicting data on whether such variation is modulated by cue trading or individual differences in speech style. This paper examines differential cue weighting patterns in Mandarin sibilants as a test case for these hypotheses. Standardized Mandarin exhibits a three-way place contrast between retroflex, alveopalatal, and alveolar sibilants with individual differences in relative weighting of spectral center of gravity (COG) and the second formant of the following vowel (F2). In results from a speech production task, cue weights of COG and F2 are inversely correlated across speakers, demonstrating a trade-off relationship in cue use. These findings are consistent with a cue trading account of individual differences in contrast signaling.
On the applicability of 2D URANS and SST k - ω turbulence model to the fluid-structure interaction of rectangular cylinders

In this work the practical applicability of a 2D URANS approach adopting a block structured mesh and Menter's SST k-ω turbulence model in fluid-structure interaction (FSI) problems is studied using as a test case a ratio B/H = 4 rectangular cylinder. The vortex-induced vibration (VIV) and torsional flutter phenomena are analyzed based on the computation of the out-of-phase and in-phase components of the forced frequency component of lift and moment coefficients when the section is forced to periodically oscillate both in heave and pitch degrees of freedom. Also the flutter derivatives are evaluated numerically from the same forced oscillation simulations. A good general agreement has been found with both experimental and numerical data reported in the literature. This highlights the benefits of this relatively simple and straightforward approach. These methods, once their feasibility has been checked, are ready to use in parametric design of bridge deck sections and, at a later stage, in the shape optimization of deck girders considering aeroelastic constraints.
Bivalent molecular mimicry by ADP protects metal redox state and promotes coenzyme B12 repair

Significance Coenzyme B12 [adenosylcobalamin (AdoCbl)] is an essential metallocofactor for human methylmalonyl-CoA mutase (MCM). The radical chemistry-based reaction catalyzed by MCM is, however, prone to occasional inactivation via loss of the 5′-deoxyadenosylcobalamin moiety from the active site and susceptibility of the remaining cob(II)alamin intermediate to hyperoxidation. While an elaborate system comprising two chaperones engages in the off-loading and repair of inactive cofactor, it is only effective if the cob(II)alamin oxidation state is preserved. We have discovered that bivalent molecular mimicry by the common metabolite ADP is used as a strategy for conserving the cob(II)alamin oxidation state. By sealing off solvent access via a protein conformational change, ADP promotes the repair of a high-value metallocofactor needed for mitochondrial propionate metabolism.
A Lower Dose of Infection Generates a Better Long-Term Immune Response against Toxoplasma gondii

Abstract Toxoplasma gondii, an obligate intracellular pathogen, induces a strong immune response in the infected host. In the encephalitis model of infection, long-term protective immunity is mediated by CD8 T cells, with the CD4 T cell population providing important help. Most of the immune studies have used a 10- to 20-cyst dose of T. gondii, which leads to T cell dysfunctionality during the late phase of chronic infection and increases the chances of reactivation. In the current study, we compared the immune response of mice orally infected with either 2 or 10 cysts of T. gondii. During the acute phase, we demonstrate that the lower dose of infection generates a reduced number of CD4 and CD8 T cells, but the frequency of functional CD4 or CD8 T cells is similar in animals infected with two different doses. However, Ag-experienced T cells (both CD4 and CD8) are better maintained in lower dose–infected mice at 8 wk postinfection, with an increase number functional cells that exhibit lower multiple inhibitory receptor expression. In addition to better long-term T cell immunity, animals infected with a lower dose display reduced inflammation manifested by lesser Ag-specific T cell and cytokine responses during the very early stage of the acute infection. Our studies suggest a previously unappreciated role of dose-dependent early programming/imprinting of the long-term CD4/CD8 T cell response during T. gondii infection. These observations point to the need for an in-depth analysis of how early events shape long-term immunity against this pathogen.
Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial

ABSTRACT Background Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects. Research design and methods Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. Results The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study. Conclusion The study shows that the two drugs had similar bioequivalence and safety. Clinical trial registration DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076