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IntroductionThe self-referential encoding task (SRET) has a number of implicit measures which are associated with various facets of depression, including depressive symptoms. While some measures have proven robust in predicting depressive symptoms, their effectiveness can vary depending on the methodology used. Hence, understanding the relative contributions of population differences, word lists and calculation methods to these associations with depression, is crucial for translating the SRET into a clinical screening tool. MethodsThis study systematically investigated the predictive accuracy of various SRET measures across different samples, including one clinical population matched with healthy controls and two university student populations, exposed to differing word lists. Participants completed the standard SRET and its variations, including Likert scales and matrix formats. Both standard and novel SRET measures were calculated and compared for their relative and incremental contribution to their associations with depression, with mean squared error (MSE) used as the primary metric for measuring predictive accuracy. ResultsResults showed that most SRET measures significantly predicted depressive symptoms in clinical populations but not in healthy populations. Notably, models with task modifications, such as Matrix Endorsement Bias and Likert Endorsement Sum Bias, achieved the lowest mean squared error (MSE), indicating better predictive accuracy compared to standard Endorsement Bias measures. DiscussionThese findings imply that task modifications such as utilising Likert-response options and the use of longer word lists may enhance the effectiveness of screening methods in both clinical and research settings, potentially improving early detection and intervention for depression.

Processing is an inevitable step in the manufacturing of animal-based foods (ABF) and animal by-products (ABP). However, our society has reached a point where our food systems have reached unsustainable levels. The impact of ABF/ABP processing on sustainability has been arguably overlooked in comparison with production. This perspective paper aims to discuss and identify research gaps regarding the assessments of the sustainability of ABF/ABF processing. First, we describe why processing techniques can have various levels of complexity, with uses that are more or less impactful on the environment depending on the products and possible synergies. In the second part, we review how impacts on sustainability have been evaluated at global and local scales using life cycle assessments (LCA). To contribute to such an approach, we suggest novel or recently introduced types of indicators that would improve future LCA studies by capturing relevant information. In the third part, we encourage a systemic view of sustainability by considering the complexity of the whole supply chains of ABF and ABP. We highlight the current gaps or challenges in evaluating sustainability across supply chains and point the readers toward recent studies that address these limitations. We hope this perspective will help improve the design of academic and industrial studies or evaluation of ABF and ABP sustainability.

Abstract Einstein’s theory of general relativity predicts that a clock at a higher gravitational potential will tick faster than an otherwise identical clock at a lower potential, an effect known as the gravitational redshift. Here we perform a laboratory-based, blinded test of the gravitational redshift using differential clock comparisons within an evenly spaced array of 5 atomic ensembles spanning a height difference of 1 cm. We measure a fractional frequency gradient of [ − 12.4 ± 0. 7(stat) ± 2. 5(sys)] × 10−19/cm, consistent with the expected redshift gradient of − 10.9 × 10−19/cm. Our results can also be viewed as relativistic gravitational potential difference measurements with sensitivity to mm scale changes in height on the surface of the Earth. These results highlight the potential of local-oscillator-independent differential clock comparisons for emerging applications of optical atomic clocks including geodesy, searches for new physics, gravitational wave detection, and explorations of the interplay between quantum mechanics and gravity.

ABSTRACT: Objectives: Systemic strategies for combating antimicrobial resistance (AMR) currently focus on limiting antibiotic use and have been generally insufficient in preventing the rise of AMR. Additionally, they often generate other adverse incentives, such as discouraging pharmaceutical companies from investing in research and development of new antibiotics, further exacerbating the problem. This paper proposes a novel systemic strategy for tackling AMR, which we term ‘antiresistics’: any intervention (whether a small molecule, genetic element, phage, or whole organism) that reduces resistance rates in pathogen populations. A prime example of an antiresistic would be a small molecule that specifically disrupts the maintenance of antibiotic resistance plasmids. Of note, an antiresistic would be expected to have a population-level effect and not necessarily be useful on a time scale relevant to individual patients. Methods: We developed a mathematical model to assess the effect of antiresistics on population resistance levels and calibrated it to longitudinal data available at the country level. We also estimated potential effects on idealised rates for the introduction of new antibiotics. Results: The model shows that greater use of antiresistics allows for greater usage of existing antibiotics. This leads to an ability to maintain a constant overall rate of antibiotic efficacy with a slower rate of developing new antibiotics; subsequently, antiresistics have a positive benefit on the effective lifetime and thus profitability of antibiotics. Conclusions: By directly reducing resistance rates, antiresistics can provide clear qualitative benefits (which may be quantitatively large) in terms of existing antibiotic efficacy, longevity, and alignment of incentives.

IntroductionPharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort.MethodsBuffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models’ performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites.ResultsOverall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model.DiscussionThe development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.

IntroductionThe heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders.MethodsIn this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category.ResultsWe identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled “Neurotic” (C1), “Extraverted” (C2), “Anxious to please” (C3), “Self-critical” (C4), “Conscientious” (C5). The non-clinical clusters were labeled “Self-confident” (N1), “Low endorsement” (N2), “Non-neurotic” (N3), “Neurotic” (N4), “High endorsement” (N5). The combined clusters were labeled “Self-confident” (NC1), “Externalising” (NC2), “Neurotic” (NC3), “Secure” (NC4), “Low endorsement” (NC5), “High endorsement” (NC6), “Self-critical” (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism.DiscussionOverall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications.

Er3+ has received extensive attention due to its excellent optical properties, especially its emission at 1535 nm in atmospheric propagation window. Enhancement and regulation of 1535 nm emission of Er3+ is of great significance to optical communication. In this work, growing of CsPbBr3 QDs has been controlled through adjusting annealing time which would precisely regulate conduction band of CsPbBr3 QDs to match energy levels of Er3+ enabling energy transfer between Er3+ and CsPbBr3 QDs. By steady-state and transient PL emission and excitation spectroscopy, we reveal multiple energy transfer processes between Er3+ and CsPbBr3 QDs under different excitation wavelengths in Er3+ doped CsPbBr3 QDs glass: under higher energy excitation (∼378 nm), energy transfer from Er3+ to CsPbBr3 QDs and this extra energy within CsPbBr3 QDs decay via a non-radiative pathway; under lower energy excitation (∼524 nm), energy transfer from conduction band of CsPbBr3 QDs to 4S3/2 energy level of Er3+ which significantly enhances PL emission of Er3+ in near infrared region (∼1535 nm, 4I13/2 → 4I15/2). These results provide a facile approach to enhance and regulate PL emission of Er3+ in near infrared region.

Objective To investigate the effect of Traditional Chinese Medicine (TCM)characteristic nursing combined with Liuzijue Qigong on rehabilitation of cardiac function in patients with chronic heart failure (CHF). Methods A total of 80 CHF patients were randomly divided into the study group and control group, with 40 cases in each group. All patients received routine drug therapy during hospitalization. Patients in the control group were give routine care including work-rest schedule, dietary guidance, psychological care and daily care. Patients in the study group were given TCM characteristic nursing combined with Liuzijue Qigong in addition to routine care. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used to measure the patient quality of life, and outcomes of left ventricular ejection fractions (LVEF) and 6-minute walking test were measured and compared between two groups. Results Longer 6MWD and higher LEVF were reported in both groups at three months of intervention, and patients in the study group achieved better outcomes of 6MWD and higher LEVF compared with those in the control group(P＜0. 01). The score of MLHFQ decreased in both groups at three months of intervention, and score of MLHFQ in the study group was lower than that in the control group (P＜0. 01). Conclusion The TCM characteristic nursing combined with Liuzijue Qigong is potentially effective to improve the rehabilitation of cardiac function and long-term quality of life in CHF patients. (目的 探讨运用中医特色护理联合六字诀促进慢性心力衰竭患者心功能康复的效果。方法 选取2020年9月—2021年9月住院治疗的慢性心力衰竭患者80例为研究对象, 随机分为研究组和对照组, 各40例。两组患者均接受心力衰竭常规药物治疗。对照组采用常规护理, 指导患者休息与活动, 给予合理饮食指导、心理护理、生活护理等; 研究组在常规护理的基础上给予中医特色护理及气功六字诀指导。采用明尼苏达心力衰竭生活质量调查表(MLHFQ)评估患者生活质量, 记录左室射血分数(LVEF)和六分钟步行试验(6MWD)结果。结果 干预3个月时, 两组6MWD距离和LEVF均较入院时增加, 且研究组6MWD距离和LEVF较对照组改善明显, 差异有统计学意义(P＜0. 01)。干预3个月时, 两组MLHFQ评分均较入院时降低, 且研究组MLHFQ评分低于对照组, 差异有统计学意义(P＜0. 01)。结论 中医特色护理联合六字诀能改善慢性心力衰竭患者的心功能, 减轻临床症状, 提高患者的远期生活质量。)

The effects of constituted edible oils prepared from medium chain triglycerides and conjugated linoleates on fat accumulation and cognitive function of rats were investigated. Sixty SD rats were randomly divided into control (distilled water), lard, healthy oil and combined oil groups. The rats were oral administration for 4 weeks. The body weight, food intake and water consumption of rats were recorded, while the cognitive function was investigated using morris water maze. The Lee’s index, as well as the weights of perirenal, abdominal, epididymal and epicardial fat were measured, besides, the blood was obtained for blood glucose, liver function, lipid metabolism, leptin and TNF-α testing. The structure of small intestine and liver lobules was observed. Compared with the control group, the weight of perirenal, epididymal and epicardial fat, as well as TNF-α and ALT were significantly higher in the lard group. Compared with the lard group, the fasting glucose values, ALT, the weight of perirenal, epididymis and epicardial fat, as well as TNF-α were significantly lower in the healthy oil group and combined oil group. Compared with the control and lard groups, the level of triglycerides was significantly lower in the combined low group. The reconstituted oil has potential benefits on controlling the increase of triglyceride level and inflammatory response induced by high amount of oil intake.

We report a 30-year-old man involving gastrointestinal symptoms, vitreous opacity, and multiple cranial neuropathies. Transthyretin-related hereditary amyloidosis genetic testing revealed a rare c.251T > C variant p.(Phe84Ser). Only four cases with this variant have been reported before.

Abstract Biological denitrification is a crucial process in the nitrogen biogeochemical cycle, and Thermus has been reported to be a significant heterotrophic denitrifier in terrestrial geothermal environments. However, neither the denitrification potential nor the evolutionary history of denitrification genes in the genus Thermus or phylum Deinococcota is well understood. Here, we performed a comparative analysis of 23 Thermus genomes and identified denitrification genes in 15 Thermus strains. We confirmed that Thermus harbors an incomplete denitrification pathway as none of the strains contain the nosZ gene. Ancestral character state reconstructions and phylogenetic analyses showed that narG, nirS, and norB genes were acquired by the last common ancestor of Thermales and were inherited vertically. In contrast, nirK of Thermales was acquired via two distinct horizontal gene transfers from Proteobacteria to the genus Caldithermus and from an unknown donor to the common ancestor of all known Thermus species except Thermus filiformis. This study expands our understanding of the genomic potential for incomplete denitrification in Thermus, revealing a largely vertical evolutionary history of the denitrification pathway in the Thermaceae, and supporting the important role for Thermus as an important heterotrophic denitrifier in geothermal environments.

Abstract Background Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. Methods The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. Discussion This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. Trial registration ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .

Vibrio parahaemolyticus, commonly found in seafood products, is responsible for gastroenteritis resulting from the consumption of undercooked seafood. Hence, there is a need to characterize and quantify the risk involved from this pathogen. However, there has been no study reporting the quantification of hemolytic antimicrobial-resistant (AMR) Vibrio parahaemolyticus in locally farmed shellfish in Singapore. In this study, ampicillin, penicillin G, tetracycline resistant, and non-AMR hemolytic V. parahaemolyticus were surveyed and quantified in green mussel samples from different premises in the food chain (farm and retail). The occurrence data showed that 31/45 (68.9%) of farmed green mussel samples, 6/6 (100%) farm water samples, and 41/45 (91.1%) retail shellfish samples detected the presence of hemolytic V. parahaemolyticus. V. parahaemolyticus counts ranged from 1.6–5.9 Log CFU/g in the retail shellfish samples and 1.0–2.9 Log CFU/g in the farm water samples. AMR risk assessments (ARRA), specifically for ampicillin, penicillin G, tetracycline, and hemolytic (non-AMR) scenarios were conducted for the full farm-to-home and partial retail-to-home chains. The hemolytic ARRA scenario estimated an average probability of illness of 5.7 × 10−3 and 1.2 × 10−2 per serving for the full and partial chains, respectively, translating to 165 and 355 annual cases per total population or 2.9 and 6.2 cases per 100,000 population, respectively. The average probability of illness per year ratios for the three ARRAs to the hemolytic ARRA were 0.82, 0.81, and 0.47 (ampicillin, penicillin G, and tetracycline, respectively) for the full chain and 0.54, 0.39, and 0.09 (ampicillin, penicillin G, and tetracycline, respectively) for the partial chain. The sensitivity analysis showed that the overall cooking effect, initial concentrations of pathogenic V. parahaemolyticus, and harvest duration and harvest temperature were key variables influencing the risk estimates in all of the modelled ARRAs. The study findings can be used by relevant stakeholders to make informed decisions for risk management that improve food safety.

The acetyltransferase MYST1 stimulated by acetyl-CoA, and the deacetylase SIRT2 stimulated by NAD+, regulate PAX7 acetylation in muscle stem cells, which in turn, regulates stem cell self-renewal and regeneration following injury in mouse skeletal muscle.

Vibrio parahaemolyticus is a causative pathogen for gastroenteritis involving the consumption of undercooked or raw seafood. However, there is a paucity of data regarding the quantitative detection of this pathogen in finfish, while no study reported the enumeration of haemolytic antimicrobial-resistant (AMR) V. parahaemolyticus. In this study, ampicillin-, penicillin G- and tetracycline-resistant and non-AMR haemolytic V. parahaemolyticus isolates were monitored and quantified in grey mullet samples reared locally from different premises within the food chain (farm and retail). Occurrence data for haemolytic V. parahaemolyticus were 13/45 (29%) in farm fish samples, 2/6 (one third) from farm water samples and 27/45 (60%) from retail fish samples. Microbial loads for haemolytic V. parahaemolyticus microbial loads ranged from 1.9 to 4.1 Log CFU/g in fish samples and 2.0 to 3.0 Log CFU/g in farm water samples. AMR risk assessments (ARRAs) for both the full farm-to-home and partial retail-to-home chains in the risk modelling framework were conducted, specifically for ampicillin, penicillin G, tetracycline and haemolytic (non-AMR) scenarios. The haemolytic ARRA predicted an average probability of illness of 2.9 × 10−4 and 4.5 × 10−5 per serving for the farm-to-home and retail-to-home chains, respectively, translating to 57 and 148 cases annually. The ratios of the average probability of illness per year for the three ARRAs to the haemolytic ARRA were 1.1 × 10−2 and 3.0 × 10−4 (ampicillin and penicillin G, respectively) for the farm-to-home chain and 1.3, 1.6 and 0.4 (ampicillin, penicillin G and tetracycline, respectively) for the retail-to-home chain. Sensitivity analysis showed that the initial concentrations of haemolytic V. parahaemolyticus in the gills and intestines of the fish and the cooking and washing of the fish cavity were the major variables influencing risk outputs in all modelled ARRAs. The findings of this study are useful for relevant stakeholders to make informed decisions regarding risk management to improve overall food safety.

Abstract: The malaria parasite hijacks host erythrocytes to shield itself from the immune system and proliferate. Red blood cell abnormalities can provide protection from malaria by impeding parasite invasion and growth within the cell or by compromising the ability of parasites to avoid host clearance. Here, we describe 2 N-ethyl-N-nitrosourea–induced mouse lines, SptbMRI26194 and SptbMRI53426, containing single-point mutations in the erythrocyte membrane skeleton gene, β spectrin (Sptb), which exhibit microcytosis but retain a relatively normal ratio of erythrocyte surface area to volume and are highly resistant to rodent malaria. We propose the major factor responsible for malaria protection is the specific clearance of mutant erythrocytes, although an enhanced clearance of uninfected mutant erythrocytes was also observed (ie, the bystander effect). Using an in vivo erythrocyte tracking assay, we established that this phenomenon occurs irrespective of host environment, precluding the involvement of nonerythrocytic cells in the resistance mechanism. Furthermore, we recapitulated this phenotype by disrupting the interaction between ankyrin-1 and β spectrin in vivo using CRISPR/Cas9 genome editing technology, thereby genetically validating a potential antimalarial target. This study sheds new light on the role of β spectrin during Plasmodium infection and highlights how changes in the erythrocyte cytoskeleton can substantially influence malaria susceptibility with minimal adverse consequences for the host.

Allelic heterogeneity is a common phenomenon where a gene exhibits a different phenotype depending on the nature of its genetic mutations. In the context of genes affecting malaria susceptibility, it allowed us to explore and understand the intricate host–parasite interactions during malaria infections. In this study, we described a gene encoding erythrocytic ankyrin-1 (Ank-1) which exhibits allelic-dependent heterogeneous phenotypes during malaria infections. We conducted an ENU mutagenesis screen on mice and identified two Ank-1 mutations, one resulting in an amino acid substitution (MRI95845), and the other a truncated Ank-1 protein (MRI96570). Both mutations caused hereditary spherocytosis-like phenotypes and confer differing protection against Plasmodium chabaudi infections. Upon further examination, the Ank-1(MRI96570) mutation was found to inhibit intraerythrocytic parasite maturation, whereas Ank-1(MRI95845) caused increased bystander erythrocyte clearance during infection. This is the first description of allelic heterogeneity in ankyrin-1 from the direct comparison between two Ank-1 mutations. Despite the lack of direct evidence from population studies, this data further supported the protective roles of ankyrin-1 mutations in conferring malaria protection. This study also emphasized the importance of such phenomena in achieving a better understanding of host–parasite interactions, which could be the basis of future studies.