Miracle-dz/UniFAR-FTUs huggingface dataset:
GnRH Agonist and hCG (Dual Trigger) Versus hCG Trigger for Final Oocyte Maturation in Expected Normal Responders With a High Immature Oocyte Rate: Study Protocol for a Randomized, Superiority, Parallel Group, Controlled Trial

Introduction The choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate. Methods and Analysis We propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: recombinant hCG (6500 IU) will be injected only 36 hours before OPU for final oocyte maturation (hCG-only trigger); co-administration of GnRH-a and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (Dual trigger). The primary outcome is metaphase-II (MII) oocytes rate. Secondary outcomes are number of oocytes retrieved, fertilization rate, top-quality embryos rate, blastula formation rate, embryo implantation rate, clinical pregnancy rate, miscarriage rate, live birth rate, cumulative pregnancy/live birth rates, and ovarian hyperstimulation syndrome (OHSS) rate. Ethics and Dissemination The reproductive ethics committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine certified this study (Identifier: SDUTCM/2021.7.26) as ethical. All individuals will sign written informed consent. All data and biological samples will be protected according to law. The results of this study will be disseminated in a peer-reviewed scientific journal. Clinical Trial Registration [chictr.gov. cn], identifier [ChiCTR2100049292].
Two (p)ppGpp Synthetase Genes, relA and spoT, Are Involved in Regulating Cell Motility, Exopolysaccharides Production, and Biofilm Formation of Vibrio alginolyticus

The stringent response mediated by the signal molecule (p)ppGpp is involved in response to multiple environmental stresses and control of various physiological processes. Studies have revealed that (p)ppGpp strongly affects the formation and maintenance of several bacterial biofilms. However, the specific regulatory roles of (p)ppGpp in biofilms, especially in the expression of genes related to cell motility and exopolysaccharides (EPSs) production, remain poorly understood. We recently reported two (p)ppGpp synthetase genes relA and spoT from the epizootic pathogen Vibrio alginolyticus. Herein, we found that the (p)ppGpp synthetase genes of V. alginolyticus contributed to biofilm formation at low cell density and biofilm detachment at high cell density, respectively, in polystyrene microtiter plates. Quantitative reverse transcription PCR (qRT-PCR) analysis revealed that the expression levels of both EPSs and motility associated genes were consistent with the development of biofilms. Besides, the (p)ppGpp synthetase gene spoT was found to be closely involved in the regulation of flagellum, smooth/translucent colony morphology and spotty pellicle at the air-liquid interface. Interestingly, pleiotropic phenotypes of ΔrelAΔspoT were similar to that of the rpoN (σ54) deletion mutant. Meanwhile, the absence of (p)ppGpp synthetase genes significantly reduced the expression levels of rpoN at low cell density, suggesting that (p)ppGpp may mediate the formation via positively affecting the alternative sigma factor RpoN. These findings allow us to propose (p)ppGpp as a crucial regulator for biofilm development in V. alginolyticus, in view of the regulatory roles of relA and spoT in cell motility and EPSs production.
Effects of Transcranial Pulse Stimulation (TPS) on Young Adults With Symptom of Depression: A Pilot Randomised Controlled Trial Protocol

Background Since the emergence of the COVID-19 pandemic, there have been lots of published work examining the association between COVID-19 and mental health, particularly, anxiety and depression in the general populations and disease subpopulations globally. Depression is a debilitating disorder affecting individuals' level of bio-psychological-social functioning across different age groups. Since almost all studies were cross-sectional studies, there seems to be a lack of robust, large-scale, and technological-based interventional studies to restore the general public's optimal psychosocial wellbeing amidst the COVID-19 pandemic. Transcranial pulse stimulation (TPS) is a relatively new non-intrusive brain stimulation (NIBS) technology, and only a paucity of studies was conducted related to the TPS treatment on older adults with mild neurocognitive disorders. However, there is by far no study conducted on young adults with major depressive disorder nationwide. This gives us the impetus to execute the first nationwide study evaluating the efficacy of TPS on the treatment of depression among young adults in Hong Kong. Methods This study proposes a two-armed single-blinded randomised controlled trial including TPS as an intervention group and a waitlist control group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 3- month follow-up (T3). Recruitment A total of 30 community-dwelling subjects who are aged 18 and above and diagnosed with major depressive disorder (MDD) will be recruited in this study. All subjects will be computer randomised into either the intervention group or the waitlist control group, balanced by gender and age on a 1:1 ratio. Intervention All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes Baseline measurements and post-TPS evaluation of the psychological outcomes (i.e., depression, cognition, anhedonia, and instrumental activities of daily living) will also be conducted on all participants. A 3-month follow-up period will be used to assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyse data. Missing data were managed by multiple mutations. The level of significance will be set to p < 0.05. Significance of the Study Results of this study will be used to inform health policy to determine whether TPS could be considered as a top treatment option for MDD. Clinical Trial Registration ClinicalTrials.gov, identifier: NCT05006365.
Analysis of Key Control Points of Microbial Contamination Risk in Pork Production Processes Using a Quantitative Exposure Assessment Model

Pork is one of the most common foods causing microbial foodborne diseases. Since pork directly enters the market after slaughtering, the control of microbial contamination in the slaughtering processes is the key to ensuring the quality and safety of pork. The contamination level of Escherichia coli, a health-indicator bacterium, can reflect the risk level of potential pathogens. In order to assess the E. coli exposure risk of pork during slaughtering and to identify the key control points, we established an E. coli quantitative exposure assessment model for swine-slaughtering processes in slaughterhouses of different sizes. The model simulation data indicated the E. coli contamination pattern on the surfaces of swine carcasses during slaughtering. The changes in E. coli contamination were analyzed according to the simulation data of each slaughtering process. It was found that the number of E. coli after trimming in big and small slaughterhouses increased to the maximum values for the whole processes, which were 3.63 and 3.52 log10 CFU/100 cm2, respectively. The risk contribution of each slaughtering process to the E. coli contamination on the surface of terminal swine carcasses can be determined by correlation analysis. Because the absolute value of correlation coefficient during the trimming process was maximum (0.49), it was regarded as the most important key control point. This result can be further proved via the multilocus sequence typing of E. coli. The dominant sequence type before trimming processes was ST10. ST1434 began to appear in the trimming process and then became the dominant sequence type in the trimming and pre-cooling processes. The model can provide a theoretical basis for microbial hygiene supervision and risk control in swine-slaughtering processes.
A Single Transcript Knockdown-Replacement Strategy Employing 5’ UTR Secondary Structures to Precisely Titrate Rescue Protein Translation

One overarching goal of gene therapy is the replacement of faulty genes with functional ones. A significant hurdle is presented by the fact that under- or over-expression of a protein may cause disease as readily as coding mutations. There is a clear and present need for pipelines to translate experimentally validated gene therapy strategies to clinical application. To address this we developed a modular, single-transgene expression system for replacing target genes with physiologically expressed variants. In order to accomplish this, we first designed a range of 5’ UTR “attenuator” sequences which predictably diminish translation of the paired gene. These sequences provide wide general utility by allowing control over translation from high expression, ubiquitous promoters. Importantly, we demonstrate that this permits an entirely novel knockdown and rescue application by pairing microRNA-adapted shRNAs alongside their respective replacement gene on a single transcript. A noteworthy candidate for this corrective approach is the degenerative and uniformly fatal motor neuron disease ALS. A strong proportion of non-idiopathic ALS cases are caused by varied mutations to the SOD1 gene, and as clinical trials to treat ALS are being initiated, it is important to consider that loss-of-function mechanisms contribute to its pathology as strongly as any other factor. As a generalized approach to treat monogenic diseases caused by heterogeneous mutations, we demonstrate complete and predictable control over replacement of SOD1 in stable cell lines by varying the strength of attenuators.
New Insight on Vitality Differences for the Penaeid Shrimp, Fenneropenaeus chinensis, in Low Salinity Environment Through Transcriptomics

Excessive rainfall changes salinity in shrimp farming ponds in short period and exerts low salinity stress on the outdoor breeding shrimp under global warming. Fenneropenaeus chinensis can have different performance on vitality in low salinity environments. To reveal mechanisms of vitality difference in shrimp living in low saline environments. This study based on the normal and moribund F. chinensis in 10 ppt salinity environment using high-throughput sequencing identifies 1,429 differentially expressed genes (DEGs), 586 of which are upregulated, while 843 of which are downregulated in the normal group (FCN10) as compared to the moribund group (FCM10). Meanwhile, another transcriptomic analysis is conducted on the normal and moribund shrimp from 25 ppt (FCN25 vs. FCM25) salinity environment as the control, in which 1,311 DEGs (upregulated: 327 genes, downregulated: 984 genes) are identified. In this study, intersective pathways, GO (Gene Ontology) categories and DEGs from the two groups of comparative transcriptome are investigated. The two intersective pathways (Metabolism of xenobiotics by cytochrome P450, Pentose, and glucuronate interconversions) significantly enriched by DEGs are related to detoxification. In these two pathways, there is one vitality regulation-related gene (VRRG), the Dhdh (dihydrodiol dehydrogenase), which is upregulated in both the groups of FCN10 and FCN25 as compared to the groups of FCM10 and FCM25, respectively. Similarly, in the 25 top intersective GO categories, four VRRGs are revealed. Three of them are upregulated (Itgbl, kielin/chordin-like protein, Slc2a8, solute carrier family 2, facilitated glucose transporter member 8-like protein and Cyp3a30, cytochrome P450 3A30-like protein); one of them is downregulated (Slc6a9, sodium-dependent nutrient amino acid transporter 1-like protein isoform X2). These GO categories are related to transmembrane transporter activity of substance, enzyme inhibitor activity, monooxygenase activity. RT-qPCR analysis further verifies the VRRGs. The study gives new insight into understanding the vitality differences for F. chinensis, in low salinity environment. The pathways and DEGs in response to low salinity stress in modulating the vitality of F. chinensis that could serve as tools in future genetic studies and molecular breeding.
Radiomics in Gastric Cancer: First Clinical Investigation to Predict Lymph Vascular Invasion and Survival Outcome Using 18F-FDG PET/CT Images

Background Lymph vascular invasion (LVI) is an unfavorable prognostic indicator in gastric cancer (GC). However, there are no reliable clinical techniques for preoperative predictions of LVI. The aim of this study was to develop and validate PET/CT-based radiomics signatures for predicting LVI of GC preoperatively. Radiomics nomograms were also established to predict patient survival outcomes. Methods This retrospective study registered 148 GC patients with histopathological confirmation for LVI status, who underwent pre-operative PET/CT scans (Discovery VCT 64 PET/CT system) from December 2014 to June 2019. Clinic-pathological factors (age, gender, and tumor grade, etc.) and metabolic PET data (maximum and mean standardized uptake value, total lesion glycolysis and metabolic tumor volume) were analyzed to identify independent LVI predictors. The dataset was randomly assigned to either the training set or test set in a 7:3 ratios. Three-dimensional (3D) radiomics features were extracted from each PET- and CT-volume of interests (VOI) singularly, and then a radiomics signature (RS) associated with LVI status is built by feature selection. Four models with different modalities (PET-RS: only PET radiomics features; CT-RS: only CT radiomics features; PET/CT-RS: both PET and CT radiomics features; PET/CT-RS plus clinical data) were developed to predict LVI. Patients were postoperatively followed up with PET/CT every 6-12 months for the first two years and then annually up to five years after surgery. The PET/CT radiomics score (Rad-scores) was calculated to assess survival outcome, and corresponding nomograms with radiomics (NWR) or without radiomics (NWOR) were established. Results Tumor grade and maximum standardized uptake value (SUVmax) were the independent LVI predictor. 1037 CT and PET 3D radiomics features were extracted separately and reduced to 4 and 5 features to build CT-RS and PET-RS, respectively. PET/CT-RS and PET/CT-RS plus clinical data (tumor grade and SUVmax) were also developed. The ROC analysis demonstrated clinical usefulness of PET/CT-RS plus clinical data (AUC values for training and validation, respectively 0.936 and 0.914) and PET/CT-RS (AUC values for training and validation, respectively 0.881 and 0.854), which both are superior to CT-RS (0.838 and 0.824) and PET-RS (0.821 and 0.812). SUVmax and LVI were independent prognostic indicators of both OS and PFS. Decision curve analysis (DCA) demonstrated NWR outperformed NWOR and was established to assess survival outcomes. For estimation of OS and PFS, the C-indexes of the NWR were 0. 88 and 0.88 in the training set, respectively, while the C-indexes of the NWOR were 0. 82 and 0.85 in the training set, respectively. Conclusions The PET/CT-based radiomics analysis might serve as a non-invasive approach to predict LVI status in GC patients and provide effective predictors of patient survival outcomes.
The Effect of Fear of COVID-19 on Green Purchase Behavior in Pakistan: A Multi-Group Analysis Between Infected and Non-infected

The coronavirus disease 2019 (COVID-19) pandemic and its effects on an individual’s life have altered the consumer behavior. In the context of purchase and consumption, a shift from conventional to green purchase has been noticed. Although the factors underlying this shift were relatively unexplored, the study aimed to identify the factors that influenced a significant role in the green purchases during the outbreak and the relationship of these factors with green purchase behavior (GPB). Subsequently, this study investigates and interprets the role of fear of COVID-19 (FCV), psychological distress (PD), and mortality salience (MS) in predicting consumer’s GPB. This research adopted a quantitative methodology using data collected from 432 respondents in various cities across Pakistan. Smart-PLS 3 was used to evaluate the measurement model, structural model, and multi-group analysis (MGA). Despite having the negative psychological and physical impact of the pandemic, a significant proportion of customers have switched to healthier and sustainable products. This research revealed that the FCV, PD, and MS plays a substantial role in adopting GPB. All the direct relationships were positive and significant. In addition, MS and PD partially mediate the effect of FCV on GPB. Furthermore, the MGA revealed that the infected respondents were interested in purchasing green products than uninfected respondents due to their FCV; conversely, the PD and MS were higher in uninfected individuals than infected ones. However, there is a vast literature on GPB, but little has investigated the cumulative impact of FCV, PD, and MS on GPB.
Atherosclerotic Cardiovascular Disease Risk and Lipid-Lowering Therapy Requirement in China

Background Lipid-lowering therapy (LLT) is one of the key strategies for reducing the atherosclerotic cardiovascular disease (ASCVD) burden. However, little is known about the percentage of people in need of different LLT regimens to achieve optimal targets of low-density lipoprotein cholesterol (LDL-C), and the corresponding cost and benefit. Methods We conducted a simulation study based on the data from the nationwide China PEACE MPP population cohort (2015–2020), from which we included 2,904,914 participants aged 35–75 years from all the 31 provinces in mainland China. Participants were grouped based on their 10-year ASCVD risks, then entered into a Monte Carlo model which was used to perform LLT intensification simulation scenarios to achieve corresponding LDL-C goals in each risk stratification. Results After standardizing age and sex, the proportions of participants included at low, moderate, high, and very-high risk were 70.8%, 15.6%, 11.5%, and 2.1%, respectively. People who failed to achieve the corresponding LDL-C goals −8.1% at low risk, 19.6% at moderate risk, 53.2% at high risk, and 93.6% at very-high risk (either not achieving the goal or not receiving LLT)—would be in need of the LLT intensification simulation. After the use of atorvastatin 20 mg was simulated, over 99% of the population at low or moderate risk could achieve the LDL-C goals; while 11.3% at high and 24.5% at very-high risk would still require additional non-statin therapy. After the additional use of ezetimibe, there were still 4.8% at high risk and 11.3% at very-high risk in need of evolocumab; and 99% of these two groups could achieve the LDL-C goals after the use of evolocumab. Such LLT intensification with statin, ezetimibe, and evolocumab would annually cost $2.4 billion, $4.2 billion, and $24.5 billion, respectively, and prevent 264,170, 18,390, and 17,045 cardiovascular events, respectively. Conclusions Moderate-intensity statin therapy is pivotal for the attainment of optimal LDL-C goals in China, and around 10–25% of high- or very-high-risk patients would require additional non-statin agents. There is an opportunity to reduce the rising ASCVD burden in China by optimizing LLT.
Suspension-Feeding Benthic Species’ Physiological and Microbiome Response to Salmon Farming and Associated Environmental Changes

Caged salmon farming is increasingly undertaken in water bodies with strong hydrodynamics where hard and mixed substrate habitats are more prevalent. Yet, these structurally complex and heterogeneous habitats support diverse benthic communities including several cnidarians and sponges that remain poorly characterized. This study used a combination of respirometry measurements, gas chromatography and 16S rRNA metabarcoding to define the respiration rate, stable carbon (δ13C) and nitrogen isotopes (δ15N), fatty acid (FA) and microbial profiles, and assess the impact of salmon farming on four important epibenthic suspension-feeders along the western Norwegian coast: the sponges Craniella and Weberella, the soft coral Duva florida and the anemone Hormathia digitata. Our results showed striking differences in fatty acid profiles and host microbiome communities in terms of identity, functional capabilities and genetic properties across the suspension-feeders. We found evidence of increased mortality rate in specimens located near fish farm activities and of a species-specific effect on respiration rate, with D. florida showing increased activity under the farm. Effects of fish farming on the suspension feeders were also species-specific and particularly evidenced by functional microbial turnover and by alteration of overall FA profiles in the soft coral and sea anemone. In particular, D. florida showed reduced level of FAs close to the farm (0-350 m), with significant difference in composition along a distance gradient. Only H. digitata showed evidence of incorporation of organic material from the fish farm waste via fatty acids trophic markers (FATM) and stable isotope analysis. Overall, our study demonstrates that suspension feeders have taxon-specific sensitivity towards the effect of salmon farming, and identified several potential molecular indicators that could be used as surrogate of impact gradient upon further research and validation. It also provides a wealth of ecological and physiological information on some of the most common sessile epibenthic organisms within Arctic and sub-Arctic regions, enabling us to better understand their response and evaluate their resilience to environmental changes.