Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultrastructural and immunohistochemical characteristics of the olfactory organ cardinal tetra, Paracheirodon axelrodi (Characiformes: Characidae)

The cardinal tetra Paracheirodon axelrodi belongs to the family Characidae, an economically important and morphologically diverse family of fishes. Information on the olfactory system of this species is scattered and scarce. Among teleost fishes, differences exist in the shape, number, and arrangement of the olfactory lamellae, in the distribution of the sensory and nonsensory epithelium, as well as in the abundance of various receptor cell types. Here, an anatomical and morphological description of the olfactory system was carried out using light microscopic histology, immunohistochemistry, scanning electron microscopy, and transmission electron microscopy. P. axelrodi is a ditremous and isosmat species. It has an arrow‐shaped olfactory rosette arrangement. The olfactory epithelium is covering the 12–14 lamellae of the olfactory rosette and, using scanning electron microscopy, we observed that the apical surface of the olfactory epithelium carries a dense layer of mucus. Based on the histological, immunohistochemical, and ultrastructural descriptions, all characteristic sensory and nonsensory cell types of the olfactory epithelium of teleost fish were identified. Three types of olfactory receptor neurons were identified: ciliated, microvilli, and crypt cells. The distribution of sensory and nonsensory cell types is like that described in Aphyocharax anisitsi, another species of the Characidae family. A. anisitsi inhabits slow‐flowing water bodies with high‐density vegetation such as P. axelrodi.
Filament organization of the bacterial actin MreB is dependent on the nucleotide state

Through the characterization of Spiroplasma MreB5, Pande et al. show that MreB5 exhibits a nucleotide-dependent allosteric effect on filament dynamics and membrane binding. The results highlight the conserved and distinct features of MreBs in shape determination, independent of peptidoglycan synthesis machinery.
EXPERIMENTAL STUDY ON UNDERGROUND SHOCK EFFECTS UNDER REPEATED EXPLOSIONS

In order to research the decay laws of pressure wave and positive pressure actuation duration with the increasing propagation distance under the repeated penetration and explosion of conventional weapons in rock,the tests with varying scale charge and scale distance of the first drilled explosion and the repeated drilled explosion are completed.The experimental results show that the peak pressure and positive pressure actuation duration by the first drilled explosion on the same measuring points are less than those by repeated drilled explosion;the decay speeds of peak pressure and positive pressure actuation duration by the first drilled explosion are lower than those by repeated drilled explosion,and their decay tendency are in agreement with the decay laws of pressure wave in rock under the same experiment conditions.The decay curves of peak pressure and positive pressure actuation duration with increasing scale distance have been given by the analysis of test results,and the corresponding empirical formulas have been presented.The exponential decay laws of peak pressure and positive pressure actuation duration with increasing scale distance have been discovered.
Genes Differentially Expressed by Haemophilus ducreyi during Anaerobic Growth Significantly Overlap Those Differentially Expressed during Experimental Infection of Human Volunteers

In humans, H. ducreyi resides in the anaerobic environment of an abscess and appears to upregulate genes involved in anaerobic metabolism. How anaerobiosis alone affects gene transcription in H. ducreyi is unknown. ABSTRACT Haemophilus ducreyi causes cutaneous ulcers in children and the genital ulcer disease chancroid in adults. In humans, H. ducreyi is found in the anaerobic environment of an abscess; previous studies comparing bacterial gene expression levels in pustules with the inocula (∼4-h aerobic mid-log-phase cultures) identified several upregulated differentially expressed genes (DEGs) that are associated with anaerobic metabolism. To determine how H. ducreyi alters its gene expression in response to anaerobiosis, we performed RNA sequencing (RNA-seq) on both aerobic and anaerobic broth cultures harvested after 4, 8, and 18 h of growth. Principal-coordinate analysis (PCoA) plots showed that anaerobic growth resulted in distinct transcriptional profiles compared to aerobic growth. During anaerobic growth, early-time-point comparisons (4 versus 8 h) identified few DEGs at a 2-fold change in expression and a false discovery rate (FDR) of <0.01. By 18 h, we observed 18 upregulated and 16 downregulated DEGs. DEGs involved in purine metabolism, the uptake and use of alternative carbon sources, toxin production, nitrate reduction, glycine metabolism, and tetrahydrofolate synthesis were upregulated; DEGs involved in electron transport, thiamine biosynthesis, DNA recombination, peptidoglycan synthesis, and riboflavin synthesis or modification were downregulated. To examine whether transcriptional changes that occur during anaerobiosis overlap those that occur during infection of human volunteers, we compared the overlap of DEGs obtained from 4 h of aerobic growth to 18 h of anaerobic growth to those found between the inocula and pustules in previous studies; the DEGs significantly overlapped. Thus, a major component of H. ducreyi gene regulation in vivo involves adaptation to anaerobiosis. IMPORTANCE In humans, H. ducreyi resides in the anaerobic environment of an abscess and appears to upregulate genes involved in anaerobic metabolism. How anaerobiosis alone affects gene transcription in H. ducreyi is unknown. Using RNA-seq, we investigated how anaerobiosis affects gene transcription over time compared to aerobic growth. Our results suggest that a substantial component of H. ducreyi gene regulation in vivo overlaps the organism’s response to anaerobiosis in vitro. Our data identify potential therapeutic targets that could be inhibited during in vivo growth.
C‐reactive protein trajectories and the risk of all cancer types: A prospective cohort study

A single CRP measurement is insufficient to examine the association of long‐term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new‐onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific‐site cancer. Four CRP trajectories patterns were identified: low‐stable pattern (n = 43 258), moderate‐increasing pattern (n = 2591), increasing‐decreasing pattern (n = 2068) and elevated‐decreasing pattern (n = 4359). Relative to the low‐stable pattern, the moderate‐increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing‐decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing‐decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated‐decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia.
Development and internal validation of machine learning algorithms for end-stage renal disease risk prediction model of people with type 2 diabetes mellitus and diabetic kidney disease

Abstract Aims Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) and is associated with increased morbidity and mortality in patients with diabetes. Identification of risk factors involved in the progression of DKD to ESRD is expected to result in early detection and appropriate intervention and improve prognosis. Therefore, this study aimed to establish a risk prediction model for ESRD resulting from DKD in patients with type 2 diabetes mellitus (T2DM). Methods Between January 2008 and July 2019, a total of 390 Chinese patients with T2DM and DKD confirmed by percutaneous renal biopsy were enrolled and followed up for at least 1 year. Four machine learning algorithms (gradient boosting machine, support vector machine, logistic regression, and random forest (RF)) were used to identify the critical clinical and pathological features and to build a risk prediction model for ESRD. Results There were 158 renal outcome events (ESRD) (40.51%) during the 3-year median follow up. The RF algorithm showed the best performance at predicting progression to ESRD, showing the highest AUC (0.90) and ACC (82.65%). The RF algorithm identified five major factors: Cystatin-C, serum albumin (sAlb), hemoglobin (Hb), 24-hour urine urinary total protein, and estimated glomerular filtration rate. A nomogram according to the aforementioned five predictive factors was constructed to predict the incidence of ESRD. Conclusion Machine learning algorithms can efficiently predict the incident ESRD in DKD participants. Compared with the previous models, the importance of sAlb and Hb were highlighted in the current model. Highlights What is already known? Identification of risk factors for the progression of DKD to ESRD is expected to improve the prognosis by early detection and appropriate intervention. What this study has found? Machine learning algorithms were used to construct a risk prediction model of ESRD in patients with T2DM and DKD. The major predictive factors were found to be CysC, sAlb, Hb, eGFR, and UTP. What are the implications of the study? In contrast with the treatment of participants with early-phase T2DM with or without mild kidney damage, major emphasis should be placed on indicators of kidney function, nutrition, anemia, and proteinuria for participants with T2DM and advanced DKD to delay ESRD, rather than age, sex, and control of hypertension and glycemia.
Exploring the risk factors of child malnutrition in Sub-Sahara Africa: A scoping review

Background: Malnutrition prevents children from reaching their full physical and mental potential. Health and physical consequences of prolonged states of malnourishment among children are: delay in their physical growth and motor development; lower intellectual quotient (IQ), greater behavioural problems and deficient social skills; susceptibility to contracting diseases. According to the 2015 Millennium development goal (MDG) report, sub-Saharan Africa (SSA) accounts for one third of all undernourished children globally, highlighting that malnutrition still remains a major health concern for children under 5 years in the sub-region, thus buttressing the need for urgent intervention. Aim: The aim of this study is to explore the risk factors of child malnutrition in sub–Saharan Africa through a scoping review. Methods: The scoping review was conducted using the following specific subject databases: EBSCOhost, google scholar, Pub med, demographic research and research gate. Attention was paid to keywords during navigation to ensure consistency of searches in each database. Two limiters were applied in all five databases. These included the use of the English language and articles published on child malnutrition in sub Saharan Africa. Results: The researchers identified eight themes for inclusion in the findings. The themes fell into four major categories being maternal related, family related, child related as well as context related factors. These themes reflect factors associated with child malnutrition. Conclusion: This scoping review revealed that there are quite a number of risk factors that lead to child malnutrition. Therefore, there is an urgency for strategic interventions aimed at improving child nutrition through female education if the 2030 end malnutrition SDG 2.2 are to be achieved.
Do Adolescents Intervene in Intergroup Bias-based Bullying? Bystander Judgments and Responses to Intergroup Bias-based Bullying of Refugees.

This study examined 587 Turkish adolescents' (Mage = 13.14, SD = 1.61) judgments and bystander responses towards hypothetical intragroup interpersonal (Turkish victim) and intergroup bias-based (Syrian refugee victim) bullying. Intergroup factors and social-cognitive skills were assessed as predictors. Findings revealed that adolescents were less likely to see bullying as acceptable and less likely to explicitly support the bully in intragroup interpersonal bullying compared to intergroup bias-based bullying. Further, adolescents with higher theory of mind and empathy were more likely to evaluate intergroup bias-based bullying as less acceptable and more likely to challenge the bully. Adolescents' prejudice and discrimination towards refugees were predictors of bystander judgments and responses to intergroup bias-based bullying. This study provides implications for anti-bullying intervention programs.
The impact of COVID-19 on O&G trainees; where are we now?

Background and Objectives Obstetrics and Gynaecology (O&G) training continues to face challenges caused by the COVID-19 pandemic, particularly in gynaecological surgical training. This follow-up survey captures the ongoing effect on O&G trainees and highlights the future recovery plan considering the historical training gaps in benign gynaecology. Materials and Methods an anonymised survey was emailed to all O&G trainees in Kent, Surrey and Sussex (KSS). Responses were collected over 6 weeks. Main Outcome Measures and Results 53% of trainees responded. In total, 78% of trainees agreed that the pandemic had an ongoing negative effect on their physical and mental wellbeing respectively. Trainees felt the prior negative impact on obstetric training is improving, whilst 88% still experience a negative impact on their gynaecology surgical training despite the resumption of elective services in the National Health Service (NHS). 80% continue to feel the negative impact on their educational activities and 88% felt their overall training continues to be negatively impacted. 70% were positive that they would recover from this. Responses were representative of each training year. Interestingly, 95% of trainees had accepted the COVID vaccine. Conclusion despite “restoration” of normal services, the negative impact on trainees particularly benign gynaecology surgical training continues. Addressing pre-pandemic training gaps whilst tackling the surgical back- log and the needs of service provision will continue for years to follow. What is new? Future training needs to incorporate creative ways of acquiring surgical skills. It is imperative to imbed simulation training into O&G training programmes. Pastoral support is key to ensure trainees’ mental and physical well-being are prioritised and the already high burn-out rates do not worsen.
A novel clinical immune‐related prognostic model predicts the overall survival of mantle cell lymphoma

The mantle cell lymphoma (MCL) International Prognostic Index (MIPI) and combined MIPI (MIPI‐c) are commonly used for risk classification of MCL patients. However, these indexes lack immune‐related parameters. The purpose of this study was to develop a novel prognostic model that integrated clinical and immune parameters. A total of 189 patients with newly diagnosed MCL from January 2010 to June 2020 were enrolled in our study. A nomogram and immune‐related prognostic index (IRPI) were established to predict the overall survival (OS) of patients according to univariate and multivariate analyses. Discrimination and calibration were used to compare the prognostic performance of the IRPI, MIPI, and MIPI‐c. External validation was performed based on validation dataset (n = 150) from two other centers. The results for the training dataset indicated that B symptoms, platelet count, B2M level, CD4+ T‐cell count<26.7% and CD8+ T‐cell count>44.2% were predictors for OS. All the prognostic factors were integrated into the nomogram. For the overlap of confidence intervals of each variable, we assigned one point for each factor. The IRPI categorized patients into three risk categories: a score of zero indicated low risk, a score of one or two indicated intermediate risk, and a score of ≥3 indicated high risk. The IRPI showed better discrimination and calibration power than the MIPI and MIPI‐c in the training dataset and validation dataset. The novel IRPI is a refined risk stratification index and reflects the strong complementary prognostic effects between clinical and immune parameters in MCL.
Structure–activity relationship of a peptide permeation enhancer

ABSTRACT The pentapeptide L-R5 has previously been shown to transiently increase the permeability of nasal epithelial cell layers in vitro, allowing paracellular transport of molecules of up to 4 kDa. Protein kinase C zeta (PKC ζ), a member of a family of serine/threonine kinases was shown to be involved in tight junction modulation induced by L-R5. We show here that the ability of L-R5 to modulate tight junctions is comparable to other permeability enhancers such as bilobalide, latrunculin A or C10. Interaction of the peptide with the target protein occurs via electrostatic interaction, with the presence of positive charges being essential for its functionality. L-R5 is myristoylated to allow quick cell entry and onset of activity. While no epithelial cytotoxicity was detected, the hydrophobic myristoyl rest was shown to cause haemolysis. Taken together, these data show that a structural optimization of L-R5 may be possible, both from a toxicological and an efficacy point of view.
Physical activity levels, cardiovascular risk, and self-perceived barrier to physical activity in people living with HIV in Maranhão, Brazil: a short report

ABSTRACT The aim of this research was to investigate the existence of associations between habitual physical activity and cardiovascular risk in people living with HIV; and to identify self-perceived barriers to physical activity. The sample of 104 subjects was composed of people living with HIV and treatment for at least 6 months in a Specialized Care Service. Baeck’s survey, a self-perceived barrier questionnaire, medical records, and equations from Framingham’s Cardiovascular Disease were used. Linear regression models were used to investigate the association between Habitual Physical Activity score (HPA) and predicted cardiovascular risk, and descriptive statistics to investigate prevalence of self-perceived barriers. In the first model (r² = 0.212, F = 4.34, p < 0.001), increasing 1 point in the HPA score predicts the decrease by 1.04 percentage points (p.p.) Cardiovascular risk for the next 10 years. In the second model (r 2 = 0. 244, F = 4. 99, p < 0.001), increase one point the HPA score decreases by 3.729 p.p. Predicted cardiovascular risk for the next 30 years. The results confirmed an inverse association between HPA and predicted cardiovascular risk in PLHIV.
Individualized Prediction of Drug Response and Rational Combination Therapy in NSCLC Using Artificial Intelligence–Enabled Studies of Acute Phosphoproteomic Changes

Abstract We hypothesize that the study of acute protein perturbation in signal transduction by targeted anticancer drugs can predict drug sensitivity of these agents used as single agents and rational combination therapy. We assayed dynamic changes in 52 phosphoproteins caused by an acute exposure (1 hour) to clinically relevant concentrations of seven targeted anticancer drugs in 35 non–small cell lung cancer (NSCLC) cell lines and 16 samples of NSCLC cells isolated from pleural effusions. We studied drug sensitivities across 35 cell lines and synergy of combinations of all drugs in six cell lines (252 combinations). We developed orthogonal machine-learning approaches to predict drug response and rational combination therapy. Our methods predicted the most and least sensitive quartiles of drug sensitivity with an AUC of 0.79 and 0.78, respectively, whereas predictions based on mutations in three genes commonly known to predict response to the drug studied, for example, EGFR, PIK3CA, and KRAS, did not predict sensitivity (AUC of 0.5 across all quartiles). The machine-learning predictions of combinations that were compared with experimentally generated data showed a bias to the highest quartile of Bliss synergy scores (P = 0.0243). We confirmed feasibility of running such assays on 16 patient samples of freshly isolated NSCLC cells from pleural effusions. We have provided proof of concept for novel methods of using acute ex vivo exposure of cancer cells to targeted anticancer drugs to predict response as single agents or combinations. These approaches could complement current approaches using gene mutations/amplifications/rearrangements as biomarkers and demonstrate the utility of proteomics data to inform treatment selection in the clinic.
Socioecological Factors Associated With Physical Activity and Sedentary Behavior Among Workers: Using the PRECEDE-PROCEED Model

Background: Physical inactivity is a major global health problem. Industrial automation has led to an increased number of workers who are sedentary at work. We examined whether three socioecological factors (i.e., predisposing, reinforcing, and enabling factors) derived from the PRECEDE-PROCEED model would be significantly associated with the physical activity and sedentary behavior among workers. Methods: A cross-sectional study was conducted among 539 employees at an electronic manufacturing plant in Gumi, South Korea. Physical activity variables of energy expenditure (MET-min/week) and sitting time at work (minutes/day) were measured by the International Physical Activity Questionnaire and the Workforce Sitting Questionnaire, respectively. Of the socioecological factors, a predisposing factor defined as self-determined motivation was measured by the Exercise Self-Regulation Questionnaire; a reinforcing factor defined as autonomy support was measured by the Work Climate Questionnaire; and an enabling factor defined as supportive workplace environment was measured by the Perceived Workplace Environment Scale. Findings: Self-determined motivation (i.e., autonomous and controlled forms of motivation), autonomy support, and a supportive workplace environment were all significantly associated with increased physical activity energy expenditure during leisure-time. However, they were not significantly associated with sitting time on working and non-working days. Conclusion/Applications to Practice: Three socioecological factors of the PRECEDE-PROCEED model were significantly associated with leisure-time physical activity among workers. Our findings may help occupational health nurses use a socioecological approach for designing effective workplace strategies to increase leisure-time physical activity among workers.