Miracle-dz/UniFAR-FTUs huggingface dataset:
Do dietary amino acid ratios predict risk of incident hypertension among adults?

Abstract In the current study, we investigated the association between dietary amino acid ratios and the 3-year incidence of hypertension, conducted in the framework of the Tehran Lipid and Glucose Study with 4287 adults(41.9% men), aged 20–70 y. Dietary intakes of amino acids were assessed using a valid and reliable food frequency questionnaire and reported as percentage of protein. Then amino acid ratios including Leu.Ser/Thr.Trp, Leu/Trp, Leu/Thr, and Ser/Thr were calculated. We identified 429(10%) cases of hypertension during 3.1 y of follow up. The adjusted OR of the highest quartile of dietary Leu.Ser/Thr.Trp intake was 1.48 (95%CI:1.04–2.09, P for trend:0.02) compared with the lowest one. Furthermore, the OR of hypertension in the highest, compared with the lowest quartile of the leu/Thr ratio(2.19 vs 2.02) was 1.46(1.01–2.12), P for trend = 0.07. Our findings suggest that high dietary intakes of Leu.Ser/Thr.Trp ratio were associated with higher risk of incident hypertension and BP levels.
Inference of Germline Mutational Status and Evaluation of Loss of Heterozygosity in High-Depth, Tumor-Only Sequencing Data.

PURPOSE Inherited germline defects are implicated in up to 10% of human tumors, with particularly well-known roles in breast and ovarian cancers that harbor BRCA1/2-mutated genes. There is also increasing evidence for the role of germline alterations in other malignancies such as colon and pancreatic cancers. Mutations in familial cancer genes can be detected by high throughput sequencing (HTS), when applied to formalin-fixed paraffin-embedded (FFPE) tumor specimens. However, due to often lack of patient-matched control normal DNA and/or low tumor purity, there is limited ability to determine the genomic status of these alterations (germline versus somatic) and to assess the presence of loss of heterozygosity (LOH). These analyses, especially when applied to genes such as BRCA1/2, can have significant clinical implications for patient care. METHODS LOHGIC (LOH-Germline Inference Calculator) is a statistical model selection method to determine somatic-versus-germline status and predict LOH for mutations identified via clinical grade, high-depth, hybrid-capture tumor-only sequencing. LOHGIC incorporates statistical uncertainties inherent to HTS as well as specimen biases in tumor purity estimates, which we use to assess BRCA1/2 mutations in 1,636 specimens sequenced at Rutgers Cancer Institute of New Jersey. RESULTS Evaluation of LOHGIC with available germline sequencing from BRCA1/2 testing, demonstrates 93% accuracy, 100% precision, and 96% recall. This analysis highlights a differential tumor spectrum associated with BRCA1/2 mutations. CONCLUSION LOHGIC can assess LOH status for both germline and somatic mutations. It also can be applied to any gene with candidate, inherited mutations. This approach demonstrates the clinical utility of targeted sequencing in both identifying patients with potential germline alterations in tumor suppressor genes as well as estimating LOH occurrence in cancer cells, which may confer therapeutic relevance.
Imaging Habenula Volume in Schizophrenia and Bipolar Disorder

The habenula (Hb), a bilateral nucleus located next to the dorsomedial thalamus, is of particular relevance to psychiatric disorders based on preclinical evidence linking the Hb to depressive and amotivational states. However, studies in clinical samples are scant because segmentation of the Hb in neuroimaging data is challenging due to its small size and low contrast from the surrounding tissues. Negative affective states dominate the clinical course of schizophrenia and bipolar disorder and represent a major cause of disability. Diagnosis-related alterations in the volume of Hb in these disorders have therefore been hypothesized but remain largely untested. To probe this question, we used a recently developed objective and reliable semi-automated Hb segmentation method based on myelin-sensitive magnetic resonance imaging (MRI) data. We ascertained case-control differences in Hb volume from high resolution structural MRI data obtained from patients with schizophrenia (n = 95), bipolar disorder (n = 44) and demographically matched healthy individuals (n = 52). Following strict quality control of the MRI data, the final sample comprised 68 patients with schizophrenia, 32 with bipolar disorder and 40 healthy individuals. Regardless of diagnosis, age, sex, and IQ were not correlated with Hb volume. This was also the case for age of illness onset and medication (i.e., antipsychotic dose and lithium-treatment status). Case-control differences in Hb volume did not reach statistical significance; their effect size (Cohen's d) was negligible on the left (schizophrenia: 0.14; bipolar disorder: −0.03) and small on the right (schizophrenia: 0.34; bipolar disorder: 0.26). Nevertheless, variability in the volume of the right Hb was associated with suicidality in the entire patient sample (ρ = 0.29, p = 0.004) as well as in each patient group (bipolar disorder: ρ = 0.34, p = 0.04; schizophrenia: ρ = 0.25, p = 0.04). These findings warrant replication in larger samples and longitudinal designs and encourage more comprehensive characterization of Hb connectivity and function in clinical populations.
The heritability of pampiniform plexus vessel size and varicocoele in boars

Ultrasonography was used to capture a coronal-sagittal image of the veins of the pampiniform plexus (PP) and the testicular artery of 327 maternal-line boars at approximately 6 months of age at the University of Nebraska-Lincoln. Varicocoele was diagnosed by two methods. Method 1 diagnosed varicocoele when the average vessel area on one side of the scrotum was 1.5 times larger than the average vessel area on the other side of the scrotum. Method 2 diagnosed varicocoele when the average vessel area on one side of the scrotum of a boar was 1.5 times larger than the average vessel on the same side of the scrotum of the boar's cohorts (same population and year). Varicocoele was diagnosed in 23.17% and 15.1% of boars measured using method 1 and method 2, respectively. Ultrasonography showed to be an effective means to measure PP vessel size in boars and may even allow for earlier detection of varicocoele than by using palpation. Animal models were employed to estimate the heritability for: average area of right PP vessels (0.52), average area of the left PP vessels (0.46), varicocoele presence using method 1 (0.26) and varicocoele presence using method 2 (0.25). These heritability estimates suggest that vessel size and varicocoele could be selected against in breeding programmes to potentially improve boar semen quality.
High glucose‐induced complement component 3 up‐regulation via RAGE‐p38MAPK‐NF‐κB signalling in astrocytes: In vivo and in vitro studies

Diabetes is considered as a risk for cognitive decline, which is characterized by neurodegenerative alteration and innate immunity activation. Recently, complement 3 (C3), the critical central component of complement system, has been reported to play a key role in neurodegenerative alterations under pathological condition. Receptor for advanced glycation end products (RAGE) activation is confirmed to mediate several inflammatory cytokines production. However, whether C3 activation participates in the diabetic neuropathology and whether this process is regulated by RAGE activation remains unknown. The present study aimed to investigate the role of C3 in streptozotocin‐induced diabetic mice and high glucose‐induced primary astrocytes and the underlying modulatory mechanisms. The decreased synaptophysin density and increased C3 deposition at synapses were observed in the diabetic brain compared to the control brain. Furthermore, the elevated C3 was co‐localized with GFAP‐positive astrocytes in the diabetic brain slice in vivo and high glucose‐induced astrocytes culture in vitro. Diabetes/high glucose‐induced up‐regulation of C3 expression at gene, protein and secretion levels, which were attenuated by pre‐treatment with RAGE, p38MAPK and NF‐κB inhibitors separately. These results demonstrate that high glucose induces C3 up‐regulation via RAGE‐ p38MAPK‐NF‐κB signalling in vivo and in vitro, which might be associated with synaptic protein loss.
The effect of reminiscence therapy on cognitive functions, depression, and quality of life in Alzheimer patients: Randomized controlled trial

Alzheimer is a disease leading to various neuropsychiatric behavioral disorders, and the most common symptom observed during the prognosis of Alzheimer's disease is dysmnesia. The aim of the present study is to investigate the effect of reminiscence therapy on cognitive functions, depression, and quality of life in Alzheimer's patients.
A fly in a tube: Macroevolutionary expectations for integrated phenotypes

Phenotypic integration and modularity are ubiquitous features of complex organisms, describing the magnitude and pattern of relationships among biological traits. A key prediction is that these relationships, reflecting genetic, developmental, and functional interactions, shape evolutionary processes by governing evolvability and constraint. Over the last 60 years, a rich literature of research has quantified patterns of integration and modularity across a variety of clades and systems. Only recently has it become possible to contextualize these findings in a phylogenetic framework to understand how trait integration interacts with evolutionary tempo and mode. Here, we review the state of macroevolutionary studies of integration and modularity, synthesizing empirical and theoretical work into a conceptual framework for predicting the effects of integration on evolutionary rate and disparity: a fly in a tube. While magnitude of integration is expected to influence the potential for phenotypic variation to be produced and maintained, thus defining the shape and size of a tube in morphospace, evolutionary rate, or the speed at which a fly moves around the tube, is not necessarily controlled by trait interactions. Finally, we demonstrate this reduced disparity relative to the Brownian expectation for a given rate of evolution with an empirical example: the avian cranium.
Sixty years of community change in the prairie–savanna–forest mosaic of Wisconsin

Abstract Biodiversity loss is a global concern, and maintaining habitat complexity in naturally patchy landscapes can help retain regional diversity. A mosaic of prairie, savanna, and forest historically occurred across central North America but currently is highly fragmented due to human land conversion. It is unclear how each habitat type now contributes to regional diversity. Using legacy data, we resurveyed savanna plant communities originally surveyed in the 1950s to compare change in savannas to that in remnant forests and prairies. Savanna community structure and composition changed substantially over the past 60 years. Tree canopy density nearly doubled and many prairie and savanna specialist species were replaced by forest and non‐native species. All three habitats gained and lost many species since the 1950s, resulting in large changes in community composition from local colonizations and extinctions. Across all three habitats, regional species extinctions matched that of regional colonization resulting in no net change in regional species richness. Synthesis—Despite considerable species turnover within savannas, many species remain within the broader prairie–savanna–forest mosaic. Both regional extinctions and colonizations were high over the past 60 years, and maintaining the presence of all three community types—prairie, savanna and forest—on the landscape is critical to maintaining regional biodiversity.
Is Simple Better? Revisiting Non-Linear Matrix Factorization for Learning Incomplete Ratings

Matrix factorization techniques have been widely used as a method for collaborative filtering for recommender systems. In recent times, different variants of deep learning algorithms have been explored in this setting to improve the task of making a personalized recommendation with user-item interaction data. The idea that the mapping between the latent user or item factors and the original features is highly nonlinear suggest that classical matrix factorization techniques are no longer sufficient. In this paper, we propose a multilayer nonlinear semi-nonnegative matrix factorization method, with the motivation that user-item interactions can be modeled more accurately using a linear combination of non-linear item features. Firstly, we learn latent factors for representations of users and items from the designed multilayer nonlinear Semi-NMF approach using explicit ratings. Secondly, the architecture built is compared with deep-learning algorithms like Restricted Boltzmann Machine and state-of-the-art Deep Matrix factorization techniques. By using both supervised rate prediction task and unsupervised clustering in latent item space, we demonstrate that our proposed approach achieves better generalization ability in prediction as well as comparable representation ability as deep matrix factorization in the clustering task.
Assessing the role of ontogenetic movement in maintaining population structure in fish using otolith microchemistry

Abstract Identifying the mechanisms maintaining population structure in marine fish species with more than a single dispersing life stage is challenging because of the difficulty in tracking all life stages. Here, a two‐stage otolith microchemistry approach to examining life‐stage movement was adopted, tracking a year‐class from the juvenile to adult stage and inferring larval sources from clustering, in order to consider the mechanisms maintaining population structuring in North Sea cod. Clustering of near‐core chemistry identified four clusters, two of which had either a southern or northern affinity and were similar to juvenile edge chemistry. The other two clusters, common to the central North Sea, had intermediate chemical composition and may have reflected either larval mixing in this region or a lack of geographic heterogeneity in the elemental signature. From the comparison of whole juvenile and the corresponding component of adult otoliths, adults from the southern North Sea mostly recruited from adjacent nursery grounds. In contrast, many adults in the northern North Sea had a juvenile chemistry consistent with the Skagerrak and juveniles from the northern Skagerrak site had a near‐core chemistry consistent with the northern North Sea. Similarities in otolith chemistry were consistent with retention of early life stages at a regional level and also juvenile and adult fidelity. The links between the northern North Sea and Skagerrak indicate natal homing, which when considered in the context of genetic evidence is suggestive of philopatry. The approach used here should be useful in exploring the mechanisms underlying population structuring in other species with multiple dispersive life stages and calcified hard parts.
Comparison of biomechanical characteristics between male and female elite fast bowlers

ABSTRACT This study investigated ball release speed and performance kinematics between elite male and female cricket fast bowlers. Fifty-five kinematic parameters were collected for 20 male and 20 female elite fast bowlers. Group means were analysed statistically using an independent samples approach to identify differences. Significant differences were found between: ball release speed; run-up speed; the kinematics at back foot contact (BFC), front foot contact (FFC), and ball release (BR); and the timings between these key instants. These results indicate that the female bowlers generated less whole body linear momentum during the run-up than the males. The male bowlers also utilised a technique between BFC and FFC which more efficiently maintained linear momentum compared to the females. As a consequence of this difference in linear momentum at FFC, the females typically adopted a technique more akin to throwing where ball release speed was contributed to by both the whole body angular momentum and the large rotator muscles used to rotate the pelvis and torso segments about the longitudinal axis. This knowledge is likely to be useful in the coaching of female fast bowlers although future studies are required to understand the effects of anthropometric and strength constraints on fast bowling performance.
Inequalities in living well with dementia—The impact of deprivation on well‐being, quality of life and life satisfaction: Results from the improving the experience of dementia and enhancing active life study

Area level factors, such as deprivation and urban/rural settings, have been associated with variation in local resources and services and health inequality in later life. The aim of this study is to investigate the potential impact of deprivation and urban/rural areas on capability to live well with dementia and to examine whether availability of informal carers modified the associations.
Acquiring New Factual Information: Effect of Prior Knowledge

One influential theory on object knowledge is feature-based model, which proposes that the object knowledge is organized by different feature types, such as sensory/perceptual and motor/functional ones. Previous studies have shown that prior knowledge enhances the processes of acquiring and remembering relevant information. However, whether the effect of prior knowledge is applied to different types of conceptual information over time remains unclear. In this study, we addressed this question by testing memory of different types of object features at various retention intervals. The level of prior knowledge was manipulated as object features from familiar and unfamiliar categories. In Experiments 1 and 2, sentences that described the perceptual and functional features of new words were presented. Sentences with episodic features were additionally presented in Experiment 2. The participants were then tested with recognition (Experiment 1) and recall (Experiment 2) tasks at different retention intervals. The results showed that prior knowledge enhanced memory for perceptual features but not for functional and episodic features. Such enhancement depended on the recollection process. In addition, the effect of prior knowledge on perceptual features remained stable over time. This study clarified how different types of new factual information were acquired and maintained and highlighted the importance of prior knowledge in acquiring new conceptual knowledge with the passage of time.
Differential Toxicity of Alkylphenols in JEG-3 Human Placental Cells: Alteration of P450 Aromatase and Cell Lipid Composition

Alkylphenols (APs) are a diverse class of chemicals that can cross the placental barrier and interfere with embryonic and fetal development. This work investigates the comparative toxicity, ability to inhibit aromatase activity, and to alter the lipid composition of 10 alkylphenols in the human placenta choriocarcinoma cell line JEG-3. Among the selected APs, 4-dodecylphenol (DP), 4-heptylphenol (HP), and 4-cumylphenol (CP) showed the highest cytotoxicity (EC50: 18-65 µM). Aromatase inhibition was closely related to the hydrophobicity of APs. HP significantly induced the generation of reactive oxygen species (ROS) (43-fold), inhibited placental aromatase activity (IC50: 41 µM), and induced a general dose-dependent depletion of polyunsaturated lipids (10-20 µM), which were attributed to high levels of oxidative stress. In contrast, 2,4,6-tri-tert-butylphenol (TTBP) significantly induced the intracellular accumulation of triacylglycerides (TGs), whereas DP increased the synthesis of phosphatidylcholines (PCs) and TGs at the expense of diacylglycerides (DGs). Overall, this study evidences the different modes of action of alkylphenols in human placental JEG-3 cells, describes differential lipidomic fingerprints, and highlights DP, HP, CP, and TTBP as the ones that caused the most harmful effects.
Differential Effects of Autophagy-Related 10 Protein on HCV Replication and Autophagy Flux Are Mediated by Its Cysteine44 and Cysteine135

Autophagy-related 10 (ATG10) is essential for autophagy since it promotes ATG5-ATG12 complex formation. Our previous study found that there are two isoforms of the ATG10 protein, ATG10 (a longer one) and ATG10S, which have identical sequences except an absence of a 36-amino acid fragment (peptide B) in ATG10S, yet exhibit distinct effects on HCV genome replication. Here, we report the existence of two amino acids, cysteine at residue 44 and 135 (Cys44 and Cys135, respectively), in ATG10 being related to differential effects of ATG10 on HCV replication and autophagy flux. Through a series of ATG10 mutation experiments and protein modeling prediction, we found that Cys44 was involved in the dual role of the two isoforms of ATG10 protein on HCV replication and autophagy flux, and that Cys135 plays similar roles as Cys44, but the disulfide bond of Cys44-Cys135 was not verified in the ATG10 protein. Further analyses by full HCV virion infection confirmed the roles of -SH of Cys44 and Cys135 on HCV replication. ATG10 with deleted or mutated Cys44 and/or Cys135 could activate expression of innate immunity-related genes, including il28a, irf-3, irf-7, and promote complete autophagy by driving autophagosomes to interact with lysosomes via IL28A-mediation. Subcellular localization assay and chromatin immunoprecipitation assay showed that ATG10 with the sulfydryl deletion or substitution of Cys44 and Cys135 could translocate into the nucleus and bind to promoter of IL28A gene; the results indicated that ATG10 with Cys44 and/or Cys135 absence might act as transcriptional factors to trigger the expression of anti-HCV immunological genes, too. In conclusion, our findings provide important information for understanding the differential roles on HCV replication and autophagy flux between ATG10 and ATG10S, and how the structure-function relationship of ATG10 transformed by a single -SH group loss on Cys44 and Cys135 in ATG10 protein, which may be a new target against HCV replication.
Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial

Objective: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years. Summary background data: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer. Methods: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS). Results: Secondary endpoint analyses included 450 patients (95%) without metastases at baseline (mean age 64; 34% women) who received Lap (n = 225) or Open (n = 225). Median follow-up was 3.2 years (range: 0.1–5.4 yrs). LRR cumulative incidence at 2 years: Lap 5.4%; Open 3.1% [difference, 2.3%; 95% confidence interval (CI), −1.5% to 6.1%; hazard ratio (HR) 1.7; 95% CI, 0.74–3.9]. DFS at 2 years: Lap 80%; Open 82% (difference, 2.0%; 95% CI, −9.3% to 5.4%; HR for recurrence or death, 1.17; 95% CI, 0.81–1.68; P = 0.41). After adjustment for baseline factors HR = 1.07 (95% CI, 0.7–1.6). OS at 2 years: Lap 94%; Open 93% (difference 0.9%; 95% CI, −3.6% to 5.4%). Conclusions: Laparoscopic surgery for rectal cancer did not differ significantly from open surgery in effects on 2-year recurrence or DFS and OS. Confidence intervals included potentially clinically important differences favoring open resection, so that the combination of primary and secondary study endpoints may not support laparoscopic resection of rectal cancer as a routine standard of care and further follow-up is required.