Mining Clinical Notes for Physical Rehabilitation Exercise Information: Natural Language Processing Algorithm Development and Validation Study.

BACKGROUND: The rehabilitation of a patient who had a stroke requires precise, personalized treatment plans. Natural language processing (NLP) offers the potential to extract valuable exercise information from clinical notes, aiding in the development of more effective rehabilitation strategies. OBJECTIVE: This study aims to develop and evaluate a variety of NLP algorithms to extract and categorize physical rehabilitation exercise information from the clinical notes of patients who had a stroke treated at the University of Pittsburgh Medical Center. METHODS: A cohort of 13,605 patients diagnosed with stroke was identified, and their clinical notes containing rehabilitation therapy notes were retrieved. A comprehensive clinical ontology was created to represent various aspects of physical rehabilitation exercises. State-of-the-art NLP algorithms were then developed and compared, including rule-based, machine learning-based algorithms (support vector machine, logistic regression, gradient boosting, and AdaBoost) and large language model (LLM)-based algorithms (ChatGPT [OpenAI]). The study focused on key performance metrics, particularly F1-scores, to evaluate algorithm effectiveness. RESULTS: The analysis was conducted on a data set comprising 23,724 notes with detailed demographic and clinical characteristics. The rule-based NLP algorithm demonstrated superior performance in most areas, particularly in detecting the "Right Side" location with an F1-score of 0.975, outperforming gradient boosting by 0.063. Gradient boosting excelled in "Lower Extremity" location detection (F1-score: 0.978), surpassing rule-based NLP by 0.023. It also showed notable performance in the "Passive Range of Motion" detection with an F1-score of 0.970, a 0.032 improvement over rule-based NLP. The rule-based algorithm efficiently handled "Duration," "Sets," and "Reps" with F1-scores up to 0.65. LLM-based NLP, particularly ChatGPT with few-shot prompts, achieved high recall but generally lower precision and F1-scores. However, it notably excelled in "Backward Plane" motion detection, achieving an F1-score of 0.846, surpassing the rule-based algorithm's 0.720. CONCLUSIONS: The study successfully developed and evaluated multiple NLP algorithms, revealing the strengths and weaknesses of each in extracting physical rehabilitation exercise information from clinical notes. The detailed ontology and the robust performance of the rule-based and gradient boosting algorithms demonstrate significant potential for enhancing precision rehabilitation. These findings contribute to the ongoing efforts to integrate advanced NLP techniques into health care, moving toward predictive models that can recommend personalized rehabilitation treatments for optimal patient outcomes.

Composition and evolutionary characterization of the gut microbiota in pigs.

The intestinal microbiota plays significant role in the physiology and functioning of host organisms. However, there is limited knowledge of the composition and evolution of microbiota-host relationships from wild ancestors to modern domesticated species. In this study, the 16S rRNA gene V3-V4 in the intestinal contents of different pig breeds was analyzed and was compared using high-throughput sequencing. This identified 18 323 amplicon sequence variants, of which the Firmicutes and Actinobacteria phyla and Bifidobacterium and Allobaculum genera were most prevalent in wild pigs (WP). In contrast, Proteobacteria and Firmicutes predominated in Chinese Shanxi Black pigs (CSB), while Firmicutes were the most prevalent phylum in Large White pigs (LW) and Iberian pigs (IB), followed by Bacteroidetes in IB and Proteobacteria in LW. At the genus level, Shigella and Lactobacillus were most prevalent in CSB and LW, while Actinobacillus and Sarcina predominated in IB. Differential gene expression together with phylogenetic and functional analyses indicated significant differences in the relative abundance of microbial taxa between different pig breeds. Although many microbial taxa were common to both wild and domestic pigs, significant diversification was observed in bacterial genes that potentially influence host phenotypic traits. Overall, these findings suggested that both the composition and functions of the microbiota were closely associated with domestication and the evolutionary changes in the host. The members of the microbial communities were vertically transmitted in pigs, with evidence of co-evolution of both the hosts and their intestinal microbial communities. These results enhance our understanding and appreciation of the complex interactions between intestinal microbes and hosts and highlight the importance of applying this knowledge in agricultural and microbiological research.

The Protective Effect and Mechanism of a Phytochemical Extract from the Wild Vegetable Shutou (Crateva unilocularis Buch.) against Acetaminophen-Induced Liver Injury in Mice.

Acetaminophen (APAP) abuse is a common public health problem which can cause severe liver damage. However, strategies for dealing with this situation safely and effectively are very limited. The goal of the current work was to evaluate the protection and potential molecular mechanisms of an ethanol extract from shoots of the wild vegetable shutou (Crateva unilocularis Buch.) (ECS) against APAP-induced liver damage in mice. Mice orally received ECS for seven days (300 or 600 mg/kg b.w. per day) before being intraperitoneally injected with APAP (250 mg/kg). Results exhibited that ECS obviously decreased the content of alkaline phosphatase, alanine aminotransferase, aspartate transaminase, and malondialdehyde (p < 0.05). Catalase and superoxide dismutase were notably restored (p < 0.05), and the content of reduced glutathione was obviously increased (p < 0.05). Moreover, ECS significantly inhibited the secretion of interleukin-1ß and tumor necrosis factor-α (p < 0.05). Further analyses of the mechanisms showed that ECS may alleviate oxidative stress in the liver by increasing the expression of the nuclear factor erythroid-2-related factor 2 and NADH quinone oxidoreductase 1 proteins, and may suppress liver inflammation by inhibiting the expression of the phosphorylated-inhibitor kappa B alpha/inhibitor kappa B alpha, phosphorylated-nuclear factor κB/nuclear factor κB, and cyclooxygenase-2 proteins. Meanwhile, ECS inhibited hepatocyte apoptosis by enhancing B-cell lymphoma gene 2 and suppressing Bcl-2-associated X protein. In summary, ECS may be used as a dietary supplement to prevent the liver damage caused by APAP abuse.

The GR-gp78 Pathway is involved in Hepatic Lipid Accumulation Induced by Overexpression of 11ß-HSD1.

Glucocorticoids are essential participants in the regulation of lipid metabolism. On a tissue-specific level, glucocorticoid signal is controlled by 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1). Up-regulation of 11ß-HSD1 expression during non-alcoholic fatty liver disease (NAFLD) has been previously shown, while 11ß-HSD1 inhibition has been shown to reduce hepatic lipids in NAFLD, but the underlying mechanisms remain unclear. Here, in this study, we created in vitro cell culture and in vivo transgenic hepatocyte-specific 11ß-HSD1 mouse models of NAFLD to determine the regulatory mechanisms of 11ß-HSD1 during lipid metabolism dysfunction. We found that 11ß-HSD1 overexpression activated glucocorticoid receptors and promoted their nuclear translocation, and then stimulating gp78. The induction of gp78 sharply reduced expression of Insig2, but not Insig1, which led to up-regulation of lipogenesis regulatory proteins including SREBP1, FAS, SCD1, and ACC1. Our results suggested that overexpression of 11ß-HSD1 induced lipid accumulation, at least partially through the GR/gp78/Insig2/SREBP1 pathway, which may serve as a potential diagnostic and therapeutic target for treatment of NAFLD.

Structural Color Spectral Response of Dense Structures of Discoidal Particles Generated by Evaporative Assembly.

Structural color─optical response due to light diffraction or scattering from submicrometer-scale structures─is a promising means for sustainable coloration. To expand the functionality of structural color, we introduce discoidal shape anisotropy into colloidal particles and characterize how structural color reflection can be engineered. Uniaxial compression of spheres is used to prepare discoids with varying shape anisotropy and particle size. Discoids are assembled into thin films by evaporation. We find that structural color of assembled films displays components due to diffuse backscattering and multilayer reflection. As discoids become more anisotropic, the assembled structure is more disordered. The multilayer reflection is suppressed─peak height becomes smaller and peak width broader; thus, the color is predominantly from diffuse backscattering. Finally, the discoid structural color can be tuned by varying particle size and has low dependence on viewing angle. We corroborate our results by comparing experimental microstructures and measured reflection spectra with Monte Carlo simulations and calculated spectra by finite-difference time-domain simulation. Our findings demonstrate that the two tunable geometries of discoids─size and aspect ratio─generate different effects on spectral response and therefore can function as independent design parameters that expand possibilities for producing noniridescent structural color.

The role of complementary shape in protein dimerization.

Shape guides colloidal nanoparticles to form complex assemblies, but its role in defining interfaces in biomolecular complexes is less clear. In this work, we isolate the role of shape in protein complexes by studying the reversible binding processes of 46 protein dimer pairs, and investigate when entropic effects from shape complementarity alone are sufficient to predict the native protein binding interface. We employ depletants using a generic, implicit depletion model to amplify the magnitude of the entropic forces arising from lock-and-key binding and isolate the effect of shape complementarity in protein dimerization. For 13% of the complexes studied here, protein shape is sufficient to predict native complexes as equilibrium assemblies. We elucidate the results by analyzing the importance of competing binding configurations and how it affects the assembly. A machine learning classifier, with a precision of 89.14% and a recall of 77.11%, is able to identify the cases where shape alone predicts the native protein interface.

Calcium modified basalt fiber bio-carrier for wastewater treatment: Investigation on bacterial community and nitrogen removal enhancement of bio-nest.

Modified basalt fiber (MBF) is a sustainable material studied as novel wastewater treatment bio-carrier recently. This work studied the effects of calcium modification on the bacterial affinity of modified fiber (Ca-MBF), bacterial community, and nitrogen removal performance. Results showed that Ca-MBF with hydrophilic (62.66°) and positively-charged (7.80 mV) surface accelerated bacterial attachment. Volatile suspended solids on Ca-MBF (5.46 g VSS/g fiber) were increased by 2.61 times after modification, with high bacterial activity when bio-carriers were cultured in activated sludge. Extracellular polymeric substances on Ca-MBF was 4.35 times higher and consisted of more protein. Bio-nests with unique aerobic/anaerobic structure formed on the ultrafine carriers in bioreactor. Ca-MBF bioreactor exhibited total nitrogen removal efficiency above 72.2% and COD removal efficiency above 94.2% with more stable performance than unmodified carrier in long-term treatment using synthetic domestic wastewater.16S rRNA gene sequencing revealed enhanced abundance of nitrifying and denitrifying bacteria in Ca-MBF bio-nest.

Enhancement of nitrogen removal in hybrid wastewater treatment system using ferric citrate modified basalt fiber biocarrier.

Developing biofilm carriers is of great significance for efficient wastewater treatment. In this work, ferric citrate was used to modify inorganic basalt fiber (BF) biocarrier, thus improving its surface properties and the nitrogen removal in hybrid wastewater treatment system. The results showed that the iron element on modified basalt fiber (Fe-MBF) existed in the forms of ferric citrate, Fe(OH)3, Fe2O3, and FeO. The ferric deposition increased the surface roughness, hydrophilicity and reduced the electronegativity of BF. The water contact angle of BF and Fe-MBF was 117.46° and 64.85°, respectively. The surface zeta potential of BF was -17.64 mV, but shifted positively (-8.67 mV) after deposition modification. The microorganism adhesion tests showed that the attached biomass and extracellular polymeric substances (EPS) content on Fe-MBF biocarrier significantly increased and the attached bacteria had also high viability. The Fe-MBF biocarrier showed good nitrogen removal performance in the hybrid bioreactor, with total nitrogen removal efficiency up to 95.35±0.82%, increasing by about 16% compared to that with unmodified BF biocarrier. This work also provided a green modification strategy to enhance biofilm carrier in wastewater treatment.

Food-Derived High Arginine Peptides Promote Spermatogenesis Recovery in Busulfan Treated Mice.

Food-derived peptides with high arginine content have important applications in medicine and food industries, but their potential application in the treatment of oligoasthenospermia remains elusive. Here, we report that high-arginine peptides, such as Oyster peptides and Perilla purple peptides were able to promote spermatogenesis recovery in busulfan-treated mice. We found that both Opp and Ppp could increase sperm concentration and motility after busulfan-induced testicular damage in mice. Further research revealed that Opp and Ppp might promote spermatogonia proliferation, which improved blood-testis barrier recovery between Sertoli cells. Taken together, these high-arginine peptides might be used as a medication or therapeutic component of a diet prescription to improve the fertility of some oligoasthenospermia patients.

Effects of Different Dietary Flavonoids on Dipeptidyl Peptidase-IV Activity and Expression: Insights into Structure-Activity Relationship.

The inhibitory effects of 30 dietary flavonoids on dipeptidyl peptidase-IV (DPP-IV) were investigated to illustrate their quantitative structure-activity relationship (QSAR) and further explore their inhibition at the cellular level. Results of in vitro experiment show that isorhamnetin-3-O-glucoside (IC50, 6.53 ± 0.280 µM) had the strongest inhibition followed by cyanidin-3-O-glucoside (IC50, 8.26 ± 0.143 µM) and isorhamnetin-3-O-rutinoside (IC50, 8.57 ± 0.422 µM). A 3D QSAR model [comparative molecular field analysis, q2 = 0.502, optimum number of components (ONC) = 3, R2 = 0.983, F = 404.378, standard error of estimation (SEE) = 0.070, and two descriptors; comparative similarity index analysis, q2 = 0.580, ONC = 10, R2 = 0.999, F = 1617.594, SEE = 0.022, and four descriptors] indicates that the DPP-IV inhibition of flavonoid was facilitated by crucial structural factors. Position 3 of ring C favored bulky, hydrogen bond acceptors and hydrophilic and electron-donating substituents. The presence of minor and electron-withdrawing groups at position 4' of ring B and positions 5 and 7 of ring A could improve DPP-IV inhibition. Moreover, the three flavonoids mentioned above could effectively suppress DPP-IV activity and expression in Caco-2 cells. This work may supply new insights into dietary flavonoids as DPP-IV inhibitors for controlling blood glucose.

Characterization of the bacterial microbiota composition and evolution at different intestinal tract in wild pigs (Sus scrofa ussuricus).

Commensal microorganisms are essential to the normal development and function of many aspects of animal biology, including digestion, nutrient absorption, immunological development, behaviors, and evolution. The specific microbial composition and evolution of the intestinal tracts of wild pigs remain poorly characterized. This study therefore sought to assess the composition, distribution, and evolution of the intestinal microbiome of wild pigs. For these analyses, 16S rRNA V3-V4 regions from five gut sections prepared from each of three wild sows were sequenced to detect the microbiome composition. These analyses revealed the presence of 6,513 operational taxonomic units (OTUs) mostly distributed across 17 phyla and 163 genera in these samples, with Firmicutes and Actinobacteria being the most prevalent phyla of microbes present in cecum and jejunum samples, respectively. Moreover, the abundance of Actinobacteria in wild pigs was higher than that in domestic pigs. At the genus level the Bifidobacterium and Allobaculum species of microbes were most abundant in all tested gut sections, with higher relative abundance in wild pigs relative to domestic pigs, indicating that in the process of pig evolution, the intestinal microbes also evolved, and changes in the intestinal microbial diversity could have been one of the evolutionary forces of pigs. Intestinal microbial functional analyses also revealed the microbes present in the small intestine (duodenum, jejunum, and ileum) and large intestine (cecum and colon) of wild pigs to engage distinct metabolic spatial structures and pathways relative to one another. Overall, these results offer unique insights that would help to advance the current understanding of how the intestinal microbes interact with the host and affect the evolution of pigs.

Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells.

Testosterone is indispensable for sexual development and maintaining male characteristics, and deficiency of this hormone results in primary or late-onset hypogonadism (LOH). Testosterone is primarily produced in Leydig cells, where autophagy has been reported to be extremely active. However, the functional role of autophagy in testosterone synthesis remains unknown. In this study, we show that steroidogenic cell-specific disruption of autophagy influenced the sexual behavior of aging male mice because of a reduction in serum testosterone, which is similar to the symptoms of LOH. The decline in testosterone was caused mainly by a defect in cholesterol uptake in autophagy-deficient Leydig cells. Further studies revealed that once autophagic flux was disrupted, Na+/H+ exchanger regulatory factor 2 (NHERF2) accumulated in Leydig cells, resulting in the down-regulation of scavenger receptor class B, type I (SR-BI) and eventually leading to insufficient cholesterol supply. Collectively, these results reveal that autophagy promotes cholesterol uptake into Leydig cells by eliminating NHERF2, suggesting that dysfunction of autophagy might be causal in the loss of testosterone production in some patients.

Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice.

Sirt1 is a member of the sirtuin family of proteins and has important roles in numerous biological processes. Sirt1-/- mice display an increased frequency of abnormal spermatozoa, but the mechanism of Sirt1 in spermiogenesis remains largely unknown. Here, we report that Sirt1 might be directly involved in spermiogenesis in germ cells but not in steroidogenic cells. Germ cell-specific Sirt1 knockout mice were almost completely infertile; the early mitotic and meiotic progression of germ cells in spermatogenesis were not obviously affected after Sirt1 depletion, but subsequent spermiogenesis was disrupted by a defect in acrosome biogenesis, which resulted in a phenotype similar to that observed in human globozoospermia. In addition, LC3 and Atg7 deacetylation was disrupted in spermatids after knocking out Sirt1, which affected the redistribution of LC3 from the nucleus to the cytoplasm and the activation of autophagy. Furthermore, Sirt1 depletion resulted in the failure of LC3 to be recruited to Golgi apparatus-derived vesicles and in the failure of GOPC and PICK1 to be recruited to nucleus-associated acrosomal vesicles. Taken together, these findings reveal that Sirt1 has a novel physiological function in acrosome biogenesis.

The linkage specificity determination of Ube2g2-gp78 mediated polyubiquitination.

Polyubiquitin chain linkage specificity or topology is essential for its role in diverse cellular processes. Previous studies pay more attentions to the linkage specificity of the first ubiquitin moieties, whereas, little is known about the editing mechanism of linkage specificity in longer polyubiquitin chains. gp78 and its cognate E2-Ube2g2 catalyze lysine48 (K48)-linked polyubiquitin chains to promote the degradation of targeted proteins. Here, we show that the linkage specificity of the entire polyubiquitin chain is determined by the conjugation manner of the first ubiquitin molecule but not the following ones. Further study discovered that the gp78 CUE domain works as a proofreading machine during the growth of K48-linked polyubiquitin chains to ensure the linkage specificity. Together, our studies uncover a novel mechanism underlying the linkage specificity determination of longer polyubiquitin chains.

Autophagy is required for ectoplasmic specialization assembly in sertoli cells.

The ectoplasmic specialization (ES) is essential for Sertoli-germ cell communication to support all phases of germ cell development and maturity. Its formation and remodeling requires rapid reorganization of the cytoskeleton. However, the molecular mechanism underlying the regulation of ES assembly is still largely unknown. Here, we show that Sertoli cell-specific disruption of autophagy influenced male mouse fertility due to the resulting disorganized seminiferous tubules and spermatozoa with malformed heads. In autophagy-deficient mouse testes, cytoskeleton structures were disordered and ES assembly was disrupted. The disorganization of the cytoskeleton structures might be caused by the accumulation of a negative cytoskeleton organization regulator, PDLIM1, and these defects could be partially rescued by Pdlim1 knockdown in autophagy-deficient Sertoli cells. Altogether, our works reveal that the degradation of PDLIM1 by autophagy in Sertoli cells is important for the proper assembly of the ES, and these findings define a novel role for autophagy in Sertoli cell-germ cell communication.

Anthocyanins-rich extract of wild Chinese blueberry protects glucolipotoxicity-induced INS832/13 ß-cell against dysfunction and death.

As commonly observed events in diabetic patients, glucolipotoxicity induces oxidative stress, apoptosis and functional defects in ß-cells. Anthocyanins are well investigated as strong antioxidants and modulators for metabolic syndromes. Therefore, this study examined the protective effects of anthocyanins-rich extracts (BAE) from wild Chinese blueberry (Vaccinium spp.) against glucolipotoxicity in ß-cells. Results showed that INS832/13 ß-cells subjected to glucolipotoxicity were significantly decreased (p < 0.05) in cell survival rate, which were alleviated by BAE and metformin treatments. Both BAE and metformin reduced reactive oxidative species and improved the antioxidant defense system. Moreover, BAE were effective in reducing intracellular triglycerides (TG) level, restoring intracellular insulin content, lowering basal insulin secretion (BIS) and increasing glucose-stimulated insulin secretion which in turn resulted in an elevated insulin secretion index. However, metformin only demonstrated marginal effect on secretion dysfunction and had no effect (p > 0.05) on BIS or TG. Additionally, TG levels reduced by BAE treatment were correlated with BIS (p < 0.01, r = 0.9755). This study has for the first time demonstrated that anthocyanin enriched extract of wild Chinese blueberry could effectively protect ß-cells against glucolipotoxicity in vitro. These results implied the potential efficacy of BAE as a complementary measure for diabetes intervention.

Evaluation of γ- aminobutyric acid, phytate and antioxidant activity of tempeh-like fermented oats (Avena sativa L.) prepared with different filamentous fungi.

Tempeh is a popular traditional fermented food in Asia. Many tempeh-like foods are made from cereal grains. However, the information of γ-aminobutyric acid (GABA) accumulation in those tempeh-like cereal grains during fermentation is lacking. Meanwhile, little information is available on the anti-nutrient contents and antioxidant activity of tempeh-like fermented oats. The aim of the present work was to study the changes of GABA, phytate, natural antioxidants and antioxidant activity of tempeh-like fermented oats. As fermentation time progressed, the GABA, total phenolics content (TPC) and flavonoids increased rapidly. The Aspergillus oryzae-fermented oats had the highest GABA, whereas Rhizopus oryzae-fermented oats had the highest TPC. Phytate, an anti-nutrient component, was dramatically reduced in the fermented oats, especially those by A. oryzae (reduced by about 63 %). The antioxidant activities of fermented oats were also significantly enhanced after 72 h fermentation (p < 0.05). This study demonstrated that oats fermented by generally recognized as safe (GRAS) fungi can be recommended as tempeh-like functional foods with higher GABA, more natural antioxidants and lower phytate compared with native oats.

Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells.

Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of ß-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of ß-galactosidase-positive cells when treated with 0·1 µg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.