Plastic does not simply flow into the sea: River transport dynamics affected by tides and floating plants.

Plastic pollution is ubiquitous in aquatic environments worldwide. Rivers connect terrestrial and marine ecosystems, playing a key role in the transport of land-based plastic waste towards the sea. Emerging research suggests that in estuaries and tidal rivers, tidal dynamics play a significant role in plastic transport and retention dynamics. To date, observations in these systems have been limited, and plastic transport dynamics during single tidal cycles remain poorly understood. Here, we investigated plastic transport, trapping, and re-mobilization of macroplastics (> 0.5 cm) in the Saigon River, focusing on short-term dynamics of individual tidal cycles. We used GPS trackers, released at different stages of the tidal cycle (ebb, flood, neap, spring). Plastic items demonstrated dynamic and intermittent transport behavior. Items spent almost half of the time (49%) temporarily stopped, mainly due to their entrapment in vegetation, infrastructure, or deposition on riverbanks. Items were almost always re-mobilized within 10 h (85%), leading to successive phases of stopping and transport. Tidal dynamics also resulted in bidirectional transport of plastic items, with median daily total transport distance within the 40 km study reach (8.9 km day-1) over four times larger than the median daily net distance (2.0 km day-1). The median retention time of plastic items within the reach was 21 days (mean = 202 days). In total, 81% of the retrieved items were trapped within water hyacinths, emphasizing the important role of floating vegetation on river plastic transport dynamics. With this paper, we aim to provide data-driven insights into macroplastic transport and retention dynamics in a tropical tidal river. These are crucial in the design of effective intervention and monitoring strategies, and estimating net plastic emission from rivers into the sea.

The value of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, red cell distribution width, and their combination in predicting acute pancreatitis severity.

OBJECTIVE: Acute pancreatitis is one of the most common causes of acute abdominal pain requiring hospitalization worldwide. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) are novel inflammatory markers that have been investigated in various diseases associated with an inflammatory response, achieving many positive results. Evaluating the NLR, PLR, RDW, and their combination to predict acute pancreatitis severity can help clinicians have an appropriate initial treatment strategy. PATIENTS AND METHODS: This prospective cohort study enrolled 131 patients diagnosed with acute pancreatitis at Gia Dinh Hospital, Ho Chi Minh City, between December 2021 and August 2022. Patients with the following features were excluded from our study: age < 18 years old, time from symptom onset to admission of > 72 hours; patients with autoimmune disease, decompensated cirrhosis, active tuberculosis, heart failure (New York Heart Association class 4), end-stage renal failure, pregnancy, active severe acute respiratory syndrome coronavirus 2 infection, and chronic pancreatitis. RESULTS: There were 21 severe acute pancreatitis (SAP) cases (16%). The area under the receiver operating characteristic curve for predicting SAP was 0.82 for NLR, 0.72 for PLR, and 0.73 for RDW. When the cutoffs of 13.5 for NLR, 202.7 for PLR, and 13.1% for the RDW were used, the negative predictive values in predicting SAP were 93.1%, 91.9%, and 98.8%, respectively. This finding demonstrates the value of inflammatory markers in predicting SAP. The combination of these markers did not show an advantage in predicting SAP compared to the single markers. CONCLUSIONS: High NLR, PLR, and RDW are associated with SAP. These indices are good indicators for predicting SAP. In our study, the combination of inflammatory markers did not improve SAP prediction compared to the individual markers.

Diagnostic performance of magnetic resonance imaging for diagnosing acute appendicitis during pregnancy.

OBJECTIVE: This retrospective study evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) for identifying acute appendicitis during pregnancy. PATIENTS AND METHODS: This retrospective study enrolled a total of 46 pregnant patients with clinically suspected acute appendicitis who underwent 1.5 T MRI and received a final pathological diagnosis. We evaluated the imaging characteristics associated with patients diagnosed with acute appendicitis, including the appendix diameter, the appendix wall thickness, intra-appendiceal fluid collection, and peri-appendiceal fat infiltration. A bright appendix on T1-weighted 3-dimensional imaging was identified as a negative sign for appendicitis. RESULTS: Peri-appendiceal fat infiltration had the highest specificity of 97.1% for diagnosing acute appendicitis, whereas increasing appendiceal diameter had the highest sensitivity of 91.7%. The cut-off values for increasing appendiceal diameter and appendiceal wall thickness were 6.55 mm and 2.7 mm, respectively. Using these cut-off values, appendiceal diameter had a sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of 91.7%, 91.2%, 78.4%, and 96.9%, respectively, whereas these values for appendiceal wall thickness were 75.0%, 91.2%, 75.0%, and 91.2%. The combination of increasing appendiceal diameter and appendiceal wall thickness resulted in an area under the receiver operating characteristic curve value of 0.958 with Se, Sp, PPV, and NPV values of 75.0%, 100.0%, 100.0%, and 91.9%, respectively. CONCLUSIONS: All five MRI signs examined in this study had significant diagnostic value for detecting acute appendicitis during pregnancy, with p-values <0.01. The combined use of increasing appendiceal diameter and appendiceal wall thickness displayed the excellent ability to diagnose acute appendicitis in pregnant women.

The precision medicine process for treating rare disease using the artificial intelligence tool mediKanren.

There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need for novel treatment options. Identifying treatments for these disorders is challenging due to a limited understanding of disease mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive to develop new treatments. A promising avenue for treatment is drug repurposing, where FDA-approved drugs are repositioned as novel treatments. However, linking disease mechanisms to drug action can be extraordinarily difficult and requires a depth of knowledge across multiple fields, which is complicated by the rapid pace of biomedical knowledge discovery. To address these challenges, The Hugh Kaul Precision Medicine Institute developed an artificial intelligence tool, mediKanren, that leverages the mechanistic insight of genetic disorders to identify therapeutic options. Using knowledge graphs, mediKanren enables an efficient way to link all relevant literature and databases. This tool has allowed for a scalable process that has been used to help over 500 rare disease families. Here, we provide a description of our process, the advantages of mediKanren, and its impact on rare disease patients.

White Matter Diffusion Properties in Chronic Temporomandibular Disorders: An Exploratory Analysis.

Objective: To determine differences in diffusion metrics in key white matter (WM) tracts between women with chronic temporomandibular disorders (TMDs) and age- and sex-matched healthy controls. Design: Cross sectional study compared diffusion metrics between groups and explored their associations with clinical variables in subjects with TMDs. Methods: In a total of 33 subjects with TMDs and 33 healthy controls, we performed tractography to obtain diffusion metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) from the cingulum near the cingulate gyrus (CGC), the cingulum near the hippocampus (CGH), the fornix, the anterior limb of the internal capsule (ALIC), the posterior limb of the internal capsule (PLIC), and the uncinate fasciculus (UF). We compared diffusion metrics across groups and explored the relationships between diffusion metrics and clinical measures (pain chronicity and intensity, central sensitization, somatization, depression, orofacial behavior severity, jaw function limitations, disability, and interference due to pain) in subjects with TMDs. Results: We observed differences in diffusion metrics between groups, primarily in the right side of the brain, with the right CGC having lower FA and the right UF having lower FA and higher MD and RD in subjects with TMDs compared to healthy controls. No clinical measures were consistently associated with diffusion metrics in subjects with TMDs. Conclusion: The UF showed potential microstructural damage in subjects with TMDs, but further studies are needed to confirm any associations between diffusion changes and clinical measures.

Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

BACKGROUND: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF. METHODS: Twenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients. RESULTS: Mean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02-10.6, p = 0.047). CONCLUSIONS: Autoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments.

HLA-C and KIR permutations influence chronic obstructive pulmonary disease risk.

A role for hereditary influences in the susceptibility for chronic obstructive pulmonary disease (COPD) is widely recognized. Cytotoxic lymphocytes are implicated in COPD pathogenesis, and functions of these leukocytes are modulated by interactions between their killer cell Ig-like receptors (KIR) and human leukocyte antigen-Class I (HLA-Class I) molecules on target cells. We hypothesized HLA-Class I and KIR inheritance affect risks for COPD. HLA-Class I alleles and KIR genotypes were defined by candidate gene analyses in multiple cohorts of patients with COPD (total n = 392) and control smokers with normal spirometry (total n = 342). Compared with controls, patients with COPD had overrepresentations of HLA-C*07 and activating KIR2DS1, with underrepresentations of HLA-C*12. Particular HLA-KIR permutations were synergistic; e.g., the presence of HLA-C*07 + KIR2DS1 + HLA-C12null versus HLAC*07null + KIR2DS1null + HLA-C12 was associated with COPD, especially among HLA-C1 allotype homozygotes. Cytotoxicity of COPD lymphocytes was more enhanced by KIR stimulation than those of controls and was correlated with lung function. These data show HLA-C and KIR polymorphisms strongly influence COPD susceptibility and highlight the importance of lymphocyte-mediated cytotoxicity in COPD pathogenesis. Findings here also indicate that HLA-KIR typing could stratify at-risk patients and raise possibilities that HLA-KIR axis modulation may have therapeutic potential.

Development of An Individualized Risk Prediction Model for COVID-19 Using Electronic Health Record Data.

Developing an accurate and interpretable model to predict an individual's risk for Coronavirus Disease 2019 (COVID-19) is a critical step to efficiently triage testing and other scarce preventative resources. To aid in this effort, we have developed an interpretable risk calculator that utilized de-identified electronic health records (EHR) from the University of Alabama at Birmingham Informatics for Integrating Biology and the Bedside (UAB-i2b2) COVID-19 repository under the U-BRITE framework. The generated risk scores are analogous to commonly used credit scores where higher scores indicate higher risks for COVID-19 infection. By design, these risk scores can easily be calculated in spreadsheets or even with pen and paper. To predict risk, we implemented a Credit Scorecard modeling approach on longitudinal EHR data from 7,262 patients enrolled in the UAB Health System who were evaluated and/or tested for COVID-19 between January and June 2020. In this cohort, 912 patients were positive for COVID-19. Our workflow considered the timing of symptoms and medical conditions and tested the effects by applying different variable selection techniques such as LASSO and Elastic-Net. Within the two weeks before a COVID-19 diagnosis, the most predictive features were respiratory symptoms such as cough, abnormalities of breathing, pain in the throat and chest as well as other chronic conditions including nicotine dependence and major depressive disorder. When extending the timeframe to include all medical conditions across all time, our models also uncovered several chronic conditions impacting the respiratory, cardiovascular, central nervous and urinary organ systems. The whole pipeline of data processing, risk modeling and web-based risk calculator can be applied to any EHR data following the OMOP common data format. The results can be employed to generate questionnaires to estimate COVID-19 risk for screening in building entries or to optimize hospital resources.

CD70 Activation Decreases Pulmonary Fibroblast Production of Extracellular Matrix Proteins.

Idiopathic pulmonary fibrosis (IPF) is a lethal, medically refractory syndrome characterized by intrapulmonary accumulations of extracellular matrix (ECM) proteins produced by fibroblasts. Activation, clonal expansion, and differentiation of lymphocytes are also frequently present in IPF. Activated T cells are known to exert several effects that promote ECM production, but opposing homeostatic actions, wherein T cells can inhibit fibrosis, are less well understood. We found that CD27, a TNF receptor ubiquitously expressed on naive T cells, is downregulated on CD4 T cells of patients with IPF and that CD70, the sole ligand for CD27, is present on human pulmonary fibroblasts. We hypothesized that cognate engagements between lymphocyte CD27 and fibroblast CD70 could have functional consequences. Accordingly, a series of subsequent studies were conducted to examine the possible role of CD27-CD70 interactions in the regulation of fibrogenesis. Using IB, flow cytometry, RT-PCR, and kinomic assays, we found that fibroblast CD70 expression was inversely correlated with cell density and upregulated by TGF-ß1 (transforming growth factor-ß1). CD70 agonists, including T-cell-derived soluble CD27, markedly diminished fibroblast collagen and fibronectin synthesis, and these effects were potent enough to also inhibit profibrotic actions of TGF-ß1 on ECM production in vitro and in two distinct ex vivo human skin models. CD70 activation was mediated by AKT (protein kinase B) and complex interconnected signaling pathways, and it was abated by prior CD70 knockdown. These results show that the CD70-CD27 axis modulates T-cell-fibroblast interactions and may be an important regulator of fibrosis and wound healing. Fibroblast CD70 could also be a novel target for specific mechanistically based antifibrosis treatments.

Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients.

Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease. We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients. Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound. Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p < 0.01). Plasma levels of autoantibodies against a singular GRP78 peptide segment, amino acids 246-260 (anti-GRP78aa 246-260), were even more highly correlated with cIMT, especially among males with greater than or equal to moderate COPD (r s = 0.62, p = 0.001). Anti-GRP78aa 246-260 concentrations were independent of CRP, IL-6, and TNF-α levels. GRP78 autoantigen expression was upregulated among human aortic endothelial cells (HAECs) stressed by incubation with tunicamycin (an unfolded protein response inducer) or exposure to culture media flow disturbances. Autoantibodies against GRP78aa 246-260, isolated from patient plasma by immunoprecipitation, induced HAEC production of proatherosclerotic mediators, including IL-8. In conclusion, anti-GRP78 autoantibodies are highly associated with carotid atherosclerosis in COPD patients and exert atherogenic effects on HAECs. These data implicate Ag-specific autoimmunity in the pathogenesis of atherosclerosis among COPD patients and raise possibilities that directed autoantibody reduction might ameliorate vascular disease in this high-risk population.

Decrements of body mass index are associated with poor outcomes of idiopathic pulmonary fibrosis patients.

BACKGROUND: The processes that result in progression of idiopathic pulmonary fibrosis (IPF) remain enigmatic. Moreover, the course of this disease can be highly variable and difficult to accurately predict. We hypothesized analyses of body mass index (BMI), a simple, routine clinical measure, may also have prognostic value in these patients, and might provide mechanistic insights. We investigated the associations of BMI changes with outcome, plasma adipokines, and adaptive immune activation among IPF patients. METHODS: Data were analyzed in an IPF discovery cohort (n = 131) from the University of Pittsburgh, and findings confirmed in patients from the University of Alabama at Birmingham (n = 148). Plasma adipokines were measured by ELISA and T-cell phenotypes determined by flow cytometry. RESULTS: Transplant-free one-year survivals in subjects with the greatest rates of BMI decrements, as percentages of initial BMI (>0.68%/month), were worse than among those with more stable BMI in both discovery (HR = 1.8, 95%CI = 1.1-3.2, p = 0.038) and replication cohorts (HR = 2.5, 95%CI = 1.2-5.2, p = 0.02), when adjusted for age, baseline BMI, and pulmonary function. BMI decrements >0.68%/month were also associated with greater mortality after later lung transplantations (HR = 4.6, 95%CI = 1.7-12.5, p = 0.003). Circulating leptin and adiponectin levels correlated with BMI, but neither adipokine was prognostic per se. BMI decrements were significantly associated with increased proportions of circulating end-differentiated (CD28null) CD4 T-cells (CD28%), a validated marker of repetitive T-cell activation and IPF prognoses. CONCLUSIONS: IPF patients with greatest BMI decrements had worse outcomes, and this effect persisted after lung transplantation. Weight loss in these patients is a harbinger of poor prognoses, and may reflect an underlying systemic process, such as adaptive immune activation.

Analytic variability due to change of deficient plasma vials: application to one-stage clotting factor VIII assay.

The statistical process control required under International Organization for Standardization 15189 as well as economic considerations necessitates having robust methods that do not need systematic recalibration for each series of analyses. Using the concrete example of one-stage clotting factor VIII assay, we assessed the analytic variability specifically linked to changing factor VIII deficient plasma vials. The study used freeze-dried (Instrumentation Laboratory, Siemens, Stago and T-Coag) and frozen (Affinity Biologicals and Precision Biologic) factor VIII deficient plasmas. On the most widely recognized acceptability criteria and methods (i.e. those of Kallner et al. and Kasper et al.), the Stago and Instrumentation Laboratory plasmas require systematic recalibration at each vial changeover.

Activation of the Ran GTPase is subject to growth factor regulation and can give rise to cellular transformation.

Although the small GTPase Ran is best known for its roles in nucleocytoplasmic transport, mitotic spindle assembly, and nuclear envelope formation, recent studies have demonstrated the overexpression of Ran in multiple tumor types and that its expression is correlated with a poor patient prognosis, providing evidence for the importance of this GTPase in cell growth regulation. Here we show that Ran is subject to growth factor regulation by demonstrating that it is activated in a serum-dependent manner in human breast cancer cells and, in particular, in response to heregulin, a growth factor that activates the Neu/ErbB2 tyrosine kinase. The heregulin-dependent activation of Ran requires mTOR (mammalian target of rapamycin) and stimulates the capped RNA binding capability of the cap-binding complex in the nucleus, thus influencing gene expression at the level of mRNA processing. We further demonstrate that the excessive activation of Ran has important consequences for cell growth by showing that a novel, activated Ran mutant is sufficient to transform NIH-3T3 cells in an mTOR- and epidermal growth factor receptor-dependent manner and that Ran-transformed cells form tumors in mice.

Two isoforms of tissue transglutaminase mediate opposing cellular fates.

Opposing cellular responses are typically regulated by distinct sets of genes. However, tissue transglutaminase (TGase) provides an interesting example of a single gene product that has been implicated both in affording protection against cellular insults as well as in promoting cell death. Here, we shed some light on how these conflicting activities might be manifested by demonstrating that alternative transcripts of TGase differentially affect cell viability. We show that although the full-length TGase protein affords strong protection against cell death signals, a shorter version of TGase that is truncated at the 3' end, and thus called TGase-short (TGase-S), is cytotoxic. The apoptotic activity of TGase-S is not dependent on its transamidation activity because the mutation of a cysteine residue that is essential for catalyzing this reaction does not compromise the ability of TGase-S to induce cell death. Intriguingly, TGase-S undergoes inappropriate oligomer formation in cells before cell death, suggesting a novel mechanism for the apoptotic effects of this protein.

Use of basiliximab and daclizumab in kidney transplantation.

Kidney transplantation represents a major medical victory in patients with whom dialysis and medical therapy have failed. To increase survival rates and optimize the use of limited organs, both patient care and immunosuppression therapy must be improved. Reduction in rejection episodes or severity of rejection may ultimately improve long-term allograft survival. Traditional engineered monoclonal antibodies have been associated with severe cytokine release reactions and an increased risk of opportunistic infections. Basiliximab and daclizumab are chimeric and humanized monoclonal antibodies which inhibit thymus-dependent lymphocyte proliferation. Interleukin-2 also affects the proliferation of natural killer cells, macrophages and monocytes, bursa-equivalent lymphocytes, epidermal dendritic cells, and lymphokine-activated killer cells. Interleukin-2 receptor antagonists have been shown to reduce the incidence of acute rejection without increasing the incidence of opportunistic infections or malignancy. Further studies are needed to evaluate the overall effect of these agents on long-term patient and allograft survival.

[Tapeworm fauna of gallinaceans (Galliformes) of Vietnam]. / O faune lentochnykh chervei kurinykh ptits (Galliformes) V'etnama.

131 specimens of 3 species of Galliformes from Vietnam were investigated (Gallus gallus dom., G. g. jaboruillei, Francolinus pintadeanus and Lophora nycthemerus). In them 9 species of cestodes were found as follows: Davainea proglottina (Davainea, 1860), Cotugnia digonopora (Pasquale, 1890), Raillietina tetragona (Molin, 1858), R. echinobothrida (Megnin, 1880), Skrjabinia cesticillus (Molin, 1858), Paroniella tinguiana Tubangui et Masilungan, 1937, Amoebotaenia cuneata (Linstow, 1872), Echinolepis carioca (Magalhaes, 1898), Dilepidoides bauchei (Joyeux, 1924). In domestic hens there were found all 9 species of cestodes while in wild Galliformes--only 7, which are mentioned for them for the first time.