Proximity Scores Research Articles

Characterization of six clinical drugs and dietary intervention in the non-obese CDAA-HFD mouse model of MASH and progressive fibrosis.

The choline-deficient L-amino acid defined-high fat diet (CDAA-HFD) mouse model is widely used in preclinical metabolic dysfunction-associated steatohepatitis (MASH) research. To validate the CDAA-HFD mouse, we evaluated disease progression and responsiveness to dietary and pharmacological interventions with semaglutide, lanifibranor, elafibranor, obeticholic acid (OCA), firsocostat and resmetirom.Disease phenotyping was performed in C57BL/6J mice fed CDAA-HFD for 3-20 weeks and ranked using the MASLD Human Proximity Score (MHPS). Semaglutide, lanifibranor, elafibranor, OCA, firsocostat or resmetirom were profiled as treatment intervention for 8 weeks, starting after 6 weeks of CDAA-HFD feeding. Semaglutide and lanifibranor were further evaluated as early (preventive) therapy for 9 weeks, starting 3 weeks after CDAA-HFD diet feeding. Additionally, benefits of dietary intervention (chow reversal) for 8 weeks were characterized following 6 weeks of CDAA-HFD feeding. CDAA-HFD mice demonstrated a non-obese phenotype with fast onset and progression of MASH and fibrosis, high similarity to human MASH-fibrosis, and tumor development after 20 weeks of diet-induction. Semaglutide and lanifibranor partially reversed fibrosis when administered as prevention, but not as treatment intervention. Elafibranor was the only interventional drug to improve fibrosis. In comparison, chow-reversal resulted in complete steatosis regression with improved liver inflammation and fibrosis in CDAA-HFD mice. CDAA-HFD mice recapitulate histological hallmarks of advanced MASH with progressive severe fibrosis, however, in the absence of a clinical translational obese dysmetabolic phenotype. CDAA-HFD mice are suitable for profiling drug candidates directly targeting hepatic lipid metabolism, inflammation, and fibrosis. The timing of pharmacological intervention is critical for determining antifibrotic drug efficacy in the model.

Choline-deficient, high-fat diet-induced MASH in Göttingen Minipigs: characterization and effects of a chow reversal period.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) is increasing, and translational animal models are needed to develop novel treatments for this disease. The physiology and metabolism of pigs have a relatively high resemblance to humans, and the present study aimed to characterize choline-deficient and high-fat diet (CDAHFD)-fed Göttingen Minipigs as a novel animal model of MASLD/MASH. Göttingen Minipigs were fed CDAHFD for up to 5 mo, and the phenotype was investigated by the analysis of plasma parameters and repeated collection of liver biopsies. Furthermore, changes in hepatic gene expression during the experiment were explored by RNA sequencing. For a subset of the minipigs, the diet was changed from CDAHFD back to chow to investigate whether the liver pathology was reversible. Göttingen Minipigs on CDAHFD gained body weight, and plasma levels of cholesterol, AST, ALT, ALP, and GGT were increased. CDAHFD-fed minipigs developed hepatic steatosis, inflammation, and fibrosis, which in 5 of 16 animals progressed to cirrhosis. During an 11-wk chow reversal period, steatosis regressed, while fibrosis persisted. Regarding inflammation, the findings were less clear, depending on the type of readout. MASH Human Proximity Scoring (combined evaluation of transcriptional, phenotypic, and histopathological parameters) showed that CDAHFD-fed Göttingen Minipigs resemble human MASLD/MASH better than most rodent models. In conclusion, CDAHFD-fed minipigs develop a MASH-like phenotype, which, in several aspects, resembles the changes observed in human patients with MASLD/MASH. Furthermore, repeated collection of liver biopsies allows detailed characterization of histopathological changes over time in individual animals.NEW & NOTEWORTHY The physiology and metabolism of pigs have a relatively high resemblance to humans. This study characterizes a new animal model of MASLD/MASH using CDAHFD-fed Göttingen Minipigs. Göttingen Minipigs fed CDAHFD gained weight and developed hepatic steatosis, inflammation, fibrosis, and cirrhosis. After an 11-wk chow-reversal period, hepatic steatosis and some inflammatory parameters reversed. Combined evaluation of phenotypic, transcriptional, and histological parameters revealed the minipig model showed a higher resemblance to human disease than many rodent models.

The impact of preoperative treatments on the immune environment of rectal cancer.

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.

Optimizing the spatial immune landscape of CD103+CD8+ tissue-resident memory T cells in non-small cell lung cancer by neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) combined with immunotherapy is increasingly used in non-small cell lung cancer (NSCLC). Tissue-resident memory T (TRM) cells are the primary subset responding to anti-cancer immunity. However, the immunomodulatory effects of NAC on TRM cells remain unknown. We established two NSCLC cohorts including patients undergoing upfront surgery (US) and NAC followed by surgery. Beyond the unpaired comparison between the US cohort (n = 122) and NAC cohort (n = 141) with resection samples, 58 matched pre-NAC biopsy samples were available for paired comparisons. Using multiplex immunofluorescence, we characterized TRM cells (CD103+CD8+) and four heterogeneous TRM subsets, including naive TRM1 (PD-1-Tim-3-), pre-exhausted TRM2 (PD-1+Tim-3-), TRM3 (PD-1-Tim-3+), and terminally exhausted TRM4 (PD-1+Tim-3+). Cell density, cytotoxicity, and two spatial features were defined to evaluate the effect of NAC on TRM subsets. The cell densities, infiltration scores, and cancer-cell proximity scores of TRM cells, especially TRM1&2 subsets, were significantly increased after NAC and associated with better prognosis of patients. In Contrast, no significant change was observed in the TRM4 subset, which was associated with poor prognosis. Besides, the cytotoxicity of TRM subsets was unaltered after NAC. Compared with patients without major pathologic response (MPRs), patients with MPR had higher densities of TRM1&2 subsets and higher cancer-cell proximity scores of TRM2&3 subsets. Furthermore, increased density of CD31 + cancer microvessels was positively associated with both TRM and Tnon-RM cells after NAC. NAC may remodel the cell density and spatial distribution of TRM subsets, which is associated with favorable therapeutic effect and prognosis in patients with NSCLC.

Risk Factors for Recurrent Proximal Junctional Failure Following Adult Spinal Deformity Surgery: Analysis of 60 Patients Undergoing Fusion Extension Surgery for Proximal Junctional Failure.

Despite numerous studies identifying risk factors for proximal junctional failure (PJF), risk factors for recurrent PJF (R-PJF) are still not well established. Therefore, we aimed to identify the risk factors for R-PJF following adult spinal deformity (ASD) surgery. Among 479 patients who underwent ≥5-level fusion surgery for ASD, the focus was on those who experienced R-PJF at any time or did not experience R-PJF during a follow-up duration of ≥1 year. PJF was defined as a proximal junctional angle (PJA) ≥28° plus a difference in PJA ≥22° or performance of revision surgery regardless of PJA degree. The patients were divided into 2 groups according to R-PJF development: no R-PJF and R-PJF groups. Risk factors were evaluated focusing on patient, surgical, and radiographic factors at the index surgery as well as at the revision surgery. Of the 60 patients in the final study cohort, 24 (40%) experienced R-PJF. Significant risk factors included greater postoperative sagittal vertical axis (OR = 1.044), overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis (PI-LL; OR = 7.794) at the index surgery, a greater total sum of the proximal junctional kyphosis severity scale (OR = 1.145), and no use of the upper instrumented vertebra cement (OR = 5.494) at the revision surgery. We revealed that the greater postoperative sagittal vertical axis and overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis at the index surgery, a greater proximal junctional kyphosis severity scale score, and no use of upper instrumented vertebra cement at the revision surgery were significant risk factors for R-PJF. To reduce the risk of R-PJF after ASD surgery, avoiding under- and overcorrection during the initial surgery is recommended. Additionally, close assessment of the severity of PJF with timely intervention is crucial, and cement augmentation should be considered during revision surgery.

Poster 193: Long-Term Outcomes of Partial Proximal Hamstring Avulsion Repair: Average 10-Year Follow-Up

Objectives: While a growing body of literature supports the benefit of surgical repair of complete proximal hamstring avulsions involving all 3 tendons, the optimal treatment for partial proximal hamstring avulsions remains uncertain. Initial nonoperative management of partial proximal hamstring avulsions is typically recommended, but several recent studies have shown improved pain and function at short- and mid-term follow-up. However, the durability of surgical repair at long-term follow-up is unknown. The purpose of this study was to report the long-term outcomes of partial proximal hamstring avulsion repair compared to outcomes at midterm follow-up. It was hypothesized that hamstring function and patient satisfaction would remain stable over time. Methods: All patients who underwent surgical repair of a partial proximal hamstring avulsion by a single surgeon between 2006 and 2018 with a minimum 5-year follow-up were included. Institutional review board approval was obtained prior to study initiation, and all patients signed informed consent. Exclusion criteria were complete avulsions involving all 3 hamstring tendons, retraction > 2 cm, or magnetic resonance imaging (MRI) findings of isolated tendinopathy. All patients had first attempted nonoperative treatment, including nonsteroidal anti-inflammatory drugs and physical therapy. Patient characteristics were collected including age, sex, injury, laterality, sports played, level of participation, length of time from injury to intervention, and length of follow-up. Patients completed a HIPPA-compliant online questionnaire (REDCap) containing the patient-reported outcomes scores of the Lower Extremity Functional Score (LEFS), Marx Activity Rating Scale, custom LEFS (%), and custom Marx (%). A Total Proximal Hamstring Score was calculated by averaging the custom Marx score and the custom LEFS. Patient satisfaction with surgical outcome (yes/no) was also determined. A portion of the included patients had the same outcome measures available from a previous study entailing a minimum 2-year follow-up, with an average follow-up of 6.2 years. Paired comparisons of current outcome scores with earlier scores were performed using a paired Mann-Whitney U test for continuous variables and Fisher exact test for categorical variables. Results: Fifty-three patients (57 hamstrings) with a mean age at surgery of 47.4 years were included at an average follow-up time of 10.1 years. Of the 53 patients, 4 had bilateral injuries and 4 underwent revision surgery. The right (n = 29) and left (n = 28) hamstrings were equally affected with a predominance of female patients (41 female, 16 male). Running was the most common sport at the time of injury (Table 1). Excellent functional outcomes were seen at average 10.1 years (Table 2). 91.2% of patients were satisfied with the results of surgery and were able to return to their desired sport at an average of 10.9 months after surgery. Nearly 88% of hamstrings considered their strength to be >75% strength of the contralateral side, with approximately 58% of hamstrings reporting equal (100%) strength. When comparing the 44 partial hamstring repairs with outcome scores available at both midterm (6.2 years) and long-term follow-up (10.7 years), only the Marx and custom Marx scores were found to decline with time. Scores for LEFS, custom LEFS, Total Proximal Hamstring, satisfaction, and subjective strength were unchanged between midterm and long-term follow-up (Table 3). Conclusions: Excellent patient-reported outcomes and high levels of satisfaction were found at 10-year follow-up following partial proximal hamstring avulsion repair. Notably, the LEFS and custom LEFS, which are the most common patient-reported outcome measures used to assess hamstring function following injury, remained high at midterm and long-term follow-up. The Marx (12.5 vs. 8.5) and custom Marx scores (100% vs. 94%) did achieve statistically significant differences between time points, with lower scores at long-term follow-up possibly in part due to self-determined reduction in strenuous activities with aging. Patient-reported satisfaction and subjective strength remained high at long-term follow-up. Surgical repair of partial proximal hamstring avulsions remains a successful and durable treatment strategy in active patients who have failed nonoperative measures at an average follow-up exceeding 10 years.

So far, yet so close. Using networks of words to measure proximity and spillovers between firms

AbstractTextual data are the last frontier in the empirical literature on proximity between firms. While there are a growing number of studies using textual data, no robust methodology has yet emerged, nor has any attempt been made to compare the resulting findings with standard measures of proximity based on existing classification systems. The purpose of this paper is threefold. First, we propose a methodology that can be an effective and applicable tool for measuring proximity between companies. Second, we compare the resulting indicator of proximity, which we refer to as “business” proximity, with industrial and technological proximity scores based on activity codes and technology adoption, respectively. Third, we use business proximity to explain economic performance, assuming that knowledge sharing can occur between employees working in similar firms. Having established the soundness of the methodology, the empirical results confirm the substantial information content of the descriptive texts and provide evidence on the likelihood of spillover effects between firms that are close in the business and geographical dimension.

Comprehensive profiling of social mixing patterns in resource poor countries: A mixed methods research protocol.

Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling. To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures. We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member. Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.

Censored imputation of time to event outcome through survival proximity score method

The study recognized the significance of accurately addressing censoring and censored data in survival analysis as well as the possibility of biases if these concepts are not approached with caution by researchers. If censored participants are excluded from the study, the true treatment effect comparison will be inaccurate, resulting in biased study findings. In this context, there is a need for some mechanism to impute and update the status information of those patients who were lost to follow-up before the study’s end and might be due to the study-related causes. In order to resolve this issue, we developed a weighted survival proximity score method by using a weighted propensity scoring system to impute the censored values with the help of the nearest neighborhood technique and update the survival data. After imputing the censored status in the dataset, conventional survival methods are applied to evaluate the differences in hazard rates with and without applying a survival proximity score method. We found that the proposed method reduces bias and mean square error in various transitions. The goal of this work is to resolve the existing issue of censoring and explain how the survival proximity score method can be adapted to update the censored information of lost-followup individuals for therapeutic arms comparison.

Modified spatial architecture of regulatory T cells after neoadjuvant chemotherapy in non-small cell lung cancer patients

It is crucial to decipher the modulation of regulatory T cells (Tregs) in tumor microenvironment (TME) induced by chemotherapy, which may contribute to improving the efficacy of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer (NSCLC). We retrospectively collected specimens from patients with II-III NSCLC, constituting two cohorts: a neoadjuvant chemotherapy (NAC) cohort (N = 141) with biopsy (N = 58) and postoperative specimens (N = 141), and a surgery-only cohort (N = 122) as the control group. Then, the cell density (Dens), infiltration score (InS), and Treg-cell proximity score (TrPS) were conducted using a panel of multiplex fluorescence staining (Foxp3, CD4, CD8, CK, CD31, ɑSMA). Subsequently, the association of Tregs with cancer microvessels (CMVs) and cancer-associated fibroblasts (CAFs) was analyzed. Patients with NAC treatment have a higher density of Tregs in both paired (P < 0.001) and unpaired analysis (P = 0.022). Additionally, patients with NAC treatment showed higher infiltration score (paired, P < 0.001; unpaired, P = 0.014) and more CD8+T cells around Tregs (paired/unpaired, both P < 0.001). Subgroup analysis indicated that tumors with a diameter of ≤ 5 cm exhibited increase in both Dens(Treg) and InS(Treg), and gemcitabine, pemetrexed and taxel enhanced Dens(Treg) and TrPS(CD8) following NAC. Multivariate analysis identified that the Dens(Tregs), InS(Tregs) and TrPS(CD8) were significantly associated with better chemotherapy response [OR = 8.54, 95%CI (1.69, 43.14), P = 0.009; OR = 7.14, 95%CI (1.70, 30.08), P = 0.024; OR = 5.50, 95%CI (1.09, 27.75), P = 0.039, respectively] and positive recurrence-free survival [HR = 3.23, 95%CI (1.47, 7.10), P = 0.004; HR = 2.70; 95%CI (1.27, 5.72); P = 0.010; HR = 2.55, 95%CI (1.21, 5.39), P = 0.014, respectively]. Moreover, TrPS(CD8) and TrPS(CD4) were negatively correlated with the CMVs and CAFs. These discoveries have deepened our comprehension of the immune-modulating impact of chemotherapy and underscored that the modified spatial landscape of Tregs after chemotherapy should be taken into account for personalized immunotherapy, aiming to ultimately improve clinical outcomes in patients with NSCLC.

D'or: deep orienter of protein-protein interaction networks.

Protein-protein interactions (PPIs) provide the skeleton for signal transduction in the cell. Current PPI measurement techniques do not provide information on their directionality which is critical for elucidating signaling pathways. To date, there are hundreds of thousands of known PPIs in public databases, yet only a small fraction of them have an assigned direction. This information gap calls for computational approaches for inferring the directionality of PPIs, aka network orientation. In this work, we propose a novel deep learning approach for PPI network orientation. Our method first generates a set of proximity scores between a protein interaction and sets of cause and effect proteins using a network propagation procedure. Each of these score sets is fed, one at a time, to a deep set encoder whose outputs are used as features for predicting the interaction's orientation. On a comprehensive dataset of oriented PPIs taken from five different sources, we achieve an area under the precision-recall curve of 0.89-0.92, outperforming previous methods. We further demonstrate the utility of the oriented network in prioritizing cancer driver genes and disease genes. D'or is implemented in Python and is publicly available at https://github.com/pirakd/DeepOrienter.

An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD ‘human proximity score’ to define their metabolic relevance and ability to induce MASH-fibrosis. Here, we show that Western diets align closely with human MASH; high cholesterol content, extended study duration and/or genetic manipulation of disease-promoting pathways are required to intensify liver damage and accelerate significant (F2+) fibrosis development. Choline-deficient models rapidly induce MASH-fibrosis while showing relatively poor translatability. Our ranking of commonly used MASLD models, based on their proximity to human MASLD, helps with the selection of appropriate in vivo models to accelerate preclinical research.

#604 Oral administration of UNI-494 ameliorates acute kidney injury in a rat model of delayed graft function

Abstract Background and Aims There are no FDA approved drugs for the treatment of acute kidney injury (AKI), which affects 10-15% of hospitalized patients and often results in renal transplantation or lifelong dialysis. UNI-494 is a novel nicotinamide ester derivative and selective mitochondrial ATP-sensitive potassium channel activator that may be beneficial for several disease states, including AKI. We present results from a study evaluating the in vivo efficacy of oral (PO) UNI-494 in the unilateral renal ischemia-reperfusion (I/R) rat model of AKI, which is a well-established model of delayed graft function (DGF) (Cavaille-Coll, 2013). Method Rats were anesthetized, the right kidney was removed, and I/R was induced in three groups of rats by clamping the renal vessels in the left kidney for 30 minutes; a fourth group had no surgery (sham group) without clamping the renal vessels. 50 mg/kg or 100 mg/kg UNI-494 were administered PO 30 minutes prior to I/R. One I/R group and the sham group were not treated. After 24 hours of reperfusion in metabolic cages, blood samples were collected for serum creatinine (sCr), and urinary samples were collected for albumin-creatinine ratio (ACR) and the tubular injury marker neutrophil gelatinase-associated lipocalin (NGAL). The clamped left kidney was collected and processed for histology for tubular injury scores. Results In this study, I/R induced significant increases of sCr, ACR, NGAL, and proximal convoluted tubular injury scores in the vehicle treated I/R group vs No I/R sham group. A single PO dose of UNI-494 at 50 mg/kg/PO or 100 mg/kg/PO reduced the kidney functional markers sCr and ACR, the tubular injury marker (NGAL), and proximal tubular injury scores (all p &amp;lt; 0.001, Fig. 1). Conclusion The results indicate that UNI-494 dose dependently prevented AKI markers and proximal tubular injury in a rat model of AKI and therefore is a potential candidate for the prevention of DGF and other AKI clinical conditions.

Sennoside A+B Is as Effective as Polyethylene Glycol in Preparation for Small Intestine Capsule Endoscopy.

We aimed to compare the effectiveness of the polyethylene glycol (PEG) and sennoside A+B regimens after clear fluid diet and fasting in bowel preperation of capsule endoscopy. In this retrospective single-center study, patients who were consecutively examined with small bowel capsule endoscopy (SBCE) between May 2010 and March 2023 were evaluated. Patients who underwent PEG 4 L and sennoside A+B calcium 250 mL for small bowel preparation were assigned. The quality of the small bowel cleaning and the diagnostic yield in detecting of small bowel lesions were compared. Two hundred forty-two patients who underwent SBCE for various indications (PEG 74.4%, sennoside A+B 25.6%) were included in the study. The mean proximal small bowel cleaning scores was 1.97 ± 0.77 for PEG and 1.98 ± 0.04 (P = .83) for sennoside A+B; the mid small bowel cleaning scores was 1.76 ± 0.84 for PEG and 1.59 ± 0.05 (P = .108) for sennoside A+B; the mean distal small bowel cleaning scores was 1.27 ± 0.08 for PEG and 1.3 ± 0.54 (P = .805) for sennoside A+B; and the total small bowel cleaning scores was 1.66 ± 0.06 and 1.62 ± 0.04 (P = .622) for PEG and sennoside A+B, respectively. There were no significant differences regarding small bowel cleaning scores both segmentally and totally. At the same time, the diagnostic value of SBCE was similar in both groups. The effectiveness of sennoside A+B in SBCE preparation is similar to that of PEG and can be used in intestinal cleansing.

Examining Trajectories of Change on the Dynamic Risk Assessment for Offender Re-Entry (DRAOR).

Dynamic risk scales have largely been evaluated using singular assessment scores, including those obtained at the start of supervision. While this approach includes assessment of dynamic factors, it ignores changes with reassessment, failing to examine whether an instrument is truly dynamic in nature. This is problematic, as proximal risk assessments have consistently outperformed baseline assessments in the prediction of recidivism. In the current study, we examined the dynamic properties of the Dynamic Risk Assessment for Offender Reentry (DRAOR) in 4,736 adults on community supervision in Iowa, United States (N = 33,965 assessments). As expected, while clients demonstrated statistically significant changes on the DRAOR domains over time, changes were small in magnitude. We also examined the predictive validity of baseline and proximal DRAOR total and domain scores on criminal recidivism and revocation in a larger sample of 11,421 adults in the same jurisdiction. While DRAOR baseline scores did predict both outcomes, prediction did not improve with proximal scores. This conflicted with expected findings from previous research on the DRAOR in New Zealand. The results of both of these research questions indicate there was an overall lack of change reflected in this sample. Potential issues regarding implementation fidelity are discussed. Additional research is needed to examine the dynamic properties of the DRAOR in Iowa given the importance of reassessment data in community corrections.

Daytime spatial relationships in a family group of black rhinoceros Diceros bicornis at the Hiroshima City Asa Zoological Park, Japan.

Although black rhinoceros Diceros bicornis are mostly solitary in the wild, the Hiroshima City Asa Zoological Park (Asa Zoo) has kept a family group together during the daytime, with good reproductive performance over five decades. Management procedures at the zoo include temporary single housing of the mother before and after giving birth, which facilitates maintenance of a compatible family group. We recorded intra-group spatial relationships for 4 years and 4 months, during which time an adult female reared two consecutive calves. During daytime she remained in an enclosure with her new calf, one or two older offspring, and an adult male, the sire of all her offspring. Proximity (within two adult body-lengths) scores between the mother and her two calves were especially high during the first year after birth, and only slightly lower for her older offspring. The adult male had the lowest proximity scores. The spatial relationships were visualized by applying multidimensional scaling (MDS) to the proximity scores. Mother and calves were plotted close to each other, with older offspring slightly farther apart on the two-dimensional MDS representation; the adult male was more distant from the other group members. These findings indicate clear follower-type characteristics in the mother-calf pair and also older immature offspring, albeit to a lesser degree. Although black rhinoceros are generally solitary in the wild, our results duplicate observations of some wild black rhinoceros groups containing an adult female, her calf, and an older immature, with adult males being largely solitary.

Effect of Paraquat toxicity on lung and kidney organs on histopathological image assessment

Background: Paraquat is one of the active ingredients of the gramoxone type herbicide, which has very high toxicity so that it can cause poisoning and death. Paraquat causes direct cell damage by producing free radicals, which can cause pulmonary fibrosis and kidney failure. This study aims to analyze the effects of paraquat toxicity on the lungs and kidneys on histopathological features. Methods: This research is an experimental research post-test only control group design. The research subjects used stored biological material in the form of 12 lung and kidney organ samples from white rats (Rattus norvegicus) that had been treated in previous research, which were divided into 2 groups, namely the negative control group (P1, given distilled water), the positive control group (P2; given paraquat 0.01 gr/kgBW [single dose intraperitoneal]). All samples of stored biological material were made for lung and kidney preparations. The lung condition was assessed using the American Thoracic Society criteria, and the kidneys were evaluated using the Mitchell criteria with the help of the ImageJ application. Data were analyzed using the Kruskal-Wallis test and the Mann-Whitney test. Results: The Kruskal-Wallis test showed a significant difference in lung damage scores between groups with a p-value of 0.01 (p &lt;0.005). The results of the Kruskal-Wallis test of the kidneys showed substantial differences in glomerular and proximal tubular damage scores between groups with p values ​​of 0.004 and 0.009 (p &lt;0.005). The results of the Mann-Whitney test also showed significant differences between groups P1 and P2 with a lung p value = 0.008 (p&gt; 0.005) and kidney p = 0.009 (p &gt; 0.005). Conclusion: In this study, it can be concluded that induction of paraquat 0.01 gr/kgBW causes changes in the histopathological appearance of the lungs and kidneys of white rats (Rattus norvegicus) in the form of lung and kidney damage as assessed by histopathological scores.

Abstract TP211: TICI Scoring Reliability in Proximal vs Distal Vessel Thrombectomy: A Comparative Analysis

Introduction: The extended Thrombolysis in Cerebral Infarction (eTICI) scale has been demonstrated to correlate strongly with clinical outcomes. Thrombectomy has evolved into the pursuit of not only proximal but distal vessel occlusions, however the reliability of eTICI grading for distal occlusions has not been well studied. We aim to study the interrater agreement of proximal as compared to distal occlusions. Methods: A fellowship trained Neurointerventionalist retrospectively scored the Digital Subtraction Angiography(DSA) images of consecutive patients with only isolated proximal (MCA-M1 or ICA-T) or distal occlusions (MCA-M3, ACA, or PCA) that underwent MT at a single comprehensive stroke center (2022 for proximal occlusions and 2015-2022 for distals). We assessed the agreement between the Neurointerventionalist and original report for the ordinal eTICI scale using Fleiss-Cohen’s Weighted Kappa with quadratic weights. TICI distributions were compared using Wilcoxon’s rank sum test. Results: 187 patients were included in the analysis (124 Proximal and 60 patients distal: 32-M3, 20 -ACA, 8-PCA). The distribution of eTICI 0, 2a, 2b50, 2b67, 2c and 3 were comparable between proximal(MCA-M1 or ICA-T) vs distal occlusions (MCA-M3, ACA, or PCA). The Fleiss-Cohen weighted kappa coefficients were assessed. The proximal eTICI score assessment demonstrated moderate reliability with a kappa value of 0.77 (95%CI: 0.67-0.88)(Table 1A), while the distal eTICI score assessment exhibited almost perfect agreement with kappa value of 0.87 (95%CI: 0.71-1.00)(Table 1B). Conclusion: This study underscores comparable reliability of eTICI scores in assessing reperfusion post MT for distal as compared to proximal occlusions.

Examining the spatial distribution of tumor-infiltrating immune cells in patients with stage I to IIIA LUAD.

This study aimed to examine the spatial distribution of immune cells by application of Gcross function in 170 patients with stage I to IIIA lung adenocarcinoma (LUAD) and explore its prognostic value. A total of 170 stage I to IIIA LUAD patients who underwent radical surgery were enrolled. Paraffinized tumor sections were collected for 2 panels of multicolor immunofluorescence staining (panel 1: CD4, CD8, FOXP3, CD69, CD39, CD73, and DAPI; panel 2: CD68, CD163, CD20, CD11c, PDL1, IDO, and DAPI). The immune cells were categorized as CD8+, CD4+ T helper cell (CD4Th), regulatory T cell, macrophage type 1 (M1), M2, dendritic cell (DC), and B cell. The immune cell numbers were enumerated, and the immune cell proximity score was calculated employing the Gcross function. The correlation between immune cell variables and disease-free survival (DFS) was explored through univariate Cox regression analyses. Factors with P < 0.05 were subjected to multivariate analyses. According to univariate Cox regression analyses, total PDL1+ and PDL1+ DC counts were negative factors (P = 0.003 and 0.031, respectively). CD4Th and IDO-DC counts were positive factors (P = 0.022 and 0.024, respectively). The proximity score (M1 to M2) was a positive factor for DFS (P = 0.032), and the proximity score (PDL1 + DC to M1) was a negative factor (P = 0.009) according to univariate Cox analyses. In multivariate analyses, stage (IIIA vs I + II) (hazard ratio [HR]: 1.77 [95% confidence interval (CI): 1.18-2.64], P = 0.006) and proximity score (PDL1 + DC to M1) (HR: 1.60 [95% CI: 1.07-2.37], P = 0.021) were independent negative factors and CD4Th counts (HR: 0.60 [95% CI: 0.40-0.90], P = 0.013) was an independent positive factor. Our study indicated that a higher level of tumor-infiltrating CD4Th cells predicted longer DFS, and a closer proximity of PDL1+ DCs to M1 cells was associated with dismal DFS in stage I to IIIA LUAD patients.

Development and application of a proximal hamstring MRI-based scoring tool in patients undergoing proximal hamstring tendon surgical repair

PurposeAn MRI-based scoring tool assessing surgical repair after proximal hamstring avulsions may provide benefit in the context of research, while serial post-operative MRI will provide insight of what to expect in the clinical context of early re-injury requiring imaging. This study developed and assessed the reliability of a Proximal Hamstring Objective Magnetic Resonance Imaging Score (PHOMRIS), further assessing MRI-based repair status and its correlation with patient-reported outcome. Methods15 patients that underwent proximal hamstring surgical repair underwent MRI and clinical review pre-operatively and at 3-, 6- and 12-months. Clinical scores included the Lower Extremity Functional Scale (LEFS), the Perth Hamstring Assessment Tool (PHAT) and Tegner Activity Scale (TAS). The MRI-based tool assessed the conjoint (semitendinosus & biceps femoris) and semimembranosus insertion components based on bone-tendon healing, signal and retraction. Inter- and intra-observer reliability of the tool was assessed. ResultsInter-observer reliability indicated a strong correlation for the semimembranosus (rho = 0.827, p < 0.0001) and conjoint (rho = 0.851, p < 0.0001) components. Intra-observer reliability indicated a strong correlation for the semimembranosus (rho = 0.852, p < 0.0001) and conjoint (rho = 0.996, p < 0.0001) components. All clinical scores and the semimembranosus hamstrings component MRI score significantly improved (p < 0.05) over time, though the conjoint component did not (p = 0.219). At 12 months, a higher LEFS was significantly associated with a better semimembranosus MRI score (r = −0.57, p = 0.042), though no other significant correlations (p > 0.05) were observed between clinical and MRI measures. ConclusionsExcellent reliability was observed for the MRI-based scoring tool, which may prove useful in both a research and clinical setting.