Histological Data Research Articles

Relative incidence of interstitial lung diseases in Brazil.

To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

Цитологічні та морфологічні предиктори комплексного лікування інфекції акушерської хірургічної рани в породілей

Purpose - to determination of the course and effectiveness of treatment of obstetric surgical wound infection in women in labor when using drugs with sorption-detoxification and immunomodulatory properties based on the study of the morphology of the wound process through the use of histological and cytological studies. Materials and methods. In the work, histological and cytological studies were used to monitor the course of the wound process in 115 parturients with purulent wounds of the anterior abdominal wall after caesarean section and perineum after episio- and perineotomy. Women are divided into groups depending on the method of treatment: the Group I - 42 parturients with purulent wounds, who were treated with organosilicon sorbent Gentaxan; the Group II - 45 women in labor with purulent wounds, who were treated with organosilicon sorbent Gentaxan and immunomodulator Laferon; the Group III - 28 women in labor with purulent wounds, who were treated with traditional methods - with subsequent statistical processing of the obtained results. Results. Based on the analysis of cytological and histological data, it was determined that the course of reparative processes in the wound during complex treatment with a sorbent and an immunomodulator is faster than that of monotherapy with a sorbent and conventional therapy - by 1.5-2 and 4-5 days, respectively. This was confirmed by a decrease in leukocytes, microorganisms, neutrophils and an increase in lymphocytes and connective tissue cells in the wound, affected the faster cleaning of the wound of dead and non-viable tissues, the rapid elimination of swelling and inflammation in the wound, and the acceleration of reparative processes. Conclusions. The complex use of an immunomodulator and a sorbent in the treatment of purulent wounds shows an advantage over sorbent monotherapy by accelerating the reparative processes in the wound by 1.5-2 days, and over traditional therapy by 4-5 days, which makes it possible to recommend them for use in practical medicine. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

CAUSE AND EFFECT RELATIONSHIP OF BLOOD LOSS AND CAUSE OF DEATH IN INJURIES AND DISESSES

Forensic medical practice shows that the death of a person can be accompanied by blood loss, which is the result of an injury, or a manifestation of a disease, and therefore, during the forensic medical examination, it is necessary to establish a causal relationship between it and the cause of death. In order to solve these issues, the results of the autopsy, histological examination, analysis of clinical and laboratory hematological data, as well as morphological changes in the heart muscle play a leading role.&#x0D; Aim of the work. Forensic-medical substantiation of the cause of death and features of establishing a cause-and-effect relationship with blood loss in injuries and diseases.&#x0D; Materials and methods. The material of the study was cases of death due to injuries and diseases accompanied by the development of blood loss, which were analyzed in accordance with the instructive forensic and clinical materials.&#x0D; Results. Severe injuries to the human body are accompanied by the development of blood loss, the consequences of which can cause a shock reaction. Clinically, the body's reaction to blood loss occurs when more than 15 % of BCC is lost, and severe shock develops in case of blood loss of more than 25 % of BCC, which is approximately 1,25-1,5 liters of blood. In addition, the speed of blood loss is also important, as a result of which the body's protective mechanisms do not have time to compensate for it. In the case of forensic substantiation of acute blood loss as the cause of death, autopsy and histological examination data are usually used. However, blood loss of varying degrees can also accompany a number of diseases, as a result of which the body develops anemia with hypoxia, which affects the state of the cardiovascular system. In such cases, blood loss does not directly lead to death, but causes disorders in the function of the heart, in particular, exacerbation of the course of coronary disease. This pathogenetic mechanism indicates the absence of a direct causal relationship between blood loss and the onset of death. In such cases, to justify the cause of death, it is necessary to pay attention not only to the presence of clinical indicators confirming blood loss, but also to laboratory hematological data – the content of erythrocytes, the amount of hemoglobin, hematocrit, and most importantly – morphological changes of the heart, which must be described by the most thorough way&#x0D; Conclusions. Complex analysis of all morphological changes and findings during examination of corpse, clinical symptoms of diseases, results of gradual hematological investigations are used to estimate the cause of death. To avoid occurrence or exacerbation of the course of the ischemic heart diseases the monitoring of function of the cardio-vascular systems and electrocardiography in patient with blood loss as symptom of diseases should be used in clinical practice.

Breast Cancer Image Classification based on Adaptive Interpolation Approach Using Clinical Dataset

In the healthcare and bioinformatics disciplines, the categorization of breast cancer has become an emerging paradigm due to the second most common cause of cancer-related mortality in women. A biopsy is a procedure in which tissue has been examined to determine whether or not it is breast cancer through histopathologists that may lead to a mistaken diagnosis. The research is mainly focused on the patient data (884 case reports of patients) is acquired from the American Oncology Institute implemented with preprocessing techniques consists of missing values and those values are recovered with Novel Modified Interpolation (MI) Method. Deep learning networks effectively detect and assess the pattern for annotating histological data based on the labelling, which preserves time, system cost and enhances the system accuracy. This framework addressed feature acquisition and missing analysis strategies based on entropy confidence weight factor. First, the iterative patterns have been treated as a potential diagnostic rule, and the attention-based rule combination formulates the classification issue based on integrating convolutional and recurrent neural networks, and the short-term and long-term spatial correlations between patches. Second, the key part of label construction is carried out with an entropy confidence-weight factor assessment which detects and predict different patterns to construct the rule for classification. Third, optimization of clustering data by assessing missing parameters based on mean square error and the concept of interpolation to reduce data loss by around 20% and enhance the system accuracy. Simulation results show that the proposed system achieves 91.3% accuracy to state-of-art approaches, potentially allied in clinical applications. Modified Interpolation (MI) method recovered missing values with least mean square error and less data loss of 0.0123 and 1.38% respectively. This method also compared with existing Linear Interpolation (LI) method which is able to recover least men square error and data loss of 3.295 and 18.925% respectively. Comparatively the modified interpolation method recovered the missing values with less mean square error and less data loss.

Skeletal anomalies in gilthead seabream (Sparus aurata) larvae reared in different densities and water volumes

AbstractThis study describes the effects on the skeletal phenotype of two pivotal factors, density and water volume, don the hatchery (larval) phase of gilthead seabream (Sparus aurata) larvae previoulsy described for two model species (Danio rerio and Oryzias latipes) and sub‐adult (pre‐ongrowing) gilthead seabream (Sparus aurata). The experimental trial was conducted using single conditions in a pilot study, starting with a total of 615,385 eggs from the same batch. Three densities (LD low density: 25 larvae/L; MD medium density: 125 larvae/L; and HD high density: 250 larvae/L) and two water volumes (500 and 1000 L) were tested from spawning up to 60 days post‐hatching (dph) (average standard length: 1.79 cm; average dry weight: 27.11 mg). On the final samples, morphometric, anatomical, and histological data were collected for data pertinent to meristic counts and skeletal anomalies. The results (analyzed by means of multivariate analyses) indicated that the LD‐reared larvae were significantly longer and heavier than HD‐reared fish. Furthermore, LD‐reared gilthead seabream exhibited a significant reduction in the frequency of individuals with anomalies of jaws, vertebral body shape, and vertebral arches than the MD and HD conditions, which is in agreement with previous experiments carried out on model species and gilthead seabream sub‐adults.

Postinfectious epilepsy: clinical and diagnostical features

Background. According to some authors, neuroinfection agents play a role in the development of several neurological disorders, including epilepsy. For many years, it was believed that acute infectious diseases, such as tick-borne encephalitis virus and meningococcus played a leading role in the emerging epileptic process of postinfectious etiology. Regarding a role for chronically persistent infections, it has not been fully explored.Objective: to identify clinical, diagnostic, and morphological features of locally induced postinfectious epilepsy, both at disease onset upon emergence of the first epileptic seizures during acute infectious process and during their recurrence in a chronically persistent infection.Material and methods. The study included observations of 1500 patients with locally induced epilepsy admitted and treated from 2007 to 2017 in various medical inpatient and outpatient institutions. Post-infection locally induced epilepsy with clear causality link between previous neuroinfection and onset of epileptic seizure was found in 127 patients (Group 1). During initial visits, infectious agents in a cohort of patients with recurrent epileptic seizures manifested as chronic persistent infection were suspected in more than 1/3 of the 1373 subjects who sought medical aid comprising 550 people (Group 2). In addition to the clinical evaluation of patients, instrumental studies were performed, including routine electroencephalography (EEG), sleep video-EEG monitoring, magnetic resonance imaging (MRI), and some patients underwent pathomorphological examination using electron microscopy and histological techniques.Results. Gross and marked diffuse disturbances in brain bioelectrical activity were most often detected (58% and 31%, respectively) during video-EEG monitoring in Group 1, whereas moderate alterations were recorded less frequently (11% of observations). In Group 2, the majority of diffuse disturbances in brain bioelectrical activity were of moderate level (79%) followed by mild and irritative changes recorded less frequently (in 21% of cases). MRI data showed that disorders of the amygdala-hippocampal system were observed in 41 (32%) and 211 (38%) patients in Groups 1 and 2, respectively. Histological and electron microscopic data revealed a number of morphological disorders in patients with locally induced postinfectious epilepsy common with earlier described mitochondrial encephalomyopathies (mitochondrial megaconia and pleioconia) as well as a set of specific manifestations typical to such pathology.Conclusion. The conducted clinical, neurophysiological, neuroimaging, and pathomorphological studies of postinfectious epilepsy revealed specific features underlying its development at different stages, from its onset in acute infectious process to chronization in persistent infection. It was found that a comprehensive analysis of the presence and impact of infectious agents in patients with epileptic seizures is important for course and prognosis of postinfectious epilepsy, which is relevant for timely diagnosis and development of specific pharmacotherapy.

Orthokeratinized Odontogenic Keratocyst: Report of Nine Cases with Review of Literature

Abstract Formerly believed to be a subtype of odontogenic keratocyst (OKC), orthokeratinized odontogenic cyst (OOC), a rare developing odontogenic cyst, is now believed to be distinct. The clinical, radiographic, histological data are included in this report, along with a review of the literature to aid in comprehending the cyst. A retrospective search in the oral pathology department between 2018 and 2022 was conducted to recover all cases reported as OOC in SRM Dental College, Ramapuram. Radiographs and Haematoxylin and Eosin stained histological slides were re-examined. Overall, there were nine cases in which men were engaged in 80% of the instances and the group’s ages varied from 20 to 35. The primary symptoms of all of the patients were pain and edema. The vast majority of cases had an impacted tooth in the jaw. All of the lesions showed clearly visible radiolucency on orthopantomographs [OPG], with the exception of one specific case. Additionally, histological examination of each patient revealed the characteristic microscopic traits and enucleation was done to treat all the cases. OOC has a more favourable outcome than OKC due to variations in prognosis, management and must be considered distinct from OKC. Most of our cases—a large majority—involved adolescent males’ mandibles and involved pain and edema. Most were unilocular and all were radiolucent. The literature-recommended histopathological findings were present and all cases were enucleated.

A63 RESTRAINED STRESS IN MICE INDUCES TRANSLOCATION OF GUT COMMENSAL BACTERIAL INTO DISTAL ORGANS

Abstract Background Bacterial translocation is defined as the migration of bacteria from the intestinal lumen into extraintestinal tissues; this process has been implicated in the pathophysiology of gastrointestinal disorders including irritable bowel syndrome (IBS) and central nervous system disorders. In our recent study, we found that gut bacteria from patients with IBS can disrupt the mucus layer and penetrate into the lamina propria in our microbiota-humanized mouse model. It is well known that psychological stress triggers or exacerbates IBS symptoms. Furthermore, experimental stress models have been able to reproduce some features of IBS and demonstrate that gut bacteria can translocate into the mesenteric lymph node (MLN), liver, and spleen. These studies suggested that bacterial translocation might induce changes in behavior and brain function. However, the direct causal relationship between bacterial translocation and behavioral changes, and the mechanism of bacterial translocation remains unclear. Aims To investigate translocation of commensal bacteria within the gut wall and their migration into distant organs using a mouse stress model. Methods SPF C57BL/6 mice were split into 2 groups: restraint stress group (3 hrs x 7 days, n=9) and non-stress control group (n=8). After the last session of stress, we conducted light/dark preference and tail suspension tests. We collected jejunum, ileum, and colon samples for histology. We also sampled blood, MLN, liver, spleen, and brain for histology and bacterial cultures. The tissues were collected under aseptic conditions. The blood or organ homogenates were plated and incubated in aerobic and anaerobic conditions. Intestinal tissues were submitted to fluorescence in situ hybridization staining with a bacterial universal probe in combination with immunofluorescence to co-stain with e-cadherin and CD103. The images were taken by confocal microscopy. Results The chronic restrain stress-induced anxiety-like, but not depressive behavior, as assessed by the light/dark test. Compared to the controls, bacterial culture was more frequently positive in the stress group: blood (0% vs 25%), MLN (0% vs 50%), spleen (0% vs 25%), liver (0% vs 25%), and brain (25% vs 74%). The histology showed that intestinal bacteria were present within the gut wall and brain in the stress group. Interestingly, these bacteria co-localized with the goblet cells in the jejunum, ileum and colon, and CD103+ dendritic cells in the colon (Fig. 1). Conclusions We found that mice subjected to the restraint stress exhibit abnormal behavior, accompanied by bacterial infiltration into the gut wall, as well as bacterial translocation into distal organs, including brain. Our histology data suggest a potential contribution of goblet cells-dendritic cells pathway in commensal gut bacteria translocation in the restrained stress model. Intestinal bacteria were present within the gut wall in the stress group. Funding Agencies CIHR Farncombe Innovation Fund

The role of contrast-enhanced mammography in the preoperative evaluation of invasive lobular carcinoma of the breast

To assess the performance of contrast-enhanced mammography (CEM) in the preoperative staging of invasive lobular carcinoma (ILC) of the breast. The present study was a multicentre, multivendor, multinational retrospective study of women with a histological diagnosis of ILC who had undergone CEM from December 2013 to December 2021. Index lesion size and multifocality were recorded for two-dimensional (2D) mammography, CEM, and when available magnetic resonance imaging (MRI). Comparison with histological data was undertaken for women treated by primary surgical excision. Pearson correlation coefficients and Bland-Altman's analysis of agreement were used to assess differences with a significance level of 0.05. One hundred and fifteen ILC lesions were included, 46 (40%) presented symptomatically and 69 were screening detected. CEM demonstrated superior sensitivity when compared to standard mammography. The correlation between the histological size measured on the surgical excision specimen size was greater than with standard mammography (r=0.626 and 0.295 respectively, p=0.001), with 19% of lobular carcinomas not visible without a contrast agent. The sensitivity of CEM for multifocal disease was greater than standard mammography (70% and 20% respectively, p<0.0001). CEM overestimated tumour size by an average of 1.5 times, with the size difference increasing for larger tumour. When MRI was performed (n=22), tumour size was also overestimated by an average of 1.3 times. The degree of size overestimation was similar for both techniques, with the tumour size on CEM being on average 0.5 cm larger than MRI. CEM is a useful tool for the local staging of lobular carcinomas and could be an alternative to breast MRI.

Clinicopathologic Characterization of Prostatic Cancer in Dogs.

Clinicopathologic data in dogs with prostate cancer (PCa) may aid in the differentiation between tumor types and subsequent treatment decisions; however, these data are often unreported. Demographic, clinicopathologic, cytologic, histologic and survival data from dogs with primary prostatic adenocarcinoma (PRAD) (n = 56) and primary prostatic transitional cell carcinoma (P-TCC) (n = 74) were acquired from a tertiary veterinary teaching hospital from 1992 to 2022. Red blood cell distribution width (RDW) to albumin ratio (RAR) was evaluated for diagnostic utility in differentiating between PRAD and P-TCC. Sections from PRAD tumors (n = 50) were stained for androgen receptor (AR) expression, and laboratory data were compared between AR positive (AR+) and AR negative (AR-) groups. RDW was increased in PRAD, while albumin was decreased (p < 0.05). P-TCC was associated with Melamed-Wolinska bodies (MWB) and necrosis on cytology (p < 0.05). RAR had acceptable diagnostic utility in the differentiation of PCa tumors (AUC = 0.7; p < 0.05). Survival rates and metastases were equivocal. AR+ and AR- PRAD tumors did not differ in clinicopathologic data or survival (p > 0.05). In conclusion, hypoalbuminemia was significantly associated with PRAD and decreased survival, while MWB and necrosis were significantly associated with P-TCC on cytology. These clinicopathologic data may help clinicians differentiate between these tumors ante mortem to guide appropriate treatment and intervention.

Liver Elastography in Acute Liver Failure: A Pilot Study.

We aimed to assess the feasibility and reliability of sequential ultrasonographic and elastographic monitoring in acute liver failure (ALF). Observational study. ALF is a rare, life-threatening disease that requires intensive care admission and often liver transplant, where the accurate selection of patients is crucial. Liver elastography is a noninvasive tool that can measure hepatic stiffness, but previous results have been inconclusive in ALF. Patients admitted between October 2021 and March 2023 to the Liver Intensive Therapy Unit at King's College Hospital with ALF were recruited, with healthy control (HC) individuals and acute-on-chronic liver failure (ACLF) used as controls. None. Average shear wave velocity was recorded with ElastPQ on the right and left liver lobes and the spleen. Portal vein flow, hepatic artery resistive index, and peak systolic velocity were also recorded. Physiologic and histologic data were used for comparison. Forty patients with ALF, 22 patients with ACLF, and 9 HC individuals were included in the study. At admission, liver stiffness measurement (LSM) of the right lobe was statistically different between HC individuals (5.6 ± 2 kPa), ALF (31.7 ± 17 kPa), and ACLF (76.3 ± 71 kPa) patients (ALF vs. ACLF, p = 0.0301). Spleen size and stiffness discriminated between ALF (10.4 ± 2 cm and 21.4 ± 16.6 kPa) and ACLF (14 ± 2.3 cm and 42.6 ± 26 kPa). At admission, LSM was not different between ALF patients who spontaneously survived versus patients who died or were transplanted in the following 90 days. However, the trend over the first 10 days of admission was different with a peak of LSM at day 5 in spontaneous survivors followed by reduction during the recovery phase. ALF patients with poor prognosis showed a persistently increased LSM. In ALF stiffness peaks at day 5 of admission with subsequent reduction in patients spontaneously surviving, showing significant difference according to the prognosis at day 7 of admission. LSM might be useful in distinguishing acute from acute-on-chronic liver failure together with spleen volume and stiffness.

Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein–coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1β, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.

Development of biotin decorated Olaparib loaded cationic lipopolymeric hybrid nanoparticle and evaluation of its anticancer effect and pharmacokinetics for triple negative breast cancer

Olaparib is a Poly(ADP-ribose) polymerase inhibitor, established for treatment of various cancer. Owing to its poor bioavailability, shorter biological half-life and requirement of frequent dosing of high oral dose, it displays lower therapeutic response and undesired toxicity. Thus, to address these issues, in the present work, a surface charge modified biotinylated lipo-polymeric nanoparticle system for Olaparib was prepared using single-step emulsification followed by solvent evaporation method to enhance the intracellular uptake and pharmacokinetics in biological system. The resulting Olaparib loaded lipo-polymeric hybrid nanoparticle exhibited an average particle size of <150 nm with a surface zeta potential of less than +30 mV. The release profile of Olaparib loaded lipo-polymeric nanoparticle (OLA-LPHNs, St@OLA-LPHNs and St/Biotin@OLA-LPHNs) indicated a controlled type drug release pattern in comparison to pure Olaparib. In-vitro cytotoxicity of olaparib loaded nanoparticle demonstrated an improvement in IC50 of Olaparib by 7.6-fold times in St/Biotin@OLA-LPHNs in 4T1 cell line against free Olaparib. Subsequently, blank nanoparticle showed no cellular death which indicates no significant toxicity of nanocarrier. The apoptosis profile showed that St/Biotin@OLA-LPHNs induced significant apoptosis compared to all other groups i.e., OLA-LPHNs, St@OLA-LPHNs and Olaparib. An improved pharmacokinetic profile was observed in Olaparib loaded lipo-polymeric nanoparticle. Moreover, hematological and histological data revealed that the developed nanoparticles are safe and biocompatible to biological system. In conclusion, in the present study, the developed Olaparib loaded lipo-polymeric nanoparticles demonstrated great potential for controlled release and have opened avenues for developing an effective formulation for improving anticancer effect against triple negative breast cancer.

Explainable artificial intelligence in pathology

With the advancements in precision medicine, the demands on pathological diagnostics have increased, requiring standardized, quantitative, and integrated assessments of histomorphological and molecular pathological data. Great hopes are placed in artificial intelligence (AI) methods, which have demonstrated the ability to analyze complex clinical, histological, and molecular data for disease classification, biomarker quantification, and prognosis estimation. This paper provides an overview of the latest developments in pathology AI, discusses the limitations, particularly concerning the black box character of AI, and describes solutions to make decision processes more transparent using methods of so-called explainable AI (XAI).

Repair of a rat calvaria defect with injectable strontium (Sr)-doped polyphosphate dicalcium phosphate dehydrate (P-DCPD) ceramic bone grafts.

The trace element strontium (Sr) enhances new bone formation. However, delivering Sr, like other materials, in a sustained manner from a ceramic bone graft substitute (BGS) is difficult. We developed a novel ceramic BGS, polyphosphate dicalcium phosphate dehydrate (P-DCPD), which delivers embedded drugs in a sustained pattern. This study assessed the in vitro and in vivo performance of Sr-doped P-DCPD. In vitro P-DCPD and 10%Sr-P-DCPD were nontoxic and eluents from 10%Sr-P-DCPD significantly enhanced osteoblastic MC3T3 cell differentiation. A sustained, zero-order Sr release was observed from 10%Sr-P-DCPD for up to 70 days. When using this BGS in a rat calvaria defect model, both P-DCPD and 10% Sr-P-DCPD were found to be biocompatible and biodegradable. Histologic data from decalcified and undecalcified tissue showed that 10%Sr-P-DCPD had more extensive new bone formation compared with P-DCPD 12-weeks after surgery and the 10%Sr-P-DCPD had more organized new bone and much less fibrous tissue at the defect margins. The new bone was formed on the surface of the degraded ceramic debris within the bone defect area. P-DCPD represented a promising drug-eluting BGS for repair of critical bone defects.

Renal Injury During Viral Infections

Renal pathologies following viral infections have become an emerging public health problem in both developed and developing countries. Diagnostic criteria are complex. In most cases, they involve correlation between clinical, biological and histological data, with occasional recourse to molecular biology techniques. Several mechanisms are involved in the pathogenesis of virus-related nephropathy, including virus tropism in the kidney, formation of immune complexes in situ or in the bloodstream, direct cytopathogenic effects, and multiple organ failure. The hepatitis C virus is responsible for three main types of kidney disease: membranoproliferative glomerulnephritis, cryoglobulinemia and membranous nephropathy. Hepatitis B virus is associated with membranous nephropathy, membranoproliferative glomerulnethritis, and IgA nephropathy. HIV (human immunodeficiency virus) infection is associated with several glomerular and tubular kidney damage. HIVAN (HIV-associated nephropathy), a specific entity mainly affecting Africans and African-Americans, presents as a rapidly progressive glomerulonephritis rapidly progressing to the terminal stage. Infections secondary to adenovirus, cytomegalovirus, epstein-barr virus, poliomavirus and coronavirus are often responsible for acute or chronic tubulointerstitial nephritis. Treatment is mainly symptomatic, based on nephroprotection measures, rarely combined with antiviral therapy. Prophylaxis with vacci-nation, when available, remains the best means of preventing viral nephropathy.

Effect of Platelet-Rich Plasma at Different Initiation Times on Healing of the Bone-Tendon Interface of the Rotator Cuff in a Mouse Model.

Platelet-rich plasma (PRP) has demonstrated beneficial effects on healing of the bone-tendon interface (BTI). To determine the optimal initiation time for PRP application after rotator cuff repair in an animal model. Controlled laboratory study. A total of 136 C57BL/6 mice were included; 40 mice were used to prepare PRP, while 96 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly divided into 4 groups: a control group and 3 groups in which PRP was injected into the injury interface immediately after surgery, on the 7th postoperative day (PRP-7d), and on the 14th postoperative day. At 4 and 8 weeks postoperatively, the animals were sacrificed, blood was collected by eyeball removal, and samples of the SST-humerus complex were collected. Histological, imaging, immunological, and biomechanical data were compared among the groups using 1-way analysis of variance with the Bonferroni post hoc test. Histological analysis revealed that the fibrocartilage layer at the BTI was larger in the PRP-7d group compared to the other groups at both 4 and 8 weeks postoperatively. Moreover, the PRP-7d group exhibited improved proteoglycan content and distribution compared to the other groups. Enzyme-linked immunosorbent assay results demonstrated that at 4 weeks postoperatively, higher concentrations of transforming growth factor-β1 and platelet-derived growth factor-BB (PDGF-BB) were seen in the PRP-7d group versus the PRP-14d and control gruops (P < .05), and at 8 weeks postoperatively, the concentration of PDGF-BB was higher in the PRP-7d group versus the control group (P < .05). Biomechanical testing at 4 weeks postoperatively revealed that the failure load and ultimate strength of the SST-humerus complex were superior in the PRP-7d group compared to the other groups (P < .05), at 8 weeks, PRP-7d group was superior to the control group (P < .05). Additionally, at 8 weeks postoperatively, the PRP-7d group exhibited a greater trabecular number and trabecular thickness at the BTI compared to the PRP-14d and control gruops (P < .05). PRP promoted healing of the BTI after a rotator cuff injury at an early stage. A PRP injection on the 7th postoperative day demonstrated superior therapeutic effects compared with injections at other time points.

Course and predictors of excellent response to therapy in patients with differentiated thyroid cancer at long-term follow-up.

To investigate the long-term outcomes of differentiated thyroid cancer (DTC) and the predictive factors for excellent and incomplete responses to therapy on long-term follow-up of patients. A retrospective chart review and analysis was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Demographic, histological, and therapeutic data were collected from patients older than 13 years at the time of diagnosis, with a minimum follow-up of 18 months. Outcomes were divided into excellent, indeterminate, biochemically incomplete, and structurally incomplete responses. Odds ratios (ORs) for predictors of incomplete response at the last visit were determined. We first tested associations univariately with incomplete responses, and then variables with significant associations were included in a multivariable logistic model. Among 230 patients with DTC, 61.7% had excellent responses to therapy on long-term follow-up, and 24.3% had incomplete biochemical and structural responses. The median follow-up was 4.6 years. Factors significantly associated with incomplete response to therapy in the multivariate analysis (p<0.05) were age >55 years (OR=5) and lymph node (OR=3.4) and distant metastases (OR=29). Older age did not affect the outcome in low-risk patients with DTC but was significantly associated with incomplete responses in those with intermediate risk (p=0.04) and high risk (p=0.003). We strongly advocate incorporating age into recurrence risk assessment for patients with DTC.

Postcranial anatomy of Prestosuchus chiniquensis (Archosauria: Loricata) from the Triassic of Brazil.

Prestosuchus chiniquensis is the best represented pseudosuchian archosaur from the Pinheiros-Chiniquá Sequence, Middle-Late Triassic (Ladinian/Carnian) of the Santa Maria Supersequence, Southern Brazil. Several incomplete specimens attributed to this species have been described, but the morphology of the postcranial skeleton of P. chiniquensis is poorly known. In this contribution we present the postcranial material of the UFRGS-PV-0629-T specimen, concluding its description, as its skull and endocast have already been described. Additionally, histological data provided new information on the poorly known ontogenetic series of P. chiniquensis, and on its growth patterns suggesting a longer period of slow growth when compared to other basal Loricata species. A phylogenetic analysis placed UFRGS-PV-0629-T in a group composed by the lectotype, paralectotype, and other described P. chiniquensis specimens, further corroborating our taxonomic hypothesis, that specimens of basal Loricata collected in Brazil are closely related to each other. Due to the association of characters found in the phylogenetic analysis, the specimen UFRGS-PV-0629-T is attributed as the most complete material ever found for P. chiniquensis. As such, it is clear that the material presented here provides important new information on P. chiniquensis. Based on the results presented here, we revised the diagnosis for P. chiniquensis. However, it also evidences the need for new discoveries and studies of other specimens seeking to understand this and other closely related species, which were important components of worldwide trophic webs of the Triassic biotas.

Abstract A010: Longitudinal histology and spatial transcriptomics profiling in targeted treatment of melanoma patient-derived models interrogates persister and resistant cell populations

Abstract Over half of BRAF-mutant melanoma patients with initial response to targeted therapy will recur with resistant disease. It is thought that recurrence arises from the ability of resistant clonal populations to enter and exit a slow-cycling persister state, evading treatment in quiescence before returning to a proliferative state. However, clonal transcriptional profiles and their spatial relationships in the tumor environment are not well characterized. Through longitudinal profiling of tumors from pre-treatment through the growth of resistant tumors, we track clonal lineages and transcriptional state changes to identify recurrent evolutionary patterns. BRAF mutant patient-derived melanoma xenografts were treated with BRAF/MEK inhibitors through maximum tumor size reduction and re-growth. Spatial transcriptomics (ST) and H&amp;E histological staining were performed at five timepoints across 94 and 133 days of PDX models WM4237 and WM4007 treatment, tracking clonal populations with intact tissue structure. Deep learning feature extraction on high-resolution H&amp;E-stained images allowed the detection of histological features that co-localize with expression levels. A novel computational workflow performed integration of samples across time points, pathway enrichment analysis, and pseudotemporal ordering, allowing spatial recreation of copy number variation based clonal phylogenies and cell fate trajectory inference during the treatment course. We characterize the clonal populations by the burden of accumulated copy number variations and establish clonal phylogeny. With the added temporal resolution, ST profiling during melanoma treatment enables observation of a global shift where all lineages begin the transition into the persister transcriptional state. The drug-sensitive cells are eliminated due to treatment, and distinct transcriptional states arise due to metabolic plasticity regardless of the lineage of origin. The clones of the transient persister state constitute the minimal residual disease, where melanoma cells have an increase in invasive capacity and a slowing of the cell cycle. The ability to survive through the persister state and re-emerge into a proliferating clone where the cell cycle is upregulated varies by lineage. We observe that the transcriptional changes during emergence from dormancy show decreased invasiveness and continued reliance on oxidative respiration versus glycolysis. We compare the re-emerged resistant cell populations and pre-treatment samples to pinpoint the changes in the transcriptional state of the MAPK signaling pathway and find that sets of upregulated genes differ by the model, WM4237 and WM4007. We connect deep learning imaging features extracted from longitudinal histology profiling to ST profiles to associate histology data with the cell cycle activation, invasiveness, hypoxia state, and metabolic mode across the timepoints. We observe that the imaging features alone can be potentially used to track the evolution of the tumor cell population phenotypes during drug treatment. Citation Format: Sergii Domanskyi, Todd B. Sheridan, Brian J. Sanderson, SungHee Park, Jessica Kaster, Haiyin Li, Olga Anczukow, Meenhard Herlyn, Jeffrey H. Chuang, Jill C. Rubinstein. Longitudinal histology and spatial transcriptomics profiling in targeted treatment of melanoma patient-derived models interrogates persister and resistant cell populations [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A010.