Prognostic significance of minor high grade component in non-invasive papillary urothelial carcinoma of urinary bladder: (A study of 273 consecutive cases over a period of 3 years).

PURPOSE: Our study aimed to determine the prognostic significance of minor high-grade components (HGC) in non-invasive papillary urothelial carcinomas compared with pure low-grade and high-grade tumors. MATERIAL AND METHODS: We retrospectively retrieved 273 in-house cases of non-invasive papillary urothelial carcinomas (pTa) from 2016 to 2018 for which follow up data was available in hospital archives. We stratified our data into four main groups (G). G1, pure low-grade (n = 164); G2, HGC ≤5 % (n = 17); G3, HGC >5 % to ≤25 % (n = 14); and G4, pure high-grade (n = 78). Prognosis was assessed in terms of recurrence, grade and stage of progression, metastasis, and death. The mean follow up duration was 34.72 ± 20 months (range 20-60 months). RESULTS: All four groups showed no difference in tumor recurrence (G1 81.7 %, G2 88.2 %, G3 92.9 %, G4 92.3 % p-value 0.183). In terms of grade progression, there was no significant difference in G2 35.3 % and G3 35.7 % and both groups showed worst prognosis compared to G1 16.5 % p-value 0.04. Regarding stage progression (G1 6.7 %, G2 23.5 %, G3 28.6 %, G4 41% p-value 0.001), metastasis (G1 5.5 %, G2 5.9 %, G3 7.1 %, G4 17.9 % p-value 0.01) and death (G1 4.3 %, G2 5.9 %, G3 7.1 %, G4 15.4 % p-value 0.02) there was no significant difference in G2 and G3 and both groups showed worst prognosis than G1 and better than G4. CONCLUSION: Urothelial carcinomas with minor high-grade component ≤25 % behaved worst than pure low grade and better than pure high grade and should be treated as distinct grade entity.

Application Of New WHO Classification On Malignancies Of Sinonasal Tract: Correlation With Epidemiology And Survival In Pakistani Population.

Objectives: To analyse the clinicopathological characteristics of sinonasal malignancies in the light of the updates regarding head and neck tumours. METHODS: The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data of patients diagnosed with primary malignant tumours of the sinonasal tract between 2015 and 2020. Slides related to biopsies and resection specimens were retrieved from the institutional database and reviewed by two pathologists. Follow-up data was also obtained. Data was analysed using SPSS 20. RESULTS: Of the 245 samples, 144(58.7%) were epithelial tumours, 46(18.7%) neuroectodermal tumours, 41(16.7%) haematolymphoid tumours and 14(5.7%) were malignant soft tissue tumours. A heavy reliance was placed on immunohistochemical stains to diagnose poorly-differentiated tumours. Survival was dismal, especially with early and frequent spread to the brain (33.3% in cases of Sinonasal Undifferentiated Carcinoma). CONCLUSIONS: A wide array of sinonasal malignancies was seen. Updated knowledge of the malignancies prevalent in the region is imperative for timely diagnosis and treatment.

Software-Defined Networking: Categories, Analysis, and Future Directions.

Software-defined networking (SDN) is an innovative network architecture that splits the control and management planes from the data plane. It helps in simplifying network manageability and programmability, along with several other benefits. Due to the programmability features, SDN is gaining popularity in both academia and industry. However, this emerging paradigm has been facing diverse kinds of challenges during the SDN implementation process and with respect to adoption of existing technologies. This paper evaluates several existing approaches in SDN and compares and analyzes the findings. The paper is organized into seven categories, namely network testing and verification, flow rule installation mechanisms, network security and management issues related to SDN implementation, memory management studies, SDN simulators and emulators, SDN programming languages, and SDN controller platforms. Each category has significance in the implementation of SDN networks. During the implementation process, network testing and verification is very important to avoid packet violations and network inefficiencies. Similarly, consistent flow rule installation, especially in the case of policy change at the controller, needs to be carefully implemented. Effective network security and memory management, at both the network control and data planes, play a vital role in SDN. Furthermore, SDN simulation tools, controller platforms, and programming languages help academia and industry to implement and test their developed network applications. We also compare the existing SDN studies in detail in terms of classification and discuss their benefits and limitations. Finally, future research guidelines are provided, and the paper is concluded.

Proteomics analysis of colon cancer progression.

BACKGROUND: The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). METHODS: A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). RESULTS: Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. CONCLUSION: Nevertheless, the study has provided significant insights into CC stage progression for further investigation.

A comprehensive review of climate change impacts, adaptation, and mitigation on environmental and natural calamities in Pakistan.

The devastations and damages caused by climate change are apparent across the globe, specifically in the South Asian region where vulnerabilities to climate change among residents are high and climate change adaptation and mitigation awareness are extremely low. Pakistan's low adaptive capacity due to high poverty rate, limited financial resources and shortage of physical resources, and continual extreme climatic events including varying temperature, continual flooding, melting glaciers, saturation of lakes, earthquakes, hurricanes, storms, avalanches, droughts, scarcity of water, pest diseases, human healthcare issues, and seasonal and lifestyle changes have persistently threatened the ecosystem, biodiversity, human communities, animal habitations, forests, lands, and oceans with a potential to cause further damages in the future. The likely effect of climate change on common residents of Pakistan with comparison to the world and their per capita impact of climate change are terribly high with local animal species such as lions, vultures, dolphins, and tortoise facing extinction regardless of generating and contributing diminutively to global GHG emissions. The findings of the review suggested that GHG emissions cause climate change which has impacted agriculture livestock and forestry, weather trends and patterns, food water and energy security, and society of Pakistan. This review is a sectorial evaluation of climate change mitigation and adaption approaches in Pakistan in the aforementioned sectors and its economic costs which were identified to be between 7 to 14 billion USD per annum. The research suggested that governmental interference is essential for sustainable development of the country through strict accountability of resources and regulation implemented in the past for generating state-of-the-art climate policy.

Efficacy of Prednisolone in bronchiolitis with and without family history of atopy.

OBJECTIVE: To determine decrease in respiratory distress and hospital stay in bronchiolitis patients with and without family history of atopy when treated with prednisolone. METHODS: The multi-centre quasi-experimental study was conducted in three hospitals of Sialkot, Pakistan, from October 2017 to March 2018, and comprised patients of bronchiolitis who were divided into 2 groups on the basis of presence or absence of family history of atopy. Half of the patients in each group received oral prednisolone 2mg/kg/day for three consecutive days along with supportive care, and the remaining half received only supportive care. Patients were monitored at 12 and 24 hours for clinical response using Modified Respiratory distress Assessment Instrument score. Length of hospital stay was monitored upto 72 hours. SPSS 20 was used for data analysis. RESULTS: Of the 212 patients, 72(34%) were in the atopic group and 140(66%) in the non-atopic group. In atopic group, there was a significant respiratory distress difference observed between steroid and non-steroid subgroups at 24 hours (p=0.001) and all (100%) patients in the steroid subgroup got discharged at 24 hours, while only 8(22%) were discharged in the non-steroid subgroup. In non-atopic group, no significant improvement in corresponding terms was observed (p>0.05). CONCLUSIONS: Oral prednisolone in bronchiolitis was found to be only effective in patients with family history of atopy.

Diagnostic accuracy of glypican-3 in differentiating hepatocellular carcinoma from metastatic liver tumours.

OBJECTIVE: To determine the diagnostic accuracy of Glypican-3 in differentiating hepatocellular carcinoma from metastatic liver tumours while taking histopathology as the gold standard.. METHODS: The cross-sectional study was conducted at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, from January 1 to June 30, 2016, and comprised cases of malignant liver tumours. Samples were collected from the pathology department. Glypican-3was applied on them. Tumours were classified as positive when they showed >5% positivity and negative when showing <5% positivity. Frequencies and percentages of cases showing GPC3 positivity and negativity along with frequency and percentages of hepatocellular carcinoma and metastatic tumours were calculated. RESULTS: Of the 240 patients, 143(59.58%) were males and 97 (40.42%) were females. Overall mean age was 54.65 ± 13.46 years. On histopathology, 134 cases were hepatocellular carcinoma (55.83%) and 106 (44. 17%) cases turned out to be metastatic carcinoma. Glypican-3staining was positive in 116 (48.33%) cases and negative in 124(51.67%). Sensitivity was 82%, Specificity 94.33%, positive predictive value 94.82% and negative predictive value 80.64%. Diagnostic accuracy was 87.5%. CONCLUSIONS: Glypican-3 was found to be a highly sensitive and specific Immunohistochemistry stain distinguishing hepatocellular carcinoma from the clear majority of metastatic carcinomas of the liver.

METASTATIC RADIOIODINE AVID STRUMA OVARII ASSOCIATED WITH PSEUDO-MEIGS' SYNDROME.

We report a case of 21 years old lady who presented with ascites, left adnexal mass and elevated CA-125. With suspicion of ovarian malignancy, she underwent left salpingo-oophorectomy with omental biopsy. Histopathology revealed: 'follicular variant of papillary thyroid carcinoma arising in struma ovarii' with metastatic papillary thyroid carcinoma in omental and peritoneal nodules. Patient underwent total thyroidectomy followed by radioactive iodine therapy for metastatic omental and peritoneal disease. Post-therapy whole body scan, revealed extensive I-131 avid disease metastatic disease involving the chest, abdomen, pelvis and the musculoskeletal system. Patient was treated with multiple doses of high dose radioactive iodine. She became symptom free on supra-physiologic doses of oral thyroxin however her high thyroglobulin levels and residual radioiodine avid metastatic disease required further treatment. In literature a few cases of struma ovarii have been reported with elevated CA-125 and associated pseudo-Meigs' syndrome. The treatment for this rare disease is still not standardized and poses a therapeutic challenge. Our case emphasizes the need for a multidisciplinary approach for managing struma ovarii.

Controller-driven vector autoregression model for predicting content popularity in programmable named data networking devices.

Named Data Networking (NDN) has emerged as a promising network architecture for content delivery in edge infrastructures, primarily due to its name-based routing and integrated in-network caching. Despite these advantages, sub-optimal performance often results from the decentralized decision-making processes of caching devices. This article introduces a paradigm shift by implementing a Software Defined Networking (SDN) controller to optimize the placement of highly popular content in NDN nodes. The optimization process considers critical networking factors, including network congestion, security, topology modification, and flowrules alterations, which are essential for shaping content caching strategies. The article presents a novel content caching framework, Popularity-aware Caching in Popular Programmable NDN nodes (PaCPn). Employing a multi-variant vector autoregression (VAR) model driven by an SDN controller, PaCPn periodically updates content popularity based on time-series data, including 'request rates' and 'past popularity'. It also introduces a controller-driven heuristic algorithm that evaluates the proximity of caching points to consumers, considering factors such as 'distance cost,' 'delivery time,' and the specific 'status of the requested content'. PaCPn utilizes customized DATA named packets to ensure the source stores content with a valid residual freshness period while preventing intermediate nodes from caching it. The experimental results demonstrate significant improvements achieved by the proposed technique PaCPn compared to existing schemes. Specifically, the technique enhances cache hit rates by 20% across various metrics, including cache size, Zipf parameter, and exchanged traffic within edge infrastructure. Moreover, it reduces content retrieval delays by 28%, considering metrics such as cache capacity, the number of consumers, and network throughput. This research advances NDN content caching and offers potential optimizations for edge infrastructures.

Efficient handling of ACL policy change in SDN using reactive and proactive flow rule installation.

Software-defined networking (SDN) is a pioneering network paradigm that strategically decouples the control plane from the data and management planes, thereby streamlining network administration. SDN's centralized network management makes configuring access control list (ACL) policies easier, which is important as these policies frequently change due to network application needs and topology modifications. Consequently, this action may trigger modifications at the SDN controller. In response, the controller performs computational tasks to generate updated flow rules in accordance with modified ACL policies and installs flow rules at the data plane. Existing research has investigated reactive flow rules installation that changes in ACL policies result in packet violations and network inefficiencies. Network management becomes difficult due to deleting inconsistent flow rules and computing new flow rules per modified ACL policies. The proposed solution efficiently handles ACL policy change phenomena by automatically detecting ACL policy change and accordingly detecting and deleting inconsistent flow rules along with the caching at the controller and adding new flow rules at the data plane. A comprehensive analysis of both proactive and reactive mechanisms in SDN is carried out to achieve this. To facilitate the evaluation of these mechanisms, the ACL policies are modeled using a 5-tuple structure comprising Source, Destination, Protocol, Ports, and Action. The resulting policies are then translated into a policy implementation file and transmitted to the controller. Subsequently, the controller utilizes the network topology and the ACL policies to calculate the necessary flow rules and caches these flow rules in hash table in addition to installing them at the switches. The proposed solution is simulated in Mininet Emulator using a set of ACL policies, hosts, and switches. The results are presented by varying the ACL policy at different time instances, inter-packet delay and flow timeout value. The simulation results show that the reactive flow rule installation performs better than the proactive mechanism with respect to network throughput, packet violations, successful packet delivery, normalized overhead, policy change detection time and end-to-end delay. The proposed solution, designed to be directly used on SDN controllers that support the Pyretic language, provides a flexible and efficient approach for flow rule installation. The proposed mechanism can be employed to facilitate network administrators in implementing ACL policies. It may also be integrated with network monitoring and debugging tools to analyze the effectiveness of the policy change mechanism.

Preparation of medium- and long-chain triacylglycerols rich in n-3 polyunsaturated fatty acids by bio-imprinted lipase-catalyzed interesterification.

Medium and long-chain triacylglycerol (MLCT) rich in n-3 polyunsaturated fatty acids (PUFAs) were obtained in three-hour interesterification of fish oil with medium-chain triacylglycerol (MCTs), using lipase bio-imprinted with surfactant as a catalyst. Initially, for bio-imprinted lipase preparation, the interesterification reaction conditions were optimized, resulting in a lipase with 1.47 times higher catalytic activity compared to control (non-bio-imprinted). Afterwards, the reaction conditions for MLCT synthesis were optimized, using bio-imprinted lipase as a catalyst. The reaction reached equilibrium within first three hours at 70 °C temperature, 4 wt% lipase load, and molar ratio of substrate 1:1.5. Under these conditions, final product contained 18.52% MCT, 56.65% MLCT, and 24.83% long-chain triacylglycerol (LCT). To reduce the MCT content, a solvent extraction process was performed, yielding 2.42% MCT, 56.19% MLCT, and 41.39% LCT. The obtained structured lipids (SLs), enriched in n-3 PUFAs, offer significant health benefits, enhanced bioavailability, with potential applications in functional foods and nutraceuticals.

Identification of a Unique Morphological Pattern for the Diagnosis of Fungal Rhinosinusitis.

Fungal rhinosinusitis (FRS) is a relatively common, but often misdiagnosed disease of paranasal sinuses. The FRS is classified into invasive and non-invasive forms. The non-invasive form includes fungal ball and allergic FRS, and invasive form includes acute invasive FRS, chronic invasive FRS, and granulomatous FRS. Invasive fungal infections are associated with high morbidity and mortality, hence requiring urgent medical and surgical intervention. The histomorphology can help identify certain fungal organisms that cannot be cultured or are rarely visible in exudates. The morphologic diagnosis of tissue invasive and non-invasive fungal infection is essential for appropriate treatment. We analyzed cases of rhinosinusitis from 2017 to 2019 in Pathology Department at a tertiary care cancer hospital, Lahore, Pakistan. All clinical information was retrieved from patient records. Paraffin-embedded tissue blocks were stained with hematoxylin and eosin (H&E), special Grocott methenamine silver stain (GMS), and periodic acid Schiff stain (PAS) according to standard protocol. They were reviewed by two pathologists blinded by fungus status. A total of 169 cases of rhinosinusitis were reviewed. FRS comprised 146 (86.4%) of them. The mean age of patients with FRS was 32.8±14 years. The male:female ratio was 1.4:1. Maxillary sinus was the main site of involvement in 39 (27%) FRS cases. Aspergillus was identified in 117 (80.1%) cases of FRS. The culture reports were available in 44/146 (30.14%) FRS cases. They were negative in 22/44 (50.0%), and Aspergillus species were isolated in 18/44 (40.9%) cases of FRS. There were 84 (57.5%) cases of non-invasive FRS and 59 (40.4%) cases of invasive FRS. Among invasive FRS, there were 56 (38.4%) chronic granulomatous FRS cases including mixed patterns. Majority cases, 54 (96.4%), of chronic granulomatous FRS showed a unique crowded giant cell pattern comprising of foreign body and Langhans type giant cells. These giant cells were arranged closely forming irregular non-caseating granulomas surrounded by lymphocytes and fibrosis. Interestingly, the giant cells were scattered haphazardly without forming a granuloma as well. Fungal organisms were identified in all 56 cases of chronic granulomatous FRS. Histologically, predominant organism was Aspergillus in 48 (85.7%) on GMS and PAS stain. Our study observed a unique crowded giant cell pattern, which is a hallmark of invasive fungal infection. If pathologists are familiar with this unique pattern, they can make a quick and accurate diagnosis on histology. The physician can start antifungal treatment timely for better prognosis.

Blind Spot in the Radar of MEST-C Score: Type and Severity of Tubulointerstitial Nephritis in IgA Nephropathy.

Background: The updated version of predictive classification for immunoglobulin A nephropathy (IgAN) prognosis "The Oxford Classification" identifies five histopathological features including mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T) and crescents (C), the MEST-C. However, few studies suggest that tubulointerstitial inflammation, which is not included in the MEST-C, is also linked to disease progression and is, consequently, a neglected determinant of prognosis among others. Therefore, there is a need to evaluate this histopathological parameter in patients with IgA nephropathy. Materials and Methods: This cross-sectional descriptive study was conducted at Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. Data of histopathological and immunofluorescence proven renal biopsies (300) of IgA nephropathy patients from January 2016 through May 2022 were extracted using a convenient sampling technique. Biopsies were histologically reviewed for type and severity of tubulointerstitial inflammation, in addition to the MEST-C score. Renal biopsies of patients who had a history of transplant, autolyzed tissue, no glomeruli on histological examination, and/or a tubular atrophy/interstitial fibrosis score of 2 (T2) in MEST-C scoring were excluded. Data were analyzed using SPSS 20. An association between the variables was analyzed using the chi-square and Fischer exact tests. A p value less than 0.05 was considered statistically significant. Results: A total of 247/300 biopsies were eligible for inclusion. The mean age at the time of biopsy was 31.90 ± 12.48 with 63.6% in the age group between 21 and 40 years, and 69.6% were male. Tubulointerstitial inflammation was observed in 90.2% cases with 49.4% showing moderate while 4.5% showing severe degree of inflammation. A strong association of both the type and severity of tubulointerstitial inflammation was found with M, E, T, and C scores (p value < 0.05). Conclusion: The high-frequency and strong statistical association of tubulointerstitial inflammation with the M, E, T, and C scores in our study elucidate its prognostic role in the progression and management of IgA nephropathy.

The Expression of Mucin-4 (MUC4) in Sarcomas Apart From Sclerosing Epithelioid Fibrosarcoma and Low-Grade Fibromyxoid Sarcoma.

Background Low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF) are two rare but aggressive soft tissue sarcomas that can be difficult to distinguish due to histopathological similarities. The present study examines the diagnostic capacities of mucin-4 (MUC4), a transmembrane mucin, in identifying different types of sarcomas and broadens its evaluation to include a wide range of sarcomas. Methods Immunohistochemical (IHC) examination of tissue samples from various sarcomas was performed using a mouse anti-MUC4 monoclonal antibody. IHC was conducted on 4-mm thick formalin-fixed paraffin-embedded tissue sections after pressure cooker antigen retrieval with a mouse anti-MUC4 monoclonal antibody. Results MUC4 was shown to be highly expressed in SEF (n=13) and LGFMS (n=10), while focal positivity in synovial sarcoma (n=1). Other sarcomas, such as malignant peripheral nerve sheath tumors, fibrosarcoma, leiomyosarcoma, liposarcoma, and myxofibrosarcoma, exhibited no expression (n=0). These findings are consistent with previous research and support MUC4 specificity as a SEF and LGFMS marker. This study provides information on the diagnostic efficacy of MUC4, particularly in the context of certain subtypes. It not only helps our understanding of these unique instances, but it also provides context for histopathological and IHC findings in soft tissue sarcoma. Furthermore, this study investigates the influence of age and gender on MUC4 expression in a range of sarcomas, which was typically understudied in the literature and found no relation with expression of MUC4. Conclusion In conclusion, this study adds to our understanding of soft tissue sarcomas by emphasizing the crucial role of MUC4 in certain sarcoma subtypes while acknowledging the complex variety of the sarcoma landscape. Further research is needed to understand the molecular mechanism that governs marker expression patterns, as well as the therapeutic implications.

Expression of NKX2.2 in Non-Ewing Tumors With Round Cell Morphology.

Background Round cell sarcomas pose diagnostic challenges due to overlapping histopathological features, necessitating precise immunohistochemical markers for accurate categorization. NKX2.2 has emerged as a sensitive diagnostic tool, particularly in Ewing sarcoma. This study extends this understanding to various round-cell sarcomas, shedding light on the potential diagnostic utility of NKX2.2 beyond its established role. The nuanced exploration of NKX2.2 expression aims to enhance diagnostic strategies, prognostic assessments, and therapeutic developments in the landscape of sarcoma research. Methodology Cases were retrieved from the surgical pathology and consultation files of Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan. Representative hematoxylin and eosin-stained slides of six different types of already confirmed tumors, including lymphoblastic lymphoma, neuroblastoma, rhabdomyosarcoma, synovial sarcoma, Wilms tumor, and Ewing sarcoma, were reviewed by a panel of pathologists. Immunohistochemistry, utilizing a rabbit anti-NKX2.2 monoclonal antibody, was performed on formalin-fixed paraffin-embedded tissue sections. The presence of NKX2.2 was defined as moderate or high nuclear immunoreactivity in at least 5% of cells. Results The histopathological examination revealed characteristic features in each sarcoma subtype, aligning with established diagnostic criteria. In Lymphoblastic lymphoma, T-cell lineage was confirmed through TdT expression, while the atypical finding of focal NKX 2.2 expression hinted at genetic diversity. Neuroblastoma exhibited the expected salt and pepper chromatin pattern, with NKX 2.2 expression raising questions about its prognostic significance. Rhabdomyosarcoma presented primitive cells expressing desmin, and NKX 2.2 focal expression echoed previous subtype-associated studies. Synovial sarcoma displayed both monophasic and biphasic growth patterns and TLE1 expression, with NKX 2.2 variation suggesting tumor heterogeneity. In Wilms tumor, the characteristic WT1 expression was observed, while NKX2.2's absence reaffirmed its irrelevance in this context. Ewing sarcoma displayed the anticipated homogenous cell population, strong NKX2.2 expression, and CD99 positivity across various sites. Furthermore, age and gender impact on this range of sarcomas found no significant relation with an expression of NKX2.2. Conclusion In conclusion, the diverse expression profiles of diagnostic markers discovered in this study, particularly the atypical expression of NKX2.2 beyond its established role in Ewing sarcoma, signify a significant advancement. This unique finding accentuates the potential diagnostic importance of NKX2.2 in various sarcomas, presenting a novel dimension to our understanding of these malignancies.

IgM and C3 Deposition in Primary Focal Segmental Glomerulosclerosis (FSGS): A Clinical and Histopathological Spectrum.

Focal segmental glomerulosclerosis (FSGS) is a common renal disorder, characterized by progressive segmental sclerosis of renal glomeruli and clinical symptoms corresponding to proteinuria. Classically, it is not considered to be an antibody-mediated disease, however, IgM and C3 deposition may be seen in a subset of cases of FSGS. The impact of this immune deposition on histopathological features in renal core biopsies, on the urinary biochemical parameters, and the clinical outcomes, has not been previously investigated in our population. The aim of this study is to analyze the aforementioned parameters in patients with primary FSGS having antibody deposition as compared to those who do not have any antibody deposition. Some 155 patients diagnosed with FSGS were retrospectively enrolled in our study. The renal biopsies were reviewed for histopathological features and immunofluorescence (IF) findings of IgM and C3 glomerular deposition. These histological features were then compared with the biochemical parameters as well as the clinical outcomes of patients. The patients were assigned to Groups 1 and 2 based on the IF findings. The IgM and/or C3 glomerular deposition had a low incidence in patients with primary FSGS in our study (28.3%). Patients having IgM and C3 co-deposition had a significantly longer time duration since the onset of their clinical symptoms; active disease duration (42 months vs 22 months, p=0.049). The mean pre-treatment serum creatinine of patients with IgM and C3 co-deposition was 6.00 mg/dL as compared to 3.29 mg/dL in patients with no immune deposition (p=0.037). The immune deposition was associated with higher rates of segmental and global glomerulosclerosis, but this finding along with other evaluated histological parameters did not show statistical significance. The number of patients having IgM and/or C3 deposition and with active steroid use/renal dialysis was similar to patients having no IgM and/or C3 deposition. The IgM and/or C3 deposition in FSGS has a low incidence within and is not associated with any significant differences in histological parameters on renal core biopsies of patients from the Pakistani population. IgM and/or C3 deposition is also associated with a significantly longer duration of active disease and these patients may present with higher pre-treatment serum creatinine. Other biochemical parameters and clinical outcomes appear comparable between the groups based on the available clinical data.

Gemistocytic Differentiation in Isocitrate Dehydrogenase Mutant Astrocytomas: A Histopathological and Survival Analysis.

Gemistocytic differentiation is a rare histological feature seen in IDH mutant Astrocytomas. The 2021 World Health Organization (WHO) retains the diagnosis of IDH mutant Astrocytoma with its classical histology and tumors with the rare histological pattern of gemistocytic differentiation. Gemistocytic differentiation has historically been associated with a worse prognosis and shorter survival, and this prognostic difference has not been investigated in detail in our population. A population-based retrospective study included 56 patients with IDH mutant Astrocytoma with Gemistocytic differentiation and IDH mutant Astrocytoma diagnosed between 2010 and 2018 in our hospital. Demographic, histopathological, and clinical parameters were compared between the two groups. Gemistocyte percentage, perivascular lymphoid infiltrates, and Ki-67 proliferation index were also analyzed. A Kaplan-Meier analysis was done to analyze any prognostic difference in the overall survival time between the two groups. Patients with an IDH mutant Astrocytoma having gemistocytic differentiation had an average survival period of 2 years, while patients diagnosed with an IDH mutant Astrocytoma had an average survival time of approximately 6 years. There was a statistically significant decrease in survival time (p = 0.005) for patients with tumors with gemistocytic differentiation. The percentage of gemistocytes and the presence of perivascular lymphoid aggregates did not correlate with survival time (p = 0.303 and 0.602, respectively). Tumors with gemistocytic morphology had a higher mean Ki-67 proliferation index (4.4%) than IDH mutant Astrocytoma (2.0%, p = 0.005). Our data suggest that IDH mutant Astrocytoma with Gemistocytic differentiation is an aggressive variant of IDH mutant Astrocytoma associated with a shorter survival time and an overall worse prognosis. This data might be helpful to clinicians in the future management of IDH mutant Astrocytoma with Gesmistocytic differentiation as an aggressive tumor.

Antibiofilm Potential of Coelomic Fluid and Paste of Earthworm Pheretima posthuma (Clitellata, Megascolecidae) against Pathogenic Bacteria.

Antibiotic drug resistance is a global public health issue that demands new and novel therapeutic molecules. To develop new agents, animal secretions or products are used as an alternative agent to overcome this problem. In this study, earthworm (Pheretima posthuma) coelomic fluid (PCF), and body paste (PBP) were used to analyze their effects as antibiofilm agents against four bacterial isolates MH1 (Pseudomonas aeruginosa MT448672), MH2 (Escherichia coli MT448673), MH3 (Staphylococcus aureus MT448675), and MH4 (Klebsiella pneumoniae MT448676). Coelomic fluid extraction and body paste formation were followed by minimum inhibitory concentrations (MICs), biofilm formation time kinetics, and an antibiofilm assay, using heat and cold shock, sunlight exposure auto-digestion, and test tube methods. The results showed that the MIC values of PCF and PBP against S. aureus, P. aeruginosa, K. pneumoniae, and E. coli bacterial isolates ranged from 50 to 100 µg/mL, while, the results related to biofilm formation for P. aeruginosa, S. aureus, and K. pneumoniae strains were observed to be highly significantly increased (p < 0.005) after 72 h. E. coli produced a significant (p < 0.004) amount of biofilm after 48 h. Following time kinetics, the antibiofilm activity of PCF and PBP was tested at different concentrations (i.e., 25-200 µg/mL) against the aforementioned four strains (MH1-MH4). The findings of this study revealed that both PBP (5.61 ± 1.0%) and PCF (5.23 ± 1.5%) at the lowest concentration (25 µg/mL) showed non-significant (p > 0.05) antibiofilm activity against all the selected strains (MH1-MH4). At 50 µg/mL concentration, both PCF and PBP showed significant (p < 0.05) biofilm inhibition (<40%) for all isolates. Further, the biofilm inhibitory potential was also found to be more significant (p < 0.01) at 100 µg/mL of PCF and PBP, while it showed highly significant (p < 0.001) biofilm inhibition at 150 and 200 µg/mL concentrations. Moreover, more than 90% biofilm inhibition was observed at 200 µg/mL of PCF, while in the case of the PBP, <96% biofilm reduction (i.e., 100%) was also observed by all selected strains at 200 µg/mL. In conclusion, earthworm body fluid and paste have biologically active components that inhibit biofilm formation by various pathogenic bacterial strains. For future investigations, there is a need for further study to explore the potential bioactive components and investigate in depth their molecular mechanisms from a pharmaceutical perspective for effective clinical utilization.

Histopathological Characteristics and Prognosis of Malignant Acral Melanomas in Pakistani Patients.

Background Malignant melanoma is a common cancer in Scandanavian countries due to increased exposure to ultraviolet light. Very limited data is available on malignant melanomas in Pakistani population and further studies are needed to determine its incidence in our population. Objective The main objective of our study was to determine histopathological characteristics and prognosis of malignant foot melanomas in Pakistani patients. Material and methods After approval by the Institutional Review Board, we performed a retrospective study of 59 consecutive cases of malignant acral melanoma from the year 2016-2019. The follow-up of in-house cases was available in hospital archives. The follow-up of diagnostic patients was done through direct communication. The histological features were assessed, and the prognosis was determined in terms of recurrence, metastasis, and death. Results The main histological features assessed were Breslow thickness <1 (n=3), >1-2 (n=9), >2-4 (n=12), >4 (n=36), ulceration was present in 65% (n=39), and pathological stage 1 (n=3), stage 2 (n=9), stage 3 (n=12) and stage 4 (n=36). The margin was involved in 28.3% (n=17) cases. Recurrence was observed in 47.4% (n=28), metastasis in 55.9 % (n=33), and death was observed in 49.1% (n=29). The mean follow-up duration of 3.4 years ± 0.20 (Range 3 to 6 years). The recurrence-free survival was 2.9 ± 0.24 years, metastasis-free survival was 2.8 ± 0.237 years, and disease-specific survival was 3.4 ± 0.203 years.  Conclusion Malignant acral melanoma is fatal with high mortality rates. In our part of the world, acral melanoma has poor prognosis compared to non-acral melanomas. When compared with acral melanomas in other parts of the world prognosis is even worst. Early diagnosis and treatment are crucial in terms of patient management.

1H-NMR Metabolomics Study after Foliar and Endo-Therapy Treatments of Xylella fastidiosa subsp. pauca Infected Olive Trees: Medium Time Monitoring of Field Experiments.

Here we report the medium-term effects of foliar spray and endo-therapy treatments with different doses of a Cu/Zn citric acid biocomplex (Dentamet®) in Xylella fastidiosa infected olive trees of Salento, Apulia region (South-east Italy). Leaf extract samples from field-treated 150 years old olive trees cvs Ogliarola salentina and Cellina di Nardò were studied by 1H NMR-based metabolomics. The result of different applications of Dentamet® endo-therapy after 60, 120 and 180 days in comparison with traditional foliar spray treatment and water injection as a control have been investigated. The metabolic profile analyses, performed by 1H NMR-based metabolomic approach, indicated plant metabolites variations connected to the disease progression such as mannitol, quinic acid, and oleuropein related compounds. The best results, in terms of discrimination of the metabolic profiles with respect to water injection, were found for monthly endo-therapy treatments. Dentamet® foliar application demonstrated more specific time related progressive effectiveness with respect to intravascular treatments. Therefore, besides a possible more effective performance of endo-therapy with respect to foliar treatments, the need of further doses/frequencies trimming to obtain long-term results was also assessed. The present field studies confirmed the indication of Dentamet® effectiveness in metabolic variation induction, potentially linked with reducing the X. fastidiosa subspecies pauca related Olive Quick Decline Syndrome (OQDS) symptoms development.