Papillary Thyroid Carcinoma Concealed Within a Branchial Cyst Without Primary Thyroid Involvement: Unveiling the Enigma.

Branchial cleft cysts are congenital anomalies that form during fetal development and originate from the second branchial cleft. They typically manifest as painless masses on the side of the neck and can become symptomatic when infected. These cysts can create a cavity that may foster infection and, in rare instances, facilitate the spread of primary tumors. It is unusual to find ectopic thyroid tissue within a brachial cyst and it is even rarer to see papillary thyroid carcinoma developing from this tissue. Whenever physicians find a case of lateral neck cyst containing thyroid neoplasm without a known primary in the thyroid, there is always a confusion about whether it is a case of metastatic disease with an undetected primary tumor, or is a carcinoma originating from ectopic thyroid tissue. This is a case report of a papillary thyroid cancer that was unintentionally discovered inside a branchial cyst. So far, only five cases akin to this have been documented. There was no sign of an underlying primary thyroid tumor after the patient had a complete thyroidectomy and selected neck dissection, according to a comprehensive evaluation. This article touches on the development of thyroid tissue within branchial cysts and discusses the etiology of lateral neck tumors. The outcome for such patients appears to be favorable after cyst excision and total thyroidectomy. This article also emphasizes the importance of doing routine histopathological examinations on surgically removed samples that look benign.

Dysregulation of exosomal miRNAs and their related genes in head and neck cancer patients.

Aim: The present study aimed to figure out the potential role of exosomal microRNAs, and their targeted genes in HNC detection/diagnosis. Methods: In the present study, exosomes were extracted from the serum samples of 400 HNC patients and 400 healthy controls. Exosomes were characterized using TEM, NTA, TEM-immunogold labeling and ELISA. Quantitative PCR was used to measure the expression level of exosomal miRNA-19a, miRNA-19b and targeted genes SMAD2 and SMAD4 in HNC patients and controls. Results: The deregulation of miR-19a (p < 0.01), miR-19b (p < 0.03), SMAD2 (p < 0.04) and SMAD4 (p < 0.04) was observed in HNC patients vs controls. Conclusion: ROC curve and Kaplan-Meier analysis showed the good diagnostic/prognostic value of selected exosomal microRNAs and related genes in HNC patients.

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Exploring the effects of noise pollution on physiology and ptilochronology of birds.

Short and long-term sound-induced stress on daily basis can affect the physiology of avian individuals because they are more susceptible to sound stress in an open environment. OBJECTIVES: An ex-situ study was carried out to determine the impact of noise on physiology and ptilochronology of non-breeding male domesticated quail birds. METHODOLOGY: During 60-days long trial, male quail birds, aged 5-weeks, weighing (c.100gm) were used. Out of 72 experimental birds, 18 birds were assigned to the Control Group (G1) while remaining 54 birds were divided equally into 3 treatment groups: Road Traffic noise (G2), Military activity noise (G3) and Human Activities noise (G4). Birds were housed in standard-sized separate cages (20 ×45 × 20 cm), every bird was kept apart in separate cage in open laboratory under maintained environmental conditions. Millet seeds and water were provided to all the experimental birds ad libitum. Noise originated from several sources of recorded high-intensity music (1125 Hz/ 90 dB), was administered for 5-6 hours per day. Observations were recorded in the morning and afternoon. The experiment was conducted during the non-breeding season from August to October in triplicate. Blood sampling was done after 60 days. RESULTS: According to the current study, noise stress significantly (p<0.05) increased the concentrations of creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, uric acid, cholesterol, triglycerides, total protein, and glucose while a decline in the levels of albumin was seen in treatment birds of G3. While in terms of hematology, total white blood cells count (TWBC), total red blood cells count (TRBC), mean cell volume (MCV) & packed cell volume (PCV) concentrations were raised in blood of treatment birds of G3. In terms of hormones, noise stress significantly (p<0.05) increased the serum concentrations of Corticosterone in G3 while a significant (p<0.05) decline was observed in the concentrations of luteinizing hormone (LH), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH) in the same group. Moreover, fault bar formation in G3 was more prominent than others. CONCLUSION: Noise stress can significantly affect serology, hematology, hormonal physiology and ptilochronology in quail birds.

Performance enhancement of short-term wind speed forecasting model using Realtime data.

The ever-increasing demand for electricity has presented a grave threat to traditional energy sources, which are finite, rapidly depleting, and have a detrimental environmental impact. These shortcomings of conventional energy resources have caused the globe to switch from traditional to renewable energy sources. Wind power significantly contributes to carbon-free energy because it is widely accessible, inexpensive, and produces no harmful emissions. Better and more efficient renewable wind power production relies on accurate wind speed predictions. Accurate short-term wind speed forecasting is essential for effectively handling unsteady wind power generation and ensuring that wind turbines operate safely. The significant stochastic nature of the wind speed and its dynamic unpredictability makes it difficult to forecast. This paper develops a hybrid model, L-LG-S, for precise short-term wind speed forecasting to address problems in wind speed forecasting. In this research, state-of-the-art machine learning and deep learning algorithms employed in wind speed forecasting are compared with the proposed approach. The effectiveness of the proposed hybrid model is tested using real-world wind speed data from a wind turbine located in the city of Karachi, Pakistan. Moreover, the mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) are used as accuracy evaluation indices. Experimental results show that the proposed model outperforms the state-of-the-art legacy models in terms of accuracy for short-term wind speed in training, validation and test predictions by 98% respectively.

Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

Synthesis and analytical characterization of Ca-BTC metal organic framework.

Metal Organic framework (MOF) has been a class of great interest during the past few years owing to its decidedly applicative, easily synthesized and improved characteristics. Ca-BTC MOF is synthesized by Hydrothermal technique and reported for the first time. Its structural morphology was analyzed using XRD, SEM, and EDS, showing the tetragonal crystal structure having grain size of 24.92 nm and purity of sample respectively. FTIR, Raman Spectroscopy ensures the metal organic framework between Calcium and the tri-carboxylic group. Photoluminescence measures the energy gap of 3.792 eV, showing approximately the semiconducting behavior of synthesized material. Zeta potential having value of -13.5 mV confirms the instability having good microbial activity and conductivity i.e 0.290 mS/cm which reveals important insights into its electrical properties.

Role of exosomal miRNA-19a/19b and PTEN in brain tumor diagnosis.

Aim: The current study was designed to evaluate the diagnostic significance of the exosomal miRNAs miR-19a and miR-19b and the PTEN gene in brain tumor patients versus controls. Methods: Exosomes were extracted from the serum samples of 400 brain tumor patients and 400 healthy controls. The exosomes were characterized by scanning electron microscopy, dynamic light scattering and ELISA. Quantitative PCR was used to analyze selected exosome miRNAs and gene expression levels. Results: Analysis showed significant deregulated expression of miR-19a (p < 0.0001), miR-19b (p < 0.0001) and PTEN (p < 0.001) in patients versus controls. Spearman correlation showed a significant correlation among the selected exosomal miRNAs and the PTEN gene. Conclusion: Receiver operating characteristic curve analysis showed the good diagnostic value of exosomal miRNAs and the PTEN gene in brain tumor patients.

Deregulation of exosomal miRNAs in rheumatoid arthritis patients.

Exosomes are small-diameter endosomal vesicles secreted in all biological fluids and play biological/pathological roles in the cell. These pathological roles are played by exosome's cargo molecules through inter-cellular communication. Exosomal cargo molecules contain proteins and miRNAs. miRNAs are small non-coding RNA fragments involved in the reduction of final protein output by destabilizing or suppressing the translation of target messenger RNA (mRNA). This deregulation of the protein due to miRNAs ultimately accelerates the process of disease pathogenesis. The role of exosomal miRNAs has been investigated in different diseases and the limited number of studies have been published concerning exosomal miRNAs and rheumatoid arthritis (RA). The current study is designed to investigate the role of exosomal miRNAs (miRNA-103a-3p, miRNA-10a-5p, miRNA-204-3p, miRNA-330-3p, and miRNA-19b) in the pathogenesis of RA. Furthermore, the role of selected exosomal miRNAs in RA pathogenesis was further explored by estimating oxidative stress and histone deacetylation in RA patients. In the current study, 306 RA patients and equal numbers of age/gender-matched controls were used. The level of expression of above-mentioned exosomal miRNAs was assessed by performing qRT PCR. Deacetylation and oxidative stress assays were performed to estimate the 8-hydroxydeoxyguanosine (8-OHdG level) and histone deacetylation levels using the Enzyme-linked immunosorbent assay (ELISA). Statistical analysis indicated a significantly downregulated expression of miRNA-103a-3p (p<0.0001), miR-10a-5p (p<0.0001), miR-204-3p (p<0.0001), miR-330-3p (p<0.0001) and miR-19b (p<0.0001) in RA patients compared to controls. Significantly increased levels of 8-OHdG (p<0.0001) and histone deacetylation (p<0.0001) were observed among RA patients compared to controls. Spearman correlation showed a negative correlation between the deregulated exosomal miRNAs and increased oxidative stress and histone deacetylation in RA patients. Receiver operating characteristics (ROC) curve analysis showed a good diagnostic specificity/sensitivity of the above-mentioned exosomal miRNAs among RA patients. These analyses indicated the potential role of deregulated exosomal miRNAs in the initiation of RA by targeting oxidative stress and histone deacetylation processes.

In-vitro co-delivery of decarbazine and photosense using poly lactic-co-glycolic acid nanocarrier for combinational therapy.

PLGA (Poly lactic-co-glycolic acid) nanoparticles are a new trend for drug delivery due to their good biodegradability properties. In this study, we have synthesized PLGA nanoparticles by solvent evaporation method and loaded decarbazine (DTIC, 5-3,3-(dimethyl-ltriazeno)imidazole-4-carboxamide) and photosense (AlPc4) drug alone as well as combined with two different concentrations i-e 25 nM and 250 nM. No cytotoxicity (viability ∼ 100%) was observed for different treatment arms either alone or in co-delivery of nano-formulation for Rhabdomyosarcoma (RD) cell culture which showed the biocompatibility of carrier. On comparison, the Photodynamic therapy (PDT) alone showed more significant cell death then the combinational therapy (PDT + chemotherapy) at 2 joule /cm2 and 5 joule /cm2. Lower doses co-delivery showed light dose dependent toxicity to culture i.e., 0% death @ 2 joule /cm2, ∼ 40% death @ 5 joule /cm2. Gene expressions of four apoptosis related genes (CASP3, CASP9, PARP1 and P53) were quantified by RT-PCR which shows down regulation for all the treatment arms indicating the absence of apoptosis for the cell death during PDT and combinational therapy. It was concluded that apoptosis related genes were down-regulated and morphological changes i.e., swelling and disruption suggest that the mode of cell death was necrosis.

Molecular detection and prevalence of Theileria ovis and Anaplasma marginale in sheep blood samples collected from Layyah district in Punjab, Pakistan.

Theileria ovis and Anaplasma marginale are intracellular pathogens affecting a wide range of animals, causing huge economic losses worldwide. The present study reports the molecular evidence of Theileria ovis and Anaplasma marginale in sheep blood samples (N = 218) collected from Layyah district in Punjab (Pakistan), where economy heavily relies on livestock. A 520 base pair fragment specific for 18S ribosomal RNA gene of Theileria ovis was PCR amplified in 23/218 (10.6%) sheep blood samples, while for Anaplasma marginale, a 265 base pair fragment specific for msp1b gene was generated in 15/218 (6.9%) sheep blood samples. Two blood samples were found co-infected (0.9%) with both parasites. Amplified PCR products of both parasites were confirmed by DNA sequencing and submitted to GenBank. Prevalence of both Theileria ovis (p = 0.3) and Anaplasma marginale (p = 0.4) varied non-significantly among the investigated sheep breeds. Tick burden on dogs present with sheep herds was found associated with Theileria ovis infection in sheep (p = 0.05). It was observed that lambs (p = 0.009), sheep in small herds (p = 0.04), and tick burden on dogs present with sheep herds (p = 0.01) were associated with Anaplasma marginale infection in sheep during the present study. In conclusion, we are reporting a higher prevalence of Theileria ovis than Anaplasma marginale in blood samples of sheep collected from Layyah district. Tick-infested dogs were found to be risk factors for the transmission of both pathogens in sheep, and tick control strategies should be extended to dogs associated with sheep herds in this area.

Insights Into Mutations Induced Conformational Changes and Rearrangement of Fe2+ Ion in pncA Gene of Mycobacterium tuberculosis to Decipher the Mechanism of Resistance to Pyrazinamide.

Pyrazinamide (PZA) is the first-line drug commonly used in treating Mycobacterium tuberculosis (Mtb) infections and reduces treatment time by 33%. This prodrug is activated and converted to an active form, Pyrazinoic acid (POA), by Pyrazinamidase (PZase) enzyme. Mtb resistance to PZA is the outcome of mutations frequently reported in pncA, rpsA, and panD genes. Among the mentioned genes, pncA mutations contribute to 72-99% of the total resistance to PZA. Thus, considering the vital importance of this gene in PZA resistance, its frequent mutations (D49N, Y64S, W68G, and F94A) were investigated through in-depth computational techniques to put conclusions that might be useful for new scaffolds design or structure optimization to improve the efficacy of the available drugs. Mutants and wild type PZase were used in extensive and long-run molecular dynamics simulations in triplicate to disclose the resistance mechanism induced by the above-mentioned point mutations. Our analysis suggests that these mutations alter the internal dynamics of PZase and hinder the correct orientation of PZA to the enzyme. Consequently, the PZA has a low binding energy score with the mutants compared with the wild type PZase. These mutations were also reported to affect the binding of Fe2+ ion and its coordinated residues. Conformational dynamics also revealed that ß-strand two is flipped, which is significant in Fe2+ binding. MM-GBSA analysis confirmed that these mutations significantly decreased the binding of PZA. In conclusion, these mutations cause conformation alterations and deformities that lead to PZA resistance.