Expanding the neuroimaging findings of guanidinoacetate methyltransferase deficiency in an Iranian girl with a homozygous frameshift variant in the GAMT.

Guanidinoacetate methyltransferase deficiency (GAMTD) is a treatable neurodevelopmental disorder with normal or nonspecific imaging findings. Here, we reported a 14-month-old girl with GAMTD and novel findings on brain magnetic resonance imaging (MRI).A 14-||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||month-old female patient was referred to Myelin Disorders Clinic due to onset of seizures and developmental regression following routine vaccination at 4 months of age. Brain MRI, prior to initiation of treatment, showed high signal intensity in T2-weighted imaging in bilateral thalami, globus pallidus, subthalamic nuclei, substantia nigra, dentate nuclei, central tegmental tracts in the brainstem, and posterior periventricular white matter which was masquerading for mitochondrial leukodystrophy. Basic metabolic tests were normal except for low urine creatinine; however, exome sequencing identified a homozygous frameshift deletion variant [NM_000156: c.491del; (p.Gly164AlafsTer14)] in the GAMT. Biallelic pathogenic or likely pathogenic variants cause GAMTD. We confirmed the homozygous state for this variant in the proband, as well as the heterozygote state in the parents by Sanger sequencing.MRI features in GAMTD can mimic mitochondrial leukodystrophy. Pediatric neurologists should be aware of variable MRI findings in GAMTD since they would be misleading to other diagnoses.

Understanding impact of pre-dissolved polymers on dissolution behavior of soluble carbamazepine cocrystal.

Cocrystallization is a novel approach for tackling the lower solubility concerns when they can yield solution concentration a lot better than their corresponding parent drug in crystalline form. To get the actual solubility and dissolution gains offered by the cocrystals, phase changes in solution (dissolution) has to be interrupted. In current study, we selected commonly used polymers in order to study their effects on the super saturation of carbamezepine-succinic acid (CBZ-SUC) cocrystal during dissolution studies. To observe solid phase changes during dissolution in situ Raman spectroscopy was used. At the completion of each test the solid phase was analyzed by Fourier-transform infrared spectroscopy (FTIR) and powder X-Ray diffractometry. In polymers absence, no dissolution improvement was achieved by the cocrystal owing to its quick transformation to the stable carbamazepine dihydrate (CBZDH). Pre-dissolved PVP at 2% w/v concentration did not inhibit CBZ crystallization as a dihydrate, whereas at 0.025% w/v pre-dissolved hydroxypropyl methyl cellulose acetate succinate (HPMCAS) did stabilize the cocrystal in buffer solution (pH 6.8) for the course of time studied. This cocrystal stabilization resulted in enhanced CBZ solubility ( Ì´ 4fold) caused by cocrystal super saturation state. Seeding of this stable supersaturated state with 1% w/v CBZDH resulted in CBZ crystallization as dihydrate with ultimate loss of solubility advantage.

Evaluation of different Pakistani medicinal plants for inhibitory potential against Echis carinatus induced Phospholipase A2 toxicity.

Medicinal plants of Pakistan are known for their curative properties against snake bite as rural people have been using natural herbs for such injuries for hundreds to thousands of years. People of rural areas of Pakistan are prone to snakebite, and on the whole death due to snakebite has been increasing worldwide. The objective of this study was to test the neutralizing potential of 17 Pakistani medicinal plant extracts against phospholipase A2 activity in Echis carinatus venom. Plant material was extracted by simple maceration and fractionation of active plant extracts. Venom was collected by manual massage of the venom glands. The PLA2 enzymatic assay was performed to map out the venomous activity of Echis carinatus envenomation. Snake venom released fatty acids at different concentrations (0.1-5 mg/ml) of venom in a dose-dependent manner. Reduction of pH by 01 correlated with 133 µmol of fatty acids released at 5mg/ml of venom. All plants extract inhibited PLA2 activity, however, Curcuma longa, Citrullus colocynthis and Rubia cordifolia inhibited maximum of PLA2 activity (⁓78%) comparable to the standard antidote (p>0.5). Medicinal plants possess secondary metabolites and many active compounds that may have neutralizing or inhibiting properties against the PLA2 activity of Echis venom. Further studies such as compound analysis could provide an alternative against snakebites injuries resulting from Echis carinatus venom.

Development and validation of HPLC method for the determination of pioglitazone in human plasma.

Pioglitazone is widely used for the management of type-II diabetes mellitus. The objective of the present study was to develop a simple and cost-effective HPLC method for the quantification of pioglitazone in human plasma. The mobile phase comprises of Acetonitrile, 0.1 M ammonium acetate and glacial acetic acid (25:25:1 v/v/v) at a flow rate of 1.2 mL/min., using Macherey-Nagel Column C18, (dimensions: 5 µm; 250 × 4.6mm) with a guard column. The UV detector was set at 269nm. The method was validated according to FDA guidelines. The present method showed good linearity (R2=0.9998) from 0.1 to 2.0µg/ml standards, with a limit of detection 0.1 µg/ml. Intra-day accuracy and precision in terms of %CV (range: 93.33% to 100.4% and 3.8% to 9.2%) and interday accuracy and precision (range: 94.1% to 102.7% and 4.8% to 9.6%) were in agreement with FDA guidelines. Freeze thaw stability showed that the plasma samples could be stored for one month at -20oC without any appreciable degradation. The present method was successfully applied to the blood samples obtained from one volunteer after oral administration of 30 mg pioglitazone tablet. Some preliminary pharmacokinetic parameters were calculated. It is concluded that the present method could be conveniently used for the routine analysis of pioglitazone blood samples obtained in pharmacokinetics studies.

Development of quality standard and phytochemical analysis of Carica papaya Linn leaves.

Carica papaya Linn is the member of Caricaceae family of Kingdom Plantae. The study was executed for the development of qualitative standards of male and female leaves of the plant. The study included evaluation of macroscopial, physico-chemical and preliminary phytochemical parameters to authorize the purity and authenticity of leaf of Carica papaya Linn based on guidelines provided by WHO. Qualitative phytochemical screening of extracts revealed the existence of alkaloids, flavonoids, tannins, phenolic compounds, glycosides including cardiac glycosides, proteins and carbohydrate in different extracts of Carica papaya Linn which are majorly rich in female leaves as compared to male. Mean ash values, acid insoluble ash, water soluble ash, foaming index, swelling index and moisture contents were also evaluated which are more or less similar. FTIR profile of the samples were also generated that confirmed distinct peak values with respective functional groups exhibited by Carica papaya male and female plant. The current research reflected that female and male plant showed variations in phyto-constituents. This data will be utilized for additional Pharmacological and Instrumental evaluation of the plant which can not only be beneficial in discriminating and refining the type as well as nature of various phytochemicals present in Carica papaya male and female leaves but also establish the quality standards for future researches.

MicroRNA-196a as a Potential Diagnostic Biomarker for Esophageal Squamous Cell Carcinoma.

We observed significant up-regulation of miR-196a in esophageal squamous cell carcinoma (ESCC) as compared with their adjacent normal tissue (p = .002). Receiver operating characteristics curve analysis confirmed the suitability of miR-196a as a potential tumor marker for diagnosis of ESCC. Furthermore, analysis of miR-196a levels in saliva samples determined an average of 27-fold up-regulations in ESCC patients compared with healthy group. Our results suggest that salivary miR-196a may be a suitable noninvasive biomarker for diagnosis of ESCC. In addition, molecular pathway enrichment analysis of microRNA (miR)-196a determined focal adhesion, spliceosome and p53 signaling pathways as the most relevant pathways with miR-196a targetome.

Fucoidan improves bioactivity and vasculogenic potential of mesenchymal stem cells in murine hind limb ischemia associated with chronic kidney disease.

Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-based therapy is a promising strategy for treatment of ischemic diseases associated with CKD, the associated pathophysiological conditions lead to low survival and proliferation of transplanted MSCs. To address these limitations, we investigated the effects of fucoidan, a sulfated polysaccharide, on the bioactivity of adipose tissue-derived MSCs and the potential of fucoidan-treated MSCs to improve neovascularization in ischemic tissues of CKD mice. Treatment of MSCs with fucoidan increased their proliferative potential and the expression of cell cycle-associated proteins, such as cyclin E, cyclin dependent kinase (CDK) 2, cyclin D1, and CDK4, via focal adhesion kinase and the phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt axis. Moreover, fucoidan enhanced the immunomodulatory activity of MSCs through the ERK-IDO-1 signal cascade. Fucoidan was found to augment the proliferation, incorporation, and endothelial differentiation of transplanted MSCs at ischemic sites in CKD mice hind limbs. In addition, transplantation of fucoidan-treated MSCs enhanced the ratio of blood flow and limb salvage in CKD mice with hind limb ischemia. To our knowledge, our findings are the first to reveal that fucoidan enhances the bioactivity of MSCs and improves their neovascularization in ischemic injured tissues of CKD. In conclusion, fucoidan-treated MSCs may provide an important pathway toward therapeutic neovascularization in patients with CKD.

Report on immediate irradiation of a rapidly growing sarcoma of the scalp prior to wound closure.

Cutaneous sarcomas are primarily treated with extensive surgery, and occasionally require adjuvant radiation therapy following complete wound healing. Thus, sarcoma surgery leads to large and deep wounds, and the initiation of adjuvant radiation therapy depends on the time required for defect closure. We present the case of a male patient with pleomorphic sarcoma of the temporal skin, which was treated with multiple wide and deep excisions, instant application of an Integra(®) bilayer, and immediate radiation therapy prior to wound closure. The objective was to investigate the usefulness of a dermal substitute (Integra(®) ) in accelerating the effect of adjuvant radiation therapy on scalp defects after tumor surgery. A ring-shaped skin area - at risk for recurrence - around the Integra(®) bilayer was irradiated with a total of 59.4 Gy. No necrosis, infection, or major radiotoxicity was observed, and a subsequent split skin graft following radiation therapy remained fully vital until complete healing. In conclusion, a combined procedure consisting of sequential tumor surgery and subsequent application of a dermal substitute in conjunction with immediate initiation of adjuvant radiation therapy is, in principle, possible, and may permit innovative therapeutic options in dermatooncology and dermatosurgery.

Gastric perforation without generalized peritonitis; A very rare complication after necrosectomy for necrotizing pancreatitis.

Gastric perforation is a very rare complication of necrotizing pancreatitis. We present an interesting case of gastric perforation after necrosectomy for necrotizing pancreatitis without generalized peritonitis. Abdominal drain was seen inside the stomach on endoscopy and there were no clinical features of generalized peritonitis even after 10 days of surgery. Patient was re-explored. The drain was removed and stomach was primarily repaired. The patient recovered uneventfully and was discharged home on 6(th) post operative day. On follow-up visit after one month patient was doing very well and had no complications.

CACTUSS: Common Anatomical CT-US Space for US examinations.

PURPOSE: The detection and treatment of abdominal aortic aneurysm (AAA), a vascular disorder with life-threatening consequences, is challenging due to its lack of symptoms until it reaches a critical size. Abdominal ultrasound (US) is utilized for diagnosis; however, its inherent low image quality and reliance on operator expertise make computed tomography (CT) the preferred choice for monitoring and treatment. Moreover, CT datasets have been effectively used for training deep neural networks for aorta segmentation. In this work, we demonstrate how leveraging CT labels can be used to improve segmentation in ultrasound and hence save manual annotations. METHODS: We introduce CACTUSS: a common anatomical CT-US space that inherits properties from both CT and ultrasound modalities to produce an image in intermediate representation (IR) space. CACTUSS acts as a virtual third modality between CT and US to address the scarcity of annotated ultrasound training data. The generation of IR images is facilitated by re-parametrizing a physics-based US simulator. In CACTUSS we use IR images as training data for ultrasound segmentation, eliminating the need for manual labeling. In addition, an image-to-image translation network is employed for the model's application on real B-modes. RESULTS: The model's performance is evaluated quantitatively for the task of aorta segmentation by comparison against a fully supervised method in terms of Dice Score and diagnostic metrics. CACTUSS outperforms the fully supervised network in segmentation and meets clinical requirements for AAA screening and diagnosis. CONCLUSION: CACTUSS provides a promising approach to improve US segmentation accuracy by leveraging CT labels, reducing the need for manual annotations. We generate IRs that inherit properties from both modalities while preserving the anatomical structure and are optimized for the task of aorta segmentation. Future work involves integrating CACTUSS into robotic ultrasound platforms for automated screening and conducting clinical feasibility studies.

Anatomy-aware computed tomography-to-ultrasound spine registration.

BACKGROUND: Ultrasound (US) has demonstrated to be an effective guidance technique for lumbar spine injections, enabling precise needle placement without exposing the surgeon or the patient to ionizing radiation. However, noise and acoustic shadowing artifacts make US data interpretation challenging. To mitigate these problems, many authors suggested using computed tomography (CT)-to-US registration to align the spine in pre-operative CT to intra-operative US data, thus providing localization of spinal landmarks. PURPOSE: In this paper, we propose a deep learning (DL) pipeline for CT-to-US registration and address the problem of a need for annotated medical data for network training. Firstly, we design a data generation method to generate paired CT-US data where the spine is deformed in a physically consistent manner. Secondly, we train a point cloud (PC) registration network using anatomy-aware losses to enforce anatomically consistent predictions. METHODS: Our proposed pipeline relies on training the network on realistic generated data. In our data generation method, we model the properties of the joints and disks between vertebrae based on biomechanical measurements in previous studies. We simulate the supine and prone position deformation by applying forces on the spine models. We choose the spine models from 35 patients in VerSe dataset. Each spine is deformed 10 times to create a noise-free data with ground-truth segmentation at hand. In our experiments, we use one-leave-out cross-validation strategy to measure the performance and the stability of the proposed method. For each experiment, we choose generated PCs from three spines as the test set. From the remaining, data from 3 spines act as the validation set and we use the rest of the data for training the algorithm. To train our network, we introduce anatomy-aware losses and constraints on the movement to match the physics of the spine, namely, rigidity loss and bio-mechanical loss. We define rigidity loss based on the fact that each vertebra can only transform rigidly while the disks and the surrounding tissue are deformable. Second, by using bio-mechanical loss we stop the network from inferring extreme movements by penalizing the force needed to get to a certain pose. RESULTS: To validate the effectiveness of our fully automated data generation pipeline, we qualitatively assess the fidelity of the generated data. This assessment involves verifying the realism of the spinal deformation and subsequently confirming the plausibility of the simulated ultrasound images. Next, we demonstrate that the introduction of the anatomy-aware losses brings us closer to state-of-the-art (SOTA) and yields a reduction of 0.25 mm in terms of target registration error (TRE) compared to using only mean squared error (MSE) loss on the generated dataset. Furthermore, by using the proposed losses, the rigidity loss in inference decreases which shows that the inferred deformation respects the rigidity of the vertebrae and only introduces deformations in the soft tissue area to compensate the difference to the target PC. We also show that our results are close to the SOTA for the simulated US dataset with TRE of 3.89 mm and 3.63 mm for the proposed method and SOTA respectively. In addition, we show that our method is more robust against errors in the initialization in comparison to SOTA and significantly achieves better results (TRE of 4.88 mm compared to 5.66 mm) in this experiment. CONCLUSIONS: In conclusion, we present a pipeline for spine CT-to-US registration and explore the potential benefits of utilizing anatomy-aware losses to enhance registration results. Additionally, we propose a fully automatic method to synthesize paired CT-US data with physically consistent deformations, which offers the opportunity to generate extensive datasets for network training. The generated dataset and the source code for data generation and registration pipeline can be accessed via https://github.com/mfazampour/medphys_ct_us_registration.

Shape completion in the dark: completing vertebrae morphology from 3D ultrasound.

PURPOSE: Ultrasound (US) imaging, while advantageous for its radiation-free nature, is challenging to interpret due to only partially visible organs and a lack of complete 3D information. While performing US-based diagnosis or investigation, medical professionals therefore create a mental map of the 3D anatomy. In this work, we aim to replicate this process and enhance the visual representation of anatomical structures. METHODS: We introduce a point cloud-based probabilistic deep learning (DL) method to complete occluded anatomical structures through 3D shape completion and choose US-based spine examinations as our application. To enable training, we generate synthetic 3D representations of partially occluded spinal views by mimicking US physics and accounting for inherent artifacts. RESULTS: The proposed model performs consistently on synthetic and patient data, with mean and median differences of 2.02 and 0.03 in Chamfer Distance (CD), respectively. Our ablation study demonstrates the importance of US physics-based data generation, reflected in the large mean and median difference of 11.8 CD and 9.55 CD, respectively. Additionally, we demonstrate that anatomical landmarks, such as the spinous process (with reconstruction CD of 4.73) and the facet joints (mean distance to ground truth (GT) of 4.96 mm), are preserved in the 3D completion. CONCLUSION: Our work establishes the feasibility of 3D shape completion for lumbar vertebrae, ensuring the preservation of level-wise characteristics and successful generalization from synthetic to real data. The incorporation of US physics contributes to more accurate patient data completions. Notably, our method preserves essential anatomical landmarks and reconstructs crucial injections sites at their correct locations.

Persistent basal ganglia involvement in aminoacylase-1 deficiency: expanding imaging findings and review of literature.

BACKGROUND: Aminoacylase-1 deficiency (ACY1D) is an autosomal recessive rare inborn error of metabolism, which is caused by disease-causing variants in the ACY1. This disorder is characterized by increased urinary excretion of specific N-acetyl amino acids. Affected individuals demonstrate heterogeneous clinical manifestations which are primarily neurologic problems. In neuroimaging, corpus callosum hypoplasia, cerebellar vermis atrophy, and delayed myelination of cerebral white matter have been reported. AIMS: Finding disease-causing variant and expanding imaging findings in a patient with persistent basal ganglia involvement. METHODS: Whole-exome sequencing was performed in order to identify disease-causing variants in an affected 5-year-old male patient who presented with neurologic regression superimposed on neurodevelopmental delay following a febrile illness. He had inability to walk, cognitive impairment, speech delay, febrile-induced seizures, truncal hypotonia, moderate to severe generalized dystonia, and recurrent metabolic decompensation. RESULTS: All metabolic tests were normal except for a moderate metabolic acidosis following febrile illnesses. The results of serial brain magnetic resonance imaging (MRI) at ages 1 and 4.5 years revealed persistent bilateral and symmetric abnormal signals in basal ganglia mainly caudate and globus pallidus nuclei with progression over time in addition to a mild supratentorial atrophy. A homozygous missense variant [NM_000666.3: c.1057C>T; p.(Arg353Cys)] was identified in the ACY1, consistent with aminoacylase-1 deficiency. Variant confirmation in patient and segregation analysis in his family were performed using Sanger sequencing. CONCLUSIONS: Our findings expanded the phenotype spectrum of ACY1-related neurodegeneration by demonstrating persistent basal ganglia involvement and moderate to severe generalized dystonia.

Multitask Weakly Supervised Generative Network for MR-US Registration.

Registering pre-operative modalities, such as magnetic resonance imaging or computed tomography, to ultrasound images is crucial for guiding clinicians during surgeries and biopsies. Recently, deep-learning approaches have been proposed to increase the speed and accuracy of this registration problem. However, all of these approaches need expensive supervision from the ultrasound domain. In this work, we propose a multitask generative framework that needs weak supervision only from the pre-operative imaging domain during training. To perform a deformable registration, the proposed framework translates a magnetic resonance image to the ultrasound domain while preserving the structural content. To demonstrate the efficacy of the proposed method, we tackle the registration problem of pre-operative 3D MR to transrectal ultrasonography images as necessary for targeted prostate biopsies. We use an in-house dataset of 600 patients, divided into 540 for training, 30 for validation, and the remaining for testing. An expert manually segmented the prostate in both modalities for validation and test sets to assess the performance of our framework. The proposed framework achieves a 3.58 mm target registration error on the expert-selected landmarks, 89.2% in the Dice score, and 1.81 mm 95th percentile Hausdorff distance on the prostate masks in the test set. Our experiments demonstrate that the proposed generative model successfully translates magnetic resonance images into the ultrasound domain. The translated image contains the structural content and fine details due to an ultrasound-specific two-path design of the generative model. The proposed framework enables training learning-based registration methods while only weak supervision from the pre-operative domain is available.

Comparison of the cytoplasmic and periplasmic production of reteplase in Escherichia coli.

Reteplase is the recombinant type of tissue plasminogen activator variant. In this study, preplasmic and cytoplasmic (as inclusion body: IBs) production and activity of recombinant reteplase in E. coli were investigated and compared using a pET system (pET22b and pET15b). The cDNA of reteplase was cloned by polymerase chain reaction (PCR) amplification, sequenced, inserted into the vector pET 22b and pET15b, and expressed using isopropyl ß-D-1-thiogalactopyranoside (IPTG). The recombinant plasmid was expressed in the form of inclusion body in pET 15b and in periplasmic space in pET22b. The obtained results of inclusion body extraction from recombinant pET22b (rpET22b) and recombinant pET15b (rpET15b) plasmids using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed a band of ~39 kD. However, the obtained results of periplasmic space extraction from rpET22b plasmid showed a very weak band, while cytoplasmic expression of reteplase (pET15b) produced a strong protein band confirmed with Western blotting. Consequently, our results demonstrated that the cytoplasmic expression system is efficient for the production of reteplase protein in prokaryote systems and a high amount of reteplase was obtained from the expressed proteins in the form of IBs. The obtained activity of rpET15b plasmid showed a higher enzyme absorbance in comparison to rpET22b plasmid. This suggests rpET15b as an appropriate candidate for reteplase production.

The association between leisure-time physical activity and blood pressure changes from adolescence to young adulthood: Tehran Lipid and Glucose Study.

The effectiveness of long-term leisure time physical activity (LTPA) on blood pressure (BP) changes is still under debate. Since adolescence lifestyle behaviors shape the adulthood health profile, this study aimed to investigate the sex-specific impact of LTPA on BP changes from adolescence to young adulthood. This longitudinal study uses the data of 1412 adolescents (52% females) aged 12-18 years through a median follow-up of 12.2 years in the Tehran Lipid and Glucose Study (TLGS) framework. LTPA was calculated using the reliable and valid Iranian version of the modified activity scale (MAQ), and BP was measured at least twice by trained physicians. The linear mixed model was used to examine the study variables, considering individual and intrapersonal differences during the study. The majority of participants consistently demonstrated insufficient LTPA throughout the follow-up assessments, ranging from 54.7 to 67.1% for males and 77.7-83.4% for females. Despite a declining trend in LTPA (ß = - 2.77 for males and ß = - 1.43 for females), an increasing trend was noticeable in SBP, DBP, and BMI (ß = 1.38, ß = 1.81, ß = 0.97 for males, and ß = 0.10, ß = 0.20, ß = 0.97 for females, respectively). The unadjusted model revealed a significant trend in all variables for both sexes, except for female BP (P = 0.45 for SBP and P = 0.83 for DBP). Using the adjusted model, no significant association was observed between LTPA and changes in BP over time in both sexes. Our study indicates no association between LTPA and BP changes from adolescence to young adulthood. Insufficient LTPA levels, particularly among Iranian females, are likely the primary factor. Further research is crucial to identify appropriate LTPA levels to promote cardiovascular health and implement targeted interventions to achieve optimal LTPA levels in the Iranian population.

Expression assay of the COLQ in a family with congenital myasthenic syndrome and symptomatic carriers.

Congenital myasthenic syndromes-5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease-causing variants in the collagen-like tail subunit are the most explained etiology in synaptic CMS, causing defected acetylcholinesterase. In this study whole-exome sequencing (WES) was performed in an affected boy with muscle weakness, ophthalmoplegia, and bilateral ptosis and gene expression assay by qRT-PCR was performed in entire family. A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. Segregation analysis by Sanger sequencing confirmed the homozygous state in the proband and heterozygous state in his parents and four of the siblings. The mRNA expression level in the proband was 0.02 of a healthy person, and in the carriers were 0.42 of a healthy person. This study presents an Iranian family with two affected children and eight symptomatic carriers with attenuated mRNA expression. This study provides evidence that carriers of the COLQ disease-causing variants could become symptomatic with some yet unknown pathogenesis mechanism and underscore the importance of further investigations to elucidate this mechanism.

Double-Expressor Appendiceal Burkitt's Lymphoma: A Case Report and Literature Review.

Background: Appendiceal lymphoma is a very rare entity accounting for 0.015% of all gastrointestinal lymphoma cases. Acute appendicitis is the most common presentation of primary appendix neoplasms. Burkitt's lymphoma presenting as an acute appendicitis is a rare entity with around 21% of the cases presenting as a lower iliac fossa mass. Case Presentation. A 23-year-old male was admitted to the surgical ward as a case of acute appendicitis with localized tenderness in the right iliac fossa, positive rebound tenderness, a positive Rovsing's sign, and ultrasound findings of suspected complicated appendicitis. Appendectomy was performed. Histopathological examination of the appendectomy specimen revealed a double-expressor non-Hodgkin diffuse large cell lymphoma with Burkitt's-like morphology. He was sent for chemotherapy treatment. Conclusion: Only 34 cases of Burkitt's lymphoma have been reported to present as acute appendicitis. Histological examination following appendectomy for an apparent appendicitis is essential. Furthermore, complete blood count and a computed tomography scan aid the diagnosis of lymphoma. Double-expressor lymphoma has been shown to have poor outcomes. Therefore, prompt and aggressive treatment is vital.

Genetic Analysis of Forty MLPA-Negative Duchenne Muscular Dystrophy Patients by Whole-Exome Sequencing.

This manuscript aimed to determine the underlying point mutations causing Duchenne muscular dystrophy (DMD) in a heterogeneous group of Iranian patients, who are clinically suspected. Whole-exome sequencing was utilized to detect disease-causing variants in 40 MLPA-negative DMD patients. Disease-causing variants were detected in the DMD gene in 36/40 of the patients (90%), and 4/40 of them (10%) remained undiagnosed. WES analysis revealed that nonsense variant was the most common type in our study (23/36 of the cases). Besides, 12/36 of the cases had frameshift variant, and one of the patients had a likely pathogenic splice variant in the DMD gene. Carrier testing revealed that 21/40 of the mothers had the identified variant. Therefore, most variants were inherited (58.3%), while 19/40 were de novo (41. 7%). The present study has demonstrated the importance of performing WES to detect disease-causing point mutations in MLPA-negative DMD patients and to identify carrier females. Due to regulatory challenges, the clinical development of therapeutic approaches is time-consuming and may not be available to all patients shortly. Therefore, it appears that the techniques used to accurately detect disease-causing variants in carrier mothers are a more efficient solution to prevent the increased prevalence of DMD.

A lightweight neural network with multiscale feature enhancement for liver CT segmentation.

Segmentation of abdominal Computed Tomography (CT) scan is essential for analyzing, diagnosing, and treating visceral organ diseases (e.g., hepatocellular carcinoma). This paper proposes a novel neural network (Res-PAC-UNet) that employs a fixed-width residual UNet backbone and Pyramid Atrous Convolutions, providing a low disk utilization method for precise liver CT segmentation. The proposed network is trained on medical segmentation decathlon dataset using a modified surface loss function. Additionally, we evaluate its quantitative and qualitative performance; the Res16-PAC-UNet achieves a Dice coefficient of 0.950 ± 0.019 with less than half a million parameters. Alternatively, the Res32-PAC-UNet obtains a Dice coefficient of 0.958 ± 0.015 with an acceptable parameter count of approximately 1.2 million.