Bosnian Journal of Basic Medical Sciences <p>The BJBMS (Bosnian Journal of Basic Medical Sciences) is а premier venue for discoveries in basic and clinical biomedical science. The BJBMS was founded in 1998 and is published by the Association of Basic Medical Sciences, a nonprofit honor organization of physician-scientists.</p> <p>Broad readership and scope. The BJBMS reaches readers across a wide range of medical disciplines and sectors. The journal publishes basic and translational/clinical research submissions and reviews in all biomedical specialties, including Genetics and Molecular biology, Immunology, Microbiology, Pathology, Biochemistry, Pharmacology, Anatomy, Biomaterials, new and emerging research and diagnostic methods, new and emerging medical entities, and others.</p> Association of Basic Medical Sciences of FBIH en-US Bosnian Journal of Basic Medical Sciences 1512-8601 Microsurgical resection of giant T11/T12 conus cauda equina schwannoma <p>In this video, we highlight the anatomy involved with microsurgical resection of a giant T11/T12 conus cauda equina schwannoma. Spinal schwannoma remains the third most common intradural spinal tumor. Tumors undergoing gross total resection usually do not recur. To our knowledge, this is the first video case report of giant cauda equina schwannoma resection. A 55-year-old female presented with paraparesis and urinary retention. Lumbar spine MRI revealed a contrast-enhancing intradural extramedullary tumor at the T11/T12 level. Surgery was performed in the prone position with intraoperative neurophysiology monitoring (somatosensory and motor evoked potentials—SSEPs and MEPs). T11/T12 laminectomies were performed. After opening the dura and arachnoid, the tumor was found covered with cauda equina nerve roots. We delineated the inferior pole of the tumor, followed by opening of the capsule and debulking the tumor. Subsequently, the cranial pole was dissected from the corresponding cauda equina nerve roots. Finally, the tumor nerve origin was identified and divided after nerve stimulation confirmed the tumor arose from a sensory nerve root. The tumor was removed; histological analysis revealed a schwannoma (WHO Grade I). Postoperative MRI revealed complete resection. The patient fully recovered her neurological function. This case highlights the importance of careful microsurgical technique and gross total resection of the tumor in the view of favorable postoperative neurological recovery of the patient. Intraoperative use of ultrasound is helpful to delineate preoperatively tumor extension and confirm postoperative tumor resection.</p> Alisa Arnautovic Mirza Pojskic Kenan Arnautovic Copyright (c) 2020 Alisa Arnautovic, Mirza Pojskic, Kenan Arnautovic 2021-08-01 2021-08-01 21 4 383 385 10.17305/bjbms.2020.5153 Tranexamic acid is associated with decreased transfusion, hospital length of stay, and hospital cost in simultaneous bilateral total knee arthroplasty <p>Tranexamic acid (TXA) reduces blood loss and transfusion rates in unilateral total knee arthroplasty (TKA), but there is limited data regarding its efficacy in bilateral TKA. This study reports the impact TXA has on clinical outcomes and hospital cost of care in simultaneous, primary bilateral TKA. The 449 patients were retrospectively reviewed. Primary outcomes included the rates of allogeneic and autologous blood transfusion. Secondary outcomes included hospital length of stay (HLOS), post-hospital discharge disposition, 30-day thromboembolic events (TEE), and mean hospital cost of care. Total direct medical costs were obtained from an institutional research database and adjusted to nationally representative unit costs in 2013 inflation-adjusted dollars. Our study revealed that in patients undergoing simultaneous bilateral TKA, TXA use was associated with reduced allogeneic (OR 0.181, 95% CI 0.090-0.366, <em>p </em>&lt; 0.001) and combined allogeneic and autologous transfusion rates (OR 0.451, 95% CI 0.235-0.865, <em>p </em>= 0.017). TXA was associated with a HLOS reduction of 0.9 days (β-coefficient −0.582, 95% CI −1.008-−0.156, <em>p </em>= 0.008), an increased likelihood of hospital discharge over skilled nursing facility (SNF) (OR 2.25, 95% CI 1.117-4.531, <em>p</em> = 0.023) and reduced total hospital cost of care by 6.45% (<em>p </em>&lt; 0.001), room and board costs by 11.76% (<em>p </em>&lt; 0.001), and transfusion costs by 81.65% (<em>p </em>&lt; 0.001). In conclusion, TXA use in bilateral TKA is associated with lower blood transfusion rates, reduced hospital length of stay, reduced cost of hospital care and skilled nursing facility avoidance.</p> Ryan D'Souza Christopher Duncan Daniel Whiting Michael Brown Matthew Warner Hugh Smith Hilal Kremers Thomas Stewart Copyright (c) 2020 Ryan D'Souza, Christopher Duncan, Daniel Whiting, Michael Brown, Matthew Warner, Hugh Smith, Hilal Kremers, Thomas Stewart 2021-08-01 2021-08-01 21 4 471 476 10.17305/bjbms.2020.5060 Can NLR, PLR and LMR be used as prognostic indicators in patients with pulmonary embolism? A commentary <p>We read with great interest the article “Prognostic role of NLR, PLR, and LMR in patients with pulmonary embolism” by Köse et al.[1]. They found that the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were related to the prognosis and clinical severity of patients with pulmonary embolism (PE). First of all, we congratulate the authors for their invaluable contribution to literature. However, we think that some points should be discussed regarding the use of these laboratory parameters.</p> <p>White blood cell subtypes NLR, PLR, and LMR, have been associated with many inflammatory diseases, including PE [2,3]. These parameters, which can be easily determined by simple and easy measurement of systemic inflammation, maintain their importance today. However, these parameters are affected by many factors such as trauma, local or systemic infection, acute coronary syndromes, and malignancy [3-5]. For these reasons, it would be better for the authors to mention these factors and exclude them from the tables that included malignancy and trauma patients in the study.</p> <p>It is known that drugs, including steroids, can increase neutrophils and decrease lymphocytes and therefore affect NLR, PLR, and LMR values [6]. Consequently, it will be more valuable to exclude patients who use drugs that may affect laboratory parameters. Besides, plasma inflammatory biomarkers are time-dependent variables. The time of sample collection and the time from the onset of the symptom to the sampling may impact the parameters [3-6]. Therefore, it is essential to identify the time from the first symptom to sample collection and the factors that may affect it. In conclusion, because NLR, PLR, and LMR can be affected by many factors, prospective studies with large populations are needed to show the accuracy of use in critically ill patients.</p> Cihan Bedel Mustafa Korkut Hamit Hakan Armağan Copyright (c) 2020 Cihan Bedel, Mustafa Korkut, Hamit Hakan Armağan 2021-08-01 2021-08-01 21 4 501 501 10.17305/bjbms.2020.5236 Can NLR, PLR and LMR be used as prognostic indicators in patients with pulmonary embolism? Author’s reply on commentary <p>We appreciate the comments made by Dr Bedel and colleagues. NLR, PLR and LMR are affected by various diseases such as oncological, collagen tissue, inflammatory, or severe renal/liver diseases [1]. Because of this, we have listed some of the above-mentioned disorders in the tables. Hematological diseases, collagen tissue disease, inflammatory diseases, congenital heart disease, or severe renal/liver disease were therefore excluded from the study. However, the presence of malignancy did not affect our results in regression analysis.<br>Platelets swell until 120 minutes in ethylene diamine tetra acetic (EDTA) and until 60 minutes in citrate [2]. Authors suggest that optimal measuring time should not exceed 120 minutes. The blood samples of the patients were taken within 1 hour after their emergency admission. All blood samples in our study were tested within 1 hour of collection [3]. We used EDTA for whole blood anticoagulation. The mean duration of symptoms prior to admission was 5.04 ± 6.9 days. <br>The drugs such as corticosteroids affect inflammatory parameters. Therefore, we excluded inflammatory diseases without emphasizing corticosteroids or other anti-inflammatory drugs.</p> Nuri Kose Tarık Yıldırım Fatih Akın Seda Elçim Yıldırım Ibrahim Altun Copyright (c) 2020 Nuri Kose, Tarık Yıldırım, Fatih Akın, Seda Elçim Yıldırım, Ibrahim Altun 2021-08-01 2021-08-01 21 4 502 502 10.17305/bjbms.2020.5292 Epigenetically inactivated RASSF1A as a tumor biomarker <p><em>RASSF1A,</em> one of the eight isoforms of the <em>RASSF1</em> gene, is a tumor suppressor gene that influences tumor initiation and development. In cancer, <em>RASSF1A</em> is frequently inactivated by mutations, loss of heterozygosity, and, most commonly, by promoter hypermethylation. Epigenetic inactivation of <em>RASSF1A</em> was detected in various cancer types and led to significant interest; current research on <em>RASSF1A</em> promoter methylation focuses on its roles as an epigenetic tumor biomarker. Typically, researchers analyzed genomic DNA (gDNA) to measure the amount of <em>RASSF1A </em>promoter methylation. Cell-free DNA (cfDNA) from liquid biopsies is a recent development showing promise as an early cancer diagnostic tool using biomarkers, such as <em>RASSF1A</em>. This review discusses the evidence on aberrantly methylated <em>RASSF1A</em> in gDNA and cfDNA from different cancer types and its utility for early cancer diagnosis, prognosis, and surveillance. We compared methylation frequencies of <em>RASSF1A</em> in gDNA and cfDNA in various cancer types. The weaknesses and strengths of these analyses are discussed. In conclusion, although the importance of <em>RASSSF1A</em> methylation to cancer has been established is included in several diagnostic panels, its diagnostic utility is still experimental.</p> Dora Raos Monika Ulamec Ana Katusic Bojanac Floriana Bulic-Jakus Davor Jezek Nino Sincic Copyright (c) 2021 Dora Raos, Monika Ulamec, Ana Katusic Bojanac, Floriana Bulic-Jakus, Davor Jezek, Nino Sincic 2021-08-01 2021-08-01 21 4 386 397 10.17305/bjbms.2020.5219 Stomach-specific c-Myc overexpression drives gastric adenoma in mice through AKT/mammalian target of rapamycin signaling <p>Gastric cancer (GC) is one of the most common malignant cancers in the world.<em> c-Myc</em>, a well-known oncogene, is commonly amplified in many cancers, including gastric cancer. However, it is still not completely understood how<em> c-Myc</em> functions in GC. Here, we generated a stomach-specific <em>c-Myc</em> transgenic mouse model to investigate its role in GC. We found that overexpression of <em>c-Myc </em>in <em>Atp4b<sup>+</sup></em> gastric parietal cells could induce gastric adenoma in mice. Mechanistically, <em>c-Myc</em> promoted tumorigenesis via the AKT/mTOR pathway. Furthermore, AKT inhibitor (MK-2206) or mTOR inhibitor (Rapamycin) inhibited the proliferation of <em>c-Myc</em> overexpressing gastric cancer cell lines. Thus, our findings highlight that gastric tumorigenesis can be induced by <em>c-Myc</em> overexpression through activation of the AKT/mTOR pathway.</p> Jing Liu Wenxin Feng Min Liu Hanyu Rao Xiaoxue Li Yan Teng Xiao Yang Jin Xu Weiqiang Gao Li Li Copyright (c) 2020 Jing Liu, Wenxin Feng, Min Liu, Hanyu Rao, Xiaoxue Li, Yan Teng, Xiao Yang, Jin Xu, Weiqiang Gao, Li Li 2021-08-01 2021-08-01 21 4 434 446 10.17305/bjbms.2020.4978 Accelerated atherosclerosis in premenopausal women with rheumatoid arthritis – 15-year follow-up <p>Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased mortality and morbidity due to the higher cardiovascular risk in these patients. Traditional risk factors are not the only answer for the accelerated atherosclerosis. In a long-term prospective study, we investigated the relationship between asymptomatic atherosclerosis and traditional risk factors and inflammatory markers in patients with RA and matched healthy controls. We studied the laboratory test results, the concentrations of inflammatory mediators, matrix metalloproteases (MMP), and inflammation markers in a total of 70 (60 at follow-up) premenopausal healthy women with RA and 40 (34 at follow-up) matched controls. We used the B-mode ultrasound imaging of carotid arteries for the detection of asymptomatic atherosclerosis. Correlation with different factors was evaluated. Statistically significant higher values of inflammatory markers such as selective adhesion molecules ICAM and VCAM, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and MMP-3 in the patients group were found in the follow-up study. More plaques were found in the patients group (42.4% vs. 12.9%; <em>p</em>=0.005), as compared with the controls group. The patients had also higher values of cIMT (<em>p</em>=0.001). Using bivariate regression analysis only VCAM was found as a prognostic factor for plaque occurrence (r= 0. 341, <em>p</em>=0.016), but not for cIMT (r= -0.130, <em>p</em>=0.327) in premenopausal female patients with RA after the follow-up. Therefore, asymptomatic atherosclerosis is accelerated in premenopausal women with RA. The results of our follow-up study showed the association between inflammation and accelerated atherosclerosis. Furthermore, VCAM was found to have a statistically significant correlation with plaque occurrence in these patients.&nbsp;</p> Metka Koren Krajnc Radovan Hojs Iztok Holc Željko Knez Artur Pahor Copyright (c) 2020 Metka Koren Krajnc, Radovan Hojs, Iztok Holc, Željko Knez, Artur Pahor 2021-08-01 2021-08-01 21 4 477 483 10.17305/bjbms.2020.5176 The association between serine hydroxymethyl transferase 1 gene hypermethylation and ischemic stroke <p>This study aimed to determine the correlation between serine hydroxymethyl transferase 1 (<em>SHMT1</em>) gene methylation and ischemic stroke. A total of 202 age- and sex-matched individuals were included. Quantitative methylation-specific polymerase chain reaction (qMSP-PCR) was used to analyze the DNA methylation level. The plasma homocysteine (Hcy) concentration was much higher in ischemic cases than in controls (<em>p</em> = 0.009), while the high-density lipoprotein (HDL) levels in stroke cases were considerably lower than in controls (<em>p</em> = 0.005). A significantly higher level of <em>SHMT1</em> methylation was observed in the ischemic strokes (58.82 ± 17.83%) compared to that in the controls (42.59 ± 20.76%, <em>p</em> &lt; 0.001). The <em>SHMT1</em> methylation level was strongly correlated with HDL concentration in the healthy controls (r = 0.517, <em>p</em> &lt; 0.001), while the high plasma level of Hcy showed strong association with <em>SHMT1</em> methylation in ischemic strokes (r = 0.346, <em>p</em> &lt; 0.001). Receiver operating characteristic (ROC) analysis of curve indicated that <em>SHMT1</em> methylation has been an acceptable indicator for ischemic stroke in female patients [all sexes, area under the curve (AUC) = 0.71, <em>p</em> &lt; 0.001; male patients AUC = 0.62, <em>p</em> = 0.032; and female patients AUC = 0.79, <em>p</em> &lt; 0.001] and in all ages (AUC = 0.71, <em>p</em> &lt; 0.001). In our samples, DNA methylation levels of the <em>STHMI</em> gene were significantly correlated with ischemic stroke in Han Chinese. <em>STHMI</em> hypermethylation was significantly associated with the high Hcy concentration in ischemic stroke and had value as a potential indicator for female ischemic stroke.</p> Junnan Wang Junqing Gu Yi Huang Yuanjian Fang Jinhui Lin Copyright (c) 2020 Junnan Wang, Junqing Gu, Yi Huang, Yuanjian Fang, Jinhui Lin 2021-08-01 2021-08-01 21 4 454 460 10.17305/bjbms.2020.5188 MPTP-induced mouse model of Parkinson’s disease: A promising direction of therapeutic strategies <p>Among the popular animal models of Parkinson’s disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.</p> Musa Mustapha Che Norma Mat Taib Copyright (c) 2021 Che Norma Mat Taib, Musa Mustapha 2021-08-01 2021-08-01 21 4 422 433 10.17305/bjbms.2020.5181 Computed tomography in the diagnosis of intraperitoneal effusions: The role of texture analysis <p>The morphological changes advocating for peritoneal carcinomatosis are inconsistent and may be visible only in later stages of the disease. However, malignant ascites represents an early sign, and this fluid exhibits specific histological characteristics. This study aimed to quantify the fluid properties on computed tomography (CT) images of intraperitoneal effusions through texture analysis and evaluate its utility in differentiating benign and malignant collections. Fifty-two patients with histologically proven benign (n=29) and malignant (n=23) intraperitoneal effusions who underwent CT examinations were retrospectively included. Texture analysis of the fluid component was performed on the non-enhanced phase of each examination using dedicated software. Fisher and the probability of classification error and average correlation coefficients were used to select two sets of ten texture features, whose ability to distinguish between the two types of collections were tested using a k-nearest-neighbor classifier. Also, each of the selected feature’s diagnostic power was assessed using univariate and receiver operating characteristics analysis with the calculation of the area under the curve. The k-nearest-neighbor classifier was able to distinguish between the two entities with 71.15% accuracy, 73.91% sensitivity, and 68.97% specificity. The highest-ranked texture parameter was Inverse Difference Moment (<em>p</em>=0.0023; area under the curve=0.748), based on which malignant collections could be diagnosed with 95.65% sensitivity and 44.83% specificity. Although successful, the texture assessment of benign and malignant collections most likely does not reflect the cytological differences between the two groups.</p> Csaba Csutak Paul-Andrei Ștefan Roxana-Adelina Lupean Lavinia Manuela Lenghel Carmen Mihaela Mihu Andrei Lebovici Copyright (c) 2020 Csaba Csutak, Paul-Andrei Ștefan, Roxana-Adelina Lupean, Lavinia Manuela Lenghel, Carmen Mihaela Mihu, Andrei Lebovici 2021-08-01 2021-08-01 21 4 488 494 10.17305/bjbms.2020.5048 Assessment of Wnt pathway selected gene expression levels in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with low bone mass <p>The purpose of the study was to assess the expression of selected genes of the Wnt pathway: <em>APC, AXIN1, CTNNB1, DKK1, GSK3β, KREMEN1, SFRP1, </em>and <em>WNT1</em> in peripheral blood mononuclear cells (PBMC) of patients, selected in consideration of their bone mineral density (BMD), and the occurrence of low-energy fractures. The study involved 45 postmenopausal women, divided into four groups, according to BMD and fracture history. Measurements of laboratory parameters and RNA expression in PBMC cells were carried out in material, collected once at the inclusion visit. The densitometric examination was performed on all participants. In the analysis of the relative expression levels (RELs) of the studied genes in the entire population, we observed an overexpression for SFRP1 in 100% of samples and <em>WNT1</em>. In addition, the REL of <em>DKK1, APC,</em> and <em>GSK3β</em> genes were slightly elevated versus the calibrator. In contrast, <em>CTNNB1</em> and <em>AXIN1</em> presented with a slightly decreased RELs. Analysis did not show any significant differences among the groups in the relative gene expression levels (<em>p </em>&lt; 0.05) of particular genes. However, we have observed quite numerous interesting correlations between the expression of the studied genes and BMD, the presence of fractures, and laboratory parameters, both in the whole studied population as well as in selected groups. In conclusion, the high level of <em>CTNNB1</em> expression maintains normal BMD and/or protects against fractures. It also appears that the changes in expression levels of the Wnt pathway genes in PBMCs reflect the expected changes in bone tissue.</p> Michal Stuss Monika Migdalska-Sek Ewa Brzezianska-Lasota Marta Michalska-Kasiczak Pawel Bazela Ewa Sewerynek Copyright (c) 2020 Michal Stuss, Monika Migdalska-Sęk, Ewa Brzezianska-Lasota, Marta Michalska-Kasiczak, Pawel Bazela, Ewa Sewerynek 2021-08-01 2021-08-01 21 4 461 470 10.17305/bjbms.2020.5179 Dishevelled family proteins (DVL1-3) expression in intrauterine growth restriction (IUGR) placentas <p>Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic proteins that are involved in canonical and non-canonical Wnt signaling pathway during embryonic development. The role of DVL proteins in the placental tissue remains mostly unknown. In the current study, we explored the role of Dishevelled proteins in naturally invasive tissue, trophoblast. Formalin-fixed paraffin-embedded samples of 15 term placentas from physiologic term pregnancies and 15 term placentas from pregnancies complicated with intrauterine growth restrictions (IUGR) were used for the study. Expression levels of mRNA for DVL1, DVL2, and DVL3 in placentas were analyzed by quantitative real-time PCR (qRTPCR). DVL1, DVL2, and DVL3 protein expression were semi-quantitatively analyzed using immunohistochemistry. The expression of DVL2 and DVL3 proteins was significantly higher in trophoblasts in placental villi from IUGR pregnancies compared with the control group of term placentas. In contrast, DVL3 protein expression was significantly higher in endothelial cells in placental villi from IUGR pregnancies compared with normal term placentas. The observed differences at protein levels between normal and IUGR placentas were not confirmed at the mRNA levels of DVL genes. Our data indicate the active involvement of DVL proteins in IUGR-related placentas. No significant changes were observed in DVL mRNA levels between the two groups of placentas. Further studies are required to explore the clinical relevance of these observations.</p> Ida Marija Sola Alan Serman Valentina Karin-Kujundzic Frane Paic Anita Skrtic Paula Slatina Luka Kakarigi Semir Vranic Ljiljana Serman Copyright (c) 2020 Ida Marija Sola, Alan Serman, Valentina Karin-Kujundzic, Frane Paic, Anita Skrtic, Paula Slatina, Luka Kakarigi, Semir Vranic, Ljiljana Serman 2021-08-01 2021-08-01 21 4 447 453 10.17305/bjbms.2020.5422 A novel homozygous exon2 deletion of TRIM32 gene in a Chinese patient with sarcotubular myopathy: A case report and literature review <p>Sarcotubular myopathy (STM) is a rare autosomal recessive myopathy caused by <em>TRIM32</em> gene mutations. It is predominantly characterized by the weakness of the proximal limb and mild to moderate elevation of creatine kinase (CK) levels. In this study, we describe a 50-year-old Chinese man who exhibited a <em>proximal</em>-to-<em>distal</em> weakness in the muscles of the lower limbs and who had difficulty standing up from a squat position. The symptoms gradually became more severe. He denied a history of cognitive or cardiological problems. The patient’s parents and children were healthy. Histopathological examination revealed dystrophic changes and irregular slit-shaped vacuoles containing amorphous materials. Whole-exome sequencing consisting of protein-encoding regions of 19,396 genes was performed, the results of which identified one novel homozygous 2kb deletion chr9.hg19: g.119460021_119461983del (exon2) in the <em>TRIM32 </em>gene. This was confirmed at the homozygous state with quantitative real-time PCR. Here, we present a Chinese case of STM with one novel mutation in <em>TRIM32</em> and provide a brief summary of all known pathogenic mutations in <em>TRIM32</em>.</p> Xiao-Jing Wei Jing Miao Zhi-Xia Kang Yan-Lu Gao Zi-Yi Wang Xue-Fan Yu Copyright (c) 2020 Xiao-Jing Wei, Jing Miao, Zhi-Xia Kang, Yan-Lu Gao, Zi-Yi Wang, Xue-Fan Yu 2021-08-01 2021-08-01 21 4 495 500 10.17305/bjbms.2020.5288 Machine learning as the new approach in understanding biomarkers of suicidal behavior <p>In psychiatry, compared to other medical fields, the identification of biological markers that would complement current clinical interview, and enable more objective and faster clinical diagnosis, implement accurate monitoring of treatment response and remission, is grave. Current technological development enables analyses of various biological marks in high throughput scale at reasonable costs, and therefore ‘omic’ studies are entering the psychiatry research. However, big data demands a whole new plethora of skills in data processing, before clinically useful information can be extracted. So far the classical approach to data analysis did not really contribute to identification of biomarkers in psychiatry, but the extensive amounts of data might get to a higher level, if artificial intelligence in the shape of machine learning algorithms would be applied. Not many studies on machine learning in psychiatry have been published, but we can already see from that handful of studies that the potential to build a screening portfolio of biomarkers for different psychopathologies, including suicide, exists.</p> Alja Videtič Paska Katarina Kouter Copyright (c) 2021 Alja Videtič Paska, Katarina Kouter 2021-08-01 2021-08-01 21 4 398 408 10.17305/bjbms.2020.5146 Recent advances of targeted therapy in relapsed/refractory acute myeloid leukemia <p>Despite advances in the understanding of disease pathobiology, treatment for relapsed or refractory acute myeloid leukemia (R/R AML) remains challenging. The prognosis of R/R AML remains extremely poor despite chemotherapy and bone marrow transplants. Discoveries on recurrent and novel genetic mutations, such as FLT3-ITD and IDH1/IDH2, critical signaling pathways, and unique molecular markers expressed on the surface of leukemic cells have been under investigation for the management of R/R AML. Other than monoclonal antibodies, diabodies, and triabodies are new targeted therapies developed in recent years and will be the new direction of immunotherapy. Targeted agents combined intensive regimens can be viable options for salvage therapy and as bridges to allogeneic transplant. Future directions will focus on novel, efficient and targeted combinations, low-toxicity maintenance, and individualized precision strategies. Here, we review the major recent advances of targeted therapies in the treatment of R/R AML.</p> Jiale Ma Zheng Ge Copyright (c) 2021 Jiale Ma, Zheng Ge 2021-08-01 2021-08-01 21 4 409 421 10.17305/bjbms.2020.5485 Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches <p>This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing severe acute respiratory syndrome coronavirus 2 epidemic. Whole genome sequence of four samples from coronavirus disease 2019 (COVID-19) outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, and England). The constructed phylogenetic tree indicates possible multiple independent introduction events. The data presented contribute to a better understanding of COVID-19 in the current reemergence of the disease.</p> Teufik Goletic Rijad Konjhodzic Nihad Fejzic Sejla Goletic Toni Eterovic Adis Softic Aida Kustura Lana Salihefendic Maja Ostojic Maja Travar Visnja Mrdjen Nijaz Tihic Sead Jazic Sanjin Musa Damir Marjanovic Mirsada Hukic Copyright (c) 2021 Teufik Goletic 2021-08-01 2021-08-01 21 4 484 487 10.17305/bjbms.2020.5381 Serum glial fibrillary acidic protein as a biomarker of brain injury in premature neonates <p>Neonatal brain injury is a serious adverse outcome of prematurity. Early detection of high risk premature neonates to develop neonatal brain injury is not currently feasible. The predictive value of many biomarkers has been tested, but none is used currently in clinical practice. The purpose of this study was to determine the levels and predictive value of serum glial fibrillary acidic protein (GFAP) in a prospective longitudinal case-control study during the first three days of life in premature neonates (&lt;34 weeks of gestation) that later developed either intraventricular hemorrhage or periventricular leukomalacia. Each case (n=29) was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. No significant difference on GFAP levels was observed between the groups. Nevertheless, neonates with brain injury presented more frequently GFAP levels above the lowest detection limit (0.056 ng/ml) and this trend was significantly different during all days. The effectiveness of GFAP as an early biomarker of neonatal brain injury in premature neonates seems to be limited.</p> Dimitra Metallinou Grigorios Karampas Georgia Nyktari Nicoletta Iacovidou Katerina Lykeridou Demetrios Rizos Copyright (c) 2021 Dimitra Metallinou, Grigorios Karampas, Georgia Nyktari , Nicoletta Iacovidou , Katerina Lykeridou , Demetrios Rizos 2021-07-19 2021-07-19 21 4 10.17305/bjbms.2021.6205 Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: A comprehensive review <p><span style="font-weight: 400;">Stem cell therapy has been used to treat several types of diseases, and it is expected that its therapeutic uses shall increase as novel lines of evidence begin to appear. Furthermore, stem cells have the potential to make new tissues and organs. Thus, some scientists propose that organ transplantation will significantly rely on stem cell technology and organogenesis in the future. Stem cells and its robust potential to differentiate into specific types of cells and regenerate tissues and body organs, have been investigated by numerous clinician scientists and researchers for their therapeutic effects. Degenerative diseases in different organs have been the main target of stem cell therapy. Neurodegenerative diseases such as Alzheimer's, musculoskeletal diseases such as osteoarthritis, congenital cardiovascular diseases, and blood cell diseases such as leukemia are among the health conditions that have benefited from stem cell therapy advancements. One of the most challenging parts of the process of incorporating stem cells into clinical practice is controlling their division and differentiation potentials. Sometimes, their potential for&nbsp; uncontrolled growth will make these cells tumorigenic. Another caveat in this process is the ability to control the differentiation process. While stem cells can easily differentiate into a wide variety of cells,&nbsp; a paracrine effect controlled activity, being in an appropriate medium will cause abnormal differentiation leading to treatment failure. In this review, we aim to provide an overview of the therapeutic effects of stem cells in diseases of various organ systems. In order to advance this new treatment to its full potential, researchers should focus on establishing methods to control the differentiation process, while policymakers should take an active role in providing adequate facilities and equipment for these projects. Large population clinical trials are a necessary tool that will help build trust in this method. Moreover, improving social awareness about the advantages and adverse effects of stem cell therapy is required to develop a rational demand in the society, and consequently, healthcare systems should consider established stem cell-based therapeutic methods in their treatment algorithms.</span></p> <p>&nbsp;</p> Alireza Ebrahimi Hanie Ahmadi Zahra Pourfraidon Ghasrodashti Nader Tanide Reza Shahriarirad Amirhossein Erfani Keivan Ranjbar Soheil Ashkani-Esfahani Copyright (c) 2021 Alireza Ebrahimi , Hanie Ahmadi, Zahra Pourfraidon Ghasrodashti, Nader Tanide, Reza Shahriarirad , Amirhossein Erfani, Keivan Ranjbar , Soheil Ashkani-Esfahani 2021-07-13 2021-07-13 21 4 10.17305/bjbms.2021.5508 Resveratrol ameliorates neuronal apoptosis and cognitive impairment by activating the SIRT1/RhoA pathway in rats after anesthesia with sevoflurane <p><span style="font-weight: 400;">Studies have shown that long-term exposure to sevoflurane (SEV) may cause postoperative cognitive dysfunction. This study aimed to investigate the effects of resveratrol (RES) treatment on the changes in the cognitive function of rats after prolonged anesthesia with SEV. Seventy-six adult male rats were used in this study. The SEV model was established under continuous anesthesia for 6 h. Rats were randomly classified into four groups as follows: control, SEV+vehicle, SEV+pre-RES (RES was administered 24 h before establishing the SEV model), and SEV+post-RES (RES was administered 1 h after establishing the SEV model) groups. Neurobehavioral outcomes and the potential mechanism underlying RES-mediated neuroprotection through the SIRT1/RhoA signaling pathway were evaluated. The water maze test showed that long-term exposure to SEV may lead to loss of learning and memory ability in rats (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05). Compared with the SEV+vehicle group, the RES treatment groups showed significantly improved neurobehavioral scores (<em>p</em>&lt;0.05). Additionally, the SEV+pre-RES group had a better outcome than the SEV+vehicle group on days 1 or 2 (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05), unlike the SEV+post-RES group (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&gt;0.05). Western blotting showed that SIRT1, RhoA, and cleaved Caspase-3 (CC3) expression significantly increased in the SEV+vehicle group (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05), while Bcl2 expression decreased (p &lt; 0.05). RES treatment further upregulated SIRT1 and Bcl2 expression and downregulated the expression of RhoA and CC3 (</span><em><span style="font-weight: 400;">p</span></em><span style="font-weight: 400;">&lt;0.05). In conclusion, RES treatment improved cognitive dysfunction by reducing neuronal apoptosis in adult rats exposed to SEV. RES partly exerted a neuroprotective effect through the activation of the SIRT1/RhoA signaling pathway. </span></p> <p><audio style="display: none;" controls="controls"></audio></p> <p><audio style="display: none;" controls="controls"></audio></p> Qiaoyun Zhou Yingfeng Deng Xuelian Hu Yinye Xu Copyright (c) 2021 Qiaoyun Zhou, Yingfeng Deng, Xuelian Hu, Yinye Xu 2021-07-06 2021-07-06 21 4 10.17305/bjbms.2021.5997 Perineural spread in head and neck malignancies: imaging findings - an updated literature review <p>Perineural spread (PNS) represents the tumor’s ability to disseminate along nerves. The aim of this article is to review the relevant literature about the PNS in head and neck tumors (HN). The important information for imaging analysis is summarized in a diagnostic flow-chart. The pathogenesis, clinical signs, prognostic importance, and technical considerations for computer tomography and magnetic resonance imaging are briefly discussed. The anatomical pathways of the cranial nerves (CNs) and the main check-points are synthesized. Most commonly affected nerves are the trigeminal and facial, although any of the CNs may be involved. The described imaging features represent important clues for an optimal differential diagnosis. PNS worsens the prognosis and significantly changes the treatment, thus radiologists should be aware of this entity and be able to find it on imaging in the appropriate clinical context.</p> Olga Medvedev Mihaela Hedesiu Anca Ciurea Manuela Lenghel Horatiu Rotar Cristian Dinu Rares Roman Dragos Termure Csaba Csutak Copyright (c) 2021 Olga Medvedev, MIhaela Hedesiu, Anca Ciurea, Manuela Lenghel , Horatiu Rotar, Cristian Dinu, Rares Roman, Dragos Termure, Csaba Csutak 2021-06-29 2021-06-29 21 4 10.17305/bjbms.2021.5897