Comparison of ultra-long gonadotropin releasing hormone agonist versus standard downregulation in women with adenomyosis undergoing frozen-thawed embryo transfer: a randomized clinical trial.

BACKGROUND: Adenomyosis can lead to infertility and failure of in vitro fertilization. Limited evidence suggests that the use of long-term treatment with gonadotropin-releasing hormone (GnRH) agonists followed by frozen-thawed embryo transfer (FET) may be the preferred approach for women with adenomyosis. OBJECTIVE: The aim of this randomized controlled trial is to compare the efficacy of an ultra-long GnRH agonist with standard downregulation in women with adenomyosis undergoing FET. MATERIALS AND METHODS: This randomized controlled trial enrolled 72 women with adenomyosis diagnosed by sonographic criteria who underwent FET cycles at the Avicenna Infertility Center. These women were randomly assigned to two equal groups: one received GnRH agonist treatment for three months before the FET cycle and the other served as the standard downregulation group. Results were reported as chemical and clinical pregnancy rates. RESULTS: The two groups were similar in age, body mass index, anti-Müllerian hormone levels, number of previous pregnancies and miscarriages, presence of uterine myomas, and endometriosis. However, the total dose of estradiol used until embryo transfer was significantly higher in the ultra-long GnRH agonist group than in the standard group (96.14 mg vs. 80.52 mg, p-value = 0.004). Nevertheless, chemical and clinical pregnancy rates did not differ significantly between the two groups. CONCLUSIONS: Ultra-long GnRH agonist downregulation did not improve the chemical and clinical pregnancy rate in the FET cycle in women with adenomyosis compared with standard GnRH agonist downregulation in the other words, ultra-long GnRH agonist downregulation is not superior to standard protocol. In women with adenomyosis (without history of endometriosis), downregulation of standard GnRH agonists prior to frozen-thawed embryo transfer may be the preferred embryo transfer protocol to gain higher clinical/chemical pregnancy rate. TRIAL REGISTRATION: Clinical trial registry: IRCT20160717028967N9, available at: https://irct.behdasht.gov.ir/trial/36103 .

The evaluation of nightshade elimination diet (NED) on inflammatory and rheumatologic markers of rheumatoid arthritis patients: study protocol for a randomized controlled trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease with a global prevalence rate of 1%. Patients with RA often associate specific foods like tomatoes and eggplants with adverse symptoms. These plants contain solanine, which could potentially contribute to bone and joint damage. Despite patient reports, there is a lack of randomized controlled trials (RCTs) investigating the effects of nightshades on patients with RA. This study aims to assess the effect of nightshade elimination diet (NED) on inflammatory and rheumatologic marker levels in rheumatoid arthritis patients for the first time. METHODS: A single-blinded controlled trial will be conducted to evaluate the effect of an NED on 40 participants over 8 weeks (2 months). Participants will be equally divided into intervention and placebo groups. Both groups will receive general anti-inflammatory dietary recommendations, with the intervention group undergoing an NED during the study. Clinical symptoms will be assessed using questionnaires, and blood samples will be collected to measure relevant indicators. DISCUSSION: This RCT signifies a groundbreaking exploration into NED effects on RA markers, potentially initiating crucial discussions in the field. Its outcomes could serve as a cornerstone for larger and more robust trials, offering pivotal insights to nutritionists and physicians for the nuanced management of patients with RA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20230220057465N1 ( https://irct.behdasht.gov.ir/trial/68959 ). Registered on 8 April 2023.

Metabolic Fingerprinting of Serum and Seminal Plasma of Testicular Cancer Patients Using Raman Spectroscopy: A Pilot Study.

Background: Testicular cancer (TC) is a relatively rare type of cancer in men. Early diagnosis of TC remains challenging. Metabolomics holds promise in offering valuable insights in this regard. In this study, a metabolic fingerprinting approach was employed to identify potential biomarkers in both serum and seminal plasma of TC patients. Methods: A total of 9 patients with testicular cancer and 10 controls were included in the study. The metabolic fingerprinting approach was utilized as a rapid diagnostic tool to analyze the metabolome in serum and seminal plasma of TC patients in comparison to fertile men. Raman spectroscopy was applied for the analysis of metabolites in these biological samples. Results: Principal component analysis (PCA) and functional group analysis showed that the differentiation between serum samples from healthy men and TC patients was not possible. However, when analyzing seminal plasma, a significant difference was found between the two groups (p<0.05). Functional group analysis of serum only showed an increase in tryptophan concentration ratio in TC patients as compared to healthy men (p=0.03). In contrast, in seminal plasma of TC patients, this increase was observed in all analyzed compounds, including phenylalanine, tyrosine, lipids, proteins, phenols (p<0.001). Conclusion: Our study highlights the potential of metabolic fingerprinting as a fast diagnostic tool for screening TC patients, with seminal plasma serving as a valuable biological sample. Furthermore, several potential biomarkers, particularly phenylalanine, were identified in seminal plasma. This research contributes to our understanding of TC pathogenesis and has the potential to pave the way for early detection and personalized treatment approaches.

TgVax452, an epitope-based candidate vaccine targeting Toxoplasma gondii tachyzoite-specific SAG1-related sequence (SRS) proteins: immunoinformatics, structural simulations and experimental evidence-based approaches.

BACKGROUND: The highly expressed surface antigen 1 (SAG1)-related sequence (SRS) proteins of T. gondii tachyzoites, as a widespread zoonotic parasite, are critical for host cell invasion and represent promising vaccine targets. In this study, we employed a computer-aided multi-method approach for in silico design and evaluation of TgVax452, an epitope-based candidate vaccine against T. gondii tachyzoite-specific SRS proteins. METHODS: Using immunoinformatics web-based tools, structural modeling, and static/dynamic molecular simulations, we identified and screened B- and T-cell immunodominant epitopes and predicted TgVax452's antigenicity, stability, safety, adjuvanticity, and physico-chemical properties. RESULTS: The designed protein possessed 452 residues, a MW of 44.07 kDa, an alkaline pI (6.7), good stability (33.20), solubility (0.498), and antigenicity (0.9639) with no allergenicity. Comprehensive molecular dynamic (MD) simulation analyses confirmed the stable interaction (average potential energy: 3.3799 × 106 KJ/mol) between the TLR4 agonist residues (RS09 peptide) of the TgVax452 in interaction with human TLR4, potentially activating innate immune responses. Also, a dramatic increase was observed in specific antibodies (IgM and IgG), cytokines (IFN-γ), and lymphocyte responses, based on C-ImmSim outputs. Finally, we optimized TgVax452's codon adaptation and mRNA secondary structure for efficient expression in E. coli BL21 expression machinery. CONCLUSION: Our findings suggest that TgVax452 is a promising candidate vaccine against T. gondii tachyzoite-specific SRS proteins and requires further experimental studies for its potential use in preclinical trials.

Assessing Heterogeneity Effects on Points A, B, and Organs at Risk Doses in High-dose-Rate Brachytherapy for Cervical Cancer - A Comparison of 192Ir and 60Co Sources Using Monte Carlo N-Particle 5.

Purpose: The present article deals with investigating the effects of tissue heterogeneity consideration on the dose distribution of 192Ir and 60Co sources in high-dose-rate brachytherapy (HDR-BT). Materials and Methods: A Monte Carlo N-Particle 5 (MCNP5) code was developed for the simulation of the dose distribution in homogeneous and heterogeneous phantoms for cervical cancer patients. The phantoms represented water-equivalent and human body-equivalent tissues. Treatment data for a patient undergoing HDR-BT with a 192Ir source were used as a reference for validation, and for 60Co, AAPM Task Group 43 methodology was also applied. The dose values were calculated for both source types in the phantoms. Results: The results showed a good agreement between the calculated dose in the homogeneous phantom and the real patient's treatment data, with a relative difference of less than 5% for both sources. However, when comparing the absorbed doses at critical points such as Point A right, Point A left, Point B right, Point B left, bladder International Commission on Radiation Units and Measurement (ICRU) point, and recto-vaginal ICRU point, the study revealed significant percentage differences (approximately 5.85% to 12.02%) between the homogeneous and heterogeneous setups for both 192Ir and 60Co sources. The analysis of dose-volume histograms (DVH) indicated that organs at risk, notably the rectum and bladder, still received doses within recommended limits. Conclusions: The study concludes that 60Co and 192Ir sources can be effectively used in HDR-BT, provided that careful consideration is given to tissue heterogeneity effects during treatment planning to ensure optimal therapeutic outcomes.

Altered brain connectivity in mild cognitive impairment is linked to elevated tau and phosphorylated tau, but not to GAP-43 and Amyloid-ß measurements: a resting-state fMRI study.

Mild Cognitive Impairment (MCI) is a neurological condition characterized by a noticeable decline in cognitive abilities that falls between normal aging and dementia. Along with some biomarkers like GAP-43, Aß, tau, and P-tau, brain activity and connectivity are ascribed to MCI; however, the link between brain connectivity changes and such biomarkers in MCI is still being investigated. This study explores the relationship between biomarkers like GAP-43, Aß, tau, and P-tau, and brain connectivity. We enrolled 25 Participants with normal cognitive function and 23 patients with MCI. Levels of GAP-43, Aß1-42, t-tau, and p-tau181p in the CSF were measured, and functional connectivity measures including ROI-to-voxel (RV) correlations and the DMN RV-ratio were extracted from the resting-state fMRI data. P-values below 0.05 were considered significant. The results showed that in CN individuals, higher connectivity within the both anterior default mode network (aDMN) and posterior DMN (pDMN) was associated with higher levels of the biomarker GAP-43. In contrast, MCI individuals showed significant negative correlations between DMN connectivity and levels of tau and P-tau. Notably, no significant correlations were found between Aß levels and connectivity measures in either group. These findings suggest that elevated levels of GAP-43 indicate increased functional connectivity in aDMN and pDMN. Conversely, elevated levels of tau and p-tau can disrupt connectivity through various mechanisms. Thus, the accumulation of tau and p-tau can lead to impaired neuronal connectivity, contributing to cognitive decline.

Polygenic hazard score predicts synaptic and axonal degeneration and cognitive decline in Alzheimer's disease continuum.

BACKGROUND: Growth associated protein-43 (GAP-43) and neurofilaments light (NFL) are biomarkers of synaptic and axonal injury, and are associated with cognitive decline in Alzheimer's disease (AD) contiuum. We investigated whether Polygenic Hazard Score (PHS) is associated with specific biomarkers and cognitive measures, and if it can predict the relationship between GAP-43, NFL, and cognitive decline in AD. METHOD: We enrolled 646 subjects: 93 with AD, 350 with mild cognitive impairment (MCI), and 203 cognitively normal controls. Variables included GAP-43, plasma NFL, and PHS. A PHS of 0.21 or higher was considered high risk while a PHS below this threshold was considered low risk. A subsample of 190 patients with MCI with four years of follow-up cognitive assessments were selected for longitudinal analysis . We assessed the association of the PHS with AD biomarkers and cognitive measures, as well as the predictive power of PHS on cognitive decline and the conversion of MCI to AD. RESULTS: PHS showed high diagnostic accuracy in distinguishing AD, MCI, and controls. At each follow-up point, high risk MCI patients showed higher level of cognitive impairment compared to the low risk group. GAP-43 correlated with all follow-up cognitive tests in high risk MCI patients which was not detected in low risk MCI patients. Moreover, high risk MCI patients progressed to dementia more rapidly compared to low risk patients. CONCLUSION: PHS can predict cognitive decline and impacts the relationship between neurodegenerative biomarkers and cognitive impairment in AD contiuum. Categorizing patients based on PHS can improve the prediction of cognitive outcomes and disease progression.

Readiness for advance care planning and related factors in the general population: a cross sectional study in Iran.

CONTEXT: Advance Care Planning (ACP), as a process for expressing and recording patients' preferences about end-of-life care, has received increasing attention in recent years. However, implementing ACP has been challenging in Iran. OBJECTIVES: To assess the readiness for advance care planning and related factors in the general population of Iran. METHODS: This cross-sectional study was conducted on the general population of Iran in 2022. The data was collected using demographic information questionnaire and The RACP Scale. The purpose and methodology of the research was explained to all participants, and upon their agreement an informed consent was obtained. Participants were invited to fill out the questionnaires wherever is more convenient for them, either alone or if needed, with the help of the researcher to protect their privacy. Chi-square, fisher exact test and multiple logistic Regression model were used to assess the effective factors on the RACP. The data were analyzed by SPSS software version 26. RESULTS: A total of 641 people with an average age of 36.85 ± 12.05 years participated in this study. Of those, 377 (58.8%) had high RACP. The logistics model showed an association between the chance of readiness for receiving ACP with participants' education level, such that the chance of readiness in those with Master's or Ph.D. degrees was three times higher than those with a diploma (p = 0.00, OR:3.178(1.672, 6.043)). However, the chances of readiness in those with bachelor's degrees was not significantly different from those with a diploma (p = 0.936, OR: 0.984 (0.654, 1.479)). Moreover, the chance of readiness was 1.5 higher in participants over 40 years of age compared with participants under the age of 40 (P = 0.01, OR: 1.571(1.10, 2.23)). CONCLUSION: According to the findings of this study, it can be concluded that there is a relatively RACP among people in Iranian society. The readiness of individuals for ACP increases by their age and education level. Therefore, by holding appropriate training intervention, we can increase the readiness of the public for ACP to improve their end-of-life outcome.

Distributed safe formation tracking control of multiquadcopter systems using barrier Lyapunov function.

Coordinating the movements of a robotic fleet using consensus-based techniques is an important problem in achieving the desired goal of a specific task. Although most available techniques developed for consensus-based control ignore the collision of robots in the transient phase, they are either computationally expensive or cannot be applied in environments with dynamic obstacles. Therefore, we propose a new distributed collision-free formation tracking control scheme for multiquadcopter systems by exploiting the properties of the barrier Lyapunov function (BLF). Accordingly, the problem is formulated in a backstepping setting, and a distributed control law that guarantees collision-free formation tracking of the quads is derived. In other words, the problems of both tracking and interagent collision avoidance with a predefined accuracy are formulated using the proposed BLF for position subsystems, and the controllers are designed through augmentation of a quadratic Lyapunov function. Owing to the underactuated nature of the quadcopter system, virtual control inputs are considered for the translational (x and y axes) subsystems that are then used to generate the desired values for the roll and pitch angles for the attitude control subsystem. This provides a hierarchical controller structure for each quadcopter. The attitude controller is designed for each quadcopter locally by taking into account a predetermined error limit by another BLF. Finally, simulation results from the MATLAB-Simulink environment are provided to show the accuracy of the proposed method. A numerical comparison with an optimization-based technique is also provided to prove the superiority of the proposed method in terms of the computational cost, steady-state error, and response time.

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.

BACKGROUND: Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. The main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c. METHOD: In this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated. RESULTS: The designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment. CONCLUSIONS: As far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients.

Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis.

Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive Escherichia coli (pks+ E. coli) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.

Detecting Alzheimer's Disease Stages and Frontotemporal Dementia in Time Courses of Resting-State fMRI Data Using a Machine Learning Approach.

Early, accurate diagnosis of neurodegenerative dementia subtypes such as Alzheimer's disease (AD) and frontotemporal dementia (FTD) is crucial for the effectiveness of their treatments. However, distinguishing these conditions becomes challenging when symptoms overlap or the conditions present atypically. Resting-state fMRI (rs-fMRI) studies have demonstrated condition-specific alterations in AD, FTD, and mild cognitive impairment (MCI) compared to healthy controls (HC). Here, we used machine learning to build a diagnostic classification model based on these alterations. We curated all rs-fMRIs and their corresponding clinical information from the ADNI and FTLDNI databases. Imaging data underwent preprocessing, time course extraction, and feature extraction in preparation for the analyses. The imaging features data and clinical variables were fed into gradient-boosted decision trees with fivefold nested cross-validation to build models that classified four groups: AD, FTD, HC, and MCI. The mean and 95% confidence intervals for model performance metrics were calculated using the unseen test sets in the cross-validation rounds. The model built using only imaging features achieved 74.4% mean balanced accuracy, 0.94 mean macro-averaged AUC, and 0.73 mean macro-averaged F1 score. It accurately classified FTD (F1 = 0.99), HC (F1 = 0.99), and MCI (F1 = 0.86) fMRIs but mostly misclassified AD scans as MCI (F1 = 0.08). Adding clinical variables to model inputs raised balanced accuracy to 91.1%, macro-averaged AUC to 0.99, macro-averaged F1 score to 0.92, and improved AD classification accuracy (F1 = 0.74). In conclusion, a multimodal model based on rs-fMRI and clinical data accurately differentiates AD-MCI vs. FTD vs. HC.

Prospective Randomized Trial of Na/K Citrate for the Prevention of Contrast-Induced Nephropathy in High-risk Patients.

Background: Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) refers to an acute kidney injury (AKI) occurring after exposure to contrast media, commonly used in diagnostic procedures or therapeutic angiographic interventions. Recently, Na/K citrate, used for urine alkalinization, has been assessed for preventing CIN. This experiment evaluated Na/K citrate's efficacy in preventing CIN in high-risk patients undergoing cardiac catheterization. Methods: A prospective randomized clinical trial involved 400 patients with moderate- to high-risk factors for CIN undergoing elective percutaneous coronary intervention (PCI). They were randomly assigned to either the control or Na/K citrate groups. The Na/K citrate group (n = 200) received a 5 g Na/K citrate solution diluted in 200 mL water 2 hours before and 4 hours after the first administration, along with intravenous hydration for 2 hours before and 6 hours after the procedure. In contrast, the control group (n = 200) received only intravenous hydration. Serum creatinine (SCr) levels were measured before contrast exposure and 48 hours afterward. CIN was defined as a 25% increase in serum creatinine (SCr) or > 0.5 mg/dL 48 hours after contrast administration. The significance level was set at P ˂ 0.05. Results: CIN was observed in 33 patients (16.5%) in the control group and 6 patients (3%) in the Na/K citrate group. The incidence of CIN was found to have a significant difference between the 2 groups 48 hours after receiving the radiocontrast agent (P < 0.001). Conclusion: Our results show that Na/K citrate is helpful and substantially reduces the incidence of CIN.

Association of Recalled Childhood Sex-Typed Behavior with Sexual Orientation and Gender Identity in Iranian Adult Males and Females.

Same-sex sexual attraction in both males and females has been associated with childhood sex-atypical behavior. Gynephilic females recall behaving in a manner that is less female-typical and more male-typical compared to cisgender androphilic females, whereas androphilic males recall behaving in a manner that is less male-typical and more female-typical compared to cisgender gynephilic males. In addition, male and female ambiphilic individuals exhibit intermediate levels of childhood sex-atypicality. In this study, we examined recalled childhood sex-typed behavior among Iranian cisgender gynephilic males (n = 236), cisgender ambiphilic males (n = 51), cisgender androphilic males (n = 191), transgender androphilic males (n = 60), cisgender androphilic females (n = 243), cisgender ambiphilic females (n = 96), cisgender gynephilic females (n = 32), and transgender gynephilic females (n = 122). Both cisgender androphilic males and cisgender gynephilic females recalled elevated childhood sex-atypicality, scoring intermediate between cisgender gynephilic males and cisgender androphilic females. Male and female ambiphilic participants scored intermediate between their other- and same-sex attracted cisgender counterparts. Transgender androphilic males exhibited hyper-feminized childhood behavior, scoring even more female-typical than cisgender androphilic females. Transgender gynephilic females recalled behaving as male-typical as cisgender gynephilic males. Consistent with previous research, our findings from Iran - a non-Western, Middle Eastern culture - provide cross-cultural support for the universality of childhood sex-atypicality as a normative developmental precursor of monosexual or ambisexual same-sex attraction in both males and females who are cisgender and transgender.

Unmasking the NLRP3 inflammasome in dendritic cells as a potential therapeutic target for autoimmunity, cancer, and infectious conditions.

Proper and functional immune response requires a complex interaction between innate and adaptive immune cells, which dendritic cells (DCs) are the primary actors in this coordination as professional antigen-presenting cells. DCs are armed with numerous pattern recognition receptors (PRRs) such as nucleotide-binding and oligomerization domain-like receptors (NLRs) like NLRP3, which influence the development of their activation state upon sensation of ligands. NLRP3 is a crucial component of the immune system for protection against tumors and infectious agents, because its activation leads to the assembly of inflammasomes that cause the formation of active caspase-1 and stimulate the maturation and release of proinflammatory cytokines. But, when NLRP3 becomes overactivated, it plays a pathogenic role in the progression of several autoimmune disorders. So, NLRP3 activation is strictly regulated by diverse signaling pathways that are mentioned in detail in this review. Furthermore, the role of NLRP3 in all of the diverse immune cells' subsets is briefly mentioned in this study because NLRP3 plays a pivotal role in modulating other immune cells which are accompanied by DCs' responses and subsequently influence differentiation of T cells to diverse T helper subsets and even impact on cytotoxic CD8+ T cells' responses. This review sheds light on the functional and therapeutic role of NLRP3 in DCs and its contribution to the occurrence and progression of autoimmune disorders, prevention of diverse tumors' development, and recognition and annihilation of various infectious agents. Furthermore, we highlight NLRP3 targeting potential for improving DC-based immunotherapeutic approaches, to be used for the benefit of patients suffering from these disorders.

Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumours.

BACKGROUND: The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. METHODS: The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA). RESULTS: A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 0.011). CONCLUSIONS: SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.