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Accelerator-based BNCT for patients with recurrent glioblastoma: a multicenter phase II study.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab067. Epub 2021 May 20.

Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan.

Background: Boron neutron capture therapy (BNCT) utilizes tumor-selective particle radiation. This study aimed to assess the safety and efficacy of accelerator-based BNCT (AB-BNCT) using a cyclotron-based neutron generator (BNCT 30) and B-boronophenylalanine (SPM-011) in patients with recurrent malignant glioma (MG) (primarily glioblastoma [GB]).

Methods: This multi-institutional, open-label, phase II clinical trial involved 27 recurrent MG cases, including 24 GB cases, who were enrolled from February 2016 to June 2018. Read More

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Anti-PD-1 checkpoint blockade monotherapy in the orthotopic GL261 glioma model: the devil is in the detail.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab066. Epub 2021 May 14.

Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.

The GL261 cell line, syngeneic on the C57BL/6 background, has, since its establishment half a century ago in 1970, become the most commonly used immunocompetent murine model of glioblastoma. As immunotherapy has entered the mainstream of clinical discourse in the past decade, this model has proved its worth as a formidable opponent against various immunotherapeutic combinations. Although advances in surgical, radiological, and chemotherapeutic interventions have extended mean glioblastoma patient survival by several months, 5-year survival postdiagnosis remains below 5%. Read More

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An integrative analysis of genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA detects noninvasive diagnostic markers for gliomas.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab049. Epub 2021 Apr 16.

State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, and The Collaborative Innovation Centre for Brain Science, Fudan University, Shanghai, China.

Background: Gliomas, especially the high-grade glioblastomas (GBM), are highly aggressive tumors in the central nervous system (CNS) with dismal clinical outcomes. Effective biomarkers, which are not currently available, may improve clinical outcomes through early detection. We sought to develop a noninvasive diagnostic approach for gliomas based on 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA). Read More

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Prospective prediction of clinical drug response in high-grade gliomas using an ex vivo 3D cell culture assay.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab065. Epub 2021 May 7.

KIYATEC, Inc., Greenville, South Carolina, USA.

Background: Clinical outcomes in high-grade glioma (HGG) have remained relatively unchanged over the last 3 decades with only modest increases in overall survival. Despite the validation of biomarkers to classify treatment response, most newly diagnosed (ND) patients receive the same treatment regimen. This study aimed to determine whether a prospective functional assay that provides a direct, live tumor cell-based drug response prediction specific for each patient could accurately predict clinical drug response prior to treatment. Read More

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Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men.

Basic Clin Androl 2021 Jun 17;31(1):15. Epub 2021 Jun 17.

Department of Andrology, Urology and Renal Transplantation, Claude Huriez Hospital, Lille University Hospital, 1 Place de Verdun, 59045, Lille Cedex, France.

Background: Testicular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. Read More

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Irradiation of mutant mouse models of spinal plexiform neurofibromas drives pathologic progression and decreases survival.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab063. Epub 2021 Apr 23.

Department of Radiation Oncology, School of Medicine, University of California, San Francisco, San Francisco, California, USA.

Background: Genetically susceptible individuals can develop malignancies after irradiation of normal tissues. In the context of therapeutic irradiation, it is not known whether irradiating benign neoplasms in susceptible individuals promotes neoplastic transformation and worse clinical outcomes. Individuals with Neurofibromatosis 1 (NF1) are susceptible to both radiation-induced second malignancies and spontaneous progression of plexiform neurofibromas (PNs) to malignant peripheral nerve sheath tumors (MPNSTs). Read More

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Glioma-associated microglia/macrophages augment tumorigenicity in canine astrocytoma, a naturally occurring model of human glioma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab062. Epub 2021 May 4.

Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

Background: Glioma-associated microglia/macrophages (GAMs) markedly influence glioma progression. Under the influence of transforming growth factor beta (TGFB), GAMs are polarized toward a tumor-supportive phenotype. However, neither therapeutic targeting of GAM recruitment nor TGFB signaling demonstrated efficacy in glioma patients despite efficacy in preclinical models, underscoring the need for a comprehensive understanding of the TGFB/GAM axis. Read More

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MR spectroscopic imaging predicts early response to anti-angiogenic therapy in recurrent glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab060. Epub 2021 Apr 15.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Background: Determining failure to anti-angiogenic therapy in recurrent glioblastoma (GBM) (rGBM) remains a challenge. The purpose of the study was to assess treatment response to bevacizumab-based therapy in patients with rGBM using MR spectroscopy (MRS).

Methods: We performed longitudinal MRI/MRS in 33 patients with rGBM to investigate whether changes in N-acetylaspartate (NAA)/Choline (Cho) and Lactate (Lac)/NAA from baseline to subsequent time points after treatment can predict early failures to bevacizumab-based therapies. Read More

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The role of alteration and 4q12 amplification in IDH-WT glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab050. Epub 2021 Mar 31.

Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas, USA.

Background: Recent studies have identified that glioblastoma IDH-wildtype (GBM IDH-WT) might be comprised of molecular subgroups with distinct prognoses. Therefore, we investigated the correlation between genetic alterations and survival in 282 GBM IDH-WT patients, to identify subgroups with distinct outcomes.

Methods: We reviewed characteristics of GBM IDH-WT (2009-2019) patients analyzed by next-generation sequencing interrogating 205 genes and 26 rearrangements. Read More

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5-Aminolevulinic acid-guided resection improves the overall survival of patients with glioblastoma-a comparative cohort study of 343 patients.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab047. Epub 2021 Mar 26.

Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK.

Background: 5-Aminolevulic acid-guided surgery (5-ALA-GS) improves the extent of resection (EoR) and progression-free survival in patients with glioblastoma multiforme (GBM).

Methods: A single-center retrospective cohort study of adult patients with GBM who had surgical resection between 2013 and 2019, 5-ALA guided versus a non-5-ALA cohort. The primary outcome was the overall survival (OS). Read More

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Who stays in medication treatment for opioid use disorder? A national study of outpatient specialty treatment settings.

J Subst Abuse Treat 2021 Jul 18;126:108329. Epub 2021 Feb 18.

Department of Population Health, NYU Grossman School of Medicine, United States of America.

Background: Maintenance treatments with medications for opioid use disorder (MOUD) are highly effective at reducing overdose risk while patients remain in care. However, few patients initiate medication and retention remains a critical challenge across settings. Much remains to be learned about individual and structural factors that influence successful retention, especially among populations dispensed MOUD in outpatient settings. Read More

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Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab052. Epub 2021 Apr 9.

Competence Center for Methodology and Statistics, Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg.

Background: Despite advances in the treatment of cancers over the last years, treatment options for patients with recurrent glioblastoma (rGBM) remain limited with poor outcomes. Many regimens have been investigated in clinical trials; however, there is a lack of knowledge on comparative effectiveness. The aim of this systematic review is to provide an overview of existing treatment strategies and to estimate the relative efficacy of these regimens in terms of progression-free survival (PFS) and overall survival (OS). Read More

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Characteristics of diffuse hemispheric gliomas, H3 G34-mutant in adults.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab061. Epub 2021 Apr 19.

Cancer Initiation and Tumoral Cell Identity Department, Cancer Research Centre of Lyon (CRCL) INSERM 1052, CNRS 5286, Lyon, France.

Background: Diffuse hemispheric gliomas, H3 G34-mutant (DHG H3G34-mutant) constitute a distinct type of aggressive brain tumors. Although initially described in children, they can also affect adults. The aims of this study were to describe the characteristics of DHG H3G34-mutant in adults and to compare them to those of established types of adult WHO grade IV gliomas. Read More

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Bintrafusp alfa (M7824), a bifunctional fusion protein targeting TGF-β and PD-L1: results from a phase I expansion cohort in patients with recurrent glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab058. Epub 2021 Apr 9.

Austin Brain Tumor Center, Austin, Texas, USA.

Background: For patients with recurrent glioblastoma (rGBM), there are few options following treatment failure with radiotherapy plus temozolomide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β "trap") fused to a human IgG1 antibody blocking PD-L1.

Methods: In this phase I, open-label expansion cohort (NCT02517398), patients with rGBM that progressed after radiotherapy plus temozolomide received bintrafusp alfa 1200 mg Q2W until disease progression, unacceptable toxicity, or trial withdrawal. Read More

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NBAT1/CASC15-003/USP36 control MYCN expression and its downstream pathway genes in neuroblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab056. Epub 2021 Apr 9.

Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.

Background: has been an attractive therapeutic target in neuroblastoma considering the widespread amplification of the locus in neuroblastoma, and its established role in neuroblastoma development and progression. Thus, understanding neuroblastoma-specific control of expression at the transcriptional and post-transcriptional level would lead to identification of novel -dependent oncogenic pathways and potential therapeutic strategies.

Methods: By performing loss- and gain-of-function experiments of the neuroblastoma hotspot locus 6p22. Read More

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Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab053. Epub 2021 Apr 8.

Amsterdam University Medical Centers, location VU University Medical Center, Neurosurgical Center Amsterdam, Amsterdam, Netherlands.

Background: The impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery. Read More

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Multiparametric MRI texture analysis in prediction of glioma biomarker status: added value of MR diffusion.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab051. Epub 2021 Apr 8.

Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Background: Early identification of glioma molecular phenotypes can lead to understanding of patient prognosis and treatment guidance. We aimed to develop a multiparametric MRI texture analysis model using a combination of conventional and diffusion MRI to predict a wide range of biomarkers in patients with glioma.

Methods: In this retrospective study, patients were included if they (1) had diagnosis of gliomas with known , , , , , and status from surgical pathology and (2) had preoperative MRI including FLAIR, T1c+ and diffusion for radiomic texture analysis. Read More

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Hypermetabolism and impaired cerebrovascular reactivity beyond the standard MRI-identified tumor border indicate diffuse glioma extended tissue infiltration.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab048. Epub 2021 Mar 30.

Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: Diffuse gliomas exhibit diffuse infiltrative growth, often beyond the magnetic resonance imaging (MRI)-detectable tumor lesion. Within this lesion, hypermetabolism and impaired cerebrovascular reactivity (CVR) are found, but its exact distribution pattern into the peritumoral environment is unknown. Our aim was to better characterize the extent of diffuse glioma tissue infiltration, beyond the visible lesion (ie, beyond the T1-contrast-enhancing lesion and/or T2/FLAIR-defined tumor border), with metabolic positron emission tomography (PET), and functional MRI CVR (blood oxygenation-level-dependent CVR [BOLD-CVR]) mapping. Read More

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CovidNeuroOnc: A UK multicenter, prospective cohort study of the impact of the COVID-19 pandemic on the neuro-oncology service.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab014. Epub 2021 Jan 28.

Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Liverpool, UK.

Background: The COVID-19 pandemic has profoundly affected cancer services. Our objective was to determine the effect of the COVID-19 pandemic on decision making and the resulting outcomes for patients with newly diagnosed or recurrent intracranial tumors.

Methods: We performed a multicenter prospective study of all adult patients discussed in weekly neuro-oncology and skull base multidisciplinary team meetings who had a newly diagnosed or recurrent intracranial (excluding pituitary) tumor between 01 April and 31 May 2020. Read More

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January 2021

Comparison of the Effects of Different Testicular Sperm Extraction Methods on the Embryonic Development of Azoospermic Men in Intracytoplasmic Sperm Injection (ICSI) Cycles: A Retrospective Cohort Study.

Biomed Res Int 2021 17;2021:5515247. Epub 2021 May 17.

Reproductive Medical Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Background: The effects of different testicular sperm extraction methods on the embryonic development and clinical outcome of azoospermic men in intracytoplasmic sperm injection (ICSI) cycles have not been researched. Our goal was to evaluate the effect of different sperm retrieval methods used for patients with OA or NOA on the embryonic development and clinical outcomes during the ICSI cycles.

Methods: This was a retrospective cohort study. Read More

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Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 newly diagnosed disease.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab028. Epub 2021 Feb 12.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: Glioblastoma (GB) is the most common malignant brain tumor with a dismal prognosis despite standard of care (SOC). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) beyond the SOC.

Methods: We included RCTs that investigated the addition of a new treatment to the SOC in patients with newly diagnosed GB. Read More

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February 2021

Lessons learned from contemporary glioblastoma randomized clinical trials through systematic review and network meta-analysis: part 2 recurrent glioblastoma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab029. Epub 2021 Feb 12.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.

Background: There exists no consensus standard of treatment for patients with recurrent glioblastoma (GB). Here we used a network meta-analysis on treatments from randomized control trials (RCTs) to assess the effect on overall survival (OS) and progression-free survival (PFS) to determine if any consensus treatment can be determined for recurrent GB.

Methods: We included all recurrent GB RCTs with at least 20 patients in each arm, and for whom patients underwent standard of care at the time of their GB initial diagnosis. Read More

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February 2021

Integrative molecular characterization of pediatric spinal ependymoma: the UK Children's Cancer and Leukaemia Group study.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab043. Epub 2021 Mar 8.

Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK.

Background: Pediatric spinal ependymomas (SP-EPNs) are rare primary central nervous system tumors with heterogeneous clinical course. Considering that ependymomas in children are biologically distinct from their adult counterparts, this study aimed to define the molecular landscape of SP-EPNs in children.

Methods: In this retrospective study, we have collected tumor samples from 27 SP-EPN patients younger than 18 years and carried out the histological review, DNA methylation, and gene expression profiling. Read More

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A Novel Balanced Chromosomal Translocation in an Azoospermic Male: A Case Report.

J Reprod Infertil 2021 Apr-Jun;22(2):133-137

Molecular Stress and Stem Cell Biology Group, School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India.

Background: Balanced translocation and azoospermia as two main reasons for recurrent pregnancy loss are known to be the leading causes of infertility across the world. Balanced translocations in azoospermic males are very rare and extensive studies need to be performed to elucidate the translocation status of the affected individuals.

Case Presentaion: The cytogenetic characterization of a 28 year old male and his female partner is reported in this study. Read More

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Evaluation of Microdissection Testicular Sperm Extraction (mTESE), Outcomes and Predictive Factors in Ireland: The Gold Standard for Men with Non-Obstructive Azoospermia.

J Reprod Infertil 2021 Apr-Jun;22(2):103-109

Department of Urology, University Hospital Waterford, Waterford, Ireland.

Background: Microdissection testicular sperm extraction (mTESE) is the gold standard approach in sperm retrieval in men with non-obstructive azoospermia (NOA). The purpose of the study was to assess the outcomes for Irish men who have undergone mTESE with a single surgeon.

Methods: This is a retrospective, single cohort study. Read More

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Combined F-FET PET and diffusion kurtosis MRI in posttreatment glioblastoma: differentiation of true progression from treatment-related changes.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab044. Epub 2021 Mar 10.

Institute of Neuroscience and Medicine, Research Centre Juelich, Juelich, Germany.

Background: Radiological differentiation of tumor progression (TPR) from treatment-related changes (TRC) in pretreated glioblastoma is crucial. This study aimed to explore the diagnostic value of diffusion kurtosis MRI combined with information derived from -(2-[F]-fluoroethyl)-l-tyrosine (F-FET) PET for the differentiation of TPR from TRC in patients with pretreated glioblastoma.

Methods: Thirty-two patients with histomolecularly defined and pretreated glioblastoma suspected of having TPR were included in this retrospective study. Read More

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H3K27M and promoter mutations are poor prognostic factors in surgical cases of adult thalamic high-grade glioma.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab038. Epub 2021 Feb 28.

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Background: Thalamic high-grade gliomas (HGGs) are rare tumors with a dismal prognosis. H3K27M and telomerase reverse transcriptase promoter () mutations reportedly contribute to poor prognoses in HGG cases. We investigated the outcomes of surgically treated adult thalamic HGGs to evaluate the prognostic significance of H3K27M and mutations. Read More

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February 2021

The state of neuro-oncology during the COVID-19 pandemic: a worldwide assessment.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab035. Epub 2021 Feb 20.

Departments of Medicine and Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.

Background: It remains unknown how the COVID-19 pandemic has changed neuro-oncology clinical practice, training, and research efforts.

Methods: We performed an international survey of practitioners, scientists, and trainees from 21 neuro-oncology organizations across 6 continents, April 24-May 17, 2020. We assessed clinical practice and research environments, institutional preparedness and support, and perceived impact on patients. Read More

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February 2021

The Oxygen Saturation in the Retinal Vessels of Patients with Diabetes Mellitus - The Search for Determinants.

Klin Monbl Augenheilkd 2021 May 17. Epub 2021 May 17.

Augenklinik, Technische Universität Dresden, Deutschland.

Introduction: Oxygen saturation in retinal vessels can be non-invasively measured by a new method. It is known that oxygen extraction is lowered in diabetic retinopathy. In the cross-sectional study presented here, it has been investigated whether diabetes-specific changes and typical accompanying diseases could influence the measurements in oximetry. Read More

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Pathogenic variants of ATG4D in infertile men with non-obstructive azoospermia identified using whole-exome sequencing.

Clin Genet 2021 May 14. Epub 2021 May 14.

Reproductive Medicine Centre, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility, and it is primarily associated with genetic defects. We performed whole-exome sequencing of 236 patients with NOA and identified a homozygous pathogenic variant of autophagy-related 4D cysteine peptidase (ATG4D) in two siblings from a consanguineous family and compound heterozygous pathogenic variants of ATG4D in two sporadic cases. The expression of LC3B, a regulator of autophagic activity, was significantly decreased, and the apoptosis rate of spermatogenic cells in testicular tissues was increased. Read More

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