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OBJECTIVE: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted. RESULTS: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels (t=-3.546, P < 0.001), lower testosterone levels (t=-2.089, P=0.037), and a higher rate of hyperglycemia (χ2=12.772, P=0.002) compared with those with non-vascular ED. The patients with arterial ED were older (t=3.953, P < 0.001), had a higher rate of hyperglycemia (χ2=9.518, P=0.009), and a higher estrogen/testosterone ratio (t=2.330, P=0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age (t=3.567, P < 0.001), lower testosterone levels (t=-2.288, P=0.022), a higher rate of hyperglycemia (χ2=12.877, P=0.002), and a larger estrogen/testosterone ratio (t=2.096, P=0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED (OR=1.009, 95%CI: 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor (OR=0.381, 95%CI: 0.219-0.661). Older age was a risk factor for arterial ED (OR=0.960, 95%CI: 0.938-0.982). Additionally, older age (OR=0.976, 95%CI: 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L (OR=0.591, 95%CI: 0.399-0.876) were also risk factors for mixed arterio-venous ED. CONCLUSION: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.
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Disfunción Eréctil , Pene , Testosterona , Humanos , Masculino , Estudios Retrospectivos , Pene/irrigación sanguínea , Testosterona/sangre , Disfunción Eréctil/fisiopatología , Ultrasonografía Doppler en Color , Estrógenos/sangre , Persona de Mediana Edad , Factores de Edad , AdultoRESUMEN
BACKGROUND: According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. METHODS: From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. RESULTS: The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). CONCLUSIONS: The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.
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Preservación de la Fertilidad , Neoplasias , Análisis de Semen , Humanos , Masculino , Adolescente , Preservación de la Fertilidad/métodos , Estudios Retrospectivos , Neoplasias/radioterapia , China/epidemiología , Adulto Joven , Infertilidad Masculina/etiología , Infertilidad Masculina/prevención & control , Criopreservación/métodos , NiñoRESUMEN
Lithium-sulfur (Li-S) batteries are one of the most promising energy storage devices due to their environmental friendliness, low cost, and high specific capacity. However, the slow electrochemical kinetics and the "shuttle effect" have seriously hindered their commercialization. Herein, the nanoflower Bi2S3âMoS2 (BMS) heterostructure is synthesized by a two-step hydrothermal method, and then the Bi2S3âMoS2-Polypropylene (BMS-PP) interlayer is constructed. The heterostructure is rich in active sites, in which BMS has strong adsorption to lithium polysulfides (LiPSs) and can effectively anchor LiPSs while catalyzing LiPSs and promote the redox of Li2S at the same time, which can improve the utilization of active substances. More importantly, the d-band center can be tuned by the formation of Bi2S3âMoS2 heterostructure. Thus, Li-S batteries containing the BMS-PP interlayer show excellent rate performance (841.6 mAh g-1 at 5 C) and cycling performance (70.3% capacity retention after 500 cycles at 3 C). This work provides a new route for high-performance lithium-sulfur batteries.
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Optical multiplexing technologies, by utilizing various dimensions of light, can effectively expand the information capacity and density for holography but may also lead to multiplexing cross talk. Here, we propose and demonstrate a novel, to our knowledge, multiplicative-noise-multiplexing holography by utilizing the orthogonality between multiplicative noises as a multiplexing dimension. The results prove that this holography can provide a new multiplexing dimension, significantly enhancing information capacity and effectively lowering cross talk. This promising scheme for ultrahigh-capacity holography has the potential to address the limitations of traditional holographic multiplexing technologies.
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Due to their high energy density and cost-effectiveness, lithium-sulfur batteries (LSBs) are considered highly promising for the next generation of energy storage technologies. However, the soluble lithium-polysulfides (LiPSs) notorious for causing the shuttle effect and the sluggish redox kinetics have hindered their practical commercialization. To tackle these challenges, a heterostructural catalyst featuring NiS-NiCo2O4 interfaces is developed, which serves as an interlayer for LSBs. These interfacial sites leverage the advantages of polar NiCo2O4 and conductive NiS, enabling smooth Li+ diffusion, rapid electron transport, and effective immobilization of LiPSs. This synergistic approach promotes the conversion of sulfur species, resulting in a high discharge capacity of 526 mAh g-1 at 3 C for cells with the NiS-NiCo2O4 interlayer. Additionally, remarkable cycling stability is achievable with an areal sulfur loading of ≈5.0 mg cm-2. It is believed that this research paves the way for practical applications of LSBs.
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Azoospermia , Testículo , Humanos , Masculino , Testículo/cirugía , Azoospermia/diagnóstico , Azoospermia/cirugía , Recuperación de la Esperma , Microdisección , Estudios Retrospectivos , Semen , EspermatozoidesRESUMEN
Objective: To build a prediction model for live birth delivery per intracytoplasmic sperm injection (ICSI) in iNOA patients by obtaining sperm by microdissection testicular sperm extraction (mTESE). Methods: A retrospective cohort study of 377 couples with iNOA male partners treated with 519 mTESE-ICSI cycles was conducted from September 2013 to July 2021 at the Reproductive Medical Centre of Peking University Third Hospital. Following exclusions, 377 couples with iNOA male partners treated with 482 mTESE-ICSIs were included. A prediction model for live birth delivery per ICSI cycle was built by multivariable logistic regression and selected by 10-fold cross-validation. Discrimination was evaluated by c-statistics and calibration was evaluated by the calibration slope. Results: The live birth delivery rate per mTESE-ICSI cycle was 39.21% (189/482) in these couples. The model identified that the presence of motile sperm during mTESE, bigger testes, higher endometrial thickness on the day of human chorionic gonadotrophin (hCG) administration (ET-hCG), and higher quality embryos are associated with higher live birth delivery success rates. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the mean ROC curve was 0.71 ± 0.05 after 10-fold cross-validation, indicating that the prediction model had certain prediction precision. A calibration plot with an estimated intercept of -1.653 (95% CI: -13.403 to 10.096) and a slope of 1.043 (95% CI: 0.777 to 1.308) indicated that the model was well-calibrated. Conclusion: Our prediction model will provide valuable information about the chances of live birth delivery in couples with iNOA male partners who have a plan for mTESE-ICSI treatment. Therefore, it can improve and personalize counseling for the medical treatment of these patients.
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Azoospermia , Embarazo , Femenino , Humanos , Masculino , Azoospermia/terapia , Nacimiento Vivo/epidemiología , Estudios Retrospectivos , Modelos Estadísticos , Pronóstico , SemenRESUMEN
Genetic studies have elucidated the critical roles of Phf7 in germline development in animals; however, the exact etiology of Phf7 mutations leading to male infertility and the possibility of mechanism-based therapy are still unclear and warrant further investigation. Using the Phf7 knockout mouse model, we verified that genetic defects were responsible for male infertility by preventing histone-to-protamine exchange, as previously reported. The deficiency of spermatogenesis caused by Phf7 deletion through the endogenous retrovirus-mediated activation of the immune pathway is a common mechanism of infertility. Furthermore, we identified PPARα as a promising target of immunity and inflammation in the testis, where endogenous retroviruses are suppressed, and Phf7 as a crucial regulator of endogenous retrovirus-mediated immune regulation and revealed its role as an epigenetic reader. The loss of Phf7 activates immune pathways, which can be rescued by the PPARα agonist astaxanthin. These results showed that astaxanthin is a potential therapeutic agent for treating male infertility. The findings in our study provide insights into the molecular mechanisms underlying male infertility and suggest potential targets for future research and therapeutic development.
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Introduction: Milk fat is the most variable nutrient in milk, and recent studies have shown that rumen bacteria are closely related to milk fat. However, there is limited research on the relationship between rumen bacteria and milk fatty. Fatty acids (FAs) are an important component of milk fat and are associated with various potential benefits and risks to human health. Methods: In this experiment, forty-five healthy Holstein dairy cows with alike physiological and productive conditions were selected from medium-sized dairy farms and raised under the same feeding and management conditions. The experimental period was two weeks. During the experiment, raw milk and rumen fluid were collected, and milk components were determined. In this study, 8 high milk fat percentage (HF) dairy cows and 8 low milk fat percentage (LF) dairy cows were selected for analysis. Results: Results showed that the milk fat percentage in HF group was significantly greater than that of the dairy cows in the LF group. 16S rRNA gene sequencing showed that the rumen bacterial abundance of HF dairy cows was significantly higher than that in LF dairy cows; at the genus level, the bacterial abundances of Prevotellaceae_UCG-001, Candidatus_Saccharimonas, Prevotellaceae_UCG-003, Ruminococcus_1, Lachnospiraceae_XPB1014_group, Lachnospiraceae_AC2044_group, probable_genus_10 and U29-B03 in HF group were significantly higher than those in the LF group. Spearman rank correlation analysis indicated that milk fat percentage was positively related to Prevotellaceae_UCG-001, Candidatus_Saccharimonas, Prevotellaceae_UCG-003, Ruminococcus_1, Lachnospiraceae_XPB1014_group, Lachnospiraceae_AC2044_group, probable_genus_10 and U29-B03. Furthermore, Prevotellaceae_UCG-001 was positively related to C14:0 iso, C15:0 iso, C18:0, Ruminococcus_1 with C18:1 t9, Lachnospiraceae_AC2044_group with C18:1 t9 and C18:1 t11, U29-B03 with C15:0 iso. Discussion: To sum up, rumen bacteria in dairy cows are related to the variation of milk fat, and some rumen bacteria have potential effects on the deposition of certain fatty acids in raw milk.
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The precursors that appear when geological disasters occur are geotechnical deformations. This paper studies the TDR (Time Domain Reflection) measurement technology for the distributed measurement of geotechnical deformation using parallel spiral wire as a sensor, which is used for monitoring and early warning detection of geological disasters. Based on the mechanism of the electromagnetic field distribution parameters of the parallel spiral sensing wire, the relationship between the stretching amount of the parallel spiral wire and the change in its characteristic impedance is analyzed. When the parallel spiral wire is buried in the soil, the geotechnical deformation causes the parallel spiral wire to be stretched, and according to its characteristic impedance change, the stretching position and the stretching degree can be obtained, thus realizing the distributed measurement of geotechnical deformation. Based on this principle, the TDR measurement system is developed, and a local single-point stretching amount and stretching positioning experiment are designed for the parallel spiral sensing line to verify the effectiveness of the sensing technology and the usability of the measurement system.
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Commercial polymer separators usually have limited porosity, poor electrolyte wettability, and poor thermal and mechanical stability, which can deteriorate the performance of battery, especially at high current densities. In this work, a functional polyethylene (PE) separator is prepared by surface engineering a layer of Ti-doped SiO2 @Al2 O3 particles (denoted as ST@Al2 O3 -PE) with strong Lewis acid property and uniform porous structure on one side of the PE separator. On the other hand, ST@Al2 O3 particles with abundant pore structures and large cavities can store a large amount of electrolyte, providing a shortened pathway for lithium-ion transport, and the Lewis acid sites and porous structure of the ST@Al2 O3 can tune Li plating/stripping behavior and stabilize the lithium metal anode. The ST@Al2 O3 -PE separators exhibit better ionic conductivity (5.55 mS cm-1 ) and larger lithium-ion transference number (0.62). At a current density of 1 mA cm-2 , Li/Li symmetric cells with ST@Al2 O3 -PE separator can be stably cycled for more than 400 h, and both lithium iron phosphate /Li cells and lithium cobaltate/Li cells with ST@Al2 O3 -PE separator have good cycling and rate performance. This work provides a new strategy for developing functional separators and promoting the application of lithium metal batteries.
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Background: Mucolipidosis type II (MLII), or I-cell disease, is a rare lysosomal storage disease (LSD) caused by variants in the GNPTAB gene. MLII patients exhibit clinical phenotypes in the prenatal or neonatal stage, such as marked dysmorphic features, cardiac involvement, respiratory symptoms, dysostosis multiplex, severe growth abnormalities, and mental and motor developmental abnormalities. The median age at diagnosis for MLII is 0.7 years, the median survival is 5.0 years, and the median age at death is 1.8 years. No cure for MLII exists. Methods: Sanger sequencing of the GNPTAB gene identified the compound heterozygous mutations c.673C > T in exon 7 and c.1090C > T in exon 9, which were novel double heterozygous mutations first reported in China. For the first time, we describe our experience in the use of HSCT for MLII. Our patient underwent HSCT with cells from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor at 12 months of age. Myeloid neutrophil and platelet engraftment occurred on Days 10 and 11, respectively. Results: The patient's limb muscle tension was significantly reduced, and his gross and fine motor skills were improved four months after transplantation. DST(Developmental Screen Test) results showed that the patient's fine motor skills and mental development were improved compared with before HSCT. Conclusion: MLII is a very severe lysosomal storage disease, to date, only 3 cases have been reported on the use of HSCT to treat MLII. Our data show that HSCT is a potential way to prolong the life of patients and improve their quality of life. Due to the lack of comparable data and time, the exact benefit remains unclear in MLII patients. Longer-term follow-up and in-depth prospective studies are indispensable.
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MOTIVATION: Gene expression is characterized by stochastic bursts of transcription that occur at brief and random periods of promoter activity. The kinetics of gene expression burstiness differs across the genome and is dependent on the promoter sequence, among other factors. Single-cell RNA sequencing (scRNA-seq) has made it possible to quantify the cell-to-cell variability in transcription at a global genome-wide level. However, scRNA-seq data are prone to technical variability, including low and variable capture efficiency of transcripts from individual cells. RESULTS: Here, we propose a novel mathematical theory for the observed variability in scRNA-seq data. Our method captures burst kinetics and variability in both the cell size and capture efficiency, which allows us to propose several likelihood-based and simulation-based methods for the inference of burst kinetics from scRNA-seq data. Using both synthetic and real data, we show that the simulation-based methods provide an accurate, robust and flexible tool for inferring burst kinetics from scRNA-seq data. In particular, in a supervised manner, a simulation-based inference method based on neural networks proves to be accurate and useful when applied to both allele and nonallele-specific scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: The code for Neural Network and Approximate Bayesian Computation inference is available at https://github.com/WT215/nnRNA and https://github.com/WT215/Julia_ABC, respectively.
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Perfilación de la Expresión Génica , Transcriptoma , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia de ARN/métodos , Programas Informáticos , Teorema de Bayes , Cinética , Funciones de Verosimilitud , Análisis de la Célula Individual/métodos , ARNRESUMEN
Introduction: Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is a powerful analytical technique that has been applied to a wide variety of applications ranging from proteomics to clinical diagnostics. One such application is its use as a tool for discovery assays, such as monitoring the inhibition of purified proteins. With the global threat from antimicrobial-resistant (AMR) bacteria, new and innovative solutions are required to identify new molecules that could revert bacterial resistance and/or target virulence factors. Here, we used a whole cell-based MALDI-TOF lipidomic assay using a routine MALDI Biotyper Sirius system operating in linear negative ion mode combined with the MBT Lipid Xtract kit to discover molecules targeting bacteria that are resistant to polymyxins, which are considered last-resort antibiotics. Methods: A library of 1200 natural compounds was tested against an E. coli strain expressing mcr-1, which is known to modify lipid A by adding phosphoethanolamine (pETN), making the strain resistant to colistin. Results and Discussion: Using this approach, we identified 8 compounds that led to a decrease in this lipid A modification by MCR-1 and could potentially be employed to revert resistance. Taken together, as-proof-of-principle, the data we report here represent a new workflow based on the analysis of bacterial lipid A by routine MALDI-TOF for the discovery of inhibitors that could target bacterial viability and/or virulence.
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Glioblastoma (GBM) recurrence originates from invasive margin cells that escape surgical debulking, but to what extent these cells resemble their bulk counterparts remains unclear. Here, we generated three immunocompetent somatic GBM mouse models, driven by subtype-associated mutations, to compare matched bulk and margin cells. We find that, regardless of mutations, tumors converge on common sets of neural-like cellular states. However, bulk and margin have distinct biology. Injury-like programs associated with immune infiltration dominate in the bulk, leading to the generation of lowly proliferative injured neural progenitor-like cells (iNPCs). iNPCs account for a significant proportion of dormant GBM cells and are induced by interferon signaling within T cell niches. In contrast, developmental-like trajectories are favored within the immune-cold margin microenvironment resulting in differentiation toward invasive astrocyte-like cells. These findings suggest that the regional tumor microenvironment dominantly controls GBM cell fate and biological vulnerabilities identified in the bulk may not extend to the margin residuum.
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Neoplasias Encefálicas , Glioblastoma , Células-Madre Neurales , Animales , Ratones , Glioblastoma/genética , Glioblastoma/patología , Diferenciación Celular , Microambiente Tumoral , Células-Madre Neurales/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologíaRESUMEN
Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10-15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human testicular single-cell transcriptomes from 17 iNOA patients, which are classified into four classes with different arrest periods and variable cell proportions based on the gene expression patterns and pathological features. Genes related to the cell cycle, energy production, and gamete generation show obvious abnormalities in iNOA germ cells. This work identifies several candidate causal genes for iNOA, including CD164, LELP1, and TEX38, which are significantly downregulated in iNOA germ cells. Notably, CD164 knockdown promotes apoptosis in spermatogonia. Cellular communications between spermatogonial stem cells and Sertoli cells are disturbed in iNOA patients. Moreover, BOD1L2, C1orf194, and KRTCAP2 are found to indicate testicular spermatogenic capacity in a variety of testicular diseases, such as Y-chromosome microdeletions and Klinefelter syndrome. In general, this study analyzes the pathogenesis of iNOA from the perspective of germ cell development, transcription factor (TF) regulatory networks, as well as germ cell and somatic cell interactions, which provides new ideas for clinical diagnosis.
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Azoospermia , Infertilidad Masculina , Humanos , Masculino , Azoospermia/genética , Azoospermia/metabolismo , Azoospermia/patología , Infertilidad Masculina/patología , Testículo/metabolismo , Testículo/patología , Células GerminativasRESUMEN
Lithium-sulfur batteries (LSBs) have become very promising next-generation energy-storage technologies owing to their high energy densities and cost-effectiveness. However, the poor electrical conductivity of the active material, volume changes that occur during cycling, the "shuttle effect" involving lithium polysulfides (LiPSs), and lithium dendrite growth limit their commercializability. Herein, the preparation of a CC@VS2 -VO2 @Li2 S@C electrode prepared by the in situ growth of a VS2 -VO2 heterostructure on carbon cloth (CC), loaded with Li2 S, and finally coated with a carbon shell, is reported. The cell with the CC@VS2 -VO2 @Li2 S@C cathode exhibits superior cycling stability and rate performance owing to synergy between its various components. The cell delivers a high discharge specific capacity of 919.8 mA g-1 at 0.2 C, with a capacity of 588.9 mAh g-1 retained after 500 cycles with an average capacity attenuation of 0.072% per cycle. The cell exhibits discharge capacities of 937.6, 780.2, 641.9, 541, and 462.8 mAh g-1 at current densities of 0.2, 0.5, 1, 2, and 3 C, respectively. This study provides a new approach for catalyzing LiPS conversion and promoting LSB applications.
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Background: Male reproductive health has become a serious public health concern, and semen quality is essential to male reproduction. We aimed to investigate geographical differences in the semen quality of sperm donors from northern and southern China by enrolling donors across the country. Methods: A total of 1,012 sperm donors were enrolled in this study between 2015 and 2019. Donors were first divided into two parts based on their birthplace according to the "Qinling-Huaihe" line, and secondly, by their residential latitude. Finally, donors were re-classified into two groups (typically north and south) which contained 667 samples. Results: Statistically significant differences in sperm concentration were observed among men from different latitudes in China (P=0.04). The sperm concentrations of males from 18° to 27° north latitude were significantly lower than those from 36° to 45° and 45° to 54° [median 131, 134, and 146, respectively, P=0.021 (18° to 27° vs. 36° to 45°) and P=0.01 (18° to 27° vs. 45° to 54°)]. Conclusion: We hypothesize environmental pollution and mental stress due to the increased population size may be the main factors underlying differences in the sperm quality of men in northern and southern China.
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Mathematical oncology provides unique and invaluable insights into tumour growth on both the microscopic and macroscopic levels. This review presents state-of-the-art modelling techniques and focuses on their role in understanding glioblastoma, a malignant form of brain cancer. For each approach, we summarize the scope, drawbacks and assets. We highlight the potential clinical applications of each modelling technique and discuss the connections between the mathematical models and the molecular and imaging data used to inform them. By doing so, we aim to prime cancer researchers with current and emerging computational tools for understanding tumour progression. By providing an in-depth picture of the different modelling techniques, we also aim to assist researchers who seek to build and develop their own models and the associated inference frameworks. Our article thus strikes a unique balance. On the one hand, we provide a comprehensive overview of the available modelling techniques and their applications, including key mathematical expressions. On the other hand, the content is accessible to mathematicians and biomedical scientists alike to accommodate the interdisciplinary nature of cancer research.