Risk Of Brain Cancer Research Articles

Association of eczema with risk of pan-cancers: a two-sample Mendelian randomization study

Abstract Background Both eczema and tumor are associated with immune disorders. Although several investigations have observed the relationship between eczema and certain cancers, evidence for causality is lacking. Methods We conducted a two-sample Mendelian randomization (MR) study to examine and explore the genetic association between eczema and pan-cancers. Upon satisfying the three core assumptions of MR, we analyzed the causality between eczema and 15 site-specific cancers utilizing an inverse variance weighted method. We verified the results through a series of sensitivity and reverse direction analyses. The exposure and outcome datasets were substituted from the FinnGen and genome-wide association studies catalog databases. A meta-analysis on primary and validation analyses was performed to combine the estimates of MR study. Results Based on the MR analysis results, eczema was associated with an increased risk of lung cancer (odds ratio [OR] = 1.0427, 95% confidence interval [CI] = 1.0082–1.0783, P = 0.0148) and brain cancer (OR = 1.0285, 95% CI = 1.0120–1.0452, P = 0.0007) and decreased risk of colorectal cancer (OR = 0.9324, 95% CI = 0.8774–0.9909, P = 0.0242) and malignant neoplasm of the kidney (OR = 0.9323, 95% CI = 0.8834–0.9839, P = 0.0108). The sensitivity analysis indicated that the results were stable and reliable, and the reverse MR analyses demonstrated no causation between the cancers of interest and eczema. Conclusions Our results identified eczema as a genetic risk factor for lung and brain cancer and a protective factor for colorectal cancer and malignant neoplasm of the kidney. No connection was observed between eczema and other cancers. Further evidence from epidemiological and mechanistic studies is needed to elucidate these findings in detail.

Association between radiotherapy and the risk of second primary malignancies in breast cancer patients with different estrogen receptor statuses.

Breast cancer is the most common cancer among women. Second primary malignancies (SPMs) related to radiotherapy are significant complications. This study aims to investigate the correlation between radiotherapy and the occurrence of SPMs in breast cancer patients with different estrogen receptor statuses. We used data from the Surveillance, Epidemiology, and End Results (SEER) database, selecting estrogen receptor(+) and estrogen receptor(-) breast cancer patients from 1990 to 2015, with SPMs as the outcome measure. Fine-Gray competing risks regression and Poisson regression were employed to analyze the relationship between radiotherapy and the risk of SPMs in different estrogen receptor status groups. Radiotherapy was associated with an increased risk of lung cancer, melanoma, non-Hodgkin lymphoma, and leukemia in estrogen receptor(+) patients. In estrogen receptor(-) patients, radiotherapy was linked to an increased risk of brain cancer and leukemia. The cumulative incidence, standardized incidence ratio, and subgroup analyses showed consistent results. In the dynamic assessment of radiotherapy-related risks, estrogen receptor(+) patients aged 50-70 exhibited a higher risk of leukemia and melanoma. Lung cancer risk was highest during a latency period of 20-30 years, while melanoma, non-Hodgkin lymphoma, and leukemia risks peaked within the first 10 years. For estrogen receptor(-) patients, brain cancer risk was higher between ages 50 and 70, and leukemia risk was elevated between ages 20 and 50. Postoperative radiotherapy for breast cancer is associated with an increased risk of SPMs, with risks varying by estrogen receptor status and SPM type. Further research into the prevention of radiotherapy-related SPMs in different estrogen receptor status groups is crucial.

Pediatric Carotid Injury after Blunt Trauma and the Necessity of CT and CTA-A Narrative Literature Review.

Background: Blunt carotid injury (BCI) in pediatric trauma is quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/blunt cerebrovascular injury (BCVI) on pediatric patients after blunt trauma is, what routine diagnostics looks like, if a computed tomography (CT)/computed tomography angiography (CTA) scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects. Methods: This narrative literature review includes reviews, systematic reviews, case reports and original studies in the English language between 1999 and 2020 that deal with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure for children were included in this study. For literature research, Medline (PubMed) and the Cochrane library were used. Results: Pediatric BCI/BCVI shows an overall incidence between 0.03 and 0.5% of confirmed BCI/BCVI cases due to pediatric blunt trauma. In total, 1.1-3.5% of pediatric blunt trauma patients underwent CTA to detect BCI/BCVI. Only 0.17-1.2% of all CTA scans show a positive diagnosis for BCI/BCVI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligrays (mGy), whereas a computed tomography angiography needs at least 138 mGy. A cumulative dose of about 50 mGy almost triples the risk of leukemia, and a cumulative dose of about 60 mGy triples the risk of brain cancer. Conclusions: Given that a BCI/BCVI could have extensive neurological consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. CT and CTA are mostly used in routine BCI/BCVI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are established BCI/BCVI screening options, as well as duplex ultrasound.

Validation of mobile phone use recall in the multinational MOBI-kids study.

Potential differential and non-differential recall error in mobile phone use (MPU) in the multinational MOBI-Kids case-control study were evaluated. We compared self-reported MPU with network operator billing record data up to 3 months, 1 year, and 2 years before the interview date from 702 subjects aged between 10 and 24 years in eight countries. Spearman rank correlations, Kappa coefficients and geometric mean ratios (GMRs) were used. No material differences in MPU recall estimates between cases and controls were observed. The Spearman rank correlation coefficients between self-reported and recorded MPU in the most recent 3 months were 0.57 and 0.59 for call number and for call duration, respectively. The number of calls was on average underestimated by the participants (GMR = 0.69), while the duration of calls was overestimated (GMR = 1.59). Country, years since start of using a mobile phone, age at time of interview, and sex did not appear to influence recall accuracy for either call number or call duration. A trend in recall error was seen with level of self-reported MPU, with underestimation of use at lower levels and overestimation of use at higher levels for both number and duration of calls. Although both systematic and random errors in self-reported MPU among participants were observed, there was no evidence of differential recall error between cases and controls. Nonetheless, these sources of exposure measurement error warrant consideration in interpretation of the MOBI-Kids case-control study results on the association between children's use of mobile phones and potential brain cancer risk.

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study.

Atopic dermatitis ranks among the prevalent skin disorders. Research has indicated a potential association with brain cancer. Yet, establishing a direct causal relationship between atopic dermatitis and brain cancer continues to be challenging. We extracted single nucleotide polymorphisms (SNPs) significantly associated with atopic dermatitis (sample size=382 254) at a genome-wide level from a large Finnish Genome-Wide Association Study (GWAS) dataset (n cases=15 208, n controls=367 046). Summary data for 372 622 cases of brain cancer (n cases=606, n controls=372 016) were obtained via the IEU Open GWAS database. We employed the Inverse Variance Weighted (IVW) method as our primary analytical approach for Mendelian Randomization (MR) analysis. Additionally, heterogeneity was measured using Cochran's Q value, and horizontal pleiotropy was evaluated using MR-Egger 、Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave-one-out analyses. The risk of brain cancer increases with the presence of atopic dermatitis, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs),(OR=1.0005; 95% CI=1.0001, 1.0009;p=0.0096). However, when conducting the analysis in reverse, no significant link was observed. The findings from our study indicate a causative link between atopic dermatitis and brain cancer, highlighting the importance of conducting broader clinical investigations into their potential association going forward.

THE INFLUENCE OF QUERCETIN ON THE PRODUCTION OF REACTIVE OXYGEN-NITROGEN FORMS IN THE STRUCTURE OF THE INTERSTITIAL SPACE OF RAT TESTICLES WITH LONG-TERM EFFECT OF TRIPTORELIN

Quercetin is a flavonoid commonly found in fruits, vegetables, and seeds. Flavonoids can help prevent cardiovascular diseases, reduce the risk of degenerative brain processes and cancer. Studies have shown that blocking the synthesis of luteinising hormone can lead to oxidative stress in the liver, heart, and salivary glands of rats. The purpose of this study was to assess alterations in the interstitial space of rat testes, identify sources of nitric oxide production, and measure the intensity of oxidative stress in the testes during long-term experimental central blocking of luteinising hormone synthesis by tryptorelin. The study was conducted on 15 sexually mature male white rats. The animals were divided into two groups. The first group (control) received a subcutaneous injection of 0.9% sodium chloride solution. The second group (experimental) received a subcutaneous injection of tryptorelin at a dose of 0.3 mg/kg of active ingredient for 365 days, with simultaneous addition of quercetin to the diet, which was administered orally through a gastric tube three times a day. Total nitric oxide production was assessed by measuring the activity of total NO synthase (gNOS). The activity of gNOS was determined by the increase in nitrite (NO2-) after incubation in Tris-buffered saline. The nitrite concentration was determined using the Gris-Ilosvay reagent at a wavelength of 540 nm. The activity of the inducible (iNOS) and constitutive (cNOS) isoforms was also determined using a selective iNOS inhibitor, aminoguanidine hydrochloride. The production of superoxide anion radical (O2--) was measured by the increase in the formation of diformazan resulting from the reaction of O2-- with nitroblue tetrazolium after incubation in a buffered solution containing sodium hydroxide. The administration of quercetin mitigates the adverse effects of tryptorelin on the structural and functional components of the connective tissue in the rat testes. This effect is observed on day 365 and is characterised by fibrosis and impaired nitric oxide production by constitutive isoforms of NO synthase.

Effect of quercetin administration on electron microscopic changes in testicular interstitial endocrinocytes during long-term central blockade of luteinising hormone in rats

Quercetin is a flavonoid with potential health benefits and it may help prevent cardiovascular diseases, reduce the risk of degenerative brain processes and cancer, and has antioxidant properties that neutralise free radicals. Substances in this group also have antioxidant properties, which help the body protect itself from the harmful effects of free radicals by neutralising these unstable molecules. Research indicates that the impact of free radicals on cell structure is associated with the development of chronic diseases such as diabetes, cancer, and cardiovascular pathologies. The aim of the study was to investigate the effect of quercetin administration on electron microscopic changes in the interstitial endocrinocytes of the testes under long-term central blockade of the synthesis of luteinising hormone by tryptorelin. The experiment involved 35 sexually mature male white rats. They were divided into two groups: the control group (I) received saline, while group II received subcutaneous injections of tryptorelin at a dose of 0.3 mg of active ingredient per kg of rat body weight to induce experimental central deprivation of luteinising hormone synthesis and additionally, quercetin was administered three times a day by gastric tube in terms of body weight. The study has demonstrated that the administration of tryptorelin results in structural and functional changes in the connective tissue components of rat testes. Specifically, there are quantitative and qualitative disorders in the population of interstitial endocrine cells, as well as electron microscopic changes at the subcellular level. Various pathological changes and abnormalities in the functional activity of the internal components of the cell were detected on days 270 and 365 of the experiment. The frequency, number, and size of Reinke crystals in relation to the cell volume correlated with changes in cells and increased at later stages of the study. A similar correlation with testosterone levels has not been found in the literature, which leads us to classify Reinke crystals as the result of degenerative processes in the cell. Thus, additional administration of quercetin reduces the adverse effect of tryptorelin and delays the onset of changes in the structure of interstitial endocrinocytes from day 180 to later observation periods.

Exploring Longitudinal MRI-Based Deep Learning Analysis in Parkinson’s Patients - A Short Survey Focus on Handedness

&lt;p class="MsoNormal" style="text-align: justify;"&gt;&lt;span lang="EN-US" style="mso-bidi-font-size: 10.5pt; font-family: Nunito; color: #212529; background: white;"&gt;Parkinson&amp;rsquo;s Disease (PD) is a prevalent progressive neurodegenerative condition affecting millions globally. Research has found that individuals with PD have a reduced risk of certain cancers, such as colon, lung, and rectal cancers, but an increased risk of brain cancer. Therefore, there is an urgent need for the development of advanced PD diagnostic methods and for investigating the relationships between risk factors, such as lifestyle due to handedness associated with various types of cancers. Recent ad- vancements in magnetic resonance imaging have enhanced PD diagnosis, reducing misdiagnosis and facilitating more accurate disease progression monitoring. Nevertheless, challenges exist, particularly in the distinction of PD between left-handed and right-handed patients over time. This survey provides an overview of contemporary deep learning-based imag- ing analysis methodologies, encompassing both non-longitudinal and lon- gitudinal contexts. We also explore existing limitations and prospects for refinement to gain deeper insights. These insights are poised to inform the development of personalized treatment strategies for PD patients while elucidating the current disparities between deep learning models and their efficacious implementation in clinical practice.&lt;/span&gt;&lt;/p&gt;

Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars

While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful. To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer. A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium were included. The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating). The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index. After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer. In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex

Although the Food and Drug Administration has authorized the marketing of “heat-not-burn” (HnB) electronic cigarettes as a modified risk tobacco product (MRTP), toxicological effects of HnB smoke exposure on the brain are still unexplored. Here, paramagnetic resonance of the prefrontal cortex (PFC) of HnB-exposed rats shows a dramatic increase in reactive radical species (RRS) yield coupled with an inflammatory response mediated by NF-κB-target genes including TNF-α, IL-1β, and IL-6 and the downregulation of peroxisome proliferator-activated receptor (PPAR) alpha and gamma expression. The PFC shows higher levels of 8-hydroxyguanosine, a marker of DNA oxidative damage, along with the activation of antioxidant machinery and DNA repair systems, including xeroderma pigmentosum group C (XPC) protein complex and 8-oxoguanine DNA glycosylase 1. HnB also induces the expression of drug-metabolizing enzymes such as CYP1A1, CYP2A6, CYP2B6, and CYP2E, particularly involved in the biotransformation of nicotine and several carcinogenic agents such as aldehydes and polycyclic aromatic hydrocarbons here recorded in the HnB stick smoke. Taken together, these effects, from disruption of redox homeostasis, inflammation, PPAR manipulation along with enhanced bioactivation of neurotoxicants, and upregulation of cMYC protooncogene to impairment of primary cellular defense mechanisms, suggest a possible increased risk of brain cancer. Although the HnB device reduces the emission of tobacco toxicants, our findings indicate that its consumption may carry a risk of potential adverse health effects, especially in non-smokers so far. Further studies are needed to fully understand the long-term effects of these devices.

Association between psychiatric disorders and glioma risk: evidence from Mendelian randomization analysis

BackgroundObservational studies have explored the association of psychiatric disorders and the risk of brain cancers. However, the causal effect of specific mental illness on glioma remains elusive due to the lack of solid evidence.MethodsWe performed a two-sample bidirectional Mendelian randomization (MR) analysis to explore the causal relationships between 5 common psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, autism spectrum disorder, and panic disorder) and glioma. Summary statistics for psychiatric disorders and glioma were extracted from Psychiatric Genomics Consortium (PGC) and 8 genome-wide association study (GWAS) datasets respectively. We calculated the MR estimates for odds ratio of glioma associated with each psychiatric disorder by using inverse-variance weighting (IVW) method. Sensitivity analyses such as weighted median estimator, MR-Egger and MR-PRESSO were leveraged to assess the strength of causal inference.ResultsA total of 30,657 participants of European ancestry were included in this study. After correction for multiple testing, we found that genetically predicted schizophrenia was associated with a statistically significant increase in odds of non-glioblastoma multiforme (non-GBM) (OR = 1.13, 95% CI: 1.03–1.23, P = 0.0096). There is little evidence for the causal relationships between the other 4 psychiatric disorders with the risk of glioma.ConclusionsIn this MR analysis, we revealed an increased risk of non-GBM glioma in individuals with schizophrenia, which gives an insight into the etiology of glioma.

Mendelian randomization combined with multi-omics explores the relationship between heart failure and cancer.

Background: Whether there is an association between HF (HF) and cancer has not been conclusively established, and it is not clear whether patients with cancer can share similar hospitalization strategies and outcomes with patients with HF. Methods: Genome-wide association summary statistics were performed using a two-sample Mendelian randomization (MR) method for HF patients and cancer patients from the GWAS directory, with co-localization and Summary Data-Based Mendelian Randomization (SMR) analyses to identify HF-associated genes, and transcriptomic analyses to analyze the roles of these genes in the clinical diagnosis and targeted therapies of multiple cancer types. Results: Two-sample MR analysis showed that increased risk of HF was associated with decreased risk of cervical, brain, breast, colorectal, lung, and skin cancers, and co-localization combined with SMR analysis identified ABO and SURF1 as HF-associated genes, and transcriptomic analyses showed that ABO is a risk factor for HF and a protective factor against cancer, whereas SURF1 is a protective factor against HF and a protective factor against cancer. Conclusion: There was no causal relationship between heart failure and cancers (Cervical, brain, breast, colorectal, lung and skin cancers) risk factors, however there was a trend toward a negative causal relationship between heart failure and cancers (Cervical, brain, breast, colorectal, lung and skin cancers) occurrence.

Unveiling the etiological impact of GST-M1, GST-T1, and P53 genotypic variations on brain carcinogenesis.

Functional variants of glutathione-S-transferase (GST)-M1, GST-T1, p53 might modulate brain cancer risk by altering the rate of metabolism and clearance of carcinogens from the brain tissue. In this study, the role of GST-M1, GST-T1, p53 polymorphisms on brain tumor was investigated. Brain tumor tissues of 143 patients were obtained from the Gulhane Training and Research Hospital, Department of Neurosurgery between 2019 and 2020. In the xenobiotic mechanism, the null allele frequency in the GST-T1, GST-M1 gene regions of Phase II enzymes by qPCR method were investigated. Single nucleotide polymorphism encoding Arg/Pro conversion in the p53 gene region was analyzed in 120 cases by sequence analysis method. The data were analyzed statistically with patient's demographic and clinical data. GST-M1, GST-T1, p53 genotypes of the patient group were determined. The most frequent genotype was null genotype (0/0) for GST-M1 (χ2 = 39.756, p < 0.001). GST-M1 genotype frequencies were 30.8%, 23.1%, 44.3% for 1/1, 1/0, 0/0, respectively. The most frequent genotype was GST-T1 1/1 following by GST-T1 1/0 (χ2 = 0.335, p = 0.846). GST-T1 genotype frequencies were 64.3%, 30.8%, 4.9% for 1/1, 1/0, 0/0, respectively. GST-M1 null genotype might be associated with the development of brain tumors. Genotype distribution obtained in p53 exon 4 codon 72; Arg/Arg was determined as 31 (25.8%), Arg/Pro 70 (58.3%), and Pro/Pro 19 (15.8%) in the case group, while there were 18 (38.3%), 23 (48.9%), and 6 (12.8%) respectively in the control group. However, the genotype distribution of p53 exon 4 codon 72 among tumorous tissue did not significantly vary from healthy control tissues (χ²=2.536, p = 0.281). The null allele frequency encountered in the GST-M1, GST-T1 gene regions is consistent with the rates in the gene pool called Caucasian in the literature. GST-M1 gene polymorphism may play a crucial role in brain carcinogenesis in Turkish patients. This study based on clinical data is thought to help to understand the important epidemiological features of brain tumors.

Discontinuation Of Long-Established Hydroxyprogesterone Caproate; Call For Awareness And Drug-Substitutes: A Letter To The Editor.

Madam, 17-Hydroxyprogesterone caproate is a synthetic progestin medication used to prevent preterm birth in pregnant women with a prior history of preterm birth. The drug has been used worldwide, including in Pakistan (local brand names Gravibinan and Proluton) for the prevention of PTBs and recurrent miscarriages. The drug is potent, cost-effective and readily available as IM injections. The FDA approved drug in 2011 after the Meis trial, which was regarded as a game-changer. [1] But many subsequent trials showed that the drug did not significantly lowered the risks of preterm births. The PROLONG study, much larger than the Meis trial, that was conducted in association with the FDA between 2009 and 2018 as a confirmatory trial showed practice-changing results that 17 OHPC did not significantly reduce the risk of PTB and neonatal morbidity, hence not confirming treatment efficacy. [2] The FDA ultimately in 2023 issued a statement recalling Makena (17-OHPC) and its generics from the market stating that the drug had no significant role in reducing the risk of PTBs and has potential risks to the offspring in the long term. [3] A study by C. Murphy et. al published in the American Journal of Obstetrics and Gynecology showed an increased risk of prostate, colorectal and pediatric brain cancer in offspring exposed to 17 OHPC especially during the first trimester. [4] Micronized progesterones (locally available as Progefik and U-Progest) on the contrary, are chemically similar to human progesterone and are therefore regarded as ‘body-identical’. They are administered orally or vaginally and have similar effects as 17-OHPC in the prevention of PTB. A comparative study in India by Shambhavi et.al was one of the various studies to show that no significant difference in the two medications for the prevention of PTB and neonatal morbidity. [5] Micronized progesterone has largely gained popularity in recent years and has replaced 17-OHPC in preventing PTBs especially in women with short cervix. 17-OHPC is still being widely prescribed in Pakistan. Efforts should be made to spread awareness among the healthcare practitioners regarding the disapproval by FDA for continued use of 17-OHPC. Pakistan’s Drug Regulation Authority needs to act accordingly regarding the continued approval of the drug in the country and spread awareness about its substitutes with better potency and reduced risks. Moreover, continued research about the efficacy of other progesterones administered to reduce PTBs and their potential risk factors in the long run is needed.

Molecular programs of regional specification and neural stem cell fate progression in macaque telencephalon.

During early telencephalic development, intricate processes of regional patterning and neural stem cell (NSC) fate specification take place. However, our understanding of these processes in primates, including both conserved and species-specific features, remains limited. Here, we profiled 761,529 single-cell transcriptomes from multiple regions of the prenatal macaque telencephalon. We deciphered the molecular programs of the early organizing centers and their cross-talk with NSCs, revealing primate-biased galanin-like peptide (GALP) signaling in the anteroventral telencephalon. Regional transcriptomic variations were observed along the frontotemporal axis during early stages of neocortical NSC progression and in neurons and astrocytes. Additionally, we found that genes associated with neuropsychiatric disorders and brain cancer risk might play critical roles in the early telencephalic organizers and during NSC progression.

Adjusting for Berkson error in exposure in ordinary and conditional logistic regression and in Poisson regression

BackgroundINTEROCC is a seven-country cohort study of occupational exposures and brain cancer risk, including occupational exposure to electromagnetic fields (EMF). In the absence of data on individual exposures, a Job Exposure Matrix (JEM) may be used to construct likely exposure scenarios in occupational settings. This tool was constructed using statistical summaries of exposure to EMF for various occupational categories for a comparable group of workers.MethodsIn this study, we use the Canadian data from INTEROCC to determine the best EMF exposure surrogate/estimate from three appropriately chosen surrogates from the JEM, along with a fourth surrogate based on Berkson error adjustments obtained via numerical approximation of the likelihood function. In this article, we examine the case in which exposures are gamma-distributed for each occupation in the JEM, as an alternative to the log-normal exposure distribution considered in a previous study conducted by our research team. We also study using those surrogates and the Berkson error adjustment in Poisson regression and conditional logistic regression.ResultsSimulations show that the introduced methods of Berkson error adjustment for non-stratified analyses provide accurate estimates of the risk of developing tumors in case of gamma exposure model. Alternatively, and under some technical assumptions, the arithmetic mean is the best surrogate when a gamma-distribution is used as an exposure model. Simulations also show that none of the present methods could provide an accurate estimate of the risk in case of stratified analyses.ConclusionWhile our previous study found the geometric mean to be the best exposure surrogate, the present study suggests that the best surrogate is dependent on the exposure model; the arithmetic means in case of gamma-exposure model and the geometric means in case of log-normal exposure model. However, we could present a better method of Berkson error adjustment for each of the two exposure models. Our results provide useful guidance on the application of JEMs for occupational exposure assessments, with adjustment for Berkson error.

Nitrate ingestion from drinking water and dietary sources and risk of brain cancer in the Agricultural Health Study

Nitrate ingestion from drinking water and dietary sources and risk of brain cancer in the Agricultural Health Study

Association between multiple sclerosis and cancer risk: An extensive review/meta and Mendelian randomization analyses.

Observational investigations examining cancer risk among multiple sclerosis (MS) patients have produced contradictory findings. Herein, we performed an extensive review and meta-analysis to evaluate the correlation and causation between MS and cancer incidence. We systematically screened for published articles examining cancer incidences among MS patients within the Cochrane Library, PubMed, and Embase databases. Next, we employed STATA v.16.0 for data analysis. Following meta-analysis, we performed a two-sample Mendelian randomization (MR) analysis to uncover the underlying mechanism behind the MS-mediated regulation of certain cancers. Overall, we selected 18 articles encompassing 14 individual cancers incidences and a total of 368,952 patients for meta-analysis. Based on our analysis, there was reduced pancreatic (ES=0.68; 95% CI: 0.49-0.93; I 2=0%) and ovarian cancer (ES=0.65; 95% CI: 0.53-0.80; I 2=86.7%) co-occurrences among MS patients. Meanwhile, the incidences of breast (ES=1.10; 95% CI: 1.01-1.21; I 2=60.9%) and brain cancers (ES=1.94; 95% CI: 1.12-3.37; I 2=56.1%) were elevated among the same population. However, MR analysis revealed the opposite relation between MS and breast cancer risk (OR=0.94392; 95% CI: 0.91011-0.97900, P=0.002). Moreover, it revealed strong incidence of lung cancer (OR=1.0004; 95% CI: 1.0001-1.0083, P=0.001) among MS patients, as evidenced by the inverse variance weighting estimator. Lastly, MR found that other forms of cancers were not significantly related to MS. Using meta-analysis, we demonstrated that MS patients exhibited enhanced pancreatic and ovarian cancer risk, and diminished breast and brain cancer risk. However, using MR analysis, we discovered an inverse relation between MS and breast cancer risk, and additionally saw an uptick in lung cancer co-occurrence among MS patients.

Causal associations of hyperthyroidism with prostate cancer, colon cancer, and leukemia: a Mendelian randomization study.

Observational studies have shown that hyperthyroidism may increase the risk of cancer, but their causal effects and direction are unclear. We conducted a two-sample Mendelian randomization (MR) study to explore the associations between genetic predisposition to hyperthyroidism and nine common types of cancer, including prostate, lung, breast, colon, leukemia, brain, skin, bladder, and esophagus cancer. We obtained summary statistics of hyperthyroidism and nine types of cancers from genome-wide association studies (GWAS). MR analysis is performed to investigate the potential causal relationship between hyperthyroidism and cancers. The inverse variance weighted (IVW) as the primary method was carried out. The robustness of the results was evaluated by sensitivity analysis. Genetically predicted hyperthyroidism was associated with a declining risk of occurrence of prostate cancer (odds ratio (OR)IVW= 0.859, P= 0.0004; OR MR-Egger=0.828, P= 0.03; OR weighted median= 0.827, P=0.0009). Additionally, there was a significant association between genetically predicted hyperthyroidism and colon cancer (OR IVW= 1.13, P= 0.011; OR MR-Egger= 1.31, P= 0.004; OR weighted median= 1.18, P= 0.0009). Hyperthyroidism was also suggestively correlated with a higher risk of leukemia based on the result of IVW and weighted median (OR IVW= 1.05, P= 0.01; OR weighted median= 1.08, P= 0.001). Results from a two-sample MR analysis suggested that hyperthyroidism was not associated with the risk of lung cancer, breast cancer, brain cancer, skin cancer, bladder cancer, and esophageal cancer. Our study provides evidence of a causal relationship between hyperthyroidism and the risk of prostate cancer, rectal cancer, and leukemia. Further research is needed to clarify the associations between hyperthyroidism and other cancers.