Spatio-Temporal Trend and Geographic Disparity of Infertility Prevalence in Burkina Faso, 2011 to 2020

Background: Infertility affected 10% to 25% of couples globally, and about half of the infertility cases were reported in sub-Saharan Africa. Infertility poses significant social, cultural, and health challenges, particularly for women who often face stigmatization. However, comprehensive and nationally representative data, including prevalence, temporal trends, and risk factors, are lacking, prompting a study in Burkina Faso to address the need for informed policies and programs in infertility care and management. Objectives: This study aims to better understand the spatiotemporal trend of infertility prevalence in Burkina Faso. Methodology: This is a retrospective population-based study of women infertility from healthcare facilities in Burkina Faso, during January 2011 to December 2020. We calculated the prevalence rates of infertility and two disparity measures, and examined the spatiotemporal trend of infertility. Results: Over the 10-year period (2011 to 2020), 143,421 infertility cases were recorded in Burkina Faso healthcare facilities, resulting of a mean prevalence rate of 3.61‰ among childbearing age women and 17.87‰ among women who consulted healthcare facilities for reproductive issues (except contraception). The findings revealed a significant increase of infertility, with the prevalence rate varied from 2.75‰ in 2011 to 4.62‰ in 2020 among childbearing age women and from 13.38‰ in 2011 to 26.28‰ in 2020 among women who consulted healthcare facilities for reproductive issues, corresponding to an estimate annual percentage change of 8.31% and 9.80% respectively. There were significant temporal and geographic variations in the prevalence of infertility. While relative geographic disparity decreased, absolute geographic disparity showed an increasing trend over time. Conclusion: The study highlights an increasing trend of infertility prevalence and significant geographic variation in Burkina Faso, underscoring the urgent necessity for etiologic research on risk factors, psychosocial implications, and economic consequences to inform effective interventions and mitigate the socioeconomic impact of infertility.

Esophageal squamous cell cancer in a highly endemic region

AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α(8-iso PGF2α).METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence ofesophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus(HIV) serology. Urine was collected, and 8-iso PGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine.RESULTS: Forty five controls(mean age 54.2 ± 15.3, 31 male) and 27 cases(mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases(median 16.8) than controls(median 23.2), P = 0.01. Histopathologically, 25/27(93%) were squamous cell carcinoma and 2/27(7%) adenocarcinoma. More cases smoked cigarettes(OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly(P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups(P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases(0.03 ng/mg creatinine) than controls(0.01 ng/mg creatinine)(OR = 2.35, 95%CI: 1.19-4.65, P = 0.014).CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not.

Stroma-targeting strategies in pancreatic cancer:Past lessons,challenges and prospects

Pancreatic ductal adenocarcinoma(PDAC)is projected to emerge as the second leading cause of cancer-related death after 2030.Extreme treatment resistance is perhaps the most significant factor that underlies the poor prognosis of PDAC.To date,combination chemotherapy remains the mainstay of treatment for most PDAC patients.Compared to other cancer types,treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and shorterlived.Aside from typically harboring genetic alterations that to date remain undruggable and are drivers of treatment resistance,PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting cancer progression and treatment resistance.However,emerging evidence also suggests that indiscriminate targeting and near complete depletion of stroma may promote PDAC aggressiveness and lead to detrimental outcomes.These conflicting results undoubtedly warrant the need for a more in-depth understanding of the heterogeneity of tumor stroma in order to develop modulatory strategies in favor of tumor suppression.The advent of novel techniques including single cell RNA sequencing and multiplex immunohistochemistry have further illuminated the complex heterogeneity of tumor cells,stromal fibroblasts,and immune cells.This new knowledge is instrumental for development of more refined therapeutic strategies that can ultimately defeat this disease.Here,we provide a concise review on lessons learned from past stromatargeting strategies,new challenges revealed from recent preclinical and clinical studies,as well as new prospects in the treatment of PDAC.

表皮生长因子/HER2抑制剂在非小细胞肺癌患者治疗中的作用综述

晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)仍然是主要的全球健康问题。尽管可逆性表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂厄洛替尼可改善复发与再发NSCLC患者的生存期,但也存在明显的局限性,包括仅对少数患者亚群具有临床疗效、生存率较低及产生耐药性。EGFR和HER2的非可逆性抑制剂是临床开发的新型药物,有可能预防并克服第一代EGFR抑制剂的获得性耐药。

A Study of Zoledronic Acid as Neo-Adjuvant, Perioperative Therapy in Patients with Resectable Pancreatic Ductal Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by abundant granulocytic myeloid-derived suppressor cells (G-MDSC = CD45+/Lin﹣/CD33+/CD11b+/CD15+), which infiltrate tumors and suppress anti-tumor immunity. We have previously demonstrated in a murine model of PDAC that zoledronic acid (ZA) depletes G-MDSC resulting in decreased tumor growth and improved survival. We report here the results of a phase 1 clinical trial (NCT00892242) using ZA as neo-adjuvant, perioperative therapy in patients with non-metastatic, resectable pancreatic adenocarcinoma. Methods: Eligible PDAC patients received ZA (4 mg) IV 2 weeks prior to surgery. Patients then received 2 additional doses of ZA 4 weeks apart. Blood and bone marrow were obtained from patients prior to treatment with ZA and 3 months after surgery for analysis of G-MDSC by flow cytometry. Results: Twenty-three patients received pre-operative ZA with at least 6 months of follow-up. Only 15 PDAC patients had nonmetastatic PDAC, which was amenable to resection. ZA was well tolerated, and all adverse events were grade 1 or 2. The most common adverse events were fatigue, abdominal pain/discomfort, anorexia, and arthralgia. Of resected PDAC patients treated with ZA, 1- and 2-year overall survival (OS) was 85.7% and 33.3%, respectively, with a median OS of 18 months. This group had a 1- and 2-year progression-free survival (PFS) of 26.9% and 8.9%, respectively, with a median PFS of 12 months. The prevalence of G-MDSC was unchanged in the blood and bone marrow of PDAC patients pre- and post-treatment with ZA. Conclusion: ZA is safe and well tolerated as neo-adjuvant, peri-operative therapy in PDAC patients. In this small study, we did not observe a difference in OS or PFS compared to historical controls. Also, there was no difference in the prevalence of G-MDSC in the blood and bone marrow of PDAC patients pre- and post-treatment with ZA.

Statistical Significance of Geographic Heterogeneity Measures in Spatial Epidemiologic Studies

Assessing geographic variations in health events is one of the major tasks in spatial epidemiologic studies. Geographic variation in a health event can be estimated using the neighborhood-level variance that is derived from a generalized mixed linear model or a Bayesian spatial hierarchical model. Two novel heterogeneity measures, including median odds ratio and interquartile odds ratio, have been developed to quantify the magnitude of geographic variations and facilitate the data interpretation. However, the statistical significance of geographic heterogeneity measures was inaccurately estimated in previous epidemiologic studies that reported two-sided 95% confidence intervals based on standard error of the variance or 95% credible intervals with a range from 2.5th to 97.5th percentiles of the Bayesian posterior distribution. Given the mathematical algorithms of heterogeneity measures, the statistical significance of geographic variation should be evaluated using a one-tailed P value. Therefore, previous studies using two-tailed 95% confidence intervals based on a standard error of the variance may have underestimated the geographic variation in events of their interest and those using 95% Bayesian credible intervals may need to re-evaluate the geographic variation of their study outcomes.

Statistical Assessment of Neighborhood Socioeconomic Deprivation Environment in Spatial Epidemiologic Studies

Neighborhood socioeconomic deprivation has been associated with health behaviors and outcomes. However, neighborhood socioeconomic status has been measured inconsistently across studies. It remains unclear whether appropriate socioeconomic indicators vary over geographic areas and geographic levels. The aim of this study is to compare the composite socioeconomic index to six socioeconomic indicators reflecting different aspects of socioeconomic environment by both geographic areas and levels. Using 2000 U.S. Census data, we performed a multivariate common factor analysis to identify significant socioeconomic resources and constructed 12 composite indexes at the county, the census tract, and the block group levels across the nation and for three states, respectively. We assessed the agreement between composite indexes and single socioeconomic variables. The component of the composite index varied across geographic areas. At a specific geographic region, the component of the composite index was similar at the levels of census tracts and block groups but different from that at the county level. The percentage of population below federal poverty line was a significant contributor to the composite index, regardless of geographic areas and levels. Compared with non-component socioeconomic indicators, component variables were more agreeable to the composite index. Based on these findings, we conclude that a composite index is better as a measure of neighborhood socioeconomic deprivation than a single indicator, and it should be constructed on an area- and unit-specific basis to accurately identify and quantify small-area socioeconomic inequalities over a specific study region.

Tissue-specific features of innate lymphoid cells in antiviral defense

Innate lymphocytes(ILCs)rapidly respond to and protect against invading pathogens and cancer.ILCs include natural killer(NK)cells,ILC1s,ILC2s,ILC3s,and lymphoid tissue inducer(LTi)cells and include type I,type II,and type III immune cells.While NK cells have been well recognized for their role in antiviral immunity,other ILC subtypes are emerging as players in antiviral defense.Each ILC subset has specialized functions that uniquely impact the antiviral immunity and health of the host depending on the tissue microenvironment.This review focuses on the specialized functions of each ILC subtype and their roles in antiviral immune responses across tissues.Several viruses within infection-prone tissues will be highlighted to provide an overview of the extent of the ILC immunity within tissues and emphasize common versus virus-specific responses.

Beyond just a tight fortress:contribution of stroma to epithelial-mesenchymal transition in pancreatic cancer

Novel effective treatment is direly needed for patients with pancreatic ductal adenocarcinoma(PDAC).Therapeutics that target the driver mutations,especially the KRAS oncoprotein and its effector cascades,have been ineffective.It is increasing clear that the extensive fibro-inflammatory stroma(or desmoplasia)of PDAC plays an active role in the progression and therapeutic resistance of PDAC.The desmoplastic stroma is composed of dense extracellular matrix(ECM)deposited mainly by the cancer-associatedfibroblasts(CAFs)and infiltrated with various types of immune cells.The dense ECM functions as a physical barrier that limits tumor vasculatures and distribution of therapeutics to PDAC cells.In addition,mounting evidence have demonstrated that both CAFs and ECM promote PDAC cells aggressiveness through multiple mechanisms,particularly engagement of the epithelial-mesenchymal transition(EMT)program.Acquisition of a mesenchymal-like phenotype renders PDAC cells more invasive and resistant to therapyinduced apoptosis.Here,we critically review seminal and recent articles on the signaling mechanisms by which each stromal element promotes EMT in PDAC.We discussed the experimental models that are currently employed and best suited to study EMT in PDAC,which are instrumental in increasing the chance of successful clinical translation.

Cancer vaccines:shared tumor antigens return to the spotlight

Sahin et al.recently reported interim data from a phase 1 clinical trial(NCT02410733)treating melanoma patients with a RNAlipoplex vaccine(RNA-LPX),targeting melanoma TAA.1 The trial is a multicenter,non-randomized,open-label,dose-escalation trial designed to evaluate the safety and tolerability of BNT111 targeting four melanoma TAA(NY-ESO-1,MAGE-A3,tyrosinase,and TPTE).Secondary endpoints include vaccine-induced immune responses and clinical response of patients with measurable disease.

PHGDH as a mechanism for resistance in metabolically-driven cancers

At the forefront of cancer research is the rapidly evolving understanding of metabolic reprogramming within cancer cells.The expeditious adaptation to metabolic inhibition allows cells to evolve and acquire resistance to targeted treatments,which makes therapeutic exploitation complex but achievable.3-phosphoglycerate dehydrogenase(PHGDH)is the rate-limiting enzyme of de novo serine biosynthesis and is highly expressed in a variety of cancers,including breast cancer,melanoma,and Ewing’s sarcoma.This review will investigate the role of PHGDH in normal biological processes,leading to the role of PHGDH in the progression of cancer.With an understanding of the molecular mechanisms by which PHGDH expression advances cancer growth,we will highlight the known mechanisms of resistance to cancer therapeutics facilitated by PHGDH biology and identify avenues for combatting PHGDH-driven resistance with inhibitors of PHGDH to allow for the development of effective metabolic therapies.

Innate and adaptive resistance mechanisms to arginine deprivation therapies in sarcoma and other cancers

Many cancers lack functional expression of the enzyme argininosuccinate synthetase 1(ASS1)that is necessary for synthesis of L-arginine.These cancers must import arginine for survival and growth,and this reliance can be targeted by arginine-degrading extracellular enzymatic drugs,most commonly PEGylated arginine deiminase.These enzymes can become targets of the immune system,reducing their effectiveness,but PEGylation improves the in vivo stability.Arginine deprivation causes cell death in some cancers,but others gain resistance by expressing ASS1 after a starvation response is induced.Other resistance mechanisms are possible and explored,but these have not been observed specifically in response to arginine deprivation.Future studies,especially focusing on the mechanisms of ASS1 upregulation and metabolic adaptations,may yield insights into preventing or taking advantage of resistance adaptations to make arginine deprivation therapy more effective.

驱动基因作为肺癌预防和治疗的靶标(英文)

下一代测序(next generation sequencing,NGS)已经被广泛用于鉴定导致肺癌最重要的驱动基因。与Sanger测序等传统测序策略相比,NGS具有若干突出优势,包括能测定全基因组、全外显子组或转录组中几乎所有基因的序列,能同时检测如碱基替换(突变)、插入、缺失、拷贝数变种、结构变种、基因融合等等。近几年来,科学家们成功地对肺腺癌、鳞癌和小细胞癌等三种肺癌进行了若干综合性的NGS研究,一方面验证了此前已发现的肺癌驱动基因的重要性,另一方面揭示了一些此前在肺癌中未被深入研究的重要驱动基因。在所研究的大多数肺癌样本中存在这些基因的功能性体细胞基因变异,导致了对肺癌发展具有直接影响的关键信号通路的异常。可以预期,不断被发现了解的新肺癌驱动基因将为发现肺癌预防和治疗最佳靶标提供前所未有的机遇。

增生平用于口腔癌化学预防(英文)

增生平(ZSP,又称anti-tumor B,ATB)是一种由山豆根、拳参、北败酱、夏枯草、白鲜皮、黄药子等组成的中药复方。以前的研究显示增生平对人食管癌(主要是鳞状细胞癌)有显著的化学预防效用。我们系统地研究评价了增生平对4-硝基喹啉-1-氧化物诱导的A/J小鼠口腔癌发生发展的影响,发现增生平减少了约60%的口腔癌。对7,12-二甲苯并(a)蒽诱导的仓鼠口腔癌也观察到了类似的结果。进而在口腔白斑患者中开展了一个随机临床实验,结果发现增生平(每日三次,每次4片,持续8—12个月)在68%的患者中减少了口腔病变的大小,而在安慰剂组只有17%(P<0.01)。这些结果显示增生平可能是一种强效的人口腔癌化学预防试剂。

Immune checkpoint inhibitor resistance in soft tissue sarcoma

The emergence of immunotherapy as a cancer therapy has dramatically changed the treatment paradigm of systemic cancer therapy.There have been several trials evaluating immune checkpoint blockade(ICI)in soft tissue sarcoma.While there is generally a limited response in sarcoma,a subset of patients has durable responses to immunotherapy.This is attributable to a variety of factors including histologic subtype,tumor-infiltrating lymphocytes,and the tumor microenvironment among others.There is ongoing translational and clinical research evaluating ICI resistance in sarcoma and identifying therapeutic strategies to overcome this resistance.Herein,we provide a review of the current data,proposed mechanisms of resistance,and potential approaches to overcome this resistance.

Add-on plasmonic patch as a universal fluorescence enhancer

Fluorescence-based techniques are the cornerstone of modern biomedical optics,with applications ranging from bioimaging at various scales(organelle to organism)to detection and quantification of a wide variety of biological species of interest.However,the weakness of the fluorescence signal remains a persistent challenge in meeting the ever-increasing demand to image,detect,and quantify biological species with low abundance.Here,we report a simple and universal method based on a flexible and conformal elastomeric film with adsorbed plasmonic nanostructures,which we term a“plasmonic patch,”that provides large(up to 100-fold)and uniform fluorescence enhancement on a variety of surfaces through simple transfer of the plasmonic patch to the surface.We demonstrate the applications of the plasmonic patch in improving the sensitivity and limit of detection(by more than 100 times)of fluorescence-based immunoassays implemented in microtiter plates and in microarray format.The novel fluorescence enhancement approach presented here represents a disease,biomarker,and application agnostic ubiquitously applicable fundamental and enabling technology to immediately improve the sensitivity of existing analytical methodologies in an easy-to-handle and cost-effective manner,without changing the original procedures of the existing techniques.