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H19: An Oncogenic Long Non-coding RNA in Colorectal Cancer. H19:结直肠癌中的致癌长非编码 RNA。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-12-29 eCollection Date: 2023-12-01 DOI: 10.59249/TDBJ7410
Prerana R Chowdhury, Shamala Salvamani, Baskaran Gunasekaran, Hoh B Peng, Vaidehi Ulaganathan

Colorectal cancer (CRC) has been recorded amongst the most common cancers in the world, with high morbidity and mortality rates, and relatively low survival rates. With risk factors such as chronic illness, age, and lifestyle associated with the development of CRC, the incidence of CRC is increasing each year. Thus, the discovery of novel biomarkers to improve the diagnosis and prognosis of CRC has become beneficial. Long non-coding RNAs (lncRNAs) have been emerging as potential players in several tumor types, one among them is the lncRNA H19. The paternally imprinted oncofetal gene is expressed in the embryo, downregulated at birth, and reappears in tumors. H19 aids in CRC cell growth, proliferation, invasion, and metastasis via various mechanisms of action, significantly through the lncRNA-microRNA (miRNA)-messenger RNA (mRNA)-competitive endogenous RNA (ceRNA) network, where H19 behaves as a miRNA sponge. The RNA transcript of H19 obtained from the first exon of the H19 gene, miRNA-675 also promotes CRC carcinogenesis. Overexpression of H19 in malignant tissues compared to adjacent non-malignant tissues marks H19 as an independent prognostic marker in CRC. Besides its prognostic value, H19 serves as a promising target for therapy in CRC treatment.

大肠癌(CRC)是世界上最常见的癌症之一,发病率和死亡率都很高,而存活率却相对较低。由于慢性疾病、年龄和生活方式等风险因素与 CRC 的发病有关,CRC 的发病率正在逐年上升。因此,发现新的生物标志物以改善 CRC 的诊断和预后已变得十分有益。长非编码 RNA(lncRNA)已成为多种肿瘤类型的潜在参与者,lncRNA H19 就是其中之一。这种父系印记的胎盘上基因在胚胎中表达,出生后下调,并在肿瘤中重新出现。H19 通过各种作用机制帮助 CRC 细胞生长、增殖、侵袭和转移,主要是通过 lncRNA-microRNA(miRNA)-信使 RNA(mRNA)-竞争性内源性 RNA(ceRNA)网络,其中 H19 就像一个 miRNA 海绵。从 H19 基因第一个外显子获得的 H19 的 RNA 转录物 miRNA-675 也能促进 CRC 癌变。与邻近的非恶性组织相比,H19 在恶性组织中的过表达标志着 H19 是 CRC 的一个独立预后标志。除了预后价值外,H19 还是治疗 CRC 的一个有希望的靶点。
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引用次数: 0
Protective Effects of Chia Seeds and Omega-3 Fatty Acid against Cyclophosphamide-Induced Oligospermia in Male Wistar Rats: Potential Risks of Adverse Drug Interaction with Chia Seeds. Chia Seeds 和 Omega-3 脂肪酸对环磷酰胺诱导的雄性 Wistar 大鼠少精症的保护作用:奇异籽与药物不良相互作用的潜在风险。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-12-29 eCollection Date: 2023-12-01 DOI: 10.59249/PAEJ4854
Prince B Vaghela, Archana M Navale, Chirangi B Patel, Nishant H Patidar, Prachi D Nahar, Farmi Patel, Zainab Pathan, Barsha Kumari

Objectives: The aim of this study was to investigate whether chia (Salvia hispanica) seeds, which are rich in omega-3 fatty acids, amino acids, and vitamins with antioxidant properties, can mitigate the negative effects on male reproductive function caused by cyclophosphamide, a frequently used chemotherapeutic agent. Methods: Male wistar rats are divided into seven groups (n=6). All groups except the normal control (NC) received cyclophosphamide (30mg/kg, i.p.) for the first 5 days. The standard group received clomiphene citrate (0.25 mg/kg, p.o.). Treatment groups T1%, T5%, T10%, and ω-3 received 1%, 5%, and 10% chia seeds in the diet, and 880 mg/kg omega-3 fatty acid (p.o) respectively for 15 days. The effect on the reproductive system was evaluated by analysis of epididymal sperm characteristics, biochemical parameters, and serum testosterone level. Results: Clomiphene citrate improved oligospermia via hormone mediated effect. Chia seeds and omega-3 fatty acid treatment also showed improvement in reproductive parameters including oxidative stress and histological features of the testes. Omega-3 fatty acid treatment was more effective for the prevention of cyclophosphamide toxicity on testes as compared to chia seeds. Nasal bleeding was noted in several animals subjected to chia seed treatment. This occurrence might be attributed to chia seeds' impact on coagulation and/or platelet function, potentially heightened due to chemotherapy associated bone marrow suppression. Conclusions: In our study, chia seeds as well as omega-3 fatty acid treatment were found to be protective against cyclophosphamide-induced reproductive toxicity in rats. However, the adverse effect of hemorrhage associated with drug interaction of chia seeds with cytotoxic chemotherapeutic drugs needs careful attention and further investigation.

研究目的本研究旨在探讨富含欧米伽-3 脂肪酸、氨基酸和具有抗氧化特性的维生素的奇异籽(西班牙鼠尾草)能否减轻常用化疗药物环磷酰胺对男性生殖功能的负面影响。研究方法雄性wistar大鼠分为7组(n=6)。除正常对照组(NC)外,其他各组在头 5 天均接受环磷酰胺(30 毫克/千克,静脉注射)治疗。标准组接受枸橼酸氯米芬(0.25 毫克/千克,口服)。治疗组T1%、T5%、T10%和ω-3分别在饮食中添加1%、5%和10%的奇亚籽,以及880毫克/千克的ω-3脂肪酸(p.o.),持续15天。通过分析附睾精子特征、生化指标和血清睾酮水平,评估了对生殖系统的影响。结果枸橼酸氯米芬通过激素介导作用改善了少精症。奇异籽和欧米伽-3脂肪酸治疗也改善了生殖参数,包括氧化应激和睾丸组织学特征。与奇异籽相比,欧米伽-3 脂肪酸治疗对预防环磷酰胺对睾丸的毒性更有效。接受奇异籽治疗的几只动物出现了鼻出血。这可能是由于奇异籽对凝血和/或血小板功能的影响,而化疗相关的骨髓抑制可能会增强这种影响。结论:在我们的研究中发现,奇异籽和ω-3脂肪酸处理对环磷酰胺诱导的大鼠生殖毒性具有保护作用。然而,奇异籽与细胞毒性化疗药物相互作用引起的出血不良反应还需要仔细关注和进一步研究。
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引用次数: 0
CRNDE: A Pivotal Oncogenic Long Non-Coding RNA in Cancers. CRNDE:癌症中至关重要的致癌长非编码 RNA。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-12-29 eCollection Date: 2023-12-01 DOI: 10.59249/VHYE2306
Yi Zhen Hor, Shamala Salvamani, Baskaran Gunasekaran, Koh Rhun Yian

Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.

结直肠癌差异表达(CRNDE)是一种长非编码 RNA,最初被发现在结直肠癌(CRC)中异常表达,也被观察到在其他各种人类恶性肿瘤中表达升高。最近的研究积累了大量证据,表明 CRNDE 是一种致癌物质,对与癌症进展相关的关键细胞过程产生影响。特别是,它与 microRNA 和蛋白质之间的调控相互作用已被证明可调节导致癌变和肿瘤发生的途径。本综述将全面概述 CRNDE 在结直肠癌、肝癌、胶质瘤、肺癌、宫颈癌、胃癌和前列腺癌中的作用,阐明其参与调节增殖、凋亡、迁移、侵袭、血管生成和放射/化疗耐药性的机制。此外,该综述还强调了 CRNDE 作为一种多方面生物标记物的潜力,因为它存在于不同的生物样本中,且性质稳定,从而突出了其在诊断、治疗和预后方面的应用。本综述旨在提供有关 CRNDE 介导的肿瘤发生的全面见解,并将 CRNDE 确定为未来临床干预的一个有前途的靶点。
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引用次数: 0
OMA1 and YME1L as a Diagnostic Panel in Hepatocellular Carcinoma. 将 OMA1 和 YME1L 作为肝细胞癌的诊断面板
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-12-29 eCollection Date: 2023-12-01 DOI: 10.59249/BWBY8971
Shimaa A Abass, Nabil Mohie Abdel-Hamid, Ahmed M Elshazly, Walied Abdo, Sherin Zakaria

Identifying new hepatocellular carcinoma (HCC)-driven signaling molecules and discovering their molecular mechanisms are crucial for efficient and better outcomes. Recently, OMA1 and YME1L, the inner mitochondrial proteases, were displayed to be associated with tumor progression in various cancers; however, their role in HCC has not yet been studied. Therefore, we evaluated the possible role of OMA1/YME1L in HCC staging and discussed their potential role in cellular apoptosis and proliferation. Our study was performed using four groups of male albino rats: a normal control and three diethyl nitrosamine-treated groups for 8, 16, and 24 weeks. The OMA1 and YME1L, matrix-metalloproteinase-9 (MMP-9), and cyclin D1 content were measured in liver tissues, while alpha-fetoprotein (AFP) level was assessed in serum. Additionally, Ki-67 expression was evaluated by immunohistochemistry. The relative hepatic expression of Bax, and tissue inhibitor matrix metalloproteinase (TIMP-3) was measured. Herein, we confirmed for the first time that OMA1 is down-regulated while YME1L is up-regulated in HCC in the three studied stages with subsequent inhibition of apoptosis and cell cycle progression. Furthermore, these proteases have a possible role in metastasis. These newly recognized results suggested OMA1 and YME1L as possible diagnostic tools and therapeutic targets for HCC management.

确定新的肝细胞癌(HCC)信号传导分子并发现其分子机制对于有效和更好地治疗至关重要。最近,线粒体内部蛋白酶 OMA1 和 YME1L 被证实与多种癌症的肿瘤进展有关,但它们在 HCC 中的作用尚未得到研究。因此,我们评估了 OMA1/YME1L 在 HCC 分期中的可能作用,并讨论了它们在细胞凋亡和增殖中的潜在作用。我们的研究使用了四组雄性白化大鼠:一组正常对照组和三组二乙基亚硝胺处理组,处理时间分别为 8 周、16 周和 24 周。我们测量了肝组织中的 OMA1 和 YME1L、基质金属蛋白酶-9(MMP-9)和细胞周期蛋白 D1 的含量,同时评估了血清中甲胎蛋白(AFP)的水平。此外,还通过免疫组化评估了 Ki-67 的表达。还测量了 Bax 和组织抑制基质金属蛋白酶(TIMP-3)在肝脏中的相对表达。在此,我们首次证实,在所研究的三个阶段中,OMA1 在 HCC 中被下调,而 YME1L 则被上调,从而抑制了细胞凋亡和细胞周期的进展。此外,这些蛋白酶还可能在转移中发挥作用。这些新发现表明,OMA1 和 YME1L 可作为诊断工具和治疗 HCC 的靶点。
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引用次数: 0
Expanding OBSL1 Mutation Phenotype: Disproportionate Short Stature, Barrel Chest, Thoracic Kyphoscoliosis, Hypogonadism, and Hypospadias. 扩大型OBSL1突变表型:身材矮小、桶状胸脯、胸部后凸畸形、性腺功能减退和尿道下裂。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI: 10.59249/RLAU6003
Mine Koprulu, Rana Muhammad Kamran Shabbir, Sara Mumtaz, Aslıhan Tolun, Sajid Malik

We present a Pakistani kinship afflicted with a syndrome with features including short stature, reduced sitting height, orofacial symptoms including prominent forehead and thick eyebrows, short and broad thorax, and variable features such as long philtrum, short broad neck, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Phenotypic variation even within different sibships was considerable. The unique combination of the phenotypic characteristics prompted us to determine the shared homozygosity regions in patient genomes and the pathogenic variants by next generation technologies like single nucleotide polymorphism (SNP) genotyping and whole exome sequencing (WES). Through these analyses, we detected homozygous OBSL1 c.848delG (p.Gly283AlafsTer54) as the causal variant. Biallelic variants in OBSL1 are known to cause Three M Syndrome 2 (3M2), a rare disorder of growth retardation with characteristic facial dysmorphism and musculoskeletal abnormalities. Affected members of the family do not have the 3M2 hallmark features of dolichocephaly, hypoplastic midface, anteverted nares, low nasal bridge, pectus excavatum, sacral hyperlordosis, spina bifida occulta, anterior wedging of thoracic vertebrae, prominent heels, and prominent talus. Moreover, they have some variable features not typical for the syndrome such as round face, disproportionate short stature, barrel chest, thoracic kyphoscoliosis, hypogonadism, and hypospadias. Our study facilitated genetic diagnosis in the family, expanded the clinical phenotype for 3M2, and unraveled the considerable clinical variation within the same kinship. We conclude that unbiased molecular analyses such as WES should be more integrated into healthcare, particularly in populations with high parental consanguinity, given the potential of such analyses to facilitate diagnosis.

我们报告一名巴基斯坦亲属患有一种综合征,其特征包括身材矮小、坐高降低、口面症状包括前额突出和眉毛浓密、胸部短而宽,以及多种特征,如人中长、脖子短而宽、桶状胸、胸部后凸、性腺功能减退和尿道下裂。表型变异甚至在不同的同胞体内也是相当大的。表型特征的独特组合促使我们通过单核苷酸多态性(SNP)基因分型和全外显子组测序(WES)等下一代技术来确定患者基因组和致病性变体中的共享纯合子区域。通过这些分析,我们检测到纯合的OBSL1 c.848delG(p.Gly283AlafsTer54)是致病变体。已知OBSL1的双等位基因变异会导致Three M Syndrome 2(3M2),这是一种罕见的生长迟缓疾病,具有特征性的面部畸形和肌肉骨骼异常。受影响的家族成员没有3M2的标志性特征,如小头畸形、面中部发育不全、鼻孔前倾、低鼻梁、漏斗胸、骶骨前凸、隐性脊柱裂、胸椎前楔入、突出的跟部和突出的距骨。此外,他们有一些不典型的综合征的可变特征,如圆脸、不成比例的矮小、圆胸、胸部后凸畸形、性腺功能减退和尿道下裂。我们的研究促进了该家族的基因诊断,扩大了3M2的临床表型,并揭示了同一亲缘关系中相当大的临床变异。我们的结论是,考虑到此类分析有助于诊断的潜力,WES等无偏见的分子分析应更多地纳入医疗保健,特别是在父母血亲较高的人群中。
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引用次数: 0
Homozygous Mutations in Thyroid Peroxidase (TPO) in Hypothyroidism with Intellectual Disability, Developmental Delay, and Hearing and Ocular Anomalies in Two Families: Severe Manifestation of Untreated TPO-deficiency Poses a Diagnostic Dilemma. 甲状腺过氧化物酶(TPO)的纯合突变在两个家族的智力残疾、发育迟缓、听力和视力异常的甲状腺功能减退症中:未经治疗的TPO缺乏症的严重表现带来诊断难题。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI: 10.59249/SSRG6507
Syeda Farwa Naqvi, Esra Yıldız-Bölükbaşı, Muhammad Afzal, Gökhan Nalbant, Sara Mumtaz, Aslıhan Tolun, Sajid Malik

Intellectual disability (ID) involves compromised intellectual, learning and cognitive skills, and behavioral capabilities with reduced psychomotor skills. One of the preventable causes of ID is congenital hypothyroidism (CH), which may be due to biallelic mutations in thyroid peroxidase (TPO). In low- and middle-income countries with no newborn screening programs, CH poses a great risk of ID and long-term morbidity. We report two large Pakistani families with a total of 16 patients afflicted with CH. Detailed clinical and behavioral assessments, SNP-based homozygosity mapping, linkage analysis, and exome sequencing were performed. Initially, affected individuals were referred as suffering ID (in 11 of 16 patients) and developmental delay (in 14). Secondary/associated features were verbal apraxia (in 13), goiter (in 12), short stature (in 11), limb hypotonia (in 14), no pubertal onset (five of 10 of age ≥14 years), high myopia (in eight), muscle cramps (in six), and in some, variable microcephaly and enuresis/encopresis, fits, chronic fatigue, and other behavioral symptoms, which are not characteristics of CH. Molecular genetic analyses led to the discovery of homozygous variants in TPO: novel missense variant c.719A>G (p.Asp240Gly) in family 1 and rare c.2315A>G (p.Tyr772Cys) in family 2. In low-resource countries where neonatal screening programs do not include a CH test, the burden of neurodevelopmental disorders is likely to be increased due to untreated CH. Secondly, in the background of the high prevalence of recessive disorders due to high parental consanguinity, the severe manifestation of TPO-deficiency mimics a wide range of neurological and other presentations posing a diagnostic dilemma.

智力残疾包括智力、学习和认知技能受损,以及心理运动技能下降的行为能力。ID的可预防原因之一是先天性甲状腺功能减退症(CH),这可能是由于甲状腺过氧化物酶(TPO)的双等位基因突变。在没有新生儿筛查项目的中低收入国家,CH存在很大的ID和长期发病风险。我们报告了两个巴基斯坦大家庭,共有16名CH患者。进行了详细的临床和行为评估、基于SNP的纯合子定位、连锁分析和外显子组测序。最初,受影响的个体被称为患有ID(16名患者中有11名)和发育迟缓(14名)。次要/相关特征为言语失用症(13例)、甲状腺肿(12例)、身材矮小(11例)、肢体张力减退(14例)、未青春期发作(10例中有5例年龄≥14岁)、高度近视(8例)、肌肉痉挛(6例),在某些情况下,可变小头症和遗尿/尿崩、痉挛、慢性疲劳和其他行为症状,这些都不是CH的特征。分子遗传学分析导致在TPO中发现纯合变体:家族1中的新错义变体c.719A>G(p.Asp240Gly)和家族2中的罕见变体c.2315A>G(p.Tyr772Cys)。在低资源国家,新生儿筛查项目不包括CH检测,由于未经治疗的CH,神经发育障碍的负担可能会增加。其次,在父母高血亲导致隐性疾病高患病率的背景下,TPO缺乏症的严重表现模拟了造成诊断困境的广泛的神经和其他表现。
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引用次数: 0
"Big Data" Analyses Underlie Clinical Discoveries at the Aortic Institute. 主动脉研究所的“大数据”分析掩盖了临床发现。
IF 2.5 3区 工程技术 Q2 BIOLOGY Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI: 10.59249/LNDZ2964
Mohammad A Zafar, Bulat A Ziganshin, Yupeng Li, Nicolai P Ostberg, John A Rizzo, Maryann Tranquilli, Sandip K Mukherjee, John A Elefteriades

This issue of the Yale Journal of Biology and Medicine (YJBM) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets). 1. Ascending aortic aneurysms should be resected at 5 cm to prevent dissection and rupture. 2. Indexing aortic size to height improves aortic risk prognostication. 3. Aortic root dilatation is more malignant than mid-ascending aortic dilatation. 4. Ascending aortic aneurysm patients with bicuspid aortic valves do not carry the poorer prognosis previously postulated. 5. The descending and thoracoabdominal aorta are capable of rupture without dissection. 6. Female patients with TAA do more poorly than male patients. 7. Ascending aortic length is even better than aortic diameter at predicting dissection. 8. A "silver lining" of TAA disease is the profound, lifelong protection from atherosclerosis. From Modern "Big Data" Machine Learning/Artificial Intelligence analysis: 1. Machine learning models for TAA: outperforming traditional anatomic criteria. 2. Genetic testing for TAA and dissection and discovery of novel causative genes. 3. Phenotypic genetic characterization by Artificial Intelligence. 4. Panel of RNAs "detects" TAA. Such findings, based on (a) long-standing application of advanced conventional statistical analysis to large clinical data sets, and (b) recent application of advanced machine learning/artificial intelligence to large genetic data sets at the Yale Aortic Institute have advanced the diagnosis and medical and surgical treatment of TAA.

本期《耶鲁生物学与医学杂志》(YJBM)聚焦于医学研究中的大数据和精确分析。在耶鲁-纽黑文医院主动脉研究所,我们的绝大多数研究都来自我们的胸主动脉瘤(TAA)患者的大型前瞻性临床数据库,并辅以超大型基因测序文件。通过在这些临床和遗传数据库中应用先进的统计和人工智能技术,实现了以下基本临床和科学发现:来自传统“大数据”(大数据集)的分析。1.升主动脉瘤应在5cm处切除,以防止夹层和破裂。2.将主动脉大小与高度进行指数化可提高主动脉风险预测。3.主动脉根部扩张比升主动脉中段扩张更恶性。4.患有二叶主动脉瓣的升主动脉瘤患者的预后并不比先前假设的差。5.降主动脉和胸腹主动脉能够在不剥离的情况下破裂。6.女性TAA患者的表现比男性患者差。7.在预测主动脉夹层时,上行主动脉长度甚至优于主动脉直径。8.TAA疾病的“一线希望”是对动脉粥样硬化的终身保护。来自现代“大数据”机器学习/人工智能分析:1。TAA的机器学习模型:优于传统解剖标准。2.TAA基因检测及新致病基因的分离与发现。3.利用人工智能进行表型遗传表征。4.RNA小组“检测”TAA。这些发现基于(a)先进的传统统计分析在大型临床数据集中的长期应用,以及(b)耶鲁主动脉研究所最近在大型遗传数据集中应用先进的机器学习/人工智能,促进了TAA的诊断、医疗和外科治疗。
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引用次数: 0
What Brings You in Today? Sex, Race, Substance Type, and Other Sociodemographic and Health-Related Characteristics Predict if Substance Use is the Main Reason for a Clinical Encounter. 今天是什么吸引你?性别、种族、物质类型和其他社会形态和健康相关特征可以预测药物使用是否是临床接触的主要原因。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI: 10.59249/UDRG5942
Natasia S Courchesne-Krak, Carla B Marienfeld, Wayne Kepner

Background: Substance-related diagnoses (SRDs) are a common healthcare presentation. This study identified sociodemographic and health-related characteristics associated with having an SRD as the primary reason for a clinical encounter compared to those with an SRD who are treated for other reasons. Methods: Electronic health record (EHR) data on patients with an SRD (n=12,358, ages 18-90) were used to assess if an SRD was the primary reason for a clinical encounter from January 1, 2012-January 1, 2018. Patients were matched on key demographic characteristics at a 1:1 ratio. Adjusting for covariates, odds ratios, and 95% confidence intervals were calculated. Results: In the matched cohort of 8,630, most reported male sex (65.8%), White race (70.0%), and single marital status (62.7%) with a mean age of 47.2 (SD=14.6). Patient reported female sex, Black race, age 70+, married status, and low-income (<$50,000) were associated with a lower likelihood of presenting to care for an SRD as the primary reason for a clinical encounter. A nicotine-, alcohol-, opioid-, or stimulant-related diagnosis was associated with a higher likelihood of presenting to care for an SRD as the primary reason for the clinical visit. Conclusion: This is the first study to investigate whether sociodemographic and health-related characteristics were associated with having an SRD as the primary reason for a clinical encounter. Using rigorous methods, we investigated a unique clinical question adding new knowledge to predictors of patients seeking clinical care. Understanding these predictors can help us better align service provision with population needs and inform new approaches to tailoring care.

背景:物质相关诊断(SRD)是一种常见的医疗保健表现。与那些因其他原因接受治疗的SRD患者相比,这项研究确定了与SRD相关的社会人口统计学和健康相关特征是临床遭遇的主要原因。方法:使用SRD患者(n=12358,年龄18-90岁)的电子健康记录(EHR)数据来评估SRD是否是2012年1月1日至2018年1月31日临床遭遇的主要原因。患者在关键人口统计学特征上以1:1的比例进行匹配。计算协变量、比值比和95%置信区间的调整。结果:在8630名匹配队列中,大多数患者报告了男性(65.8%)、白人(70.0%)和单身状态(62.7%),平均年龄为47.2岁(SD=14.6)。患者报告了女性、黑人、年龄70岁以上、已婚状态,和低收入(结论:这是第一项调查社会人口统计学和健康相关特征是否与SRD作为临床遭遇的主要原因有关的研究。我们使用严格的方法,调查了一个独特的临床问题,为寻求临床护理的患者的预测因素增加了新的知识。了解这些预测因素可以帮助我们更好地调整服务与人口需求的愿景,并为量身定制护理的新方法提供信息。
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引用次数: 0
A Stop-gain Variant c.220C>T (p.(Gln74*)) in FLNB Segregates with Spondylocarpotarsal Synostosis Syndrome in a Consanguineous Family. FLNB中的一个停增变异株c.220C>T(p.(Gln74*))在一个血缘家族中分离并伴有强直性脊柱炎综合征。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI: 10.59249/UTCP9818
Hamna Shahid, Nazish Shakoor, Anisa Bibi, Asma Saleem Qazi, Rida Fatima Saeed, Aqeela Nawaz, Sajid Malik, Sara Mumtaz

Spondylocarpotarsal synostosis (SCT) syndrome is a very rare and severe form of skeletal dysplasia. The hallmark features of SCT are disproportionate short stature, scoliosis, fusion of carpal and tarsal bones, and clubfoot. Other common manifestations are cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Homozygous variants in FLNB are known to cause SCT. This study was aimed to investigate the phenotypic and genetic basis of unique presentation of SCT syndrome segregating in a consanguineous Pakistani family. Three of the four affected siblings evaluated had severe short stature, short trunk, short neck, kyphoscoliosis, pectus carinatum, and winged scapula. The subjects had difficulty in walking and gait problems and complained of knee pain and backache. Roentgenographic examination of the eldest patient revealed gross anomalies in the axial skeleton including thoracolumbar and cervical fusion of ribs, severe kyphoscoliosis, thoracic and lumbar lordosis, coxa valga, fusion of certain carpals and tarsals, and clinodactyly. The patients had normal faces and lacked other typical features of SCT like cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Whole exome sequencing (WES) of two affected siblings led to the discovery of a rare stop-gain variant c.220C>T (p.(Gln74*)) in exon 1 of the FLNB gene. The variant was homozygous and segregated with the malformation in this family. This study reports extensive phenotypic variability in SCT and expands the mutation spectrum of FLNB.

强直性脊柱炎(SCT)综合征是一种非常罕见和严重的骨骼发育不良。SCT的标志性特征是不成比例的身材矮小、脊柱侧弯、腕骨和跗骨融合以及马蹄内翻足。其他常见表现为腭裂、传导性和感音神经性听力损失、关节僵硬和牙釉质发育不全。已知FLNB中的纯合变体会导致SCT。本研究旨在探讨在一个有血缘关系的巴基斯坦家庭中SCT综合征分离的独特表现的表型和遗传基础。在评估的四个受影响的兄弟姐妹中,有三个患有严重的身材矮小、躯干短、脖子短、后凸畸形、隆突和带翼肩胛骨。受试者有行走困难和步态问题,并抱怨膝盖疼痛和背痛。对年龄最大的患者进行的X线检查显示,轴骨出现严重异常,包括胸腰椎和颈椎肋骨融合、严重后凸、胸腰椎前凸、髋外翻、某些腕骨和跗骨融合以及斜指畸形。患者面部正常,缺乏其他典型的SCT特征,如腭裂、传导性和感音神经性听力损失、关节僵硬和牙釉质发育不全。两个受影响兄弟姐妹的全外显子组测序(WES)导致在FLNB基因的外显子1中发现了一种罕见的停止增益变体c.220C>T(p.(Gln74*))。该变体是纯合的,并与该家族的畸形分离。本研究报道了SCT的广泛表型变异,并扩展了FLNB的突变谱。
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引用次数: 0
Ophthalmology at the Forefront of Big Data Integration in Medicine: Insights from the IRIS Registry Database. 医学大数据集成前沿的眼科学:来自IRIS注册数据库的见解。
IF 2.7 3区 工程技术 Q1 Medicine Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI: 10.59249/VUPM2510
Austen N Knapp, Theodore Leng, Ehsan Rahimy

Ophthalmology stands at the vanguard of incorporating big data into medicine, as exemplified by the integration of The Intelligent Research in Sight (IRIS) Registry. This synergy cultivates patient-centered care, demonstrates real world efficacy and safety data for new therapies, and facilitates comprehensive population health insights. By evaluating the creation and utilization of the world's largest specialty clinical data registry, we underscore the transformative capacity of data-driven medical paradigms, current shortcomings, and future directions. We aim to provide a scaffold for other specialties to adopt big data integration into medicine.

眼科学站在将大数据纳入医学的前沿,例如整合了视觉智能研究(IRIS)注册中心。这种协同作用培养了以患者为中心的护理,展示了新疗法的真实疗效和安全性数据,并促进了全面的人群健康见解。通过评估世界上最大的专业临床数据注册中心的创建和利用情况,我们强调了数据驱动的医学范式的变革能力、当前的不足和未来的方向。我们的目标是为其他专业将大数据集成到医学中提供一个支架。
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引用次数: 0
期刊
Yale Journal of Biology and Medicine
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