Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Anaplastic Thyroid Cancer: The Trajectory of Prolonged Diagnosis and Short Survival

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Purpose: Anaplastic thyroid cancer (ATC) is almost uniformly lethal in its progression, but due to its rarity and complexity, its presentation is difficult to recognize and manage by physicians and patients alike. Delayed diagnosis is common and makes ATC virtually untreatable. We aim to examine the number of appointments with healthcare providers, imaging studies performed, and admission days as metrics of delayed diagnosis in order to identify opportunities to expedite care of ATC patients in the future. Methods: A retrospective electronic medical record review was conducted to include 8 patients from January 2016 to December 2018. Both pre- and post-diagnosis variables were examined and include: number of unique encounters, type/number of imaging studies, demographics (sex, ethnicity, residence, employment, religion, language, marital status), days admitted inpatient, time to diagnosis, and specific medical specialties utilized. Pre- and post-diagnosis imaging studies included computer tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), radiographs (X-ray), and positron emission tomography (PET). IRB approval was obtained through the UA BEACON© registry. Results: We analyzed 4 women and 4 men with ATC whose mean time to diagnosis (TTD) from initial chief complaint was 53 days. In that time, 12 clinicians per patient (median) provided care. Men had a far longer mean TTD compared to women (75 vs 31 days), as well as longer mean inpatient admission for evaluation (19 vs 11 days). After ATC diagnosis, the median number of encounters per patient rose to 24.5, reflecting multispecialty care required for treatment. Here also, men had more median post-diagnosis specialist encounters than women (41.5 vs 11). Female patients had a median number of 4 imaging studies pre-diagnosis and 2 imaging studies post-diagnosis while male patients had a median number of 6 imaging studies pre-diagnosis and 12.5 imaging studies post-diagnosis. Discussion: This study suggests that male patients with ATC have a more difficult trajectory both pre- and post-diagnosis compared to female patients. They require longer time and more imaging studies before physicians arrive at the ATC diagnosis. Subsequently, men stay longer in the hospital, still with significantly higher numbers of studies and physician encounters. The root causes of this gender discrepancy are unclear and likely multifactorial, but could represent greater ATC disease severity and gender-specific barriers to care. This study highlights the need to recognize early signs of ATC and consider this diagnosis sooner.This item is part of the College of Medicine - Phoenix Scholarly Projects 2021 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]

Reconfigurable pickering emulsions with functionalized carbon nanotubes

Pickering emulsions (PEs) achieve interfacial stabilization by colloidal particle surfactants and are commonly used in food, cosmetics, and pharmaceuticals. Carbon nanotubes (CNTs) have recently been used as stabilizing materials to create dynamic single emulsions. In this study, we used the formation of Meisenheimer complexes on functionalized CNTs to fabricate complex biphasic emulsions containing hydrocarbons (HCs) and fluorocarbons (FCs). The reversible nature of Meisenheimer complex formation allows for further functionalization at the droplet–water interface. The strong affinity of fluorofluorescent perylene bisimide (F-PBI) to the CNTs was used to enhance the assembly of CNTs on the FC–water interface. The combination of different concentrations of the functionalized CNTs and the pelene additive enables predictable complex emulsion morphologies. Reversible morphology reconfiguration was explored with the addition of molecular surfactants. Our results show that the interfacial properties of functionalized CNTs have considerable utility in the fabrication of complex dynamic emulsions

Transmissibility of coronavirus disease 2019 in Chinese cities with different dynamics of imported cases

Background Monitoring the reproduction number (Rt) of the disease could help determine whether there is sustained transmission in a population, but areas with similar epidemic trends could have different transmission dynamics given the risk from imported cases varied across regions. In this study, we examined the Rt of coronavirus disease 2019 (COVID-19) by taking different dynamics of imported cases into account and compared the transmissibility of COVID-19 at different intervention periods in Hangzhou and Shenzhen. Methods We obtained the daily aggregated counts of laboratory-confirmed imported and local cases of COVID-19 infections in Hangzhou and Shenzhen from January 1 to March 13, 2020. Daily Rt and piecewise Rt before and after Wuhan lockdown were estimated, accounting for imported cases. Results Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was around 0.1 to 0.7 before the Wuhan lockdown. After the lockdown of Wuhan and the initialization of measures in response to the outbreak, local transmission was well-controlled as indicated by a low estimated value of piecewise Rt, 0.15 (95% CI [0.09–0.21]). On the contrary, Rt obtained for Hangzhou ranged from 1.2 to 4.9 with a piecewise Rt of 2.55 (95% CI [2.13–2.97]) before the lockdown of Wuhan due to the surge in local cases. Because of the Wuhan lockdown and other outbreak response measures, Rt dropped below unity in mid-February. Conclusions Even though Shenzhen had more cases than Hangzhou, local transmission did not sustain probably due to limited transmission from imported cases owing to the reduction in local susceptibles as residents left the city during Chunyun. The lockdown measures and local outbreak responses helped reduce the local transmissibility

Resection of Pheochromocytoma Improves Diabetes Mellitus in the Majority of Patients.

BackgroundCatecholamine excess in patients with pheochromocytoma often results in impaired glucose tolerance, leading to diabetes mellitus. Little data are available on the long-term effect of surgery on diabetes.ObjectiveThe primary aim of this study was to determine the likelihood of diabetes cure after surgery, while secondary objectives were to determine risk factors for development of diabetes preoperatively and persistence of diabetes postoperatively.MethodsAll patients undergoing surgery for pheochromocytoma from 1996 to 2015 were retrospectively reviewed to identify those with a preoperative diagnosis of diabetes. Demographic and diabetes-specific data were collected. Median follow-up was 52.1 months.ResultsOverall, 153 patients underwent surgery. Diabetes was seen in 36 (23.4%) patients. Eight patients met the exclusion criteria and were removed from the final analysis, while 22 (78.6%) patients had complete resolution of diabetes. Four patients remained on medication with improved control. Overall, 93.0% of patients had improvement of their diabetes; two patients did not improve. Patients with large, symptomatic tumors were more likely to develop preoperative diabetes, and diabetes was more likely to persist in patients who had an elevated body mass index (BMI).ConclusionsDiabetes was found concurrently with pheochromocytoma in 23% of patients, more often in those with large, symptomatic tumors. The majority of patients had long-term resolution of diabetes after successful resection; however, some patients may continue to require treatment of diabetes after operation, especially those with a higher BMI

Incidence, Risk Factors, and Clinical Outcomes of Incidental Parathyroidectomy During Thyroid Surgery.

BackgroundThe reported rate of incidental parathyroidectomy (IP) during thyroid surgery is between 5.2 and 21.6 %. Current literature reports wide discrepancy in incidence, risk factors, and outcomes. Thus study was designed to address definitively the topic of IP and identify associated risk factors and clinical outcomes with this multi-institutional study.MethodsThis retrospective cohort study included 1767 total thyroidectomies that occurred between 1995 and 2014 at two academic centers. Pathologic reports were reviewed for the presence of unintentionally removed parathyroid glands. Demographics, potential risk factors, and postoperative calcium levels were compared with matched control group. Logistic regression, t tests, and Chi squared tests were used when appropriate.ResultsIP occurred in 286 (16.2 %) of thyroidectomies. Risk factors for IP were: malignancy, neck dissection, and lymph node metastases (p = 0.005, <0.001, and <0.001). Fifty-three (19.2 %) of IPs were intrathyroidal. Those with IP were more likely to have postoperative biochemical (65.6 vs. 42.0 %; p < 0.001) and symptomatic (13.4 vs. 8.1 %; p = 0.044) hypocalcemia than controls. The number of parathyroids identified intraoperatively was inversely correlated with the number of parathyroid glands in the specimen (p < 0.001).ConclusionsOur findings indicate that malignancy, lymph node dissection, and metastatic nodal disease are risk factors for IP. Patients with IP were more likely to have postoperative biochemical and symptomatic hypocalcemia than controls, showing that there is a physiologic consequence to IP. Additionally, intraoperative surgeon identification of parathyroid glands results in a lower incidence of IP, highlighting the importance of awareness of parathyroid anatomy during thyroid surgery

Limited role for meteorological factors on the variability in COVID-19 incidence: A retrospective study of 102 Chinese cities.

While many studies have focused on identifying the association between meteorological factors and the activity of COVID-19, we argue that the contribution of meteorological factors to a reduction of the risk of COVID-19 was minimal when the effects of control measures were taken into account. In this study, we assessed how much variability in COVID-19 activity is attributable to city-level socio-demographic characteristics, meteorological factors, and the control measures imposed. We obtained the daily incidence of COVID-19, city-level characteristics, and meteorological data from a total of 102 cities situated in 27 provinces/municipalities outside Hubei province in China from 1 January 2020 to 8 March 2020, which largely covers almost the first wave of the epidemic. Generalized linear mixed effect models were employed to examine the variance in the incidence of COVID-19 explained by different combinations of variables. According to the results, including the control measure effects in a model substantially raised the explained variance to 45%, which increased by >40% compared to the null model that did not include any covariates. On top of that, including temperature and relative humidity in the model could only result in < 1% increase in the explained variance even though the meteorological factors showed a statistically significant association with the incidence rate of COVID-19. In conclusion, we showed that very limited variability of the COVID-19 incidence was attributable to meteorological factors. Instead, the control measures could explain a larger proportion of variance