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1.
Am J Hypertens ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712567

RESUMEN

BACKGROUND: To compare pharmacological treatment of hypotension and orthostatic hypotension (OH) initiated based upon a blood pressure (BP) threshold, regardless of symptoms (TXT), to usual care pharmacological treatment of symptomatic hypotension (UC), during acute inpatient rehabilitation (AIR) following spinal cord injury (SCI). METHODS: Block randomization, based on the neurological level of injury as: cervical lesions (C1-C8); high thoracic lesions (T1-T5) and low thoracic lesions (T6-T12), was used to determine responses to the primary question "was the therapy session affected by low BP or concern for low BP development?". Study participants and therapists were unaware of group assignment. RESULTS: A total of 66 participants enrolled; 25 (38%) in the TXT group, 29 (44%) in the UC group, and 12 (18%) withdrew. Responses to the primary question were recorded for 32 participants, 15 in the TXT and 17 in the UC group. There was an average of 81±51 therapy sessions/participant in the TXT and 60±27 sessions/participant in the UC group. Of those therapy sessions, low BP or concerns for low BP affected an average of 9±8 sessions/participant in the TXT group and 10±12 sessions/participant in the UC group. Neither the total number of therapy sessions (p=0.16) nor group assignment (p=0.83) significantly predicted the number of sessions affected by low BP. CONCLUSIONS: These data are not conclusive but indicate that the treatment of asymptomatic hypotension and OH does not increase time spent in therapy compared to usual care treatment of symptomatic hypotension and OH in newly injured patients with SCI.

2.
J Neurotrauma ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38661533

RESUMEN

Spinal cord injury (SCI) negatively impacts individuals' functional independence, and motor and sensory function. Intense walking training has been shown to facilitate recovery for individuals with chronic SCI. Powered robotic exoskeletons provide therapists with a tool that allows them to conduct walking training with less therapist effort as compared to conventional walking training. Exoskeletal-assisted walking (EAW) has been studied in the chronic SCI population with preliminary reports showing benefits in mobility, health, and quality-of-life outcomes. However, few reports have studied EAW's benefits in the acute (<90 days post) SCI population at a time when neural plasticity is most dynamic and modifiable. The purpose of the study was to conduct a pilot randomized controlled trial (RCT) to understand the effects of incorporated EAW in acute inpatient rehabilitation (AIR) for individuals with SCI on functional, motor, and sensory recovery. The study outcomes included the Spinal Cord Independence Measure (SCIM) III and International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and sensory scores that were assessed by unblinded assessors. We also recorded EAW session data, including adverse events, walking and up time, step counts, Borg Rating of Perceived Exertion (RPE), and compliance with scheduled EAW training. From August 2019 to July 2022, 16 participants completed the AIR with incorporated EAW, and 12 completed the standard AIR, all with SCI and preserved leg function within 90 days post-injury. During each session, the AIR with incorporated EAW group averaged 34.3 (±9.4) min of up time, 25.4 (±7.7) min of walk time, and 536 (±157) steps. Analysis via two-by-two mixed-effects models showed significant increases in the SCIM total score and ISNCSCI total motor and sensory scores over time for the AIR with incorporated EAW group [SCIM total score: F(1, 26) = 5.59, p = 0.03; total motor score: F(1, 26) = 8.06, p < 0.01; total sensory score: F(1, 19.2) = 5.08, p = 0.04], outperforming the standard AIR group. The AIR with incorporated EAW group showed 13, 14, and 22 points higher changes in the SCIM total score, total motor score, and total sensory score (respectively) by discharge compared with the standard AIR group. Incorporating EAW into AIR may facilitate functional, motor, and sensory recovery for individuals with SCI during AIR better than standard AIR. However, the study had a limited sample size. Further studies are needed to clarify the effects of EAW in AIR.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38437821

RESUMEN

PURPOSE: To describe a vision-threatening adverse event of a novel CAR T-cell immunotherapy for metastatic prostate cancer. METHODS: Observational Case Report. PATIENT: 77-year-old male with history of metastatic prostate cancer and pulmonary embolism enrolled in a clinical trial investigating the use of CAR T-cell immunotherapy for treatment of metastatic prostate cancer presented with a subjective left temporal visual disturbance. RESULTS: The patient was found to have bilateral extensive choroidal detachments on examination. OCT macula demonstrated no intraretinal fluid or supraretinal fluid in both eyes. B-scan of both eyes redemonstrated choroidal detachments in both eyes and no retinal detachment in either eye. The patient was initiated on a topical and systemic steroid regimen and experienced symptomatic and clinical improvement. CONCLUSION: We exhibit a case of bilateral choroidal detachments secondary to systemic reaction to a novel immunotherapy for metastatic cancer successfully treated with systemic and topical steroids. Close follow up may be required for patients receiving similar novel immunotherapeutic regimens.

4.
Nat Commun ; 15(1): 1449, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38365845

RESUMEN

Horizontal gene transfer (HGT) and gene duplication are often considered as separate mechanisms driving the evolution of new functions. However, the mobile genetic elements (MGEs) implicated in HGT can copy themselves, so positive selection on MGEs could drive gene duplications. Here, we use a combination of modeling and experimental evolution to examine this hypothesis and use long-read genome sequences of tens of thousands of bacterial isolates to examine its generality in nature. Modeling and experiments show that antibiotic selection can drive the evolution of duplicated antibiotic resistance genes (ARGs) through MGE transposition. A key implication is that duplicated ARGs should be enriched in environments associated with antibiotic use. To test this, we examined the distribution of duplicated ARGs in 18,938 complete bacterial genomes with ecological metadata. Duplicated ARGs are highly enriched in bacteria isolated from humans and livestock. Duplicated ARGs are further enriched in an independent set of 321 antibiotic-resistant clinical isolates. Our findings indicate that duplicated genes often encode functions undergoing positive selection and horizontal gene transfer in microbial communities.


Asunto(s)
Transferencia de Gen Horizontal , Genes Bacterianos , Humanos , Genes Bacterianos/genética , Transferencia de Gen Horizontal/genética , Bacterias/genética , Farmacorresistencia Microbiana/genética , Antibacterianos/farmacología
5.
J Appl Crystallogr ; 56(Pt 5): 1610-1615, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37791354

RESUMEN

The LauePt program is a popular and easy-to-use crystallography tool for indexing and simulating X-ray Laue patterns, but its previous versions lack search functions for recognizing Laue patterns taken from crystals with unknown orientations. To overcome this obstacle, a major upgrade of the program, called LauePt4, is presented with three robust search schemes implemented: (i) crystal rotation along a single diffraction vector, (ii) a look-up method to search for reflection pairs matching the interplanar angle of two selected diffraction spots, and (iii) a more efficient look-up scheme to search for reflection triplets matching three interplanar angles. Extensive tests show that all these schemes, together with the convenient graphical user interfaces and highly optimized computing algorithms, are reliable and powerful for recognizing and fitting Laue patterns of any crystal taken under any diffraction geometry.

6.
BMJ Open ; 13(6): e066897, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37280023

RESUMEN

OBJECTIVES: To (1) understand what behaviours, beliefs, demographics and structural factors predict US adults' intention to get a COVID-19 vaccination, (2) identify segments of the population ('personas') who share similar factors predicting vaccination intention, (3) create a 'typing tool' to predict which persona people belong to and (4) track changes in the distribution of personas over time and across the USA. DESIGN: Three surveys: two on a probability-based household panel (NORC's AmeriSpeak) and one on Facebook. SETTING: The first two surveys were conducted in January 2021 and March 2021 when the COVID-19 vaccine had just been made available in the USA. The Facebook survey ran from May 2021 to February 2022. PARTICIPANTS: All participants were aged 18+ and living in the USA. OUTCOME MEASURES: In our predictive model, the outcome variable was self-reported vaccination intention (0-10 scale). In our typing tool model, the outcome variable was the five personas identified by our clustering algorithm. RESULTS: Only 1% of variation in vaccination intention was explained by demographics, with about 70% explained by psychobehavioural factors. We identified five personas with distinct psychobehavioural profiles: COVID Sceptics (believe at least two COVID-19 conspiracy theories), System Distrusters (believe people of their race/ethnicity do not receive fair healthcare treatment), Cost Anxious (concerns about time and finances), Watchful (prefer to wait and see) and Enthusiasts (want to get vaccinated as soon as possible). The distribution of personas varies at the state level. Over time, we saw an increase in the proportion of personas who are less willing to get vaccinated. CONCLUSIONS: Psychobehavioural segmentation allows us to identify why people are unvaccinated, not just who is unvaccinated. It can help practitioners tailor the right intervention to the right person at the right time to optimally influence behaviour.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , Adulto , Humanos , Estados Unidos/epidemiología , Vacunas contra la COVID-19/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Autoinforme , Intención , Probabilidad , Vacunación
7.
Sci Rep ; 13(1): 6988, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37193707

RESUMEN

Holistic interventions to overcome COVID-19 vaccine hesitancy require a system-level understanding of the interconnected causes and mechanisms that give rise to it. However, conventional correlative analyses do not easily provide such nuanced insights. We used an unsupervised, hypothesis-free causal discovery algorithm to learn the interconnected causal pathways to vaccine intention as a causal Bayesian network (BN), using data from a COVID-19 vaccine hesitancy survey in the US in early 2021. We identified social responsibility, vaccine safety and anticipated regret as prime candidates for interventions and revealed a complex network of variables that mediate their influences. Social responsibility's causal effect greatly exceeded that of other variables. The BN revealed that the causal impact of political affiliations was weak compared with more direct causal factors. This approach provides clearer targets for intervention than regression, suggesting it can be an effective way to explore multiple causal pathways of complex behavioural problems to inform interventions.


Asunto(s)
COVID-19 , Humanos , Teorema de Bayes , COVID-19/prevención & control , Vacunas contra la COVID-19 , Intención , Vacunación
8.
Soc Indic Res ; 165(2): 453-471, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36339657

RESUMEN

Social media become an important space where people receive and share up-to-date health-related information during the rapid global spread of the novel coronavirus (COVID-19). While information sharing in social media has been shown to improve relations, reduce stress, and enhance life satisfaction, little is known about reciprocal sharing. Situated in COVID-19 pandemic, this study conceptualizes information sharing as a communication process during which sharers expect the receivers to reciprocate, while receivers feel obligated to return the favor. Building upon social exchange theory and studies on social media sharing, the study tested a model of moderated mediation in which sharing of COVID-19 information was predicted to enhance life satisfaction by encouraging reciprocal sharing, i.e., information reciprocity. Subjective norms, attitudes, and perceived usefulness of the information was predicted to moderate the mediation. The hypothesized mediation was supported by data from a survey of 511 online participants in China. Furthermore, the indirect effect appeared stronger among the respondents who found the information more useful, reported more positive attitude, or perceived more subjective norms. The findings suggest that expected reciprocation may be an important incentive for social sharing, and received reciprocation may be a central part of the mechanism through which sharing benefits the sharer. Policymakers and communicators may need to take information reciprocity into consideration when designing health information campaign to confront communal threats.

9.
Front Physiol ; 13: 977735, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36388109

RESUMEN

The treatment of atrial fibrillation (AF) continues to be a significant clinical challenge. While genome-wide association studies (GWAS) are beginning to identify AF susceptibility genes (Gudbjartsson et al., Nature, 2007, 448, 353-357; Choi et al., Circ. Res., 2020, 126, 200-209; van Ouwerkerk et al., Circ. Res., 2022, 127, 229-243), non-genetic risk factors including physical, chemical, and biological environments remain the major contributors to the development of AF. However, little is known regarding how non-genetic risk factors promote the pathogenesis of AF (Weiss et al., Heart Rhythm, 2016, 13, 1868-1877; Chakraborty et al., Heart Rhythm, 2020, 17, 1,398-1,404; Nattel et al., Circ. Res., 2020, 127, 51-72). This is, in part, due to the lack of a robust and reliable animal model induced by non-genetic factors. The currently available models using rapid pacing protocols fail to generate a stable AF phenotype in rodent models, often requiring additional genetic modifications that introduce potential sources of bias (Schüttler et al., Circ. Res., 2020, 127, 91-110). Here, we report a novel murine model of AF using an inducible and tissue-specific activation of diphtheria toxin (DT)-mediated cellular injury system. By the tissue-specific and inducible expression of human HB-EGF in atrial myocytes, we developed a reliable, robust and scalable murine model of AF that is triggered by a non-genetic inducer without the need for AF susceptibility gene mutations.

10.
Am J Ophthalmol Case Rep ; 28: 101747, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36393905

RESUMEN

Purpose: To describe a patient with orbital apocrine hidrocystoma presenting with ptosis and subsequent management. Observations: A 43-year-old woman presented to the oculoplastic surgery clinic with a left-sided ptosis and enlarging but painless mass in the sulcus of the left upper eyelid. Magnetic resonance imaging demonstrated a large, circumscribed T2 bright cystic lesion in the extraconal space. Surgical excision and histopathology confirmed a diagnosis of apocrine hidrocystoma. Conclusions: Although uncommon, ptosis may be a presenting symptom of an orbital apocrine hidrocystoma, which should be considered in the differential diagnosis for an extraconal cystic lesion. Apocrine hidrocystomas are benign tumors and are cured with surgical excision with rare recurrence.

11.
J Neurol Surg B Skull Base ; 83(Suppl 2): e31-e39, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35832987

RESUMEN

Objectives The objective of this study is to elucidate the impact of income on short-term outcomes in a cerebellopontine angle (CPA) tumor resection population. Design This is a retrospective regression analysis. Setting This study was done at a single, multihospital, urban academic medical center. Participants Over 6 years (from June 7, 2013, to April 24, 2019), 277 consecutive CPA tumor cases were reviewed. Main Outcome Measures Outcomes studied included readmission, emergency department evaluation, unplanned return to surgery, return to surgery after index admission, and mortality. Univariate analysis was conducted among the entire population with significance set at a p -value <0.05. The population was divided into quartiles based on median household income and univariate analysis conducted between the lowest (quartile 1 [Q1]) and highest (quartile 4 [Q4]) socioeconomic quartiles, with significance set at a p -value <0.05. Stepwise regression was conducted to determine the correlations among study variables and to identify confounding factors. Results Regression analysis of 273 patients demonstrated decreased rates of unplanned reoperation ( p = 0.015) and reoperation after index admission ( p = 0.035) at 30 days with higher standardized income. Logistic regression between the lowest (Q1) and highest (Q4) socioeconomic quartiles demonstrated decreased unplanned reoperation ( p = 0.045) and decreasing but not significant reoperation after index admission ( p = 0.15) for Q4 patients. No significant difference was observed for other metrics of morbidity and mortality. Conclusion Higher socioeconomic status is associated with decreased risk of unplanned reoperation following CPA tumor resection.

12.
J Neurotrauma ; 39(23-24): 1636-1644, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35579968

RESUMEN

Assessment of the degree of impaired autonomic nervous system (ANS) function is not part of routine clinical practice during inpatient rehabilitation following traumatic spinal cord injury (SCI). The goal of this investigation was to determine the utility of the International Standards for Neurologic Classification of SCI (ISNCSCI) and the recently revised International Standards to document remaining Autonomic Function after SCI (ISAFSCI) in documenting cardiovascular ANS impairment during inpatient rehabilitation following traumatic SCI. Beat-to-beat recording of supine heart rate (HR) and blood pressure (BP) were collected at the bedside for estimation of total cardiovascular ISAFSCI score, cardio-vagal modulation (i.e., high frequency HR variability [HFHRV]) and sympathetic vasomotor regulation (i.e., Mayer wave component of systolic BP [SBPmayer]). A total of 41 participants completed baseline testing, which was conducted 11 ± 5 days from the admission ISNCSCI examination. There were no differences in supine HR or BP based on the ISNCSCI or ISAFSCI assessments. The HFHRV was generally lower with more distal lesions (r2 = 0.15; p = 0.01), and SBPmayer was significantly lower in those with American Spinal Injury Association Impairment Scale (AIS) A compared with AIS B, C, D (Cohen's d = -1.4; p < 0.001). There were no significant differences in HFHRV or SBPmayer in patients with or without ISAFSCI evidence of cardiovascular ANS impairment. These preliminary data suggest that neither the ISNCSCI nor the ISAFSCI are sensitive to changes in ANS cardiovascular function following traumatic SCI. Bedside assessment of HR and BP variabilities may provide insight, but are not readily available in the clinical setting. Further research is required to evaluate methods that accurately assess the degree of ANS impairment following traumatic SCI.


Asunto(s)
Sistema Cardiovascular , Traumatismos de la Médula Espinal , Traumatismos Vertebrales , Humanos , Sistema Nervioso Autónomo , Frecuencia Cardíaca , Traumatismos Vertebrales/complicaciones
13.
Auton Neurosci ; 240: 102973, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35366432

RESUMEN

BACKGROUND: Low blood pressure (BP) may lead to reduced cerebral blood flow velocity (CBFv) during an orthostatic challenge in newly injured patients with traumatic spinal cord injury (SCI), which, may relate to the neurological level of injury (NLI) as documented on the International Standards for the Neurologic Classification of SCI (ISNCSCI), or to evidence of cardiovascular autonomic impairment as determined by the International Standards to document remaining Autonomic Function after SCI (ISAFSCI). OBJECTIVE: To examine the influence of patient demographics, ISNCSCI and ISAFSCI scores on hemodynamic responses to a bedside sit-up test in newly injured patients with SCI. DESIGN: Cross-sectional, prospective analysis. METHODS: A modified sit-up test was conducted at the bedside with the hips at an angle between 45° and 90° and the legs horizontal, level with the hips. Heart rate, BP, and CBFv were recorded for 10 min in the supine and seated positions. RESULTS: Fifty-three newly injured patients (median 39.5 days post-injury) with traumatic SCI were enrolled. Overall, 28 (53%) patients met ISAFSCI criteria, and the number of criteria met (total score) was significantly related to orthostatic changes in CBFv. Change in SBP and change in CBFv were not significantly related, but NLI and total sensory score from the ISNCSCI were significant predictors of the change in CBFv. CONCLUSIONS: Total ISAFSCI score, NLI and sensory scores were positively associated with orthostatic changes in CBFv. Long term follow-up should be considered to determine the consequences of diminished CBFv on cognitive function and quality of life following SCI.


Asunto(s)
Calidad de Vida , Traumatismos de la Médula Espinal , Sistema Nervioso Autónomo , Estudios Transversales , Hemodinámica , Humanos
15.
J Bone Joint Surg Am ; 104(11): 959-970, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-35333812

RESUMEN

BACKGROUND: Suicide and depression among orthopaedic surgeons have recently emerged as rising concerns. Prior research has suggested that orthopaedic surgeons have the highest prevalence of suicide among surgical specialties. We sought to determine the factors associated with depression and suicidal ideation (SI) in orthopaedics, including subspecialty. METHODS: A survey including demographic questions, the Beck Depression Inventory, and the Columbia-Suicide Severity Rating Scale was administered electronically via a listserv to the orthopaedic subspecialties of trauma, adult reconstruction, hand and upper extremity, shoulder and elbow, foot and ankle, spine, pediatrics, sports medicine, and oncology. The responses were quantified according to previously published criteria. The associations of demographic factors, training, and current practice environment with depression and suicidality were assessed using Fisher exact tests. Reverse stepwise multivariable logistic regression models were developed to identify factors associated with depression and SI. RESULTS: The responses were obtained from 661 board-certified, practicing orthopaedic surgeons. In this study, 156 surgeons (23.6%) endorsed some level of active SI in their lifetime, 200 surgeons (30.3%) reported either active or passive SI in their lifetime, and 33 surgeons (5%) reported that, on at least 1 occasion in their lifetime, they had experienced active SI with a specific plan and intention to harm themselves. Gender, relationship status, having children, and residency and/or current practice region were significantly associated with depression and/or SI. Younger age, divorce, adult reconstruction and foot and ankle subspecialties, and attending residency in the Western U.S. were found on multivariable testing to be associated with symptoms of depression and SI (odds ratios, 1.03 [per 1-year decrease in age] to 8.28). CONCLUSIONS: Symptoms of depression and suicidality are not uncommon among orthopaedic surgeons, and variation by gender, relationship status, and geographic location are supported by prior research. Based on our results, depression and/or SI likely affect someone close to you or someone with whom you work. The normalization of discussions surrounding emotional well-being, depression, and SI is imperative.


Asunto(s)
Cirujanos Ortopédicos , Ortopedia , Suicidio , Adulto , Niño , Depresión/diagnóstico , Humanos , Cirujanos Ortopédicos/educación , Ortopedia/educación , Ideación Suicida
16.
Br J Neurosurg ; 36(2): 196-202, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33423556

RESUMEN

PURPOSE: It is well documented that the interaction between many social factors can affect clinical outcomes. However, the independent effects of economics on outcomes following surgery are not well understood. The goal of this study is to investigate the role socioeconomic status has on postoperative outcomes in a cerebellopontine angle (CPA) tumor resection population. MATERIALS AND METHODS: Over 6 years (07 June 2013 to 24 April 2019), 277 consecutive CPA tumor cases were reviewed at a single, multihospital academic medical center. Patient characteristics obtained included median household income, Charlson Comorbidity Index (CCI), race, BMI, tobacco use, amongst 23 others. Outcomes studied included readmission, ED evaluation, unplanned return to surgery (during and after index admission), return to surgery after index admission, and mortality within 90 days, in addition to reoperation and mortality throughout the entire follow-up period. Univariate analysis was conducted amongst the entire population with significance set at a p value <0.05. The population was divided into quartiles based on median household income and univariate analysis conducted between the lowest (Q1) and highest (Q4) socioeconomic quartiles, with significance set at a p value <0.05. Stepwise regression was conducted to determine the correlations amongst study variables and identify confounding factors. RESULTS: Regression analysis of 273 patients did not find household income to be associated with any of the long-term outcomes assessed. Similarly, a Q1 vs Q4 comparison did not yield significantly different odds of outcomes assessed. CONCLUSION: Although not statistically significant, the odds ratios suggest socioeconomic status may have a clinically significant effect on postsurgical outcomes. Further studies in larger, matched populations are necessary to validate these findings.


Asunto(s)
Neuroma Acústico , Hospitalización , Humanos , Neuroma Acústico/cirugía , Procedimientos Neuroquirúrgicos , Readmisión del Paciente , Reoperación , Estudios Retrospectivos , Clase Social
17.
Artículo en Inglés | MEDLINE | ID: mdl-36730596

RESUMEN

PURPOSE: To determine whether maribavir is effective at treating ganciclovir-resistant cytomegalovirus retinitis. METHODS: Retrospective case report of a lung transplant patient with bilateral cytomegalovirus retinitis documented with serum and aqueous humor studies and color fundus photographs. RESULTS: A 72-year-old lung transplant patient with active ganciclovir-resistant cytomegalovirus was treated with intravitreal foscarnet therapy in one eye. Retinitis developed in the contralateral eye and was managed with systemic maribavir alone. Active retinitis regressed in both the eye treated with intravitreal foscarnet and the un-injected eye. CONCLUSIONS: This patient's results suggest that systemic maribavir is an effective treatment for treatment-resistant cytomegalovirus retinitis.

18.
Nat Commun ; 12(1): 6893, 2021 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-34824250

RESUMEN

Replicative immortality is a hallmark of cancer, and can be achieved through telomere lengthening and maintenance. Although the role of telomere length in cancer has been well studied, its association to genomic features is less well known. Here, we report the telomere lengths of 392 localized prostate cancer tumours and characterize their relationship to genomic, transcriptomic and proteomic features. Shorter tumour telomere lengths are associated with elevated genomic instability, including single-nucleotide variants, indels and structural variants. Genes involved in cell proliferation and signaling are correlated with tumour telomere length at all levels of the central dogma. Telomere length is also associated with multiple clinical features of a tumour. Longer telomere lengths in non-tumour samples are associated with a lower rate of biochemical relapse. In summary, we describe the multi-level integration of telomere length, genomics, transcriptomics and proteomics in localized prostate cancer.


Asunto(s)
Neoplasias de la Próstata/genética , Telómero/genética , Variaciones en el Número de Copia de ADN , Epigenoma , Fusión Génica , Genómica , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteoma , Telomerasa/genética , Telomerasa/metabolismo , Transcriptoma
19.
Front Artif Intell ; 4: 612551, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34337389

RESUMEN

Developing data-driven solutions that address real-world problems requires understanding of these problems' causes and how their interaction affects the outcome-often with only observational data. Causal Bayesian Networks (BN) have been proposed as a powerful method for discovering and representing the causal relationships from observational data as a Directed Acyclic Graph (DAG). BNs could be especially useful for research in global health in Lower and Middle Income Countries, where there is an increasing abundance of observational data that could be harnessed for policy making, program evaluation, and intervention design. However, BNs have not been widely adopted by global health professionals, and in real-world applications, confidence in the results of BNs generally remains inadequate. This is partially due to the inability to validate against some ground truth, as the true DAG is not available. This is especially problematic if a learned DAG conflicts with pre-existing domain doctrine. Here we conceptualize and demonstrate an idea of a "Causal Datasheet" that could approximate and document BN performance expectations for a given dataset, aiming to provide confidence and sample size requirements to practitioners. To generate results for such a Causal Datasheet, a tool was developed which can generate synthetic Bayesian networks and their associated synthetic datasets to mimic real-world datasets. The results given by well-known structure learning algorithms and a novel implementation of the OrderMCMC method using the Quotient Normalized Maximum Likelihood score were recorded. These results were used to populate the Causal Datasheet, and recommendations could be made dependent on whether expected performance met user-defined thresholds. We present our experience in the creation of Causal Datasheets to aid analysis decisions at different stages of the research process. First, one was deployed to help determine the appropriate sample size of a planned study of sexual and reproductive health in Madhya Pradesh, India. Second, a datasheet was created to estimate the performance of an existing maternal health survey we conducted in Uttar Pradesh, India. Third, we validated generated performance estimates and investigated current limitations on the well-known ALARM dataset. Our experience demonstrates the utility of the Causal Datasheet, which can help global health practitioners gain more confidence when applying BNs.

20.
J Med Internet Res ; 23(5): e22933, 2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-33878015

RESUMEN

BACKGROUND: The COVID-19 pandemic has impacted people's lives at unprecedented speed and scale, including how they eat and work, what they are concerned about, how much they move, and how much they can earn. Traditional surveys in the area of public health can be expensive and time-consuming, and they can rapidly become outdated. The analysis of big data sets (such as electronic patient records and surveillance systems) is very complex. Google Trends is an alternative approach that has been used in the past to analyze health behaviors; however, most existing studies on COVID-19 using these data examine a single issue or a limited geographic area. This paper explores Google Trends as a proxy for what people are thinking, needing, and planning in real time across the United States. OBJECTIVE: We aimed to use Google Trends to provide both insights into and potential indicators of important changes in information-seeking patterns during pandemics such as COVID-19. We asked four questions: (1) How has information seeking changed over time? (2) How does information seeking vary between regions and states? (3) Do states have particular and distinct patterns in information seeking? (4) Do search data correlate with-or precede-real-life events? METHODS: We analyzed searches on 38 terms related to COVID-19, falling into six themes: social and travel; care seeking; government programs; health programs; news and influence; and outlook and concerns. We generated data sets at the national level (covering January 1, 2016, to April 15, 2020) and state level (covering January 1 to April 15, 2020). Methods used include trend analysis of US search data; geographic analyses of the differences in search popularity across US states from March 1 to April 15, 2020; and principal component analysis to extract search patterns across states. RESULTS: The data showed high demand for information, corresponding with increasing searches for coronavirus linked to news sources regardless of the ideological leaning of the news source. Changes in information seeking often occurred well in advance of action by the federal government. The popularity of searches for unemployment claims predicted the actual spike in weekly claims. The increase in searches for information on COVID-19 care was paralleled by a decrease in searches related to other health behaviors, such as urgent care, doctor's appointments, health insurance, Medicare, and Medicaid. Finally, concerns varied across the country; some search terms were more popular in some regions than in others. CONCLUSIONS: COVID-19 is unlikely to be the last pandemic faced by the United States. Our research holds important lessons for both state and federal governments in a fast-evolving situation that requires a finger on the pulse of public sentiment. We suggest strategic shifts for policy makers to improve the precision and effectiveness of non-pharmaceutical interventions and recommend the development of a real-time dashboard as a decision-making tool.


Asunto(s)
COVID-19/epidemiología , Conducta en la Búsqueda de Información , Motor de Búsqueda/tendencias , Humanos , Estudios Longitudinales , Pandemias , SARS-CoV-2/aislamiento & purificación , Estados Unidos/epidemiología
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