bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of family health history in surveys vs electronic health record data mapped to the observational medical outcomes partnership data model in the All of Us Research Program
Authors: Cronin Robert M , Halvorson Alese E , Springer Cassie , Feng Xiaoke , Sulieman Lina , Loperena-Cortes Roxana , Mayo Kelsey , Carroll Robert J , Chen Qingxia , Ahmedani Brian K , Karnes Jason , Korf Bruce , O’Donnell Christopher J , Qian Jun , Ramirez Andrea H 
Published: November 2020

Abstract

Objective
Family health history is important to clinical care and precision medicine. Prior studies show gaps in data collected from patient surveys and electronic health records (EHRs). The All of Us Research Program collects family history from participants via surveys and EHRs. This Demonstration Project aims to evaluate availability of family health history information within the publicly available data from All of Us and to characterize the data from both sources.

Materials and Methods
Surveys were completed by participants on an electronic portal. EHR data was mapped to the Observational Medical Outcomes Partnership data model. We used descriptive statistics to perform exploratory analysis of the data, including evaluating a list of medically actionable genetic disorders. We performed a subanalysis on participants who had both survey and EHR data.

Results
There were 54 872 participants with family history data. Of those, 26% had EHR data only, 63% had survey only, and 10.5% had data from both sources. There were 35 217 participants with reported family history of a medically actionable genetic disorder (9% from EHR only, 89% from surveys, and 2% from both). In the subanalysis, we found inconsistencies between the surveys and EHRs. More details came from surveys. When both mentioned a similar disease, the source of truth was unclear.

Conclusions
Compiling data from both surveys and EHR can provide a more comprehensive source for family health history, but informatics challenges and opportunities exist. Access to more complete understanding of a person’s family health history may provide opportunities for precision medicine.
Quantitation of Δ8-THC, Δ9-THC, Cannabidiol and 10 Other Cannabinoids and Metabolites in Oral Fluid by HPLC–MS-MS
Authors: Lin Lin , Amaratunga Piyadarsha , Reed Jerome , Huang Pornkamol , Lemberg Bridget Lorenz , Lemberg Dave 
Published: December 2020

Abstract
Quantitative analysis of Δ9-tetrahydrocannabinol (Δ9-THC) in oral fluid has gained increasing interest in clinical and forensic toxicology laboratories. New medicinal and/or recreational cannabinoid products require laboratories to distinguish different patterns of cannabinoid use. This study validated a high-performance liquid chromatography-tandem mass spectrometry method for 13 different cannabinoids, including (-)-trans-Δ8-tetrahydrocannabinol (Δ8-THC), (-)-trans-Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), Δ9-tetrahydrocannabinolic acid-A (Δ9-THCA-A), cannabidiolic acid (CBDA), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THCCOOH), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabidiorcol (CBD-C1), cannabichromene (CBC), cannabinol (CBN) and cannabigerol (CBG), in oral fluid. Baseline separation was achieved in the entire quantitation range between Δ9-THC and its isomer Δ8-THC. The quantitation range of Δ9-THC, Δ8-THC and CBD was from 0.1 to 800 ng/mL. Two hundred human subject oral fluid samples were analyzed with this method after solid phase extraction. Among the 200 human subject oral fluid samples, all 13 cannabinoid analytes were confirmed in at least one sample. Δ8-THC was confirmed in 11 samples, with or without the presence of Δ9-THC. A high concentration of 11-OH-Δ9-THC or Δ9-THCCOOH (&gt;400 ng/mL) was confirmed in three samples. CBD, Δ9-THCA-A, THCV, CBN and CBG were confirmed in 74, 39, 44, 107 and 112 of the 179 confirmed Δ9-THC-positive samples, respectively. The quantitation of multiple cannabinoids and metabolites in oral fluid simultaneously provides valuable information for revealing cannabinoid consumption and interpreting cannabinoid-induced driving impairment.
GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma
Authors: Natsumeda Manabu , Miyahara Hiroaki , Yoshimura Junichi , Nakata Satoshi , Nozawa Takanori , Ito Junko , Kanemaru Yu , Watanabe Jun , Tsukamoto Yoshihiro , Okada Masayasu , Oishi Makoto , Hirato Junko , Wataya Takafumi , Ahsan Sama , Tateishi Kensuke , Yamamoto Tetsuya , Rodriguez Fausto J , Takahashi Hitoshi , Hovestadt Volker , Suva Mario L , Taylor Michael D , Eberhart Charles G , Fujii Yukihiko , Kakita Akiyoshi 
Published: November 2020

Abstract
Glioma-associated oncogene homolog 3 (GLI3), whose main function is to inhibit GLI1, has been associated with neuronal differentiation in medulloblastoma. However, it is not clear what molecular subtype(s) show increased GLI3 expression. GLI3 levels were assessed by immunohistochemistry in 2 independent cohorts, including a total of 88 cases, and found to be high in both WNT- and SHH-activated medulloblastoma. Analysis of bulk mRNA expression data and single cell RNA sequencing studies confirmed that GLI1 and GLI3 are highly expressed in SHH-activated medulloblastoma, whereas GLI3 but not GLI1 is highly expressed in WNT-activated medulloblastoma. Immunohistochemical analysis has shown that GLI3 is expressed inside the neuronal differentiated nodules of SHH-activated medulloblastoma, whereas GLI1/2 are expressed in desmoplastic areas. In contrast, GLI3 is diffusely expressed in WNT-activated medulloblastoma, whereas GLI1 is suppressed. Our data suggest that GLI3 may be a master regulator of neuronal differentiation and morphology in these subgroups.
Lack of survival advantage among re-resected elderly glioblastoma patients: a SEER-Medicare study
Authors: Goldman Debra A , Reiner Anne S , Diamond Eli L , DeAngelis Lisa M , Tabar Viviane , Panageas Katherine S 
Published: November 2020

Abstract

Background
The survival benefit of re-resection for glioblastoma (GBM) remains controversial, owing to the immortal time bias inadequately considered in many studies where re-resection was treated as a fixed, rather than a time-dependent factor. Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we assessed treatment patterns for older adults and evaluated the association between re-resection and overall survival (OS), accounting for the timing of re-resection.

Methods
This retrospective cohort study included elderly patients (age ≥66) in the SEER-Medicare linked database diagnosed with GBM between 2006 and 2015 who underwent initial resection. Time-dependent Cox regression was used to assess the association between re-resection and OS, controlling for age, gender, race, poverty level, geographic region, marital status, comorbidities, receipt of radiation + temozolomide, and surgical complications.

Results
Our analysis included 3604 patients with median age 74 (range: 66–96); 54% were men and 94% were white. After initial resection, 44% received radiation + temozolomide and these patients had a lower hazard of death (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.26–0.31, P &lt; .001). In total, 9.5% (n = 343) underwent re-resection. In multivariable analyses, no survival benefit was seen for patients who underwent re-resection (HR: 1.12, 95% CI: 0.99–1.27, P = .07).

Conclusions
Re-resection rates were low among elderly GBM patients, and no survival advantage was observed for patients who underwent re-resection. However, patients who received standard of care at initial diagnosis had a lower risk of death. Older adults benefit from receiving radiation + temozolomide after initial resection, and future studies should assess the relationship between re-resection and OS taking the time of re-resection into account.
Case series review of neuroradiologic changes associated with immune checkpoint inhibitor therapy
Authors: Gatson Na Tosha N , Makary Mina , Bross Shane P , Vadakara Joseph , Maiers Tristan , Mongelluzzo Gino J , Leese Erika N , Brimley Cameron , Fonkem Ekokobe , Mahadevan Anand , Sarkar Atom , Panikkar Rajiv 
Published: November 2020

Abstract
While immuno-oncotherapy (IO) has significantly improved outcomes in the treatment of systemic cancers, various neurological complications have accompanied these therapies. Treatment with immune checkpoint inhibitors (ICIs) risks multi-organ autoimmune inflammatory responses with gastrointestinal, dermatologic, and endocrine complications being the most common types of complications. Despite some evidence that these therapies are effective to treat central nervous system (CNS) tumors, there are a significant range of related neurological side effects due to ICIs. Neuroradiologic changes associated with ICIs are commonly misdiagnosed as progression and might limit treatment or otherwise impact patient care. Here, we provide a radiologic case series review restricted to neurological complications attributed to ICIs, anti-CTLA-4, and PD-L-1/PD-1 inhibitors. We report the first case series dedicated to the review of CNS/PNS radiologic changes secondary to ICI therapy in cancer patients. We provide a brief case synopsis with neuroimaging followed by an annotated review of the literature relevant to each case. We present a series of neuroradiological findings including nonspecific parenchymal and encephalitic, hypophyseal, neural (cranial and peripheral), meningeal, cavity-associated, and cranial osseous changes seen in association with the use of ICIs. Misdiagnosis of radiologic abnormalities secondary to neurological immune-related adverse events can impact patient treatment regimens and clinical outcomes. Rapid recognition of various neuroradiologic changes associated with ICI therapy can improve patient tolerance and adherence to cancer therapies.
Evaluation and management of chimeric antigen receptor (CAR) T-cell-associated neurotoxicity
Authors: Gonzalez Castro Luis Nicolas , Dietrich Jorg 
Published: November 2020

Abstract
Adoptive cell therapies are a group of cancer immunotherapies that involve the infusion of engineered immune cells targeting specific tumor antigens, with chimeric antigen receptor (CAR) T cells at the vanguard of this revolution in cancer therapy. Several CAR T-cell products have been approved for the treatment of leukemia and lymphoma and many more are currently undergoing evaluation in clinical trials for the treatment of other liquid and solid malignancies. Despite their remarkable effectiveness, as with other immunotherapies, CAR T cells are frequently associated with systemic and neurologic toxicity. There has been a major effort by many institutions to develop specific protocols to guide the management of treatment-associated toxicities (eg, cytokine release syndrome [CRS]). However, neurotoxic effects of CAR T-cell therapies are more difficult to evaluate and treat, not easily lending themselves to an algorithmic approach to diagnosis and management. Given the steadily expanding use of CAR T-cell therapies for various malignancies, it is of critical importance for neuro-oncologists to be familiar with the clinical presentation and management principles of CAR T-cell-associated neurotoxicity. Here, we present key principles for the evaluation and management of patients affected by CAR T-cell-associated neurotoxicity based on the most recent evidence.
Analytical Performance of the Exacto Test HIV Self-Test: A Cross-Sectional Field Study in the Democratic Republic of the Congo
Authors: Tonen-Wolyec Serge , Muwonga Masidi Jérémie , Kamanga Lukusa Luc Ferdinand , Nsiku Dikumbwa Gaetan , Sarassoro Angèle , Bélec Laurent 
Published: November 2020

Abstract
The Democratic Republic of the Congo (DRC) has begun implementing HIV self-testing to boost the first “95” of the UNAIDS 95-95-95 targets by 2025. This study aims to assess the performance and usability of the Exacto Test HIV (Biosynex, Strasbourg, France) self-test in the lab and in the field. The Exacto Test HIV self-test demonstrated high virological performance (sensitivity, 99.6%; specificity, 100%) in the lab and in the field in the hand of untrained users (sensitivity, 100%; specificity, 98.9%). Taken together, the excellent performance and usability characteristics of the Exacto Test HIV (Biosynex) self-test make the kit a viable option for HIV self-testing in the DRC.
Spatial distribution of the X-ray-emitting plasma of U Geminorum in quiescence and outburst
Authors: Takeo Mai , Hayashi Takayuki , Ishida Manabu , Nakaniwa Nozomi , Maeda Yoshitomo 
Published: November 2020

Abstract
We present our analysis of the Suzaku data of U Geminorum (U Gem) from 2012 both in quiescence and outburst. Unlike SS Cygni (SS Cyg), the hard X-ray flux of U Gem is known to increase at times of optical outburst. A sophisticated spectral model and reliable distance estimate now reveal that this can be attributed to the fact that the mass accretion rate onto the white dwarf (WD) does not exceed the critical rate that causes the optically thin to thick transition of the boundary layer. From comparison of the X-ray and optical light curves, the X-ray outburst peak seems to be retarded by 2.1 ± 0.5 d, although there remains uncertainty in the X-ray peak identification, due to short data coverage. The larger delay than SS Cyg (0.9–1.4 d) also supports the lower accretion rate in U Gem. A fluorescent iron 6.4 keV emission line bears significant information about the geometry of the X-ray-emitting hot plasma and the accretion disk (AD) that reflects the hard X-ray emission. Our reflection simulation has shown that the optically thick AD is truncated at a distance of 1.20–1.25 times the white dwarf radius (RWD) in quiescence, and the accreting matter in the disk turns into the optically thin hard-X-ray-emitting plasma at this radius. In outburst, on the other hand, our spectral analysis favors the picture that the optically thick disk reaches the WD surface, although disk truncation can take place in the region of &lt;1.012 RWD. From the profile of the 6.4 keV line, we have also discovered that the accreting matter is heated up close to the maximum temperature immediately after the matter enters the boundary layer at the disk truncation radius. This is consistent with the fact that the hard X-ray spectra of dwarf novae, in general, can be well represented with the cooling flow model.
Identifying the Costs of a Public Health Success: Arsenic Well Water Contamination and Productivity in Bangladesh
Authors: Pitt Mark M , Rosenzweig Mark R , Hassan M Nazmul 
Published: December 2020

Abstract
We exploit recent molecular genetics evidence on the genetic basis of arsenic excretion and unique information on family links among respondents living in different environments from a large panel survey to uncover the hidden costs of arsenic poisoning in Bangladesh. We provide for the first time estimates of the effects of the ingestion and retention of inorganic arsenic on direct measures of cognitive and physical capabilities as well as on the schooling attainment, occupational structure, entrepreneurship, and incomes of the rural Bangladesh population. We also provide new estimates of the effects of the consumption of foods grown and cooked in arsenic-contaminated water on individual arsenic concentrations. The estimates are based on arsenic biomarkers obtained from a sample of members of rural households in Bangladesh who are participants in a long-term panel survey following respondents and their coresident household members over a period of 26 years.
Sleep in ostrich chicks (Struthio camelus)
Authors: Lyamin Oleg I , Kibalnikov Anton S , Siegel Jerome M 
Published: November 2020

AbstractIt has been reported that adult ostriches displayed the longest episodes of rapid eye movement (REM) sleep (up to 5 min) and more REM sleep (24% of the nighttime) than any other bird species. If the mammalian ontogenetic trend exists in the ostrich, then the amounts of REM and the duration of sleep episodes in young ostriches may be greater than those reported in adults. We investigated sleep in 1.5–3.5 month old ostrich chicks. Recordings were conducted during nighttime (20:00–08:00), the main sleep period in ostriches, which are diurnal. The polygrams were scored in 4-s epochs for waking, non-rapid eye movement (NREM) sleep and REM sleep, as in other bird studies. REM sleep in ostrich chicks occurred during both cortical EEG activation and during slow waves, as was described in adult ostriches. The chicks spent 69.3% ± 1.5% of the night in NREM sleep. REM sleep occupied 14.1% ± 1.8% of the night or 16.8% ± 2.0% of nighttime sleep. Episodes of REM sleep lasted on average 10 ± 1 s and ranged between 4 and 40 s. Therefore, the total amount and duration of REM sleep episodes in ostrich chicks were substantially smaller than reported in adult ostriches while the amounts of NREM sleep did not greatly differ. The developmental profile of REM sleep ontogenesis in the ostrich may be remarkably different from what has been reported in all studied mammals and birds.
Comparative efficacy and safety of hypnotics for insomnia in older adults: a systematic review and network meta-analysis
Authors: Chiu Hsiao-Yean , Lee Hsin-Chien , Liu Jen-Wei , Hua Shi-Jun , Chen Pin-Yuan , Tsai Pei-Shan , Tu Yu-Kang 
Published: November 2020

AbstractStudy ObjectivesTo compare the efficacy and safety of various hypnotics for identifying the best treatments for insomnia in older adults.MethodsWe searched the EMBASE, PubMed, ClinicalTrials.gov, and ProQuest Dissertations and Theses A&I databases from the inception to September 12, 2020. Only randomized controlled trials comparing hypnotics with either another hypnotic or placebo for insomnia treatment in elderly people were included. Sleep outcomes, including total sleep time, sleep onset latency, wake after sleep onset, sleep efficiency, were derived from polysomnography, valid questionnaires, or sleep diaries.ResultsWe identified 24 articles with 5917 older adults. Eszopiclone and low-dose doxepin were ranked the optimal therapy for prolonging objective and subjective total sleep time (26.69 and 28.19 min), respectively, compared to placebo. Zaleplon was the most effective therapy in reducing objective and subjective sleep onset latency (–21.63 and –15.86 min) compared with control. Temazepam was the best treatment for objective and subjective wake after sleep onset (–25.29 and –22.25 min) compared with control. Low-dose doxepin appeared to be the effective treatment for increasing objective sleep efficiency (6.08%) Triazolam showed the higher risk of overall adverse events (odds ratio, 1.96, 95% confidence interval 1.03–3.74) when compared to zaleplon.ConclusionsConsidering study quality and the potential adverse effects of benzodiazepines and nonbenzodiazepines, low-dose doxepin seems to be the optimal pharmacotherapy for the improvements in total sleep time and sleep efficiency. Future RCTs investigating the treatment effects of hypnotics, particularly low-dose doxepin, on insomnia in older adults are warranted.PROSPERO Registration number: CRD42016046301.
Disparities in Documented Drug Use Disorders Between Transgender and Cisgender U.S. Veterans Health Administration Patients
Authors: Frost Madeline C. , Blosnich John R. , Lehavot Keren , Chen Jessica A. , Rubinsky Anna D. , Glass Joseph E. , Williams Emily C. 
Published: November 2020

Objectives:
Transgender people—those whose gender identity differs from their sex assigned at birth—are at risk for health disparities resulting from stressors such as discrimination and violence. Transgender people report more drug use than cisgender people; however, it is unclear whether they have higher likelihood of drug use disorders. We examined whether transgender patients have increased likelihood of documented drug use disorders relative to cisgender patients in the national Veterans Health Administration (VA).

Methods:
Electronic health record data were extracted for VA outpatients from 10/1/09 to 7/31/17. Transgender status and past-year documentation of drug use disorders (any, opioid, amphetamine, cocaine, cannabis, sedative, hallucinogen) were measured using diagnostic codes. Logistic regression models estimated odds ratios for drug use disorders among transgender compared to cisgender patients, adjusted for age, race/ethnicity and year. Effect modification by presence of ≥1 mental health condition was tested using multiplicative interaction.

Results:
Among 8,872,793 patients, 8619 (0.1%) were transgender. Transgender patients were more likely than cisgender patients to have any drug use disorder (Adjusted Odds Ratio [aOR] 1.67, 95% confidence interval [CI] 1.53–1.83), amphetamine (aOR 2.22, 95% CI 1.82–2.70), cocaine (aOR 1.59, 95% CI 1.29–1.95), and cannabis (aOR 1.82, 95% CI 1.62–2.05) use disorders. There was no significant interaction by presence of ≥1 mental health condition.

Conclusions:
Transgender VA patients may have higher likelihood of certain drug use disorders than cisgender VA patients, particularly amphetamine use disorder. Future research should explore mechanisms underlying disparities and potential barriers to accessing treatment and harm reduction services faced by transgender people.
Management of infected nonunions of the femur and tibia with compression-distraction osteogenesis coupled with modern methods at a tertiary military establishment: a prospective case series
Authors: Kaul Rajiv , Akhoon Neha , Mugdum Girish , Prasad Manish 
Published: November 2020

Background:
Infected nonunions pose a daunting challenge to any orthopaedic surgeon. The essence of treatment is a radical debridement for eradication of infection coupled with various approaches to address the bone gap. Bone transport and acute docking along with a corticotomy and distraction osteogenesis have stood the test of time. Our purpose was to evaluate the treatment outcome of the modified Ilizarov technique in infected nonunions of the femur and tibia.

Methods:
Twenty-six patients with infected femoral and tibial nonunions underwent aggressive debridement and either bifocal compression-distraction osteogenesis or bone transport using an Ilizarov frame. Adjuvant methods such as local antibiotic delivery systems, bone marrow aspirate concentrate (BMAC) injections, pulsatile recombinant parathyroid hormone (PTH) injections, and negative pressure wound therapy (NPWT) were deployed, as deemed necessary, in specific situations.

Results:
The mean follow-up period was 24.2 mo. The mean time to union was 267.7 days. Union was achieved in 25 cases with complete eradication of infection. Bone results as per the Association for Study of Application of Methods of Ilizarov (ASAMI) scoring system were excellent in 19 patients, good in four, fair in two, and poor in one. The average duration for external fixation was 8.9 mo. Complications occurred in 30.8% of patients.

Conclusions:
The Ilizarov method, by itself or in combination with modern methods, gives satisfactory bone and functional results. Complication rates depend upon the surgeon’s adherence to the cardinal principles of Ilizarov.

Level of Evidence:
Level IV.