Benzodiazepine use in medical cannabis authorization adult patients from 2013 to 2021: Alberta, Canada.

BACKGROUND: Benzodiazepines are a class of medications that are being frequently prescribed in Canada but carry significant risk of harm. There has been increasing clinical interest on the potential "sparing effects" of medical cannabis as one strategy to reduce benzodiazepine use. The objective of this study as to examine the association of medical cannabis authorization with benzodiazepine usage between 2013 and 2021 in Alberta, Canada. METHODS: A propensity score matched cohort study with patients on regular benzodiazepine treatment authorized to use medical cannabis compared to controls who do not have authorization for medical cannabis. A total of 9690 medically authorized cannabis patients were matched to controls. To assess the effect of medical cannabis use on daily average diazepam equivalence (DDE), interrupted time series (ITS) analysis was used to assess the change in the trend of DDE in the 12 months before and 12 months after the authorization of medical cannabis. RESULTS: Over the follow-up period after medical cannabis authorization, there was no overall change in the DDE use in authorized medical cannabis patients compared to matched controls (- 0.08 DDE, 95% CI: - 0.41 to 0.24). Likewise, the sensitivity analysis showed that, among patients consuming ≤5 mg baseline DDE, there was no change immediately after medical cannabis authorization compared to controls (level change, - 0.04 DDE, 95% CI: - 0.12 to 0.03) per patient as well as in the month-to-month trend change (0.002 DDE, 95% CI: - 0.009 to 0.12) per patient was noted. CONCLUSIONS: This short-term study found that medical cannabis authorization had minimal effects on benzodiazepine use. Our findings may contribute ongoing evidence for clinicians regarding the potential impact of medical cannabis to reduce benzodiazepine use. HIGHLIGHTS: • Medical cannabis authorization had little to no effect on benzodiazepine usage among patients prescribed regular benzodiazepine treatment in Alberta, Canada. • Further clinical research is needed to investigate the potential impact of medical cannabis as an alternative to benzodiazepine medication.

Beyond conventional bounds: Surpassing system limits for stereotactic ablative (SAbR) lung radiotherapy using CBCT-based adaptive planning system.

PURPOSE: Online adaptive radiotherapy relies on a high degree of automation to enable rapid planning procedures. The Varian Ethos intelligent optimization engine (IOE) was originally designed for conventional treatments so it is crucial to provide clear guidance for lung SAbR plans. This study investigates using the Ethos IOE together with adaptive-specific optimization tuning structures we designed and templated within Ethos to mitigate inter-planner variability in meeting RTOG metrics for both online-adaptive and offline SAbR plans. METHODS: We developed a planning strategy to automate the generation of tuning structures and optimization. This was validated by retrospective analysis of 35 lung SAbR cases (total 105 fractions) treated on Ethos. The effectiveness of our planning strategy was evaluated by comparing plan quality with-and-without auto-generated tuning structures. Internal target volume (ITV) contour was compared between that drawn from CT simulation and from cone-beam CT (CBCT) at time of treatment to verify CBCT image quality and treatment effectiveness. Planning strategy robustness for lung SAbR was quantified by frequency of plans meeting reference plan RTOG constraints. RESULTS: Our planning strategy creates a gradient within the ITV with maximum dose in the core and improves intermediate dose conformality on average by 2%. ITV size showed no significant difference between those contoured from CT simulation and first fraction, and also trended towards decreasing over course of treatment. Compared to non-adaptive plans, adaptive plans better meet reference plan goals (37% vs. 100% PTV coverage compliance, for scheduled and adapted plans) while improving plan quality (improved GI (gradient index) by 3.8%, CI (conformity index) by 1.7%). CONCLUSION: We developed a robust and readily shareable planning strategy for the treatment of adaptive lung SAbR on the Ethos system. We validated that automatic online plan re-optimization along with the formulated adaptive tuning structures can ensure consistent plan quality. With the proposed planning strategy, highly ablative treatments are feasible on Ethos.

18 F-DCFPyL positron emission tomography/magnetic resonance imaging-guided ultrasound fusion biopsy is an identical pathway in prostate cancer diagnosis.

BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.

Fracture rate increases after immune checkpoint inhibitor treatment: a potential new immune related adverse event.

INTRODUCTION: T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use. METHODS: Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline. RESULTS: The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34-4.27). CONCLUSIONS: Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event.

Right arcuate fasciculus as outcome predictor after low-frequency repetitive transcranial magnetic stimulation in nonfluent aphasic stroke.

BACKGROUND AND PURPOSE: A reliable neuroimaging biomarker to predict language improvement after neuromodulation in post-stroke aphasia is lacking. It is hypothesized that aphasic patients with stroke injuries in the left primary language circuits but with sufficient right arcuate fasciculus (AF) integrity might respond to low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), leading to language improvement. This study aimed to assess the microstructural indices of the right AF before LF-rTMS treatment and further correlate with language improvement after the treatment. METHODS: Thirty-three patients with at least 3 months after stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double-blind study. All patients received real 1-Hz LF-rTMS (n = 16) or sham stimulation (n = 17) at the right pars triangularis for 10 consecutive weekdays. Fractional anisotropy, axial diffusivity, radial diffusivity and apparent diffusion coefficient of the right AF were extracted using diffusion tensor imaging before the rTMS treatment and correlated with the measured functional improvement by the Concise Chinese Aphasia Test. RESULTS: The Concise Chinese Aphasia Test change scores revealed a stronger language improvement in auditory/reading comprehension and expression in the rTMS group than in the sham group. Regression analysis showed that the pre-treatment fractional anisotropy, axial diffusivity and apparent diffusion coefficient of the right AF significantly correlated with the expression abilities (R2 > 0.700, p < 0.044) and comprehension abilities (R2 > 0.702, p < 0.039) in the rTMS group. CONCLUSIONS: It was concluded that the right AF could be a predictor in language recovery induced by LF-rTMS after the injuries of primary language circuits.

The role of differentially expressed miR-660 in peripheral blood lymphocytes of patients with pulmonary tuberculosis.

OBJECTIVE: This study aimed to investigate the significance of miRNA expression levels in peripheral blood lymphocytes of patients clinically diagnosed with pulmonary tuberculosis. METHOD: Pulmonary tuberculosis-related datasets in the Gene Expression Omnibus (GEO) database were analyzed, and DE-miRNAs were screened for Gene Ontology (GO) analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment to construct a DE-miRNA-DE-mRNA network. The peripheral blood lymphocytes of 10 patients with pulmonary tuberculosis, 10 patients with rifampicin-resistant tuberculosis and 10 healthy volunteers were selected for validation of RNA expression levels. qRT-PCR was done to verify the expression of DE-miRNA, and western blotting was done to check the expression levels of genes of associated pathways. RESULTS: Differential expression of miR-660 was found in pulmonary tuberculosis through data analysis and literature mining. The differential expression was also confirmed by qRT-PCR in samples from patients and healthy controls. The expression of miR-660 was significantly upregulated (p < 0.01) in patients with pulmonary tuberculosis and rifampicin-resistant pulmonary tuberculosis compared with the healthy controls. According to western blotting results, the expression levels of P-NF-κB and AKT in patients with pulmonary tuberculosis and NF-κB, P-NF-κB, AKT and p-AKT in patients with rifampicin-resistant tuberculosis were significantly upregulated (p < 0.01). CONCLUSION: The high expression levels of miR-660 may activate the AKT/NF-κB signalling pathway and has the potential to serve as a potential biomarker for the diagnosis of pulmonary tuberculosis.

Reconstruction of the Sources and Their Contributions to 129I in Northern Xinjiang, China.

Anthropogenic 129I, as a long-lived fission product and volatile radionuclide, can be used to investigate dispersion of air masses and the deposition of atmospheric pollution. Surface soil and soil core samples were collected from Northern Xinjiang and analyzed for 127I and 129I. The results show that 129I/127I atomic ratios in surface soil are inhomogeneous with a range of (2.07-106) × 10-9, and the maximum values in each soil core occurred at surface-subsurface layers (0-15 cm) at undisturbed sites. The dominant source of 129I in Northern Xinjiang is European nuclear fuel reprocessing plant (NFRP) releases, accounting for at least 70% of the total inventory; less than 20% of 129I originates from the global fallout of atmospheric nuclear weapons tests; less than 10% comes from the regional deposition of nuclear weapons tests at the Semipalatinsk site; and the regional deposition from the nuclear weapons tests at the Lop Nor site is insignificant. The European NFRP-derived 129I was transported to Northern Xinjiang via long-distance atmospheric dispersion with the westerlies through Northern Eurasia. The distribution of 129I in the surface soil in Northern Xinjiang is mainly controlled by topography, wind fields, land utilization, and vegetation coverage.

On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

Clinical experience on patient-specific quality assurance for CBCT-based online adaptive treatment plan.

PURPOSE: Ethos CBCT-based adaptive radiotherapy (ART) system can generate an online adaptive plan by re-optimizing the initial reference plan based on the patient anatomy at the treatment. The optimization process is fully automated without any room for human intervention. Due to the change in anatomy, the ART plan can be significantly different from the initial plan in terms of plan parameters such as the aperture shapes and number of monitor units (MUs). In this study, we investigated the feasibility of using calculation-based patient specific QA for ART plans in conjunction with measurement-based and calculation-based QA for initial plans to establish an action level for the online ART patient-specific QA. METHODS: A cohort of 98 cases treated on CBCT-based ART system were collected for this study. We performed measurement-based QA using ArcCheck and calculation-based QA using Mobius for both the initial plan and the ART plan for analysis. For online the ART plan, Mobius calculation was conducted prior to the delivery, while ArcCheck measurement was delivered on the same day after the treatment. We first investigated the modulation factors (MFs) and MU numbers of the initial plans and ART plans, respectively. The γ passing rates of initial and ART plan QA were analyzed. Then action limits were derived for QA calculation and measurement for both initial and online ART plans, respectively, from 30 randomly selected patient cases, and were evaluated using the other 68 patient cases. RESULTS: The difference in MF between initial plan and ART-plan was 12.9% ± 12.7% which demonstrates their significant difference in plan parameters. Based on the patient QA results, pre-treatment calculation and measurement results are generally well aligned with ArcCheck measurement results for online ART plans, illustrating their feasibility as an indicator of failure in online ART QA measurements. Furthermore, using 30 randomly selected patient cases, the γ analysis action limit derived for initial plans and ART plans are 89.6% and 90.4% in ArcCheck QA (2%/2 mm) and are 92.4% and 93.6% in Mobius QA(3%/2 mm), respectively. According to the calculated action limits, the ArcCheck measurements for all the initial and ART plans passed QA successfully while the Mobius calculation action limits flagged seven and four failure cases respectively for initial plans and ART plans, respectively. CONCLUSION: An ART plan can be substantially different from the initial plan, and therefore a separate session of ART plan QA is needed to ensure treatment safety and quality. The pre-treatment QA calculation via Mobius can serve as a reliable indicator of failure in online ART plan QA. However, given that Ethos ART system is still relatively new, ArcCheck measurement of initial plan is still in practice. It may be skipped as we gain more experience and have better understanding of the system.

Evaluating machine learning enhanced intelligent-optimization-engine (IOE) performance for ethos head-and-neck (HN) plan generation.

PURPOSE: Varian Ethos utilizes novel intelligent-optimization-engine (IOE) designed to automate the planning. However, this introduced a black box approach to plan optimization and challenge for planners to improve plan quality. This study aims to evaluate machine-learning-guided initial reference plan generation approaches for head & neck (H&N) adaptive radiotherapy (ART). METHODS: Twenty previously treated patients treated on C-arm/Ring-mounted were retroactively re-planned in the Ethos planning system using a fixed 18-beam intensity-modulated radiotherapy (IMRT) template. Clinical goals for IOE input were generated using (1) in-house deep-learning 3D-dose predictor (AI-Guided) (2) commercial knowledge-based planning (KBP) model with universal RTOG-based population criteria (KBP-RTOG) and (3) an RTOG-based constraint template only (RTOG) for in-depth analysis of IOE sensitivity. Similar training data was utilized for both models. Plans were optimized until their respective criteria were achieved or DVH-estimation band was satisfied. Plans were normalized such that the highest PTV dose level received 95% coverage. Target coverage, high-impact organs-at-risk (OAR) and plan deliverability was assessed in comparison to clinical (benchmark) plans. Statistical significance was evaluated using a paired two-tailed student t-test. RESULTS: AI-guided plans were superior to both KBP-RTOG and RTOG-only plans with respect to clinical benchmark cases. Overall, OAR doses were comparable or improved with AI-guided plans versus benchmark, while they increased with KBP-RTOG and RTOG plans. However, all plans generally satisfied the RTOG criteria. Heterogeneity Index (HI) was on average <1.07 for all plans. Average modulation factor was 12.2 ± 1.9 (p = n.s), 13.1 ± 1.4 (p = <0.001), 11.5 ± 1.3 (p = n.s.) and 12.2 ± 1.9 for KBP-RTOG, AI-Guided, RTOG and benchmark plans, respectively. CONCLUSION: AI-guided plans were the highest quality. Both KBP-enabled and RTOG-only plans are feasible approaches as clinics adopt ART workflows. Similar to constrained optimization, the IOE is sensitive to clinical input goals and we recommend comparable input to an institution's planning directive dosimetric criteria.

An electrochemiluminescence resonance energy transfer biosensor based on CDs/PAMAM/rGO nanocomposites and Au@Ag2S nanoparticles for PML/RARα fusion gene detection.

In recent years, electrochemiluminescence resonance energy transfer (ECL-RET) with low background signal and high specificity has attracted much attention among researchers. Herein, we established a novel ECL-RET biosensor for PML/RARα fusion gene detection. In this ECL-RET system, carbon dots (CDs) with low toxicity and prominent electrochemical activity were used as donor and Au@Ag2S core-shell nanoparticles (Au@Ag2S NPs) were employed as ECL acceptor. The Au@Ag2S NPs possessed a wide ultraviolet-visible (UV-vis) absorption spectrum between 500 nm and 700 nm, which completely overlapped with the ECL spectrum of CDs. Furthermore, the CDs-decorated poly-amidoamine/reduced graphene oxide (CDs/PAMAM/rGO) nanocomposites were prepared to improve the ECL signals and served as a substrate to stably load capture probe deoxyribonucleic acid (DNA). Based on the ECL-RET biosensing strategy, the Au@Ag2S NPs-labeled assistant probes and target DNA could pair with capture probes to form the sandwich-type DNA structure and the distance between donor and accepter was closed, leading to quenching of the ECL signal of CDs. The ECL-RET biosensor represented eminent analytical performance for PML/RARα fusion gene detection with a wide linear relationship from 5 fM to 500 pM and a low detection limit of 0.72 fM, which provided a novel technical means and theoretical basis for detection and diagnosis of acute promyelocytic leukemia.

Identification of DSPP novel variants and phenotype analysis in dentinogenesis dysplasia Shields type II patients.

OBJECTIVES: To investigate the genetic causes and teeth characteristics of dentin dysplasia Shields type II(DD-II) in three Chinese families. MATERIALS AND METHODS: Data from three Chinese families affected with DD-II were collected. Whole-exome sequencing (WES) and whole-genome sequencing (WGS) were conducted to screen for variations, and Sanger sequencing was used to verify mutation sites. The physical and chemical characteristics of the affected teeth including tooth structure, hardness, mineral content, and ultrastructure were investigated. RESULTS: A novel frameshift deletion mutation c.1871_1874del(p.Ser624fs) in DSPP was found in families A and B, while no pathogenic mutation was found in family C. The affected teeth's pulp cavities were obliterated, and the root canals were smaller than normal teeth and irregularly distributed comprising a network. The patients' teeth also had reduced dentin hardness and highly irregular dentinal tubules. The Mg content of the teeth was significantly lower than that of the controls, but the Na content was obviously higher than that of the controls. CONCLUSIONS: A novel frameshift deletion mutation, c.1871_1874del (p.Ser624fs), in the DPP region of the DSPP gene causes DD-II. The DD-II teeth demonstrated compromised mechanical properties and changed ultrastructure, suggesting an impaired function of DPP. Our findings expand the mutational spectrum of the DSPP gene and strengthen the understanding of clinical phenotypes related to the frameshift deletion in the DPP region of the DSPP gene. CLINICAL RELEVANCE: A DSPP mutation can alter the characteristics of the affected teeth, including tooth structure, hardness, mineral content, and ultrastructure.

The impact of integrating emotion focused components into psychological therapy: A randomized controlled trial.

OBJECTIVES: This paper presents a randomized controlled trial on assimilative integration, which is aimed at integrating elements from other orientations within one approach to enrich its conceptual and practical repertoire. Elements from Emotion-Focused Therapy (EFT) were integrated into a form of cognitive behavior therapy: Psychological Therapy (PT). In one treatment condition, EFT was added to PT (+EFT) with the intent to enhance therapists' working with emotions. In the other condition, concepts and interventions based on the socialpsychological self-regulation approach were added to PT (+SR). Our assumption was that the +EFT would lead to greater and deeper change, particularly in the follow-up assessments. METHOD: Patients (n = 104) with anxiety, depression, or adjustment disorders were randomized to the two conditions and treated by 38 therapists who self-selected between the conditions. Primary outcome was symptom severity at 12-month follow-up; secondary outcomes included several measures such as interpersonal problems and quality of life. Variables were assessed at baseline, after 8 and 16 sessions, at posttreatment, and at 6- and 12-month follow-up. RESULTS: Contrary to our hypothesis, no significant between-group effects were found. CONCLUSION: The findings first suggest the difficulty of topping an already very effective approach to psychotherapy. Alternative interpretations were that the EFT training, while corresponding to regular practice in AI, was not sufficient to make a difference in outcome, or that while profiting from the enhancement of abilities for working with emotions, this was outbalanced by negative effects of difficulties related to the implementation of the new elements.

Determination of 93Mo in Radioactive Samples of Sulfuric Acid Media from Nuclear Facilities.

93Mo is an important radionuclide in view of radioactive waste repository because of its long half-life and high mobility in the environment. 93Mo decays by electron capture without any measurable gamma ray emission. The concentration of 93Mo in most of the radioactive waste is many orders of magnitude lower than the major activation product radionuclides, which makes the accurate determination of 93Mo a big challenge. A new analytical method for the determination of 93Mo in sulfuric acid media from nuclear power reactor was developed. 93Mo was separated from most of the radionuclides by cation exchange chromatography followed by the removal of sulfate by CaSO4 precipitation. A further purification of 93Mo, especially from anion species of 51Cr and 125Sb, was achieved by anion exchange chromatography and a short alumina column separation. The chemical yield of 93Mo in the entire separation procedure reached about 75%, and the decontamination factors for all potential interfering radionuclides were 1.5 × 106-1.6 × 108. The purified 93Mo was measured by liquid scintillation counting through counting its low-energy Auger electrons. A detection limit of 2 mBq/g for 93Mo in 50 g sample was achieved by this method, which enables the quantitative determination of 93Mo in most of the radioactive samples in the decommissioning waste and coolant water of nuclear power reactors. The developed method has been successfully applied to determine 93Mo in coolant water of nuclear power reactors, providing a robust analytical approach of 93Mo for the radiological characterization of radioactive wastes.

Growth of non-English-language literature on biodiversity conservation.

English is widely recognized as the language of science, and English-language publications (ELPs) are rapidly increasing. It is often assumed that the number of non-ELPs is decreasing. This assumption contributes to the underuse of non-ELPs in conservation science, practice, and policy, especially at the international level. However, the number of conservation articles published in different languages is poorly documented. Using local and international search systems, we searched for scientific articles on biodiversity conservation published from 1980 to 2018 in English and 15 non-English languages. We compared the growth rate in publications across languages. In 12 of the 15 non-English languages, published conservation articles significantly increased every year over the past 39 years, at a rate similar to English-language articles. The other three languages showed contrasting results, depending on the search system. Since the 1990s, conservation science articles in most languages increased exponentially. The variation in the number of non-English-language articles identified among the search systems differed markedly (e.g., for simplified Chinese, 11,148 articles returned with local search system and 803 with Scopus). Google Scholar and local literature search systems returned the most articles for 11 and 4 non-English languages, respectively. However, the proportion of peer-reviewed conservation articles published in non-English languages was highest in Scopus, followed by Web of Science and local search systems, and lowest in Google Scholar. About 20% of the sampled non-English-language articles provided no title or abstract in English; thus, in theory, they were undiscoverable with English keywords. Possible reasons for this include language barriers and the need to disseminate research in countries where English is not widely spoken. Given the known biases in statistical methods and study characteristics between English- and non-English-language studies, non-English-language articles will continue to play an important role in improving the understanding of biodiversity and its conservation.

RESUMEN: El inglés es reconocido como el idioma de la ciencia y las publicaciones en inglés (PI) cada vez son más. Con frecuencia se asume que el número de publicaciones en idiomas diferentes al inglés está disminuyendo. Esta suposición contribuye al uso reducido de las publicaciones que no están en inglés en las ciencias, prácticas y políticas de la conservación, especialmente a nivel internacional. Sin embargo, el número de artículos de conservación publicados en diferentes idiomas está muy mal documentado. Usamos sistemas de búsqueda locales e internacionales para buscar artículos científicos sobre la conservación de la biodiversidad publicados entre 1980 y 2018 en inglés y en quince idiomas diferentes al inglés. También comparamos la tasa de incremento de publicaciones en los diferentes idiomas. En doce de los quince idiomas diferentes al inglés, los artículos de conservación publicados incrementaron significativamente cada año durante los últimos 39 años, una tasa similar a los artículos en inglés. Los otros tres idiomas mostraron resultados contrastantes según el sistema de búsqueda. Desde la década de 1990, los artículos sobre ciencias de la conservación incrementaron exponencialmente en la mayoría de los idiomas. La variación en el número de artículos identificados en idiomas diferentes al inglés difirió notablemente de acuerdo con los sistemas de búsqueda (p. ej.: en el caso del chino simplificado, obtuvimos 11,148 artículos con el sistema de búsqueda local y 803 con Scopus). Google Scholar y los sistemas locales de búsqueda arrojaron la mayor cantidad de artículos en 11 y 4 idiomas diferentes al inglés, respectivamente. Sin embargo, la proporción de artículos sobre conservación revisados por pares y publicados en idiomas diferentes al inglés fue mayor en Scopus, seguida por Web of Science y los sistemas locales de búsqueda, con la menor proporción en Google Scholar. Aproximadamente el 20% de la muestra de artículos en idiomas diferentes al inglés no contaban con título o con resumen en inglés; por lo tanto, en teoría, eran imposibles de encontrar mediante palabras clave en inglés. Las posibles explicaciones de esto incluyen las barreras del idioma y la necesidad de difundir la investigación en países en los que el inglés no se habla extensamente. Con los sesgos conocidos de los métodos estadísticos y de las características de estudio entre los trabajos en inglés y en otros idiomas, los artículos en idiomas diferentes al inglés seguirán desempeñando un papel importante en el entendimiento de la biodiversidad y su conservación. Incremento de la Literatura sobre la Conservación de la Biodiversidad en Idiomas Diferentes al Inglés.

COVID-19 case prediction via wastewater surveillance in a low-prevalence urban community: a modeling approach.

Estimating and predicting the epidemic size from wastewater surveillance results remains challenging for the practical implementation of wastewater-based epidemiology (WBE). In this study, by employing a highly sensitive detection method, we documented the time series of SARS-CoV-2 RNA occurrence in the wastewater influent from an urban community with a 360,000 population in Japan, from August 2020 to February 2021. The detection frequency of the viral RNA increased during the outbreak events of COVID-19 and the highest viral RNA concentration was recorded at the beginning of January 2021, amid the most serious outbreak event during the study period. We found that: (1) direct back-calculation still suffers from great uncertainty dominated by inconsistent detection and the varying gap between the observed wastewater viral load and the estimated patient viral load, and (2) the detection frequency correlated well with reported cases and the prediction of the latter can be carried out via data-driven modeling methods. Our results indicate that wastewater virus occurrence can contribute to epidemic surveillance in ways more than back-calculation, which may spawn future wastewater surveillance implementations.

Comparison between 18 F-DCFPyL PET and MRI for the detection of transition zone prostate cancer.

BACKGROUND: We aimed to compare the diagnostic performance of 18 F-DCFPyL positron emission tomography (PET) and multiparameter magnetic resonance imaging (mp-MRI) in detecting transition zone (TZ) prostate cancer (PCa). METHODS: This retrospective study included 20 patients who underwent 18 F-DCFPyL PET/MRI and 32 patients who underwent 18 F-DCFPyL PET/CT and MRI from January 2019 to June 2020. All patients had TZ lesions and underwent prostate biopsies. One senior (reader 1) and one junior (reader 2) nuclear medicine physician evaluated each TZ lesion independently, according to the molecular imaging prostate-specific membrane antigen scoring system and the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). The histologic diagnosis of prostate biopsy was used as the reference standard. The diagnostic performance of the two methods was compared in terms of inter-reader agreement and area under the receiver operating characteristic (AUC-ROC) curve. RESULTS: Of the 52 patients, 43 had TZ PCa. For inter-reader agreement, the kappa value was 0.883 for 18 F-DCFPyL PET and 0.393 for mp-MRI. For PET, both readers had the same diagnostic sensitivity, specificity, and accuracy of 93.0%, 77.8%, and 90.4%, respectively. For mp-MRI, the diagnostic sensitivity, specificity, and accuracy was 67.4%, 33.3%, and 61.5% for reader 1, and 51.2%, 44.4%, and 51.9% for reader 2, respectively. PET outperformed mp-MRI for both readers with an AUC of 0.872 for PET versus 0.584 for mp-MRI, p = .0209 for reader 1, and an AUC of 0.860 for PET versus 0.505 for mp-MRI, p = .0213 for reader 2. Among the 43 patients with TZ PCa, 18 F-DCFPyL PET detected a distant bone metastasis missed by the CT in one case and two small lymph node metastases missed by the CT and MRI in another case. CONCLUSIONS: These results suggest that 18 F-DCFPyL PET, which was almost independent of the experience of the readers, was more objective in the evaluation of TZ lesions, and had higher diagnostic value than mp-MRI.

On the Quality Control for the Determination of Ultratrace-Level 236U and 233U in Environmental Samples by Accelerator Mass Spectrometry.

Our recent attempt to determine ultratrace-level 236U and 233U in small-volume seawater samples was challenged by high and unstable procedure blanks in our environmental radioactivity laboratory, which used to be a spent fuel research facility. Through intercomparison experiments with different laboratories and background checks on the chemical reagents and laboratory dust, the resuspended U-bearing dust was identified as the dominating source of the 236U and 233U contamination. With the implementation of background control (especially dust control) measures, the procedure blanks and detection limits of 236U and 233U for the radiochemical separation procedure have been significantly improved by three orders of magnitudes. With well-controlled blanks, the analytical precision for 236U and 233U predominantly relies on the AMS counting statistics. Background check and dust control are strongly recommended before the analyses of environmental-level long-lived radionuclides (such as 236U and 233U) that are conducted in the former or active nuclear facilities, even if clearance of radioactivity relevant for radioprotection was achieved.

Conditional Lpar1 gene targeting identifies cell types mediating neuropathic pain.

LPA1 is one of six known receptors (LPA1-6) for lysophosphatidic acid (LPA). Constitutive Lpar1 null mutant mice have been instrumental in identifying roles for LPA-LPA1 signaling in neurobiological processes, brain development, and behavior, as well as modeling human neurological diseases like neuropathic pain. Constitutive Lpar1 null mutant mice are protected from partial sciatic nerve ligation (PSNL)-induced neuropathic pain, however, the cell types that are functionally responsible for mediating this protective effect are unknown. Here, we report the generation of an Lpar1flox/flox conditional null mutant mouse that allows for cre-mediated conditional deletion, combined with a PSNL pain model. Lpar1flox/flox mice were crossed with cre transgenic lines driven by neural gene promoters for nestin (all neural cells), synapsin (neurons), or P0 (Schwann cells). CD11b-cre transgenic mice were also used to delete Lpar1 in microglia. PSNL-initiated pain responses were reduced following cre-mediated Lpar1 deletion with all three neural promoters as well as the CD11b promoter, supporting involvement of Schwann cells, central and/or peripheral neurons, and microglia in mediating pain. Interestingly, rescue responses were nonidentical, implicating distinct roles for Lpar1-expressing cell types. Our results with a new Lpar1 conditional mouse mutant expand an understanding of LPA1 signaling in the PSNL model of neuropathic pain.

Prior adherence to statins is a predictor of subsequent adherence and persistence to oral, but not parenteral, osteoporosis medications.

INTRODUCTION: Although bisphosphonates are effective for treating osteoporosis, patient adherence is variable. We conducted this study to determine if prior adherence with another medication used to treat chronic asymptomatic conditions predicts adherence with bisphosphonates. MATERIALS AND METHODS: Retrospective cohort study using linked population-level data for the entire Canadian province of Alberta between April 1, 2009 and March 31, 2017. We examined all new users of an oral or parenteral osteoporosis treatment over the age of 20 who had filled at least one statin prescription in the prior 12 months before the start date of the osteoporosis treatment. Adherence was defined based on medication possession ratio (MPR) and > = 80% was deemed good adherence. Persistence was defined as continuous treatment without an interruption of treatment for more than 56 days. RESULTS: Of 20,612 new users of oral bisphosphonates and 1538 new users of parenteral treatments, prior good adherence with statins was independently associated with both short term [adjusted Odds Ratio (aOR) 1.34 (95% CI 1.26-1.42) at 1 year] and long term [aOR 1.35 (1.20-1.51) at 5 years] adherence with oral bisphosphonates. However, there was no association between prior statin adherence and adherence [OR 0.94 (0.74, 1.20)] or persistence [(OR 0.96 (0.76, 1.22)] with parenteral osteoporosis therapies. Other factors associated with oral bisphosphonate adherence at 1 year included older age, history of bone mineral density scan, and history of pap smear. CONCLUSIONS: Prior adherence to statins is a predictor of subsequent short-term and long-term adherence and persistence with oral bisphosphonates but not parenteral osteoporosis therapies.