bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-small low-threshold mid-infrared plasmonic nanowire lasers based on n-doped GaN
Authors: Zheng Jiahui , Yan Xin , Zhang Xia , Ren Xiaomin
Published: February 2023

An ultra-small mid-infrared plasmonic nanowire laser based on n-doped GaN metallic material is proposed and studied by the finite-difference time-domain method. In comparison with the noble metals, nGaN is found to possess superior permittivity characteristics in the mid-infrared range, beneficial for generating low-loss surface plasmon polaritons and achieving strong subwavelength optical confinement. The results show that at a wavelength of 4.2 µm, the penetration depth into the dielectric is substantially decreased from 1384 to 163 nm by replacing Au with nGaN, and the cutoff diameter of nGaN-based laser is as small as 265 nm, only 65% that of the Au-based one. To suppress the relatively large propagation loss induced by nGaN, an nGaN/Au-based laser structure is designed, whose threshold gain has been reduced by nearly half. This work may pave the way for the development of miniaturized low-consumption mid-infrared lasers.
Agreement test of P value versus Bayes factor for sample means comparison: analysis of articles from the Angle Orthodontist journal
Authors: Srimaneekarn Natchalee , Leelachaikul Pattamon , Thiradilok Sasipa , Manopatanakul Somchai
Published: February 2023

Background

Researchers are cautioned against misinterpreting the conventional P value, especially while implementing the popular t test. Therefore, this study evaluated the agreement between the P value and Bayes factor (BF01) results obtained from a comparison of sample means in published orthodontic articles.

Methods

Data pooling was undertaken using the modified PRISMA flow diagram. Per the inclusion criteria applied to The Angle Orthodontist journal for a two-year period (November 2016 to September 2018), all articles that utilised the t test for statistical analysis were selected. The agreement was evaluated between the P value and Bayes factor set at 0.05 and 1, respectively. The percentage of agreement and Kappa coefficient were calculated. Plotting of effect size against P value and BF01 was analysed.

Results

From 265 articles, 82 utilised the t test. Of these, only 37 articles met the inclusion criteria. The study identified 793 justifiable t tests (438 independent-sample and 355 dependent-sample t tests) for which the agreement percentage and Kappa coefficient were found to be 93.57% and 0.87, respectively. However, when anecdotal evidence (1/3 < BF01 < 3) was considered, almost half of the studies missed statistical significance. Furthermore, two-thirds of the significantly reported P values (0.01 < P < 0.05; 30 independent-sample and 20 dependent-sample t tests) showed only anecdotal evidence (1/3 < BF01 < 1). Moreover, BF01 indicated moderate evidence (BF01 > 3) for approximately one-third of the total studies, with nonsignificant P values (P > 0.05). Furthermore, accompanying the P values, the effect sizes, especially for studies with independent-sample t tests, were very high with a strong potential to show substantive significance. Although it is best to extend the statistical calculation of a doubted P value (just below 0.05), especially for orthodontic innovation, orthodontists may reach a balanced decision relying on cephalometric measurements.

Conclusions

The Kappa coefficient indicated perfect agreement between the two methods. BF01 restricted this judgement to approximately half of them, with two-thirds of these studies showing nonsignificant P values. Simple extensions of statistical calculations, especially effect size and BF01, can be useful and should be considered when finalising statistical analyses, especially for orthodontic studies without cephalometric analysis.
Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition
Authors: Yammine S. G. , Huybrechts I. , Biessy C. , Dossus L. , Panico S. , Sánchez M. J. , Benetou V. , Turzanski-Fortner R. , Katzke V. , Idahl A. , Skeie G. , Olsen K. Standahl , Tjønneland A. , Halkjaer J. , Colorado-Yohar S. , Heath A. K. , Sonestedt E. , Sartor H. , Schulze M. B. , Palli D. , Crous-Bou M. , Dorronsoro A. , Overvad K. , Gurrea A. Barricarte , Severi G. , Vermeulen R. C.H. , Sandanger T. M. , Travis R. C. , Key T. , Amiano P. , Van Guelpen B. , Johansson M. , Sund M. , Tumino R. , Wareham N. , Sacerdote C. , Krogh V. , Brennan P. , Riboli E. , Weiderpass E. , Gunter M. J. , Chajès V.
Published: February 2023

Background

Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods

This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons.

Results

Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5−Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk.

Conclusion

Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
The influence of meteorological factors and total malignant tumor health risk in Wuhu city in the context of climate change
Authors: Pan Zhipeng , Yu Lingxiang , Shao Ming , Ma Yubo , Cheng Yuting , Wu Ye , Xu Shanshan , Zhang Congjun , Zhu Jiansheng , Pan Faming , Sun Guoping
Published: February 2023

With the increasing severity of the malignant tumors situation worldwide, the impacts of climate on them are receiving increasing attention. In this study, for the first time, all-malignant tumors were used as the dependent variable and absolute humidity (AH) was innovatively introduced into the independent variable to investigate the relationship between all-malignant tumors and meteorological factors. A total of 42,188 cases of malignant tumor deaths and meteorological factors in Wuhu City were collected over a 7-year (2014–2020) period. The analysis method combines distributed lagged nonlinear modeling (DLNM) as well as generalized additive modeling (GAM), with prior pre-analysis using structural equation modeling (SEM). The results showed that AH, temperature mean (T mean) and diurnal temperature range (DTR) all increased the malignant tumors mortality risk. Exposure to low and exceedingly low AH increases the malignant tumors mortality risk with maximum RR values of 1.008 (95% CI: 1.001, 1.015, lag 3) and 1.016 (95% CI: 1.001, 1.032, lag 1), respectively. In addition, low and exceedingly low T mean exposures also increased the risk of malignant tumors mortality, the maximum RR was 1.020 (95% CI: 1.006, 1.034) for low T mean and 1.035 (95% CI: 1.014, 1.058) for exceedingly low T mean. As for DTR, all four levels (exceedingly low, low, high, exceedingly high, from low to high) of exposure increased the risk of death from malignant tumors, from exceedingly low to exceedingly high maximum RR values of 1.018 (95% CI: 1.004, 1.032), 1.011 (95% CI: 1.005, 1.017), 1.006 (95% CI: 1.001, 1.012) and 1.019 (95% CI: 1.007, 1.031), respectively. The results of the stratified analysis suggested that female appear to be more sensitive to humidity, while male require additional attention to reduce exposure to high level of DTR.
Participation in screening for breast and cervical cancer among women with current or previous drug use: a survey study
Authors: Garpenhag Lars , Dahlman Disa
Published: February 2023

Background

Women with current or previous drug use (WCPDU) have an increased risk of poor breast and cervical cancer outcomes. Screening is known to decrease the mortality of these common cancer forms, but screening participation has been sparsely investigated among women with drug dependency. The aim of this study was to assess participation in screening for breast and cervical cancer among WCPDU.

Methods

We recruited WCPDU to a survey study, from six opioid substitution treatment (OST) clinics and one needle exchange program (NEP) in Malmö, Sweden, and through the Drug Users Union in Stockholm, Sweden. The survey was constructed according to results from focus group discussions about cancer screening in a sample of women in OST. Survey data were analyzed using descriptive statistics. We analyzed associations between non-compliance to screening and healthcare contact (OST, NEP or none) by logistic regression analysis; unadjusted and adjusted for age, native language, housing situation, educational attainment and main source of income.

Results

A total of 298 women (median age 43 years) responded to the survey. The self-reported compliance with cancer screening recommendations was 29% for breast cancer screening and 41% for cervical cancer screening. Non-compliance with cervical cancer screening was associated with NEP participation in univariate but not multivariate analysis. We did not find an association between non-compliance with breast cancer screening and healthcare contact. Non-compliance with screening for cervical cancer was also associated with unstable housing in univariate and multivariate analyses, and inversely associated with increasing age in a univariate analysis. Non-compliance with breast cancer was associated with unstable housing in a univariate analysis, and inversely associated with not having Swedish as a native language in a multivariate analysis.

Conclusion

The self-reported compliance with the national cancer screening programs for breast cancer and cervical cancer of WCPDU is notably lower than in the Swedish general population. Women with unstable housing seem to be particularly vulnerable to non-compliance with cancer screening. Interventions to minimize barriers to cancer screening are crucial to decrease the increased cancer morbidity and mortality among WCPDU.
Impact of the COVID-19 pandemic on treatment for mental health needs: a perspective on service use patterns and expenditures from commercial medical claims data
Authors: Li Ta-Hsin , Kamin Leah , George Judy , Saiz Fernando Suarez , Meyer Pablo
Published: February 2023

Objective

To examine changes in use patterns, cost of healthcare services before and after the outbreak of the COVID-19 pandemic, and their impacts on expenditures for patients receiving treatment for depression, anxiety, eating disorders, and substance use.

Methods

This cross-sectional study employed statistical tests to analyze claims in MarketScan® Commercial Database in March 2020-February 2021 and quarterly from March 2020 to August 2021, compared to respective pre-pandemic periods. The analysis is based on medical episodes created by the Merative™ Medical Episode Grouper (MEG). MEG is a methodology that groups medical and prescription drug claims to create clinically relevant episodes of care.

Results

Comparing year-over-year changes, proportion of patients receiving anxiety treatment among all individuals obtaining healthcare services grew 13.7% in the first year of the pandemic (3/2020–2/2021) versus 10.0% in the year before the pandemic (3/2019–2/2020). This, along with a higher growth in price per episode (5.5% versus 4.3%) resulted in a greater increase in per claimant expenditure ($0.61 versus $0.41 per month). In the same periods, proportion of patients receiving treatment for depression grew 3.7% versus 6.9%, but per claimant expenditure grew by same amount due to an increase in price per episode (4.8%). Proportion of patients receiving treatment for anorexia started to increase 21.1% or more in the fall of 2020. Patient proportion of alcohol use in age group 18–34 decreased 17.9% during the pandemic but price per episode increased 26.3%. Patient proportion of opioid use increased 11.5% in March–May 2020 but decreased or had no significant changes in subsequent periods.

Conclusions

We investigated the changes in use patterns and expenditures of mental health patients before and after the outbreak of the COVID-19 pandemic using claims data in MarketScan®. We found that the changes and their financial impacts vary across mental health conditions, age groups, and periods of the pandemic. Some changes are unexpected from previously reported prevalence increases among the general population and could underlie unmet treatment needs. Therefore, mental health providers should anticipate the use pattern changes in services with similar COVID-19 pandemic disruptions and payers should anticipate cost increases due, in part, to increased price and/or service use.
Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy
Authors: Liu Zaoqu , Shi Meixin , Ren Yuqing , Xu Hui , Weng Siyuan , Ning Wenjing , Ge Xiaoyong , Liu Long , Guo Chunguang , Duo Mengjie , Li Lifeng , Li Jing , Han Xinwei
Published: February 2023

The incidence and mortality of cancer are the major health issue worldwide. Apart from the treatments developed to date, the unsatisfactory therapeutic effects of cancers have not been addressed by broadening the toolbox. The advent of immunotherapy has ushered in a new era in the treatments of solid tumors, but remains limited and requires breaking adverse effects. Meanwhile, the development of advanced technologies can be further boosted by gene analysis and manipulation at the molecular level. The advent of cutting-edge genome editing technology, especially clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), has demonstrated its potential to break the limits of immunotherapy in cancers. In this review, the mechanism of CRISPR-Cas9-mediated genome editing and a powerful CRISPR toolbox are introduced. Furthermore, we focus on reviewing the impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy (knockout or knockin). Finally, we discuss the CRISPR-Cas9-based genome-wide screening for target identification, emphasis the potential of spatial CRISPR genomics, and present the comprehensive application and challenges in basic research, translational medicine and clinics of CRISPR-Cas9.
Polycyclic aromatic hydrocarbons in urban particle matter exacerbate movement disorder after ischemic stroke via potentiation of neuroinflammation
Authors: Tanaka Miki , Okuda Tomoaki , Itoh Kouichi , Ishihara Nami , Oguro Ami , Fujii-Kuriyama Yoshiaki , Nabetani Yu , Yamamoto Megumi , Vogel Christoph F. A. , Ishihara Yasuhiro
Published: February 2023

Background

A recent epidemiological study showed that air pollution is closely involved in the prognosis of ischemic stroke. We and others have reported that microglial activation in ischemic stroke plays an important role in neuronal damage. In this study, we investigated the effects of urban aerosol exposure on neuroinflammation and the prognosis of ischemic stroke using a mouse photothrombotic model.

Results

When mice were intranasally exposed to CRM28, urban aerosols collected in Beijing, China, for 7 days, microglial activation was observed in the olfactory bulb and cerebral cortex. Mice exposed to CRM28 showed increased microglial activity and exacerbation of movement disorder after ischemic stroke induction. Administration of core particles stripped of attached chemicals from CRM28 by washing showed less microglial activation and suppression of movement disorder compared with CRM28-treated groups. CRM28 exposure did not affect the prognosis of ischemic stroke in null mice for aryl hydrocarbon receptor, a polycyclic aromatic hydrocarbon (PAH) receptor. Exposure to PM2.5 collected at Yokohama, Japan also exacerbated movement disorder after ischemic stroke.

Conclusion

Particle matter in the air is involved in neuroinflammation and aggravation of the prognosis of ischemic stroke; furthermore, PAHs in the particle matter could be responsible for the prognosis exacerbation.
Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer’s disease in APP/PS1 mouse
Authors: Wang Shang , Zhu Taiyang , Ni Wanyan , Zhou Chao , Zhou Hui , Lin Li , Hu Yuting , Sun Xiaoyu , Han Jingjing , Zhou Yan , Jin Guoliang , Zu Jie , Shi Hongjuan , Yang Xingxing , Zhang Zuohui , Hua Fang
Published: February 2023

Background

Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer’s disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD.

Methods

In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid β-protein (Aβ), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction.

Results

The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aβ deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus.

Conclusions

The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aβ clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.
The impact of digital financial inclusion on household carbon emissions: evidence from China
Authors: Zhou Yu , Zhang Caijiang , Li Zhangwen
Published: February 2023

The role of digital financial inclusion in economic development has been widely appreciated, and its carbon emission mitigating effect on the household sector needs to be noticed. This study investigates the impact of digital financial inclusion on household carbon emissions based on panel data for 30 Chinese provinces from 2011 to 2020. The results show that digital financial inclusion has a significant and robust mitigation effect on household carbon emissions and that digital financial inclusion impacts mainly from the breadth of coverage and the degree of digitization. The heterogeneity test results show that this mitigation effect is mainly found in the central and western inland regions as well as in the northern regions with high winter heating demand. In addition, this mitigation effect is mainly found in urban rather than rural areas. The results of the mechanism analysis show that digital financial inclusion reduces household carbon emissions through two pathways, electricity consumption and natural gas consumption share, and no significant mediating effect is observed for residential consumption share. The results of this study shed light on the relationship between digital financial inclusion and carbon emissions in the household sector and provide a reference for decision-making to address household carbon emission mitigation in China.
Proteome network analysis of skeletal muscle in lignan-enriched nutmeg extract-fed aged mice
Authors: Lee Je-Ho , Kang Hyuno , Ban Gyung-Tae , Kim Beom Kyu , Lee JaeHyeon , Hwang Heeyoun , Yoo Hwa-Seung , Cho Kun , Choi Jong-Soon
Published: February 2023

Sarcopenia, characterized by reduced muscle mass and fiber number leading to muscular atrophy, has been associated with serious socioeconomic challenges among the elderly in developed countries. Therefore, preventing sarcopenia could be a promising strategy for achieving a healthy aging society. Nutmeg (Myristica fragrans) has been used as a spice to increase flavor and prevent putrefaction of food. Nutmeg contains various bioactive components that improve muscle activity. To determine the potential effect of lignan-enriched nutmeg extract (LNX) on sarcopenia, LNX (100 mg/kg body weight)-fed aged mice were subjected to forced exercise. Herein, aged (22-month-old) mice fed LNX for three weeks exhibited a shortened and thickened soleus muscle. The ratio of the soleus muscle mass (%) to body weight was significantly increased in LNX-fed aged mice. The relative increase in muscle mass in LNX-fed aged mice improved exercise activities, including rotarod, swimming, and grip strength test results. Proteome profiles of the soleus muscle of LNX-fed mice were used to analyze protein–protein interaction network. Several myosin heavy chain isoforms were found to interact with actin, ACTA1, which functions as a hub protein. Furthermore, the expression of myogenic proteins, such as MYH1, MYH4, and ACTA1, was dose-dependently increased in vivo. In result, our functional proteomic analysis revealed that feeding LNX restored muscle proteins in aged mice.
Paleomagnetic constraint of the age and duration of the Taupō Eruption, New Zealand
Authors: Hasegawa Takeshi , Greve Annika , Gravley Darren M. , Kusu Chie , Kaneda Yasuaki , Shibata Shohei , Okada Makoto , Kósik Szabolcs , Mochizuki Nobutatsu , Turner Gillian
Published: February 2023

We have carried out paleomagnetic analyses of tephras from the Taupō eruption, one of the most violent eruptions on Earth in the past 5000 years. Pyroclastic deposits were collected with 7 cm3 cubes pushed into each unit of the Taupō eruption sequence, consisting of airfall units and overlying ignimbrite. Where possible, we targeted fine-ash layers and matrix, as lapilli sized material can significantly affect the quality of the analysis. The samples were oriented using a collection device specially designed to maximize accuracy. All samples were subjected to alternating field demagnetization, while samples from Taupō ignimbrite (Y7)—the only unit deposited hot were also subjected to thermal demagnetization. The characteristic remanent magnetizations (ChRMs) for specimens from unit Y1, the lower and upper parts of unit Y4, and unit Y7 are well determined (α95 < 3.3°). The declinations and inclinations of site-mean ChRMs range from 3.0° to 7.1° and − 53.4° to − 56.2°, respectively, in close agreement with published results from lithic fragments of the Taupō ignimbrite (Y7). The mean ChRM of unit Y3 does not fit within 95% confidence limits of the ChRM of other units. We presume this is a consequence of unit Y3 samples containing relatively coarse grains and of probable secondary process of the deposit. This outlier aside, our results show consistency between thermoremanent magnetizations of ignimbrite and detrital remanences of co-eval ashfalls, thus validating our method for further tephra research. Both geological observations and paleomagnetic estimation using angular difference suggest that the duration of the Taupō eruption sequence was less than a few tens of years. Furthermore, matching the overall mean ChRM direction (Dec = 4.3°, Inc = − 55.3°, α95 = 1.3°, N = 38 specimens) to the New Zealand paleosecular variation record using the MATLAB dating tool, most likely supports a younger age (ca. 310 CE) than the reported wiggle match eruption age of 232 ± 10 CE.

Graphical Abstract
Autoimmune encephalitis: an observational study from South India
Authors: Ramesh Rithvik , Hazeena Philo , Shanmugam Sundar , Venkatasubramanian Shankar , Perumal Santhosh , Shankar Vijaya , Radhakrishna Pedapati
Published: February 2023

Background

Ever since AE was acknowledged as a potentially treatable cause of encephalitis, it has been increasingly recognised worldwide. Data suggests that these disorders are under-recognized, which calls for an increased awareness of the varying clinical, laboratory, electrophysiological and radiological presentations of the different types of autoimmune encephalitis. This cross-sectional observational study included all patients diagnosed with AE, who presented to a tertiary care centre from June 2016 to January 2021. Data were collected including patient’s demography, clinical, laboratory, radiological and electrophysiology studies, management and outcomes.

Results

31 study participants were included, of which 13 patients were anti-NMDA antibody positive, 12 patients were anti-LGI1 antibody positive, 2 patients were anti-CASPR2 antibody positive, 2 were positive for dual positive status (anti-LGi1 and anti-CASPR2), and one each for anti-GABA-B and anti-GAD 65. There was a marginal male predilection with overall seizures being the most common symptom (68%) followed by behavioural disturbance (64.5%), and impairment of consciousness (32.3%). Patients with Anti-NMDA encephalitis were likely to be young females, with CSF pleocytosis, a more protracted hospital course with more chances of relapse and residual disease, while the patients with anti-Lgi1 encephalitis were likely to be older males with a shorter, less severe hospital course.

Conclusion

The present study detailed the demographic, clinical, imaging, laboratory and EEG characteristics of 31 AE patients from a tertiary centre. The findings concurred with the literature and demonstrate the diverse spectrum of clinical manifestations of patients with AE, present with.
Safety of sheathless vascular access using braided 4 F selective catheters for common body interventions – a retrospective study
Authors: Nadjiri Jonathan , Geith Tobias , Mühlmann Marc , Waggershauser Tobias , Paprottka Philipp M.
Published: February 2023

Background

Besides other factors, complication rate of transarterial interventions depends on the size of the vascular access. Therefore, the vascular access is mostly chosen as small as possible while still allowing all planned parts of the intervention.

This retrospective analysis is to evaluate the safety and feasibility of sheathless arterial interventions for a broad spectrum of interventions in daily practice.

Methods

All sheathless interventions using a 4 F main catheter between May 2018 and September 2021 were included in the evaluation. Additionally, intervention parameters such as type of catheter, use of microcatheter and required change of main catheters were assessed. Information about the use about sheathless approach and catheters were obtained from the material registration system. All catheters were braided.

Results

503 sheathless interventions with 4 F catheters from the groin were documented. The spectrum comprised bleeding embolization, diagnostic angiographies, arterial DOTA-TATE-therapy, uterine fibroid embolization, transarterial chemotherapy, transarterial radioembolization and others. In 31 cases (6 %) a change of the main catheter was required. In 381 cases (76 %) a microcatheter was utilized. No clinically relevant adverse events were observed (grade 2 or higher [CIRSE AE-classification]). None of the cases later required conversion to a sheath-based intervention.

Conclusions

Sheathless interventions with a 4 F braided catheter from the groin are safe and feasible. It allows for a broad spectrum of interventions in daily practice.
Tailoring dissemination strategies to increase evidence-informed policymaking for opioid use disorder treatment: study protocol
Authors: Crable Erika L. , Grogan Colleen M. , Purtle Jonathan , Roesch Scott C. , Aarons Gregory A.
Published: February 2023

Background

Policy is a powerful tool for systematically altering healthcare access and quality, but the research to policy gap impedes translating evidence-based practices into public policy and limits widespread improvements in service and population health outcomes. The US opioid epidemic disproportionately impacts Medicaid members who rely on publicly funded benefits to access evidence-based treatment including medications for opioid use disorder (MOUD). A myriad of misaligned policies and evidence-use behaviors by policymakers across federal agencies, state Medicaid agencies, and managed care organizations limit coverage of and access to MOUD for Medicaid members. Dissemination strategies that improve policymakers’ use of current evidence are critical to improving MOUD benefits and reducing health disparities. However, no research describes key determinants of Medicaid policymakers’ evidence use behaviors or preferences, and few studies have examined data-driven approaches to developing dissemination strategies to enhance evidence-informed policymaking. This study aims to identify determinants and intermediaries that influence policymakers’ evidence use behaviors, then develop and test data-driven tailored dissemination strategies that promote MOUD coverage in benefit arrays.

Methods

Guided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework, we will conduct a national survey of state Medicaid agency and managed care organization policymakers to identify determinants and intermediaries that influence how they seek, receive, and use research in their decision-making processes. We will use latent class methods to empirically identify subgroups of agencies with distinct evidence use behaviors. A 10-step dissemination strategy development and specification process will be used to tailor strategies to significant predictors identified for each latent class. Tailored dissemination strategies will be deployed to each class of policymakers and assessed for their acceptability, appropriateness, and feasibility for delivering evidence about MOUD benefit design.

Discussion

This study will illuminate key determinants and intermediaries that influence policymakers’ evidence use behaviors when designing benefits for MOUD. This study will produce a critically needed set of data-driven, tailored policy dissemination strategies. Study results will inform a subsequent multi-site trial measuring the effectiveness of tailored dissemination strategies on MOUD benefit design and implementation. Lessons from dissemination strategy development will inform future research about policymakers’ evidence use preferences and offer a replicable process for tailoring dissemination strategies.
Turning parameters optimization for TC21 Ti-alloy using Taguchi technique
Authors: Sobh Arafa Soliman , Sayed Esraa M. , Barakat Azza F. , Elshaer Ramadan N.
Published: February 2023

Background

The development of materials fabrication is an important trend in materials engineering. TC21 Ti-alloy is one of these materials’ trends. Investigations of different characteristics of TC21 Ti-alloy such as weldability, formability, and machinability will consume a large number of specimens. This work aims to study the machinability characteristics of TC21 Ti-alloy. The minimum number of experimental trials and optimal cutting conditions will be obtained by applying the orthogonal array (OA) L9 Taguchi technique. To achieve this aim, experimental work will be conducted under three varying cutting parameters, each one of them with three levels: cutting speeds (V) of 80, 100, and 120 m/min, feed rates (f) of 0.05, 0.10, and 0.15 mm/rev, and cutting depth (a) of 0.2, 0.4, and 0.6 mm.

Results

The results revealed that the cutting depth and cutting speed with percentages contribution of 40.8% and 48.6%, respectively, are the most significant parameters of surface roughness and wear of the tool insert. However, the least significant parameters are cutting speed and feed rate with percentages contribution of 20.2% and 2.3%, respectively.

Conclusions

Minimum surface roughness at V = 80 m/min, f = 0.10 mm/rev, and a = 0.4 mm is 0.16 µm, and maximum surface roughness at V = 80 m/min, f = 0.15 mm/rev, and a = 0.6 mm is 0.72 µm. Minimum tool wear at V = 100 m/min, f = 0.15 mm/rev, and a = 0.2 is 187.770 µm, and the maximum tool wear at V = 80 m/min, f = 0.10 mm/rev, and a = 0.4 mm is 274.896 µm.
Prevalence of post-traumatic stress disorder and validity of the Impact of Events Scale – Revised in primary care in Zimbabwe, a non-war-affected African country
Authors: Abas Melanie A. , Müller Monika , Gibson Lorna J. , Derveeuw Sarah , Dissanayake Nirosha , Smith Patrick , Verhey Ruth , Danese Andrea , Chibanda Dixon
Published: February 2023

Background

A critical step in research on the epidemiology of post-traumatic stress disorder (PTSD) in low-resource settings is the validation of brief self-reported psychometric tools available in the public domain, such as the Impact Event Scale – Revised (IES-R).

Aims

We aimed to investigate the validity of the IES-R in a primary healthcare setting in Harare, Zimbabwe.

Method

We analysed data from a survey of 264 consecutively sampled adults (mean age 38 years; 78% female). We estimated the area under the receiver operating characteristic curve and sensitivity, specificity and likelihood ratios for different cut-off points of the IES-R, against a diagnosis of PTSD made using the Structured Clinical Interview for DSM-IV. We performed factor analysis to evaluate construct validity of the IES-R.

Results

The prevalence of PTSD was 23.9% (95% CI 18.9–29.5). The area under the curve for the IES-R was 0.90. At a cut-off of ≥47, the sensitivity of the IES-R to detect PTSD was 84.1 (95% CI 72.7–92.1) and specificity was 81.1 (95% CI 75.0–86.3). Positive and negative likelihood ratios were 4.45 and 0.20, respectively. Factor analysis revealed a two-factor solution, with both factors showing good internal consistency (Cronbach's factor-1α= 0.95, factor-2α= 0.76). In apost hocanalysis, we found the brief six-item IES-6 also performed well, with an area under the curve of 0.87 and optimal cut-off of 15.

Conclusions

The IES-R and IES-6 had good psychometric properties and performed well for indicating possible PTSD, but at higher cut-off points than those recommended in the Global North.
Darolutamide Plus Androgen-Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase III ARASENS Trial
Authors: Hussain Maha , Tombal Bertrand , Saad Fred , Fizazi Karim , Sternberg Cora N. , Crawford E. David , Shore Neal , Kopyltsov Evgeny , Kalebasty Arash Rezazadeh , Bögemann Martin , Ye Dingwei , Cruz Felipe , Suzuki Hiroyoshi , Kapur Shivani , Srinivasan Shankar , Verholen Frank , Kuss Iris , Joensuu Heikki , Smith Matthew R.
Published: February 2023

PURPOSE

For patients with metastatic hormone-sensitive prostate cancer, metastatic burden affects outcome. We examined efficacy and safety from the ARASENS trial for subgroups by disease volume and risk.

METHODS

Patients with metastatic hormone-sensitive prostate cancer were randomly assigned to darolutamide or placebo plus androgen-deprivation therapy and docetaxel. High-volume disease was defined as visceral metastases and/or ≥ 4 bone metastases with ≥ 1 beyond the vertebral column/pelvis. High-risk disease was defined as ≥ 2 risk factors: Gleason score ≥ 8, ≥ 3 bone lesions, and presence of measurable visceral metastases.

RESULTS

Of 1,305 patients, 1,005 (77%) had high-volume disease and 912 (70%) had high-risk disease. Darolutamide increased overall survival (OS) versus placebo in patients with high-volume (hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.82), high-risk (HR, 0.71; 95% CI, 0.58 to 0.86), and low-risk disease (HR, 0.62; 95% CI, 0.42 to 0.90), and in the smaller low-volume subgroup, the results were also suggestive of survival benefit (HR, 0.68; 95% CI, 0.41 to 1.13). Darolutamide improved clinically relevant secondary end points of time to castration-resistant prostate cancer and subsequent systemic antineoplastic therapy versus placebo in all disease volume and risk subgroups. Adverse events (AEs) were similar between treatment groups across subgroups. Grade 3 or 4 AEs occurred in 64.9% of darolutamide patients versus 64.2% of placebo patients in the high-volume subgroup and 70.1% versus 61.1% in the low-volume subgroup. Among the most common AEs, many were known toxicities related to docetaxel.

CONCLUSION

In patients with high-volume and high-risk/low-risk metastatic hormone-sensitive prostate cancer, treatment intensification with darolutamide, androgen-deprivation therapy, and docetaxel increased OS with a similar AE profile in the subgroups, consistent with the overall population. [Media: see text]
Longitudinal Profiling of Endogenous Steroids in Blood Using the Athlete Biological Passport Approach
Authors: Equey Tristan , Salamin Olivier , Ponzetto Federico , Nicoli Raul , Kuuranne Tiia , Saugy Jonas , Saugy Martial , Aikin Reid , Baume Norbert
Published: February 2023

Context

Detection of endogenous anabolic androgenic steroids (EAAS), like testosterone (T), as doping agents has been improved with the launch of the Steroidal Module of the Athlete Biological Passport (ABP) in urine samples.

Objective

To target doping practices with EAAS, particularly in individuals with low level of biomarkers excreted in urine, by including new target compounds measured in blood.

Design

T and T/androstenedione (T/A4) distributions were obtained from 4 years of anti-doping data and applied as priors to analyze individual profiles from 2 T administration studies in female and male subjects.

Setting

Anti-doping laboratory. Elite athletes (n = 823) and male and female clinical trials subjects (n = 19 and 14, respectively).

Intervention(s)

Two open-label administration studies were carried out. One involved a control phase period followed by patch and then oral T administration in male volunteers and the other followed female volunteers during 3 menstrual cycles with 28 days of daily transdermal T application during the second month.

Main outcome measure(s)

Serum samples were analyzed for T and A4 and the performance of a longitudinal ABP-based approach was evaluated for T and T/A4.

Results

An ABP-based approach set at a 99% specificity flagged all female subjects during the transdermal T application period and 44% of subjects 3 days after the treatment. T showed the best sensitivity (74%) in response to transdermal T application in males.

Conclusions

Inclusion of T and T/A4 as markers in the Steroidal Module can improve the performance of the ABP to identify T transdermal application, particularly in females.
Imaging of Brain Tumors
Authors: Jordan Justin T. , Gerstner Elizabeth R.
Published: February 2023

OBJECTIVE

This article focuses on neuroimaging as an essential tool for diagnosing brain tumors and monitoring response to treatment.

LATEST DEVELOPMENTS

Neuroimaging is useful at all stages of brain tumor care. Technologic advances have improved the clinical diagnostic capability of neuroimaging as a vital complement to history, examination, and pathologic assessment. Presurgical evaluations are enriched by novel imaging techniques, through improved differential diagnosis and better surgical planning using functional MRI (fMRI) and diffusion tensor imaging. The common clinical challenge of differentiating tumor progression from treatment-related inflammatory change is aided by novel uses of perfusion imaging, susceptibility-weighted imaging (SWI), spectroscopy, and new positron emission tomography (PET) tracers.

ESSENTIAL POINTS

Using the most up-to-date imaging techniques will facilitate high-quality clinical practice in the care of patients with brain tumors.
The Right Imaging Protocol for the Right Patient
Authors: Pinter Nandor K.
Published: February 2023

OBJECTIVE

This article provides a high-level overview of the challenge of choosing the right imaging approach for an individual patient. It also presents a generalizable approach that can be applied to practice regardless of specific imaging technologies.

ESSENTIAL POINTS

This article constitutes an introduction to the in-depth, topic-focused analyses in the rest of this issue. It examines the broad principles that guide placing a patient on the right diagnostic trajectory, illustrated with real-life examples of current protocol recommendations and cases of advanced imaging techniques, as well as some thought experiments. Thinking about diagnostic imaging strictly in terms of imaging protocols is often inefficient because these protocols can be vague and have numerous variations. Broadly defined protocols may be sufficient, but their successful use often depends largely on the particular circumstances, with special emphasis on the relationship between neurologists and radiologists.
Imaging of Skull Base Tumors
Authors: Bi Wenya Linda
Published: February 2023

OBJECTIVE

This article provides an overview of imaging modalities and findings associated with common skull base tumors including meningiomas and how to use imaging features to guide surveillance and treatment decision making.

LATEST DEVELOPMENTS

Ease of access to cranial imaging has led to a higher number of incidentally diagnosed skull base tumors, which merit careful consideration for management with observation or treatment. The point of origin of the tumor dictates the pattern of anatomic displacement and involvement by the tumor as it grows. Careful study of vascular encroachment on CT angiography, as well as the pattern and extent of bony invasion on CT, abets treatment planning. Quantitative analyses of imaging, such as with radiomics, may further elucidate phenotype-genotype associations in the future.

ESSENTIAL POINTS

Combinatorial application of CT and MRI analyses improves the diagnosis of skull base tumors, clarifies their point of origin, and dictates the extent of treatment needed.
Trends and In-Hospital Mortality for Perioperative Myocardial Infarction After the Introduction of a Diagnostic Code for Type 2 Myocardial Infarction in the United States Between 2016 and 2018
Authors: Rubin Daniel S. , Lin Antonia Z. , Ward R. Parker , Nagele Peter
Published: February 2023

BACKGROUND:

The frequency of perioperative myocardial infarction has been declining; however, previous studies have only described type 1 myocardial infarctions. Here, we evaluate the overall frequency of myocardial infarction with the addition of an International Classification of Diseases 10th revision (ICD-10-CM) code for type 2 myocardial infarction and the independent association with in-hospital mortality.

METHODS:

A longitudinal cohort study spanning the introduction of the ICD-10-CM diagnostic code for type 2 myocardial infarction using the National Inpatient Sample (NIS) from 2016 to 2018. Hospital discharges that included a primary surgical procedure code for intrathoracic, intraabdominal, or suprainguinal vascular surgery were included. Type 1 and type 2 myocardial infarctions were identified using ICD-10-CM codes. We used segmented logistic regression to estimate change in frequency of myocardial infarctions and multivariable logistic regression to determine the association with in-hospital mortality.

RESULTS:

A total of 360,264 unweighted discharges were included, representing 1,801,239 weighted discharges, with median age 59 and 56% female. The overall incidence of myocardial infarction was 0.76% (13,605/1,801,239). Before the introduction of type 2 myocardial infarction code, there was a small baseline decrease in the monthly frequency of perioperative myocardial infarctions (odds ratio [OR], 0.992; 95% confidence interval [CI], 0.984–1.000; P  =  .042), but no change in the trend after the introduction of the diagnostic code (OR, 0.998; 95% CI, 0.991–1.005; P  =  .50). In 2018, where there was an entire year where type 2 myocardial infarction was officially a diagnosis, the distribution of myocardial infarction type 1 was 8.8% (405/4580) ST elevation myocardial infarction (STEMI), 45.6% (2090/4580) non-ST elevation myocardial infarction (NSTEMI), and 45.5% (2085/4580) type 2 myocardial infarction. STEMI and NSTEMI were associated with increased in-hospital mortality (OR, 8.96; 95% CI, 6.20–12.96; P < .001 and OR, 1.59; 95% CI, 1.34–1.89; P < .001). A diagnosis of type 2 myocardial infarction was not associated with increased odds of in-hospital mortality (OR, 1.11; 95% CI, 0.81–1.53; P  =  .50) when accounting for surgical procedure, medical comorbidities, patient demographics, and hospital characteristics.

CONCLUSIONS:

The frequency of perioperative myocardial infarctions did not increase after the introduction of a new diagnostic code for type 2 myocardial infarctions. A diagnosis of type 2 myocardial infarction was not associated with increased in-patient mortality; however, few patients received invasive management that may have confirmed the diagnosis. Further research is needed to identify what type of intervention, if any, may improve outcomes in this patient population.
Notch signaling in development and homeostasis
Authors: Gozlan Oren , Sprinzak David
Published: February 2023

Notch signaling is a highly conserved signaling pathway that coordinates cellular differentiation during the development and homeostasis in numerous organs and tissues across metazoans. Activation of Notch signaling relies on direct contact between neighboring cells and mechanical pulling of the Notch receptors by the Notch ligands. Notch signaling is commonly used in developmental processes to coordinate the differentiation into distinct cell fates of neighboring cells. In this Development at a Glance article, we describe the current understanding of the Notch pathway activation and the different regulatory levels that control the pathway. We then describe several developmental processes where Notch is crucial for coordinating differentiation. These examples include processes that are largely based on lateral inhibition mechanisms giving rise to alternating patterns (e.g. SOP selection, hair cell in the inner ear and neural stem cell maintenance), as well as processes where Notch activity is oscillatory (e.g. somitogenesis and neurogenesis in mammals).