bluuebunny/crossref_metadata_2025 huggingface dataset:
Choice of Statistical Tools for Outlier Removal Causes Substantial Changes in Analyte Reference Intervals in Healthy Populations
Authors: Hickman Peter E , Koerbin Gus , Potter Julia M , Glasgow Nicholas , Cavanaugh Juleen A , Abhayaratna Walter P , West Nic P , Glasziou Paul
Published: August 2020

Background

Reference intervals are an important aid in medical practice as they provide clinicians a guide as to whether a patient is healthy or diseased.

Outlier results in population studies are removed by any of a variety of statistical measures. We have compared several methods of outlier removal and applied them to a large body of analytes from a large population of healthy persons.

Methods

We used the outlier exclusion criteria of Reed-Dixon and Tukey and calculated reference intervals using nonparametric and Harrell-Davis statistical methods and applied them to a total of 36 different analytes.

Results

Nine of 36 analytes had a greater than 20% difference in the upper reference limit, and for some the difference was 100% or more.

Conclusions

For some analytes, great importance is attached to the reference interval. We have shown that different statistical methods for outlier removal can cause large changes to reported reference intervals. So that population studies can be readily compared, common statistical methods should be used for outlier removal.
Influence of BMI percentile on craniofacial morphology and development in children and adolescents
Authors: Danze Adam , Jacox Laura Anne , Bocklage Clare , Whitley John , Moss Kevin , Hardigan Patrick , Garcia-Godoy Cristina E , Jackson Tate Harris
Published: August 2020

Background

The prevalence of childhood and adolescent obesity is increasing worldwide. Reports suggest that elevated body mass index (BMI) is associated with larger craniofacial dimensions and advanced dental and skeletal development. Such an association is important for timing orthodontic treatment relative to pubertal growth and dental eruption.

Materials and Methods

To evaluate associations between BMI, craniofacial morphology, dental age, and cervical vertebrae maturation staging (CVMS), 400 participants were consecutively selected (8–15 years, n = 200 overweight and obese BMI >85%, 200 normal weight) from the University of North Carolina database. Records were analysed for cephalometric measures, Demirjian index values, and CVMS. Bivariate statistics and linear regression analysis evaluated whether CVMS, dental age, and cephalometric dimensions varied with BMI.

Results

Overweight/obese children and adolescents had a proportionally larger bimaxillary prognathic skeletal pattern compared to those of normal weight. These cephalometric measurements [articulare–gnathion (Ar–Gn), condylion–anterior nasal spine (Co–ANS), sella–gonion (S–Go), nasion–menton (N–Me), anterior nasal spine–menton (ANS–Me), sella-nasion-A point (SNA), sella-nasion-B point (SNB), and sella-nasion-pogonion (SNPg)] were significantly different [statistically (P < 0.05) and clinically (>2 mm or >2 degrees)] between the two study groups, with a linear relationship between BMI percentile and craniofacial dimension. The overweight/obese BMI group had a mean dental age 1.4 years advanced relative to the normal weight group (P < 0.05), with an advancement of nearly one CVM stage between the ages of 12 and 14 (P < 0.05).

Limitations

The study is retrospective.

Conclusions

Obese/overweight children and adolescents have proportionally larger antero-posterior and vertical dimensions and are more likely to experience advanced dental and skeletal maturation. Obese/overweight subjects may enter their growth spurt at a younger age and have earlier eruption of teeth, affecting treatment timing. BMI percentile should be a consideration for orthodontic treatment in growing patients.
Loss of daptomycin susceptibility in clinical Staphylococcus epidermidis infection coincided with variants in WalK
Authors: Brazeau Nicholas F , Levinson Kara J , Schranz Asher , Moser Kara A , Hollis Ian , Iyer Prashanth , Chien Christopher , Bowen Amanda , van Duin David , Lachiewicz Anne , Andermann Tessa , Jones Melissa , Miller Melissa , Juliano Jonathan J , Bartelt Luther A
Published: August 2020

Daptomycin (DAP) is key in treating multidrug-resistant Staphylococcus infections. Diminished susceptibility to DAP is emerging among Staphylococcus epidermidis strains although mechanisms for non-susceptibility (NS) remain poorly understood. We report a case of persistent S. epidermidis bacteremia in which loss of DAP susceptibility arose during prolonged treatment. Whole genome sequencing identified two mutations, Q371del and P415L, in a single-affected gene, WalK, that coincided with the emergence of DAP-NS. Protein modeling of the mutations predicted a disruption of WalK protein configuration. The emergence of mutations in a single-gene during DAP exposure raises concerns in an era of increasingly treatment-resistant infections.

Lay summary: Daptomycin is an important antibiotic for fighting Staphylococcus infections. We identified variants in the WalK gene that were coincident with resistance in a clinical Staphylococcus epidermidis infection. Clinicians, hospital epidemiologists, and microbiology laboratories need to be aware of the potential for the evolution of drug resistance during prolonged daptomycin therapy.
Subjective Aging and Incident Cardiovascular Disease
Authors: Stephan Yannick , Sutin Angelina R , Wurm Susanne , Terracciano Antonio
Published: August 2020

Objectives

Subjective aging, including subjective age and self-perceptions of aging (SPA), predicts health-related outcomes in older adults. Despite its association with cardiovascular risk factors, little is known about the association between subjective aging and the incidence of cardiovascular disease. Therefore, the present study examined whether subjective age and SPA are related to the incidence of heart conditions and stroke.

Methods

The sample comprises 10,695 participants aged 50–100 years from the Health and Retirement Study. Subjective age, SPA, demographic factors, and health-related behaviors, body mass index (BMI), hypertension, diabetes, and depressive symptoms were assessed at baseline. Self-reported physician diagnosis of heart conditions and stroke were assessed biennially over up to 9 years of follow-up.

Results

Controlling for demographic factors, an older subjective age and more negative SPA were related to a higher risk of incident heart conditions and stroke. Feeling older and holding negative SPA were associated with around 40% higher risk of experiencing heart conditions over time. An older subjective age and negative SPA were related to almost twofold and 30% higher risk of incident stroke, respectively. Health risk behaviors, BMI, hypertension, diabetes, and depressive symptoms accounted for part of the associations between subjective aging and heart diseases and stroke.

Conclusions

Consistent with the literature on subjective aging and cardiovascular risk factors, this large prospective study indicates that an older subjective age and negative SPA increase the risk of incident stroke and other cardiovascular diseases.
A web-based health education module and its impact on the preventive practices of health-care workers during the COVID-19 pandemic
Authors: Abbas Kiran , Nawaz S Muhammad A , Amin Nazish , Soomro Fareena M , Abid Kanza , Ahmed Moiz , Sayeed Khalid A , Ghazanfar Shamas , Qureshi Noorulain
Published: August 2020

Proper training on the preventive measures against COVID-19 among health-care workers is crucial for mitigating the spread of viral infection. The present study evaluated the efficacy of a brief web-based module on the practice of hand hygiene and respiratory etiquette among respective health-care workers. A comparative study was conducted with a total of 500 participants. A self-reported questionnaire was used for both pre- and post-intervention evaluation. The post-intervention assessment was conducted 1–2 weeks following the intervention. The difference in the practice of hand hygiene and respiratory etiquettes during work hours was recorded. We found that the intervention resulted in an evident difference in the use of alcohol-based hand sanitizer by the participating doctors before examining the patient. Interns showed a much higher propensity to wash their hands for at least 20 s, relative to other health-care workers. The difference between pre- and post-intervention handwashing for >5 times/day was 6.5% in females and 4.5% in males. In short, the study was able to demonstrate that a web-based health education module is an effective tool for the education and promotion of preventative measures in hospital setups, which may ultimately aid in halting the spread of COVID-19 among health-care workers.
Promotion of somatic CAG repeat expansion by Fan1 knock-out in Huntington’s disease knock-in mice is blocked by Mlh1 knock-out
Authors: Loupe Jacob M , Pinto Ricardo Mouro , Kim Kyung-Hee , Gillis Tammy , Mysore Jayalakshmi S , Andrew Marissa A , Kovalenko Marina , Murtha Ryan , Seong IhnSik , Gusella James F , Kwak Seung , Howland David , Lee Ramee , Lee Jong-Min , Wheeler Vanessa C , MacDonald Marcy E
Published: August 2020

Recent genome-wide association studies of age-at-onset in Huntington’s disease (HD) point to distinct modes of potential disease modification: altering the rate of somatic expansion of the HTT CAG repeat or altering the resulting CAG threshold length-triggered toxicity process. Here, we evaluated the mouse orthologs of two HD age-at-onset modifier genes, FAN1 and RRM2B, for an influence on somatic instability of the expanded CAG repeat in Htt CAG knock-in mice. Fan1 knock-out increased somatic expansion of Htt CAG repeats, in the juvenile- and the adult-onset HD ranges, whereas knock-out of Rrm2b did not greatly alter somatic Htt CAG repeat instability. Simultaneous knock-out of Mlh1, the ortholog of a third HD age-at-onset modifier gene (MLH1), which suppresses somatic expansion of the Htt knock-in CAG repeat, blocked the Fan1 knock-out-induced acceleration of somatic CAG expansion. This genetic interaction indicates that functional MLH1 is required for the CAG repeat destabilizing effect of FAN1 loss. Thus, in HD, it is uncertain whether the RRM2B modifier effect on timing of onset may be due to a DNA instability mechanism. In contrast, the FAN1 modifier effects reveal that functional FAN1 acts to suppress somatic CAG repeat expansion, likely in genetic interaction with other DNA instability modifiers whose combined effects can hasten or delay onset and other CAG repeat length-driven phenotypes.
Community-level impacts of trawl selectivity in the Eastern Mediterranean Sea assessed using an ecosystem modelling approach
Authors: Saygu İsmet , Heymans Johanna J , Fox Clive , Özbilgin Hüseyin , Bentley Jacob W , Eryaşar Ahmet Raif , Gökçe Gökhan
Published: August 2020

Switching from the traditional 40- or 44-mm diamond mesh codends to 50-mm diamond mesh (D50) or 40-mm square mesh (S40) codends is known to improve the size selection for commercial species and reduce discarding in the Mediterranean demersal trawl fisheries. This change has been recommended in the General Fisheries Commission for the Mediterranean and European Commission regulations. However, ecosystem-based assessment of improved selectivity still remains a challenge, and that is the aim of this study. For this purpose, an Ecopath model was developed and used to initialize dynamic simulations in Ecosim. The simulations changed gear-specific fishing mortality rates to represent the shifting from traditional codend to alternative codends. Our results suggest that the use of D50 or S40 codends would have a positive impact on the ecosystem as a whole and on the stock status of several commercial and non-commercial groups. Mixed trophic impact analysis indicated that, for species, like red mullet, the S40 codend was significantly better than the D50 codend. This information can be useful to policymakers, particularly for the areas where red mullet is the main target species and could inform trawl mesh options in the eastern Mediterranean.
Optimal error estimates and recovery technique of a mixed finite element method for nonlinear thermistor equations
Authors: Gao Huadong , Sun Weiwei , Wu Chengda
Published: August 2020

This paper is concerned with optimal error estimates and recovery technique of a classical mixed finite element method for the thermistor problem, which is governed by a parabolic/elliptic system with strong nonlinearity and coupling. The method is based on a popular combination of the lowest-order Raviart–Thomas mixed approximation for the electric potential/field $(\phi , \boldsymbol{\theta })$ and the linear Lagrange approximation for the temperature $u$. A common question is how the first-order approximation influences the accuracy of the second-order approximation to the temperature in such a strongly coupled system, while previous work only showed the first-order accuracy $O(h)$ for all three components in a traditional way. In this paper, we prove that the method produces the optimal second-order accuracy $O(h^2)$ for $u$ in the spatial direction, although the accuracy for the potential/field is in the order of $O(h)$. And more importantly, we propose a simple one-step recovery technique to obtain a new numerical electric potential/field of second-order accuracy. The analysis presented in this paper relies on an $H^{-1}$-norm estimate of the mixed finite element methods and analysis on a nonclassical elliptic map. We provide numerical experiments in both two- and three-dimensional spaces to confirm our theoretical analyses.
Preterm Birth Impacts the Timing and Excursion of Oropharyngeal Structures during Infant Feeding
Authors: Edmonds C E , Catchpole E A , Gould F D H , Bond L E , Stricklen B M , German R Z , Mayerl C J
Published: August 2020

Synopsis

Swallowing in mammals requires the precise coordination of multiple oropharyngeal structures, including the palatopharyngeal arch. During a typical swallow, the activity of the palatopharyngeus muscle produces pharyngeal shortening to assist in producing pressure required to swallow and may initiate epiglottal flipping to protect the airway. Most research on the role of the palatopharyngeal arch in swallowing has used pharyngeal manometry, which measures the relative pressures in the oropharynx, but does not quantify the movements of the structures involved in swallowing. In this study, we assessed palatopharyngeal arch and soft palate function by comparing their movements in a healthy population to a pathophysiological population longitudinally through infancy (term versus preterm pigs). In doing so, we test the impact of birth status, postnatal maturation, and their interaction on swallowing. We tracked the three-dimensional (3D) movements of radiopaque beads implanted into relevant anatomical structures and recorded feeding via biplanar high-speed videofluoroscopy. We then calculated the total 3D excursion of the arch and soft palate, the orientation of arch movement, and the timing of maximal arch constriction during each swallow. Soft palate excursion was greater in term infants at both 7 and 17 days postnatal, whereas arch excursion was largely unaffected by birth status. Maximal arch constriction occurred much earlier in preterm pigs relative to term pigs, a result that was consistent across age. There was no effect of postnatal age on arch or soft palate excursion. Preterm and term infants differed in their orientation of arch movement, which most likely reflects both differences in anatomy and differences in feeding posture. Our results suggest that the timing and coordination of oropharyngeal movements may be more important to feeding performance than the movements of isolated structures, and that differences in the neural control of swallowing and its maturation in preterm and term infants may explain preterm swallowing deficits.
Metabolism Study of N-Methyl 2-Aminoindane (NM2AI) and Determination of Metabolites in Biological Samples by LC–HRMS
Authors: Mestria Serena , Odoardi Sara , Federici Sofia , Bilel Sabrine , Tirri Micaela , Marti Matteo , Strano Rossi Sabina
Published: August 2020

Since the widespread diffusion of new psychoactive substances, forensic laboratories are often required to identify new drugs and their metabolites for which information or reference standards are lacking. We performed a study on N-methyl-2-aminoindane (NM2AI) metabolism in silico and in vivo, in order to identify the main metabolites to be screened in the different biological samples. We performed the in silico metabolism prediction of NM2AI using MetaSiteTM software and subsequently verified the presence of metabolites in the blood, urine and hair of mice after NM2AI administration. The samples were analyzed by liquid chromatography–high-resolution mass spectrometry (LC–HRMS) with a benchtop Orbitrap Exactive mass detector. This allowed the evaluation of the agreement between software prediction and experimental results in biological samples. LC–HRMS analysis identified seven main metabolites in the urine. They were identified, by their accurate masses and fragmentation patterns, as 2-aminoindane (2AI), two hydroxy-2AI and four hydroxy-NM2AI; one of the hydroxy-NM2AI and one of the hydroxy-2AI underwent also to conjugation. NM2AI and 2AI were also detected by LC–HRMS in the hair and blood. Based on these findings, we developed an LC–HRMS method for the screening of NM2AI and metabolites in urine, blood and hair samples. This can be of primary effectiveness to uncover the abuse of NM2AI and related possible intoxications.
Sexual dimorphism of the major chela and sex ratio as indicators of the mating system in the estuarine snapping shrimpAlpheus colombiensisWicksten, 1988 (Decapoda: Caridea: Alpheidae)
Authors: Azofeifa-Solano Juan C , Sibaja-Cordero Jeffrey A , Wehrtmann Ingo S
Published: August 2020

The sexual selection over traits that favor access to mating partners could promote the emergence of sexual dimorphism when the pressure is different between sexes. Monogamous species are considered to have a low degree of sexual dimorphism. The highly diverse snapping shrimps are usually regarded as monogamous, but the mating system has been studied only in few species. We aimed to provide insights into the mating system and sexual dimorphism of Alpheus colombiensisWicksten, 1988. The adult sex ratio was female biased, and solitary ovigerous females were found, suggesting a temporary mate guarding type of mating system. Our results also revealed sexual dimorphism on the snapping claw, which is larger in males than in females. The male’s snapping claw is probably under sexual selection, which can be mediated by male-male competition or female choice. We also estimated the A. colombiensis female size at maturity at 5.2 ± 0.76 mm. Our results contradict the common idea that snapping shrimps are monogamous species, and support that A. colombiensis probably have a temporary mate guarding (e.g., males can sexually interact with more than one female, in opposition to sexual monogamy). This study also sustains the growing evidence that alpheid shrimps display snapping claw sexual dimorphism.
Reproductive biology of the freshwater shrimpMacrobrachium tenellum(Smith, 1871) (Decapoda: Caridea: Palaemonidae) in Mexico
Authors: López-Uriarte Ernesto , Vega-Villasante Fernando , Wehrtmann Ingo S , Cortés-Jacinto Edilmar , García-Guerrero Marcelo U , Badillo-Zapata Daniel , Chong-Carrillo Olimpia , Vargas-Ceballos Manuel A
Published: August 2020

We analyzed the reproductive cycle of females of the palaemonid shrimp Macrobrachium tenellum (Smith, 1871) collected in the Ameca River, between the Jalisco and Nayarit states, Mexico. We studied the seasonal occurrence of ovigerous females during the year, their relationship with abiotic factors, and the size of the first sexual maturity. The study included 7,100 specimens of M. tenellum, of which 2,791 (39.3%) were males, 3,559 (50.1%) females, and 750 undifferentiated (10.6%). The sex ratio of the total (male-female) population differed significantly from the expected 1:1 with more females. A total of 309 females carried eggs (8.7% of all collected females). Ovigerous females, which were collected in three of the four sampling sites, were found almost year-round (with the exception of March and December), and their number showed a significant positive correlation with water temperature and rainfall. The size of first maturity (TL50%) for all collected females was 55.7 mm total length (TL), ranging from 64.3 mm TL to 42.7 mm TL. The results revealed that the population of M. tenellum in the Ameca River has a continuous reproductive period associated with the rainy season and increasing water temperature.
Breast Cancer Screening Trials: Endpoints and Overdiagnosis
Authors: Jatoi Ismail , Pinsky Paul F
Published: August 2020

Screening mammography was assessed in 9 randomized trials initiated between 1963 and 1990, with breast cancer-specific mortality as the primary endpoint. In contrast, breast cancer detection has been the primary endpoint in most screening trials initiated during the past decade. These trials have evaluated digital breast tomosynthesis, magnetic resonance imaging, and ultrasound, and novel screening strategies have been recommended solely on the basis of improvements in breast cancer detection rates. Yet, the assumption that increases in tumor detection produce reductions in cancer mortality has not been validated, and tumor-detection endpoints may exacerbate the problem of overdiagnosis. Indeed, the detection of greater numbers of early stage breast cancers in the absence of a subsequent decline in rates of metastatic cancers and cancer-related mortality is the hallmark of overdiagnosis. There is now evidence to suggest that both ductal carcinoma in situ and invasive cancers are overdiagnosed as a consequence of screening. For each patient who is overdiagnosed with breast cancer, the adverse consequences include unnecessary anxiety, financial hardships, and a small risk of morbidity and mortality from unnecessary treatments. Moreover, the overtreatment of breast cancer, as a consequence of overdiagnosis, is costly and contributes to waste in health-care spending. In this article, we argue that there is a need to establish better endpoints in breast cancer screening trials, including quality of life and composite endpoints. Tumor-detection endpoints should be abandoned, because they may lead to the implementation of screening strategies that increase the risk of overdiagnosis.
Validation of the NSABP/NRG Oncology 8-Gene Trastuzumab-benefit Signature in Alliance/NCCTG N9831
Authors: Pogue-Geile Katherine L , Song Nan , Serie Daniel J , Wang Ying , Gavin Patrick G , Kim Rim S , Tanaka Noriko , Fumagalli Debora , Taniyama Yusuke , Li Zhuo , Rastogi Priya , Swain Sandra M , Mamounas Eleftherios P , Geyer Charles E , Wolmark Norman , Lucas Peter C , Paik Soonmyung , Thompson E Aubrey
Published: August 2020

Our objective was to validate the NSABP 8-gene trastuzumab-benefit signature, developed and initially validated in NRG Oncology/NSABP B-31 in Alliance/NCCTG N9831. The B-31 and N9831 trials demonstrated the benefit of adding trastuzumab to chemotherapy in the adjuvant setting for HER2+ breast cancer patients. NSABP investigators utilized gene expression profiles of N9831 patients (N = 892) to blindly assign patients to large-, moderate-, or no-trastuzumab benefit groups and then NCCTG investigators assessed the degree of trastuzumab benefit using Cox models adjusted for age, nodes, estrogen receptor/progesterone receptor status, tumor size, and grade. Hazard ratios and 2-sided P values for recurrence-free survival of the predicted large- (n = 387), moderate- (n = 401), and no-benefit (n = 104) groups, based on the 8-gene signature were 0.47 (95% CI = 0.31 to 0.73, P < .001), 0.60 (95% CI = 0.39 to 0.92, P = .02), and 1.54 (95% CI = 0.59 to 4.02, P = .38), respectively (Pinteraction  = .02), providing validation of the 8-gene signature in an independent study.
The Enforceability of Noncompete Clauses in the Medical Profession: A Review by the Workforce Committee and the Medicolegal Committee of the Council of State Neurosurgical Societies
Authors: Huntoon Kristin , Stacy Jason , Cioffi Susie , Swartz Karin , Mazzola Catherine , Profitt Caleb , Adogwa Owoicho
Published: August 2020

BACKGROUND

In both academic and private practice, noncompete clauses are common in many neurological surgery contracts. Noncompete agreements vary, depending on various factors, including the surgeon’s subspecialty, location, and business-related considerations. Each individual state’s law on contracts determines the extent to which noncompete clauses are enforceable.

OBJECTIVE

To evaluate the disparate approaches of various states regarding the enforceability of these clauses and their components.

METHODS

This review surveys several of the most populous states’ law regarding noncompete clauses. This analysis includes an evaluation of state statutes and common law regarding noncompete clauses. It also relies on legal treatises and law review articles.

RESULTS

The enforceability of the noncompete clause depends on the state in which the physician is employed.

CONCLUSION

It is imperative that individuals understand the content of any noncompete clauses in their contract, as well the climate of the state in which they practice. The state's approach determines whether any part or all of the noncompete agreement is enforceable. A review by the Workforce Committee and the Medico-legal Committee of the Council of State Neurosurgical Societies (CSNS) provides explanation of the common elements in restrictive covenants or noncompete clauses and reviews the enforceability of these clauses.
Identification of the activity source of CO2 electroreduction by strategic catalytic site distribution in stable supramolecular structure system
Authors: Sun Sheng-Nan , Li Ning , Liu Jiang , Ji Wen-Xin , Dong Long-Zhang , Wang Yi-Rong , Lan Ya-Qian
Published: August 2020

Identification of the real catalytic site in CO2 reduction reaction (CO2RR) is critical for the rational design of catalysts and the understanding of reactive mechanisms. In this study, the catalytic activity of pyridine-containing materials was for the first time structurally demonstrated in CO2RR by crystalline supramolecular coordination compounds model system. The system consists of three stable supramolecular coordination compounds (Ni-TPYP, Ni-TPYP-1 and Ni-TPP) with different numbers (4, 2 and 0) of active pyridine groups (i.e. uncoordinated pyridine nitrogen atoms). The electrocatalytic test results show that with the decrease of the number of active pyridine groups, the CO2RR performance is gradually reduced, mainly showing the reduction of highest FECO (99.8%, 83.7% and 25.6%, respectively). The crystallographic, experimental and theoretical evidences prove that the CO2RR activity is more likely derived from uncoordinated pyridine nitrogen than the electrocatalytic inert metal nickel in porphyrin center. This work serves as an important case study for the identification of electrocatalytic activity of pyridine-containing materials in CO2RR by simple supramolecular model system.
Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP)
Authors: Zhu Zhirong , Wang Qi , Liao Hongze , Liu Ming , Liu Zhenxing , Zhang Youheng , Zhu Wei-Hong
Published: August 2020

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with ‘always-on’ fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented ‘amphiphilic AIEgen’ sensor QM-SO3-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial ‘fluorescence-off’ state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate (ATP)-sensitive potassium (KATP) on the endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected ‘always-on’ fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens' targetability.
Development of aggregated state chemistry accelerated by aggregation-induced emission
Authors: Xie Yujun , Li Zhen
Published: August 2020

The foundation of aggregation-induced emission (AIE) has greatly affected the design strategies of luminous materials, and accelerated the relevant theoretical and practical application investigation. The AIE concept also inspires the exploration on “aggregated state chemistry” and enlightens new research areas of room-temperature phosphorescence and mechanoluminescence.
Very Light Daily Smoking in Young Adults: Relationships Between Nicotine Dependence and Lapse
Authors: Ashe Melinda L , Wilson Stephen J
Published: August 2020

Introduction

Very light daily smoking is increasingly common among young adults. Evidence suggests that levels of nicotine dependence vary significantly among young adults who engage in very light daily smoking. However, the links between dependence and clinically relevant outcomes (eg, lapse) in this population remain unclear. The goal of this study was to address this gap by evaluating how well different nicotine dependence scales predict lapse behavior among very light daily smoking young adults.

Aims and Methods

Very light daily smokers (1–5 cigarettes/day) aged 18–25 participated in an initial laboratory session, during which nicotine dependence was assessed using four commonly used measures: the Fagerstrӧm Test for Cigarette Dependence (FTCD), the Hooked On Nicotine Checklist (HONC), the Transdisciplinary Tobacco Use Research Centers (TTURC) Nicotine Dependence Inventory, and the Wisconsin Inventory of Smoking Dependence Motives (WISDM). After a baseline period, eligible participants (n = 40) completed a 10-day abstinence incentive period in which they attempted to refrain from smoking to earn monetary rewards. Cox proportional hazards models were used to test whether dependence predicted days to first lapse.

Results

FTCD scores significantly predicted days to lapse, as did scores on the FTCD item assessing time to first cigarette of the day (TTFC). No other dependence measures predicted time to lapse. Both the FTCD and TTFC continued to independently predict time to lapse after controlling for smoking frequency and duration.

Conclusions

The FTCD may be a particularly useful tool for capturing clinically meaningful variability in nicotine dependence among young adults who engage in very light daily smoking.

Implications

This is the first study to directly link self-reported nicotine dependence with the ability to achieve and maintain abstinence among very light daily smoking young adults. The results may aid clinicians in selecting among variable measures of nicotine dependence when assessing and treating this population.
Economic Evaluation of Extended Early Intervention Service vs Regular Care Following 2 Years of Early Intervention: Secondary Analysis of a Randomized Controlled Trial
Authors: Groff Michael , Latimer Eric , Joober Ridha , Iyer Srividya N , Schmitz Norbert , Abadi Sherezad , Abdel-Baki Amal , Casacalenda Nicola , Margolese Howard C , Jarvis G Eric , Malla Ashok
Published: August 2020

Cost-effectiveness studies of early intervention services (EIS) for psychosis have not included extension beyond the first 2 years. We sought to evaluate the cost-effectiveness of a 3-year extension of EIS compared to regular care (RC) from the public health care payer’s perspective. Following 2 years of EIS in a university setting in Montreal, Canada, patients were randomized to a 3-year extension of EIS (n = 110) or RC (n = 110). Months of total symptom remission served as the main outcome measure. Resource use and cost data for publicly covered health care services were derived mostly from administrative systems. The incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were produced. Relative cost-effectiveness was estimated for those with duration of untreated psychosis (DUP) of 12 weeks or less vs longer. Extended early intervention had higher costs for psychiatrist and nonphysician interventions, but total costs were not significantly different. The ICER was $1627 per month in total remission. For the intervention to have an 80% chance of being cost-effective, the decision-maker needs to be willing to pay $5942 per month of total symptom remission. DUP ≤ 12 weeks was associated with a reduction in costs of $12 276 even if no value is placed on additional months in total remission. Extending EIS for psychosis for people, such as those included in this study, may be cost-effective if the decision-maker is willing to pay a high price for additional months of total symptom remission, though one commensurate with currently funded interventions. Cost-effectiveness was much greater for people with DUP ≤12 weeks.
The Association Between Endplate Changes and Risk for Early Severe Cage Subsidence Among Standalone Lateral Lumbar Interbody Fusion Patients
Authors: Okano Ichiro , Jones Conor , Rentenberger Colleen , Sax Oliver C. , Salzmann Stephan N. , Reisener Marie-Jacqueline , Shue Jennifer , Carrino John A. , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Hughes Alexander P.
Published: August 2020

Study Design.

Retrospective case series.

Objective.

The aim of this study was to investigate the association of Modic type endplate changes with the risk of severe subsidence after standalone lateral lumbar interbody fusion (SA-LLIF).

Summary of Background Data.

It has been reported that certain endplate radiolographic features are associated with higher regional bone mineral density (BMD) in the adjacent vertebrae in the lumbar spine. It remains unclear whether these changes have protective effects against osteoporotic complications such as cage subsidence after lumbar surgery.

Methods.

We reviewed patients undergoing SA-LLIF from 2007 to 2016 with a follow-up >6 months. Cage subsidence was assessed utilizing the grading system by Marchi et al. As potential contributing factors for cage subsidence, we measured the endplate volumetric BMD (EP-vBMD) and the standard trabecular volumetric BMD measurement in the vertebral body. Modic changes (MC) on magnetic resonance imaging were measured as a qualitative factor for endplate condition. Univariate analysis and multivariate logistic regression analyses with a generalized mixed model were conducted.

Results.

Two hundred six levels in 97 patients were included in the final analysis. Mean age (± SD) was 66.7 ± 10.7. Sisty-sdpercent of the patients were female. Severe subsidence was observed in 66 levels (32.0%). After adjusting for age, bone morphogenetic protein (BMP) use, and number of levels fused, the presence of MC type 2 was significantly associated with lower risk of severe subsidence (OR = 0.28 [0.09–0.88], P = 0.029). Whereas, EP-vBMD did not demonstrate a statistical significance (p = 0.600).

Conclusion.

The presence of a Modic type 2 change was significantly associated with lower odds of severe subsidence after SA-LLIF. Nonetheless, this significant association was independent from regional EP-vBMD values. This finding suggests that microstructural and/or material property changes associated with Modic type 2 changes might have a protective effect in this patient population.

Level of Evidence: 4
Establishment of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Immunosuppressant Levels in the Peripheral Blood Mononuclear Cells of Chinese Renal Transplant Recipients
Authors: Chen Bing , Lu Jia-Qian , Shao Kun , Zhai Xiao-Hui , An Hui-Min , Shi Hao-Qiang , Zhou Pei-Jun
Published: August 2020

Background:

Monitoring immunosuppressant levels, such as mycophenolic acid (MPA), cyclosporin A (CsA), and tacrolimus (TAC), in peripheral blood mononuclear cells (PBMCs) could be useful in organ transplant patients administered individualized therapy. The authors developed a liquid chromatography-tandem mass spectrometry assay technique to simultaneously determine immunosuppressant levels in PBMCs and assess their pharmacokinetics in Chinese renal allograft recipients.

Methods:

PBMCs were isolated from the whole blood of 27 Chinese renal transplant patients using Ficoll-Paque Plus solution, and cell number was determined; acetonitrile treatment for protein precipitation, and gradient elution was performed on an Agilent Eclipse XDB-C18 column (3.5 μm, 2.1 × 100 mm) with mobile phase: water and methanol (containing 2 mM ammonium formate); flow rate: 0.3 mL·min−1.

Results:

The calibration curves of MPA, CsA, and TAC had a linear range (ng·mL−1): 0.098–39.2 (r = 0.9987), 0.255–102 (r = 0.9969), and 0.028–11.2 (r = 0.9993), respectively. The extraction effects, matrix effects, and mean relative recovery of these immunosuppressants were 70.4%–93.2%, 72.7%–96.5%, and 90.1%–112.4%, respectively. The within-day and between-day coefficients of variation were <15%. The AUC0–12 of MPA in PBMCs correlated well with those in plasma. The level of MPA, CsA, and TAC in PBMCs might be more stable during dosing interval.

Conclusions:

The derived liquid chromatography-tandem mass spectrometry assay is suitable for simultaneously monitoring different immunosuppressants in PBMCs. Pharmacokinetic of MPA, CsA, and TAC displayed considerable interindividual variability. Intracellular monitoring of immunosuppressants may facilitate individualized therapy for renal allograft recipients.
Safety and Efficacy of Tigecycline in Intensive Care Unit Patients Based on Therapeutic Drug Monitoring
Authors: Fan Guangjun , Jin Liu , Bai Hansheng , Jiang Kang , Xie Jiao , Dong Yalin
Published: August 2020

Objective:

Tigecycline exerts significant beneficial effects against drug-resistant bacterial infections. The largely empirical medications used in clinical practice are often associated with wide individual differences in efficacy and safety. We investigated the associations between the pharmacokinetics of tigecycline and its efficacy and safety in intensive care unit (ICU) patients, with the aim of facilitating clinical applications of tigecycline.

Methods:

ICU patients who were prescribed tigecycline in a hospital setting were prospectively included. Factors related to the clinical efficacy and safety of tigecycline were assessed by univariate and multivariate analyses.

Results:

This study included 45 patients, from whom a total of 63 blood samples were collected to determine steady-state trough plasma concentrations (Cmin) of tigecycline. The Cmin of tigecycline was 417.1 ± 263.8 ng/mL (mean ± SD). The multivariate analysis showed that the APACHE II scores [odds ratio (OR) = 0.874, 95% confidence interval (CI) = 0.733–0.901, P = 0.048] were significantly correlated with the efficacy of tigecycline, whereas there was no correlation between Cmin of tigecycline and efficacy. In safety, the risk factors significantly associated with hepatotoxicity were sex (OR = 0.562, 95% CI = 0.191–0.774, P = 0.023), APACHE II score (OR = 1.061, 95% CI = 1.039–1.392, P = 0.045), and Cmin (OR = 1.210, 95% CI = 1.014–1.336, P = 0.008). The optimal cut-off for hepatotoxicity in ICU patients treated with tigecycline was 474.8 ng/mL.

Conclusions:

There was considerable variability in the Cmin of tigecycline among the ICU patients in this study and it is at risk of high exposure in women. Cmin can be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL.
Automated Keratopigmentation in Boston Type 1 Keratoprosthesis: An Aesthetic Alternative
Authors: Camerati Matias , Jaque Neal , Lievano Jose , Henriquez Maria A. , Izquierdo Luis
Published: August 2020

Two male patients, aged 64 and 55 years old, presented at the cornea department for a Boston type 1 keratoprosthesis (Kpro I) implantation after multiple corneal graft failures. After surgery, they achieved a best corrected visual acuity of 20/200 and 20/150, respectively. However, they manifested photophobia and aesthetic complaints. Both patients underwent keratopigmentation to improve the aesthetic outcome using vegetable pigments, after mechanical corneal deepithelization, with no intraoperative or postoperative incidents or adverse events. After 1-year follow-up, the patients presented the same best corrected visual acuity with improvement of the aesthetic outcome.
Accuracy of the 4-Stage Balance Test and Sensor-Based Trunk Sway as Fall Risk Assessment Tools in the Emergency Department
Authors: Southerland L. T. , Kloos A. D. , Slattery L. , Tan Y. , Young G. , Rosenthal J. , Kegelmeyer D. A.
Published: August 2020

Purpose:

Falls are the leading cause of injury-related emergency department (ED) visits in older adults, but we lack a sensitive screening tool for fall risk. We evaluated the sensitivity and specificity of the 4-Stage Balance Test (4SBT) to identify older adults at risk of falling in an ED setting and whether accelerometry-based trunk sway measures could improve identification.

Methods:

Participants were 63 ambulatory adults 65 years and older in the ED, of which 47% reported a fall in the past year. Outcome measures were the 4SBT and trunk sway. Participants identified as being at risk of falling received recommendations for follow-up care. Participants were contacted 8 ± 2 weeks after their ED visits to assess compliance with ED recommendations.

Results:

No strong association was found between reported falls and completion of the first 3 positions of the 4SBT (P = .063). The best model was staggered stance plus average anterior-posterior sway and posterior sway of the thorax (P = .004, area under receiver operating curve = 0.8). On follow-up, 21% of those identified as being at risk, and available for follow-up, had fallen; 2 reported multiple falls.

Conclusions:

Administration of the first 2 positions of the 4SBT combined with measurement of posterior sway is a quick method for fall risk assessment in the ED.
Preventing epilepsy after traumatic brain injury: A propensity score analysis
Authors: Liou Jaw-Horng , Chang Yen-Lin , Lee Hsu-Tung , Wu Ming-Fen , Hou Yu-Chi , Liou Wen-Shyong
Published: August 2020

Background:

Due to the potential consequences of post-traumatic epilepsy (PTE) exacerbating secondary injury following traumatic brain injury (TBI), the use of antiepileptic drugs (AEDs) is an accepted option for seizure prophylaxis. However, there is only a paucity of data that can be found regarding outcomes surrounding the use of AEDs. The purpose of this retrospective study is to evaluate whether the prophylactic administration of AEDs significantly decreased the incidence of PTE, when considering the severity of TBI.

Methods:

All trauma patients who had been newly diagnosed with TBI from January 1, 2010 to December 31, 2017 were retrospectively analyzed. Statistical comparisons were made using the chi-square test, Mann-Whitney U test, and Cox regression modeling. After excluding any exposed subjects with no appropriate match, patients who had received AED prophylaxis were matched by propensity score with those who did not receive AEDs. All of the TBI populations were followed up until June 30, 2018.

Results:

We identified 1316 patients who met the inclusion and exclusion criteria in our matched cohort through their propensity scores, where 138 patients had been receiving prophylactic AEDs and 138 patients had not. Baseline characteristics were similar in gender, age, Glasgow Coma Scale (GCS) scores, and risk factors of PTE including skull fracture, chronic alcoholism, subdural hematoma, epidural hematoma, and intracerebral hematoma. After adjusting for those risk factors, the relative incidence of seizure was not statistically significant in either of the groups (p = 0.566).

Conclusion:

In our cohort analysis, AED prophylaxis was ineffective in preventing seizures, as the rate of seizures was similar whether patients had been receiving the drugs or not. We therefore concluded that the benefits of routine prophylactic anticonvulsant therapy in patients with TBI need to be re-evaluated.
Using lung ultrasound changes to evaluate the response of recruitment maneuver in a patient recovering from coronavirus disease 2019 with acute respiratory distress syndrome
Authors: Hsiao Yi-Han , Lin Yi-Tsung , Liao Hsien-Tzung , Yang Kuang-Yao , Chen Yuh-Min
Published: August 2020

Lung ultrasound (LUS) is widely used in intensive care units because it provides timely information noninvasively. The use of LUS is recommended to minimize transfers in critically ill patients with coronavirus disease 2019 (COVID-19) during the pandemic. The clinical efficacies of bedside chest X-ray (CXR) and LUS have not been compared in these patients. Herein, we demonstrated serial LUS changes in a 75-year-old woman recovering from COVID-19 with acute respiratory distress syndrome (ARDS) in need of veno-venous extracorporeal membrane oxygenation support. LUS initially revealed extensive consolidation in the bilateral lower lung (BLL) fields with coalescent B-lines. While the patient recovered from ARDS, the findings gradually changed to discrete B-lines and small pleural consolidations. The LUS findings were more sensitive than those of the CXR in detecting re-expansion of the lungs by showing B-lines instead of consolidations in the BLL fields immediately after recruitment maneuver (RM). Compared with physiological parameters, LUS findings provided more precise information about the parts of the lungs that had been recruited by RM. Therefore, we encourage intensivists to extend their use of LUS in critically ill patients with COVID-19 and ARDS to acquire real-time information for a quick response and minimize the risk of viral transmission.
Certified Nursing Assistants’ Barriers and Facilitators to Accessing and Using Worksite Health Promotion Programs
Authors: Kim Mhinjine , Lin Yu Chen , Luna Geraldine , Ma Jun , Stiehl Emily
Published: August 2020

Objective:

Certified nursing assistants (CNAs) are low-wage healthcare workers who provide direct care to nursing home residents, yet also experience significant health disparities. However, limited research has been conducted on CNAs’ perceived barriers and facilitators to workplace health promotion (WHP) participation.

Method:

Informed by the Consolidated Framework for Implementation Research (CFIR), 24 CNA semi-structured, in-depth interviews were conducted in two Chicagoland nursing homes.

Results:

Key barriers were time-constraints and lack of staffing, lack of access to WHP programs, and limited organizational and employer support. Facilitators included the availability of WHP programs, breaks, and other workplace benefits, and enhanced leadership and familial support.

Conclusion:

An effective WHP program must attempt to minimize the work-related, organizational, and environmental barriers while supporting high motivation of CNAs in health promotion. We offer some suggestions for enhancing CNAs’ WHP access and utilization.