bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in plasma and urine metabolites associated with empagliflozin in patients with type 1 diabetes
Authors: Liu Hongyan , Sridhar Vikas S. , Montemayor Daniel , Lovblom Leif Erik , Lytvyn Yuliya , Ye Hongping , Kim Jiwan , Ali Mir Tariq , Scarr Daniel , Lawler Patrick R. , Perkins Bruce A. , Sharma Kumar , Cherney David Z. I.
Published: July 2021

Aim

To examine the impact of the sodium‐glucose co‐transporter‐2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes.

Material and Methods

Participants (n = 40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8‐week, open‐label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate ≤ 0.1) for further analysis.

Results

Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P < .0001), biosynthesis of unsaturated fatty acids (P = .0045), butanoate (P < .0001), propanoate (P = .0053), and alanine, aspartate and glutamate (P < .0050) metabolites were increased after empagliflozin treatment under clamped euglycaemia. Of the urine metabolite groups, only butanoate metabolites (P = .0005) were significantly increased. Empagliflozin treatment also attenuated the increase in a number of urine metabolites observed with acute hyperglycaemia.

Conclusions

Empagliflozin was associated with increased lipid and TCA cycle metabolites in participants with type 1 diabetes, suggesting a shift in metabolic substrate use and improved mitochondrial function. These effects result in more efficient energy production and may contribute to end‐organ protection by alleviating local hypoxia and oxidative stress.
Antiseizure effects of the cannabinoids in the amygdala‐kindling model
Authors: Fallah Merrick S. , Dlugosz Lukasz , Scott Brian W. , Thompson Miles D. , Burnham W. McIntyre
Published: July 2021

Objective

Focal impaired awareness seizures (FIASs) are the most common seizure type in adults and are often refractory to medication. Management of FIASs is clinically challenging, and new interventions are needed for better seizure control. The amygdala‐kindling model is a preclinical model of FIASs with secondary generalization. The present study assessed the efficacy of cannabidiol (CBD), ∆9‐tetrahydrocannabinol (THC), and a combination of CBD and THC in a 15:1 ratio at suppressing focal and secondarily generalized seizures in the amygdala‐kindled rat.

Methods

Fully kindled, male Sprague Dawley rats, with bipolar electrodes implanted in the right amygdala, were given either CBD (0–320 mg/kg), THC (0–40 mg/kg), or a combination of CBD and THC (15:1 ratio, multiple doses) intraperitoneally. Suprathreshold kindling stimulation was administered 1 h (THC) or 2 h (CBD) after drug injection, and outcomes were assessed using focal electroencephalographic recording and the Racine seizure scale.

Results

CBD alone produced a partial suppression of both generalized seizures (median effective dose [ED50] = 283 mg/kg) and focal seizures (ED40= 320 mg/kg) at doses that did not produce ataxia. THC alone also produced partial suppression of generalized (ED50= 10 mg/kg) and focal (ED50= 30 mg/kg) seizures, but doses of 10 mg/kg and above produced hypolocomotion, although not ataxia. The addition of a low dose of THC to CBD (15:1) left‐shifted the CBD dose–response curve, producing much lower ED50s for both generalized (ED50= 26 + 1.73 mg/kg) and focal (ED50= 40 + 2.66 mg/kg) seizures. No ataxia or hypolocomotion was seen at these doses of the CBD + THC combination.

Significance

CBD and THC both have antiseizure properties in the amygdala‐kindling model, although THC produces suppression of the amygdala focus only at doses that produce hypolocomotion. The addition of small amounts of THC greatly improves the effectiveness of CBD. A combination of CBD and THC might be useful for the management of FIASs.
Prediction of seizure recurrence risk following discontinuation of antiepileptic drugs
Authors: Contento Margherita , Bertaccini Bruno , Biggi Martina , Magliani Matteo , Failli Ylenia , Rosati Eleonora , Massacesi Luca , Paganini Marco
Published: July 2021

Objective

Discontinuation of antiepileptic drugs (AEDs) in seizure‐free patients is an important goal because of possible long‐term side effects and the social stigma burden of epilepsy. The purpose of this work was to assess seizure recurrence risk after suspension of AEDs, to evaluate predictors for recurrence, and to investigate the recovery of seizure control after relapse. In addition, the accuracy of a previously published prediction model of seizure recurrence risk was estimated.

Methods

Seizure‐free patients with epilepsy who had discontinued AEDs were retrospectively enrolled. The frequency of seizure relapses after AED withdrawal as well as prognosis after recurrence were assessed and the predictive role of baseline clinical‐demographic variables was evaluated. The aforementioned prediction model was also validated and its accuracy assessed at different seizure‐relapse probability levels.

Results

The enrolled patients (n = 133) had been followed for a median of 3 years (range 0.8–33 years) after AED discontinuation; 60 (45%) of them relapsed. Previous febrile seizures in childhood (hazard ratio [HR] 3.927; 95% confidence interval [CI] 1.403–10.988), a seizure‐free period on therapy of less than 2 years (HR 2.313; 95% CI 1.193–4.486), and persistent motor deficits (HR 4.568; 95% CI 1.412–14.772) were the clinical features associated with relapse risk in univariate analysis. Among these variables, only a seizure‐free period on therapy of less than 2 years was associated with seizure recurrence in multivariate analysis (HR 2.365; 95% CI 1.178–4.7444). Pharmacological control of epilepsy was restored in 82.4% of the patients who relapsed. In this population, the aforementioned prediction model showed an unsatisfactory accuracy.

Significance

A period of freedom from seizure on therapy of less than 2 years was the main predictor of seizure recurrence. The accuracy of the previously described prediction tool was low in this cohort, thus suggesting its cautious use in real‐world clinical practice.
Summer study abroad in Japan: Maximizing intercultural competency development through self‐guided cultural exploration and reflection tasks
Authors: Fukuda Makiko , Nishikawa Chávez Katsuo
Published: July 2021

This study analyzes how self‐guided cultural exploration and reflection (SCER) tasks affect the development of intercultural competency (ICC) of students participating in a study abroad program. The Intercultural Effectiveness Scale (IES) was used to measure students' ICC development before and after a 6‐week faculty‐led study abroad program in Japan. The SCER tasks encouraged students to examine Japanese history, cuisine, politics, architecture, economy, communication style, and behaviors, and gain a sophisticated understanding of the Japanese culture through the lens of unique Japanese perspectives. The results reveal significant gains in overall IES scales, in particular, student's continuous learning and interpersonal engagement saw the most change. Analysis of student reflections further demonstrates the positive impact of culturally bridging experiences on self‐awareness and cultural exploration. We argue that the impact of perspective‐shifting practices, combined with students' first‐hand intercultural experience improves student's level of hardiness. Finally, student reflections reveal the important role that the SCER tasks have on initiating a meaningful dialogue with their host families.
LABOR MARKET SEARCH, INFORMALITY, AND SCHOOLING INVESTMENTS
Authors: Bobba Matteo , Flabbi Luca , Levy Santiago
Published: July 2021

We develop a search and matching model where jobs can be formal or informal. Workers choose schooling and search for jobs. Firms post vacancies in each schooling market and decide the job's formality status. Upon meeting, workers and firms bargain over wages. The equilibrium size of the informal sector is an endogenous function of labor market fundamentals and institutions. We estimate the model using labor force survey data from Mexico and exploiting the exogenous variation induced by a noncontributory social program. Counterfactual experiments show that eliminating informal jobs increases schooling investments but decreases welfare for both workers and firms.
Progressive legislation but lukewarm policies: The Brazilian response to Venezuelan displacement
Authors: Zapata Gisela P. , Tapia Wenderoth Vicente
Published: July 2021

Fleeing from the country's humanitarian crisis, around 224,000 Venezuelans, half of whom requested protection as refugees, had crossed the border into Brazil as of December 2019. The paper uses a case study approach combining quantitative and documentary evidence to systematically examine the Brazilian political‐institutional response to this mass displacement. Although Brazil has been internationally praised as a model, its policy response has been far more complex and ambiguous, lacking the clear progressive character ascribed to it. Despite having a ‘progressive’ migration and refugee legal framework, the state's framing of this displacement as a temporary ‘migration crisis’ has led to the militarization of migration management and the adoption of ad hoc regularization mechanisms for the temporary settlement of Venezuelans, with little articulation with other long‐term intersectorial socio‐economic policies. This case illustrates how countries in the global south manage the tensions between securitization and human rights concerns in their migration governance.
Circadian periodicity affects the type of ventricular arrhythmias and efficacy of implantable defibrillator therapies
Authors: Vergara Pasquale , Pignalberi Carlo , Pisanò Ennio C. , Maglia Giampiero , Della Bella Paolo , Zanotto Gabriele , Iacopino Saverio , Solimene Francesco , Calvi Valeria , Marini Massimiliano , Giammaria Massimo , Biffi Mauro , Rovaris Giovanni , Caravati Fabrizio , Quartieri Fabio , Curnis Antonio , Rapacciuolo Antonio , Senatore Gaetano , Pedretti Stefano , Saporito Davide , Dello Russo Antonio , Santobuono Vincenzo E. , Pepi Patrizia , Duca Antonio , Baroni Matteo , Falasconi Giulio , Giacopelli Daniele , Gargaro Alessio , D'Onofrio Antonio
Published: July 2021

Introduction

Factors influencing malignant arrhythmia onset are not fully understood. We explored the circadian periodicity of ventricular arrhythmias (VAs) in patients with implantable cardioverter and cardiac resynchronization defibrillators (ICD/CRT‐D).

Methods

Time, morphology (monomorphic/polymorphic), and mode of termination (anti‐tachycardia pacing [ATP] or shock) of VAs stored in a database of remote monitoring data were adjudicated. Episodes were grouped in six 4‐h timeslots from 00:00 to 24:00. Circadian distributions and adjusted marginal odds ratios (ORs), with 95% confidence interval (CI), were analyzed using mixed‐effect models and logit generalized estimating equations, respectively, to account for within‐subject correlation of multiple episodes.

Results

Among 1303 VA episodes from 446 patients (63% ICD and 37% CRT‐D), 120 (9%) self‐extinguished, and 842 (65%) were terminated by ATP, 343 (26%) by shock. VAs clustered from 08:00 to 16:00 with 44% of episodes, as compared with 22% from 00:00 to 08:00 (p < .001) and 34% from 16:00 to 24:00 (p = .005). Episodes were more likely to be polymorphic at night with an adjusted marginal OR of 1.66 (CI, 1.15–2.40; p = .007) at 00:00–04:00 versus other timeslots. Episodes were less likely to be terminated by ATP in the 00:00–04:00 (success‐to‐failure ratio, 0.67; CI, 0.46–0.98; p = .039) and 08:00–12:00 (0.70; CI, 0.51–0.96; p = .02) timeslots, and most likely to be terminated by ATP between 12:00 and 16:00 (success‐to‐failure ratio 1.42; CI, 1.06–1.91; p = .02).

Conclusion

VAs did not distribute uniformly over the 24 h, with a majority of episodes occurring from 08:00 to 16:00. Nocturnal episodes were more likely to be polymorphic. The efficacy of ATP depended on the time of delivery.
Genetic variability of Edwardsiella piscicida isolates from Mississippi catfish aquaculture with an assessment of virulence in channel and channel × blue hybrid catfish
Authors: López‐Porras Adrián , Griffin Matt J. , Armwood Abigail R. , Camus Alvin C. , Waldbieser Geoffrey C. , Ware Cynthia , Richardson Bradley , Greenway Terrence E. , Rosser Thomas Graham , Aarattuthodiyil Suja , Wise David J.
Published: July 2021

The bacterium Edwardsiella piscicida causes significant losses in global aquaculture, particularly channel (Ictalurus punctatus) × blue (I. furcatus) hybrid catfish cultured in the south‐eastern United States. Emergence of E. piscicida in hybrid catfish is worrisome given current industry trends towards increased hybrid production. The project objectives were to assess intraspecific genetic variability of E. piscicida isolates recovered from diseased channel and hybrid catfish in Mississippi; and determine virulence associations among genetic variants. Repetitive extragenic palindromic sequence‐based PCR (rep‐PCR) using ERIC I and II primers was used to screen 158 E. piscicida diagnostic case isolates. A subsample of 39 E. piscicida isolates, representing predominant rep‐PCR profiles, was further characterized using BOX and (GTG)5 rep‐PCR primers, virulence gene assessment and multilocus sequence analysis (MLSA) targeting housekeeping genes gyrb, pgi and phoU. The MLSA provided greater resolution than rep‐PCR, revealing 5 discrete phylogroups that correlated similarly with virulence gene profiles. Virulence assessments using E. piscicida representatives from each MLSA group resulted in 14‐day cumulative mortality ranging from 22% to 54% and 63 to 72% in channel and hybrid fingerlings, respectively. Across all phylogroups, mortality was higher in hybrid catfish (p < .05), supporting previous work indicating E. piscicida is an emerging threat to hybrid catfish aquaculture in the south‐eastern United States.
Coupling electronic nose with GC–MS improves flavor recognition and grade differentiation of Zhenjiang aromatic vinegar
Authors: Wang Li , Huang Xingyi , Wang Chengquan , Aheto Joshua Harrington , Chang Xianhui , Yu Shanshan , Zhang Xiaorui , Wang Yu
Published: July 2021

In this study, the flavor volatile profiles of five grades of Zhenjiang aromatic vinegar (ZAV) were compared using a gas chromatography‐mass spectrometer (GC–MS) and electronic nose (E‐nose). A total of 55 volatile compounds were identified, with 14 volatile compounds, including furfural, acetic acid, tetramethylpyrazine, phenethyl acetate, and phenylethyl alcohol, being identified as the key volatile compounds causing significant differences between different grades of ZAV samples. Principal component analysis (PCA) analysis of E‐nose data revealed that the W5S, W1W, W2W, W1S, and W2S sensors with high signal intensity to all ZAV samples correctly categorized the five grades of ZAV samples. The correlation analysis results suggested that the response signal intensities of W5S, W1W, and W2W had significant positive correlations with the abundances of acetic acid, isobutyric acid, ethyl phenylacetate, 3‐hydroxy‐2‐butanone, 2,3‐butanedione, 2‐acetylfuran, etc., adding to the evidence that W5S, W1W, and W2W sensors were sensitive to nitrogen oxides, sulfur compounds, pyrazines, and aromatic components. Based on the findings, it is possible to conclude that E‐nose, in conjunction with chemometric pattern recognition methods, can be used to differentiate between different grades of ZAV based on volatile compounds.

Practical Applications

Different grades of Zhenjiang aromatic vinegar (ZAV) were distinguished by physical and chemical detection of total acid, nonvolatile acid, amino acid nitrogen and other indicators. In order to simplify the detection work, this study was to establish a rapid and feasible method for achieving ZAV grades differentiation according to their flavor volatile compounds. PCA of E‐nose data showed that the five grades of ZAV samples were well classified by the W5S, W1W, W2W, W1S, and W2S sensors. The correlation analysis results suggested that the response signal intensities of W5S, W1W, and W2W had significant positive correlations with the abundances of acetic acid, isobutyric acid, ethyl phenylacetate, 3‐hydroxy‐2‐butanone, etc., which adds to the proof that W5S, W1W, and W2W sensors were sensitive to nitrogen oxides, sulfur compounds, pyrazines and aromatic components. Therefore, E‐nose can be used as a rapid and nondestructive testing tool for quality measurements of ZAV.
Analysis of flood impacts on masonry structures and mitigation measures
Authors: Xiao Shiyun , Li Na , Guo Xiaoyang
Published: July 2021

The impact of floods can be devastating to buildings, especially in countries and villages in mountainous areas. Based on the flood impact risk analysis results, two methods are suggested by authors to improve the flood impact defense capability of rural buildings in this paper: increasing the strength of the mortar used in masonry structures, as well as adding reinforced concrete (RC) columns and circle beams to masonry structures. The impact of floods on the reinforced masonry structures is simulated numerically, and the failure process, stress, and deformation behaviors of masonry structures are analyzed. Compared to the computational results of normal masonry structures, the advantages of the two methods proposed in this manuscript are studied. Increasing the mortar strength slows the rate of damage to the masonry structure but does not improve the deformation or the failure behaviors. Increasing the mortar strength slightly decreases the first principal stress on the mortar and brick elements but has no effect on the third principal stress. Adding the RC frames not only delays the damage to the building and improves the failure behavior of the masonry structure but also decreases the first and third principle stresses of the brick and mortar elements.
Small sizes, big strategies: the relationship between female size, matrotrophy and superfetation throughout the reproductive lives of poeciliid fishes
Authors: Saleh‐Subaie N. , Johnson J. B. , Zúñiga‐Vega J. J.
Published: July 2021

In viviparous fishes, females of species that exhibit matrotrophy (post‐fertilization maternal provisioning to developing embryos) and superfetation (ability of females to bear simultaneously multiple broods of embryos at distinct developmental stages) increase less in mass and volume during pregnancy than females of species that lack these traits. Such a reduction in reproductive allocation may provide greater benefits to young and small females for two reasons. First, they could devote energy and resources to both growth and reproduction. Second, they could compensate for the space restrictions that are inherent to a small body size because both superfetation and matrotrophy maximize fecundity for any given ovarian volume. In this study, we test the hypothesis that both matrotrophy and superfetation will decrease over female reproductive lifespan (i.e. as they grow larger). We examined reproductive females from 77 populations of 13 species of the family Poeciliidae. Remarkably, we found support for the matrotrophy prediction in only three populations. As expected, in these populations, small females were more matrotrophic than larger females, which in turn exhibited a predominantly lecithotrophic strategy. In one population, we found the opposite pattern—the degree of matrotrophy actually increased in larger females. With respect to superfetation, none of the populations showed a pattern consistent with our prediction. In fact, in five populations the pattern was opposite to our expectation—larger females produced more simultaneous broods than smaller females. Our findings reveal that the degree of matrotrophy and superfetation can vary throughout the adult lifespans of poeciliid fishes, but such ontogenetic shifts are not common in natural populations.
35 Years on the Road from Research to Practice: A Review of Studies on Four Content Enhancement Routines for Inclusive Subject‐Area Classes, Part I
Authors: Schumaker Jean Bragg , Fisher Joseph B.
Published: July 2021

This article is the first part of a two‐part article focusing on the 35‐year journey of a team of researchers as they navigated the research‐to‐practice road related to the development of the Content Enhancement Routines, instructional routines to be used during inclusive subject‐area instruction. Part I tells the story of the first half of that journey and highlights the original validation research studies that were conducted on four Content Enhancement Routines: the Concept Mastery Routine, the Concept Comparison Routine, the Concept Anchoring Routine, and the Question Exploration Routine. Each study utilizes some type of experimental research design to determine the effects of teachers’ use of the routine on the test performance of subgroups of secondary students within inclusive classes. The subgroups included students with disabilities and students without disabilities—high achievers, normal achievers, and low achievers. In all of the studies, the students who participated in the instructional routine earned significantly higher test scores than students who participated in a standard lecture/discussion lesson. Additionally, where significant differences were found, the performance of each subgroup of students that participated in the instructional routine was significantly higher than the performance of their paired subgroup that participated in the lecture/discussion lesson.
Discordant Pleistocene population size histories in a guild of hymenopteran parasitoids
Authors: Walton William , Stone Graham N. , Lohse Konrad
Published: July 2021

Signatures of past changes in population size have been detected in genome‐wide variation in many species. However, the causes of such demographic changes and the extent to which they are shared across co‐distributed species remain poorly understood. During Pleistocene glacial maxima, many temperate European species were confined to southern refugia. While vicariance and range expansion processes associated with glacial cycles have been widely documented, it is unclear whether refugial populations of co‐distributed species have experienced shared histories of population size change. We analyse whole‐genome sequence data to reconstruct and compare demographic histories during the Quaternary for Iberian refuge populations in a single ecological guild (seven species of chalcid parasitoid wasps associated with oak cynipid galls). For four of these species, we find support for large changes in effective population size (Ne) through the Pleistocene that coincide with major climate events. However, there is little evidence that the timing, direction and magnitude of demographic change are shared across species, suggesting that demographic histories in this guild are largely idiosyncratic, even at the scale of a single glacial refugium.
Polar bear‐adapted Ursidibacter maritimus are remarkably conserved after generations in captivity
Authors: Espinosa‐Gongora Carmen , Hansen Mie Johanne , Bertelsen Mads Frost , Bojesen Anders Miki
Published: July 2021

Most species in the bacterial family of Pasteurellaceae colonize one specific host species. Vertebrates of very different evolutionary descent including fish, turtles, marsupials, eutherians and birds are colonized by different members of Pasteurellaceae. This one‐to‐one microbial‐host species partnership makes Pasteurellaceae species valuable candidates to study biodiversity, bacterial‐host co‐evolution and host adaptation, and their widespread distribution across vertebrates provide the possibility to collect a wide array of data, where wildlife species are essential. However, obtaining samples from wild animals comes with logistic, technical and ethical challenges, and previous microbiota studies have led to the presumption that captive animals are poor models for microbial studies in wildlife. Here, we show that colonization of polar bears by Ursidibacter maritimus is unaffected by factors related to captivity, reflecting a deep symbiotic bond to the host. We argue that the study of ecological and evolutionary principles in captive wildlife is possible for host‐adapted taxa such as those in the Pasteurellaceae family. Moreover, studying captive, often trained animals protects wild populations from the stress associated with obtaining samples.
RNA N6‐methyladenosine modification suppresses replication of rice black streaked dwarf virus and is associated with virus persistence in its insect vector
Authors: Tian Shuping , Wu Nan , Zhang Lu , Wang Xifeng
Published: July 2021

N6 methylation of adenosine (m6A) was recently discovered to play a role in regulating the life cycle of various viruses by modifying viral and host RNAs. However, different studies on m6A effects on the same or different viruses have revealed contradictory roles for m6A in the viral life cycle. In this study, we sought to define the role of m6A on infection by rice black streaked dwarf virus (RBSDV), a double‐stranded RNA virus, of its vector small brown planthopper (SBPH). Infection by RBSDV decreased the level of m6A in midgut cells of SBPHs. We then cloned two genes (LsMETTL3 and LsMETTL14) that encode m6A RNA methyltransferase in SBPHs. After interference with expression of the two genes, the titre of RBSDV in the midgut cells of SBPHs increased significantly, suggesting that m6A levels were negatively correlated with virus replication. More importantly, our results revealed that m6A modification might be the epigenetic mechanism that regulates RBSDV replication in its insect vector and maintains a certain virus threshold required for persistent transmission.
‘Something than which nothing greater can be thought’ and Kant'sEns Realissimum
Authors: Jackson Morgan Keith
Published: July 2021

In this paper, I explore Kant's much-studied critique of the ontological argument, seeking to place Immanuel Kant and Anselm of Canterbury more directly in contact with one another; I do this in two ways. First, I discuss the historical reception of the ontological argument in Kant's eighteenth century context. Second, I move the discussion away from the firstCritique, and look towards Kant's Pre-critical discussion of the ontological argument inThe Only Possible Argument, where he initially sets out his primary objection. By shifting the focus towards these areas of Kant's thought, I aim to achieve three interrelated goals. First, I show that Kant had a limited knowledge of the history and origins of the ontological argument, which was transmitted to him through Leibniz, Wolff, and Baumgarten, who put a Cartesian spin on it. Second, I provide textual evidence which shows that Kant's objection does not succeed against Anselm's argument. Third, I elucidate that Kant's identification of God as theens realissimumis compatible with Anselm's identification of God as ‘something than which nothing greater can be thought’.
Analysis of the response to two pharmacological protocols in patients with oral lichen planus: A randomized clinical trial
Authors: Polizzi Alessandro , Santonocito Simona , Lo Giudice Antonino , Alibrandi Angela , De Pasquale Rocco , Isola Gaetano
Published: July 2021

Objective

To evaluate the effectiveness of two different therapies on oral lichen planus (OLP) treatment through the analysis of OLP symptoms and signs and to analyze the risk of side effects related to the adopted protocols.

Methods

Thirty‐eight patients with OLP were selected according to van der Meij and van der Waal clinical and histopathological criteria. Through a randomized design, 19 patients received Tacrolimus 0.1% ointment (T group) and 19 an anti‐inflammatory mouthwash (M group) composed of calcium hydroxide 10%, hyaluronic acid 0.3%, umbelliferone, and oligomeric proanthocyanidins. The patients were examined on a regular basis for OLP symptoms, signs, and disease severity score changes over a 3‐month follow‐up period.

Results

Both treatments were effective in the reduction of OLP signs and symptoms. However, at 3 months (T3), in comparison with the M group, T group patients showed significantly lower mean values of OLP signs (p = 0.035), symptoms (p = 0.045), and disease severity scores (p = 0.041). Moreover, the Spearman test showed that there was a significant correlation between OLP signs and symptoms at each follow‐up session in all patients.

Conclusions

Both treatments demonstrated a significant approach to control OLP. However, tacrolimus determined a more effective improvement in OLP signs and symptoms compared to anti‐inflammatory mouthwash at 3‐month follow‐up.
Improved Perioperative Sleep Quality or Quantity Reduces Pain after Total Hip or Knee Arthroplasty: A Systematic Review and Meta‐Analysis
Authors: Shen Song‐po , Wang Ying‐jie , Zhang Qiang , Qiang Hua , Weng Xi‐sheng
Published: July 2021

Objective

To investigate the effects of improved perioperative sleep on pain, analgesic consumption, and postoperative nausea and vomiting (PONV) in patients who were undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Methods

Original studies published from 1 January 1970 to 30 September 2020 were queried in three unique databases using a common search term. The searches sought randomized controlled trials (RCT) investigating the effectiveness of sleep quality or quantity interventions for pain control early after TKA or THA. Grey literature was also searched by screening trial registers. There was no limitation on published language and patients. Two reviewers then assessed studies for eligibility. Eligible studies should have primary outcomes including perioperativeWe have comfirmed the edits. visual analogue scale (VAS) pain score and analgesic consumption; and secondary outcomes including side effects, such as PONV. Data extracted from the literature were abstracted into a comma‐separated database spreadsheet using Microsoft Excel. A meta‐analysis was then performed. Pooled statistics were calculated with weighting by inverse variance assuming a random effect model. I2 was calculated as a quantifier of heterogeneity and interpreted according to the Cochrane manual. All data analysis was performed using Revman software.

Results

From a total of 1285 potential records identified in the electronic search, six studies eventually fulfilled the eligibility criteria. The six controlled RCTs consisted of 207 patients in the sleep‐improving group and 209 patients in the control group. The severity of rest pain was significantly lower in the sleep‐improving group compared with the control group at day 1 and day 3 postoperatively; the severity of active pain was significantly lower in the sleep‐improving group compared with the control group at day 3 postoperatively. Data concerning analgesic drugs could not undergo a meta‐analysis due to the difference of eligible studies. No significant difference was found in the incidence of PONV between the sleep‐improving group and the control group.

Conclusion

Improved perioperative sleep, regardless of quality or quantity, could significantly reduce the pain level at the early stage after TKA or THA, thus the total amount of analgesic drugs consumed was decreased, without significant increase in the incidence of PONV.
Does bureaucratic representation enhance overall organizational accountability in policing?
Authors: Kang Seong C. , Chang Ahrum , Williams Brian N.
Published: July 2021

Many representative bureaucracy studies examine outcomes in the context of passive and active representation, but relatively few have investigated the effects of passive representation on outcomes for the organization as a whole. To address this gap, we analyze data from a national law enforcement survey in the United States on formal citizen complaints regarding allegations of excessive use of physical force. This measure aligns with a three‐dimensional accountability framework consisting of information, discussion, and consequences. The analysis finds that greater representation in lower‐level leadership is positively associated with a higher percentage of sustained citizen allegations of use of force, while representation in upper leadership generates mixed findings. The results contribute to the literature by highlighting the differential effects of representation in multiple leadership positions and by providing implications for overall organizational accountability.
Innovating the product innovation process to enable co‐creation
Authors: Roberts Deborah. L. , Palmer Roger , Hughes Mathew
Published: July 2021

Organizations now look beyond their boundaries to locate NPD resources among suppliers, lead users, customers, and consumers. Consumer involvement in an innovation process implies considerable changes in traditional innovation practice and management. Consumers become partners in co‐creation, a form of open innovation, and not mere objects of study. However, what is little known is how managers can innovate to enable co‐creation. This paper presents an in‐depth, single case study of a global confectionery brand and its multinational owner. We discuss the co‐creation process undertaken to innovate both the product and the innovation process itself. We propose a process for new product development and discuss changes implicit with its adoption.
Replanting life: ecological and human restoration
Authors: Marques de Abreu Alan Henrique , Makhlouta Alonso Jorge , da Silva Abel Elton Luis , Lima Filho Pedro , Pereira Reis Paulo Henrique , dos Santos Leles Paulo Sérgio
Published: July 2021

Brazil has one of the largest prison populations globally, with high occupancy and recidivism rates. The possibility of professional training and work while serving time can be decisive to avoid recidivism and promote the resocialization of former inmates. The Replanting Life Program (Programa Replantando Vida–PRV) employs, trains, and remunerates inmates to work in ecological restoration activities, including seed collection, production of forest tree seedlings, planting, and water resources management. This study assesses the PRV's environmental benefits between 2015 and 2019, along with prisoners' motivation and perception of personal changes after working with ecological restoration. Recidivism rates among the participants were also determined. Between 2015 and 2019, the PRV nurseries produced 1,014,960 seedlings and collected more than 3 tons of seeds from 248 Atlantic Forest species. The PRV promoted ecological restoration and environmental education in more than 60 municipalities of Rio de Janeiro state. During this period, 326 prisoners worked in the PRV with ecological restoration for at least a month. The primary motivation that led inmates to seek job opportunities in the PRV was the right to remission, followed by professional training. Among the benefits perceived by prisoners for their lives, the most mentioned were the increased sense of responsibility, professional training, and family appreciation. PRV participants that worked in ecological restoration activities had recidivism rates of 22%, which is lower than the national average. It is possible to conclude from the PRV experience that prison work in ecological restoration, associated with professional training and income generation, can promote environmental benefits, reduce recidivism, and humanize the prison system.
Longitudinal bidirectionality of emotion knowledge and inhibitory control in low‐income children using cross‐lagged panels
Authors: Farrell Carmen Brown , Gilpin Ansley Tullos
Published: July 2021

Understanding how to support children from low‐income families as they begin kindergarten is paramount, because they may have delays in developing cognitive and social skills in preschool, putting them at risk for poorer outcomes. Importantly, further research needs to be conducted on how specific constructs that relate to school readiness interact, such as inhibitory control (IC) and emotion knowledge (EK). Previous research has examined relations between IC and EK, but the directionality reported is inconsistent, and few studies have the longitudinal data necessary to assess the interaction fully. Thus, the present study (N = 539) aimed to expand previous research by assessing the directionality of the relationship over four time points using cross‐lagged panel models in a low‐income population. The results showed positive bidirectional relations between the two constructs from preschool to kindergarten, but not kindergarten to first grade, perhaps indicating a shift in these constructs’ interdependency to increased specificity. This study clarified the directionality of these related constructs from preschool into first grade, expanding previous research that focuses on this interaction primarily in the preschool years in samples of convenience. Implications for curricula and intervention for children from low‐income families are discussed.
A novel automated approach to rapid and precise in vivo measurement of hair morphometrics using a smartphone
Authors: Majd Ali , AlJasser Mohammed , Mirzaalian Hengameh , Shapiro Jerry , Hamarneh Ghassan , Lui Harvey , Santos Leopoldo Duailibe Nogueira , Chu Thomas , Lee Tim K.
Published: July 2021

Background

Although many hair disorders can be readily diagnosed based on their clinical appearance, their progression and response to treatment are often difficult to monitor, particularly in quantitative terms. We introduce an innovative technique utilizing a smartphone and computerized image analysis to expeditiously and automatically measure and compute hair density and diameter in patients in real time.

Methods

A smartphone equipped with a dermatoscope lens wirelessly transmits trichoscopy images to a computer for image processing. A black‐and‐white binary mask image representing hair and skin is produced, and the hairs are thinned into single‐pixel‐thick fiber skeletons. Further analysis based on these fibers allows morphometric characteristics such as hair shaft number and diameters to be computed rapidly. The hair‐bearing scalps of fifty participants were imaged to assess the precision of our automated smartphone‐based device in comparison with a specialized trichometry device for hair shaft density and diameter measurement. The precision and operation time of our technique relative to manual trichometry, which is commonly used by hair disorder specialists, is determined.

Results

An equivalence test, based on two 1‐sided t tests, demonstrates statistical equivalence in hair density and diameter values between this automated technique and manual trichometry within a 20% margin. On average, this technique actively required 24 seconds of the clinician's time whereas manual trichometry necessitated 9.2 minutes.

Conclusion

Automated smartphone‐based trichometry is a rapid, precise, and clinically feasible technique which can significantly facilitate the assessment and monitoring of hair loss. Its use could be easily integrated into clinical practice to improve standard trichoscopy.
Cryptic promoter activation occurs by at least two different mechanisms in the Arabidopsis genome
Authors: Kudo Hisayuki , Matsuo Mitsuhiro , Satoh Soichirou , Hata Takayuki , Hachisu Rei , Nakamura Masayuki , Yamamoto Yoshiharu Y. , Kimura Hiroshi , Matsui Minami , Obokata Junichi
Published: July 2021

In gene‐trap screening of plant genomes, promoterless reporter constructs are often expressed without trapping of annotated gene promoters. The molecular basis of this phenomenon, which has been interpreted as the trapping of cryptic promoters, is poorly understood. Here, we found that cryptic promoter activation occurs by at least two different mechanisms using Arabidopsis gene‐trap lines in which a firefly luciferase (LUC) open reading frame (ORF) without an apparent promoter sequence was expressed from intergenic regions: one mechanism is ‘cryptic promoter capturing’, in which the LUC ORF captured pre‐existing promoter‐like chromatin marked by H3K4me3 and H2A.Z, and the other is ‘promoter de novo origination’, in which the promoter chromatin was newly formed near the 5′ end of the inserted LUC ORF. The latter finding raises a question as to how the inserted LUC ORF sequence is involved in this phenomenon. To examine this, we performed a model experiment with chimeric LUC genes in transgenic plants. Using Arabidopsis psaH1 promoter–LUC constructs, we found that the functional core promoter region, where transcription start sites (TSSs) occur, cannot simply be determined by the upstream nor core promoter sequences; rather, its positioning proximal to the inserted LUC ORF sequence was more critical. This result suggests that the insertion of the coding sequence alters the local distribution of TSSs in the plant genome. The possible impact of the two types of cryptic promoter activation mechanisms on plant genome evolution and endosymbiotic gene transfer is discussed.
Genome assembly of the Chinese maize elite inbred line RP125 and its EMS mutant collection provide new resources for maize genetics research and crop improvement
Authors: Nie Shujun , Wang Bo , Ding Haiping , Lin Haijian , Zhang Li , Li Qigui , Wang Yujiao , Zhang Bin , Liang Anping , Zheng Qi , Wang Hui , Lv Huayang , Zhu Kun , Jia Minghui , Wang Xiaotong , Du Jiyuan , Zhao Runtai , Jiang Zhenzhen , Xia Caina , Qiao Zhenghao , Li Xiaohu , Liu Boyan , Zhu Hongbo , An Rong , Li Yucui , Jiang Qian , Chen Benfang , Zhang Hongkai , Wang Dening , Tang Changxiao , Yuan Yang , Dai Jie , Zhan Jing , He Weiqiang , Wang Xuebo , Shi Jian , Wang Bin , Gong Min , He Xiujing , Li Peng , Huang Li , Li Hui , Pan Chao , Huang Hong , Yuan Guangsheng , Lan Hai , Nie Yongxin , Li Xinzheng , Zhao Xiangyu , Zhang Xiansheng , Pan Guangtang , Wu Qingyu , Xu Fang , Zhang Zhiming
Published: July 2021

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan‐genome characterization. In this study, we generated a high‐quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long‐read sequencing and Hi‐C scaffolding, which yield highly contiguous, chromosome‐length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high‐quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: “missing a small part” in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis‐like cell death were detected in qk1 endosperm. Our study provides the community with a high‐quality genome sequence and a large collection of mutant germplasm.
Peri‐transfusion quality‐of‐life assessment for patients with myelodysplastic syndromes
Authors: Abel Gregory A. , Klepin Heidi D. , Magnavita Emily S. , Jaung Tim , Lu Wen , Shallis Rory M. , Hantel Andrew , Bahl Nupur E. , Dellinger‐Johnson Rebecca , Winer Eric S. , Zeidan Amer M.
Published: July 2021

Background

Many patients with myelodysplastic syndromes (MDS) receive red cell transfusions to relieve symptoms associated with anemia, with transfusions triggered by hemoglobin level. It is not known if patients' quality of life (QOL) improves after transfusion, nor if peri‐transfusion QOL assessment (PTQA) can guide future transfusion decisions.

Study Design and Methods

We conducted a prospective pilot study of adults with MDS at three centers. Participants, who had to have hemoglobin ≥7.5, completed an MDS‐specific measure of QOL (the Quality of Life in Myelodysplasia Scale, [QUALMS]) 1 day before and 7 days after red cell transfusion. A report was sent to each patient and provider before the next transfusion opportunity, indicating whether there were clinically significant changes in QOL. We assessed the proportion of patients experiencing changes in QOL, and with a follow‐up questionnaire, whether they perceived their PTQA data were used for future transfusion decisions.

Results

From 2018 to 2020, 62 patients enrolled (mean age 73 years) and 37 completed both pre‐ and post‐transfusion QOL assessments. Of these, 35% experienced a clinically significant increase in QUALMS score 7 days after transfusion; 46% no change; and 19% a decrease. Among those completing the follow‐up questionnaire, 23% reported that PTQA results were discussed by their provider when considering repeat transfusion.

Conclusions

These data suggest PTQA is feasible for patients with MDS. Moreover, while helpful for some, for many others, red cell transfusion may not achieve its intended goal of improving QOL. PTQA offers a strategy to inform shared decision‐making regarding red cell transfusion.
Canine junctional epidermolysis bullosa due to a novel mutation in LAMA3 with severe upper respiratory involvement
Authors: Herrmann Ina , Linder Keith E. , Meurs Kathryn M. , Friedenberg Steven G. , Cullen Jonah , Olby Natasha , Bizikova Petra
Published: July 2021

Background

Junctional epidermolysis bullosa (JEB) is a group of congenital blistering skin diseases characterized by clefting through the lamina lucida of the basement membrane zone.

Objectives

To characterize the clinical and morphological features of a congenital mechanobullous disease in a litter of puppies with severe upper respiratory involvement, and to identify an associated genetic variant.

Animals

Five of eight puppies in an Australian cattle dog cross‐bred litter showed signs of skin fragility. Three were stillborn and one died at one month of age. The two surviving puppies were presented with blistering skin disease and severe respiratory distress. Additionally, one unaffected sibling was examined and blood was obtained for genetic testing.

Methods and materials

Post‐mortem examination, histopathological evaluation and electron microscopy were performed. Whole genome sequencing (WGS) of one affected puppy was compared to a database of 522 dogs of 55 different breeds for variant analysis. Sanger sequencing of one additional affected and one unaffected sibling confirmed the variant.

Results

Clinically, severe mucocutaneous ulcers occurred in frictional areas with claw sloughing. Histopathological results revealed subepidermal clefts and electron microscopy confirmed the split in the lamina lucida. Post‐mortem examination documented extensive pharyngeal and laryngeal lesions with granulation tissue and fibrinous exudate obscuring the airway. Moderate tracheal hypoplasia contributed. The WGS revealed a novel missense variant in the laminin α3‐chain XP_537297.2p(Asp2867Val), with an autosomal recessive mode of inheritance.

Conclusions and clinical relevance

A novel variant in LAMA3 caused a generalized and severe phenotype of JEB with an unique clinical presentation of upper airway obstruction.