bluuebunny/crossref_metadata_2025 huggingface dataset:
Allelic variation in HLA‐DRB1 is associated with development of antidrug antibodies in cancer patients treated with atezolizumab that are neutralizing in vitro
Authors: Hammer Christian , Ruppel Jane , Kamen Lynn , Hunkapiller Julie , Mellman Ira , Quarmby Valerie
Published: March 2022

The treatment of diseases with biologic agents can result in the formation of antidrug antibodies (ADA). Although drivers for ADA formation are unknown, a role for antigen presentation is likely, and variation in human leukocyte antigen (HLA) genes has been shown to be associated with occurrence of ADA for several biologics. Here, we performed an HLA‐wide association study in 1982 patients treated with the anti‐PD‐L1 antibody atezolizumab across eight clinical trials. On average, 29.8% of patients were ADA‐positive (N = 591, range of 13.5%–38.4% per study) and 14.6% of patients were positive for ADA that were neutralizing in vitro (neutralizing antibodies [NAb], N = 278, range of 6.4%–21.9% per study). In a meta‐analysis of logistic regression coefficients, we found statistically significant associations between HLA class II alleles and ADA status. The top‐associated alleles were HLA‐DRB1*01:01 in a comparison of ADA‐positive versus ADA‐negative patients (p = 3.4 × 10−5, odds ratio [OR] 1.96, 95% confidence interval [95% CI] 1.64–2.28) and HLA‐DQA1*01:01 when comparing NAb‐positive with ADA‐negative patients (p = 2.8 × 10−7, OR 2.31, 95% CI 1.98–2.66). Both alleles occur together on a common HLA haplotype, and analyses considering only NAb‐negative, ADA‐positive patients did not yield significant results, suggesting that the genetic association is mainly driven by NAb status. In conclusion, our study showed that HLA class II genotype is associated with the risk of developing ADA, and specifically NAb, in patients treated with atezolizumab, but the effect estimates suggest that immunogenetic factors are not sufficient as clinically meaningful predictors.
Dental students' knowledge and reporting of child maltreatment: Where are we at today both here and abroad?
Authors: Ivanoff Chris S. , Andonov Bogomil , Hottel Timothy L.
Published: March 2022

Introduction

The study investigates whether suspected child abuse/neglect (SCAN) training in dental school has increased dental student SCAN knowledge and, consequently, reporting.

Materials and Methods

A 25‐question survey used to assess for SCAN knowledge in 2006 was readministered to a group of dental students at one US dental school in St. Louis, MO, which has integrated SCAN training into its curriculum for at least 3 years, and one dental school in Plovdiv, Bulgaria, which has not integrated SCAN training as a control.

Results

Of 16 questions assessing for SCAN knowledge, group US students answered 14 questions correctly and performed better than US students surveyed in 2006. By comparison, group Bulgaria students with no SCAN training answered 15 questions correctly. When asked what their legal responsibilities were concerning SCAN, 96.4% of group US students knew they were required to report, whilst only half of group Bulgaria (48.9%) responded correctly. The results suggest that integrating SCAN training into the curriculum is effective in conveying this important message. However, in a question asking students whether they encountered a child at dental school who they suspected was the victim of child maltreatment and if so, how did they act, there were no indications that students at either school made any reports as the question was either answered “no” or left blank. The number of SCAN cases reported by campus authorities was also zero.

Conclusion

The results suggest that classroom training in SCAN is not motivating students to report SCAN at their dental school, despite increased knowledge.
Ketamine and sleep modulate neural complexity dynamics in cats
Authors: Pascovich Claudia , Castro‐Zaballa Santiago , Mediano Pedro A. M. , Bor Daniel , Canales‐Johnson Andrés , Torterolo Pablo , Bekinschtein Tristan A.
Published: March 2022

There is increasing evidence that the level of consciousness can be captured by neural informational complexity: for instance, complexity, as measured by the Lempel Ziv (LZ) compression algorithm, decreases during anaesthesia and non‐rapid eye movement (NREM) sleep in humans and rats, when compared with LZ in awake and REM sleep. In contrast, LZ is higher in humans under the effect of psychedelics, including subanaesthetic doses of ketamine. However, it is both unclear how this result would be modulated by varying ketamine doses, and whether it would extend to other species. Here, we studied LZ with and without auditory stimulation during wakefulness and different sleep stages in five cats implanted with intracranial electrodes, as well as under subanaesthetic doses of ketamine (5, 10, and 15 mg/kg i.m.). In line with previous results, LZ was lowest in NREM sleep, but similar in REM and wakefulness. Furthermore, we found an inverted U‐shaped curve following different levels of ketamine doses in a subset of electrodes, primarily in prefrontal cortex. However, it is worth noting that the variability in the ketamine dose–response curve across cats and cortices was larger than that in the sleep‐stage data, highlighting the differential local dynamics created by two different ways of modulating conscious state. These results replicate previous findings, both in humans and other species, demonstrating that neural complexity is highly sensitive to capture state changes between wake and sleep stages while adding a local cortical description. Finally, this study describes the differential effects of ketamine doses, replicating a rise in complexity for low doses, and further fall as doses approach anaesthetic levels in a differential manner depending on the cortex.
Pandemic restrictions in Ethiopia: Impact on family law cases in Amhara regional state courts
Authors: Getnet Asnakech
Published: March 2022

This article discusses the impact of pandemic restrictions on the family court system in Ethiopia. As lack of technological infrastructure made shifting to online services impossible, court services remained in‐person. Public health measures required a drastic reduction in case hearings in order to allow social distancing. Both federal and regional state courts were partially closed from early March 2020 to end of September 2020 and only entertained cases of “urgent” nature that affected life, liberty, and public safety. The article focuses on strategies adopted by family courts in Amhara Regional State with respect to its impacts on litigating parties in such courts. It argues partial closure of court services disrupted access to justice in family law cases and increased vulnerability of women and children. This article proposes alternative strategies other than partial closure of court services.
The development of L2 interactional competence in Arabic: The case of multiple requests
Authors: Al‐Gahtani Saad
Published: March 2022

This study explored the development of L2 learners' interactional competence in Arabic when making requests. Combining a longitudinal and cross‐sectional design, it closely examined how learners' language proficiency affected their use of multiple requests in daily‐life interactions. Participants included L2 learners (n = 40) and Saudi Arabic native speakers (NSs) (n = 10). L2 learners were evenly divided into two groups (low‐level and high‐level). They each completed three interactive role‐plays in Phase 1 and three similar scenarios in Phase 2 6 months later. The findings showed that multiple requests can be vertically (e repair) and horizontally (i.e., recapitulation) organized in the talk. Multiple requests in a vertical arrangement occurred due to L2 learners' violation of sequence organization rules. L2 learners with lower proficiency levels were more likely to make multiple requests vertically. However, as their proficiency improved, their use of vertically arranged multiple requests reduced. On the other hand, multiple requests in a horizontal arrangement occurred with increasing L2 learners' linguistic and interactional competence. At native‐like linguistic and interactional competence levels, L2 learners tended to decrease this interactional practice and adhered firmly to turn‐taking and adjacency pair rules. Furthermore, it was found that L2 learners, no matter what their proficiency level, relied heavily on Modern Standard Arabic (MSA) while Arabic NSs tended to use the Saudi dialect. Therefore, it was concluded that learners' proficiency plays a crucial role in the production of multiple requests in interaction and their reliance on MSA in daily interactions reflects their incomplete pragmatic competence.
Cost Comparison of Soil Vapor Extraction and Subslab Depressurization for Vapor Intrusion Mitigation
Authors: Lutes Christopher , Stewart Lloyd , Truesdale Robert , De Loera Jose , Zimmerman John H. , Schumacher Brian
Published: March 2022

Soil vapor extraction (SVE) can be applied for remediation, and also as an alternative to sub‐slab depressurization (SSD) for vapor intrusion (VI) mitigation. This study compares capital, operation, and treatment costs of SVE and SSD systems using data collected during a multi‐year demonstration project conducted at eight buildings in an urban setting. The capital cost of the SVE system is substantially less than the estimated total capital cost of individual SSD systems. The SVE operating costs are higher, especially in the early operating years when it is being operated for mass removal and treatment. As a result, the cumulative SVE system cost rises above that of the SSD systems in the sixth year of operation. A significant portion of the operations and maintenance cost advantage of the SSD systems comes from the assumption that off‐gas treatment is not required. Alternative cases show SVE costs are likely to be lower in scenarios where numerous small buildings requiring independent SSD systems overlie the SVE zone of influence. Conversely, SSD systems are less costly for cases with few small buildings overlying the SVE zone of influence. An additional benefit of SVE is continued mass removal. In a situation where an existing SVE can be repurposed for VI protection from residual volatile organic carbon (VOC) mass, the SVE cumulative costs over 30 years can remain lower than the cost of installing and operating SSD systems in multiple buildings.
Arthropod populations in a sub‐arctic environment facing climate change over a half‐century: variability but no general trend
Authors: Andersson Göran , von Proschwitz Ted , Fägerström Christoffer , Green Martin , Smith Henrik G. , Lindström Åke
Published: March 2022

Dramatic declines of some arthropod populations have recently received a lot of attention. Identified declines have mainly been attributed to changes in agriculture, climate, pathogen prevalence and light pollution, as well as cross‐regional effects of, e.g., drifting pesticides. However, the overall picture is complex and debated, and there is a need for systematically collected long‐term data, not least from areas relatively unaffected by humans.

We monitored the abundance of arthropods (mainly insects) in subalpine birch forest in Swedish Lapland over a period of 53 years (1968–2020), in an area comparatively unaffected by human activities. Arthropod abundance was assessed by yearly systematic counts on 24,000 birch shoots, in the second half of June. Animals were categorised into 17 different groups directly upon counting, dependent on taxonomy and life stage (imago, larva).

Overall, there was no significant change in arthropod numbers. Nor did estimates of the total biomass of arthropods (using group‐specific indices of the mass of individuals) show any significant trend.

Accordingly, there are no signs that the arthropod abundance or biomass on birch in this subarctic study site has gone through the same declines as have been reported from sites in other habitats. The reason may be that the impact of factors identified worldwide as drivers of arthropod declines so far are small or non‐existent because of the low human population density in this area.
Improvement of microwave dielectric properties of the LiNb0.6Ti0.5O3 M‐phase by doping with (Co1/3Nb2/3)4+
Authors: Wang Hang , Li Yumin M. , Zheng Liang , Bian Jianjiang
Published: March 2022

Structural evolution and microwave dielectric properties of LiNb0.6(Ti1‐x[Co1/3Nb2/3]x)0.5O3 (.05≤x≤.2) ceramics have been studied in this paper. Although the doped compositions maintain the M‐phase solid solutions, compositional fluctuation due to nonuniform dispersion of minor dopants could be observed as x < .05, and trace amount of Li2TiO3‐based solid solution (Li2TiO3ss) secondary phase presents in the x > .05 compositions. The microwave dielectric properties could be remarkably improved by the doping of (Co1/2Nb1/2)4+ in comparison to the undoped counterpart. Optimized microwave dielectric properties with Q × f = ∼6500 GHz, εr = ∼74 and τf = +8.2 ppm/°C could be obtained at x = .10 after sintering at 1050°C/2 h. The sintering temperature could be further reduced to 900°C/2 h by adding .2 wt% B2O3 without affecting significantly its microwave dielectric properties: εr = 73, Q × f = 6000 GHz, τf = +8.5 ppm/°C. The LiNb0.6(Ti1‐x[Co1/3Nb2/3]x)0.5O3 ceramics obtained in this case exhibit large dielectric permittivity coupled with much improved Q × f values, near zero τf, and low sintering temperature simultaneously, which makes it a promising high‐k microwave dielectric material for low temperature cofired ceramic applications.
I‐sharing across the aisle: Can shared subjective experience bridge the political divide?
Authors: Pinel Elizabeth C. , Fuchs Natalie A. , Benjamin Shania
Published: March 2022

The U.S. witnessed deep ideological rifts during the 2020 presidential election, with reverberations that continue to this day. Both the media reports and the research evidence reveal the passion with which people cling to their ideologies and the barriers to communication that people often erect between themselves and those who do not share their political viewpoints. Consider the insurrection at the U.S. Capitol in January 6, 2021, as an historical example of the vilification and disrespect that people express toward those with different viewpoints from their own. Here we test whether moments of shared subjective experience (i.e., I‐sharing) can facilitate liking for politically different others, as well as more productive dialogue across political lines. Drawing from previous work on the intergroup implications of I‐sharing, we predicted and found that I‐sharing increased liking for one’s interaction partner, irrespective of one’s own political preferences and irrespective whether one’s interaction partner shares those political preferences. In addition, I‐sharing (relative to not I‐sharing) promoted a greater sense among Biden supporters that they could have a productive dialogue with Trump supporters, although the parallel effect did not hold true for Trump supporters. The results point to the possibility that moments of I‐sharing can get people with differing political views to, as Biden put it so simply on November seventh, 2020, “listen to each other again.”
Acquisition of false certainty: Learners increase their confidence in the correctness of incorrect answers after online information search
Authors: von Hoyer Johannes F. , Kimmerle Joachim , Holtz Peter
Published: March 2022

Background

Explorative online information search activities are self‐regulated learning processes that require monitoring in the form of accurate metacognitive judgments about one's own knowledge. People have to judge what they know, but also understand what they do not know. Previous research has explored those two aspects in relation to each other mostly by employing measures of metacognitive calibration and points toward a potential detrimental effect of using the internet to answer knowledge test items.

Objectives

This research aimed to disentangle those two aspects of knowledge and to describe a false certainty effect (FaCE), indicating an increase in confidence in the correctness of incorrect responses in a knowledge test after online information search. We also aimed to further explore the conditions under which this effect occurs.

Methods

In two studies participants’ knowledge and on‐item confidence ratings were measured before and after a short online information search activity. In Study 1, we analyzed data of two samples with and without knowledge gain. In Study 2, we manipulated the familiarity of knowledge test items and whether there was an information search activity.

Results

Study 1 showed that false certainty occurred even when a search activity did not lead to any learning success. This FaCE, however, was stronger when there was actual knowledge gain. In Study 2, we found that the effect was caused by the information search activity itself and not by the pre‐post methodology of identical knowledge‐test items.

Implications

Our results demonstrate the emergence of increased confidence in the correctness of incorrect responses in knowledge tests after online information search activities. Educators and researchers should be aware of this undesired false certainty effect of computer‐assisted learning on individuals’ knowledge monitoring.
Association between bleeding periodontal pockets and eczemas: Results of the Northern Finland Birth Cohort 1966
Authors: Tursas Larissa , Ylipalosaari Merja , Sinikumpu Suvi‐Päivikki , Huilaja Laura , Tasanen Kaisa , Tiisanoja Antti , Tegelberg Paula , Ylöstalo Pekka , Syrjälä Anna‐Maija
Published: March 2022

Aim

To investigate whether the periodontal condition as measured by bleeding periodontal pockets is associated with atopic dermatitis, seborrheic dermatitis, and eczema nummulare.

Materials and Methods

The study population (n = 1871) was obtained from the 46‐year follow‐up study of the Northern Finland Birth Cohort 1966 study (NFBC1966). The periodontal condition was measured by the number of sites with bleeding periodontal pockets that were ≥4 mm deep. The whole skin of the participants was clinically examined, and diagnoses of skin diseases were made according to the International Classification of Diseases. Prevalence rate ratios (PRR) and 95% confidence intervals (95% CIs) were estimated using Poisson regression models with robust error variance.

Results

In this cohort, comprising 46‐year‐old participants of NFBC1966, the presence of 1–3 and ≥4 bleeding‐deepened periodontal pockets (≥4 mm deep) were associated with seborrheic dermatitis (PRR 1.9, 95% CI: 1.3–2.8 and PRR 2.2, 95% CI: 1.4–3.3, respectively) and with eczema nummulare (PRR 1.7, 95% CI: 0.9–3.1 and PRR 1.7, 95% CI: 0.9–3.3, respectively). For non‐smokers, the corresponding estimates were 1.7 for seborrheic dermatitis (95% CI: 1.1–2.6) and 1.8 (95% CI: 1.1–3.1) and 1.4 for eczema nummulare (95% CI: 0.7–2.9) and 1.2 (95% CI: 0.5–2.9), respectively. No association was found between bleeding‐deepened periodontal pockets and atopic dermatitis. Further adjustments for C‐reactive protein, diabetes, and inflammatory diseases did not essentially change the risk estimates among either the total population or the non‐smokers.

Conclusion

Bleeding periodontal pockets appeared to be associated with the presence of seborrheic dermatitis and eczema nummulare.
Trends of severe hypoglycemia in patients with type 2 diabetes in Korea: A longitudinal nationwide cohort study
Authors: Yun Jae‐Seung , Han Kyungdo , Ko Seung‐Hyun
Published: March 2022

To estimate the trends in the prevalence of severe hypoglycemia (SH) in patients with type 2 diabetes in Korea, we investigated the total number of SH episodes among type 2 diabetes patients aged ≥30 years who visited the emergency department between 2002 and 2019, using the Korean National Health Insurance Service database. The prevalence of SH events increased from 2002 to 2012; however, it has decreased gradually since 2012. In 2019, the prevalence of SH was 0.6%, with an incidence rate of 4.43 per 1,000 person‐years. Approximately 23,000 SH events occur every year in Korea. Although the incidence is steadily decreasing, there are a considerable number of SH events in type 2 diabetes patients. The decline in the incidence of SH seems to most likely be due to the increased prescription rate of hypoglycemic agents without hypoglycemia risk, less‐strict treatment goals and the individualization of therapy.
The beyond the gap filling approach: Modeling facial and interproximal tissues and improving esthetics for anterior flapless immediate implant placement
Authors: Tosta Mauro , Fahl Newton , Chambrone Leandro , Duarte Wagner
Published: March 2022

Objective

Maintenance of adequate interproximal tissue height between an implant and a natural tooth or between adjacent implants represents an esthetic challenge in implant dentistry. The aim of this case report is to describe a modified technique referred to as the beyond the gap filling (BGF) approach designed to improve the horizontal and vertical components of the facial aspect and particularly the height of interproximal bone peaks around immediately placed implants into fresh extraction sockets.

Clinical Considerations

Four patients (five teeth) requiring anterior tooth extraction were treated with the BGF approach that included: (a) minimally traumatic tooth extraction; (b) immediate implant placement without flap elevation; (c) installation of a narrow profile healing abutment to protect the implant during grafting; (d) grafting with a construct with 90% bovine bone granules and 10% porcine collagen packed coronally to the facial and interproximal bone walls above the level of the bone crest; and (e) delivery of an immediate restoration.

Conclusions

The current report suggests that the level/height of the interproximal bone crests between an implant and a natural tooth or between two adjacent implants can be improved by the BGF approach and, consequently, papilla height can be maintained in cases with a high risk of papilla height collapse and, consequently, esthetic outcomes can be maximized.

Clinical Significance

The BGF is a simple technique to be used by clinicians to prevent significant papilla collapse in anterior immediate implants and consequently achieve maximum esthetic outcomes in implant dentistry.
Impact of maturity on mechanical and textural properties and rheological properties modeling of wood apple fruit (Limonia acidissima)
Authors: Murakonda Sahithi , Dwivedi Madhuresh
Published: March 2022

Wood apple (Limonia acidissima) is monsoonal fruit comprising of pulp with an exterior hard shell. The investigation of mechanical and textural properties according to maturity stages (unripe, semi‐ripe, and ripe) and rheological modeling of ripe fruits is beneficial for post‐harvest maturity grader and processing equipment development. The compression mechanical properties of whole fruit at maturity stages along the x‐axis, y‐axis, and z‐axis orientations recorded minimum rupture force (962.73 N) for ripe fruits followed by semi‐ripe and unripe along z‐axis and maximum force (2,256.2 N) for unripe fruits along y‐axis. The pulp puncture test at maturity stages for textural properties recorded reduced hardness value with maturity having 12.84, 4.30, and 3.88 N for unripe, semi‐ripe, and ripe fruits, respectively. The rheological properties for ripe fruits pulp validated cross and Carreau‐Yasuda best‐fit models (R2 = 0.9) for steady shear indicating non‐Newtonian, shear‐thinning behavior as viscosity (η) reduced from 1,508.45 Pa s while dynamic shear for frequency sweep test indicated elastic behavior as storage modulus G′ > loss modulus G″ and tan δ < 1 for power model (R2 = 0.9). The mechanical and textural properties of wood apple exhibited significant variance according to the maturity of the fruit.

Practical Applications

Wood apple, despite being underutilized in the global fruit trade, has vast application in nutraceuticals industries. The steady shear flow properties of wood apple pulp can be used in engineering design applications such as manufacturing, packaging, and storage; they can be utilized to determine flow parameters and predict the degree of structural breakdown with shear. Because of the numerous processing systems in use, it is essential to precisely forecast rheological behavior. Oscillatory experiments of wood apple pulp can be used to study pulp structure, the strength of pulp and dependency on the shear rate of pulp. The findings of this study will substantially assist food processing industries in producing wood apple pulp‐based products.
Vaginal misoprostol and intravenous oxytocin for success of termination in the second‐trimester intrauterine fetal demise: A randomized controlled clinical trial
Authors: Asadi Nasrin , Vafaei Homeira , Hessami Kamaran , Darabi Mohammad Hasan , Kasraeian Maryam , Faraji Azam , Alavi Azin , Abdi Nazanin , Gissuei Atena , Roozmeh Shohre , Bazrafshan Khadije , Gharibpour Fereshteh
Published: March 2022

Aim

To compare the success rate of vaginal misoprostol versus intravenous (IV) oxytocin in termination of pregnancy in the second trimester intrauterine fetal death (IUFD).

Methods

This was an open‐label randomized controlled study for 106 women with second trimester IUFD. Patients were randomly divided into two groups: women given vaginal misoprostol (400 mcg every 6 h up to 48 h) versus those given IV oxytocin (starting with 50 units up to a maximum of 300 units). When the first‐line treatment (as mentioned above) failed, treatment methods were replaced with each other. When the second‐line treatment failed, the patients underwent dilation and evacuation.

Results

The first‐line treatment yielded the successful rate of 88.7% versus 73.7% for misoprostol versus oxytocin, respectively (p = 0.047). Among those with first‐line treatment failure, the second‐line treatment yielded success rate of 85.7% versus 83.3% for misoprostol versus oxytocin (p = 0.891). The mean duration of induction to delivery in women with successful response to first‐line treatment was 28.72 and 20.55 h after initially receiving misoprostol versus oxytocin, respectively (p < 0.001). While during second‐line treatment, this mean interval was not significantly different among those with misoprostol versus oxytocin (p = 0.128). No severe adverse events were observed.

Conclusion

Vaginal misoprostol was associated with higher termination rate than oxytocin without adverse events when used as the first‐line treatment. Both methods yielded the same success rate when used as the second‐line treatment.
General Versus Vocational Education in High School: Cross‐Sectional Associations with Student's Health
Authors: Coledam Diogo Henrique Constantino , Frotta Beatriz Marinho , Ré Alessandro Hervaldo Nicolai
Published: March 2022

BACKGROUND

The aim of the present study was to analyze the association between course type and health among high school students.

METHODS

A cross‐sectional study with 675 Brazilian high school students. The independent variable was course type (general or vocational) and dependent variables were health characteristics. All information was obtained by a self‐report questionnaire and the following health characteristics were analyzed: mental health, physical activity, sedentary behavior, food consumption, daytime sleepiness, tobacco use, alcohol consumption, aggression, and musculoskeletal symptoms. The prevalence ratio (PR) was estimated by Poisson regression.

RESULTS

Vocational students presented a higher prevalence in 7 of the 20 mental health symptoms analyzed (PR = 1.21‐1.64), daytime sleepiness (PR = 1.39‐1.71), and musculoskeletal symptoms in neck, shoulders, low back, and knees (PR = 1.31‐1.41), and a lower likelihood of being physically active (PR = 0.59‐0.70). Conversely, vocational students showed lower sedentary behavior on TV and videogames during the week (PR = 0.35‐0.46), consumption of snacks, cookies, and crackers (PR = 0.56‐0.72), and experiences of aggression (PR = 0.13‐0.17), all P < .05.

CONCLUSIONS

High school can affect students' health distinctly, indicating that intervention programs and health monitoring should be specific to course type.
Detection of orthotospoviruses in medicinal plants in China
Authors: Wang Zhe , Song Xuhong , Anane Rex Frimpong , Chen Lu , Chen Zeli , Gao Like , Li Shangyun , Wen Guosong , Zhao Mingfu
Published: March 2022

The genus Orthotospovirus contains a variety of viruses that infect more than 1000 plant species of 82 families. Nine medicinal plant species were found to exhibit symptoms that are typical of plant viral infections. Foliar samples of diseased plants were taken, and double‐antibody sandwich ELISA (DAS‐ELISA) and reverse transcription polymerase chain reaction (RT‐PCR) analyses were used to detect the viruses in the diseased plants. The results revealed that Capsicum chlorosis orthotospovirus (CaCV) was present in Salvia miltiorrhiza and Valeriana jatamansi. Impatiens necrotic spot orthotospovirus (INSV) was identified in Plantago asiatica, Scrophularia ningpoensis and Iris tectorum. Tomato spotted wilt orthotospovirus (TSWV) was detected in Perilla frutescens, while Tomato zonate spot orthotospovirus (TZSV) was found in Codonopsis spp., Marsdenia tenacissima and Dipsacus asper. Phylogenetic tree analysis also reflected the high consistency of sequences. To our knowledge, this is the first report of CaCV in Salvia miltiorrhiza and Valeriana jatamansi and INSV in Plantago asiatica, Scrophularia ningpoensis and Iris tectorum. This is also the first report of TSWV infecting Perilla frutescens and TZSV infecting Codonopsis spp., Marsdenia tenacissima and Dipsacus asper.
Midwest rural‐urban disparities in use of patient online services for COVID‐19
Authors: Huang Ming , Wen Andrew , He Huan , Wang Liwei , Liu Sijia , Wang Yanshan , Zong Nansu , Yu Yue , Prigge Julie E. , Costello Brian A. , Shah Nilay D. , Ting Henry H. , Doubeni Chyke , Fan Jung‐Wei , Liu Hongfang , Patten Christi A.
Published: March 2022

Purpose

Rural populations are disproportionately affected by the COVID‐19 pandemic. We characterized urban‐rural disparities in patient portal messaging utilization for COVID‐19, and, of those who used the portal during its early stage in the Midwest.

Methods

We collected over 1 million portal messages generated by midwestern Mayo Clinic patients from February to August 2020. We analyzed patient‐generated messages (PGMs) on COVID‐19 by urban‐rural locality and incorporated patients’ sociodemographic factors into the analysis.

Findings

The urban‐rural ratio of portal users, message senders, and COVID‐19 message senders was 1.18, 1.31, and 1.79, indicating greater use among urban patients. The urban‐rural ratio (1.69) of PGMs on COVID‐19 was higher than that (1.43) of general PGMs. The urban‐rural ratios of messaging were 1.72‐1.85 for COVID‐19‐related care and 1.43‐1.66 for other health care issues on COVID‐19. Compared with urban patients, rural patients sent fewer messages for COVID‐19 diagnosis and treatment but more messages for other reasons related to COVID‐19‐related health care (eg, isolation and anxiety). The frequent senders of COVID‐19‐related messages among rural patients were 40+ years old, women, married, and White.

Conclusions

In this Midwest health system, rural patients were less likely to use patient online services during a pandemic and their reasons for its use differ from urban patients. Results suggest opportunities for increasing equity in rural patient engagement in patient portals (in particular, minority populations) for COVID‐19. Public health intervention strategies could target reasons why rural patients might seek health care in a pandemic, such as social isolation and anxiety.
Virtual approach of the aesthetical fit between hair colours and skin tones in women of different ethnical origin backgrounds
Authors: Galliano Anthony , Guerin Myriam , Lambert Valerie , Favrot Ioanna , Seneca David , Lequeux Fabien , Flament Frédéric , Sleurs Anna , Foster Berkly , Phung Edmund , Lee Kyung Moon , Houghton Jeff
Published: March 2022

Objective

To determine the aesthetical accordance between a given skin tone and the 11 possible colours of head hairs, covered by a marketed hair colouration product.

Material and methods

The photographs of professional top models, representing several ancestries (non‐Hispanic European and Euro–American, East Asian, Hispanic Euro–American, and African–American ancestries), were used to virtually modify skin tones (from light, medium to dark) and hair colour by an artificial intelligence (AI)‐based algorithm. Hence, 117 modified photographs were then assessed by five local panels of about 60 women each (one in China, one in France and three in US). The same questionnaire was given to the panels, written in their own language, asking which and how both skin tones and hair colours fit preferentially (or not appreciated), asking in addition the reasons of their choices, using fixed wordings.

Results

Answers from the five panels differed according to origin or cultural aspects, although some agreements were found among both non‐Hispanic European and Euro‐American groups. The Hispanic American panel in US globally much appreciated darker hair tones (HTs). Two panels (East Asian in China and African American in US) and part of non‐Hispanic European panel in France declared appreciating all HTs, almost irrespective with the skin tone (light, medium and dark). This surprising result is very likely caused by gradings (in %) that differ by too low values, making the establishment of a decisive or significant assessment. By nature highly subjective (culturally and/or fashion driven), the assessments should be more viewed as trends, an unavoidable limit of the present virtual approach. The latter offers nevertheless a full respect of ethical rules as such objective could hardly be conducted in vivo: applying 10 or 11 hair colourations on the same individual is an unthinkable option.

Conclusion

The virtual approach developed in the present study that mixes two major facial coloured phenotypes seems at the crossroad of both genetic backgrounds and the secular desire of a modified appearance. Nonetheless, this methodology could afford, at the individual level in total confidentiality, a great help to subjects exposed to some facial skin disorders or afflictions.
A novel HLA‐A null allele, HLA‐A*31:188N, identified by next‐generation sequencing in a Chinese individual
Authors: Gao Su‐Qing
Published: March 2022

The HLA‐A*31:188N allele differs from A*31:01:02:01 by a single nucleotide deletion in exon 3.
Loss of intermediate filament IFB‐1 reduces mobility, density, and physiological function of mitochondria in Caenorhabditis elegans sensory neurons
Authors: Barmaver Syed Nooruzuha , Muthaiyan Shanmugam Muniesh , Chang Yen , Bayansan Odvogmed , Bhan Prerana , Wu Gong‐Her , Wagner Oliver I.
Published: March 2022

Mitochondria and intermediate filament (IF) accumulations often occur during imbalanced axonal transport leading to various types of neurological diseases. It is still poorly understood whether a link between neuronal IFs and mitochondrial mobility exist. In Caenorhabditis elegans, among the 11 cytoplasmic IF family proteins, IFB‐1 is of particular interest as it is expressed in a subset of sensory neurons. Depletion of IFB‐1 leads to mild dye‐filling and significant chemotaxis defects as well as reduced life span. Sensory neuron development is affected and mitochondrial transport is slowed down leading to reduced densities of these organelles. Mitochondria tend to cluster in neurons of IFB‐1 mutants likely independent of the fission and fusion machinery. Oxygen consumption and mitochondrial membrane potential is measurably reduced in worms carrying mutations in the ifb‐1 gene. Membrane potential also seems to play a role in transport such as carbonyl cyanide p‐(trifluoromethoxy)phenylhydrazone treatment led to increased directional switching of mitochondria. Mitochondria co‐localize with IFB‐1 in worm neurons and appear in a complex with IFB‐1 in pull‐down assays. In summary, we propose a model in which neuronal IFs may serve as critical (transient) anchor points for mitochondria during their long‐range transport in neurons for steady and balanced transport.
Chronic superphysiologic AMH promotes premature luteinization of antral follicles in human ovarian xenografts
Authors: Man Limor , Lustgarten Guahmich Nicole , Kallinos Eleni , Caiazza Barbara , Khan Monica , Liu Zong-Ying , Patel Ritaben , Torres Carmen , Pepin David , Yang He S. , Bodine Richard , Zaninovic Nikica , Schattman Glenn , Rosenwaks Zev , James Daylon
Published: March 2022

Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and provides a diagnostic measure of reproductive reserve in women; however, the impact of AMH on folliculogenesis is poorly understood. We cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and downstream single-cell RNA sequencing of granulosa and theca/stroma cell fractions. A total of 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals (>10 weeks). In the context of exogenous AMH, follicles exhibited a decreased ratio of primordial to growing follicles and antral follicles of increased diameter. Transcriptomic analysis and immunolabeling revealed a marked increase in factors typically noted at more advanced stages of follicle maturation, with granulosa and theca/stroma cells also displaying molecular hallmarks of luteinization. These results suggest that superphysiologic AMH alone may contribute to ovulatory dysfunction by accelerating maturation and/or luteinization of antral-stage follicles.
KLF15 cistromes reveal a hepatocyte pathway governing plasma corticosteroid transport and systemic inflammation
Authors: Jiang Zhen , Elsarrag Selma Z. , Duan Qiming , LaGory Edward L. , Wang Zhe , Alexanian Michael , McMahon Sarah , Rulifson Ingrid C. , Winchester Sarah , Wang Yi , Vaisse Christian , Brown Jonathan D. , Quattrocelli Mattia , Lin Charles Y. , Haldar Saptarsi M.
Published: March 2022

Circulating corticosteroids orchestrate stress adaptation, including inhibition of inflammation. While pathways governing corticosteroid biosynthesis and intracellular signaling are well understood, less is known about mechanisms controlling plasma corticosteroid transport. Here, we show that hepatocyte KLF15 (Kruppel-like factor 15) controls plasma corticosteroid transport and inflammatory responses through direct transcriptional activation of
Serpina6
, which encodes corticosteroid-binding globulin (CBG).
Klf15
-deficient mice have profoundly low CBG, reduced plasma corticosteroid binding capacity, and heightened mortality during inflammatory stress. These defects are completely rescued by reconstituting CBG, supporting that KLF15 works primarily through CBG to control plasma corticosterone homeostasis. To understand transcriptional mechanisms, we generated the first KLF15 cistromes using newly engineered
Klf15
3xFLAG
mice. Unexpectedly, liver KLF15 is predominantly promoter enriched, including
Serpina6
, where it binds a palindromic GC-rich motif, opens chromatin, and transactivates genes with minimal associated direct gene repression. Overall, we provide critical mechanistic insight into KLF15 function and identify a hepatocyte-intrinsic transcriptional module that potently regulates systemic corticosteroid transport and inflammation.
Umpolung carbonyls enable direct allylation and olefination of carbohydrates
Authors: Kan Jian , Chen Zhangpei , Qiu Zihang , Lv Leiyang , Li Chenchen , Li Chao-Jun
Published: March 2022

Mother Nature has its own arts to build a vast number of carbohydrates; however, there is still a lack of tools for selective functionalization of native carbohydrates through C─C bond formation. Such a long-standing challenge for the synthetic community lies into the intrinsic problems related to the innate properties of carbohydrates, e.g., the ease to oligomerization or polymerization, the difficulty of chemoselectivity control in the presence of multiple hydroxyl groups, the great challenge to retain the multiple chiral centers during the transformation, etc. Here, by applying an umpolung strategy of carbohydrate carbonyls, we report a direct deoxygenative allylation and olefination of carbohydrates to tackle the abovementioned issues. The reaction is compatible with a wide range of natural carbohydrates, providing a direct synthetic method to use carbohydrates as multiple C-centered chiral synthons to achieve C─C bond cross-coupling reactions. Furthermore, the synthetic applicability is demonstrated by late-stage modifications of natural products and pharmaceutical derivatives.
Isolation and Identification of a Large Green Alga Virus (
Chlorella
Virus XW01) of
Mimiviridae
and Its Virophage (
Chlorella
Virus Virophage SW01) by Using Unicellular Green Algal Cultures
Authors: Sheng Yijian , Wu Zhenqi , Xu Shengzhong , Wang Yongjie
Published: March 2022

Parasitic virophages are small unicellular eukaryotic dsDNA viruses that rely on the viral factories of coinfecting giant/large dsDNA viruses for propagation. Presently, the identified eukaryotic hosts of isolated virophages were restricted to a free-living amoeba,
Acanthamoeba polyphaga
, and a widespread marine heterotrophic flagellate,
Cafeteria roenbergensis
.
Longitudinal association between visual disability and cognitive function among middle-aged and older adults in China
Authors: He Ye , Song Weitao , Jiang Xin , Wang Chao , Zhou Yi , Lu Bing , Zhou Minwen
Published: March 2022

Background/aims

To determine the associations between visual disability and cognitive decline in Chinese middle-aged and older adults.

Methods

A total of 6748 subjects were enrolled into this longitudinal, population-based, nationally representative study from two waves of the China Health and Retirement Longitudinal Study. Lagged dependent variable regression was used to model the independent associations between self-reported visual disability and cognitive function including memory and mental status.

Results

The mean age of the 6748 individuals was 56.33 years, and 3350 (49.6%) were women. The prevalence of visual disability was 3.8%, which increased with age (p<0.001). Both memory and mental status score worsened over time (all p<0.001). After controlling for covariates, lagged dependent variable regression models showed that visual disability at baseline was significantly associated with memory decline after 7 years (β=−0.252, p=0.046). After stratifying by age groups, this association was only significant in the 55–64 age group (β=−0.372, p=0.033). In addition, both memory and mental status in 2011 predicted memory decline over 7 years (p=0.024 and p=0.045, respectively).

Conclusions

Our results suggest that visual disability may be a risk factor of memory decline, but not mental status among middle-aged and elderly adults in China. Future studies are needed to further corroborate the association between visual disability and cognitive decline and to determine whether interventions to preserve good visual function can prevent cognitive decline.
Bicuspid aortic valve: evolving knowledge and new questions
Authors: Sun Byung Joo , Song Jae-Kwan
Published: March 2022

Bicuspid aortic valve (BAV), a common congenital anomaly with various morphological phenotypes, is also characterised by marked heterogeneity in clinical presentations including clinically silent condition with mild valvulo-aortopathy, progressive valvulopathy and complex valvulo-aortopathy with shorter life expectancy. The clinical importance of using a general and unified nosology for BAV is well-accepted by opinion leaders and an international consensus statement has been recently published, which will serve as an important scientific platform for BAV. This review describes the current knowledge of BAV based on clinical studies, addresses several unresolved issues requiring investigators’ attention and highlights the necessity of prospective studies with a very long follow-up duration for better appreciation of BAV-associated valvulo-aortopathy. In addition, the progression of valvular calcification in patients with BAV and its potential contribution to development of valvulopathy will be discussed.
Detection of copy number variants associated with late-onset conditions in ~16 200 pregnancies: parameters for disclosure and pregnancy outcome
Authors: Daum Hagit , Segel Reeval , Meiner Vardiella , Goldberg Yael , Zeligson Sharon , Weiss Omri , Stern Shira , Frumkin Ayala , Zenvirt Shamir , Ganz Gael , Shkedi-Rafid Shiri
Published: March 2022

Background

Copy number variants (CNVs) associated with late-onset medical conditions are rare but important secondary findings in chromosomal microarray analysis (CMA) performed during pregnancy. Here, we critically review the cases at two tertiary centres to assess the criteria which guide the disclosure of such findings and develop a disclosure decision tool (DDT) aimed at facilitating disclosure decision. Parental decisions on receiving CNVs associated with risks for late-onset conditions were also recorded.

Methods

Prenatal CMAs in Hadassah and Shaare Zedek Medical Centers from November 2013 to October 2021 were reviewed for CNVs associated with late-onset conditions. The DDT proposed uses a five-parameter scoring system, which considers the severity, median age of onset, penetrance, understanding of genotype-phenotype correlation and actionability of the finding.

Results

Out of 16 238 prenatal CMAs, 16 (0.1%) harboured CNVs associated with late-onset conditions, 15 of which were disclosed. Outcome information was available on 13 of the 16 pregnancies, all of which continued to delivery.

Conclusions

Our suggested DDT will help clinicians to quantitatively weigh the variables associated with CNVs of this type and arrive at a well thought out clinical decision regarding disclosure. Although the prevalence of late-onset conditions as a major finding in the prenatal setup is low, it is expected to rise with the increasing use of non-invasive CMA testing and whole exome and genome sequencing.
Acute myocarditis caused by COVID-19 disease and following COVID-19 vaccination
Authors: Kornowski Ran , Witberg Guy
Published: March 2022

Myocarditis and pericarditis are inflammatory conditions of the heart that present a range of symptoms, often including chest pain, fatigue, breathlessness and palpitations that may be irregular due to cardiac rhythm disturbances. Myocarditis has been proposed to account for a fraction of cardiac injury among patients infected with SARS-CoV-2 and associated systemic inflammation; and it might be one of the reasons for the high mortality seen in COVID-19 patients. Furthermore, following vaccination with mRNA COVID-19 vaccines (ie, Comirnaty and Spikevax), myocarditis and pericarditis can develop within a few days of vaccination, particularly following the second dose. Based on recent reviewed data, the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have determined that the risk for both of these conditions is overall ‘very rare’ (~1 in 10 000 vaccinated people may be clinically affected), with the highest risk among younger males. Both EMA and FDA agree that the benefits of all authorised COVID-19 vaccines continue to outweigh their risks, given the threat of serious COVID-19 illness and related complications. Since myocarditis has a very wide clinical spectrum, ranging from mild to fulminant life-threatening disease, we present in this review a sum of the latest findings and considerations for the proper diagnosis and management of affected patients.
Amyloid-beta-related angiitis: a treatable rapidly progressive dementia
Authors: Nasir Memoona , Nortey Donald , Malek Naveed , Valerio Fernanda , Chaudhuri Abhijit
Published: March 2022

A 73-year-old woman developed cognitive decline over 1 year. MR scan of the brain showed a focal asymmetrical leukoencephalopathy involving the right frontal, temporal, parietal and occipital lobes. Extensive laboratory investigations found no cause but brain biopsy identified amyloid-beta-related angiitis (ABRA), a potentially treatable cause of rapid-onset dementia. We gave intravenous methylprednisolone and then two courses of intravenous cyclophosphamide, after which her cognitive skills gradually but significantly improved over several months.