bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective analysis of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy for advanced or recurrent non‐small cell lung cancer
Authors: Isono Taisuke , Kagiyama Naho , Shibata Shun , Nakajima Hitomi , Matsui Yuma , Takano Kenji , Nishida Takashi , Hosoda Chiaki , Kawate Eriko , Kobayashi Yoichi , Ishiguro Takashi , Takaku Yotaro , Kurashima Kazuyoshi , Yanagisawa Tsutomu , Takayanagi Noboru
Published: March 2021

Background

Although clinical trials have investigated the addition of pembrolizumab to chemotherapy for non‐small cell lung cancer, none have investigated the addition of chemotherapy to pembrolizumab.

Methods

We conducted a retrospective study of 71 NSCLC patients including 33 treated with pembrolizumab plus chemotherapy (combination therapy group) and 38 treated with pembrolizumab monotherapy (monotherapy group) from 1 May 2016 to 31 August 2020.

Results

Eleven of 33 (33.3%) patients in the combination therapy group and 37 of 38 (97.4%) patients in the monotherapy group had programmed cell death ligand‐1 (PD‐L1) tumor proportion score (TPS) ≥50%. Objective response rate (ORR) and median overall survival (OS) were not significantly different between the combination therapy group and monotherapy group (54.5% vs. 47.4, p = 0.637 and 16.6 vs. 27.0 months, p = 0.463). In patients with PD‐L1 TPS ≥50%, ORR and median OS were not different between the combination therapy group and the monotherapy group (63.6% vs. 48.6%, p = 0.499 and not reached vs. 27.0 months, p = 0.976). Thirty‐three (100%) patients experienced adverse events (AEs) in the combination therapy group and 32 (84.2%) in the monotherapy group. Treatment discontinuation at 1 year due to AEs occurred more frequently in the combination therapy group (45.2%) than in the monotherapy group (21.1%).

Conclusion

There was no significant difference in ORR and OS between the two groups, and treatment discontinuation was more frequent in the combination group. A randomized controlled trial is needed to evaluate the addition of chemotherapy to pembrolizumab for first‐line treatment in patients with PD‐L1 TPS ≥50%.
Ibrutinib modulates Aβ/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer's disease
Authors: Lee Hyun‐ju , Jeon Seong Gak , Kim Jieun , Kang Ri Jin , Kim Seong‐Min , Han Kyung‐Min , Park HyunHee , Kim Ki‐taek , Sung You Me , Nam Hye Yeon , Koh Young Ho , Song Minseok , Suk Kyoungho , Hoe Hyang‐Sook
Published: March 2021

We previously demonstrated that ibrutinib modulates LPS‐induced neuroinflammation in vitro and in vivo, but its effects on the pathology of Alzheimer's disease (AD) and cognitive function have not been investigated. Here, we investigated the effects of ibrutinib in two mouse models of AD. In 5xFAD mice, ibrutinib injection significantly reduced Aβ plaque levels by promoting the non‐amyloidogenic pathway of APP cleavage, decreased Aβ‐induced neuroinflammatory responses, and significantly downregulated phosphorylation of tau by reducing levels of phosphorylated cyclin‐dependent kinase‐5 (p‐CDK5). Importantly, tau‐mediated neuroinflammation and tau phosphorylation were also alleviated by ibrutinib injection in PS19 mice. In 5xFAD mice, ibrutinib improved long‐term memory and dendritic spine number, whereas in PS19 mice, ibrutinib did not alter short‐ and long‐term memory but promoted dendritic spinogenesis. Interestingly, the induction of dendritic spinogenesis by ibrutinib was dependent on the phosphorylation of phosphoinositide 3‐kinase (PI3K). Overall, our results suggest that ibrutinib modulates AD‐associated pathology and cognitive function and may be a potential therapy for AD.
Cellular aging beyond cellular senescence: Markers of senescence prior to cell cycle arrest in vitro and in vivo
Authors: Ogrodnik Mikolaj
Published: March 2021

The field of research on cellular senescence experienced a rapid expansion from being primarily focused on in vitro aspects of aging to the vast territories of animal and clinical research. Cellular senescence is defined by a set of markers, many of which are present and accumulate in a gradual manner prior to senescence induction or are found outside of the context of cellular senescence. These markers are now used to measure the impact of cellular senescence on aging and disease as well as outcomes of anti‐senescence interventions, many of which are at the stage of clinical trials. It is thus of primary importance to discuss their specificity as well as their role in the establishment of senescence. Here, the presence and role of senescence markers are described in cells prior to cell cycle arrest, especially in the context of replicative aging and in vivo conditions. Specifically, this review article seeks to describe the process of “cellular aging”: the progression of internal changes occurring in primary cells leading to the induction of cellular senescence and culminating in cell death. Phenotypic changes associated with aging prior to senescence induction will be characterized, as well as their effect on the induction of cell senescence and the final fate of cells reviewed. Using published datasets on assessments of senescence markers in vivo, it will be described how disparities between quantifications can be explained by the concept of cellular aging. Finally, throughout the article the applicational value of broadening cellular senescence paradigm will be discussed.
Changes in Alcohol Use and Drinking and Driving Outcomes From Before Arrest for Driving Under the Influence to After Interlock Removal
Authors: Voas Robert B. , Tippetts Anthony Scott , Romano Eduardo , Nochajski Thomas H. , Manning Amy R. , Taylor Eileen , Scherer Michael
Published: March 2021

Background

Half of the offenders convicted of impaired driving in the United States are sentenced to install alcohol ignition interlock devices (IIDs), which prevent them from starting their vehicles if they have been drinking. No research has yet explored offenders’ patterns of alcohol consumption and driving under the influence of alcohol (DUI) from the time before the arrest to the time period after the IID is installed. This study aims to fill that gap in knowledge.

Methods

Using the Timeline Follow‐back interview procedure, we assessed the daily drinking of 153 convicted DUI offenders’ self‐reported total alcohol consumption and rates of self‐reported driving after drinking over 4 phases: before DUI arrest, between arrest and IID installation, during the phase on the interlock, and after the interlock is removed. Because information about behaviors in each period was not available for every participant, comparisons were made using paired‐sample contrasts.

Results

Compared with before the arrest, total alcohol use decreased by 50% in the 4‐month phase following arrest and before IID installation, though it did not change much afterward. The frequency of drinking and driving decreased sharply after the arrest (−82%), with further decrease upon installation of the interlock (−58%, p = 0.05). The frequency of drinking and driving after the IID was removed returned to preinstallation drinking and driving status (+58%, p = 0.01).

Conclusions

Participants made significant adjustments to their drinking behavior by adhering to the traditional DUI driving restrictions in the postarrest phase. Although installation of an IID was not associated with a significant change in drinking, it further reduced the frequency of drinking and driving. Evaluations of the IID experience should take into account information on an individual's drinking and DUI behaviors not only before the IID was installed, but before the individual was arrested.
A conserved haplotype in Wagyu cattle contains RAB4A whose encoded protein regulates glucose trafficking in muscle and fat cells
Authors: Hudson N. J. , Porto‐Neto L. , Naval‐Sanchez M. , Lyons R. E. , Reverter Antonio
Published: March 2021

The Wagyu breed of taurine cattle possess favourable genetics for intramuscular fat (IMF) but genomic loci associated with the trait remain under characterised. Here, we report the identification of a previously unidentified genomic region possessing a particular haplotype structure in Wagyu. Through deployment of a genome‐wide haplotype detection analysis that captures regions conserved in a target population but not other populations we screened 100 individual Wagyu and contrasted them with 100 individuals from two independent comparison breeds, Charolais and Angus, using high‐density SNPs. An extreme level of Wagyu conservation was assigned to a single genomic window (spanning genomic coordinates BTA28:41 088–300 265 bp). In fact, a five‐SNP region spanning 27 096 bp is almost perfectly conserved among the 100 Wagyu individuals assayed and partially overlaps RAB4A. Focussing in, two consecutive SNPs (genomic coordinates 236 949 and 239 950) are apparently fixed within the Wagyu (BB and AA respectively), but at mixed frequencies in the other two breeds. These SNPs are located in the two introns straddling exon 7. In a separate analysis using the 1000 Bulls database, we found that, coincident with exon 7 of RAB4A first allele frequencies were highest in the high IMF Japanese Native (Wagyu) breeds (0.78) and lowest in the low IMF indicine breeds (Nelore and Brahman), with intermediate marbling breeds (Angus and Charolais) assigned intermediate rankings (0.42). RAB4A is known to encode a protein that regulates intracellular trafficking of the insulin‐regulated glucose transporter GLUT4. RAB4A can be considered an attractive new positional candidate for IMF development.
Drivers of farm commercialization in Nigeria and Tanzania
Authors: Owusu Obed , İşcan Talan B.
Published: March 2021

While total factor productivity (TFP) difference between the subsistence and commercial farm types is negligible, a large number of subsistence‐based farms remain outside the market economy, and national policies have emphasized the need to bring them into the fold of commercial agriculture. Improving market access may help induce greater farm commercialization and thus greater investment in agriculture. However, there is little empirical evidence on farm‐level factors that stimulate agricultural commercialization in SSA. Using a nationally representative panel data from the Living Standards Measurement Study‐Integrated Surveys on Agriculture, this article estimates the likelihood of being a commercial versus a subsistence farmer and the likelihood of transitioning from one farm type to another based on observable characteristics in Nigeria and Tanzania. The analysis demonstrates that although a substantial proportion of farms have no market participation in a given year, there are rich transition dynamics over time. The results from the probit regression show that resource endowments (land, labor, chemical use) and farm characteristics (multicropping system; irrigation; crop types such as fruits, vegetables, and cash crops; and animal traction use) do matter for market participation and the transitioning of subsistence farms into a market economy. These variables are positively correlated with farm commercialization and increase the likelihood of market participation. Overall, policies aimed at improving farmers' access to resources and promoting sustainable smallholder agriculture could be instrumental in raising productivity in agriculture and enhancing marketable agricultural output.
Osteogenic effect of low‐intensity pulsed ultrasound and whole‐body vibration on peri‐implant bone. An experimental in vivo study
Authors: Shobara Kenta , Ogawa Toru , Shibamoto Aya , Miyashita Makiko , Ito Akiyo , Sitalaksmi Ratri M.
Published: March 2021

Objectives

The aims of this study were (i) to compare the osteogenic impact of low‐intensity pulsed ultrasound (LIPUS) and low‐magnitude high‐frequency (LMHF) loading achieved with whole‐body vibration (WBV) on peri‐implant bone healing and implant osseointegration in rat tibiae, and (ii) to examine their combined effect on these processes.

Material and methods

Titanium implants were inserted in the bilateral tibiae of 28 Wistar rats. Rats were randomly divided into four groups: LIPUS + WBV, LIPUS, WBV, and control. LIPUS was applied to the implant placement site for 20 min/day on 5 days/week (1.5 MHz and 30 mW/cm2). WBV was applied for 15 min/day on 5 days/week (50 Hz and 0.5 g). In the LIPUS + WBV group, both stimuli were applied under the same stimulation conditions as in the LIPUS and WBV groups. After 4 weeks of treatment, peri‐implant bone healing and implant osseointegration were assessed using removal torque (RT) tests, micro‐CT analyses of relative gray (RG) value, and histomorphometrical analyses of bone‐to‐implant contact (BIC) and peri‐implant bone formation (BV/TV).

Results

The LIPUS + WBV group had significantly greater BIC than the WBV and control groups. Although there were no significant intergroup differences in RT, RG value, and BV/TV, these variables tended to be greater in the LIPUS + WBV group than the other groups.

Conclusions

The combination of LIPUS and LMHF loading may promote osteogenic activity around the implant. However, further study of the stimulation conditions of LIPUS and LMHF loading is necessary to better understand the osteogenic effects and the relationship between the two stimuli.
Analysis of malignant melanoma risk and outcomes in solid organ transplant recipients: Assessment of transplant candidacy and the potential role of checkpoint inhibitors
Authors: Zwald Fiona , Carvajal Richard D. , Walker John , Sawinski Deirdre , Al‐Adra David
Published: March 2021

Malignant melanoma (MM) causes tremendous morbidity and mortality in the solid organ transplant population and may arise in three different clinical scenarios: (1) pretransplant melanoma; (2) de novo melanoma post transplantation and (3) donor‐derived melanoma. This manuscript primarily addresses the first two scenarios with respect to the evaluation and management of pretransplant MM, consideration of transplant candidacy and the occurrence and management of de novo MM post transplantation. The authors outline current evidence describing risks associated with pre‐transplant melanoma to support recently established expert opinion for transplant candidacy.
Vorteile, Sicherheit und Nebenwirkungen der Tumeszenz‐Lokalanästhesie bei dermatologischen Operationen an Säuglingen
Authors: Roerden Alisa , Neunhoeffer Felix , Götz Angelika , Häfner Hans‐Martin , Kofler Lukas
Published: March 2021

Die Tumeszenz‐Lokalanästhesie (TLA) spielt bei dermatochirurgischen Eingriffen eine wichtige Rolle. Die TLA bietet etliche Vorteile, wie lang anhaltende Betäubung, reduzierte Blutung während der Operation und Vermeidung möglicher Komplikationen einer Vollnarkose. Einfache Durchführung, günstiges Risikoprofil und breites Indikationsspektrum sind weitere Gründe dafür, dass TLA zunehmend auch bei Säuglingen eingesetzt wird. Es gibt nicht nur viele Indikationen für chirurgische Exzisionen im Säuglingsalter, wie angeborene Naevi, sondern es hat auch erhebliche Vorteile, wenn diese Exzisionen in einem frühen Alter durchgeführt werden. Dazu zählen die geringere Größe der Läsionen sowie die unproblematische Wundheilung und Geweberegeneration im Säuglingsalter. Dennoch müssen hinsichtlich der Anwendung der TLA bei Säuglingen einige Aspekte berücksichtigt werden, darunter die Dosierung, eine veränderte Plasmaproteinbindung und die Notwendigkeit einer adäquaten und lang anhaltenden Schmerzkontrolle.
Double scope recovery technique to manage procedure‐related trouble during wire trimming with a Loop cutter
Authors: Nagatomo Shuzaburo , Minoda Yosuke , Ihara Eikichi
Published: March 2021

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Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes
Authors: Dahl Kirsten , Brooks Ashley , Almazedi Firas , Hoff Søren Tetens , Boschini Cristina , Bækdal Tine A.
Published: March 2021

Aim

To assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D).

Materials and Methods

In this randomized, double‐blind, single‐centre, crossover trial, subjects with T2D received once‐daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12‐week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat‐rich) at the end of each treatment period. The primary endpoint was area under the glucose 0–5‐h curve (AUC0–5h) after the standard breakfast.

Results

Fifteen subjects were enrolled (mean age 58.2 years, HbA1c 6.9%, body weight 93.9 kg, diabetes duration 3.1 years; 13 [86.7%] males). Fasting concentrations of glucose were significantly lower, and C‐peptide significantly greater, with oral semaglutide versus placebo. Postprandial glucose (AUC0–5h) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC0–5h/5h) and glucagon AUC0–5h were also significantly reduced, with similar results after the fat‐rich breakfast. Fasting concentrations of triglycerides, very low‐density lipoprotein (VLDL) and apolipoprotein B48 (ApoB48) were significantly lower with oral semaglutide versus placebo. AUC0–8h for triglycerides, VLDL and ApoB48, and triglycerides iAUC0–8h/8h, were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC0–1h) with oral semaglutide versus placebo. One serious adverse event (acute myocardial infarction) occurred during oral semaglutide treatment.

Conclusion

Oral semaglutide significantly improved fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying.
Intergenerational income mobility and transmission channels in a transition economy: Evidence from China*
Authors: Yan Weibo , Deng Xiaolan
Published: March 2021

For a large transition economy characterized by urban–rural segmentation, regional disparity and multiple ethnicities, the information transmitted by an integrated measure of intergenerational income mobility is quite limited. Using the method of TS2SLS, this paper estimates the overall and the structure of intergenerational income mobility in recent China. After careful consideration of potential life‐cycle, attenuation and co‐residence biases, our preferred intergenerational income elasticity is 0.41 for father–children and 0.56 for mother–children, which suggests a low level of intergenerational mobility. We then focus on the structure of the mobility regarding age cohort, gender, ethnicity, region, registration type and income percentile. By investigating possible channels, our results show that (a) the role of non‐cognitive characteristics, cognitive abilities, education, occupation and party membership jointly account for nearly 63% of intergenerational transmission, (b) education and occupation are two dominant channels, and (c) non‐cognitive characteristics and cognitive abilities have direct and indirect effects on intergenerational transmission.
Soil carbon persistence governed by plant input and mineral protection at regional and global scales
Authors: Chen Leiyi , Fang Kai , Wei Bin , Qin Shuqi , Feng Xuehui , Hu Tianyu , Ji Chengjun , Yang Yuanhe
Published: March 2021

Elucidating the processes underlying the persistence of soil organic matter (SOM) is a prerequisite for projecting soil carbon feedback to climate change. However, the potential role of plant carbon input in regulating the multi‐layer SOM preservation over broad geographic scales remains unclear. Based on large‐scale soil radiocarbon (∆14C) measurements on the Tibetan Plateau, we found that plant carbon input was the major contributor to topsoil carbon destabilisation despite the significant associations of topsoil ∆14C with climatic and mineral variables as well as SOM chemical composition. By contrast, mineral protection by iron–aluminium oxides and cations became more important in preserving SOM in deep soils. These regional observations were confirmed by a global synthesis derived from the International Soil Radiocarbon Database (ISRaD). Our findings illustrate different effects of plant carbon input on SOM persistence across soil layers, providing new insights for models to better predict multi‐layer soil carbon dynamics under changing environments.
Climate‐driven impacts of exotic species on marine ecosystems
Authors: Bennett Scott , Santana‐Garcon Julia , Marbà Núria , Jorda Gabriel , Anton Andrea , Apostolaki Eugenia T. , Cebrian Just , Geraldi Nathan R. , Krause‐Jensen Dorte , Lovelock Catherine E. , Martinetto Paulina , Pandolfi John M. , Duarte Carlos M.
Published: March 2021

Aim

Temperature is fundamental to the physiological and ecological performance of marine organisms, but its role in modulating the magnitude of ecological impacts by exotic species remains unresolved. Here, we examine the relationship between thermal regimes in the range of origin of marine exotic species and sites of measured impact, after human‐induced introduction. We compare this relationship with the magnitude of impact exerted by exotic species on native ecosystems.

Location

Global.

Time period

1977–2017 (meta‐analysis).

Major taxa studied

Marine exotic species.

Methods

Quantitative impacts of exotic species in marine ecosystems were obtained from a global database. The native range of origin of exotic species was used to estimate the realized thermal niche for each species and compared with the latitude and climatic conditions in recipient sites of recorded impact of exotic species. The difference in median temperatures between recipient sites and the thermal range of origin (i.e., thermal midpoint anomaly) was compared with the magnitude of effect sizes by exotic species on native species, communities and ecosystems.

Results

Recorded impacts occurred predominantly within the thermal niche of origin of exotic species, albeit with a tendency toward higher latitudes and slightly cooler conditions. The severity of impacts by exotic species on abundance of native taxa displayed a hump‐shaped relationship with temperature. Peak impacts were recorded in recipient sites that were 2.2°C cooler than the thermal midpoint of the range of origin of exotic species, and impacts decreased in magnitude toward higher and lower thermal anomalies.

Main conclusions

Our findings highlight how temperature and climatic context influence ecological impacts by exotic species in marine ecosystems and the implications for existing and novel species interactions under climate change.
Efficacy and cost‐effectivity analysis of outpatient parenteral antimicrobial therapy unit in infectious disease clinical practices: Turkey perspective
Authors: Bastug Aliye , Oksuz Ergun , Kazancioglu Sumeyye , Malhan Simten , Ozbay Bahadır Orkun , Bodur Hurrem
Published: March 2021

Background

Outpatient parenteral antimicrobial treatment (OPAT) has become a common treatment modality in developed countries. OPAT units are not widespread in Turkey, and their cost‐effectivity analysis has not been studied, yet.

Aims

To analyze the clinical efficacy and cost‐effectiveness of the OPAT unit, based on a 1000‐bed teaching hospital.

Methods

The records of patients, who were treated between October 2013 and December 2017, in an OPAT unit of a tertiary hospital in Ankara, were obtained retrospectively. The cost that would arise if the patients were hospitalized for the same treatment period with the same diagnosis was calculated and compared with the actual treatment cost of the patients in the OPAT unit.

Results

A total of 594 patients who received antimicrobial treatment at the OPAT unit were enrolled. The mean age of the patients was 55.39 ± 16.37 years and 313 (52.7%) were males. Based on the end‐of‐treatment goals, 98.5% of the patients reached the treatment goal. An indirect cost analysis revealed that the OPAT unit was 487.625 94 TL/129.008 78 $ less costly than inpatient parenteral antibiotic treatment. In other words, OPAT cost was 75% of the equivalent inpatient costs. It was also determined that a total of 7078 bed days and 11.9 bed days per person were saved.

Conclusions

OPAT units should be expanded increasingly in Turkey. The evaluation together with the health care system conditions in Turkey revealed that the OPAT program is safe, effective, and cost‐efficient.
Blast counts are lower in the aspirate as compared to trephine biopsy in acute myeloid leukemia and myelodysplastic syndrome expressing CD56
Authors: Drexler Beatrice , Tzankov Alexandar , Martinez Maria , Baerlocher Severin , Passweg Jakob R. , Dirnhofer Stefan , Tsakiris Dimitrios A. , Dirks Jan
Published: March 2021

Introduction

CD56 is aberrantly expressed in myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Considering the adhesion effects of CD56, blast quantification in bone marrow might depend on the technique used to obtain respective diagnostic specimens. Therefore, the objective of our study was to investigate the impact of CD56‐expression on blast counts in myeloid neoplasms comparing bone marrow aspirates to biopsies.

Methods

We retrospectively analyzed 75 patients diagnosed with MDS and AML. We compared patients with (n = 36) and without (n = 39) CD56‐expression by flow cytometry with respect to their blast quantities assessed on bone marrow aspirates versus biopsies.

Results

The frequency of CD56‐expression on blasts correlated with higher blast counts on biopsies vs. aspirate smears (rs = 0.52; P = .001). This difference in blast counts was only significant in the CD56 high expressing subgroup (median 68%, 5.5%‐95% in biopsy compared to median 32.5%, 1.5%‐90% in aspirate; P < .01). The percentage of CD56‐positive blasts among the total blast population was lower in the peripheral blood compared to bone marrow (median 31%, 6%‐88% vs. 55%, 14%‐98%; P = .016). The discrepancy in the blast count between the aspirate and trephine biopsy would have led to misclassification of four cases as MDS instead of AML, if diagnosis had based on the bone marrow aspirate blast count alone.

Conclusion

Counting blasts in bone marrow aspirates of CD56‐positive AML and MDS may be linked to underestimation, potentially leading to misclassification of these myeloid neoplasms, and should therefore be adjusted considering the results obtained on trephine biopsies for reliable diagnosis.
Rule learning transfer across linguistic and visual modalities in 7‐month‐old infants
Authors: Bulf Hermann , Quadrelli Ermanno , Brady Shannon , Nguyen Bryan , Macchi Cassia Viola , Johnson Scott P.
Published: March 2021

Rule learning (RL) refers to infants’ ability to extract high‐order, repetition‐based rules from a sequence of elements and to generalize them to new items. RL has been demonstrated in both the auditory and the visual modality, but no studies have investigated infants’ transfer of learning across these two modalities, a process that is fundamental for the development of many complex cognitive skills. Using a visual habituation procedure within a cross‐modal RL task, we tested 7‐month‐old infants’ transfer of learning both from speech to vision (auditory‐visual—AV—condition) and from vision to speech (visual‐auditory—VA—condition). Results showed a transfer of learning in the AV condition, but only for those infants who were able to efficiently extract the rule during the learning (habituation) phase. In contrast, in the VA condition infants provided no evidence of RL. Overall, this study indicates that 7‐month‐old infants can transfers high‐order rules across modalities with an advantage for transferring from speech to vision, and that this ability is constrained by infants’ individual differences in the way they process the to‐be‐learned rules.
Charge injection and decay of nanoscale dielectric films resolved via dynamic scanning probe microscopy
Authors: Moran Thomas J. , Suzuki Keigo , Hosokura Tadasu , Khaetskii Alexander , Huey Bryan D.
Published: March 2021

To satisfy continual demands for higher performance dielectrics in multi‐layer ceramic capacitors and related microelectronic devices, novel characterization methods are necessary for mapping materials properties down to the nanoscale, where enabling materials developments are increasingly relevant. Accordingly, an atomic force microscopy‐based approach is implemented for characterizing insulator performance based on the mapping of discharging dynamics. Following surface charging by biasing a conducting tip contacting a dielectric surface, consecutive non‐contact Kelvin force surface potential mapping (KPFM) reveals charge dissipation via exponential decay. In barium titanate (BTO) thin films engineered with distinct microstructures but identical thicknesses, discharging rates vary by up to a factor of 2, with smaller grain size correlating to longer dissipation times, providing insight into optimal microstructures for improved capacitor performance. High‐resolution potential mapping as a function of time thereby provides a route for directly investigating charge injection and discharging mechanisms in dielectrics, which are increasingly engineered down to the nanoscale and have global implications given the trillions of such devices manufactured each year.
Gulf Coast vicariance shapes phylogeographic history of a North American freshwater mussel species complex
Authors: Keogh Sean M. , Johnson Nathan A. , Williams James D. , Randklev Charles R. , Simons Andrew M.
Published: March 2021

Aim

Freshwater mussels share habitat and are parasites of freshwater fishes during the larval life stage. Therefore, models of fish biogeography may also explain the historical biogeography of freshwater mussels. We tested this assumption using predictions of three biogeographic models constructed for northern Gulf of Mexico drainages on a freshwater mussel species complex. Specifically, we tested (1) if speciation was due to vicariant events of fluctuating sea levels that separated lineages east‐west of the Mobile Basin (Central Gulf Coast speciation hypothesis), (2) if the timing of divergences occurred 8.5–3.5 MYA (Gulf Coast allopatric speciation model) and (3) if diversification in Mississippi River populations was recent and for evidence of population increase consistent with range expansion into northern deglaciated regions (Pleistocene glaciation model).

Location

Eastern North America.

Taxon

Freshwater mussels (Bivalvia: Unionidae), Lampsilis teres and L. floridensis.

Methods

We collected 249 specimens from 73 localities across the group's distribution. We used three molecular markers (COI, NDI & ITSI) to conduct time calibrated Bayesian phylogenetic analyses, phylogeographic analyses (AMOVA & SAMOVA) and demographic analyses including Bayesian skyline plots.

Results

Lampsilis teres and L. floridensis are allopatric species whose distributions meet at the eastern edge of the Mobile Basin. Speciation was estimated to occur in the late Miocene. Populations from isolated river systems surrounding the Gulf of Mexico are almost all monophyletic. Mississippi drainage samples formed a shallow clade with recent diversification and showed evidence of recent population expansion.

Main conclusions

The historical biogeography of the L. teres species complex is broadly consistent with tested ichthyofaunal models. The timing of speciation and intraspecific divergences correspond to low sea‐level events suggesting that Gulf Coast sea‐level fluctuations are responsible for dispersal (sea‐level recession) and subsequent cladogenesis (sea‐level inundation). Consistent with numerous other freshwater studies, we found the Mobile Basin to be a suture zone, which may be due to the narrow, offshore continental shelf.
Holocene plant diversity dynamics show a distinct biogeographical pattern in temperate Europe
Authors: Roleček Jan , Abraham Vojtěch , Vild Ondřej , Svobodová Svitavská Helena , Jamrichová Eva , Plesková Zuzana , Pokorný Petr , Kuneš Petr
Published: March 2021

Aim

Pollen has been used before to reconstruct Holocene plant diversity changes in broadly delimited regions such as continents and countries. In this study we ask whether finer‐scale differences in plant diversity, which are of interest to biogeographers and ecologists, are also detectable in the fossil pollen record coming from a single, biogeographically complex region of temperate Europe.

Location

Central Europe (Czech Republic, Slovakia).

Taxon

Vascular plants.

Methods

Fossil pollen extracted from 18 high‐quality profiles was used as a proxy of past plant diversity. Pollen counts of tree taxa were corrected by pollen productivities and pollen assemblages were resampled to 100 grains per sample and 150 grains per 500‐year time window. SiZer analysis was used to test and visualize multi‐scale diversity patterns. SiZer maps were compared using principal coordinate analysis, and linear modelling was used to identify the best predictors. Pollen composition was analysed using non‐metric multidimensional scaling. K‐means clustering and indicator species analysis were used to interpret ordination results.

Results

Mean Holocene plant diversity is significantly predicted by latitude, whilst its temporal pattern varies by biogeographical region. Major differences were found between the Mesic and Montane Hercynia (relatively low diversity, increasing only in the Late Holocene) and Pannonia, the Carpathians and the Warm Hercynia (higher diversity, increasing from the Early or Middle Holocene onwards). The low diversity in the Middle and Late Holocene is associated with the prevalence of woody and acidophilic taxa. High diversity is associated with numerous grassland and minerotrophic wetland taxa, crops and weeds.

Main conclusions

Plant diversity and its changes during the Holocene are geographically structured across temperate Europe. The main causes appear to be differences between biogeographical regions in the dynamics of landscape openness and vegetation composition. The differences reflect spatial patterns in climate and human impact and their temporal changes.
Utility of fluoroscopy alone for monitoring of intrathoracic bleeding complications during transvenous lead extraction
Authors: Issa Ziad F. , Issa Tariq Z.
Published: March 2021

Background

Transvenous lead extraction (TLE) carries a significant risk of major complications, namely bleeding into the pericardial sac or thoracic cavity. While echocardiographic imaging has been recommended for intraprocedural monitoring for those complications, no studies had examined the potential benefits of fluoroscopy alone as an alternative to echocardiography. The aim of this study was to evaluate the utility of fluoroscopy for monitoring intrathoracic bleeding complications during TLE.

Methods

This is a single‐center retrospective study of consecutive patients who underwent TLE of a pacemaker or ICD lead with fluoroscopy‐only monitoring. At the beginning of each TLE procedure, baseline fluoroscopic images were obtained for both lung fields and the cardiac silhouette. Similar images were acquired again when hypotension develops during the procedure.

Results

Fluoroscopy alone (without echocardiographic imaging) was used in 783 consecutive patients (54% women; average age, 71.5 ± 12.9 years) who underwent TLE. There were 93 patients (11.9%) who experienced significant hypotension. Fluoroscopy showed no obvious cause for hypotension in 63 patients. Right ventricular inversion was implied by fluoroscopy in 27 patients. Fluoroscopy detected new pericardial effusion in two patients and new right pleural effusion in one patient, which prompted halting the extraction procedure and therapeutic intervention. Additionally, routine fluoroscopic images revealed the development of an unsuspected new small left pleural effusion in one patient and a pericardial effusion in another. In‐hospital mortality rate was 0%.

Conclusions

In selected patients undergoing TLE, fluoroscopy can provide valuable information for identifying or excluding cardiovascular causes during periods of intraprocedural hemodynamic instability.
Improving day surgery rates of anterior cruciate ligament reconstruction surgery in surgical units not dedicated to performing day surgery: A retrospective observational cohort study
Authors: Lucocq James , Khalil Mostafa , Roberts Louise , Dalgleish Stephen , Jariwala Arpit
Published: March 2021

Background and aims

Current guidance advises that at least 90% of anterior cruciate ligament reconstructions are performed as day‐case operations. Same‐day surgery rates achieved by surgical units have significant clinical and financial implications. The primary aim of this multi‐centre study was to determine the rate of admission and causes for admissions in patients undergoing anterior cruciate ligament reconstruction.

Method

Patient documentations were studied for those who underwent an elective anterior cruciate ligament reconstruction between January 2015 and April 2019. Contributing factors related to admission length were investigated and included patient age, gender, body mass index (BMI), operating surgeon, operating hospital, American Society of Anaesthesiology (ASA) grade, and position of the patient on the operating list. Both univariate and multivariate analysis were conducted using the STATA/IC 16.1 statistical package.

Results

The day surgery rate of anterior cruciate ligament reconstructions were 52% (50/95). Patients positioned later on the operating list were more likely to be admitted post‐operatively (OR, 4.49; P = .002; 95% CI, 1.72‐11.69) and this was the only factor associated with admission. A large majority of admitted patients (95.6%) were admitted without a clinical cause and were otherwise safe for same‐day discharge.

Conclusions

The day surgery rate for ACL reconstruction remains low, despite an extremely low complication rate. Reconfiguration of the operating lists and positioning anterior cruciate ligament reconstructions earlier in the day will likely increase the same‐day discharge rate and reduce associated costs.
Prescriber perspectives on low‐value prescribing: A qualitative study
Authors: Walter Eric L. , Dawdani Alicia , Decker Alison , Hamm Megan E. , Pickering Aimee N. , Hanlon Joseph T. , Thorpe Carolyn T. , Roberts Mark S. , Fine Michael J. , Gellad Walid F. , Radomski Thomas R.
Published: March 2021

Background

Health systems are increasingly implementing interventions to reduce older patients' use of low‐value medications. However, prescribers' perspectives on medication value and the acceptability of interventions to reduce low‐value prescribing are poorly understood.

Objective

To identify the characteristics that affect the value of a medication and those factors influencing low‐value prescribing from the perspective of primary care physicians.

Design

Qualitative study using semi‐structured interviews.

Setting

Academic and community primary care practices within University of Pittsburgh Medical Center health system.

Participants

Sixteen primary care physicians.

Measurements

We elicited 16 prescribers' perspectives on definitions and examples of low‐value prescribing in older adults, the factors that incentivize them to engage in such prescribing, and the characteristics of interventions that would make them less likely to engage in low‐value prescribing.

Results

We identified three key themes. First, prescribers viewed low‐value prescribing among older adults as common, characterized both by features of the medications themselves and of the particular patients to whom they were prescribed. Second, prescribers described the causes of low‐value prescribing as multifactorial, with factors related to patients, prescribers, and the health system as a whole, making low‐value prescribing a default practice pattern. Third, interventions addressing low‐value prescribing must minimize the cognitive load and time pressures that make low‐value prescribing common. Interventions increasing time pressure or cognitive load, such as increased documentation, were considered less acceptable.

Conclusions

Our findings demonstrate that low‐value prescribing is a well‐recognized phenomenon, and that interventions to reduce low‐value prescribing must consider physicians' perspectives and address the specific patient, prescriber and health system factors that make low‐value prescribing a default practice.
Housing Design and Modifications for Individuals With Intellectual and Developmental Disabilities and Complex Behavioral Needs: Scoping Review
Authors: Casson Jane , Hamdani Yani , Dobranowski Kristin , Lake Johanna , McMorris Carly , Gonzales Angela , Lunsky Yona , Balogh Robert
Published: March 2021

Background

Behavioral challenges exhibited by individuals with IDD can signal a poor person–environment relationship. There remains limited understanding about the physical characteristics of successful housing for this population. This article summarizes research on housing design for individuals with IDD who engage in behaviors that challenge.

Specific Aims

Original, peer‐reviewed research on the physical environment of housing was reviewed to determine the characteristics that can be modified to meet the needs of individuals with IDD who engage in behaviors that challenge.

Method

Electronic databases and reference lists of relevant publications were searched for peer reviewed empirical research related to housing design for behaviors that challenge. Two reviewers independently applied inclusion criteria to identify studies. Content analysis identified housing features.

Findings

Fourteen studies were identified that described inadequate and successful housing characteristics. Elements such as location, layout, safety, stimulation, and homelikeness were reported to contribute to successful housing.

Discussion

Design of the physical environment has important policy and practice implications for supported housing that addresses behaviors that challenge. The development of design tools, guidelines, and personalized housing for this population is discussed.
Sleep does not aid the generalisation of binocular disparity‐based learning to the other visual hemifield
Authors: Klinzing Jens G. , Nienborg Hendrikje , Rauss Karsten
Published: March 2021

Visual perceptual learning refers to long‐lasting performance improvements on a visual skill – an ability supported by plastic changes in early visual brain areas. Visual perceptual learning has been shown to be induced by training and to benefit from consolidation during sleep, presumably via the reactivation of learning‐associated neuronal firing patterns. However, previous studies have almost exclusively relied on a single paradigm, the texture discrimination task, on which performance improvements may rely on higher‐order rather than lower‐level perceptual skills. In the present study, we tested whether sleep has beneficial effects on a visual disparity discrimination task. We confirm previous findings in showing that the ability to discriminate different disparities is unaffected by sleep during a 12‐hr retention period after training. Importantly, we extend these results by providing evidence against an effect of sleep on the generalisation of improved disparity discrimination across the vertical meridian. By relying on a between‐subject design, we further exclude carry‐over effects as a possible confound present in previous findings. These data argue against sleep as an important factor in the consolidation of a low‐level perceptual skill. This sets important constraints on models of the role of sleep and sleep‐associated neural reactivation in the consolidation of non‐declarative memories.
Linking Evangelical Subculture and Phallically Insecure Masculinity Using Google Searches for Male Enhancement
Authors: Perry Samuel L. , Whitehead Andrew L.
Published: March 2021

Numerous studies document the connection between American evangelicalism and male insecurity stemming from essentialist, phallocentric conceptions of masculinity. Yet data have often been confined to individuals’ responses in surveys or qualitative interviews. This limits our understanding because individuals may lie about the most personal sources of insecurity (even to themselves) and such data are difficult to aggregate to broader subcultural influences. Building on a moral communities’ framework, in this research note we analyze Google Trends data and focus on the prevalence of explicit searches for “male enhancement” terms and phrases, simultaneously indicating (1) the internalization of a subculture that prioritizes essentialist, phallocentric standards of masculinity and (2) a privately felt failure to meet those standards. Even after accounting for a host of state‐level confounds, the preponderance of evangelicals in a state consistently predicts more Google searches for terms and phrases like “male enhancement,” “ExtenZe,” “penis pump,” “penis enlargement,” and others. We theorize that the largely patriarchal―and increasingly embattled and radicalized―evangelical subculture explicitly or implicitly promotes equating masculinity with physical strength and size, leaving men influenced by that subculture (whether evangelical or not) to seek solutions for their privately felt failure to measure up.
Comparison of C‐reactive protein concentrations in dogs with Bordetella bronchiseptica infection and aspiration bronchopneumonia
Authors: Canonne Aude Morgane , Menard Maud , Maurey Christelle , Benchrekroun Ghita , Fernandes Rodrigues Nina , Billen Frédéric , Clercx Cecile
Published: March 2021

Background

C‐reactive protein (CRP) is a well‐known acute‐phase protein in dogs that may discriminate bacterial bronchopneumonia from other pulmonary conditions. Bronchopneumonia caused by Bordetella bronchiseptica (Bb) is common but the associated increase in CRP concentration in naturally infected dogs has not been fully explored.

Objective

To compare CRP concentrations of dogs with Bb infection, with or without radiographic pulmonary lesions, to dogs with aspiration bronchopneumonia (ABP).

Animals

Sixteen dogs with Bb infection and 36 dogs with ABP.

Methods

Retrospective study. C‐reactive protein concentrations and thoracic radiographs were available for each dog.

Results

Eleven dogs with Bb infection had alveolar lesions. In all dogs, CRP concentration was mildly increased (14‐38 mg/L). In the 5 dogs without alveolar lesions, CRP concentration was within the reference range in all but 1 dog, in which it was slightly increased. Median CRP concentration was significantly higher in dogs with alveolar lesions (20 mg/L) compared with dogs without alveolar lesions (5 mg/L; p < .002). In dogs with Bb infection, median duration of clinical signs was not different between dogs with normal CRP concentration and dogs with increased concentration. In dogs with Bb infection either with or without alveolar lessions, median CRP concentration was significantly lower (20 mg/L) than in dogs with ABP (118 mg/L; p < .001).

Conclusions and Clinical Importance

In contrast to dogs with APB, CRP was not a good marker for the diagnosis of dogs suspected to have bordetellosis. Confirmation of Bb infection still requires lower airway sampling.