bluuebunny/crossref_metadata_2025 huggingface dataset:
The average dust attenuation curve at z ∼ 1.3 based on HST grism surveys
Authors: Battisti A J , Bagley M B , Baronchelli I , Dai Y S , Henry A L , Malkan M A , Alavi A , Calzetti D , Colbert J , McCarthy P J , Mehta V , Rafelski M , Scarlata C , Shivaei I , Wisnioski E
Published: April 2022

We present the first characterization of the average dust attenuation curve at z ∼ 1.3 by combining rest-frame ultraviolet through near-IR photometry with Balmer decrement (H α/H β) constraints for ∼900 galaxies with 8 ≲ log (M⋆/M⊙) < 10.2 at 0.75 < z < 1.5 in the HST WFC3 IR Spectroscopic Parallel and 3D-HST grism surveys. Using galaxies in SDSS, we establish that the (H α + [N ii])/[O iii] line ratio and stellar mass are good proxies for the Balmer decrement in low-spectral resolution grism data when only upper limits on H β are available and/or H α is blended with [N ii]. The slope of the z ∼ 1.3 attenuation curve ($A(0.15\, \rm{\mu m})/A(V)=3.15$) and its normalization (RV = 3.26) lie in-between the values found for z = 0 and z ∼ 2 dust attenuation curves derived with similar methods. These provide supporting evidence that the average dust attenuation curve of star-forming galaxies evolves continuously with redshift. The z ∼ 1.3 curve has a mild 2175 Å feature (bump amplitude, Eb = 0.83; ∼25 per cent that of the MW extinction curve), which is comparable to several other studies at 0 < z ≲ 3, and suggests that the average strength of this feature may not evolve significantly with redshift. The methods we develop to constrain dust attenuation from HST grism data can be applied to future grism surveys with JWST, Euclid, and RST. These new facilities will detect millions of emission line galaxies and offer the opportunity to significantly improve our understanding of how and why dust attenuation curves evolve.
Remnant masses of core collapse supernovae in the jittering jets explosion mechanism
Authors: Shishkin Dmitry , Soker Noam
Published: April 2022

We conduct one-dimensional (1D) stellar evolution simulations of non-rotating stars with initial masses in the range of $11\!-\!48 \, \mathrm{M}_{\odot }$ to the time of core collapse and, using a criterion on the specific angular momentum fluctuations in the inner convective zones, estimate the masses of the neutron star (NS) remnants according to the jittering jets explosion mechanism. From the 1D simulations, we find that several convective zones with specific angular momentum fluctuations of $j_{\rm {conv}} \gtrsim 2.5 \times 10^{15} {\, \rm cm}^2 {\, \rm s}^{-1}$ develop near the edge of the iron core in all models. For this condition for explosion, we find the NS remnant masses to be in the range of $1.3\!-\!1.8 \, \mathrm{M}_\odot$, while if we require twice as large values, i.e. $j_{\rm {conv}} \gtrsim 5 \times 10^{15} {\, \rm cm}^2 {\, \rm s}^{-1}$, we find the NS remnant masses to be in the range of $1.4\!-\!2.8 \, \mathrm{M}_\odot$ (the upper values here might form black holes). Note that in general, the formation of black holes in the jittering jets explosion mechanism requires a rapidly rotating pre-collapse core, while we simulate non-rotating stars.
Exotic image formation in strong gravitational lensing by clusters of galaxies – III. Statistics with HUDF
Authors: Meena Ashish Kumar , Bagla Jasjeet Singh
Published: April 2022

We study the image formation near point singularities (swallowtail and umbilics) in the simulated strongly lensed images of Hubble Ultra Deep Field (HUDF) by the Hubble Frontier Fields (HFF) clusters. In this work, we only consider nearly half of the brightest (a total of 5271) sources in the HUDF region. For every HFF cluster, we constructed 11 realizations of strongly lensed HUDF with an arbitrary translation of the cluster centre within the central region of HUDF and an arbitrary rotation. In each of these realizations, we visually identify the characteristic/exotic image formation corresponding to the different point singularities. We find that our current results are consistent with our earlier results based on different approaches. We also study time delay in these exotic image formations and compare it with typical five-image geometries. We find that the typical time delay in exotic image formations is an order of magnitude smaller than the typical time delay in a generic five-image geometry.
The mitoXplorer 2.0 update: integrating and interpreting mitochondrial expression dynamics within a cellular context
Authors: Marchiano Fabio , Haering Margaux , Habermann Bianca Hermine
Published: April 2022

Mitochondria are subcellular organelles present in almost all eukaryotic cells, which play a central role in cellular metabolism. Different tissues, health and age conditions are characterized by a difference in mitochondrial structure and composition. The visual data mining platform mitoXplorer 1.0 was developed to explore the expression dynamics of genes associated with mitochondrial functions that could help explain these differences. It, however, lacked functions aimed at integrating mitochondria in the cellular context and thus identifying regulators that help mitochondria adapt to cellular needs. To fill this gap, we upgraded the mitoXplorer platform to version 2.0 (mitoXplorer 2.0). In this upgrade, we implemented two novel integrative functions, network analysis and transcription factor enrichment, to specifically help identify signalling or transcriptional regulators of mitochondrial processes. In addition, we implemented several other novel functions to allow the platform to go beyond simple data visualization, such as an enrichment function for mitochondrial processes, a function to explore time-series data, the possibility to compare datasets across species and an IDconverter to help facilitate data upload. We demonstrate the usefulness of these functions in three specific use cases. mitoXplorer 2.0 is freely available without login at http://mitoxplorer2.ibdm.univ-mrs.fr.
Targeted delivery to macrophages and dendritic cells by chemically modified mannose ligand-conjugated siRNA
Authors: Uehara Keiji , Harumoto Toshimasa , Makino Asana , Koda Yasuo , Iwano Junko , Suzuki Yasuhiro , Tanigawa Mari , Iwai Hiroto , Asano Kana , Kurihara Kana , Hamaguchi Akinori , Kodaira Hiroshi , Atsumi Toshiyuki , Yamada Yoji , Tomizuka Kazuma
Published: April 2022

Extrahepatic delivery of small interfering RNAs (siRNAs) may have applications in the development of novel therapeutic approaches. However, reports on such approaches are limited, and the scarcity of reports concerning the systemically targeted delivery of siRNAs with effective gene silencing activity presents a challenge. We herein report for the first time the targeted delivery of CD206-targetable chemically modified mannose–siRNA (CMM–siRNA) conjugates to macrophages and dendritic cells (DCs). CMM–siRNA exhibited a strong binding ability to CD206 and selectively delivered contents to CD206-expressing macrophages and DCs. Furthermore, the conjugates demonstrated strong gene silencing ability with long-lasting effects and protein downregulation in CD206-expressing cells in vivo. These findings could broaden the use of siRNA technology, provide additional therapeutic opportunities, and establish a basis for further innovative approaches for the targeted delivery of siRNAs to not only macrophages and DCs but also other cell types.
Pleiotropic MLLT10 variation confers risk of meningioma and estrogen-mediated cancers
Authors: Walsh Kyle M , Zhang Chenan , Calvocoressi Lisa , Hansen Helen M , Berchuck Andrew , Schildkraut Joellen M , Bondy Melissa L , Wrensch Margaret , Wiemels Joseph L , Claus Elizabeth B
Published: April 2022

Background

Risk of tumors of the breast, ovary, and meninges has been associated with hormonal factors and with one another. Genome-wide association studies (GWAS) identified a meningioma risk locus on 10p12 near previous GWAS hits for breast and ovarian cancers, raising the possibility of genetic pleiotropy.

Methods

We performed imputation-based fine-mapping in three case-control datasets of meningioma (927 cases, 790 controls), female breast cancer (28 108 cases, 22 209 controls), and ovarian cancer (25 509 cases, 40 941 controls). Analyses were stratified by sex (meningioma), estrogen receptor (ER) status (breast), and histotype (ovarian), then combined using subset-based meta-analysis in ASSET. Lead variants were assessed for association with additional traits in UK Biobank to identify potential effect-mediators.

Results

Two-sided subset-based meta-analysis identified rs7084454, an expression quantitative trait locus (eQTL) near the MLLT10 promoter, as lead variant (5.7 × 10–14). The minor allele was associated with increased risk of meningioma in females (odds ratio (OR) = 1.42, 95% Confidence Interval (95%CI):1.20–1.69), but not males (OR = 1.19, 95%CI: 0.91–1.57). It was positively associated with ovarian (OR = 1.09, 95%CI:1.06–1.12) and ER+ breast (OR = 1.05, 95%CI: 1.02–1.08) cancers, and negatively associated with ER– breast cancer (OR = 0.91, 95%CI: 0.86–0.96). It was also associated with several adiposity traits (P < 5.0 × 10–8), but adjusting for body mass index did not attenuate its association with meningioma. MLLT10 and ESR1 expression were positively correlated in normal meninges (P = .058) and meningioma tumors (P = .0065).

Conclusions

We identify a MLLT10 eQTL positively associated with risk of female meningioma, ER+ breast cancer, ovarian cancer, and obesity, and implicate a potential estrogenic mechanism underlying this pleiotropy.
The Prognostic Value of TP53 Alteration in Patients with Head and Neck Squamous Cell Carcinoma Receiving Immunotherapy
Authors: Jiang Chao , Zhou Xuanchen , Han Jie , Yue Zhiyong , Li Butuo
Published: April 2022

The article by Wilson et al., published in the February 2021 issue, reported the prognostic value of circulating tumor DNA (ctDNA) sequencing in head and neck squamous cell carcinoma (HNSCC), noting TP53 as the most altered and concordant gene in ctDNA and tDNA. This Letter to the Editor further considers the role of TP53 alteration in the prognosis prediction of immunotherapy in HNSCC.
Variable Genomic Landscapes of Advanced Melanomas with Heavy Pigmentation
Authors: Huang Richard S P , Tse Julie Y , Harries Lukas , Graf Ryon P , Lin Douglas I , Murugesan Karthikeyan , Hiemenz Matthew C , Parimi Vamsi , Janovitz Tyler , Decker Brennan , Severson Eric , Levy Mia A , Ramkissoon Shakti H , Elvin Julia A , Ross Jeffrey S , Williams Erik A
Published: April 2022

Background

In the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors.

Materials and Methods

Our case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel).

Results

Of the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.0% (165/1268) were HPMel and 87.0% (1103/1268) were LPMel. In the HPMel cohort, we saw a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than in the LPMel group (11.4 mut/Mb), although there was substantial overlap. In examining characteristic secondary genomic alterations (GA), we found that the frequencies of GA in TERTp, CDKN2A, TP53, and PTEN were significantly lower in the HPMel cases than in LPMel. A higher rate of GA in CTNNB1, APC, PRKAR1A, and KIT was identified in the HPMel cohort compared with LPMel.

Conclusions

In this study, we quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation and showed that CGP can be used in these patients to identify biomarkers that can guide treatment decisions for HPMel patients. Using this practical clinical definition for tumor pigmentation, our results indicate that HPMel are frequent at 13% of melanoma samples, and in general appear molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression.
Incumbency and Identity: The 2021 Senedd Election
Authors: Larner Jac M , Wyn Jones Richard , Poole Ed Gareth , Surridge Paula , Wincott Daniel
Published: April 2022

Taking place amid a global pandemic, the 2021 Senedd Election saw Welsh Labour returned as the largest party at the sixth consecutive occasion since the institution’s founding in 1999. Results for opposition parties were mixed: the Conservatives achieved their highest ever vote share but their seat tally fell short of pre-election expectations, and Plaid Cymru again made little progress. Using data from the 2021 Welsh Election Study, we explore the election campaign and results, and offer a first analysis of vote choice. We find that Labour not only benefitted from incumbency advantages drawn from voters’ approval of the Welsh Government’s handling of the pandemic, but through its use of symbols, branding and messaging, the party continues to remain attuned to a national identity position that broadly aligns with that of the electorate as a whole.
Regulation of ppGpp Synthesis and Its Impact on Chloroplast Biogenesis during Early Leaf Development in Rice
Authors: Ito Kazuhiro , Ito Doshun , Goto Mina , Suzuki Sae , Masuda Shinji , Iba Koh , Kusumi Kensuke
Published: April 2022

Guanosine tetraphosphate (ppGpp) is known as an alarmone that mediates bacterial stress responses. In plants, ppGpp is synthesized in chloroplasts from GTP and ATP and functions as a regulator of chloroplast gene expression to affect photosynthesis and plant growth. This observation indicates that ppGpp metabolism is closely related to chloroplast function, but the regulation of ppGpp and its role in chloroplast differentiation are not well understood. In rice, ppGpp directly inhibits plastidial guanylate kinase (GKpm), a key enzyme in GTP biosynthesis. GKpm is highly expressed during early leaf development in rice, and the GKpm-deficient mutant, virescent-2 (v2), develops chloroplast-deficient chlorotic leaves under low-temperature conditions. To examine the relationship between GTP synthesis and ppGpp homeostasis, we generated transgenic rice plants over-expressing RSH3, a protein known to act as a ppGpp synthase. When RSH3 was overexpressed in v2, the leaf chlorosis was more severe. Although the RSH3 overexpression in the wild type caused no visible effects, pulse amplitude modulation fluorometer measurements indicated that photosynthetic rates were reduced in this line. This finding implies that the regulation of ppGpp synthesis in rice is involved in the maintenance of the GTP pool required to regulate plastid gene expression during early chloroplast biogenesis. We further investigated changes in the expressions of RelA/SpoT Homolog (RSH) genes encoding ppGpp synthases and hydrolases during the same period. Comparing the expression of these genes with the cellular ppGpp content suggests that the basal ppGpp level is determined by the antagonistic action of multiple RSH enzymatic activities during early leaf development in rice.
Celebrating Mendel, McClintock, and Darlington: On end-to-end chromosome fusions and nested chromosome fusions
Authors: Lysak Martin A
Published: April 2022

The evolution of eukaryotic genomes is accompanied by fluctuations in chromosome number, reflecting cycles of chromosome number increase (polyploidy and centric fissions) and decrease (chromosome fusions). Although all chromosome fusions result from DNA recombination between two or more nonhomologous chromosomes, several mechanisms of descending dysploidy are exploited by eukaryotes to reduce their chromosome number. Genome sequencing and comparative genomics have accelerated the identification of inter-genome chromosome collinearity and gross chromosomal rearrangements and have shown that end-to-end chromosome fusions (EEFs) and nested chromosome fusions (NCFs) may have played a more important role in the evolution of eukaryotic karyotypes than previously thought. The present review aims to summarize the limited knowledge on the origin, frequency, and evolutionary implications of EEF and NCF events in eukaryotes and especially in land plants. The interactions between nonhomologous chromosomes in interphase nuclei and chromosome (mis)pairing during meiosis are examined for their potential importance in the origin of EEFs and NCFs. The remaining open questions that need to be addressed are discussed.
Linker histone variant HIS1-3 and WRKY1 oppositely regulate salt stress tolerance in Arabidopsis
Authors: Wu Xi , Xu Jiena , Meng Xingnan , Fang Xue , Xia Minghui , Zhang Jing , Cao Shuqing , Fan Tingting
Published: April 2022

The salt overly sensitive (SOS) pathway plays an important role in plant salt stress; however, the transcriptional regulation of the genes in this pathway is unclear. In this study, we found that Linker histone variant HIS1-3 and WRKY1 oppositely regulate the salt stress response in Arabidopsis (Arabidopsis thaliana) through the transcriptional regulation of SOS genes. The expression of HIS1-3 was inhibited by salt stress, and the disruption of HIS1-3 resulted in enhanced salt tolerance. Conversely, the expression of WRKY1 was induced by salt stress, and the loss of WRKY1 function led to increased salt sensitivity. The expression of SOS1, SOS2, and SOS3 was repressed and induced by HIS1-3 and WRKY1, respectively, and HIS1-3 regulated the expression of SOS1 and SOS3 by occupying the WRKY1 binding sites on their promoters. Moreover, WRKY1 and HIS1-3 acted upstream of the SOS pathway. Together, our results indicate that HIS1-3 and WRKY1 oppositely modulate salt tolerance in Arabidopsis through transcriptional regulation of SOS genes.
The rice transcription factor Nhd1 regulates root growth and nitrogen uptake by activating nitrogen transporters
Authors: Li Kangning , Zhang Shunan , Tang Shuo , Zhang Jun , Dong Hongzhang , Yang Shihan , Qu Hongye , Xuan Wei , Gu Mian , Xu Guohua
Published: April 2022

Plants adjust root architecture and nitrogen (N) transporter activity to meet the variable N demand, but their integrated regulatory mechanism remains unclear. We have previously reported that a floral factor in rice (Oryza sativa), N-mediated heading date-1 (Nhd1), regulates flowering time. Here, we show that Nhd1 can directly activate the transcription of the high-affinity ammonium (NH4+) transporter 1;3 (OsAMT1;3) and the dual affinity nitrate (NO3−) transporter 2.4 (OsNRT2.4). Knockout of Nhd1 inhibited root growth in the presence of NO3− or a low concentration of NH4+. Compared to the wild-type (WT), nhd1 and osamt1;3 mutants showed a similar decrease in root growth and N uptake under low NH4+ supply, while nhd1 and osnrt2.4 mutants showed comparable root inhibition and altered NO3− translocation in shoots. The defects of nhd1 mutants in NH4+ uptake and root growth response to various N supplies were restored by overexpression of OsAMT1;3 or OsNRT2.4. However, when grown in a paddy field with low N availability, nhd1 mutants accumulated more N and achieved a higher N uptake efficiency (NUpE) due to the delayed flowering time and prolonged growth period. Our findings reveal a molecular mechanism underlying the growth duration-dependent NUpE.
Differences in functional brain organization during gesture recognition between autistic and neurotypical individuals
Authors: Trujillo James P , Özyürek Asli , Kan Cornelis C , Sheftel-Simanova Irina , Bekkering Harold
Published: April 2022

Persons with and without autism process sensory information differently. Differences in sensory processing are directly relevant to social functioning and communicative abilities, which are known to be hampered in persons with autism. We collected functional magnetic resonance imaging data from 25 autistic individuals and 25 neurotypical individuals while they performed a silent gesture recognition task. We exploited brain network topology, a holistic quantification of how networks within the brain are organized to provide new insights into how visual communicative signals are processed in autistic and neurotypical individuals. Performing graph theoretical analysis, we calculated two network properties of the action observation network: ‘local efficiency’, as a measure of network segregation, and ‘global efficiency’, as a measure of network integration. We found that persons with autism and neurotypical persons differ in how the action observation network is organized. Persons with autism utilize a more clustered, local-processing-oriented network configuration (i.e. higher local efficiency) rather than the more integrative network organization seen in neurotypicals (i.e. higher global efficiency). These results shed new light on the complex interplay between social and sensory processing in autism.
Gentrifiers Evading Stigma: Social Integrationists in the Neighborhood of the Future
Authors: Parker Jeffrey Nathaniel , Ternullo Stephanie
Published: April 2022

How does the moral calculus of gentrification change for self-conscious newcomers in neighborhoods with a reputation deemed unworthy of preserving? In pointing to a set of practices distinct from “pioneering” accounts of gentrification, Brown-Saracino (2007) identified social preservationists as figures who seek to preserve authentic community and the marginalized old-timers who embody it. Using the deviant case of Bridgeport—a historically White neighborhood in Chicago with a deeply historical and persistent reputation for racism —we examine how self-conscious newcomers orient themselves to the gentrification process when the old-timers are not considered a marginalized group worth protecting, but rather a powerful group with problematic racial views. Whereas Brown-Saracino identified the importance of “selecting the old-timer” among a set of potential representatives of a valorized past, we suggest that in this case, newcomers fight to redefine a neighborhood based on a socially desirable future. Drawing on two distinct sets of ethnographic and interview-based data, we outline how this process has unfolded. We conclude that Bridgeport’s story points to the importance of examining how gentrification ideologies emerge from the collision of personal commitments and neighborhood context, as neighborhood newcomers balance their ethics, concerns over personal reputation, and salient aspects of their new homes, including place reputation.
Feminism at the Crossroads of Neoliberalism and Neoconservatism: Restructuring Women’s Labor in the Context of Family Leave Reform in Finland
Authors: Ylöstalo Hanna
Published: April 2022

This article analyzes the convergences of neoliberalism, neoconservatism, and feminism in the context of Nordic welfare state reform. Using Finland’s ongoing family leave reform as an illustrative example, the article shows that neoliberalism, neoconservatism, and feminism find common ground in welfare state reform where workfare policies are intensified and the dismantling of the public provision is coupled with extended private sphere norms. The article unfolds neoliberal and neoconservative feminisms in the public policy context. It demonstrates that neoliberal and neoconservative feminisms contribute to restructuring women’s labor by locating women as subjects critical to capitalist growth, competitive economies, national wealth, and balanced state budgets as providers of productive and reproductive labor. Moreover, they associate women’s productive and reproductive labor with freedom and emancipation.
Beef cows housed in mud during late gestation have greater net energy requirements compared with cows housed on wood chip bedding
Authors: Nickles Kirsten R , Relling Alejandro E , Garcia-Guerra Alvaro , Fluharty Francis L , Kieffer Justin , Parker Anthony J
Published: April 2022

Mud increases net energy requirements for cattle because mud and precipitation compromise the ability of the hair coat to insulate and maintain core body temperature of the cow. The increase in energy required for a gestating cow to compensate for a muddy environment is unknown. The objective of this study was to evaluate effects of muddy conditions on cow body weight (BW) and fetal growth during late gestation. Sixteen multiparous Angus cows (n = 8/treatment) were paired based on initial BW and one cow from each pair was randomly allocated to either the mud (MUD) or control (CON) treatment on day 213 of gestation. Pens in the CON group were bedded with wood chips, while pens in the MUD group were designed to create a muddy lot (average depth of 23.6 ± 5.8 cm). Cows were housed outdoors individually and fed the same diet that consisted of a limit-fed total mixed ration. Each pair was fed to meet energy and protein requirements for maintenance and gestation. From day 213 to 269 of gestation, cows were weighed and sampled for blood metabolites weekly. Data were analyzed as a randomized complete block design with repeated measurements (SAS 9.4). Though cows consumed the same amount of dry matter, cows in the MUD treatment weighed 37.4 kg less than cows in the CON treatment (P < 0.01) by day 269 of gestation. Cows in the MUD treatment decreased approximately half a body condition score (BCS), while cows in the CON treatment gained approximately 1 BCS during the treatment period (P < 0.01). There was no evidence of a treatment × day of gestation effect for 12th rib back fat (P = 0.85), rump fat (P = 0.48), total plasma protein concentrations (P = 0.85), or plasma 3-methylhistidine (P = 0.84); however, there was a marginally significant treatment × day of gestation effect for plasma non-esterified fatty acid concentration (P = 0.09). Despite differences in cow BW at the end of the treatment period, calf birth weight (P = 0.66) and calf total plasma protein (P = 0.27) were not different; however, the divergence in cow BW remained marginally significant at parturition (P = 0.06). These results indicate that mud increased net energy requirements for cows in the MUD treatment, as calf birth weight was not different but maternal BW was decreased compared with cows in the CON treatment.
Elevated ozone decreases the activity of Rubisco in poplar but not its activation under fluctuating light
Authors: Xu Yansen , Feng Zhaozhong , Peng Jinlong , Tarvainen Lasse
Published: April 2022

Increasing tropospheric ozone (O3) is well-known to decrease leaf photosynthesis under steady-state light through reductions in biochemical capacity. However, the effects of O3 on photosynthetic induction and its biochemical limitations in response to fluctuating light remain unclear, despite the rapid fluctuations of light intensity occurring under field conditions. In this study, two hybrid poplar clones with different O3 sensitivities were exposed to elevated O3. Dynamic photosynthetic CO2 response measurements were conducted to quantify the impact of elevated O3 and exposure duration on biochemical limitations during photosynthetic induction. We found that elevated O3 significantly reduced the steady-state light-saturated photosynthetic rate, the maximum rate of carboxylation (Vcmax) and Rubisco content. In addition, elevated O3 significantly decreased the time constants for slow phases and weighting of the fast phase of the Vcmax induction in poplar clone ‘546’ but not in clone ‘107’. However, elevated O3 did not affect the time, it took to reach a given percentage of full Vcmax activation or photosynthetic induction in either clone. Overall, photosynthetic induction was primarily limited by the activity of Rubisco rather than the regeneration of ribulose-1,5-biphosphate regardless of O3 concentration and exposure duration. The lack of O3-induced effects on the activation of Rubisco observed here would simplify the simulation of impacts of O3 on nonsteady-state photosynthesis in dynamic photosynthetic models.
Evaluation of a Virtual Team-Based Project Designed to Improve Chronic Wound Patient Care in Ontario, Canada
Authors: Fan Angela , Elliott James A. , Jaimangal-Persaud Reneeka , Soleas Eleftherios K. , Smith Karen , Mohan Andrew , Wicher Camilla , Sibbald R. Gary
Published: April 2022

OBJECTIVE

To evaluate the effectiveness of the Extension for Community Healthcare Outcomes Ontario Skin and Wound Care project, a virtual team-based endeavor designed to improve the care of patients with chronic wounds.

METHODS

The study team conducted phone interviews with healthcare professionals (n = 8) regarding their patients (n = 10). The management recommendations were grouped, and the study participants questioned concerning the implementation of the recommendations. Interviews were recorded and transcribed, and the transcripts were analyzed for common themes. The Queen’s University Research Ethics Board approved this study.

RESULTS

Interviews documented improvement in 50% of patients; the other half of the patients did not improve because of patient- and healthcare-system barriers. Three of five nonhealing patients were nonadherent regarding compression, and only one of six suggested biopsies were carried out. The investigators noted three primary reasons for the lack of recommendation implementation: (1) could not obtain a diagnostic procedure, (2) lack of a diagnosis, and (3) patient was reluctant to make a lifestyle change. Major themes included problems in care coordination and suboptimal patient and provider education, along with other obstacles to management.

CONCLUSIONS

Participants stated that the project provided a beneficial learning experience. The findings highlighted a lack of integrated and coordinated interprofessional chronic wound care.
Temperature Management in the ICU
Authors: Drewry Anne , Mohr Nicholas M.
Published: April 2022

Objective:

Temperature abnormalities are recognized as a marker of human disease, and the therapeutic value of temperature is an attractive treatment target. The objective of this synthetic review is to summarize and critically appraise evidence for active temperature management in critically ill patients.

Data Sources:

We searched MEDLINE for publications relevant to body temperature management (including targeted temperature management and antipyretic therapy) in cardiac arrest, acute ischemic and hemorrhagic stroke, traumatic brain injury, and sepsis. Bibliographies of included articles were also searched to identify additional relevant studies.

Study Selection:

English-language systematic reviews, meta-analyses, randomized trials, observational studies, and nonhuman data were reviewed, with a focus on the most recent randomized control trial evidence.

Data Extraction:

Data regarding study methodology, patient population, temperature management strategy, and clinical outcomes were qualitatively assessed.

Data Synthesis:

Temperature management is common in critically ill patients, and multiple large trials have been conducted to elucidate temperature targets, management strategies, and timing. The strongest data concerning the use of therapeutic hypothermia exist in comatose survivors of cardiac arrest, and recent trials suggest that appropriate postarrest temperature targets between 33°C and 37.5°C are reasonable. Targeted temperature management in other critical illnesses, including acute stroke, traumatic brain injury, and sepsis, has not shown benefit in large clinical trials. Likewise, trials of pharmacologic antipyretic therapy have not demonstrated improved outcomes, although national guidelines do recommend treatment of fever in patients with stroke and traumatic brain injury based on observational evidence associating fever with worse outcomes.

Conclusions:

Body temperature management in critically ill patients remains an appealing therapy for several illnesses, and additional studies are needed to clarify management strategies and therapeutic pathways.
Post–COVID-19 Cardiovascular Evaluation in National Collegiate Athletic Association Division I Athletes
Authors: Krystofiak Jason , Kim Mitchell , Navia Aixa , Lander Jeffrey , Altobelli Anthony , Vucic Esad , Womack Jason , Toto Diana , Siddiqui Adil , Bershad Joshua , Kostis William J.
Published: April 2022

Objective:

To evaluate the necessity of cardiac testing after a COVID-19 diagnosis as it relates to myocarditis in collegiate athletes.

Design:

Cross-sectional retrospective case series.

Setting:

National Collegiate Athletic Association Division I University.

Patients:

One hundred sixty-five collegiate athletes diagnosed with COVID-19 by reverse transcriptase-polymerase chain reaction or immunoglobulin G antibody between August and December 2020 without exclusion.

Interventions:

All participants underwent cardiac workup consisting of serum troponin, electrocardiogram, transthoracic echocardiogram, and cardiac magnetic resonance (CMR). All results were reviewed by team physicians and sports cardiologists.

Main Outcome Measures:

Prevalence of myocarditis and abnormality on cardiac testing after COVID-19 infection at a single institution.

Results:

One (0.61% [95% CI, 0.02%-3.3%] asymptomatic athlete had CMR findings of an age-indeterminate myocardial injury with further cardiac testing being otherwise normal. No athlete had CMR abnormalities consistent with acute myocarditis by the modified Lake Louise Criteria.

Conclusions:

Occurrence of myocarditis was lower in this population compared with other studies. No student athlete was permanently disqualified from participation because of testing. A stratified, risk-based testing strategy with CMR may be more appropriate than a universal screening strategy.
Cutaneous Ewing Sarcoma Presenting as a Second Primary Malignancy in a Child
Authors: Daley Jessica , Williams Nathan , Salgado Claudia M. , Schultz Charles , Meade Julia , Ozolek John , Lindsey Brock , Bailey Kelly M.
Published: April 2022

Ewing sarcoma is an EWS-ETS family member-driven malignancy that most commonly arises from bone. Cutaneous Ewing sarcoma is a rare variant which harbors an EWS-ETS family fusion but demonstrates an immunohistochemical staining pattern distinct from classic Ewing tumors. EWSR1 fluorescence in situ hybridization testing interpretation can be challenging in the setting of cutaneous Ewing sarcoma, making an integrated histologic and sequencing approach key for an accurate diagnosis. Here, we report a pediatric patient with a history of neuroblastoma treated with surgery only that developed a cutaneous nodule and was diagnosed with cutaneous Ewing sarcoma as a second primary cancer.
Disparities in telehealth utilization in patients with pain during COVID-19
Authors: Mueller Bridget R. , Lawrence Steven , Benn Emma , Nirenberg Sharon , Kummer Benjamin , Jette Nathalie , George Mary-Catherine , Robinson-Papp Jessica
Published: April 2022

Introduction:

The shift from in-person visits to telehealth visits during the COVID-19 pandemic presented unique challenges for patients with pain. Disparities in health care access already existed, and the impact of telehealth on these inequities has not been studied.

Objectives:

To identify sociodemographic characteristics of patients with pain obtaining care through video, telephone, and in-person visits as social distancing restrictions evolved during the COVID-19 pandemic.

Methods:

Using our institutional clinical data warehouse, we identified 3314 patients with pain receiving care at a large academic institution in New York City during a baseline period (September 23, 2019–March 22, 2020) and counted telephone, video, and in-person visits during the following conditions: a shutdown period (March 23, 2020–May 23, 2020), when nonessential in-person visits were strictly limited, and a reopening period (May 23, 2020–September 23, 2020), when restrictions were relaxed and in-person visits were available. Patients were categorized into 4 groups based on the technology used to complete a visit: (1) video, (2) telephone, (3) in-person, and (4) no visit.

Results:

Patients who were older, publicly insured, and identified as Black or Hispanic were overrepresented in the telephone visit group during shutdown and the in-person group during reopening. A video visit during shutdown increased the likelihood of continued video visit use during reopening despite the return of in-person visits.

Conclusions:

Results show differences in how patients with pain accessed clinical care in a socially distanced world and that flexibility in method of health care delivery may reduce barriers to access. Future research will identify factors (eg, Internet access, digital literacy, provider–patient relationships) driving heterogeneity in telehealth use in patients with pain.
Three-Year Clinical Outcomes and Quality of Life after Retromuscular Resorbable Mesh Repair Using Fibrin Glue
Authors: Morris Martin P. , Patel Viren , Christopher Adrienne N. , Broach Robyn , Harbison Sean P. , Fischer John P.
Published: April 2022

Background:

With 400,000 hernias repaired annually, there is a need for development of efficient and effective repair techniques. Previously, the authors’ group compared perioperative outcomes and hospital costs of patients undergoing ventral hernia repair with retromuscular mesh using suture fixation versus fibrin glue. This article reports on 3-year postoperative outcomes, including hernia recurrence, long-term clinical outcomes, and patient-reported quality of life.

Methods:

Patients who underwent ventral hernia repair performed by a single surgeon between 2015 to 2017 were identified. Patients with retromuscular resorbable mesh placed were included and matched by propensity score. Primary outcomes included hernia recurrence, surgical-site infection, surgical-site occurrence, and surgical-site occurrence/surgical-site infection requiring procedural interventions. Secondary outcomes included quality of life as assessed by the Hernia-Related Quality of Life Survey.

Results:

Sixty-three patients were eligible, and 46 patients were matched (23 suture fixation and 23 fibrin glue), with a median age of 62 years, a median body mass index of 29 kg/m2, and a median defect size of 300 cm2 (interquartile range, 180 to 378 cm2). Median follow-up was 36 months (interquartile range, 31 to 36 months). There was no difference in the incidence of hernia recurrence (13.0 percent for suture fixation and 8.7 percent for fibrin glue; p = 0.636) or other postoperative outcomes between techniques (all p > 0.05). Five patients required reoperation because of a complication (10.9 percent). Overall quality of life improved preoperatively to postoperatively at all time points (all p < 0.05), and no differences in quality-of-life improvement were seen between techniques (p > 0.05).

Conclusion:

Ventral hernia repair with atraumatic resorbable retromuscular mesh fixation using fibrin glue demonstrates equivalent postoperative clinical and quality-of-life outcomes when compared to mechanical suture fixation.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
The Free Tissue Transfer–Masquelet–Reamer-Irrigator-Aspirator Bone Graft Orthoplastic Approach for Lower Extremity Reconstruction
Authors: Maruccia Michele , Vicenti Giovanni , Carrozzo Massimiliano , Caizzi Gianni , Di Summa Pietro G. , Moretti Biagio , Giudice Giuseppe , Elia Rossella
Published: April 2022

The management of critical-sized bone and soft-tissue defects of the lower extremity poses unique challenge to reconstructive surgeons. The aim of this article is to present the authors’ current orthoplastic approach for the management of extended (more than 6 cm) osteocutaneous defects of the lower extremity, based on a sequential combination of two stages: free flap for soft-tissue coverage and the Masquelet technique (first step) followed by reamer-irrigator-aspirator cancellous bone graft and definitive osteosynthesis (second step). This study was a single-center observational retrospective review of prospectively collected data. Adult patients (>18 years of age) with segmental bone loss of the lower extremity caused by acute trauma (Gustilo type IIIB fracture) or nonunion (septic/aseptic) who were treated with the free flap for soft-tissue coverage–Masquelet technique–reamer-irrigator-aspirator approach between January of 2017 and December of 2020 were included. Time of consolidation and early and late complications were recorded. A total of 11 patients (nine male patients and two female patients) with a mean age of 45.8 years were identified. The average bone gap length (standard deviation) was 87.3 (24.9) mm. An anterolateral thigh flap was harvested in all cases. The average duration of the first stage (i.e., time from antibiotic cement spacer placement and free flap to time of bone grafting) was 50.4 days (range, 40 to 62 days). Bone consolidation was achieved in all cases after an average period (standard deviation) of 20.4 (3.3) weeks, with acceptable functional outcomes. The free flap for soft-tissue coverage–Masquelet technique–reamer-irrigator-aspirator approach could be considered a viable option in patients with segmental critical-sized bone defects associated with a large soft-tissue deficit of the lower extremity.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
An Anatomic Analysis of Fibula Flap Mandible Reconstructions: Implications for Endosseous Implant Placement
Authors: Rosen Evan B. , Kyle Gazdeck R. , Goldman Debra A. , Panchal Hina , Jones Emily , Nguyen Jennifer P. , Allen Robert J. , Nelson Jonas A. , Huryn Joseph M. , Matros Evan
Published: April 2022

Background:

Precise planning and evaluation of the fibula bone are necessary if immediate endosseous implant placement is considered. Limited information is available on the anatomical dimensions or density of fibula used in mandibular reconstructions. This study aimed to describe the morphology and dimensions of the fibula used to reconstruct segmental mandibular defects and contrast the findings with the native mandible.

Methods:

A retrospective analysis was performed of patients who underwent segmental mandibulectomy reconstructed with osteocutaneous fibula flaps and had at least one postoperative computed tomography scan. Fibula cross sectional dimensions and densities were evaluated with three-dimensional software. Radiographic measurements were obtained from the contralateral mandible medial to the first molar for comparison.

Results:

Four hundred seventy-seven fibula cross sections from 159 segments were evaluated. Cross-sectional oval, quadrilateral, triangular, and pentagonal shapes differed significantly in proportion (p < 0.001). Thirty-eight percent of segments (95 percent CI, 30 to 46 percent) had differences in cross-section height greater than 1 mm (p < 0.001). Between segments within the same patient, the median height difference was 1.58 mm (range, 0.14 to 6 mm). The superior cortex density was significantly higher for the fibula than the native mandible; however, the medullary space density was significantly lower (p < 0.001).

Conclusions:

The current study comprises the most comprehensive description of fibula morphology in mandibular reconstructions and highlights the significant variability that exists. The findings provide justification for the added time and cost of computer-aided design and computer-aided manufacturing in centers interested in performing immediate dental implant placement, as the technology provides the necessary precision and accuracy.
Common Revisions after Penile Inversion Vaginoplasty: Techniques and Clinical Outcomes
Authors: Morris Martin P. , Wang Chien-Wei , Lane Megan , Morrison Shane D. , Kuzon William M.
Published: April 2022

Up to one-third of patients are reported to undergo secondary surgical revision to address functional and aesthetic concerns after penile inversion vaginoplasty. The most commonly performed revisions are posterior introital web release, clitoroplasty, labiaplasty, and urethroplasty. To illustrate effective strategies for each of these revisions, this Video Plus article reviews the case of a 32-year-old transgender woman undergoing revision surgery to correct functionally limiting posterior introital webbing and to improve clitoral and labial appearance. Intraoperative steps and postoperative considerations are detailed in the accompanying videos.
External Genital Revisions after Gender-Affirming Penile Inversion Vaginoplasty: Surgical Assessment, Techniques, and Outcomes
Authors: Dy Geolani W. , Salibian Ara A. , Blasdel Gaines , Zhao Lee C. , Bluebond-Langner Rachel
Published: April 2022

Background:

Following gender-affirming penile inversion vaginoplasty or vulvoplasty, patients may seek vulvar revision procedures for a variety of common aesthetic and functional concerns. These indications for revision and accompanying techniques are not well-described in the literature.

Methods:

Patients who underwent vulvar revision surgery at the authors’ institution were identified, and patient demographics, surgical indications, operative details, and complications were described. Common complaints requiring external genital revision were sorted into four categories: clitoral, labial, introital, and urethral.

Results:

Thirty-five patients with a history of vaginoplasty underwent vulvar revision between May of 2017 and December of 2019. The mean age at surgical correction was 38.9 years. Ten patients (28.6 percent) had undergone prior secondary procedures (range, 1 to 3). Mean follow-up after revision surgery was 10.7 ± 8.7 months (range, 0 to 30.6 months). The majority of patients underwent concurrent revisions in multiple “categories”. Labial aesthetic concerns were most common (n = 27, 77.1 percent), followed by clitoral (n = 20, 57.1 percent), urologic (n = 17, 48.6 percent), and introital complaints (n = 12, 34.3 percent). Twelve patients (34.3 percent) had canal stenosis requiring concurrent robot-assisted canal revision with peritoneal flaps. Complications included labial abscess (n = 1) and deep vein thrombosis (n = 1). Three patients (8.6 percent) underwent subsequent external genital revisions. Management approaches and surgical techniques for each of these common revision categories are provided.

Conclusion:

As more individuals seek vaginoplasty and vulvoplasty, surgeons must be prepared to address a range of common aesthetic and functional complaints requiring vulvar revision.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Dose-Limiting Bone Marrow Toxicities After Peptide Receptor Radionuclide Therapy Are More Prevalent in Women Than in Men
Authors: Minczeles Noémie S. , de Herder Wouter W. , Konijnenberg Mark W. , Feelders Richard A. , Brabander Tessa , Hofland Johannes
Published: April 2022

Purpose

Peptide receptor radionuclide therapy (PRRT) can cause dose-limiting toxicities (DLTs) of the bone marrow, liver, and kidneys. It is yet unknown whether women and men are equally at risk of these DLTs.

Methods

Neuroendocrine tumor patients treated with 177Lu-DOTATATE between 2000 and 2015 in our phase II trial with available laboratory data were included. For all DLTs, the highest Common Terminology Criteria for Adverse Events (version 4.03) grades that occurred from the start of PRRT until 3 months after the last cycle were scored.

Results

At baseline, women (n = 439) had a significantly lower body mass index, Karnofsky Performance Score, hemoglobin level, and creatinine clearance and a significantly higher platelet level than men (n = 534). Both groups received a median activity of 29.6 GBq (800 mCi). After the start of PRRT, women more frequently developed grade ≥2 thrombocytopenia compared with men (25% vs 18%, P = 0.004) due to a significant increase in grade ≥3 thrombocytopenia (11% vs 6%, P = 0.008). Furthermore, the incidence of grade ≥3 anemia was higher in women (7% vs 3%, P = 0.002). In the multivariable regression model, female sex (odds ratio, 2.50; 95% confidence interval, 1.67–3.74) was confirmed to be an independent risk factor for grade ≥2 thrombocytopenia, among baseline platelet count, bone metastases, uptake on 111In-DTPA-octreotide scan, Karnofsky Performance Score, alkaline phosphatase, lymphocytes, albumin, and renal function.

Conclusions

Female neuroendocrine tumor patients more often experienced PRRT-induced toxicities of platelets and hemoglobin than males, but this did not lead to a lower cumulative activity.