bluuebunny/crossref_metadata_2025 huggingface dataset:
The Collected Peter Pan
Authors: Barrie J. M.
Published: February 2024

Peter Pan, the boy who refused to grow up, is one of the immortals of children's literature. J. M. Barrie first created Peter Pan as a baby, living in secret with the birds and fairies in the middle of London, but as the children for whom he invented the stories grew older, so too did Peter, reappearing in Neverland, where he was aided in his epic battles by the motherly and resourceful Wendy Darling. Since then Peter Pan has become a cultural icon and symbol for escapism and innocence, remaining popular with both children and adults.

In this collected edition, Robert Douglas-Fairhurst brings together five of the main versions of the Peter Pan story, from Peter Pan's first appearance in The Little White Bird, to his novelisation of the story, the stage version, and unrealised silent film script. This edition contains an introduction and notes, detailed explanatory notes, original illustrations, and appendices that include Barrie's coda to the play that was only performed once.
Near-ultraviolet radiation toward molecular cloud N4 in W 50/SS 433: Evidence for direct interaction of the jet with molecular cloud
Authors: Yamamoto Hiroaki , Ishikawa Tatsumi , Takeuchi Tsutomu T
Published: February 2024

We compared the molecular clouds in the western part of SS 433 with near-ultraviolet radiation data obtained from GALEX. Near-ultraviolet radiation is prominently confirmed toward only N4, while no near-ultraviolet radiation is detected toward N1, N2, or N3. The radiative region of near-ultraviolet radiation is nearly the same as the CO-emitting region in N4, and does not extend beyond the jet seen in X-ray radiation. Near-ultraviolet radiation cannot be explained solely by broad-band continuous radiation and may originate from line emissions. The intensity of near-ultraviolet radiation exhibits an anti-correlation with that of 13CO(J = 3–2) emission. This anti-correlation, along with strong far-infrared radiation in the region with weaker near-ultraviolet radiation intensity compared to its surroundings, suggests that near-ultraviolet radiation originates from behind the molecular cloud, heating up the interstellar dust in N4. Subsequently, the dust in N4 reradiates in the far-infrared band. In the same region, a high peak TMB ratio of 12CO(J = 3–2)$/$12CO(J = 1–0) of ∼0.9, and a high kinetic temperature of Tk ∼ 56 K in the molecular cloud, indicate that CO molecules are highly excited, and the molecular cloud is heated through photoelectric heating. This heating results from electrons released due to the photoelectric effect caused by the phenomenon where interstellar dust absorbs near-ultraviolet radiation. In terms of the timescale of near-ultraviolet radiation originating from line emissions, near-ultraviolet radiation towards N4 cannot be explained by the shock of the blast wave from a supernova that created W 50. These findings also suggest that N4 directly interacts with the jet from SS 433. As a result of this direct interaction, near-ultraviolet radiation is emitted from an interacting layer between the jet and N4.
Overcoming constraints to measuring O2 diffusivity and consumption of intact roots
Authors: Jiménez Juan de la Cruz , Armstrong William , Colmer Timothy D , Pedersen Ole
Published: February 2024

A method using O2 microsensors enables detailed quantification of respiratory O2 consumption and diffusive resistance to O2 of individual root cell layers.
Transcription factors VviWRKY10 and VviWRKY30 co-regulate powdery mildew resistance in grapevine
Authors: Zhou Min , Wang Hongyan , Yu Xuena , Cui Kaicheng , Hu Yang , Xiao Shunyuan , Wen Ying-Qiang
Published: February 2024

Grapevine (Vitis vinifera) is an economically important fruit crop worldwide. The widely cultivated grapevine is susceptible to powdery mildew caused by Erysiphe necator. In this study, we used CRISPR-Cas9 to simultaneously knock out VviWRKY10 and VviWRKY30 encoding two transcription factors reported to be implicated in defense regulation. We generated 53 wrky10 single mutant transgenic plants and 15 wrky10 wrky30 double mutant transgenic plants. In a 2-yr field evaluation of powdery mildew resistance, the wrky10 mutants showed strong resistance, while the wrky10 wrky30 double mutants showed moderate resistance. Further analyses revealed that salicylic acid (SA) and reactive oxygen species contents in the leaves of wrky10 and wrky10 wrky30 were substantially increased, as was the ethylene (ET) content in the leaves of wrky10. The results from dual luciferase reporter assays, electrophoretic mobility shift assays and chromatin immunoprecipitation (ChIP) assays demonstrated that VviWRKY10 could directly bind to the W-boxes in the promoter of SA-related defense genes and inhibit their transcription, supporting its role as a negative regulator of SA-dependent defense. By contrast, VviWRKY30 could directly bind to the W-boxes in the promoter of ET-related defense genes and promote their transcription, playing a positive role in ET production and ET-dependent defense. Moreover, VviWRKY10 and VviWRKY30 can bind to each other's promoters and mutually inhibit each other's transcription. Taken together, our results reveal a complex mechanism of regulation by VviWRKY10 and VviWRKY30 for activation of measured and balanced defense responses against powdery mildew in grapevine.
Molecular regulatory mechanisms of staminate strobilus development and dehiscence in Torreya grandis
Authors: Chen Weijie , Jiang Baofeng , Zeng Hao , Liu Zhihui , Chen Wenchao , Zheng Shan , Wu Jiasheng , Lou Heqiang
Published: February 2024

Gymnosperms are mostly dioecious, and their staminate strobili undergo a longer developmental period than those of angiosperms. However, the underlying molecular mechanisms remain unclear. This study aimed to identify key genes and pathways involved in staminate strobilus development and dehiscence in Torreya grandis. Through weighted gene co-expression network analysis (WGCNA), we identified fast elongation-related genes enriched in carbon metabolism and auxin signal transduction, whereas dehiscence-related genes were abundant in alpha-linolenic acid metabolism and the phenylpropanoid pathway. Based on WGCNA, we also identified PHYTOCHROME-INTERACTING FACTOR4 (TgPIF4) as a potential regulator for fast elongation of staminate strobilus and 2 WRKY proteins (TgWRKY3 and TgWRKY31) as potential regulators for staminate strobilus dehiscence. Multiple protein-DNA interaction analyses showed that TgPIF4 directly activates the expression of TRANSPORT INHIBITOR RESPONSE2 (TgTIR2) and NADP-MALIC ENZYME (TgNADP-ME). Overexpression of TgPIF4 significantly promoted staminate strobilus elongation by elevating auxin signal transduction and pyruvate content. TgWRKY3 and TgWRKY31 bind to the promoters of the lignin biosynthesis gene PHENYLALANINE AMMONIA-LYASE (TgPAL) and jasmonic acid metabolism gene JASMONATE O-METHYLTRANSFERASE (TgJMT), respectively, and directly activate their transcription. Overexpression of TgWRKY3 and TgWRKY31 in the staminate strobilus led to early dehiscence, accompanied by increased lignin and methyl jasmonate levels, respectively. Collectively, our findings offer a perspective for understanding the growth of staminate strobili in gymnosperms.
The tree peony DREB transcription factor PrDREB2D regulates seed α-linolenic acid accumulation
Authors: Yang Weizong , Xin Ziwei , Zhang Qingyu , Zhang Yanlong , Niu Lixin
Published: February 2024

α-Linolenic acid (ALA), an essential fatty acid (FA) for human health, serves as the precursor of 2 nutritional benefits, docosahexaenoic acid and eicosapentaenoic acid, and can only be obtained from plant foods. We previously found that phospholipid:diacylglycerol acyltransferase 2 (PrPDAT2) derived from ALA-rich tree peony (Paeonia rockii) can promote seed ALA accumulation. However, the regulatory mechanism underlying its promoting effect on ALA accumulation remains unknown. Here, we revealed a tree peony dehydration-responsive element binding transcription factor, PrDREB2D, as an upstream regulator of PrPDAT2, which is involved in regulating seed ALA accumulation. Our findings demonstrated that PrDREB2D serves as a nucleus-localized transcriptional activator that directly activates PrPDAT2 expression. PrDREB2D altered the FA composition in transient overexpression Nicotiana benthamiana leaves and stable transgenic Arabidopsis (Arabidopsis thaliana) seeds. Repressing PrDREB2D expression in P. rockii resulted in decreased PrPDAT2 expression and ALA accumulation. In addition, PrDREB2D strengthened its regulation of ALA accumulation by recruiting the cofactor ABA-response element binding factor PrABF2b. Collectively, the study findings provide insights into the mechanism of seed ALA accumulation and avenues for enhancing ALA yield via biotechnological manipulation.
Population epigenetics: DNA methylation in the plant omics era
Authors: Liu Jie , Zhong Xuehua
Published: February 2024

DNA methylation plays an important role in many biological processes. The mechanisms underlying the establishment and maintenance of DNA methylation are well understood thanks to decades of research using DNA methylation mutants, primarily in Arabidopsis (Arabidopsis thaliana) accession Col-0. Recent genome-wide association studies (GWASs) using the methylomes of natural accessions have uncovered a complex and distinct genetic basis of variation in DNA methylation at the population level. Sequencing following bisulfite treatment has served as an excellent method for quantifying DNA methylation. Unlike studies focusing on specific accessions with reference genomes, population-scale methylome research often requires an additional round of sequencing beyond obtaining genome assemblies or genetic variations from whole-genome sequencing data, which can be cost prohibitive. Here, we provide an overview of recently developed bisulfite-free methods for quantifying methylation and cost-effective approaches for the simultaneous detection of genetic and epigenetic information. We also discuss the plasticity of DNA methylation in a specific Arabidopsis accession, the contribution of DNA methylation to plant adaptation, and the genetic determinants of variation in DNA methylation in natural populations. The recently developed technology and knowledge will greatly benefit future studies in population epigenomes.
Transfer learning promotes acquisition of individual BCI skills
Authors: Kumar Satyam , Alawieh Hussein , Racz Frigyes Samuel , Fakhreddine Rawan , Millán José del R
Published: February 2024

Subject training is crucial for acquiring brain–computer interface (BCI) control. Typically, this requires collecting user-specific calibration data due to high inter-subject neural variability that limits the usability of generic decoders. However, calibration is cumbersome and may produce inadequate data for building decoders, especially with naïve subjects. Here, we show that a decoder trained on the data of a single expert is readily transferrable to inexperienced users via domain adaptation techniques allowing calibration-free BCI training. We introduce two real-time frameworks, (i) Generic Recentering (GR) through unsupervised adaptation and (ii) Personally Assisted Recentering (PAR) that extends GR by employing supervised recalibration of the decoder parameters. We evaluated our frameworks on 18 healthy naïve subjects over five online sessions, who operated a customary synchronous bar task with continuous feedback and a more challenging car racing game with asynchronous control and discrete feedback. We show that along with improved task-oriented BCI performance in both tasks, our frameworks promoted subjects’ ability to acquire individual BCI skills, as the initial neurophysiological control features of an expert subject evolved and became subject specific. Furthermore, those features were task-specific and were learned in parallel as participants practiced the two tasks in every session. Contrary to previous findings implying that supervised methods lead to improved online BCI control, we observed that longitudinal training coupled with unsupervised domain matching (GR) achieved similar performance to supervised recalibration (PAR). Therefore, our presented frameworks facilitate calibration-free BCIs and have immediate implications for broader populations—such as patients with neurological pathologies—who might struggle to provide suitable initial calibration data.
Release of ballast material during sea-ice melt enhances carbon export in the Arctic Ocean
Authors: Swoboda Steffen , Krumpen Thomas , Nöthig Eva-Maria , Metfies Katja , Ramondenc Simon , Wollenburg Jutta , Fahl Kirsten , Peeken Ilka , Iversen Morten
Published: February 2024

Globally, the most intense uptake of anthropogenic carbon dioxide (CO2) occurs in the Atlantic north of 50°N, and it has been predicted that atmospheric CO2 sequestration in the Arctic Ocean will increase as a result of ice-melt and increased primary production. However, little is known about the impact of pan-Arctic sea-ice decline on carbon export processes. We investigated the potential ballasting effect of sea-ice derived material on settling aggregates and carbon export in the Fram Strait by combining 13 years of vertical flux measurements with benthic eDNA analysis, laboratory experiments, and tracked sea-ice distributions. We show that melting sea-ice in the Fram Strait releases cryogenic gypsum and terrigenous material, which ballasts sinking organic aggregates. As a result, settling velocities of aggregates increased ≤10-fold, resulting in ≤30% higher carbon export in the vicinity of the melting ice-edge. Cryogenic gypsum is formed in first-year sea-ice, which is predicted to increase as the Arctic is warming. Simultaneously, less sea-ice forms over the Arctic shelves, which is where terrigenous material is incorporated into sea-ice. Supporting this, we found that terrigenous fluxes from melting sea-ice in the Fram Strait decreased by >80% during our time-series. Our study suggests that terrigenous flux will eventually cease when enhanced sea-ice melt disrupts trans-Arctic sea-ice transport and thus, limit terrigenous-ballasted carbon flux. However, the predicted increase in Arctic primary production and gypsum formation may enhance gypsum-ballasted carbon flux and compensate for lowered terrigenous fluxes. It is thus unclear if sea-ice loss will reduce carbon export in the Arctic Ocean.
Gender discrimination and family stressors: Perceptions and experiences of women police officers
Authors: Schafer Joseph , Dunlap Brenna , Mancini Michael , Linhorst Donald
Published: February 2024

Women police officers may experience discrimination and work–life balance challenges that can impede their entry into and advancement and retention within police organizations. This study used in-depth interviews with 14 women police officers in the St. Louis, MO, metropolitan region to examine workplace stressors, experiences within policing, and perceptions of whether and how gender influenced those stressors and experiences. Participants expressed that they experienced discrimination based on gender, including direct discrimination, such as denial of specialized training, denial of lateral changes in duty assignments, and barriers to career advancement, and indirect discrimination in the form of teasing, harassment, and higher expectations. Many participants also reported they deployed coping strategies to insulate themselves from those experiences, isolated themselves from situations that might result in discrimination or harassment, or sought ways to mitigate the harm of those experiences. Police departments must create environments that support not just gender representation but gender equity.
Anti-carbamylated protein antibodies drive AEC II toward a profibrotic phenotype by interacting with carbamylated TLR5
Authors: Xu Wei , Huang Minghua , Dong Rongrong , Yan Suyan , An Yan , Liu Baocheng , Ma Zhenzhen , Mu Kun , Yang Qingrui
Published: February 2024

Objectives

This study looked at the role of anti-carbamylated protein (anti-CarP) antibodies in contributing to lung fibrosis in CTD-associated interstitial lung disease (ILD) in an autoantigen-dependent manner.

Methods

ELISA was used to test serum samples, including 89 from the CTD-ILD group and 170 from the non-CTD-ILD group, for anti-CarP levels. Male C57BL/6 mice were used for the pulmonary fibrosis model and anti-CarP treatment in vivo (n = 5) and patient serum-derived or commercialized anti-CarP was used for cell treatment. We identified the carbamylated membrane protein via immunofluorescence (IF) and co-immunoprecipitation followed by mass spectrometry (MS) analysis. Quantitative RT-PCR, IF and western blot were performed to explore the antigen-dependent role of anti-CarP. A native electrophoretic mobility shift assay and MS analysis were used to verify direct interaction and carbamylation sites.

Results

A significantly higher serum anti-CarP level was observed in CTD with ILD than without ILD. In vivo, intrapulmonary delivery of anti-CarP induces epithelial–mesenchymal transition (EMT) and microfibrotic foci. Carbamylation was enriched in type II alveolar epithelial cells (AEC II). A novel carbamylated membrane receptor, specifically recognized by anti-CarP, was identified as toll-like receptor 5 (TLR5). We found anti-CarP induces the nuclear translocation of NF-κB and downstream events, including EMT and expression of inflammatory cytokines in AEC II, which were reversed by TLR5 blocking or TLR5 knockdown. Moreover, up to 12 lysine carbamylation sites were found in TLR5 ectodomain, allowing the interaction of anti-CarP with carbamylated TLR5.

Conclusions

Overall, we found anti-CarP drives aberrant AEC II activation by interacting with carbamylated TLR5 to promote ILD progression.
The Role of Childhood Trauma in Affective Stress Recovery in Early Psychosis: An Experience Sampling Study
Authors: Ader Leonie , Schick Anita , Vaessen Thomas ,   GROUP investigators, Alizadeh Behrooz Z , van Amelsvoort Therese , Cahn Wiepke , de Haan Lieuwe , Schirmbeck Frederike , Simons Claudia J P , van Os Jim , Veling Wim , Morgan Craig , Kempton Matthew J , Valmaggia Lucia , McGuire Philip , Myin-Germeys Inez , Lafit Ginette , Reininghaus Ulrich
Published: February 2024

Background and Hypotheses

Affective recovery, operationalized as the time needed for affect to return to baseline levels after daily stressors, may be a putative momentary representation of resilience. This study aimed to investigate affective recovery in positive and negative affect across subclinical and clinical stages of psychosis and whether this is associated with exposure to childhood trauma (sexual, physical, and emotional abuse).

Study Design

We used survival analysis to predict the time-to-recovery from a daily event-related stressor in a pooled sample of 3 previously conducted experience sampling studies including 113 individuals with first-episode psychosis, 162 at-risk individuals, and 94 controls.

Study Results

Negative affective recovery (ie, return to baseline following an increase in negative affect) was longer in individuals with first-episode psychosis compared with controls (hazard ratio [HR] = 1.71, 95% confidence interval [CI; 1.03, 2.61], P = .04) and in at-risk individuals exposed to high vs low levels of emotional abuse (HR = 1.31, 95% CI [1.06, 1.62], P = .01). Positive affective recovery (ie, return to baseline following a decrease in positive affect) did not differ between groups and was not associated with childhood trauma.

Conclusions

Our results give first indications that negative affective recovery may be a putative momentary representation of resilience across stages of psychosis and may be amplified in at-risk individuals with prior experiences of emotional abuse. Understanding how affective recovery contributes to the development of psychosis may help identify new targets for prevention and intervention to buffer risk or foster resilience in daily life.
Food is Medicine and implementation science: A recipe for health equity
Authors: Figueroa Roger , Houghtaling Bailey
Published: February 2024

Diet-related chronic diseases such as Type II diabetes, cardiometabolic diseases, and cancer are among the leading causes of death in the USA. Nutrition security has emerged as a target outcome and a national priority for preventative medicine and the treatment of diet-related chronic diseases. Food is Medicine (FIM) initiatives encompass programs and interventions to meet priority population’s needs across food and nutrition security continuums as a mechanism to address persistent food and nutrition inequities. In this position statement, we draw on implementation science, specifically the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework and health equity principles to provide guidance on FIM initiatives. As the FIM evidence base continues to grow, we encourage the EPIS framework be applied as one lens through which we can improve our understanding of FIM implementation among multiple contexts to understand what works, for whom, and under what circumstances. Ultimately, this position statement aims to call to action the incorporation of implementation science and equity principles into FIM efforts.
Osteology of the two-fingered oviraptorid Oksoko avarsan (Theropoda: Oviraptorosauria)
Authors: Funston Gregory F
Published: February 2024

Oviraptorosaurs are among the most diverse and best-known extinct theropod groups. Their bizarre anatomy and their social and reproductive behaviour are now well understood. Among the oviraptorid subclade, the two-fingered Oksoko avarsan is particularly well-represented. It is known from several exquisite skeletons, preserving not only the entire skeleton, but multiple stages through ontogeny, providing an exemplar for understanding the anatomy of oviraptorids and the changes that their skeletons experienced over their lifetimes. Here I comprehensively describe the osteology of Oksoko avarsan and comment on its ontogenetic variation. Excellent preservation of the specimens provides unparalleled detail into the anatomy of an oviraptorid, providing valuable context for interpreting other oviraptorosaurs. Several changes are observed to occur through ontogeny relating to robustness of the bones and proportions of the skeleton, but there is little evidence suggesting that discrete features like the cranial crest arose late in ontogeny. Instead, early development of the cranial crest in oviraptorids, and its internal connection with the nasal passages and other pneumatic spaces, argue in favour of a role in vocalization, perhaps alongside sexual display. Detailed anatomical and ontogenetic data, like those provided by known specimens of Oksoko avarsan, are necessary to help to underpin ongoing research into the palaeobiology and macroevolution of Oviraptorosauria.
Tracer‐based lipidomics enables the discovery of disease‐specific candidate biomarkers in mitochondrial β‐oxidation disorders
Authors: Schwantje Marit , Mosegaard Signe , Knottnerus Suzan J. G. , van Klinken Jan Bert , Wanders Ronald J. , van Lenthe Henk , Hermans Jill , IJlst Lodewijk , Denis Simone W. , Jaspers Yorrick R. J. , Fuchs Sabine A. , Houtkooper Riekelt H. , Ferdinandusse Sacha , Vaz Frédéric M.
Published: February 2024

Carnitine derivatives of disease‐specific acyl‐CoAs are the diagnostic hallmark for long‐chain fatty acid β‐oxidation disorders (lcFAOD), including carnitine shuttle deficiencies, very‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD), long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MPTD). The exact consequence of accumulating lcFAO‐intermediates and their influence on cellular lipid homeostasis is, however, still unknown. To investigate the fate and cellular effects of the accumulating lcFAO‐intermediates and to explore the presence of disease‐specific markers, we used tracer‐based lipidomics with deuterium‐labeled oleic acid (D9‐C18:1) in lcFAOD patient‐derived fibroblasts. In line with previous studies, we observed a trend towards neutral lipid accumulation in lcFAOD. In addition, we detected a direct connection between the chain length and patterns of (un)saturation of accumulating acylcarnitines and the various enzyme deficiencies. Our results also identified two disease‐specific candidate biomarkers. Lysophosphatidylcholine(14:1) (LPC(14:1)) was specifically increased in severe VLCADD compared to mild VLCADD and control samples. This was confirmed in plasma samples showing an inverse correlation with enzyme activity, which was better than the classic diagnostic marker C14:1‐carnitine. The second candidate biomarker was an unknown lipid class, which we identified as S‐(3‐hydroxyacyl)cysteamines. We hypothesized that these were degradation products of the CoA moiety of accumulating 3‐hydroxyacyl‐CoAs. S‐(3‐hydroxyacyl)cysteamines were significantly increased in LCHADD compared to controls and other lcFAOD, including MTPD. Our findings suggest extensive alternative lipid metabolism in lcFAOD and confirm that lcFAOD accumulate neutral lipid species. In addition, we present two disease‐specific candidate biomarkers for VLCADD and LCHADD, that may have significant relevance for disease diagnosis, prognosis, and monitoring.
Does Operative Level Impact Dysphagia Severity After Anterior Cervical Discectomy and Fusion?
Authors: Paziuk Taylor , Mazmudar Aditya S. , Issa Tariq Z. , Henry Tyler W. , Patel Alpesh A. , Hilibrand Alan S. , Schroeder Gregory D. , Kepler Christopher K. , Vaccaro Alexander R. , Rihn Jeffrey A. , Brodke Darrel S. , Bisson Erica F. , Karamian Brian A.
Published: February 2024

Study Design.

Prospective multicenter cohort study.

Objective.

To explore the association between operative level and postoperative dysphagia after anterior cervical discectomy and fusion (ACDF).

Background.

Dysphagia is common after ACDF and has several risk factors, including soft tissue edema. The degree of prevertebral soft tissue edema varies based on the operative cervical level. However, the operative level has not been evaluated as a source of postoperative dysphagia.

Patients and Methods.

Adult patients undergoing elective ACDF were prospectively enrolled at 3 academic centers. Dysphagia was assessed using the Bazaz Questionnaire, Dysphagia Short Questionnaire, and Eating Assessment Tool-10 (EAT-10) preoperatively and at 2, 6, 12, and 24 weeks postoperatively. Patients were grouped based on the inclusion of specific surgical levels in the fusion construct. Multivariable regression analyses were performed to evaluate the independent effects of the number of surgical levels and the inclusion of each particular level on dysphagia symptoms.

Results.

A total of 130 patients were included. Overall, 24 (18.5%) patients had persistent postoperative dysphagia at 24 weeks and these patients were older, female, and less likely to drink alcohol. There was no difference in operative duration or dexamethasone administration. Patients with persistent dysphagia were significantly more likely to have C4-C5 included in the fusion construct (62.5% vs. 34.9%, P = 0.024) but there were no differences based on the inclusion of other levels. On multivariable regression, the inclusion of C3-C4 or C6-C7 was associated with more severe EAT-10 (β: 9.56, P = 0.016 and β: 8.15, P = 0.040) and Dysphagia Short Questionnaire (β: 4.44, P = 0.023 and (β: 4.27, P = 0.030) at 6 weeks. At 12 weeks, C3-C4 fusion was also independently associated with more severe dysphagia (EAT-10 β: 4.74, P = 0.024).

Conclusion.

The location of prevertebral soft tissue swelling may impact the duration and severity of patient-reported dysphagia outcomes at up to 24 weeks postoperatively. In particular, the inclusion of C3-C4 and C4-C5 into the fusion may be associated with dysphagia severity.
Long-term Outcomes After Adult Spinal Deformity Surgery Using Lateral Interbody Fusion
Authors: Tsutsui Shunji , Hashizume Hiroshi , Iwasaki Hiroshi , Takami Masanari , Ishimoto Yuyu , Nagata Keiji , Yamada Hiroshi
Published: February 2024

Study Design:

Retrospective cohort study.

Objective:

To investigate long-term outcomes after short or long fusion for adult spinal deformity using lateral interbody fusion.

Summary of Background Data:

Lateral interbody fusion is commonly used in adult spinal deformity surgery. Favorable short-term outcomes have been reported, but not long-term outcomes. Lateral interbody fusion with strong ability to correct deformity may allow the selection of short fusion techniques.

Materials and Methods:

We retrospectively reviewed adults who underwent this surgery with a minimum of 5 years of follow-up. Short fusion with the uppermost instrumented vertebra in the lumbar spine was performed in patients without degenerative changes at the thoracolumbar junction (S-group); others underwent long fusion with the uppermost instrumented vertebra in the thoracic spine (L-group). We assessed radiographic and clinical outcomes.

Results:

Short fusion was performed in 29 of 54 patients. One patient per group required revision surgery. Of the remainder, with similar preoperative characteristics and deformity correction between groups, correction loss (pelvic incidence-lumbar lordosis, P=0.003; pelvic tilt, P=0.005; sagittal vertical axis, P˂0.001) occurred within 2 years postoperatively in the S-group, and sagittal vertical axis continued to increase until the 5-year follow-up (P=0.021). Although there was a significant change in Oswestry disability index in the S-group (P=0.031) and self-image of Scoliosis Research Society 22r score in both groups (P=0.045 and 0.02) from 2- to 5-year follow-up, minimum clinically important differences were not reached. At 5-year follow-up, there was a significant difference in Oswestry Disability Index (P=0.013) and Scoliosis Research Society 22r scores (function: P=0.028; pain: P=0.003; subtotal: P=0.006) between the groups, but satisfaction scores were comparable and Oswestry Disability Index score (29.8%) in the S-group indicated moderate disability.

Conclusions:

Health-related quality of life was maintained between 2- and 5-year follow-up in both groups. Short fusion may be an option for patients without degenerative changes at the thoracolumbar junction.

Level of Evidence:

III
Degeneration of Cervical Multifidus Muscles Negatively Affects Physical Activity-related Quality of Life After Laminoplasty for Degenerative Cervical Myelopathy
Authors: Iwamae Masayoshi , Tamai Koji , Suzuki Akinobu , Terai Hidetomi , Hoshino Masatoshi , Kato Minori , Toyoda Hiromitsu , Takahashi Shinji , Yabu Akito , Sawada Yuta , Nakamura Hiroaki
Published: February 2024

Study Design:

A retrospective cohort study.

Objective:

The study aimed to investigate the related factors affecting physical activity-related quality of life (QOL) after 2 years of cervical laminoplasty for degenerative cervical myelopathy (DCM), focusing on the degree of preoperative degeneration of the cervical multifidus muscles.

Summary of Background Data:

The association between paraspinal muscle degeneration and clinical outcomes after spinal surgery is being investigated. The effect of preoperative degeneration of the cervical multifidus muscles in patients undergoing cervical laminoplasty is ambiguous.

Methods:

Patients who underwent laminoplasty for DCM and followed up for more than 2 years were reviewed. To evaluate physical QOL, the physical component summary (PCS) of the 36-Item Short-Form Health Survey (SF-36) was recorded at 2 years postoperatively. The degree of preoperative degeneration in the multifidus muscles at the C4 and C7 levels on axial T2-weighted magnetic resonance imaging (MRI) was categorized according to the Goutallier grading system. The correlation between 2-year postoperative PCS and each preoperative clinical outcome, radiographic parameter, and MRI finding, including Goutallier classification, was analyzed. Variables with a P value <0.10 in univariate analysis were included in multiple linear regression analysis.

Results:

In total, 106 consecutive patients were included. The 2-year postoperative PCS demonstrated significant correlation with age (R=−0.358, P=0.002), preoperative JOA score (R=0.286, P=0.021), preoperative PCS (R=0.603, P<0.001), C2-C7 lordotic angle (R=−0.284, P=0.017), stenosis severity (R=−0.271, P=0.019), and Goutallier classification at the C7 level (R=−0.268, P=0.021). In multiple linear regression analysis, sex (β=−0.334, P=0.002), age (β=−0.299, P=0.013), preoperative PCS (β=0.356, P=0.009), and Goutallier classification at the C7 level (β=−0.280, P=0.018) were significantly related to 2-year postoperative PCS.

Conclusions:

Increased degeneration of the multifidus muscle at the C7 level negatively affected physical activity-related QOL postoperatively. These results may guide spine surgeons in predicting physical activity-related QOL in patients with DCM after laminoplasty.

Level of Evidence:

Level III.
Safety and Efficacy of Outpatient Anterior Cervical Disk Replacement (ACDR) in an Ambulatory Surgery Center Versus Hospital Setting
Authors: Patel Neil , Carota Hanley Kailey , Coban Daniel , Changoor Stuart , Abdelmalek George , Sinha Kumar , Hwang Ki , Emami Arash
Published: February 2024

Study Design:

Retrospective cohort analysis.

Objective:

To compare clinical outcomes of outpatient anterior cervical disk replacements (ACDR) performed in free-standing private ambulatory surgery centers versus tertiary hospital centers.

Summary of Background Data:

ACDR is an increasingly popular technique for treating various degenerative pathologies of the cervical spine. There has been an increase in the utilization of ambulatory surgery centers (ASCs) for outpatient cervical procedures due to economic and convenience benefits; however, a paucity of literature exists in evaluating long-term safety and efficacy of ACDRs performed in ASCs versus outpatient hospital centers.

Methods:

A retrospective cohort review of all patients undergoing 1- or 2-level ACDRs at 2 outpatient ASCs and 4 tertiary care medical centers from 2012 to 2020, with a minimum follow-up of 24 months, was performed. Approval by each patient’s insurance and patient preference determined distribution into an ASC or non-ASC. Demographics, perioperative data, length of follow-up, complications, and revision rates were analyzed. Functional outcomes were assessed using VAS and NDI at follow-up visits.

Results:

One hundred seventeen patients were included (65 non-ASC and 52 ASC). There were no significant differences in demographics or length of follow-up between the cohorts. ASC patients had significantly lower operative times (ASC: 89.5 minutes vs. non-ASC: 110.5 minutes, P<0.001) and mean blood loss (ASC: 17.5 mL vs. non-ASC: 25.3 mL, P<0.001). No significant differences were observed in rates of dysphagia (ASC: 21.2% vs. non-ASC: 15.6%, P<0.001), infection (ASC: 0.0% vs. non-ASC: 1.6%, P=0.202), ASD (ASC: 1.9% vs. non-ASC: 1.6%, P=0.202), or revision (ASC: 1.9% vs. non-ASC: 0.0%, P=0.262). Both groups demonstrated significant improvements in VAS and NDI scores (P<0.001), but no significant differences in the degree of improvement were observed.

Conclusions:

Our 2-year results demonstrate that ACDRs performed in ASCs may offer the advantages of reduced operative time and blood loss without an increased risk of postoperative complications.
Vancomycin Three Ways: Multimodal Utilization of Intraoperative Antibiosis in Complex Foot and Ankle Infection
Authors: Mastrangelo Sand , Granruth Caroline , Serra-Lopez Viviana , Headen Alvis , Ndu Anthony
Published: February 2024

Osteomyelitis of the foot and ankle is an unfortunate, albeit pervasive, complication faced by orthopedic surgeons and their patients. Chronic osteomyelitis confers a great risk of amputation and protracted hospital admission in patients with diabetes, existing orthopedic hardware, and/or compromised tissue perfusion. The current standard of practice in the treatment of osteomyelitis is the initiation of broad antibiotic coverage followed by subsequent narrowing informed by culture data and sensitivities. While mild to moderate infections are treated with oral antibiotics, more severe infections are often treated using intravenous (IV) antibiotics. Vancomycin, in its IV form, is frequently administered intraoperatively for patients with osteomyelitis as it confers adequate coverage of common causative organisms, including staphylococcus aureus. However, given the diminished blood flow to distal extremities commonly seen in patients experiencing this complication, inadequate distribution of oral or IV antibiotics may occur. This is especially problematic, as it leads to an increased risk of recurrent infection and the ultimate need for amputation. Here, we present an alternate method of intraoperative vancomycin administration for patients with chronic osteomyelitis in the form of paste, powder, and injectable slurry. Postoperatively, oral or IV antibiotics are continued based on OR culture susceptibility. We found this to be an effective way to administer intraoperative antibiotics to ensure adequate osseous and soft tissue penetration in patients with complicated osteomyelitis of the foot and ankle.

Level of Evidence: III.
Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis
Authors: Vaara Suvi T. , Serpa Neto Ary , Bellomo Rinaldo , Adhikari Neill K. J. , Dreyfuss Didier , Gallagher Martin , Gaudry Stephane , Hoste Eric , Joannidis Michael , Pettilä Ville , Wang Amanda Y. , Kashani Kianoush , Wald Ron , Bagshaw Sean M. , Ostermann Marlies ,   on behalf of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Investigators
Published: February 2024

OBJECTIVES:

Among patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.

DESIGN:

Secondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).

SETTING:

One hundred-fifty-three ICUs in 13 countries.

PATIENTS:

Altogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Total mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p < 0.001). The median time to RRT initiation among patients allocated to the standard strategy was longest in Europe compared with North America and ANZ (p < 0.001; p < 0.001). Continuous RRT was the initial RRT modality in 60.8% of patients in North America and 56.8% of patients in Europe, compared with 96.4% of patients in ANZ (p < 0.001). After adjustment for predefined baseline characteristics, compared with North American and European patients, those in ANZ were more likely to survive to ICU (p < 0.001) and hospital discharge (p < 0.001) and to 90 days (for ANZ vs. Europe: risk difference [RD], –11.3%; 95% CI, –17.7% to –4.8%; p < 0.001 and for ANZ vs. North America: RD, –10.3%; 95% CI, –17.5% to –3.1%; p = 0.007).

CONCLUSIONS:

Among STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions.
Early Experience With Two-Fraction Spine Stereotactic Body Radiation Therapy in Treating Spinal Metastases
Authors: Ekpunobi Ifeanyi O. , McClelland Shearwood
Published: February 2024

Objectives:

Spinal metastases are common in metastatic cancer, affecting around 40% of patients. The primary treatment involves radiation therapy, transitioning from conventional external beam radiation therapy (EBRT) to stereotactic body radiation therapy (SBRT) for its superior, durable response. While spine SBRT has gained popularity in the United States, Level I evidence supporting it over EBRT is limited to a Canadian trial using a 2-fraction SBRT regimen. We present our findings from one of the earliest US experiences of 2-fraction spine SBRT for spinal metastases.

Methods:

A retrospective analysis of patients with metastatic spine cancer receiving 2-fraction spine SBRT at a single center was conducted. Patients received treatment based on Level 1 evidence (24 Gy in 2 fractions). Follow-up records were assessed for local control outcomes and toxicity.

Results:

Twenty patients since August 2022 have been treated with 2-fraction spine SBRT. Most patients were treated at 1 (45%) or 2 (40%) spinal levels, with the thoracic (55%) and lumbar (50%) spine being the most common locations. Common primary sites included the lung (30%), breast (20%), esophagus (15%), and prostate (10%). The rate of local control was 100%, while the rate of vertebral compression fracture was 15%. No esophageal or bowel toxicity occurred, and no fractures required intervention.

Conclusions:

These findings suggest that 2-fraction spine SBRT is safe and effective, consistent with existing Level I evidence. Our local control rate exceeding 95% aligns with the literature, indicating the feasibility and achievability of implementing this approach in the United States over a short period of time.
The Moderating Role of Collectivism on Physical Activity and Family Support
Authors: Shin Chanam , Belyea Michael
Published: February 2024

Background:

An important value among Korean Americans is collectivism or giving a group priority over the individual. This value, family support, and demographic characteristics have been reported to influence health behaviors among this group. Yet, no study has examined how collectivism, family support, and demographic characteristics interact with each other and then influence physical activity among Korean American adults. The purpose of the study was to examine the association between family support and physical activity, and the moderating role of demographic characteristics and collectivism on this association among Korean American adults.

Methods:

A descriptive, cross-sectional study was conducted with a sample of 110 Korean American adults 18 years and older, residing in a Southwestern city in the United States. Self-administered questionnaires were used to measure demographics, collectivism, family support, and physical activity.

Results:

Data analysis using a zero-inflated negative binomial regression model revealed a positive relationship between family support and physical activity, while age and gender were moderators of the relationship between family support and physical activity. Collectivism was positively related to physical activity and moderated the relationship between family support and physical activity.

Conclusion:

These findings indicate the significance of collectivism and family support that influence Korean American adults' physical activity.
Therapeutic Monitoring of Palbociclib, Ribociclib, Abemaciclib, M2, M20, and Letrozole in Human Plasma: A Novel LC-MS/MS Method
Authors: Posocco Bianca , Zanchetta Martina , Orleni Marco , Gagno Sara , Montico Marcella , Peruzzi Elena , Roncato Rossana , Gerratana Lorenzo , Corsetti Serena , Puglisi Fabio , Toffoli Giuseppe
Published: February 2024

Background:

Therapeutic drug monitoring (TDM) using cyclin-dependent kinase inhibitors (CDK4/6is) is a novel approach for optimizing treatment outcomes. Currently, palbociclib, ribociclib, and abemaciclib are the available CDK4/6is and are primarily coadministered with letrozole. This study aimed to develop and validate an LC-MS/MS method for the simultaneous analysis of CDK4/6is, 2 active metabolites of abemaciclib (M2 and M20), and letrozole in human plasma for use in TDM studies.

Methods:

Sample pretreatment comprised protein precipitation with methanol and dilution of the supernatant with an aqueous mobile phase. Chromatographic separation was achieved using a reversed-phase XBridge BEH C18 column (2.5 μm, 3.0 × 75 mm XP), with methanol serving as the organic mobile phase and pyrrolidine–pyrrolidinium formate (0.005:0.005 mol/L) buffer (pH 11.3) as the aqueous mobile phase. A triple quadrupole mass spectrometer was used for the detection, with the ESI source switched from negative to positive ionization mode and the acquisition performed in multiple reaction monitoring mode.

Results:

The complete validation procedure was successfully performed in accordance with the latest regulatory guidelines. The following analytical ranges (ng/mL) were established for the tested compounds: 6–300, palbociclib and letrozole; 120–6000, ribociclib; 40–800, abemaciclib; and 20–400, M2 and M20. All results met the acceptance criteria for linearity, accuracy, precision, selectivity, sensitivity, matrix effects, and carryover. A total of 85 patient samples were analyzed, and all measured concentrations were within the validated ranges. The percent difference for the reanalyzed samples ranged from −11.2% to 7.0%.

Conclusions:

A simple and robust LC-MS/MS method was successfully validated for the simultaneous quantification of CDK4/6is, M2, M20, and letrozole in human plasma. The assay was found to be suitable for measuring steady-state trough concentrations of the analytes in patient samples.
Flipping Tradition on Its Head: A Single-Institution Study on United States Medical Licensing Examination Step Order
Authors: Zeng Steven L. , Harris Raiven , Tian William M. , Emovon Emmanuel O. , Phillips Brett T.
Published: February 2024

Given the recent change in Step 1 grading, medical students are faced with decisions surrounding the optimal Step examination order and timing. There is a current lack of guidance outside commonly used United States Medical Licensing Examination study blogs. The aim of this study was to characterize current practices in Step examination order and understand the factors influencing student examination preference. To gather data, we used a 24-item survey and electronically distributed it through three separate email requests to medical students. Participants included medical students (MS1-4) attending a single institution, interested in a surgical residency. In total, 56 students responded to the survey (response rate of 20%). Most students (63.6%) opted to take Step 2 before Step 1. Justifications included the perceived importance of Step 2 for residency applications (33.3%), the change to pass/fail grading (27.0%), the relevance of Step 2 after rotations (27.0%), and a desire to obtain a Step 2 score earlier (7.9%). Step examination order did not lead to differences in Step 2 score (P = 0.459), time used to prepare for Step 1 (P = 0.396), or time used to prepare for Step 2 (P = 0.078). Due to the perceived importance of Step 2, most medical students at our institution who are interested in pursuing a surgical residency are reversing the traditional Step examination order. As this may represent a national trend, additional work needs to be done to provide guidance to medical students and identify the optimal step examination testing strategy.