bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic small cell lung cancer presenting as acute appendicitis: a case report
Authors: Connell Louis , Ng Ziqin , Tai Wei Zhong , Allanson Ben
Published: March 2023

We present a case of extensive stage small cell lung cancer presenting as perforated appendicitis secondary to an appendiceal metastasis. This is a rare presentation with only six reported cases in the literature. Surgeons must be aware of unusual causes for perforated appendicitis as in our case the prognosis can be dire. A 60-year-old man presented with an acute abdomen and septic shock. Urgent laparotomy and a subtotal colectomy were performed. Further imaging suggested the malignancy was secondary to a primary lung cancer. Histopathology demonstrated a ruptured small cell neuroendocrine carcinoma in the appendix with thyroid transcription factor 1 positive immunohistochemistry. Unfortunately, the patient deteriorated due to respiratory compromise and was palliated day six postoperatively. Surgeons should consider a broad differential diagnosis for the cause of acute perforated appendicitis as this can rarely be due to a secondary metastatic deposit from a widespread malignant process.
A rare case of retropharyngeal liposarcoma: a rare location of a rare diagnosis
Authors: Arshad Wajiha , Maqbool Shahzaib , Kiany Javeria A , Raza Ali , Farooq Umer , Ali Qasim , Lee Ka Y
Published: March 2023

We report a case of retropharyngeal liposarcoma in a 53-year-old female, who had complaints of neck swelling accompanied with dysphagia, orthopnea and dysphonia. Clinical examination revealed huge multinodular swelling in front of neck with bilateral extension, more prominent on left side and moving with deglutition. The diagnosis of retropharyngeal liposarcoma was established following CT scan, MRI and incisional biopsy. Surgical excision of mass along with near total thyroidectomy was performed. Postoperative hospital stay was uneventful. She remained well in follow-up period of 1 year as well. In conclusion, retropharyngeal liposarcoma is a rare tumor. A review of the literature explores the reasons behind the late presentation as well as the difficulties in diagnosis and treatment of this rare tumor.
The role of SWEET4 proteins in the post-phloem sugar transport pathway of Setaria viridis sink tissues
Authors: Chen Lily , Ganguly Diep R , Shafik Sarah H , Danila Florence , Grof Christopher P L , Sharwood Robert E , Furbank Robert T
Published: March 2023

In the developing seeds of all higher plants, filial cells are symplastically isolated from the maternal tissue supplying photosynthate to the reproductive structure. Photoassimilates must be transported apoplastically, crossing several membrane barriers, a process facilitated by sugar transporters. Sugars Will Eventually be Exported Transporters (SWEETs) have been proposed to play a crucial role in apoplastic sugar transport during phloem unloading and the post-phloem pathway in sink tissues. Evidence for this is presented here for developing seeds of the C4 model grass Setaria viridis. Using immunolocalization, SvSWEET4 was detected in various maternal and filial tissues within the seed along the sugar transport pathway, in the vascular parenchyma of the pedicel, and in the xylem parenchyma of the stem. Expression of SvSWEET4a in Xenopus laevis oocytes indicated that it functions as a high-capacity glucose and sucrose transporter. Carbohydrate and transcriptional profiling of Setaria seed heads showed that there were some developmental shifts in hexose and sucrose content and consistent expression of SvSWEET4 homologues. Collectively, these results provide evidence for the involvement of SWEETs in the apoplastic transport pathway of sink tissues and allow a pathway for post-phloem sugar transport into the seed to be proposed.
The glutathione-dependent alarm triggers signalling responses involved in plant acclimation to cadmium
Authors: Iven Verena , Vanbuel Isabeau , Hendrix Sophie , Cuypers Ann
Published: March 2023

Cadmium (Cd) uptake from polluted soils inhibits plant growth and disturbs physiological processes, at least partly due to disturbances in the cellular redox environment. Although the sulfur-containing antioxidant glutathione is important in maintaining redox homeostasis, its role as an antioxidant can be overruled by its involvement in Cd chelation as a phytochelatin precursor. Following Cd exposure, plants rapidly invest in phytochelatin production, thereby disturbing the redox environment by transiently depleting glutathione concentrations. Consequently, a network of signalling responses is initiated, in which the phytohormone ethylene is an important player involved in the recovery of glutathione levels. Furthermore, these responses are intricately connected to organellar stress signalling and autophagy, and contribute to cell fate determination. In general, this may pave the way for acclimation (e.g. restoration of glutathione levels and organellar homeostasis) and plant tolerance in the case of mild stress conditions. This review addresses connections between these players and discusses the possible involvement of the gasotransmitter hydrogen sulfide in plant acclimation to Cd exposure.
Transcriptomic and metabolomic analysis reveals that symbiotic nitrogen fixation enhances drought resistance in common bean
Authors: López Cristina Mª , Alseekh Saleh , Torralbo Fernando , Martínez Rivas Félix J , Fernie Alisdair R , Amil-Ruiz Francisco , Alamillo Josefa M
Published: March 2023

Common bean (Phaseolus vulgaris L.), one of the most important legume crops, uses atmospheric nitrogen through symbiosis with soil rhizobia, reducing the need for nitrogen fertilization. However, this legume is particularly sensitive to drought conditions, prevalent in arid regions where this crop is cultured. Therefore, studying the response to drought is important to sustain crop productivity. We have used integrated transcriptomic and metabolomic analysis to understand the molecular responses to water deficit in a marker-class common bean accession cultivated under N2 fixation or fertilized with nitrate (NO3–). RNA-seq revealed more transcriptional changes in the plants fertilized with NO3– than in the N2-fixing plants. However, changes in N2-fixing plants were more associated with drought tolerance than in those fertilized with NO3–. N2-fixing plants accumulated more ureides in response to drought, and GC/MS and LC/MS analysis of primary and secondary metabolite profiles revealed that N2-fixing plants also had higher levels of abscisic acid, proline, raffinose, amino acids, sphingolipids, and triacylglycerols than those fertilized with NO3–. Moreover, plants grown under nitrogen fixation recovered from drought better than plants fertilized with NO3–. Altogether we show that common bean plants grown under symbiotic nitrogen fixation were more protected against drought than the plants fertilized with nitrate.
LONG HYPOCOTYL IN FAR-RED 1 mediates a trade-off between growth and defence under shade in Arabidopsis
Authors: Sng Benny Jian Rong , Vu Kien Van , Choi Ian Kin Yuen , Chin Hui Jun , Jang In-Cheol
Published: March 2023

Plants respond to vegetative shade with developmental and physiological changes that are collectively known as shade avoidance syndrome (SAS). Although LONG HYPOCOTYL IN FAR-RED 1 (HFR1) is known to be a negative regulator of SAS by forming heterodimers with other basic helix-loop-helix (bHLH) transcription factors to inhibit them, its function in genome-wide transcriptional regulation has not been fully elucidated. Here, we performed RNA-sequencing analyses of Arabidopsis thaliana hfr1-5 mutant and HFR1 overexpression line [HFR1(ΔN)-OE] to comprehensively identify HFR1-regulated genes at different time points of shade treatment. We found that HFR1 mediates the trade-off between shade-induced growth and shade-repressed defence, by regulating the expression of relevant genes in the shade. Genes involved in promoting growth, such as auxin biosynthesis, transport, signalling and response were induced by shade but suppressed by HFR1 under both short and long durations of shade. Likewise, most ethylene-related genes were shade-induced and HFR1-repressed. However, shade suppressed defence-related genes, while HFR1 induced their expression, especially under long durations of shade treatment. We demonstrated that HFR1 confers increased resistance to bacterial infection under shade.
Wigner Distribution Deconvolution Adaptation for Live Ptychography Reconstruction
Authors: Bangun Arya , Baumeister Paul F , Clausen Alexander , Weber Dieter , Dunin-Borkowski Rafal E
Published: March 2023

We propose a modification of Wigner distribution deconvolution (WDD) to support live processing ptychography. Live processing allows to reconstruct and display the specimen transmission function gradually while diffraction patterns are acquired. For this purpose, we reformulate WDD and apply a dimensionality reduction technique that reduces memory consumption and increases processing speed. We show numerically that this approach maintains the reconstruction quality of specimen transfer functions as well as reduces computational complexity during acquisition processes. Although we only present the reconstruction for scanning transmission electron microscopy datasets, in general, the live processing algorithm we present in this paper can be applied to real-time ptychographic reconstruction for different fields of application.
Weight Changes in Young Service Members After Lower Limb Amputation: Insights From Group-Based Trajectory Modeling
Authors: Gunterstockman Brittney Mazzone , Russell Esposito Elizabeth , Yoder Adam , Smith Clair , Farrokhi Shawn
Published: March 2023

Introduction

Weight gain can contribute to osteoarthritis, cardiovascular disease, low back pain, and poor health-related quality of life. Weight trajectory patterns have been described in older veterans with limb loss; however, there is limited evidence of changes in weight in younger veterans with limb loss.

Materials and Methods

Service members with unilateral or bilateral lower limb amputations (LLAs) (and without an upper limb amputation) were included in this retrospective cohort analysis (n = 931). The mean postamputation baseline weight was 78.0 ± 14.1 kg. Bodyweight and sociodemographic data were extracted from clinical encounters within electronic health records. Group-based trajectory modeling assessed weight change patterns 2 years postamputation.

Results

Three weight change trajectory groups were identified: 58% (542 of 931) of the cohort had stable weight, 38% (352 of 931) had weight gain (mean gain = 19.1 kg), and 4% (31 of 931) had weight loss (mean loss = 14.5 kg). Individuals with bilateral amputations were more frequently noted in the weight loss group compared with those with unilateral amputations. Individuals with LLAs because of trauma other than blasts were more frequently found in the stable weight group compared with those with amputations because of disease or a blast. Younger individuals (<20 years old) with amputations were more likely to be in the weight gain group compared with older individuals.

Conclusions

More than half the cohort maintained a stable weight for two years after amputation, and more than a third experienced weight gain during the same time frame. Knowledge of underlying factors that were associated with weight gain could inform preventative strategies for young individuals with LLAs.
A UV census of the environments of stripped-envelope supernovae
Authors: Sun Ning-Chen , Maund Justyn R , Crowther Paul A
Published: March 2023

This paper reports an environmental analysis of 41 uniformly selected stripped-envelope supernovae (SESNe) based on deep ultraviolet–optical images acquired by the Hubble Space Telescope. Young stellar populations are detected in most SN environments and their ages are derived with a hierarchical Bayesian approach. The age distributions are indistinguishable between Type IIb and Type Ib, while that for Type Ic is systematically younger. This suggests that the Type Ic SN progenitors are more massive, while the Type IIb and Type Ib SNe have very similar progenitor masses. Our result supports a hybrid envelope-stripping mechanism, in which the hydrogen envelopes of the SESN progenitors are stripped via a mass-insensitive process (e.g. binary interaction), while the helium envelopes are stripped via a mass-sensitive process (e.g. stellar wind of the post-binary interaction progenitor). We also provide progenitor constraints for three Type Ibn SNe and two broad-lined Type Ic SNe. All these results demonstrate the importance of the very diverse mass-loss processes in the origins of SESNe.
Investigation of genotoxic effect of octyl gallate used as an antioxidant food additive in in vitro test systems
Authors: Avuloglu Yilmaz Ece , Yuzbasioglu Deniz , Unal Fatma
Published: March 2023

Several antioxidant food additives are added to oils, soups, sauces, chewing gum, potato chips, and so on. One of them is octyl gallate. The purpose of this study was to evaluate the potential genotoxicity of octyl gallate in human lymphocytes, using in vitro chromosomal abnormalities (CA), sister chromatid exchange (SCE), cytokinesis block micronucleus cytome (CBMN-Cyt), micronucleus-FISH (MN-FISH), and comet tests. Different concentrations (0.031, 0.063, 0.125, 0.25, and 0.50 μg/ml) of octyl gallate were used. A negative (distilled water), a positive (0.20 μg/ml Mitomycin-C), and a solvent control (8.77 μl/ml ethanol) were also applied for each treatment. Octyl gallate did not cause changes in chromosomal abnormalities, micronucleus, nuclear bud (NBUD), and nucleoplasmic bridge (NPB) frequency. Similarly, there was no significant difference in DNA damage (comet assay), percentage of centromere positive and negative cells (MN-FISH test) compared to the solvent control. Moreover, octyl gallate did not affect replication and nuclear division index. On the other hand, it significantly increased the SCE/cell ratio in three highest concentrations compared to solvent control at 24 h treatment. Similarly, at 48 h treatment, the frequency of SCE raised significantly compared to solvent controls at all the concentrations (except 0.031 μg/ml). An important reduction was detected in mitotic index values in the highest concentration at 24 h treatment and almost all concentrations (except 0.031 and 0.063 µg/ml) at 48 h treatment. The results obtained suggest that octyl gallate has no important genotoxicological action on human peripheral lymphocytes at the concentrations applied in this study.
Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart
Authors: Milenkovic Ivan , Santos Vieira Helaine Graziele , Lucas Morghan C , Ruiz-Orera Jorge , Patone Giannino , Kesteven Scott , Wu Jianxin , Feneley Michael , Espadas Guadalupe , Sabidó Eduard , Hübner Norbert , van Heesch Sebastiaan , Völkers Mirko , Novoa Eva Maria
Published: March 2023

The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this heterogeneity leads to functionally diverse ‘specialized ribosomes’ is still a controversial topic. Here, we explore the biological function of RPL3L (uL3L), a ribosomal protein (RP) paralogue of RPL3 (uL3) that is exclusively expressed in skeletal muscle and heart tissues, by generating a viable homozygous Rpl3l knockout mouse strain. We identify a rescue mechanism in which, upon RPL3L depletion, RPL3 becomes up-regulated, yielding RPL3-containing ribosomes instead of RPL3L-containing ribosomes that are typically found in cardiomyocytes. Using both ribosome profiling (Ribo-seq) and a novel orthogonal approach consisting of ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), we find that RPL3L modulates neither translational efficiency nor ribosome affinity towards a specific subset of transcripts. In contrast, we show that depletion of RPL3L leads to increased ribosome–mitochondria interactions in cardiomyocytes, which is accompanied by a significant increase in ATP levels, potentially as a result of fine-tuning of mitochondrial activity. Our results demonstrate that the existence of tissue-specific RP paralogues does not necessarily lead to enhanced translation of specific transcripts or modulation of translational output. Instead, we reveal a complex cellular scenario in which RPL3L modulates the expression of RPL3, which in turn affects ribosomal subcellular localization and, ultimately, mitochondrial activity.
A Practical Guide to Relugolix: Early Experience With Oral Androgen Deprivation Therapy
Authors: Kasparian Saro , Wei Oren , Tsai Ni-Chun , Palmer Joycelynne , Pal Sumanta , Lyou Yung , Dorff Tanya
Published: March 2023

Background

Relugolix is the newest form of androgen deprivation therapy (ADT) approved for prostate cancer. However, as an oral drug, several real-world concerns exist, particularly medication compliance, safety with other androgen receptor-targeted agents, and financial burden to patients.

Methods

A single institution retrospective chart review was conducted evaluating all patients who were prescribed relugolix for any prostate cancer indication from January 1, 2021 to January 31, 2022. Demographic data, cardiac risk factors, concomitant therapy usage, and PSA/testosterone levels, were abstracted from the chart review. Adverse effects were obtained by examining progress notes. Compliance was assessed by clinic notes as well as prescription fills by specialty pharmacy records. The reasons patients did not fill or discontinued the medication were noted.

Results

Hundred and one patients were prescribed relugolix, and 91 patients consented to research. Seventy-one (78%) patients filled the prescription to relugolix, with a median follow-up of 5 months. Prescription fill data were available for 45 (63%) patients, with 94% of days covered. The most commonly reported reason not to fill was cost at 50%. Sixty-six (93%) patients reported never missing a dose. PSA levels were available in 71 (100%) patients with 69 (97%) showing stable or improved PSA. Testosterone levels were available in 61 (86%) of patients, which showed 61 (100%) stable or successful castration. Twenty-four (34%) patients used relugolix in combination. No new major safety signals were seen in combination therapy. Nineteen (27%) patients had switched to another form of ADT. Fifteen of these (79%) felt similar or better on relugolix therapy.

Conclusions

Compliance with relugolix seemed acceptable. No major new safety signals were seen, even in combination. Among patients who switched therapy, most tolerated relugolix similarly or better than the previous form of ADT. The cost was a major reason for patients not initiating and for discontinuing therapy.
Reciprocal regulation of flower induction byELF3αandELF3βgenerated via alternative promoter usage
Authors: Wang Peng , Li Yu , Liu Zhe , Li Xuhan , Wang Yicheng , Liu Weijuan , Li Xiao , Hu Jianjian , Zhu Wenyi , Wang Changquan , Li Shan , Gu Tingting , Xu Dongqing , Tang Chao , Wang Yingtao , Li Chao , Zhang Shaoling , Wu Juyou
Published: March 2023

Flowering is critical for sexual reproduction and fruit production. Several pear (Pyrus sp.) varieties produce few flower buds, but the underlying mechanisms are unknown. The circadian clock regulator EARLY FLOWERING3 (ELF3) serves as a scaffold protein in the evening complex that controls flowering. Here, we report that the absence of a 58-bp sequence in the 2nd intron of PbELF3 is genetically associated with the production of fewer flower buds in pear. From rapid amplification of cDNA ends sequencing results, we identified a short, previously unknown transcript from the PbELF3 locus, which we termed PbELF3β, whose transcript level was significantly lower in pear cultivars that lacked the 58-bp region. The heterologous expression of PbELF3β in Arabidopsis (Arabidopsis thaliana) accelerated flowering, whereas the heterologous expression of the full-length transcript PbELF3α caused late flowering. Notably, ELF3β was functionally conserved in other plants. Deletion of the 2nd intron reduced AtELF3β expression and caused delayed flowering time in Arabidopsis. AtELF3β physically interacted with AtELF3α, disrupting the formation of the evening complex and consequently releasing its repression of flower induction genes such as GIGANTEA (GI). AtELF3β had no effect in the absence of AtELF3α, supporting the idea that AtELF3β promotes flower induction by blocking AtELF3α function. Our findings show that alternative promoter usage at the ELF3 locus allows plants to fine-tune flower induction.
Exploring the Relationship between Federal Reform and the Representation of the People: The Case of the Belgian House of Representatives
Authors: Frateur Jakob , Bursens Peter , Meier Petra
Published: March 2023

Federal systems tend to have two venues of representation to ensure that both the people as a whole and the constituent units are represented at the federal level. While this double representation is put forward as a basic (normative) feature of federal systems, little to no empirical research has been conducted on this issue. This contribution therefore studies the representation of the people as a whole and of the constituent units in the Belgian House of Representatives by means of a representative claims analysis of 4,757 oral parliamentary questions. As federal systems tend to be dynamic, the analysis is based on six periods of federal reform through which Belgium decentralized. Our findings show that, over time, the representation of the constituent units increased and exceeded the representation of the people, providing unique empirical input for the debate about the idea that federalism is by definition beneficial for democracy. We problematize our results from a democratic point of view, as—despite being able to vote—the people as a whole are hardly any more represented by the House. Going beyond the Belgian case, we argue that processes of federalization should address the adequate representation of both the constituent units and the people.
State Attorneys General and their Challenges to Federal Policies: Insights from the Texas v. California Litigation Regarding the Affordable Care Act
Authors: Dichio Michael A , Singer Phillip
Published: March 2023

This article explains a rising trend in American politics: the increasingly prominent role the state attorneys general (AGs) play in challenging federal policies. It focuses on one particularly important case—Republican efforts to overturn the Affordable Care Act in Texas v. California. We consider how state AGs and solicitors general (SGs) drive policy efforts through litigation and the factors that contribute to their participation. We find, first, that although members of the out-of-power party in Washington are the ones who typically bring state lawsuits, the Texas litigation demonstrates that these lawsuits are also a vehicle by which members of the party in power try to achieve goals that are otherwise unattainable through the legislative process. Second, Republican AGs submerge partisan arguments in “constitution-talk” with the aim of achieving a policy goal that was defeated democratically. We reach these conclusions through content analysis of AG press releases and semi-structured interviews with litigators and other elite actors.
Early career academic's odyssey: A narrative study of her professional identity construction
Authors: Mula-Falcón Javier , Caballero Katia
Published: March 2023

Recent decades have seen a major transformation of the Spanish university system caused by changes introduced in the teaching staff evaluation procedure in which research has been prioritized. As a result, there has been a growing interest in studying how these procedures impact the way in which early career academics construct their professional identity. In this vein, this article aims to analyze how the professional identity of this group is constructed and developed in the current context of higher education. To this end, a single case study was conducted, applying a biographical-narrative approach. The results show how professional identity development has become polarized in terms of initial rejection to full acceptance of the demands of modern academia. Consequently, professional practices have also been affected by the prioritization of research over teaching, leading to the development of unethical practices to maintain competitiveness. All of these effects have contributed to high levels of stress and job dissatisfaction. Furthermore, maternity is also seen as an obstacle to female academics’ professional and academic development. Finally, our findings highlight the need for policies that provide full support aimed at helping young researchers live balanced professional lives.
Scarcity mindset reduces empathic responses to others’ pain: the behavioral and neural evidence
Authors: Li Wanchen , Meng Jing , Cui Fang
Published: March 2023

Resource scarcity pervades our life. A scarcity mindset triggered by perceiving insufficient resources has been proven to influence our cognition and behaviors, yet it remains unknown whether this mindset specifically influences empathy. The present study induced feelings of scarcity or abundance in separate groups of participants through experimental manipulation and examined the effects of both mindsets on the behavioral and neural responses to others’ pain. Behaviorally, pain intensity ratings of others’ pain were lower in the scarcity group than in the abundance group. The analysis of event-related potentials revealed that N1 amplitudes for painful and nonpainful stimuli were comparable in the scarcity group but differed significantly in the abundance group. Additionally, while both groups showed larger late positive potential amplitudes for painful stimuli than for nonpainful stimuli, this amplitude differential was significantly smaller in the scarcity group than in the abundance group. Thus, behavioral and neural evidence suggests that inducing a scarcity mindset significantly dampens the ability to empathize with others’ pain during both the early and late stages of empathic processing. These findings shed light on our understanding of how a scarcity mindset may influence social emotions and behaviors.
Green electrosynthesis of drug metabolites
Authors: Asra Ridho , Jones Alan M
Published: March 2023

In this concise review, the field of electrosynthesis (ES) as a green methodology for understanding drug metabolites linked to toxicology is exemplified. ES describes the synthesis of chemical compounds in an electrochemical cell. Compared to a conventional chemical reaction, ES operates under green conditions (the electron is the reagent) and has several industrial applications, including the synthesis of drug metabolites for toxicology testing. Understanding which circulating drug metabolites are formed in the body is a crucial stage in the development of new medicines and gives insight into any potential toxic pathologies resulting from the metabolites formed. Current methods to prepare drug metabolites directly from the drug molecule often involve time-consuming multistep syntheses. Throughout this review, the application of green ES to (i) identify drug metabolites, (ii) enable their efficient synthesis, and (iii) investigate the toxicity of the metabolites generated are highlighted.
Evaluation of oxidative stress-mediated cytotoxicity and genotoxicity of copper and flubendiamide: amelioration by antioxidants in vivo and in vitro
Authors: Mandil Rajesh , Prakash Atul , Rahal Anu , Koli Swati , Kumar Rahul , Garg Satish K
Published: March 2023

Present study was designed to evaluate toxic effects of copper (Cu) (@ 33 mg/kg b.wt.) and flubendimide (Flb) (@ 200 mg/kg b.wt.) alone and/or in combination on blood-biochemical indices, oxidative stress, and drug metabolizing enzymes (DMEs) in vivo in male Wistar rats following oral exposure continuously for 90 days and their immunotoxic (cyto-genotoxic and apoptotic) potential in vitro on thymocytes. In in vivo study, ameliorative potential of α-tocopherol was assessed, whereas α-tocopherol, curcumin, resveratrol, and catechin were evaluated for protective effect in vitro. Significantly (P < 0.05) increased AST activity and increment in total bilirubin, uric acid, creatinine, and BUN levels; however, reduction in total protein, GSH content, reduced activities of SOD and GST, and increased lipid peroxidation and GPx activity with severe degenerative changes in histopathological examination of liver and kidney in group of Cu and Flb were observed. Treatment with α-tocopherol improved biochemical variables, redox status, and histoarchitecture of liver and kidney tissues. Reduced hepatic CYP450, CYPb5, APH, UGT, and GST activities observed in both Cu and α-tocopherol alone and their combination groups, whereas significant increment in Flb alone, while α-tocopherol in combination with xenobiotics improved the activities of hepatic DMEs. Primary cell culture of thymocytes (106 cells/ml) exposed to Cu and Flb each @ 40 μM increased TUNEL+ve cells, micronuclei induction, DNA shearing, and comet formation establishes their apoptotic and genotoxic potential, whereas treatment with antioxidants showed concentration-dependent significant reduction and their order of potency on equimolar concentration (10 μM) basis is: curcumin > resveratrol > catechin = α-tocopherol.
Adenosine A2A receptor activation reduces chondrocyte senescence
Authors: Friedman Benjamin , Larranaga‐Vera Ane , Castro Cristina M. , Corciulo Carmen , Rabbani Piul , Cronstein Bruce N.
Published: March 2023

Osteoarthritis (OA) pathogenesis is associated with reduced chondrocyte homeostasis and increased levels of cartilage cellular senescence. Chondrosenescence is the development of cartilage senescence that increases with aging joints and disrupts chondrocyte homeostasis and is associated with OA. Adenosine A2A receptor (A2AR) activation in cartilage via intra‐articular injection of liposomal A2AR agonist, liposomal‐CGS21680, leads to cartilage regeneration in vivo and chondrocyte homeostasis. A2AR knockout mice develop early OA isolated chondrocytes demonstrate upregulated expression of cellular senescence and aging‐associated genes. Based on these observations, we hypothesized that A2AR activation would ameliorate cartilage senescence. We found that A2AR stimulation of chondrocytes reduced beta‐galactosidase staining and regulated levels and cell localization of common senescence mediators p21 and p16 in vitro in the human TC28a2 chondrocyte cell line. In vivo analysis similarly showed A2AR activation reduced nuclear p21 and p16 in obesity‐induced OA mice injected with liposomal‐CGS21680 and increased nuclear p21 and p16 in A2AR knockout mouse chondrocytes compared to wild‐type mice. A2AR agonism also increased activity of the chondrocyte Sirt1/AMPK energy‐sensing pathway by enhancing nuclear Sirt1 localization and upregulating T172‐phosphorylated (active) AMPK protein levels. Lastly, A2AR activation in TC28a2 and primary human chondrocytes reduced wild‐type p53 and concomitantly increased p53 alternative splicing leading to increase in an anti‐senescent p53 variant, Δ133p53α. The results reported here indicate that A2AR signaling promotes chondrocyte homeostasis in vitro and reduces OA cartilage development in vivo by reducing chondrocyte senescence.
Artificial Intelligence Screening of Medical School Applications: Development and Validation of a Machine-Learning Algorithm
Authors: Triola Marc M. , Reinstein Ilan , Marin Marina , Gillespie Colleen , Abramson Steven , Grossman Robert I. , Rivera Rafael
Published: March 2023

Purpose

To explore whether a machine-learning algorithm could accurately perform the initial screening of medical school applications.

Method

Using application data and faculty screening outcomes from the 2013 to 2017 application cycles (n = 14,555 applications), the authors created a virtual faculty screener algorithm. A retrospective validation using 2,910 applications from the 2013 to 2017 cycles and a prospective validation using 2,715 applications during the 2018 application cycle were performed. To test the validated algorithm, a randomized trial was performed in the 2019 cycle, with 1,827 eligible applications being reviewed by faculty and 1,873 by algorithm.

Results

The retrospective validation yielded area under the receiver operating characteristic (AUROC) values of 0.83, 0.64, and 0.83 and area under the precision–recall curve (AUPRC) values of 0.61, 0.54, and 0.65 for the invite for interview, hold for review, and reject groups, respectively. The prospective validation yielded AUROC values of 0.83, 0.62, and 0.82 and AUPRC values of 0.66, 0.47, and 0.65 for the invite for interview, hold for review, and reject groups, respectively. The randomized trial found no significant differences in overall interview recommendation rates according to faculty or algorithm and among female or underrepresented in medicine applicants. In underrepresented in medicine applicants, there were no significant differences in the rates at which the admissions committee offered an interview (70 of 71 in the faculty reviewer arm and 61 of 65 in the algorithm arm; P = .14). No difference in the rate of the committee agreeing with the recommended interview was found among female applicants (224 of 229 in the faculty reviewer arm and 220 of 227 in the algorithm arm; P = .55).

Conclusions

The virtual faculty screener algorithm successfully replicated faculty screening of medical school applications and may aid in the consistent and reliable review of medical school applicants.
Early Complications After Posterior Spinal Fusion in Patients With Rett Syndrome
Authors: Taylor Tristen N. , Bridges Callie S. , Nordstrom Luke A. , Hanson Darrell S. , Gerow Frank T. , Smith Brian G.
Published: March 2023

Background:

Neuromuscular scoliosis in Rett syndrome (RS) is common, progressive, and often requires posterior spinal fusion (PSF). While PSF is associated with improved overall outcomes, there is a paucity of information describing complications. We aimed to report the postoperative complications, readmissions, and reoperations for patients with RS undergoing PSF.

Methods:

Female pediatric patients with RS treated by PSF with segmental instrumentation, with or without concurrent pelvis fixation, during January 2012 to August 2022 were included. Preoperative patient characteristics, intraoperative data (estimated blood loss, cell saver, packed red blood cells transfused), postoperative complications according to the Modified Clavien-Dindo-Sink classification within 90 days, unplanned readmissions within 30 days, and unplanned reoperations within 90 days were recorded.

Results:

A total of 25 females were included. The mean (SD) age at surgery was 12.9 (1.8) years and the mean follow-up of 38.6 (24.9) months. The mean preoperative major coronal curve was 79 degrees (23 degrees) which decreased to 32 degrees (15 degrees) by the last follow-up (P<0.001). The median estimated blood loss was 600 mL and length of stay was 7 days. There were 81 total postoperative complications (3.2 complications/patient). Eight (32%) had grade IVa complications (disseminated intravascular coagulopathy, hypotensive shock, respiratory failure, chronic urosepsis). Five (20%) patients experienced seizures, 48% had pulmonary complications, and 56% had gastrointestinal complications. There were 3 readmissions (12%) within 30 days for pneumonia and 2 (8%) reoperations (an incision and drainage and C2-T2 fusion for significant kyphosis) within 90 days. One patient also had their fusion extended to the pelvis 1 year later. There were more nonambulatory patients in the group fused to the pelvis, but otherwise no differences between those fused and unfused to the pelvis.

Conclusions:

This is the largest review of early postoperative complications for patients with RS who underwent PSF. PSF effectively reduced the major coronal curve, but surgeons and families should be aware of a high postoperative seizure and respiratory complication rate, as well as 8% having reoperations within 90 days and 12% being readmitted within 30 days.

Level of Evidence:

Level IV—therapeutic study.
Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma
Authors: Mao Li , Su Sheng , Li Jia , Yu Songyang , Gong Yu , Chen Changzhou , Hu Zhiqiang , Huang Xiaowu
Published: March 2023

Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigated CAR T cells targeting MUC1 in solid cancer models, Tn-MUC1-targeted CAR T cells have not yet to be reported in ICC. In this study, we confirmed Tn-MUC1 as a potential therapeutic target for ICC and demonstrated that its expression level was positively correlated with the poor prognosis of ICC patients. More importantly, we successfully developed effective CAR T cells to target Tn-MUC1-positive ICC tumors and explored their antitumor activities. Our results suggest the CAR T cells could specifically eliminate Tn-MUC1-positive ICC cells, but not Tn-MUC1-negative ICC cells, in vitro and in vivo. Therefore, our study is expected to provide new therapeutic strategies and ideas for the treatment of ICC.
Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity
Authors: D’Ascanio Antonella M. , Mullally Jamie A. , Frishman William H.
Published: March 2023

Despite the worldwide epidemic of obesity, there remain few approved pharmacological treatment options to bridge the gap between lifestyle therapy and bariatric surgery. Cagrilintide is an amylin-analog, now being developed in combination with the GLP-1 agonist semaglutide to achieve sustained weight loss in persons with overweight and obesity. Amylin, released with insulin from beta cells in the pancreas, induces its satiating effect via both the homoeostatic and hedonic regions of the brain. Semaglutide, a GLP-1 receptor agonist, reduces appetite via GLP-1 receptors in the hypothalamus and increases the production of insulin, and reduces glucagon secretion, delaying gastric emptying. These separate, but related mechanisms of action of an amylin-analog and a GLP-1 receptor agonist appear to have an additive effect on appetite reduction. Given the heterogeneity and complex pathogenesis of obesity, combination therapy with multiple pathophysiological targets is a logical approach to increasing weight loss response with pharmacotherapy. Cagrilintide alone, as well as cagrilintide in combination with semaglutide have shown promising weight loss in clinical trials that supports the further development of this therapy for sustained weight management.
Does Fitzpatrick Score Predict Flap Loss? Microsurgical Breast Reconstruction Outcomes of Varying Skin Color
Authors: Perez Kevin , Steppe Cyrus , Teotia Sumeet S. , Haddock Nicholas T.
Published: March 2023

Background:

The aim of this study was to seek evidence that patients with darker Fitzpatrick score skin tones are more susceptible to flap loss due to unsalvaged vascular compromise in autologous flap breast reconstruction.

Methods:

This is a retrospective study conducted on patients who underwent any type of autologous flap breast reconstruction performed by the two senior authors at an academic center between January 2010 and December 2021. The sole primary outcome variable was flap loss. Patient skin tone was assessed using the Fitzpatrick scale on clinical photographs of patients.

Results:

A total of 1115 pateints underwent autologous flap breast reconstruction, of which only 56 met both exclusion and inclusion criteria with 58 individual breasts being included in the final study population. The most common race of subjects was White (n = 33; 56.9%) while the most common Fitzpatrick score skin tone was type II (n = 22; 37.9%). The Cochran-Armitage test of trend showed a statistically significant linear trend, P = 0.006, with darker Fitzpatrick score skin tones associated with a higher proportion of flap loss in patients who had vascular compromise. A logistic regression showed that none of the predictor variables were significant.

Conclusions:

Patients with darker Fitzpatrick skin tones were associated with flap loss after vascular compromise. To prevent flap loss in patients who have darker Fitzpatrick score skin tones, more aggressive flap monitoring should be taken into consideration in the immediate postoperative setting.
Comparison of Long-term Surgical Outcomes and Microsurgical Skills between Independent and Integrated Plastic Surgery Trainees
Authors: Hassan Abbas M. , Egro Francesco M. , Talanker Michael M. , Shah Nikhil R. , Liu Jun , Maricevich Renata S. , Chang Edward I. , Hanasono Matthew M. , Selber Jesse C. , Butler Charles E.
Published: March 2023

Background:

We compared the surgical skills and outcomes of microsurgical fellows who completed an independent versus integrated plastic surgery residency.

Methods:

We reviewed outcomes of abdominal wall reconstructions performed autonomously by microsurgical fellows at our institution from March 2005 to June 2019; outcome measures included hernia recurrence, surgical site occurrence, surgical site infection, length of hospital stay, unplanned return to the operating room, and 30-day readmission. The microsurgical skills were prospectively evaluated using the validated Structured Assessment of Microsurgical Skills at the start and end of the fellowship, in an animal laboratory model and clinical microsurgical cases. Multivariable hierarchical models were constructed to evaluate study outcomes.

Results:

We identified 44 fellows and 118 consecutive patients (52% women) who met our inclusion criteria. Independent fellows performed 55% (n = 65) of cases, and 45% were performed by integrated fellows. We found no significant difference in hernia recurrence, surgical site occurrences, surgical site infections, 30-day readmission, unplanned return to the operating room, or length of stay between the two groups in adjusted models. Although laboratory scores were similar between the groups, integrated fellows demonstrated higher initial clinical scores (42.0 ± 4.9 versus 37.7 ± 5.0, P = 0.04); however, the final clinical scores were similar (50.8 ± 6.0 versus 48.9 ± 5.2, P = 0.45).

Conclusions:

Independent and integrated fellows demonstrated similar long-term patient outcomes. Although integrated fellows had better initial microsurgical skills, evaluation at the conclusion of fellowship revealed similar performance, indicating that fellowship training allows for further development of competent surgeons.
How Big Is Too Big? Exploring the Relationship between Breast Implant Volume and Postoperative Complication Rates in Primary Breast Augmentations
Authors: Medor Maria C. , Bouhadana Gabriel , Churchill Isabella F. , Hemmerling Thomas , Bonapace-Potvin Michelle , Papanastasiou Constantine , Mussie Abiye , Borsuk Daniel E. , Papanastasiou Vasilios W.
Published: March 2023

Background:

There is no consensus regarding implant size as an independent risk factor for complications in primary breast augmentation. Choosing appropriate implant volume is an integral part of the preoperative planning process. The current study aims to assess the relationship between implant size and the development of complications following augmentation mammaplasty.

Methods:

A retrospective chart review of patients undergoing primary breast augmentation at the Westmount Institute of Plastic Surgery between January 2000 and December 2021 was conducted. Demographics, implant characteristics, surgical technique, postoperative complications, and follow-up times were recorded. Univariate logistic regression was used to identify independent predictors, which were then included in multivariate logistic regressions of implant volume and implant volume/body mass index (BMI) ratio regarding complications.

Results:

A total of 1017 patients (2034 breasts) were included in this study. The average implant volume used was 321.4 ± 57.5 cm3 (range: 110–605). Increased volume and volume/BMI ratio were associated with a significant increase in risk of implant rupture (odds ratio = 1.012, P < 0.001 and 1.282, P < 0.001 respectively). Rates of asymmetry were significantly associated with increases in implant volume and volume/BMI ratio (odds ratio = 1.005, P = 0.004 and 1.151, P < 0.001, respectively). No single implant volume or volume/BMI ratio above which risks of complications significantly increase was identified.

Conclusions:

Implant rupture and postoperative asymmetries are positively correlated with bigger implant volumes. Implant size could likely be a useful independent predictor of certain complications, especially in patients with high implant to BMI ratios.
Reconstruction of the Flexor Pollicis Longus Tendon with Vascularized Tendon with Ulnar Artery Preservation
Authors: Cavadas Pedro C. , Padial Beatriz
Published: March 2023

Background:

Reconstruction of the flexor pollicis longus tendon using staged grafting yields modest results. A modification of the pedicled vascularized flexor digitorum superficialis transfer, without division of the ulnar artery, was used in five patients.

Methods:

The flexor digitorum superficialis and its gliding tissue were transferred in five patients, based on a branch of the ulnar artery without division of the ulnar vessels. Functional results were evaluated using a total active range of motion and Buck-Gramko score at 10 months by an independent hand therapist.

Results:

The mean total active motion of the interphalangeal joint was 49 degrees, with a Buck-Gramko score of excellent in three cases and good in two. No complications were recorded.

Conclusion:

Reconstruction of the flexor pollicis longus tendon with single-staged vascularized FDS transfer without ulnar artery division yielded good results in a small cohort of five cases.
Bilateral Knee Soft-tissue Reconstruction after High-voltage Electrical Burn Injuries
Authors: Déniz Martínez Alejandro , Santamaría Córdoba Natalia , Ayala Parra David G.
Published: March 2023

This is the case of a 21-year-old man who had extensive and bilateral knee soft-tissue damage after a high-voltage electrical discharge. In its reconstruction, we simultaneously performed the pedicled medial sural artery perforator flap. Even though mild complications took place, this alternative proved helpful and reliable, providing an easily adjustable skin island and allowing for the patient’s rapid rehabilitation and a satisfactory aesthetic outcome. Although this flap’s reconstructive potential is known in other etiologies, the present report outlines its substantial potential in the case of electrical burn injuries, as it has barely been recognized before.