bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of sex chromosomes and primary sex ratio in the small hive beetle, a worldwide parasite of honey bees
Authors: Huang Qiang , Sim Sheina B , Geib Scott M , Childers Anna , Liu Junfeng , Wei Xiuxiu , Han Wensu , Posada-Florez Francisco , Xue Allen Z , Li Zheng , Evans Jay D
Published: July 2023

Background

The small hive beetle (SHB), Aethina tumida, has emerged as a worldwide threat to honey bees in the past two decades. These beetles harvest nest resources, feed on larval bees, and ultimately spoil nest resources with gelatinous slime together with the fungal symbiont Kodamaea ohmeri.

Results

Here, we present the first chromosome-level genome assembly for the SHB. With a 99.1% representation of conserved (BUSCO) arthropod genes, this resource enables the study of chemosensory, digestive, and detoxification traits critical for SHB success and possible control. We use this annotated assembly to characterize features of SHB sex chromosomes and a female-skewed primary sex ratio. We also found chromosome fusion and a lower recombination rate in sex chromosomes than in autosomes.

Conclusions

Genome-enabled insights will clarify the traits that allowed this beetle to exploit hive resources successfully and will be critical for determining the causes of observed sex ratio asymmetries.
Association of Neurofilament Light Chain With the Antidepressant Effects of Low-Dose Ketamine Infusion Among Patients With Treatment-Resistant Depression
Authors: Lin Wei-Chen , Su Tung-Ping , Li Cheng-Ta , Wu Hui-Ju , Bai Ya-Mei , Liu Yu-Li , Tu Pei-Chi , Chen Mu-Hong
Published: July 2023

Background

The role of neurofilament light chain (NFL) in treatment-resistant depression (TRD) is unclear. Whether baseline NFL concentrations are associated with the antidepressant effects of low-dose ketamine infusion has not been determined.

Methods

The NFL concentrations of 71 patients with TRD and 17 healthy controls were assessed. Patients with TRD were randomly administered a single infusion of 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were assessed before infusion and sequentially at postinfusion timepoints (after 240 minutes and after 2–7 and 14 days) using the Hamilton Depression Rating Scale (HDRS).

Results

After adjustment for age, sex, and body mass index, patients with TRD were more likely to have higher concentrations of NFL than healthy controls (P < .001). A generalized estimating equation model with adjustments for infusion group, age, sex, body mass index, and baseline HDRS scores showed that baseline NFL concentrations were positively associated with subsequent HDRS scores following low-dose ketamine infusion (P = .038).

Discussion

Higher concentrations of NFL were observed among patients with TRD compared with healthy controls. Baseline NFL concentrations may predict the antidepressant effects of low-dose ketamine infusion.
Hiding in Plain Sight: Victim Participation in the Search for Disappeared Persons, a Contribution to (Procedural) Justice
Authors: Jones Briony , Ott Lisa , Rauschenbach Mina , Sanchez Camilo
Published: July 2023

Enforced disappearance is a human rights violation and crime widely used in repression and armed conflict contexts. The families of the forcibly disappeared are left in a state of ambiguous loss as they search for the disappeared to satisfy their right to truth and achieve healing and closure. However, there is limited knowledge of the obstacles that hinder the search in practice and of how families can best be supported when mobilizing in search processes. Taking a multi-disciplinary approach, using insights from procedural justice research and qualitative interviews undertaken with families and other actors involved in supporting search processes in Colombia and El Salvador, we enhance and expand the scholarship that acknowledges the importance of victim participation and victims as key justice stakeholders.
Poisson Behavior for Chains of Small Quadratic Non-Residues
Authors: Basak Debmalya , Nath Kunjakanan , Zaharescu Alexandru
Published: July 2023

It is known that under the Generalized Riemann Hypothesis, the smallest quadratic non-residue modulo a prime $p$ is less than or equal to $(\log p)^{2}$. In ranges slightly larger, of size $(\log p)^{A}$ with $A>2$, we consider chains of $r$ consecutive quadratic non-residues. We prove unconditionally that for almost all primes $p$ in short intervals, these chains exhibit Poisson behavior.
Interpellation and the Politics of Belonging: A Psychoanalytical Framework
Authors: Mandelbaum Moran M
Published: July 2023

Interpellation, the production and hailing of subjectivities, is key to poststructuralist international relations (IR) theory and yet with some notable exceptions interpellation/hailing as an analytical concept remains somewhat undertheorized. This paper presents a Lacanian–Žižekian psychoanalytical theorization of interpellation in IR, while engaging with the ontology and epistemology of belonging. More specifically, this paper develops four major psychoanalytical concepts: void/lack, fantasy, jouissance, and desire, as it argues that void/lack at the subjective and objective levels renders interpellation possible and destabilises it, thus accounting for the im/possibility of belonging. This paper illustrates the psychoanalytical framework of interpellation by analyzing national-populism as manifested in the Brexit discourse in the UK as well as the interpellation in homonationalism.
The mutual regulation between γδ T cells and macrophages during wound healing
Authors: Hu Wengang , Zhang Xiaorong , Sheng Hao , Liu Zhongyang , Chen Yunxia , Huang Yong , He Weifeng , Luo Gaoxing
Published: July 2023

Macrophages are the main cells shaping the local microenvironment during wound healing. As the prime T cells in the skin, γδ T cells participate in regulating microenvironment construction, determining their mutual regulation helps to understand the mechanisms of wound healing, and explore innovative therapeutic options for wound repair. This review introduced their respective role in wound healing firstly, and then summarized the regulatory effect of γδ T cells on macrophages, including chemotaxis, polarization, apoptosis, and pyroptosis. Last, the retrograde regulation on γδ T cells by macrophages was also discussed. The main purpose is to excavate novel interventions for treating wound and provide new thought for further research.
Leprosy misdiagnosed as chronic urticaria in a migrant
Authors: Magnaterra Elisabetta , Scandagli Ilaria , Zuccaro Biancamaria , Maio Vincenza , Simi Sara , Massi Daniela , Fiallo Paolo , Francalanci Stefano , Difonzo Elisa , Pisano Luigi
Published: July 2023

A Sri Lankan man presents with the suspicion of chronic idiopathic urticaria with angioedema, but facial swelling leads to an unexpected discovery. Thickened skin, nodules and neurological symptoms reveal the true culprit. Leprosy challenges diagnosis in non-endemic regions. Vigilance and comprehensive assessment are crucial to unmask this great imitator.
Stationary-to-migratory transition in glioblastoma stem-like cells driven by a fatty acid-binding protein 7-RXRα neurogenic pathway
Authors: Liu Rong-Zong , Choi Won-Shik , Jain Saket , Xu Xia , Elsherbiny Marwa E , Glubrecht Darryl D , Tessier Anthony G , Easaw Jacob C , Fallone B Gino , Godbout Roseline
Published: July 2023

Background

Glioblastoma (GBM) stem-like cells (GSCs) are crucial drivers of treatment resistance and tumor recurrence. While the concept of “migrating” cancer stem cells was proposed a decade ago, the roles and underlying mechanisms of the heterogeneous populations of GSCs remain poorly defined.

Methods

Cell migration using GBM cell lines and patient-derived GSCs was examined using Transwell inserts and the scratch assay. Single-cell RNA sequencing data analysis were used to map GSC drivers to specific GBM cell populations. Xenografted mice were used to model the role of brain-type fatty acid-binding protein 7 (FABP7) in GBM infiltration and expansion. The mechanism by which FABP7 and its fatty acid ligands promote GSC migration was examined by gel shift and luciferase gene reporter assays.

Results

A subpopulation of FABP7-expressing migratory GSCs was identified, with FABP7 upregulating SOX2, a key modulator for GBM stemness and plasticity, and ZEB1, a prominent factor in GBM epithelial-mesenchymal transition and invasiveness. Our data indicate that GSC migration is driven by nuclear FABP7 through activation of RXRα, a nuclear receptor activated by polyunsaturated fatty acids (PUFAs).

Conclusion

Infiltrative progression in GBM is driven by migratory GSCs through activation of a PUFA-FABP7-RXRα neurogenic pathway.
Harm Reduction: A Missing Piece to the Holistic Care of Patients Who Inject Drugs
Authors: Nolan Nathanial S , Fracasso Francis Sarah M , Marks Laura R , Beekmann Susan E , Polgreen Philip M , Liang Stephen Y , Durkin Michael J
Published: July 2023

Background

The rise in injection drug use (IDU) has led to an increase in drug-related infections. Harm reduction is an important strategy for preventing infections among people who inject drugs (PWID). We attempted to evaluate the harm reduction counseling that infectious diseases physicians provide to PWID presenting with infections.

Methods

An electronic survey was distributed to physician members of the Emerging Infections Network to inquire about practices used when caring for patients with IDU-related infections.

Results

In total, 534 ID physicians responded to the survey. Of those, 375 (70%) reported routinely caring for PWID. Most respondents report screening for human immunodeficiency virus (HIV) and viral hepatitis (98%) and discussing the risk of these infections (87%); 63% prescribe immunization against viral hepatitis, and 45% discuss HIV preexposure prophylaxis (PrEP). However, 55% of respondents (n = 205) reported not counseling patients on safer injection strategies. Common reasons for not counseling included limited time and a desire to emphasize antibiotic therapy/medical issues (62%), lack of training (55%), and believing that it would be better addressed by other services (47%). Among respondents who reported counseling PWID, most recommended abstinence from IDU (72%), handwashing and skin cleansing before injection (62%), and safe disposal of needles/drug equipment used before admission (54%).

Conclusions

Almost all ID physicians report screening PWID for HIV and viral hepatitis and discussing the risks of these infections. Despite frequently encountering PWID, fewer than half of ID physicians provide safer injection advice. Opportunities exist to standardize harm reduction education, emphasizing safer injection practices in conjunction with other strategies to prevent infections (eg, HIV PrEP or hepatitis A virus/hepatitis B virus vaccination).
Cosmic-ray-driven enhancement of the C0/CO abundance ratio in W 51 C
Authors: Yamagishi Mitsuyoshi , Furuya Kenji , Sano Hidetoshi , Izumi Natsuko , Takekoshi Tatsuya , Kaneda Hidehiro , Nakanishi Kouichiro , Shimonishi Takashi
Published: July 2023

We examine spatial variations of the C0$/$CO abundance ratio (XC/CO) in the vicinity of the γ-ray supernova remnant W 51 C, based on [C i] (3P1–3P0), 12CO(1–0), and 13CO(1–0) observations with the ASTE and Nobeyama 45 m telescopes. We find that XC/CO varies in a range of 0.02–0.16 (0.05 in median) inside the molecular clouds of AV > 100 mag, where photodissociation of CO by the interstellar UV is negligible. Furthermore, XC/CO is locally enhanced by a factor of up to four near the W 51 C center, depending on the projected distance from the W 51 C center. In high-AV molecular clouds, XC/CO is determined by the ratio of the cosmic-ray (CR) ionization rate to the H2 density, and we find no clear spatial variation of the H2 density against the projected distance. Hence, the high CR ionization rate may locally enhance XC/CO near the W 51 C center. We also find that the observed spatial extent of the enhanced XC/CO (∼17 pc) is consistent with the diffusion distance of CRs with an energy of 100 MeV. This fact suggests that the low-energy CRs accelerated in W 51 C enhance XC/CO. The CR ionization rate in the XC/CO-enhanced cloud is estimated to be 3 × 10−16 s−1 on the basis of time-dependent photodissociation region simulations of XC/CO, the value of which is 30 times higher than that in the standard Galactic environment. These results demonstrate that [C i] is a powerful probe to investigate the interaction between CRs and the interstellar medium for a wide area in the vicinity of supernova remnants.
The Roles of Functional Amino Acids in Plant Growth and Development
Authors: Kawade Kensuke , Tabeta Hiromitsu , Ferjani Ali , Hirai Masami Yokota
Published: July 2023

Plants incorporate acquired carbon and nitrogen into amino acid metabolism, whereby the building blocks of proteins and the precursors of various metabolites are produced. This fundamental demand requires tight amino acid metabolism to sustain physiological homeostasis. There is increasing evidence that amino acid metabolism undergoes plastic alteration to orchestrate specific growth and developmental events. Consequently, there has been a gradual exploration of the interface at which amino acid metabolism and plant morphogenesis are mutually affected. This research progress offers an opportunity to explore amino acid metabolism, with the goal to understand how it can be modulated to serve special cellular needs and regulate specific growth and developmental pathways. Continuous improvements in the sensitivity and coverage of metabolomics technology, along with the development of chemoinformatics, have allowed the investigation of these research questions. In this review, we summarize the roles of threonine, serine, arginine and γ-aminobutyric acid as representative examples of amino acids relevant to specific developmental processes in plants (‘functional amino acids’). Our objective is to expand perspectives regarding amino acid metabolism beyond the conventional view that it is merely life-supporting machinery.
Exosome-shuttled miR-126 mediates ethanol-induced disruption of neural crest cell-placode cell interaction by targeting SDF1
Authors: Li Yihong , Cai Ting , Liu Huina , Liu Jie , Chen Shao-Yu , Fan Huadong
Published: July 2023

During embryonic development, 2 populations of multipotent stem cells, cranial neural crest cells (NCCs) and epibranchial placode cells (PCs), are anatomically adjacent to each other. The coordinated migration of NCCs and PCs plays a major role in the morphogenesis of craniofacial skeletons and cranial nerves. It is known that ethanol-induced dysfunction of NCCs and PCs is a key contributor to the defects of craniofacial skeletons and cranial nerves implicated in fetal alcohol spectrum disorder (FASD). However, how ethanol disrupts the coordinated interaction between NCCs and PCs was not elucidated. To fill in this gap, we established a well-designed cell coculture system to investigate the reciprocal interaction between human NCCs (hNCCs) and human PCs (hPCs), and also monitored the migration behavior of NCCs and PCs in zebrafish embryos. We found that ethanol exposure resulted in a disruption of coordinated hNCCs-hPCs interaction, as well as in zebrafish embryos. Treating hNCCs-hPCs with exosomes derived from ethanol-exposed hNCCs (ExoEtOH) mimicked ethanol-induced impairment of hNCCs-hPCs interaction. We also observed that SDF1, a chemoattractant, was downregulated in ethanol-treated hPCs and zebrafish embryos. Meanwhile, miR-126 level in ExoEtOH was significantly higher than that in control exosomes (ExoCon). We further validated that ExoEtOH-encapsulated miR-126 from hNCCs can be transferred to hPCs to suppress SDF1 expression in hPCs. Knockdown of SDF1 replicated ethanol-induced abnormalities either in vitro or in zebrafish embryos. On the contrary, overexpression of SDF1 or inhibiting miR-126 strongly rescued ethanol-induced impairment of hNCCs-hPCs interaction and developmental defects.
Limb anatomy of the Triassic turtles: appendicular osteology of Proterochersis (Testudinata, Proterochersidae)
Authors: Szczygielski Tomasz , Piechowski Rafał
Published: July 2023

The turtle locomotor system is heavily modified owing to the severe impact of development of the shell on the body plan of these reptiles. Although limb and girdle osteology of the earliest, Triassic turtles is relatively well understood in general, the exact impacts of variability, ontogeny and preservation (e.g. deformation) on the observed morphologies have rarely been considered in detail. Here, we describe in detail and document the osteology and intraspecific variability of the limbs and girdles of Proterochersis spp., the basalmost true turtles (Testudinata). We also provide a synthesis of currently available data and detailed comparisons with other Triassic stem turtles to gain a better understanding of the diagnostic value of the early turtle appendicular skeleton and to pave the way for future biomechanical and functional studies. Our data suggest that Proterochersis spp. could be at least partly aquatic and could change their preferred habitat during ontogeny, with larger (and, presumably, older) specimens presenting more characters suggestive of a more terrestrial environment.
Disrupted glucose homeostasis and glucagon and insulin secretion defects in Robo βKO mice
Authors: Adams Melissa T. , Waters Bayley J. , Nimkulrat Sutichot D. , Blum Barak
Published: July 2023

The axon guidance proteins, Roundabout (Robo) receptors play a critical role in morphogenesis of the islets of Langerhans. Mice with a β cell‐selective deletion of Robo (Robo βKO), show severely disrupted spatial architecture of their islets, without defects in β cell differentiation or maturity. We have recently shown that Robo βKO mice have reduced synchronous glucose‐stimulated β cell calcium oscillations in their islets in vivo, likely disrupting their pulsatile insulin secretion. Here, we analyze whole‐body metabolic regulation in Robo βKO mice. We show that Robo βKO mice have mild defects in glucose homeostasis, and altered glucagon and insulin secretion. However, we did not observe any severe whole‐body glucoregulatory phenotype following the disruption of islet architecture in Robo βKO. Our data suggest that islet architecture plays only a mild role in overall glucoregulation.
Chromatin architectural factor CTCF is essential for progesterone‐dependent uterine maturation
Authors: Hewitt Sylvia C. , Gruzdev Artiom , Willson Cynthia J. , Wu San‐Pin , Lydon John P. , Galjart Niels , DeMayo Francesco J.
Published: July 2023

Receptors for estrogen and progesterone frequently interact, via Cohesin/CTCF loop extrusion, at enhancers distal from regulated genes. Loss‐of‐function CTCF mutation in >20% of human endometrial tumors indicates its importance in uterine homeostasis. To better understand how CTCF‐mediated enhancer‐gene interactions impact endometrial development and function, the Ctcf gene was selectively deleted in female reproductive tissues of mice. Prepubertal Ctcfd/d uterine tissue exhibited a marked reduction in the number of uterine glands compared to those without Ctcf deletion (Ctcff/f mice). Post‐pubertal Ctcfd/d uteri were hypoplastic with significant reduction in both the amount of the endometrial stroma and number of glands. Transcriptional profiling revealed increased expression of stem cell molecules Lif, EOMES, and Lgr5, and enhanced inflammation pathways following Ctcf deletion. Analysis of the response of the uterus to steroid hormone stimulation showed that CTCF deletion affects a subset of progesterone‐responsive genes. This finding indicates (1) Progesterone‐mediated signaling remains functional following Ctcf deletion and (2) certain progesterone‐regulated genes are sensitive to Ctcf deletion, suggesting they depend on gene‐enhancer interactions that require CTCF. The progesterone‐responsive genes altered by CTCF ablation included Ihh, Fst, and Errfi1. CTCF‐dependent progesterone‐responsive uterine genes enhance critical processes including anti‐tumorigenesis, which is relevant to the known effectiveness of progesterone in inhibiting progression of early‐stage endometrial tumors. Overall, our findings reveal that uterine Ctcf plays a key role in progesterone‐dependent expression of uterine genes underlying optimal post‐pubertal uterine development.
Pathogenesis of vasculopathy in systemic sclerosis and its contribution to fibrosis
Authors: Kawaguchi Yasushi , Kuwana Masataka
Published: July 2023

Purpose of review

In patients with systemic sclerosis (SSc), vascular manifestations precede skin and organ fibrosis. There is increasing evidence demonstrating a pathogenic link between early vascular injury and subsequent development of tissue fibrosis.

Recent findings

Our knowledge of cellular and molecular mechanisms underlying a unique relationship between SSc-related vasculopathy and fibrosis has changed over the last few years. There is increasing evidence showing viral infection as a potential trigger elucidating vascular injury. Due to defective vascular repair machinery, this initial event results in endothelial cell activation and apoptosis as well as the recruitment of inflammatory/immune cells, leading to endothelial-to-mesenchymal transition. This sequential process induces destructive vasculopathy in capillaries, fibroproliferative vascular lesions in arteries, and excessive fibrosis in the surrounding tissue. A variety of molecular mechanisms and pathways involved in vascular remodeling linked to subsequent excessive fibrosis have been identified and serve as attractive therapeutic targets for SSc.

Endothelial injury may play a central role in connecting three features that characterize SSc pathogenesis: vasculopathy, chronic inflammation, and fibrosis. Our understanding of the processes responsible for myofibroblast differentiation triggered by vascular injury will provide the rationale for novel targeted therapies for SSc.
Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China: Findings from real-world data
Authors: He Ruoxi , Ren Xiaoxia , Huang Ke , Lei Jieping , Niu Hongtao , Li Wei , Dong Fen , Li Baicun , Wang Ye , Yang Ting , Wang Chen
Published: July 2023

Background:

Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD.

Methods:

Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared.

Results:

Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34%–3.10%), 2.09% (95% CI: 1.76%–2.43%), and 1.25% (95% CI: 0.99%–1.51%), respectively. In multivariable models, age ≥60 years (60–69 years, odds ratio [OR]: 1.90, 95% CI: 1.11–3.25; ≥80 years, OR: 2.00, 95% CI: 1.06–3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96–13.21), urban residence (OR: 1.69, 95% CI: 1.07–2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21–2.58; senior high school or above, OR: 2.61, 95% CI: 1.69–4.03), former smoking (OR: 1.79, 95% CI: 1.15–2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29–4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45–0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment.

Conclusions:

Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.
Prognosis and outcome of intrauterine treatment of fetuses with critical congenital heart disease
Authors: Zhao Liqing , Wang Lei , Xia Hongping , Wu Yurong , Jiao Xianting , Zhu Hong , Chen Sun , Sun Kun
Published: July 2023

Background:

Intrauterine valvuloplasty is an innovative therapy, which promotes ventricular growth and function in some congenital heart diseases (CHDs). The technique remains challenging and can only be performed in a few centers. This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention (FCI) in fetuses with critical CHD in an experienced tertiary center.

Methods:

Five fetal aortic valvuloplasty (FAV) or fetal pulmonary valvuloplasty (FPV) procedures were performed in our fetal heart center between August 2018 and May 2022. Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation, followed by evidence of increased blood flow across the valve and/or new regurgitation. Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods.

Results:

Five fetuses received FAV or FPV, including critical aortic stenosis ( n = 2) and pulmonary atresia with intact ventricular septum ( n = 3). The mean maternal age was 33.0 ± 2.6 years. The median gestational age (GA) at diagnosis was 24 weeks (range, 22–26 weeks). The median GA at intervention was 29 weeks (range, 28–32 weeks). All five cases underwent successful or partially successful procedures. One patient had pulmonary valve perforation without balloon dilation. No procedure-related deaths or significant complications occurred. However, one neonatal death occurred due to heart and renal failure. The median follow-up period was 29.5 months (range, 8.0–48.0 months). The four surviving patients had achieved biventricular circulation, exhibited improved valve, and ventricular development at the last follow-up visit.

Conclusion:

Intrauterine FCI could be performed safely with good prognosis in critical CHD.
Aortopathy: Effects of Lipid-Lowering Therapy
Authors: Vollaro Matthew , Sharma Tanya , Sharma Mala , Frishman William H. , Aronow Wilbert S.
Published: July 2023

Aortopathies can be congenital or acquired. Aortic atherosclerosis, abdominal aortic aneurysm, and degenerative aortic stenosis are some of the major manifestations of acquired aortopathy. Dyslipidemia, an imbalance of plasma lipid levels, is strongly associated with common aortopathies. A relationship between abdominal aortic aneurysm, degenerative aortic stenosis, and dyslipidemia has been identified in the literature but finding effective preventive strategies has been challenging. Nevertheless, lipid-lowering therapy remains a mainstay of both treatment and prevention. In patients with aortic atheroma, statins were found to be protective through the review of this study. There is currently no place for statins in the treatment or prevention of disease progression in patients with calcific aortic stenosis. Their low cost, widespread availability, and strong safety profile tip the risk-to-benefit ratio toward statins for abdominal aortic aneurysms but more research is needed. A review of proprotein convertase subtilisin/kexin type 9 inhibitors may yield similar benefits for all aortopathy patients; however, those results are not yet available.
Limited Sampling Strategy Using End of Infusion and Six-Hour Concentrations Overestimates Intravenous Busulfan Clearance Compared With Standard Six-Point Sampling in Hematopoietic Stem Cell Transplant Patients
Authors: Salman Bushra Mustafa , Al Riyami Intisar Mohammed , AalHamad Aya Hasan , Al-Khabori Murtadha
Published: July 2023

Background:

Therapeutic drug monitoring for busulfan (Bu) is important to improve outcomes of hematopoietic stem cell transplantation. However, standard therapeutic drug monitoring requires multiple samples and is inconvenient, labor-intensive, and costly. Accordingly, a limited sampling strategy (LSS) was evaluated, using 2-point sampling at end of infusion and at 6 hours, and the area-under-the-curve and Bu clearances (CLs) were compared with the results obtained from the standard sampling strategy (SSS) using 5–6 samples.

Method:

The analysis was based on retrospective clinical data from 202 patients receiving intravenous Bu before hematopoietic stem cell transplantation for malignant or nonmalignant conditions. Bu plasma concentrations were measured via liquid chromatography tandem-mass spectrometry, and pharmacokinetic parameters were calculated using the PKCNA package in R program.

Result:

A total of 502 doses were analyzed by applying SSS and LSS. Using the modified Bland–Altman plot, the mean percentage difference in CL between the SSS and LSS estimates of Bu 6-hourly regimen was −41% (Limits: −53% and −30%). In the once daily regimen, the mean difference in CL between the 2 strategies on the modified Bland–Altman plot was −22% (Limits: −66% and +22%).

Conclusions:

The Bu CL values estimated based on the BU concentration at end of infusion and at 6 hours postinfusion were significantly higher than the values obtained via the SSS.
Cross-cultural validation of the Lower Extremity Functional Scale in Serbian postmenopausal women with knee osteoarthritis
Authors: Minaković Ivana D. , Zvekić-Svorcan Jelena S. , Smuđa Mirjana N. , Živanović Dejan B. , Mikić Andrijana S. , Janković Tanja S. , Miljković Ana R.
Published: July 2023

Objective

Translation and cross-cultural validation of the Serbian version of the Lower Extremity Functional Scale (Srb-LEFS).

Methods

This prospective cross-sectional study initially included 186 postmenopausal women aged 60 to 75 years who underwent an x-ray examination of both knees, along with body mass, body height, waist circumference, knee range of motion, and blood pressure measurements. The laboratory analyses included the evaluation of fasting glucose levels and lipid profile. All participants completed the LEFS, Lequesne index, and 36-Item Short-Form Survey-RAND.

Results

The analyses revealed good internal consistency (α = 0.95), good test-retest reliability, and a two-factor structure of the Srb-LEFS. Concurrent validity analysis confirmed a significant positive correlation between Srb-LEFS scores and the 36-Item Short-Form Survey-RAND Physical Functioning subscale (r = 0.889, P < 0.0001), the Lequesne index (r = −0.976, P < 0.0001), and the Numeric Rating Scale for pain (r = −0.762, P < 0.0001). Convergent validity analyses revealed a statistically significant negative correlation between the Srb-LEFS scores and age (r = −0.25, P = 0.006), body mass index (r = −0.31, P < 0.01), and waist circumference (r = −0.37, P < 0.0001). The Srb-LEFS scores were statistically significantly higher among participants that reported moderate physical activity levels, as well as those that had fewer comorbidities, minor structural knee damage, greater knee range of motion, and greater quadriceps femoris muscle strength.

Conclusions

The Serbian version of the LEFS is feasible, valid, and reliable for use in both clinical practice and clinical studies to assess self-reported physical functioning in older individuals with knee osteoarthritis.
Identifying Palmar Skin Surface Landmark for Locating A2 Pulley during Cadaveric Dissection of the Hand
Authors: Alowais Fahad Abdullah , Alnaeem Hassan
Published: July 2023

Background:

The A2 and A4 pulleys are fibro-osseous structures that support the flexor tendon function. Injury to these pulleys can result in bowstringing and limited tendon excursion. Thus, having an understanding of the skin surface landmark of the A2 pulley is crucial to safeguard it during hand surgery.

Methods:

We performed cadaveric dissection of 62 hands. For 248 fingers, the measurement of distance A, which is half the distance between the palmar digital crease and proximal interphalangeal crease reflected in the palm, and distance B, which is the distance between the A2 pulley’s starting point and the palmar digital crease, were taken by a caliber. Statistical analysis was performed using the paired sample t test to determine whether there was a significant difference between distances A and B.

Results:

Our study revealed that there was no significant difference (p>0.05) between the measured starting point of the A2 pulley and its proposed surface landmark for the index, middle, and small fingers. Conversely, the ring finger showed a statistically significant difference of 1 mm more proximal.

Conclusions:

By measuring the distance between the palmar digital crease and proximal interphalangeal crease and reflecting it proximally in the palms, one can anticipate the location of the A2 pulley’s starting point for each digit, except for the ring finger. The ring finger’s starting point is 1 mm more proximal than the other digits. Knowing the starting point of the A2 pulley will help hand surgeons limit incisions and avoid accidental injury during hand surgery.
Endogenous Endophthalmitis Associated with Injection Drug Use Compared with Other Etiologies
Authors: Ciociola Elizabeth C. , Powell Jeffrey C. , Barnwell Eliza , Zehden Jason A. , Robbins Cason B. , Soundararajan Srinath , Singh Pali , Zhang Alice Yang , Fekrat Sharon , Greven Margaret A.
Published: July 2023

Purpose:

To compare features of endogenous endophthalmitis associated with injection drug use (IDU) to endogenous endophthalmitis from other etiologies.

Methods:

We retrospectively collected data on patients with endogenous endophthalmitis due to IDU or other causes from three academic tertiary care centers over a six-year period. Differences in presenting characteristics, culture results, treatment, and visual acuity (VA) were compared between groups.

Results:

Thirty-eight (34%) patients had IDU-associated endogenous endophthalmitis, while 75 (67%) had endogenous endophthalmitis from other causes. Compared to patients in the non-IDU group, IDU patients were significantly younger, more frequently male, had longer duration of symptoms at diagnosis, and were less likely to have bilateral disease (p<0.05 for all). IDU patients were less likely to have a systemic infection source identified (29% vs 71%, p<0.001) or have positive cultures (47% vs 80%, p<0.001). The IDU group was less likely to be admitted to the hospital (71% vs 92%, p=0.005) and less likely to receive treatment with intravenous antimicrobials (55% vs 83%, p=0.003). VA did not significantly differ between groups.

Conclusions:

Endophthalmitis related to IDU presents in younger patients with less comorbidities and frequently without positive cultures or an identifiable systemic source; therefore, a high index of suspicion is needed to identify this disease.
Deep learning-based analysis of infrared fundus photography for automated diagnosis of diabetic retinopathy with cataracts
Authors: Xue Wenwen , Zhang Juzhao , Ma Yingyan , Hou Junlin , Xiao Fan , Feng Rui , Zhao Ruiwei , Zou Haidong
Published: July 2023

Purpose:

To develop deep learning-based networks for the diagnosis of diabetic retinopathy (DR) with cataracts based on infrared fundus images.

Setting:

Shanghai General Hospital, Shanghai Eye Disease Prevention & Treatment Center, Shanghai, China.

Design:

Development and evaluation of an artificial intelligence (AI) diagnostic method.

Methods:

A total of 10 665 infrared fundus images from 4553 patients with diabetes were used to train and test the model. For image quality assessment, left and right eye classification, DR diagnosis and grading, and segmentation of 3 DR lesions, an end-to-end software using EfficientNet and UNet was developed. The accuracy and performance of the software in comparison to human experts was evaluated.

Results:

The model achieved an accuracy of 75.31% for left and right eye classification, 100% for DR grading and diagnosis tasks, and 73.67% for internal test set, with corresponding areas under the curve (AUCs) of 0.88, 1.00, and 0.89, respectively. For DR lesion segmentation, the AUCs of hemorrhagic, microangioma, and exudative lesions were 0.86, 0.66, and 0.84, respectively. In addition, a contrast test of human-machine film reading confirmed the software's high sensitivity (96.3%) and specificity (90.0%) and consistency with the manual film reading group (κ = 0.869, P < .001). This easily deployable software generated reports quickly and promoted efficient DR screening with cataracts in clinical and community settings.

Conclusions:

AI-assisted software can perform automatic analysis of infrared fundus images and has substantial application value for the diagnosis of DR patients with cataracts.
Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA
Authors: Anouti Ahmad , Patel Madhukar S. , VanWagner Lisa B. , Lee William M. , Asrani Sumeet K. , Mufti Arjmand R. , Rich Nicole E. , Vagefi Parsia A. , Shah Jigesh A. , Kerr Thomas A. , Pedersen Mark , Hanish Steven , Singal Amit G. , Cotter Thomas G.
Published: July 2023

Recent deceased-donor allocation changes in the United States may have increased high-Model for End-Stage Liver Disease (MELD) living donor liver transplantation (LDLT); however, outcomes in these patients remain poorly defined. We aimed to examine the impact of the MELD score on LDLT outcomes. Using UNOS data (January 1, 2010–December 31, 2021), LDLT recipients were identified and stratified into low-MELD (<15), intermediate-MELD (15–24), and high-MELD (≥25) groups. We compared outcomes between MELD-stratified LDLT groups and between MELD-stratified LDLT and donation after brain death liver transplantation recipients. We used Kaplan-Meier analysis to compare graft survival rates and multivariable Cox proportional hazards modeling to identify factors associated with graft outcomes. Of 3558 LDLTs, 1605 (45.1%) were low-MELD, 1616 (45.4%) intermediate-MELD, and 337 (9.5%) high-MELD. Over the study period, the annual number of LDLTs increased from 282 to 569, and the proportion of high-MELD LDLTs increased from 3.9% to 7.7%. Graft survival was significantly higher in low-MELD versus high-MELD LDLT recipients (adjusted HR = 1.36, 95% CI: 1.03–1.79); however, 5-year survival exceeded 70.0% in both groups. We observed no significant difference in graft survival between high-MELD LDLT and high-MELD donation after brain death liver transplantation recipients (adjusted HR: 1.25, 95% CI:0.99–1.58), with a 5-year survival of 71.5% and 77.3%, respectively. Low LDLT center volume (<3 LDLTs/year) and recipient life support requirement were both associated with inferior graft outcomes among high-MELD LDLT recipients. While higher MELD scores confer graft failure risk in LDLT, high-MELD LDLT outcomes are acceptable with similar outcomes to MELD-stratified donation after brain death liver transplantation recipients. Future practice guidance should consider the expansion of LDLT recommendations to high-MELD recipients in centers with expertise to help reduce donor shortage.
Combining Allograft Adipose and Fascia Matrix as an Off-the-Shelf Scaffold for Adipose Tissue Engineering Stimulates Angiogenic Responses and Activates a Proregenerative Macrophage Profile in a Rodent Model
Authors: Ziegler Mary E. , Khabaz Kameel , Khoshab Nima , Halaseh Faris F. , Chnari Evangelia , Chen Siwei , Baldi Pierre , Evans Gregory R.D. , Widgerow Alan D.
Published: July 2023

Objective

Bioscaffolds for treating soft tissue defects have limitations. As a bioscaffold, allograft adipose matrix (AAM) is a promising approach to treat soft tissue defects. Previously, we revealed that combining superficial adipose fascia matrix with AAM, components of the hypodermis layer of adipose tissue, improved volume retention, adipogenesis, and angiogenesis in rats 8 weeks after it was implanted compared with AAM alone. Here, we modified the fascia matrix and AAM preparation, examined the tissue over 18 weeks, and conducted a deeper molecular investigation. We hypothesized that the combined matrices created a better scaffold by triggering angiogenesis and proregenerative signals.

Methods

Human AAM and fascia matrix were implanted (4 [1 mL] implants/animal) into the dorsum of male Fischer rats (6–8 weeks old; ~140 g) randomly as follows: AAM, fascia, 75/25 (AAM/fascia), 50/50, and 50/50 + hyaluronic acid (HA; to improve extrudability) (n = 4/group/time point). After 72 hours, as well as 1, 3, 6, 9, 12, and 18 weeks, graft retention was assessed by a gas pycnometer. Adipogenesis (HE), angiogenesis (CD31), and macrophage infiltration (CD80 and CD163) were evaluated histologically at all time points. The adipose area and M1/M2 macrophage ratio were determined using ImageJ. RNA sequencing (RNA-seq) and bioinformatics were conducted to evaluate pathway enrichments.

Results

By 18 weeks, the adipose area was 2365% greater for 50/50 HA (281.6 ± 21.6) than AAM (11.4 ± 0.9) (P < 0.001). The M1/M2 macrophage ratio was significantly lower for 50/50 HA (0.8 ± 0.1) than AAM (0.9 ± 0.1) at 6 weeks (16%; P < 0.05). This inversely correlated with adipose area (r = −0.6; P > 0.05). The RNA-seq data revealed that upregulated adipogenesis, angiogenesis, and macrophage-induced tissue regeneration genes were temporally different between the groups.

Conclusions

Combining the fascia matrix with AAM creates a bioscaffold with an improved retention volume that supports M2 macrophage-mediated angiogenesis and adipogenesis. This bioscaffold is worthy of further investigation.
A Simplified Algorithmic Approach to Vulvar Reconstruction According to Various Types of Vulvar Defects
Authors: Han Woo Yeon , Kim Yeongsong , Han Hyun Ho
Published: July 2023

Objective

Various surgeons adopt various vulvar reconstruction methods for different types of vulvar defects to restore anatomical structures. Vulvar reconstruction has relatively few references as it is performed in many different ways. Our report aimed to create a simplified reconstruction algorithm that can be used to select the reconstruction flap and to compare clinical outcomes.

Methods

The patients who underwent vulvar reconstruction between April 2017 and May 2020 were retrospectively reviewed. The reconstruction flap was selected according to a suggested algorithm, which accounted for the defect location depending on the vulvo-thigh junctional crease—the visual landmark of the inferior pubic ramus—and proper perforator location. Postoperative surgical complications, functional outcomes, and oncologic outcomes were analyzed according to the histologic and flap types.

Results

Forty-seven patients underwent reconstruction with 31 internal pudendal artery perforator flaps (66%) and 16 profunda artery perforator flaps or transverse upper gracilis flaps (34%). The histologic type included 21 extramammary Paget disease (44.7%), 20 squamous cell carcinoma (42.6%), and 6 other types (12.8%). Postoperative complications, including wound and functional complications, occurred in 10 patients (21.3%). There were more cases of wound complications with profunda artery perforator flaps and transverse upper gracilis flaps (37.5%) than those with internal pudendal artery perforator flaps (12.9%) (P = 0.04). There were 7 cases (14.9%) of 2-year oncologic recurrence with no significant differences in terms of histologic or flap types.

Conclusions

According to our suggested simplified algorithm, various types of flaps resulted in reliable surgical outcomes with minimal complication rates and acceptable functional and oncologic outcomes, and the primary goals of vulvar reconstruction were achieved effectively. Using our algorithm, selection of the reconstruction method could be simplified and specified despite the complexity of vulvar defects.
Delayed Versus Immediate Breast Reconstruction in the Ambulatory Surgery Setting
Authors: Das Rishub K. , Mioton Lauren M. , Thayer Wesley P. , Drolet Brian C. , Perdikis Galen
Published: July 2023

Background

Breast reconstruction remains an important part of a patient's journey after the diagnosis of breast carcinoma and treatment with mastectomy. Although inpatient immediate breast reconstruction has been described, there is a paucity information about whether similar procedures are performed in the ambulatory setting.

Objective

The authors sought to investigate rates and patterns for delayed and immediate breast reconstruction in the ambulatory surgery setting using nationally representative data from 2016 to 2019.

Methods

Using the Nationwide Ambulatory Surgery Sample database, we identified patients with an International Statistical Classification of Disease and Related Health Problems, Tenth Revision, procedure code for breast reconstruction. Demographic and clinical characteristics were recorded for each encounter of breast reconstruction, and linear regression and logistic regression were used to assess for trends and disparities.

Results

National weighted estimates for ambulatory breast reconstruction increased by 15.6% from 89 237 in 2016 to 103 134 in 2019, resulting in 377 109 procedures during the study period. Inflation-adjusted total charges for ambulatory breast reconstruction were $14 billion between 2016 and 2019, or 1.7% of overall charges for ambulatory surgery. Immediate reconstruction was performed in 34.7% (95% CI, 33.4%–36.1%) of cases and increased by 46.9% from 26 930 in 2016 to 39 559 in 2019. Racial disparities were observed in access, comorbidities, and spending.

Conclusions

Our findings indicate a moderate increase in ambulatory breast reconstruction with a substantial growth in the performance of immediate breast reconstruction in the ambulatory setting.