bluuebunny/crossref_metadata_2025 huggingface dataset:
Concurrent Administration of COVID-19 and Influenza Vaccines Enhances Spike-Specific Antibody Responses
Authors: Barouch Susanna E , Chicz Taras M , Blanc Ross , Barbati Domenic R , Parker Lily J , Tong Xin , Li Wenjun , McNamara Ryan P
Published: March 2024

Background

The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear.

Methods

Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination.

Results

IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration.

Conclusions

These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza.
Primary Resistance to RET Inhibition in a RET Fusion-Positive Pancreatic Neuroendocrine Carcinoma
Authors: McKinley Blake J , Coston Tucker W , Starr Jason S
Published: March 2024

We present a 54-year-old White male with a diagnosis of stage IV pancreatic neuroendocrine carcinoma. Next-generation sequencing of the tumor/blood identified a complex tumor genome, which included a rearranged during transfection (RET) gene fusion. The patient initially received cytotoxic chemotherapy with a significant radiographic response. After 4 cycles of chemotherapy, the patient was transitioned to a clinical trial using selpercatinib, a RET inhibitor, as maintenance therapy. Unfortunately, our patient developed progression of disease at the first treatment monitoring scan. Our patient suffered primary resistance to RET-targeted therapy. Proposed mechanisms of resistance include intrinsic resistance of the nuclear receptor co-activator 4-RET fusion to RET inhibition, the RET fusion representing a passenger alteration to another tumorigenic driver pathway and/or decreased efficacy of RET inhibition after platinum-based chemotherapy. Our patient’s clinical course highlights the fact that “actionable” genomic alterations do not always equate to patient benefit.
Efficacy, Safety, and Tolerability of Tivozanib in Heavily Pretreated Patients With Advanced Clear Cell Renal Cell Carcinoma
Authors: Johns Andrew C , Campbell Matthew T , Gao Mamie , Hahn Andrew W , Lim Zita , Wang Emily , Gao Jianjun , Shah Amishi Y , Msaouel Pavlos , Tannir Nizar M
Published: March 2024

Background

Tivozanib has been approved as a third-line or later therapy for advanced renal cell carcinoma based on the TIVO-3 trial, which was conducted before immune checkpoint therapies (ICT), cabozantinib, and lenvatinib/everolimus became incorporated in the current sequential treatment paradigm for advanced clear cell RCC (ccRCC).

Methods

We performed a retrospective study of patients with advanced ccRCC treated with tivozanib at MD Anderson Cancer Center during 6/2021-7/2023. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed overall response rate (ORR), clinical benefit rate (CBR) [percentage of all treated patients who achieved radiologic response or stable disease (SD) for ≥ 6 months], progression-free survival (PFS), overall survival (OS), and safety.

Results

Of 30 analyzed patients, 23% had performance status ≥ 2; 47% had International Metastatic RCC Database Consortium (IMDC) poor-risk disease. Median number of prior therapies was 4 (range 1-8). All patients received prior ICT, 87% cabozantinib and 60% lenvatinib ± everolimus. Of 26 evaluable patients, 2 patients had confirmed partial response (ORR 7.7%); 5 patients had SD for ≥ 6 months (CBR 23.3%). Median PFS was 3.8 months (range 0.7-13.9); median OS was 14.1 months (range 0.3-28.5). Fifteen patients (50%) had ≥ 1 treatment-related adverse event (TRAE). There were 6 grade ≥ 3 TRAEs [hypertension, congestive heart failure (3), mucositis, and GI perforation (grade 5)].

Conclusions

In this cohort of heavily pretreated patients with advanced ccRCC, tivozanib yielded a modest clinical benefit in a minority of patients who received prior ICT, cabozantinib, and lenvatinib ± everolimus. TRAEs were consistent with previously published reports.
Metabolic crosstalk between hydroxylated monoterpenes and salicylic acid in tomato defense response against bacteria
Authors: Pérez-Pérez Julia , Minguillón Samuel , Kabbas-Piñango Elías , Payá Celia , Campos Laura , Rodríguez-Concepción Manuel , Espinosa-Ruiz Ana , Rodrigo Ismael , Bellés José María , López-Gresa María Pilar , Lisón Purificación
Published: March 2024

Hydroxylated monoterpenes (HMTPs) are differentially emitted by tomato (Solanum lycopersicum) plants resisting bacterial infection. We have studied the defensive role of these volatiles in the tomato response to bacteria, whose main entrance is through stomatal apertures. Treatments with some HMTPs resulted in stomatal closure and pathogenesis-related protein 1 (PR1) induction. Particularly, α-terpineol induced stomatal closure in a salicylic acid (SA) and abscisic acid-independent manner and conferred resistance to bacteria. Interestingly, transgenic tomato plants overexpressing or silencing the monoterpene synthase MTS1, which displayed alterations in the emission of HMTPs, exhibited changes in the stomatal aperture but not in plant resistance. Measures of both 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) and SA levels revealed competition for MEcPP by the methylerythritol phosphate (MEP) pathway and SA biosynthesis activation, thus explaining the absence of resistance in transgenic plants. These results were confirmed by chemical inhibition of the MEP pathway, which alters MEcPP levels. Treatments with benzothiadiazole (BTH), a SA functional analog, conferred enhanced resistance to transgenic tomato plants overexpressing MTS1. Additionally, these MTS1 overexpressors induced PR1 gene expression and stomatal closure in neighboring plants. Our results confirm the role of HMTPs in both intra- and interplant immune signaling and reveal a metabolic crosstalk between the MEP and SA pathways in tomato plants.
Convergent evolution of parrot plumage coloration
Authors: Ke Fushi , van der Zwan Henriëtte , Poon Emily Shui Kei , Cloutier Alison , Van den Abeele Dirk , van der Sluis Rencia , Sin Simon Yung Wa
Published: March 2024

Parrots have remarkable plumage coloration that result in part from a unique ability to produce pigments called psittacofulvins that yield yellow to red feather colors. Little is known about the evolution of psittacofulvin-based pigmentation. Widespread color mutations of captive-bred parrots provide perfect opportunities to study the genetic basis of this trait. An earlier study on blue budgerigars, which do not possess psittacofulvins, reveals the involvement of an uncharacterized polyketide synthase (MuPKS) in yellow psittacofulvin synthesis. The blue phenotype had repeatedly appeared in different parrot species, similar to independent experimental replications allowing the study of convergent evolution and molecular mechanism of psittacofulvin-based pigmentation. Here, we investigated the genetic basis of the blue phenotypes in two species of Agapornis parrots, Fischer's lovebird (A. fischeri) and Yellow-collared lovebird (A. personatus). Using whole-genome data, we identified a single genomic region with size <2 Mb to be strongly associated with the color difference between blue and wild-type (WT) birds in both species. Surprisingly, we discovered that the mutation associated with the blue Agapornis phenotype was identical to the previously described substitution causing the functional change of MuPKS in budgerigars. Together with the evidence of shared blue-associated haplotypes and signatures of a selective sweep in this genomic region in both species, we demonstrated both de novo mutation and interspecific introgression play a role in the evolution of this trait in different Agapornis species. The convergent substitution in the same gene in both lovebirds and budgerigars also indicates a strong evolutionary constraint on psittacofulvin-based coloration.
The maximum capability of a topological feature in link prediction
Authors: Ran Yijun , Xu Xiao-Ke , Jia Tao
Published: March 2024

Networks offer a powerful approach to modeling complex systems by representing the underlying set of pairwise interactions. Link prediction is the task that predicts links of a network that are not directly visible, with profound applications in biological, social, and other complex systems. Despite intensive utilization of the topological feature in this task, it is unclear to what extent a feature can be leveraged to infer missing links. Here, we aim to unveil the capability of a topological feature in link prediction by identifying its prediction performance upper bound. We introduce a theoretical framework that is compatible with different indexes to gauge the feature, different prediction approaches to utilize the feature, and different metrics to quantify the prediction performance. The maximum capability of a topological feature follows a simple yet theoretically validated expression, which only depends on the extent to which the feature is held in missing and nonexistent links. Because a family of indexes based on the same feature shares the same upper bound, the potential of all others can be estimated from one single index. Furthermore, a feature’s capability is lifted in the supervised prediction, which can be mathematically quantified, allowing us to estimate the benefit of applying machine learning algorithms. The universality of the pattern uncovered is empirically verified by 550 structurally diverse networks. The findings have applications in feature and method selection, and shed light on network characteristics that make a topological feature effective in link prediction.
Lattice Realization of the Axial U(1) Noninvertible Symmetry
Authors: Honda Yamato , Morikawa Okuto , Onoda Soma , Suzuki Hiroshi
Published: March 2024

In U(1) lattice gauge theory with compact U(1) variables, we construct the symmetry operator, i.e. the topological defect, for the axial U(1) noninvertible symmetry. This requires a lattice formulation of chiral gauge theory with an anomalous matter content and we employ the lattice formulation on the basis of the Ginsparg–Wilson relation. The invariance of the symmetry operator under the gauge transformation of the gauge field on the defect is realized, imitating the prescription by Karasik in continuum theory, by integrating the lattice Chern–Simons term on the defect over smooth lattice gauge transformations. The projection operator for allowed magnetic fluxes on the defect then emerges with lattice regularization. The resulting symmetry operator is manifestly invariant under lattice gauge transformations. In an appendix, we give another way of constructing the symmetry operator on the basis of a 3D $\mathbb {Z}_N$ topological quantum field theory, the level-N BF theory on the lattice.
MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases
Authors: Wu Changqiang , Chen Wei , Yan Shuang , Zhong Jie , Du Liang , Yang Chenwu , Pu Yu , Li Yang , Lin Jiafu , Zeng Mei , Zhang Xiaoming
Published: March 2024

Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven to be an effective local treatment modality but incompetent against metastases. Hence, the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a magnetic resonance imaging (MRI)-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with a programmed cell death 1 (PD-1) inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser. In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32°C to 60.7°C in 5 min. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided PTT/PDT results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.
The spectacle of automation and status aspirations: adoption of automated metro systems around the world, 2000–2020
Authors: Kang Youbin , Kim Jungmyung
Published: March 2024

Automation’s extensive impact on the labor market and economy is well recognized, but the underlying motivations for its adoption remain understudied. To address this gap, we analyze an original dataset covering 1276 cities across 148 countries, using event history analysis to examine the adoption of automated metro systems. Our research suggests that city governments are driven by status competition in their decisions to automate subway systems. We find that high-status cities are more likely to adopt automation. However, this trend diminishes when cities are preparing to host a mega-event such as the Olympics, indicating that lower-status cities use these events as opportunities to adopt automation technologies. Our finding reveals that status-driven aspirations, manifesting in the spectacle of automation, are a significant motivator for adopting automated technologies, prompting further investigation into the socio-economic factors influencing automation and the symbolic importance of technological advancement across various economic sectors.
Spindle-slow wave coupling and problem-solving skills: impact of age
Authors: Baena Daniel , Toor Balmeet , van den Berg Nicholas H , Ray Laura B , Fogel Stuart M
Published: March 2024

We examined how aging affects the role of sleep in the consolidation of newly learned cognitive strategies. Forty healthy young adults (20–35 years) and 30 healthy older adults (60–85 years) were included. Participants were trained on the Tower of Hanoi (ToH) task, then, half of each age group were assigned to either the 90-minute nap condition, or stayed awake, before retesting. The temporal co-occurrence between slow waves (SW) and sleep spindles (SP) during non-rapid eye movement sleep was examined as a function of age in relation to memory consolidation of problem-solving skills. We found that despite intact learning, older adults derived a reduced benefit of sleep for problem-solving skills relative to younger adults. As expected, the percentage of coupled spindles was lower in older compared to younger individuals from control to testing sessions. Furthermore, coupled spindles in young adults were more strongly coupled to the SW upstate compared to older individuals. Coupled spindles in older individuals were lower in amplitude (mean area under the curve; μV) compared to the young group. Lastly, there was a significant relationship between offline gains in accuracy on the ToH and percent change of spindles coupled to the upstate of the slow wave in older, but not younger adults. Multiple regression revealed that age accounted for differences in offline gains in accuracy, as did spindle coupling during the upstate. These results suggest that with aging, spindle-slow wave coupling decreases. However, the degree of the preservation of coupling with age correlates with the extent of problem-solving skill consolidation during sleep.
A variable time headway model for the mixed car-following process considering multiple front vehicles information in foggy weather
Authors: Liang Ziwei , Pang Mingbao
Published: March 2024

The aim of this work is to investigate the fog-related variable time headway (FVTH) model of connected and automated mixed flow considering multiple front vehicles information in a reduced visibility environment for driving safety. The car-following modes of mixed vehicles are analysed and the vehicle ratio for each mode based on Markov chain models is derived, where the number of front vehicles, the connected and automated vehicles penetration rate and the platoon intensity are considered. The combined coupling effect of visibility and driving speed on time headway is explored, and a variable time headway strategy is proposed. Their relationship equations are deduced as the FVTH model. The perturbation method is used to discuss the stability of traffic flow and obtain its stability judgement conditions. The proposed model was validated and the effects were discussed via simulation experiments. The results indicate that the acceleration and deceleration times of vehicles and collision possibility decrease significantly using the proposed method. When penetration rate is 50%, the number of front vehicles is three and platoon intensity is zero, the time to return to a stable state is reduced by 18.9%–30.3% and 24.7%–39.4%, respectively, and Time-Exposed Time to collision is reduced by 26.1%–48.9% and 43.7%%–65.4%, respectively, compared with the basic intelligent driver model (IDM) method, and the IDM method that considers multiple front vehicles information. As visibility decreases, the reduced degree of these indicator values increases. The driving efficiency and safety level can be enhanced.
First data on early instar Afrotropical Miltogramminae (Diptera: Sarcophagidae) reveal unexpected morphological diversity
Authors: Szpila Krzysztof , Walczak Kinga , Soszyńska Agnieszka , Pape Thomas
Published: March 2024

First instar larvae of the genera Hoplacephala Macquart, 1846 and Lamprometopia Macquart, 1846 are described for the first time, along with the first instar larva of an Afrotropical species of the genus Phylloteles Loew, 1844. Their morphology is analyzed using a combination of various microscopy techniques, confirming their close phylogenetic affinity with other members of the tribe Sarcotachinini. Substantial morphological differences are observed between the investigated genera, as well as in comparison to other known larvae of Miltogramminae. Noteworthy unique character states are identified in the shape of the cephaloskeleton, the sculpture of the integument, and the shape of the papilla of the thoracic and abdominal segments. The larva of Hoplacephala sp. stands out as the most peculiar, featuring a massive cephaloskeleton, integument armoured by cuticular scales, and modification of body papillae into fleshy processes. The first instar larva of Phylloteles picifrons Pape, 1985 possesses a large, bladder-like structure with unknown function dorsally on the first thoracic segment. All documented larvae are characterized by a maxillary palpus forming a distinct protuberance with elongated second sensillum basiconicum and the absence of a dorsal bridge of the cephaloskeleton. This last character state indicates a parasitic or parasitoid life history for all studied taxa.
Breast Implant Illness May Be Rooted in Mast Cell Activation: A Case-Controlled Retrospective Analysis
Authors: Nagy Èva S. , Westaway Mark , Danieletto Suzanne , Afrin Lawrence B.
Published: March 2024

Objective:

To investigate the possible association between breast implant illness (BII) and mast cell activation syndrome (MCAS), which often manifests increased mast cells (MCs) in assorted tissues and may explain BII symptoms.

Background:

Mechanisms by which implants cause BII symptoms remain unclear, but BII and MCAS symptom profiles heavily overlap, warranting investigation of potential linkage.

Methods:

We retrospectively analyzed 20 implant patients who underwent explantation and total capsulectomy; 15 self-reported preoperatively they had BII (subject group); 5 felt they did not [control group 1 (CG1)]. Five prophylactic mastectomy patients constituted control group 2 (CG2). Subjects and CG1 patients completed BII symptom questionnaires preoperatively and multiple points postoperatively. With CD117 staining, average and maximum mast cell counts (MCCs) in resected tissues were determined.

Results:

Mean BII symptom score 2 weeks postexplantation was reduced by 77% (P < 0.0001), and 85% by 9 months. Analysis suggested BII in CG1 patients, too, who improved similarly. Among CG2 patients, healthy breast tissue showed mean and maximum MCCs of 5.0/hpf and 6.9/hpf. Mean and maximum MCCs in capsules in BII patients were 11.7/hpf and 16.3/hpf, and 7.6/hpf and 13.3/hpf in CG1 patients. All intergroup comparisons were significantly different (P < 0.0001).

Conclusions:

MCCs in peri-implant capsules in BII patients are increased; some implanted patients appear to have unrecognized BII. Given that neoantigenic/xenobiotic exposures commonly trigger dysfunctional MCs in MCAS to heighten aberrant mediator expression driving inflammatory and other issues, further investigation of whether BII represents an implant-driven escalation of preexisting MCAS and whether an MCAS diagnosis flags risk for BII seems warranted.
Alaska Pollock-derived Gelatin Sealant has Higher Sealing Strength than, and Comparable Biocompatibility with, Fibrin Sealant in Porcine and Rat Dural Injury Models
Authors: Ono Takumi , Suzuki Taku , Nagoshi Narihito , Masugi Yohei , Maeda Kosuke , Hashimoto Shogo , Watanabe Shiharu , Iwamoto Takuji , Taguchi Tetsushi , Nakamura Masaya
Published: March 2024

Study Design.

Burst strength study in porcine dural models and functional and histological study in rat dural models.

Objective.

This study aimed to investigate the sealing strength and biocompatibility of Alaska pollock-derived gelatin (ApGltn) and fibrin sealants in disrupted dural injuries.

Summary of Background Data.

Disruption of the dura mater occurs during spine surgery, leading to cerebrospinal fluid leakage. Fibrin sealant is usually applied to ruptured sites; however, it lacks sealing strength. A novel biocompatible sealant composed of ApGltn was recently demonstrated to have good burst strength and biocompatibility in the porcine aorta.

Methods.

Ten porcine dura maters with central holes were covered with ApGltn and fibrin sealants (five samples per group). The maximum burst strength of each sealant was measured, and histological examination was performed after burst testing. Twenty-seven dura maters of male Wistar rats were used for functional and histopathological evaluations. The rats were treated with three surgical interventions: defect + ApGltn sealant; defect + fibrin sealant; defect alone (nine rats per group). Macroscopic confirmation of the sealant, hindlimb motor function analysis, and histopathological examination were performed at two, four, and eight weeks after the procedure.

Results.

The maximum burst strength of the ApGltn sealant was ~4.4 times higher than that of the fibrin sealant (68.1±12.1 vs. 15.6±8.7 mmHg; P<0.001). Histological examination confirmed that the ApGltn sealant showed tight adhesion to the dural surface, whereas a gap was observed between the fibrin sealant and the dura mater. In the rat model, the ApGltn sealant resulted in spinal function and dural histological findings similar to those of the fibrin sealant.

Conclusion.

The ApGltn sealant had a higher sealing strength than, and comparable effect on dura regeneration with, the fibrin sealant.
Insulin’s Legacy: A Century of Breakthroughs and Innovation
Authors: Hadid Somar , Zhang Emily , Frishman William H. , Brutsaert Erika
Published: March 2024

The clinical use of insulin to treat diabetes started just over 100 years ago. The past century has witnessed remarkable innovations in insulin therapy, evolving from animal organ extracts to bioengineered human insulins with ultra-rapid onset or prolonged action. Insulin delivery systems have also progressed to current automated insulin delivery systems. In this review, we discuss the history of insulin and the pharmacology and therapeutic indications for a variety of available insulins, especially newer analog insulins. We highlight recent advances in insulin pump therapy and review evidence on the therapeutic benefits of automated insulin delivery. As with any form of progress, there have been setbacks, and insulin has recently faced an affordability crisis. We address the challenges of insulin accessibility, along with recent progress to improve insulin affordability. Finally, we mention research on glucose-responsive insulins and hepato-preferential insulins that are likely to shape the future of insulin therapy.
Robot-assisted Microsurgery: Lessons Learned from 50 Consecutive Cases
Authors: Struebing Felix , Bigdeli Amir , Weigel Jonathan , Gazyakan Emre , Vollbach Felix , Panayi Adriana C. , Vogelpohl Julian , Boecker Arne , Kneser Ulrich
Published: March 2024

Background:

The potential of robot-assisted surgery in plastic and reconstructive surgery remains to be established, especially in free tissue transfer. This prospective study aimed to present our experience and findings from the first 50 consecutive cases of robot-assisted microsurgery using the Symani surgical system.

Methods:

A prospective database was maintained, recording patient demographics and surgical details for all cases of robot-assisted microsurgery in a large academic institution. All surgeons underwent an intensive training program with the Symani surgical system.

Results:

A total of 50 patients who underwent robot-assisted microsurgical reconstruction were identified. Free microsurgical tissue transfer was performed in 45 cases, targeted muscle reinnervation in four cases, and lymphovenous anastomoses in a single case. A total of 94 robot-assisted anastomoses and coaptations were performed, (46 venous and 30 arterial anastomoses, 16 nerve coaptations, two lymphovenous anastomoses). Six cases involved perforator-to-perforator anastomoses. Ninety-eight percent of attempted anastomoses were completed using the robot. Size-mismatch anastomoses, seen in 37.8% of cases, took significantly longer. Minor complications occurred in three cases and major in six cases. There were three cases of microvascular compromise requiring revision. One partial flap loss and no complete flap loss occurred.

Conclusions:

Our study highlights the immense potential of robot-assisted microsurgery, and a feasible and effective modality for various microsurgical procedures, with outcomes comparable to those of conventional microsurgery. Despite challenges, such as increased operating times and higher costs, the technology offers significant advantages, such as enhanced precision and motion scaling. We identify a slow learning curve and a necessity for higher caseloads.
Feasibility of hepatitis C elimination by screening and treatment alone in high-income countries
Authors: Tian Feng , Forouzannia Farinaz , Feng Zeny , Biondi Mia J. , Mendlowitz Andrew B. , Feld Jordan J. , Sander Beate , Wong William W.L.
Published: March 2024

Background and Aims:

Despite the availability of highly effective direct-acting antiviral therapy, chronic hepatitis C (CHC) continues to cause a major public health burden. In many high-income countries, treatment rates have been declining, which was exacerbated by the impact of the COVID-19 pandemic, threatening the ability to meet the World Health Organization (WHO)’s targets for eliminating HCV as a public health threat by 2030. We sought to model the impact of CHC in Canada, a resource-rich country with ongoing immigration from HCV-endemic regions; which relies exclusively on risk-based screening for case identification.

Approach and Results:

We developed an agent-based model to characterize the HCV epidemic in a high-income country with ongoing immigration. Combinations of prevention such as harm reduction, screening, and treatment strategies were considered. Model parameters were estimated from the literature and calibrated against historical HCV data. Sensitivity analyses were performed to assess uncertainty. Under the current status quo of risk-based screening, we predict the incidence of CHC-induced decompensated cirrhosis, HCC, and liver-related deaths would decrease by 79.4%, 76.1%, and 62.1%, respectively, between 2015 and 2030, but CHC incidence would only decrease by 11.1%. The results were sensitive to HCV transmission rate and an annual number of people initiating treatment.

Conclusions:

Current risk-based screening, and subsequent treatment, will be inadequate to achieve WHO goals. With extensive scale-up in screening, and treatment, the mortality target may be achievable, but the target for preventing new CHC cases is unlikely reachable, highlighting the importance of developing enhanced harm-reduction strategies for HCV elimination.
Safety and efficacy of off-label bulevirtide monotherapy in patients with HDV with decompensated Child-B cirrhosis—A real-world case series
Authors: Dietz-Fricke Christopher , Degasperi Elisabetta , Jachs Mathias , Maasoumy Benjamin , Reiter Florian P. , Geier Andreas , Grottenthaler Julia M. , Berg Christoph P. , Sprinzl Kathrin , Zeuzem Stefan , Gödiker Juliana , Schlevogt Bernhard , Herta Toni , Wiegand Johannes , Soffredini Roberta , Wedemeyer Heiner , Deterding Katja , Reiberger Thomas , Lampertico Pietro
Published: March 2024

Background and Aims:

Chronic hepatitis D is the most debilitating form of viral hepatitis frequently progressing to cirrhosis and subsequent decompensation. However, the HDV entry inhibitor bulevirtide is only approved for antiviral treatment of patients with compensated disease. We aimed for the analysis of real-world data on the off-label use of bulevirtide in the setting of decompensated liver cirrhosis.

Approach and Results:

We conducted a retrospective study in patients with HDV with decompensated liver disease at German, Austrian, and Italian centers. We included 19 patients (47% male, mean age: 51 years) with liver cirrhosis Child-Pugh B. The median MELD score was 12 (range 9–17) at treatment initiation. The median observation period was 41 weeks. Virologic response was achieved in 74% and normal alanine aminotransferase was observed in 74%. The combined response was achieved by 42%. The most relevant adverse events included self-limited alanine aminotransferase flares, an asymptomatic increase in bile acids, and the need for liver transplantation. Despite bile acid increases, adverse events were considered unrelated. Clinical and laboratory improvement from Child-Pugh B to A occurred in 47% (n = 9/19). Improvements in the amount of ascites were observed in 58% of the patients initially presenting with ascites (n = 7/12).

Conclusions:

This report on off-label bulevirtide treatment in patients with decompensated HDV cirrhosis shows similar virologic and biochemical response rates as observed in compensated liver disease. Significant improvements were observed in surrogates of hepatic function and portal hypertension. However, this improvement was not seen in all patients. Controlled trials are needed to confirm the safety and efficacy of bulevirtide in decompensated HDV cirrhosis.
Central retinal artery occlusion after cardioversion of atrial fibrillation
Authors: Lagha Lilia , Kalogeropoulos Dimitrios , Goverdhan Srinivas , Lotery Andrew J
Published: March 2024

Central retinal artery occlusion (CRAO) is a vascular ophthalmic emergency. Often caused by a sudden interruption of blood flow to the eye, with profound and painless vision loss, resulting in irreversible cell damage. An impacted embolus at the narrowest part of the central retinal artery is the most common cause.

Cardioversion is a medical procedure used to restore a normal heart rhythm in individuals with atrial fibrillation (AF). In some cases, cardioversion can lead to thromboembolic complications. If an embolus reaches the central retinal artery, it can block the blood flow to the retina, resulting in CRAO and subsequent vision loss.
Development of Crystalline Corneal Opacities (Steroid Keratopathy) in Dogs After Treatment With Ophthalmic Corticosteroids
Authors: Quantz Katelin R. , Jongnarangsin Kamontip K. , Harman Christine D. , Koehl Kristin L. , Jacobson Amanda L. , Nallasamy Nambi , Shaw Gillian C. , Pirie Christopher G. , Komáromy András M.
Published: March 2024

Purpose:

To retrospectively evaluate and describe the relationship between the use of topical corticosteroids and the development of crystalline corneal opacities (steroid keratopathy) in a colony of research Beagles and Beagle-derived dogs.

Methods:

Medical records of 73 purpose-bred Beagles and Beagle-derived dogs were reviewed from June 2012 to May 2021. All dogs were treated with topical ophthalmic corticosteroids for at least 21 days. In addition to regular ophthalmic examination, some dogs also had a systemic lipid profile (n = 6) performed to work up further and characterize the crystalline corneal opacities. Globes of 3 dogs were examined histopathologically.

Results:

Axial stromal crystalline corneal opacities were appreciated in 25 eyes of 14 dogs after a median of 141 days after initiating treatment (35–396 days). Multiple corticosteroids were used, including neomycin-polymyxin b-dexamethasone 0.1% ophthalmic ointment, prednisolone acetate 1% ophthalmic suspension, and difluprednate 0.05% ophthalmic emulsion (Durezol). Resolution of corneal opacity was documented in 4 of 25 eyes when ophthalmic corticosteroids were discontinued after a median of 406.5 days (271–416 days). Histopathologic examination revealed a dense band of acellular material, poorly staining with periodic acid–Schiff, subtending the corneal epithelium, and being surrounded by spindle cells.

Conclusions:

This case series documents the onset of steroid keratopathy in Beagles and Beagle-derived dogs after treatment with ophthalmic corticosteroids. Clinical resolution of steroid keratopathy lesions may be possible after discontinuation of ophthalmic corticosteroids.
Effect of laparoscopic sleeve gastrectomy on male reproductive function in Chinese men with obesity: a prospective cohort study
Authors: Gao Xiang , Li Pengzhou , Wang Guohui , Li Weizheng , Song Zhi , Zhu Shaihong , Zhu Liyong
Published: March 2024

Background:

Obesity is a widely recognized global public health issue, and bariatric surgery has emerged as an effective intervention for alleviating obesity associated health complications. However, the impact of bariatric surgery on male reproductive function remains inconclusive in the literature. The current understanding of the impact of laparoscopic sleeve gastrectomy (LSG) on male reproductive function remains ambiguous, despite its status as the most commonly performed bariatric surgery. This prospective cohort study aimed to investigate the impact of LSG on erectile function and semen quality.

Patients and methods:

A total of 34 obese patients were enrolled in this study and underwent LSG. Prior to the operation and at 3, 6, and 12 months postoperation, all participants were required to complete the International Index of Erectile Function-5 (IIEF-5) questionnaire and undergo a nocturnal erectile function test and semen quality analysis.

Results:

Within 12 months postoperation, BMI, blood lipids, and insulin resistance showed significant improvement. The IIEF-5 score increased significantly (18.88±5.97 vs. 23.78±3.19, P<0.05), and the frequency and duration of erections significantly improved compared to baseline. Sperm concentration, total motility, survival rate, and sperm morphology parameters exhibited a significant decline at 3 months but demonstrated a significant improvement at 6 and 12 months postoperation. At 12 months, sperm concentration was shown to be correlated with changes in zinc (r=0.25, P=0.033) as well as changes in testosterone (r=0.43, P=0.013).

Conclusions:

LSG has beneficial effects on erectile function, despite a transient decline in semen quality at 3 months postoperatively, followed by a significant improvement at 12 months.
Recent advances in the treatment of renal stones using flexible ureteroscopys
Authors: He Min , Dong Yonghui , Cai Wansong , Cai Jiale , Xie Yaming , Yu Mingke , Li Changjiu , Wen Liping
Published: March 2024

Upper urinary tract stones are a common urological disease that can be treated by flexible ureteroscopy (FURS) through the natural urinary tract, in addition to extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. The advantages of FURS are less trauma, faster recovery, and fewer complications, while its disadvantages include poor results of lithotripsy and stone extraction when dealing with larger stones, and prolonged operation time. Over the last two decades, the emergence of new technologies such as FURS combined with negative pressure suction, robot-assisted FURS, and artificially intelligent FURS, coupled with improvements in laser technology (the use of thulium fiber lasers and the invention of single-use flexible ureteroscopes (su-fURS) suitable for primary level application, have significantly increased the global adoption of FURS. This surge in usage holds a promising future in clinical application, benefiting a growing number of patients with renal calculi. Accompanied by changes in technical concepts and therapeutic modalities, the scope of indications for FURS is broadening, positioning it as a potential primary choice for urolithiasis treatment in the future. This review outlines the progress in employing FURS for the treatment of renal calculi in order to generate insights for further research.
Utilization and safety of off-label prothrombin complex concentrate (four-factor prothrombin complex concentrate) in a surgical population
Authors: Sandquist Katherine , Kaucher Kevin , Newell Joshua , Sarangarm Preeyaporn , Burnett Allison
Published: March 2024

The aim of this study is to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, surgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between 1 January 2017 and 30 September 2022 for a surgical or peri-procedural indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, assessed by subsequent blood product administration and hemoglobin and hematocrit reduction. Secondary outcomes included an assessment of thrombotic events within 30 days post-4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 71 patients met the inclusion criteria, with 61 patients receiving 4F-PCC for cardiac surgery and 10 patients for other intraoperative or peri-procedural indications. The mean total 4F-PCC dose was 25.0 U/kg. For the primary outcome of hemostatic efficacy, 81% of patients had excellent hemostasis; however, blood product administration was reported in 95.8% of patients post-4F-PCC. Thromboembolic events occurred in 10 (14.1%) patients and 21.1% of patients expired prior to discharge in the total cohort. Off-label 4F-PCC use in nonanticoagulated patients is reported despite a lack of robust guidance for use. Following 4F-PCC administration, hemostatic efficacy based on hemoglobin and hematocrit changes was observed; however, blood product use was frequent, and 4F-PCC administration was not without risks, including thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism, and stroke. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.
Utilization and safety of off-label prothrombin complex concentrate (4F-PCC) in a nonsurgical population
Authors: Sandquist Katherine , Kaucher Kevin , Newell Joshua , Sarangarm Preeyaporn , Burnett Allison
Published: March 2024

The aim of this study was to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, nonsurgical patient population at an academic, tertiary care center.

This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between January 1, 2017, and September 30, 2022, for a nonsurgical indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, and secondary outcomes included an assessment of blood product administration, thrombotic events within 30 days post4F-PCC administration, in-hospital mortality, and the length of hospital stay.

A total of 59 patients met the inclusion criteria, and 10 patients received 4F-PCC for coagulopathy associated with liver disease, 34 for intracranial hemorrhage (ICH), and 15 for other indications. For the primary outcome of hemostatic efficacy, 17 non-ICH patients (85%) had achieved hemostasis post-4F-PCC, and among the ICH patient population, 18 (64%) did not show expansion on repeat CT post4F-PCC, suggesting hemostasis. Blood product and hemostatic agent usage was frequent, with 72.9% of patients requiring products post-4F-PCC. Acute thromboembolic events occurred in six patients (10.2%), and in-hospital mortality occurred in 55.9% of patients.

Off-label 4F-PCC use is common despite a lack of robust guidance for use. Following 4F-PCC administration, blood product use was frequent, the incidence of in-hospital mortality was high, and thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke were reported. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.
Ruthenium-based antivenom attenuates Crotalus atrox venom mediated coagulopathy in rabbits
Authors: Nielsen Vance G.
Published: March 2024

Background

The Western diamondback rattlesnake (Crotalus atrox) is a medically important venomous snake in the Southwestern United States, injuring humans, and their companion animals. The goals of this investigation were to utilize a rabbit model of subcutaneous envenomation to assess Crotalus atrox venom coagulopathy and determine the efficacy of a ruthenium-containing antivenom (RA) in attenuating it.

Methods

Sedated New Zealand White rabbits had viscoelastic measurements of whole blood coagulation kinetics obtained from ear artery samples. Crotalus atrox venom (4 mg/kg) was injected subcutaneously and changes in coagulation determined over three hours and compared to samples obtained prior to envenomation. Other rabbits had site-directed RA injected 5 min after venom injection.

Results

A significant decrease in the velocity of clot growth and thrombus strength was observed in animals injected with venom alone. Site-directed administration of RA resulted in no change in coagulation over the 3 h following venom injection. The interaction of antivenom administration and time was significantly different in the cases of clot growth velocity and strength.

Conclusions

A novel rabbit model was used to define the toxicodynamic profile of coagulopathy of Crotalus atrox venom and demonstrate the efficacy of RA. Future investigation is planned involving other medically important venoms and RA administration.
Assessment of MUC5AC and MUC2 Immunoexpression in Glandular Odontogenic Cysts, Dentigerous Cysts, and Mucoepidermoid Carcinomas
Authors: Jot Kiran , Nayyar Vivek , Surya Varun , Kakkar Aanchal , Satapathy Shraddhanjali , Roychoudhury Ajoy , Mishra Deepika
Published: March 2024

Glandular odontogenic cysts (GOCs) and dentigerous cysts may show mucous metaplasia. Central mucoepidermoid carcinoma is very rare and mostly associated with dental cysts. It is hypothesized that odontogenic cysts showing mucus differentiation in their lining, have a propensity to transform into MEC. The present study is the first attempt to explore the relationship between odontogenic cysts [GOCs and dentigerous cysts with mucus metaplasia (DCMM)] and MEC by evaluating immunoexpression of MUC5AC and MUC2. Immunoexpression of MUC5AC and MUC2 was evaluated semiquantitatively in GOCs (20 cases), DCMMs (20 cases), and MECs (20 cases). The percentage of positive cells, intensity, and localization of immunoexpression were assessed for each marker in all cases. Of GOCs, DCMMs, and MECs cases, 85%, 70%, and 80%, respectively, were immunopositive for MUC5AC. Strong cytoplasmic immunoreactivity for MUC5AC was noted, particularly in mucous cells present diffusely within MECs. However, the immunoreactivity was limited to the epithelial lining of GOCs and DCMMs. Most of the MECs (60%) showed more than 25% positivity for MUC5AC, followed by GOCs, and the least in DMMCs. Mild cytoplasmic and nuclear positivity of MUC2 was noted only in epithelial lining cells of 70% GOCs and 45% DCMMs. Whereas, 55% of MECs displayed moderate to strong cytoplasmic and membranous immunopositivity for MUC2 exclusively within mucous cells. As MECs showed strong MUC5AC immunoreactivity in mucous cells, immunoexpression of MUC5AC in odontogenic cysts with mucus cells can possibly explain the pathogenesis of MEC from cysts. However, the variable expression of MUC2 did not give any strong evidence regarding its role as a marker.
Central Line Repair in Pediatric Patients in the Pediatric Emergency Department by Emergency Physicians—A Single-Center Experience
Authors: Baer Aluma , Weiser Giora
Published: March 2024

Introduction

Central venous catheters are more common with advanced treatments for a variety of conditions. These catheters may need to be repaired after local damage. This has been performed by those more involved with catheter placement such as pediatric surgeons and interventional radiologists. Gastroenterologists who treat many of these patients have also been involved with catheter repair. Repair by pediatric emergency physicians has not been explored. Such repairs by the emergency physician may be time saving and avoid unnecessary admissions.

Methods

This was a retrospective study of a single center's experience with catheter repair. The performers and outcomes were compared.

Results

During the study period, 52 catheter repairs were performed on 7 children. Forty of the repairs were performed by a pediatric emergency physician, 5 by pediatric surgeons, and 5 by interventional radiology. All but 1 repair was successful. Infectious complications were reported in 3 cases. None required catheter removal. The length of stay was significantly shorter for repair by emergency physician.

Conclusions

Central line catheter repair can be performed successfully by pediatric emergency physician with minimal complications. A dedicated process of repair tutoring is required and may avoid infectious complications.
Temporomandibular Joint Space in Mandibular Prognathism
Authors: Shin Dongsun , Keum Hye In , Yoo Seung Rim , Lim Hun Jun , Kim Bong Chul
Published: March 2024

This study compared the temporomandibular joint (TMJ) space between patients with normal and prognathic mandibles. The study included a total of 68 Korean individuals, and the TMJ space was measured using computed tomography. Patients with normal SNB values (normal mandible) were classified into Group 1. Patients with high SNB values (prognathic mandibles) were categorized into Group 2. The TMJ space was defined as the distance between the condylar process and the mandibular fossa, and it was significantly different between Groups 1 and 2 (1.94±0.07 mm versus 1.50±0.05 mm, P<0.01). This study confirmed that the TMJ space in patients with prognathic mandibles is narrower than that in patients with normal mandibles.