bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tyrosine kinase Yes1 is a druggable host factor of HEV
Authors: Haase Jil Alexandra , Baheerathan Abarna , Zhang Xin , Fu Rebecca Menhua , Nocke Maximilian Klaus , Decker Charlotte , Dao Thi Viet Loan , Todt Daniel , Neyts Johan , Kaptein Suzanne J.F. , Steinmann Eike , Kinast Volker 
Published: October 2024

Background:
HEV is a positive-sense, single-stranded RNA virus of the Hepeviridae family. Although HEV accounts for more than 3 million symptomatic cases of viral hepatitis per year, specific anti-HEV therapy and knowledge about HEV pathogenesis are scarce.

Methods:
To gain a deeper understanding of the HEV infectious cycle and guide the development of novel antiviral strategies, we here used an RNAi mini screen targeting a selection of kinases, including mitogen-activated protein kinases, receptor tyrosine kinases, and Src-family kinases. Further, we used state-of-the-art HEV infection models, including primary human hepatocytes and athymic nude rats.

Results:
Upon knockdown of the Src-family kinase Yes1, a significant reduction of HEV susceptibility could be observed, suggesting an important role of Yes1 in the HEV infectious cycle. Selective inhibition of Yes1 kinase activity resulted in significant inhibition of HEV infection in hepatoma cells and primary human hepatocytes, as well as in a rat HEV in vivo model system. Subsequent analysis of Y1KI during the HEV infectious life cycle indicated a role of Yes1 kinase activity in the early onset of HEV infection.

Conclusions:
We identified the dependence of HEV on Yes1 signaling, which may contribute to the so far scarce knowledge of HEV’s pathogenesis in the future. Moreover, we provide Y1KI as a novel antiviral drug candidate specifically targeting an HEV host factor.
Serum amyloid P (PTX2) attenuates hepatic fibrosis in mice by inhibiting the activation of fibrocytes and HSCs
Authors: Cong Min , Carvalho Gontijo Weber Raquel , Sakane Sadatsugu , Zhang Vivian , Jiang Chunyan , Taura Kojiro , Kodama Yuzo , DeMinicis Samuele , Ganguly Souradipta , Brafman David , Chien Shu , Kramer Michael , Lupher Mark , Brenner David A. , Xu Jun , Kisseleva Tatiana 
Published: October 2024

Background:
Liver fibrosis is caused by chronic toxic or cholestatic liver injury. Fibrosis results from the recruitment of myeloid cells into the injured liver, the release of inflammatory and fibrogenic cytokines, and the activation of myofibroblasts, which secrete extracellular matrix, mostly collagen type I. Hepatic myofibroblasts originate from liver-resident mesenchymal cells, including HSCs and bone marrow–derived CD45+ collagen type I+ expressing fibrocytes. Recombinant human serum amyloid P (hSAP), a natural inhibitor of fibrocyte activation into myofibroblasts, was shown to ameliorate experimental renal, lung, skin, and cardiac fibrosis. We investigated if hSAP can ameliorate the development of liver fibrosis of different etiologies.

Methods:
Reporter Collagen-α(1)I-GFP mice were subjected to cholestatic liver injury (by ligation of the common bile duct) or toxic liver injury (by carbon tetrachloride administration) and treated prophylactically or therapeutically with hSAP (12.5 μg/g). Primary cultures of mouse fibrocytes and HSCs were stimulated to activate with or without incubation with hSAP.

Results:
We demonstrate that treatment with hSAP suppressed hepatic fibrosis by ≈50% through dual mechanisms. hSAP prevented the recruitment of fibrocytes into the injured liver and their differentiation into myofibroblasts. Remarkably, hSAP also inhibited the activation of HSCs into myofibroblasts.

Conclusions:
Since HSCs serve as a major source of collagen type I–producing myofibroblasts and fibrocytes stimulate fibrosis, hSAP may become part of the therapy of liver fibrosis of different etiologies.
Advancements in automated external and wearable cardiac defibrillators
Authors: Aldaas Omar M. , Birgersdotter-Green Ulrika 
Published: October 2024

Purpose of review
Survival statistics for out-of-hospital cardiac arrests remain unsatisfactory. Prompt defibrillation of shockable rhythms, such as ventricular fibrillation and pulseless ventricular tachycardia, is crucial for improving survival. Automated external defibrillators (AEDs) and wearable cardiac defibrillators (WCDs) seek to improve the survival rates following out-of-hospital cardiac arrests. We aim to review the indications, utility, advancements, and limitations of AEDs and WCDs, as well as their role in contemporary and future clinical practice.

Recent findings
Recent advancements in these technologies, such as smartphone applications and drone delivery of AEDs and less inappropriate shocks and decreased size of WCDs, have increased their ubiquity and efficacy. However, implementation of this technology remains limited due to lack of resources and suboptimal patient adherence.

Summary
Out of hospital cardiac arrests continue to pose a significant public health challenge. Advancements in AEDs and WCDs aim to facilitate prompt defibrillation of shockable rhythms with the goal of improving survival rates. However, they remain underutilized due to limited resources and suboptimal patient adherence. As these technologies continue to evolve to become smaller, lighter and more affordable, their utilization and accessibility are expected to improve.
Postoperative complication rates in intraocular lens placement and fixation methods for inadequate capsular bag support: review and meta-analysis
Authors: Kanclerz Piotr , Radomski Szymon Adam , Hecht Idan , Tuuminen Raimo 
Published: October 2024

Topic:
To evaluate the complication rates of different intraocular lens (IOL) placement methods in adults with inadequate capsular bag support.

Clinical Relevance:
The surgical correction of inadequate capsular bag support for the IOL harbors several challenges, and there is a wide range of surgical procedures.

Methods:
For the purpose of this meta-analysis, surgical methods were grouped based on the location of IOL placement: (1) anterior chamber (AC) placement; (2) iris fixation, which included prepupillary or retropupillary placement of an iris-claw IOL, or iris suturing of an IOL; and (3) scleral fixation, which included scleral sutured and sutureless techniques. Only studies comparing the results of 2 or more different placement methods were analyzed. The study protocol has been registered in the PROSPERO database (CRD42023458557).

Results:
15 studies were included in the final analysis, which reported results of 1247 eyes. The overall complication rate was nonsignificantly lower in iris fixation (4.4%; 95% CI, 3.6%-5.4%, P = .150) than in AC placement (7.4%; 95% CI, 6.4%-7.9%) and scleral fixation (7.4%; 95% CI, 6.5%-8.4%). Transient corneal edema was the most common complication in AC placement (29.9%; 95% CI, 2.4%-57.5%, P < .001), compared with scleral fixation (11.9%; 95% CI, 2.6%-21.2%) and iris fixation (4.1%; 95% CI, 0.8%-7.3%). Vitreous hemorrhages were more frequently reported after scleral fixation (8.5%; 95% CI, 6.3%-11.2%, P = .006) than in AC placement (5.4%; 95% CI, 3.4%-8.5%) and iris fixation (1.4%; 95% CI, 0.4%-4.2%), and so was IOL decentration/dislocation (8.9%; 95% CI, 6.7%-11.8%, P = .047 compared with 1.1%; 95% CI, 0.4%-3.4% and 4.0%; 95% CI, 2.2%-7.3%, respectively).

Conclusions:
The risks associated with particular techniques should be taken into account in preoperative counseling and planning postoperative treatment.
Preoperative low skeletal muscle mass index assessed using L3-CT as a prognostic marker of clinical outcomes in pancreatic cancer patients undergoing surgery: a systematic review and meta-analysis
Authors: Raoul Pauline , Cintoni Marco , Coppola Alessandro , Alfieri Sergio , Tortora Giampaolo , Gasbarrini Antonio , Mele Maria Cristina , Rinninella Emanuele 
Published: October 2024

Background:
Reduction in muscle mass can be routinely quantified using computed tomography (CT) of the third lumbar vertebra (L3) during a curative pancreatic cancer (PC) course. This systematic review and meta-analysis aimed to assess the association between preoperative low skeletal muscle index (SMI) measured by L3-CT and postoperative clinical outcomes in PC resectable patients.

Methods:
Three electronic databases (PubMed, Web of Science, and Scopus) were searched for articles published through May 2023. Duplicate titles and abstracts, full-text screening, and data extraction were performed. A meta-analysis was performed for overall survival (OS), recurrence-free survival (RFS), postoperative pancreatic fistula (POPF), morbidity, and postoperative length of stay (P-LOS). The risk of bias was assessed.

Results:
A total of 2942 patients with PC from 11 studies were identified. Preoperative low SMI was found in 50.9% of PC resectable patients. Preoperative low SMI was significantly associated with adjusted OS (adjusted hazard ratio, 1.52; 95% CI 1.25–1.86, P< 0.0001). No significant associations were found between preoperative low SMI and RFS, number of POPF, significant morbidity, and P-LOS (P>0.05).

Conclusions:
SMI should be evaluated in a timely manner as a predictor of OS in PC resectable patients. Studies assessing nutritional protocols for maintaining/increasing skeletal muscle mass are required to develop a personalized nutritional approach to improve clinical outcomes.
Validation of mitochondrial FMN as a predictor for early allograft dysfunction and patient survival measured during hypothermic oxygenated perfusion
Authors: Dingfelder Jule , Kollmann Dagmar , Rauter Laurin , Pereyra David , Kacar Sertac , Weijler Anna M. , Saffarian Zadeh Tina , Tortopis Chiara , Silberhumer Gerd , Salat Andreas , Soliman Thomas , Berlakovich Gabriela , Györi Georg P. 
Published: October 2024

Hypothermic oxygenated machine perfusion (HOPE) preconditions liver grafts before transplantation. While beneficial effects on patient outcomes were demonstrated, biomarkers for viability assessment during HOPE are scarce and lack validation. This study aims to validate the predictive potential of perfusate flavin mononucleotide (FMN) during HOPE to enable the implementation of FMN-based assessment into clinical routine and to identify safe organ acceptance thresholds. FMN was measured in perfusate samples of 50 liver grafts at multiple time points. After transplantation, patients were followed up for development of early allograft dysfunction (EAD), transplantation, and 1-year survival. FMN concentrations were significantly higher for grafts that developed EAD at 5 and 60 minutes into HOPE (p = 0.008, p = 0.026). The strongest predictive potential of FMN for EAD was observed at 5 minutes of HOPE with an AUC of 0.744. Similarly, 5-minute FMN was predictive for 1-year mortality (p < 0.001), reaching a remarkable AUC of 0.890. Cutoffs for prediction of EAD (10.6 ng/mL) and early mortality (23.5 ng/mL) were determined and allowed risk stratification of grafts. Particularly, patients receiving low-risk grafts developed EAD in 9% of cases, while all patients survived the first postoperative year. In contrast, high-risk organs developed an incidence of EAD at 62%, accompanied by the necessity of retransplantation in 38% of cases. One-year mortality in the high-risk cohort was 62%. Evaluation of FMN as early as 5 minutes during HOPE allows for risk stratification of liver grafts. Low-risk grafts, according to FMN, display a negligible risk for patients. Yet, high-risk grafts are associated with increased risk for EAD, transplantation, and early mortality and should not be used for transplantation without further assessment.
Characterization of exclusive rib lesions detected by [68Ga]Ga-PSMA-11 PET/CT
Authors: Stoffels Marine , Cousin François , Lamande Maréva , Denis Chloé , Waltregny David , Hustinx Roland , Sautois Brieuc , Withofs Nadia 
Published: October 2024

Objective
The objective of this study was to characterize exclusive costal lesions detected by 68Gallium-labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA-11) PET/computed tomography (CT) at initial staging or biochemical recurrence (BCR) in prostate cancer (PCa) patients, and to identify clinical and/or PET/CT criteria associated with benign and malignant lesions.

Methods
We retrospectively identified 54 patients with PCa who underwent [68Ga]Ga-PSMA-11 PET/CT for initial staging (N = 39) or BCR (N = 15) and whose reports described rib lesions, at the exclusion of any other lesions, whether doubtful, suspicious, or established. Posttherapy prostate-specific antigen (PSA) levels were used to determine whether those lesions were benign or malignant. Each patient’s prostate-specific membrane antigen PET/CT report was classified as true positive, true negative, false positive, or false negative based on the posttherapy PSA level. We then assessed whether any clinical and/or PET/CT criteria could help differentiate benign from malignant lesions, and if any criteria were misleading.

Results
Among the 54 patients, 46 (85.2%) had 64 benign costal lesions, and eight (14.8%) had 10 malignant lesions. PET/CT reports indicated rib lesions as benign/equivocal in 38/54 (55.6%) patients and malignant in 16/54 (29.6%). Benign features on CT were the only parameter significantly associated with the final diagnosis. Factors such as patient age, maximum standardized uptake value of lesions, lesion dispersion, and malignant features described on CT were found to be misleading when deciding the malignant or benign status.

Conclusion
Most exclusive costal lesions detected by [68Ga]Ga-PSMA-11 PET/CT are benign. Apart from specific benign CT features, no clinical or PET/CT criteria reliably differentiate benign from malignant costal lesions.
Lutetium-177-prostate-specific membrane antigen therapy for prostate cancer: current status and future prospects
Authors: Wong Chris Ho-Ming , Nicoletti Rossella , Mazzone Elio , Eapen Renu S. 
Published: October 2024

Purpose of review
Lutetium-177-prostate-specific membrane antigen (Lu 177-PSMA) radioligand therapy has emerged as a promising novel strategy for advanced prostate cancer. With its increasing importance alongside with a plethora of exciting results from latest trials, we would like to summarize current evidence and advancements in Lu 177-PSMA therapy across different stages of prostate cancer.

Recent findings
In metastatic castration-resistant prostate cancer (mCRPC), early studies like the LuPSMA trial and TheraP trial demonstrated promising PSA response rates. The landmark VISION trial had established the oncological efficacy of Lu 177-PSMA as salvage therapy and demonstrated its benefit on survival outcomes. Explorations into earlier treatment settings have also been encouraging. Studies like that the PSMAfore trial, Enza-P trial and the UpFrontPSMA trial explored an earlier role of Lu 177-PSMA in mCRPC, and showed benefits when used in solitary or in junction with Docetaxel or androgen receptor pathway inhibitor. Finally, the potential use of Lu 177-PSMA as neoadjuvant therapy in localized prostate cancer is also under consideration, whose safety was demonstrated in the recent LuTectomy trial.

Summary
Lu 177-PSMA therapy represents a significant advancement in prostate cancer treatment, offering selective and targeted delivery of radiation to prostate cancer cells in patients across various disease stages. Ongoing research and collaborative efforts are essential to overcome existing challenges, optimize patient selection and integrate this therapy into standard clinical practice, ultimately improving outcomes for patients with advanced prostate cancer.
Minimizing overtreatment and maximizing oncologic outcomes in upper tract urothelial carcinoma
Authors: Zahalka Ali H. , Margulis Vitaly 
Published: October 2024

Purpose of review
An update on the latest advances in the management of upper tract urothelial carcinoma (UTUC), with an emphasis on strategies to optimize oncologic outcomes while minimizing overtreatment.

Recent findings
Recent high-quality trials have changed the landscape of UTUC treatment. Emerging tools including 3D histology and measurement of cell free tumor DNA may improve diagnostic accuracy of disease grading and staging, and be used in monitoring treatment response. Novel therapies show promise of reducing low-grade UTUC disease recurrence at the cost of significant side-effects. Platinum-based neoadjuvant chemotherapy in high-grade/muscle-invasive disease showed complete pathological response in a subset of patients, but difficult to predict responders. Adjuvant platinum-based chemotherapy exhibited a clear survival benefit, but immunotherapy did not, suggesting possible overtreatment with these agents. Molecularly-targeted therapies in metastatic UTUC have shown the greatest recent oncologic advances, but exhibit a high adverse event-rate.

Summary
Low-grade UTUC has the potential for overtreatment, as it exhibits low metastatic-potential and excellent survival. For high-grade and advanced-stage UTUC, these carry high mortality rates and require more aggressive treatment, but studies are limited by inaccurate grading and staging which can lead to overtreatment especially in the neoadjuvant setting. Emerging technologies will help improve diagnostic accuracy and noninvasive monitoring of treatment response.
Examination of Proprioceptive Reliance During Backward Walking in Individuals With Multiple Sclerosis
Authors: VanNostrand Michael , Monaghan Patrick G. , Fritz Nora E. 
Published: October 2024

Background:
Slowed somatosensory conduction in multiple sclerosis (MS) increases postural instability and decreases proprioception. Despite these delays, individuals with MS rely more on proprioception for balance compared to controls. This heightened reliance, combined with slowed signal transduction, increases fall risk. Backward walking (BW) increases proprioceptive reliance by reducing visual cues. However, no study has conclusively linked proprioception to BW. This study aims to assess proprioception’s role in BW compared to forward walking (FW) in MS and to compare differences in proprioception between MS fallers and non-fallers.

Methods:
Fifty participants (average age: 50.34 ± 11.84, median Patient Determined Disease Steps [PDDS]: 2) completed the study. Participants completed BW and FW at comfortable and fast speeds. We have previously established vibration sensation as a proxy measure for proprioception. Vibration thresholds were quantified at the great toe bilaterally using a 2-alternative forced-choice procedure.

Results:
Significant correlations were seen for vibration sensation and FW comfortable (ρ = 0.35), FW fast (ρ = 0.34), BW comfortable (ρ = 0.46), and BW fast (ρ = 0.46). After controlling for age, sex, and PDDS, vibration sensation significantly predicted performance during all walking tasks, with larger beta coefficients seen during BW (comfortable β = 0.57; fast β = 0.58) compared to FW (comfortable β = 0.41; fast β = 0.45). Fallers performed significantly worse than non-fallers for vibration sensation (P = 0.04).

Discussion and Conclusions:
Considering the notable decrease in proprioception in participants with MS and the clear distinction between fallers and non-fallers, it is crucial to conduct fall risk assessments and interventions focusing on proprioception. With its heightened reliance on proprioception, BW offers a promising method for assessing fall risk and could be an effective exercise intervention.

Video Abstract available for more insights from the authors (see the Supplemental Digital Content available at: http://links.lww.com/JNPT/A490).
Surgical Management of 2,350 Pediatric Dermoid Cysts
Authors: Ng Jinggang J , Saikali Linda M. , Massenburg Benjamin B , Wu Meagan , Romeo Dominic J , Blum Jessica D , Swanson Jordan W , Taylor Jesse A , Kreiger Portia A , Bartlett Scott P 
Published: October 2024

Background:
We examined operative and pathologic findings of a large series of dermoid cysts at a high-volume pediatric hospital over 23 years.

Methods:
A retrospective review was performed of all dermoid cysts excised from 2000 to 2023 at the Children’s Hospital of Philadelphia. Lesions were classified by location. Depth was stratified into Type 1, superficial; Type 2, subperiosteal or containing a stalk to a cranial suture; Type 3, intraosseous or intracartilaginous; Type 4, intracranial extradural; and Type 5, intracranial intradural.

Results:
Of 2,350 lesions, 2,237 (95.2%) were in the head and neck. Most common locations were lateral brow and orbit, 892 (38%); anterior neck, 303 (12.9%); and frontal, 253 (10.8%). Among the series, 67.9% were Type 1, 10.1% were Type 2, 16.5% were Type 3, 2.3% were Type 4, and 3.2% were Type 5. Older age at surgery correlated with depth among locations demonstrating intracranial extension (r=.061, p=.016). Anterior fontanelle (59.1%), nasal (16.2%), occipital (5.6%), and temporal (4.7%) lesions had the highest intracranial extension rates. Temporal (49.4%), frontal (32.8%), nasal (29.9%), and occipital (22.2%) lesions had higher rates of osseous/cartilaginous involvement. On histopathologic examination, 403 (17.1%) were ruptured. Ruptured lesions were associated with giant cell reaction (46.4 versus 5.7%, p<.001).

Conclusions:
Anterior fontanelle, nasal, occipital, and temporal lesions are at higher risk of intracranial extension and may require preoperative imaging. Frontal and parietal lesions have a lower risk of intracranial involvement. Lateral brow and orbit, periauricular, and anterior neck lesions demonstrate a higher rate of osseous involvement without intracranial tracking.
“Legislative Impact and Persistent Disparities: Post-Mastectomy Breast Reconstruction Rates in the United States Among 224,506 Patients”
Authors: Schafer Rachel E. , Ho Isabel , Potoczak Patrick S. , Misra-Hebert Anita , Nowacki Amy S. , Schwarz Graham S. 
Published: October 2024

Background:
Breast reconstruction following mastectomy for the treatment of breast cancer restores form and enhances patient satisfaction. The Affordable Care Act (ACA) of 2010 aimed to impact trends in breast reconstruction, but recent information regarding racial and ethnic disparities is lacking.

Methods:
We analyzed National Surgical Quality Improvement Program (NSQIP) data spanning 2005-2022 to investigate the impact of ACA on racial and ethnic diversity in immediate breast reconstruction post-mastectomy. Patient demographics, including race and ethnicity, were considered. Statistical analyses included Pearson chi-square tests and multivariable logistic regressions to assess trends and disparities over time.

Results:
In total, 224,506 patients met inclusion criteria. Analysis revealed that in the pre-ACA era, American Indian or Alaska Native, Asian, and Black or African American individuals underwent immediate breast reconstruction at lower rates compared to White patients (P < 0.001). Additionally, Hispanic patients were less likely to undergo breast reconstruction compared to non-Hispanic patients (28.0% vs 33.4%; P < 0.001). In the post-ACA period, this trend persisted with all racial groups undergoing immediate breast reconstruction at lower rates compared to White patients (P < 0.001). However, Hispanic patients were more likely to undergo immediate breast reconstruction compared to non-Hispanic patients (53.8% vs 47.9%, P < 0.001).

Conclusions:
Despite legislative efforts and a steady increase in immediate breast reconstruction rates over the years, racial disparities in breast reconstruction rates persist, highlighting the need for ongoing monitoring and targeted interventions to ensure equitable reconstructive care for all patients.