bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blastocyst complementation generates exogenous donor‐derived liver in ahepatic pigs
Authors: Simpson Sean G. , Park Ki‐Eun , Yeddula Sai Gautham Reddy , Waters Jerel , Scimeca Erin , Poonooru Ravikanth Reddy , Etches Rob , Telugu Bhanu P. 
Published: November 2024

AbstractLiver diseases are one of the leading causes of morbidity and mortality worldwide. Globally, liver diseases are responsible for approximately 2 million deaths annually (1 of every 25 deaths). Many of the patients with chronic liver diseases can benefit from organ transplantation. However, stringent criteria for placement on organ transplantation waitlist and chronic shortage of organs preclude access to patients. To bridge the shortfall, generation of chimeric human organs in pigs has long been considered as an alternative. Here, we report feasibility of the approach by generating chimeric livers in pigs using a conditional blastocyst complementation approach that creates a vacant niche in chimeric hosts, enabling the initiation of organogenesis through donor‐derived pluripotent cells. Porcine fetal fibroblasts were sequentially targeted for knockin of CRE into the endogenous FOXA3 locus (FOXA3CRE) followed by floxing of exon 1 of HHEX (FOXA3CREHHEXloxP/loxP) locus. The conditional HHEX knockout and constitutive GFP donor (COL1ACAG:LACZ 2A EGFP) were used as nuclear donors to generate host embryos by somatic cell nuclear transfer, and complemented and transferred into estrus synchronized surrogates. In the resulting fetuses, donor EGFP blastomeres reconstituted hepatocytes as confirmed by immunohistochemistry. These results potentially pave the way for exogenous donor‐derived hepatogenesis in large animal models.
The role of the co‐chaperone DNAJB11 in polycystic kidney disease: Molecular mechanisms and cellular origin of cyst formation
Authors: Busch Tilman , Neubauer Björn , Schmitt Lars , Cascante Isabel , Knoblich Luise , Wegehaupt Oliver , Schöler Felix , Tholen Stefan , Hofherr Alexis , Schell Christoph , Schilling Oliver , Westermann Lukas , Köttgen Michael 
Published: November 2024

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2, encoding polycystin‐1 (PC1) and polycystin‐2 (PC2), which are required for the regulation of the renal tubular diameter. Loss of polycystin function results in cyst formation. Atypical forms of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)‐resident proteins through mechanisms that are not well understood. Here, we investigate the function of DNAJB11, an ER co‐chaperone associated with atypical ADPKD. We generated mouse models with constitutive and conditional Dnajb11 inactivation and Dnajb11‐deficient renal epithelial cells to investigate the mechanism underlying autosomal dominant inheritance, the specific cell types driving cyst formation, and molecular mechanisms underlying DNAJB11‐dependent polycystic kidney disease. We show that biallelic loss of Dnajb11 causes cystic kidney disease and fibrosis, mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11 inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11‐dependent cyst formation. Proteomic analysis of Dnajb11‐ and Pkd1‐deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.
CD59 double knockout mice express a CD59ba hybrid fusion protein that mediates insulin secretion
Authors: Ekström A. , Villoutreix B. O. , Halperin J. , Renström E. , Blom A. M. , King B. C. 
Published: November 2024

AbstractCD59 is a cell‐surface inhibitor of the terminal step in the complement cascade. However, in addition to its complement inhibitory function, a non‐canonical role of CD59 in pancreatic beta cells has been identified. Two recently discovered intracellular alternative splice forms of CD59, IRIS‐1 and IRIS‐2, are involved in insulin exocytosis through interactions with SNARE‐complex components. In mice, the CD59 gene has undergone duplication and to further explore the role of CD59 in insulin secretion, blood glucose homeostasis was studied in a CD59 double knockout (CD59abKO) mouse model. However, no phenotypic deviation related to insulin secretion or blood glucose homeostasis was observed for the CD59abKO mice. Instead, a CD59ba hybrid transcript formed as a consequence of the mutation induced to generate the model was identified. This hybrid transcript is expressed in pancreatic islets of the CD59abKO mice and is comprised of the remaining exons of the two CD59 genes spliced together. Similar to canonical CD59, the CD59ba hybrid was found to be glycosylated and present on the cell surface when exogenously expressed in INS‐1 832/13 cells. Furthermore, INS‐1 832/13 cells over‐expressing the mouse CD59ba hybrid retained normal insulin secretion following siRNA‐mediated knockdown of canonical CD59. Hence, although the CD59ba hybrid has lost the complement inhibitory function, the intracellular insulin secretory function remains. These results provide further information concerning the structural requirements of CD59 in its intracellular role relative to its role as a complement inhibitor. It also highlights the importance of carefully assessing plausible consequences of induced mutations in research models.
Paravertebral versus Pectoralis-II (Interpectoral and Pectoserratus) Nerve Blocks for Postoperative Analgesia after Nonmastectomy Breast Surgery: A Randomized, Controlled, Observer-masked Noninferiority Trial
Authors: Gabriel Rodney A. , Curran Brian P. , Swisher Matthew W. , Sztain Jacklynn F. , Tsuda Paige S. , Said Engy T. , Alexander Brenton , Finneran John J. , Abramson Wendy B. , Black Jessica R. , Wallace Anne M. , Blair Sarah , Donohue Michael C. , Abdullah Baharin , Xu Nicole Y. , Cha Brannon J. , Ilfeld Brian M. 
Published: November 2024

Background:
Pectoralis-II and paravertebral nerve blocks are both used to treat pain after breast surgery. Most previous studies involving mastectomy identified little difference of significance between the two approaches. Whether this is also accurate for nonmastectomy procedures remains unknown.

Methods:
Participants undergoing uni- or bilateral nonmastectomy breast surgery anticipated to have at least moderate postoperative pain were randomized to a pectoralis-II or paravertebral block (90 mg ropivacaine per side for both). Surgeons and recovery room staff were masked to treatment group assignment, and participants were not informed of their treatment group. Injectate for pectoralis-II blocks was ropivacaine 0.3% (30 ml) per side. Injectate for paravertebral blocks was ropivacaine 0.5% (9 ml in each of two levels) per side. This study hypothesized that pectoralis-II blocks would have noninferior analgesia (numeric rating scale) and noninferior cumulative opioid consumption within the operating and recovery rooms combined (dual primary outcomes). The study was adequately powered with n = 100, but the target enrollment was raised to n = 150 to account for higher-than-anticipated variability.

Results:
The trial was ended prematurely with 119 (79%) of the original target of 150 participants enrolled due to (masked) surgeon preference. Within the recovery room, pain scores were higher in participants with pectoralis-II (n = 60) than paravertebral blocks (n = 59): median [interquartile range], 3.3 [2.3, 4.8] versus 1.3 [0, 3.6] (95% CI, 0.5 to 2.6; P < 0.001). Similarly, intravenous morphine equivalents were higher in the pectoralis-II group: 17.5 [12.5, 21.9] versus 10.0 mg [10, 20] (95% CI, 0.1 to 7.5; P = 0.004). No block-related adverse events were identified in either group.

Conclusions:
After nonmastectomy breast surgery, two-level paravertebral blocks provided superior analgesia and opioid sparing compared with pectoralis-II blocks. This is a contrary finding to the majority of studies in patients having mastectomy, in which little significant difference was identified between the two types of blocks.
Pediatric Orthopaedic Surgeons Manage Pediatric Diaphyseal Clavicle Fractures Differently Than Nonpediatric Orthopaedic Specialists
Authors: Higgins Margaret J. , Gomez Robert W. , Storino Morgan , Jessen David , Lamb Zachary J. , Jain Neil , Greenhill Dustin A. 
Published: November 2024

Background:
Pediatric clavicle fractures are often managed by physicians with and without pediatric subspecialty training. The aim of this study is to identify if variability of practice exists between pediatric orthopaedic surgeons versus nonpediatric orthopaedic specialists during management of pediatric diaphyseal clavicle fractures.

Methods:
Patients ≤18 years of age with an acute, closed diaphyseal clavicle fracture treated between January 2018 and July 2023 by a large hospital-employed multispecialty orthopaedic practice (in a regional and academic health network) were retrospectively reviewed. The study involved 26 orthopaedic surgeons (including 3 pediatric, 8 sports medicine, and 6 general) and 11 nonoperative sports medicine physicians, all of which accept patients ranging 0 to 18 years of age. Exclusion criteria included open or impending open fractures and insufficient data. Demographic, radiographic, and outpatient treatment parameters were recorded. Age groups were separated into <10 and ≥10 years old to control for age-associated differences.

Results:
Among 560 pediatric clavicle fractures, 385 met inclusion criteria (43.6% of which were treated by a pediatric orthopaedic surgeon), and 361 were treated nonoperatively. Follow-up averaged 48.8 days until orthopaedic discharge and 16.9 months until the most recent well-child visit (80% had a well-child visit after orthopaedic discharge). No patient <10 years of age had elective surgery, but pediatric orthopaedic surgeons demonstrated lower surgical rates in adolescent patients than nonpediatric specialties (4.3% vs. 14.4%, OR=3.8, P=0.027). Among the 169 nonoperative patients <10 years of age, pediatric orthopaedic surgeons completed fewer outpatient visits (2.1±0.8 vs. 2.4±0.8, P<0.037), shorter follow-up durations (28.5±18.9 vs. 41.8±22.6 d, P<0.001), less radiographic series (2.1±0.8 vs. 2.4±1.0, P<0.047), and less total radiographs (4.3±1.8 vs. 5.0±2.3, P<0.013) than nonpediatric specialists.

Conclusions:
The surgical rate of acute, closed diaphyseal clavicle fractures is lower among pediatric versus nonpediatric orthopaedic surgeons in adolescents. During nonoperative management of pediatric clavicle fractures, pediatric orthopaedic surgeons treat young patients (but not adolescents) with less outpatient visits and radiographs than nonpediatric orthopaedic physicians.

Level of Evidence:
Level III
Balancing the Interactions: Assessing Antiplatelet and Antiretroviral Therapy Drug–Drug Interactions in People Living With HIV
Authors: Matsikas Athena , Marsh Kassandra , Huynh Quy , Pashun Raymond , Papadopoulos John , Ahuja Tania 
Published: November 2024

Abstract:
The clinical effect of drug–drug interactions (DDIs) between antiplatelets and antiretroviral therapy (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with HIV (PLWH) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. Ninety-three PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n = 84, 71%), followed by ticagrelor (n = 9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown whether DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or whether underlying platelet reactivity in PLWH is associated with these events.
Evaluating Early Nerve Injury and Its Relationship With Leprosy Reactions in Patients With Leprosy: A Prospective Cohort Study
Authors: Lin Lan-Mei , Wu Hao , Zhu Wan-Rong , Dong Can-Bin , Zhang Qi , Zheng Cheng-Hui , Liang Xiao-Niu , Long Heng , Xu Jin-Hua , Ding Hong , Du Juan 
Published: November 2024

Objective:
Leprosy is an infectious disease that can be accompanied by disability caused by peripheral neuropathy. Early detection of leprosy is essential to reduce its debilitating sequelae. Ultrasound is a noninvasive test that can detect nerve loss, but ultrasound measurement depends on the skill level of operators. Radiomics is an emerging field related to the extraction and quantification of information, which may provide new solutions for early detection of neuropathy caused by leprosy. This study aimed to combine radiomics and ultrasonography to evaluate nerve damage in the early stages of leprosy in China.

Methods:
Patients were enrolled at the Wenshan Prefecture Institute of Dermatology between October 2018 and December 2022. High-resolution ultrasound imaging of the peripheral nerves was performed. Quantitative ultrasound features were extracted from the images from 5 follow-ups. Radiomic features were selected for a comparative analysis of the disease course using a linear mixed-effects model to control for potential confounding effects.

Results:
Nine patients with leprosy were enrolled in this study, consisting of 5 males and 4 females with an average age of 34.44 ± 13.58 years. With the change of treatment time, the ultrasound radiomics features of different parts of the linear mixed-effects model showed a trend of change: the nerve density (mean, skewness) was improved, the fascicular structure (kurtosis) was restored, and the abnormal morphological features in some parts were reduced (P < 0.05). Patients with type 1 leprosy reactions exhibited a lower mean and skewness, higher kurtosis, and increased quantitative morphological characteristics.

Conclusion:
The study provided the feasibility of ultrasound radiomics to digitally visualize the progression of nerve damage in leprosy patients. Ultrasound radiomics can be a low-cost method with high-throughput characteristics for clinical operators of different skill levels in early nerve injury detection of leprosy.
Do transition to practice hour requirements make a difference in adverse action and medical malpractice payment reports: An analysis from the National Practitioner Data Bank
Authors: Dillon Deborah 
Published: November 2024

ABSTRACT

Background:
The transition to practice (TTP) hour requirement presents a barrier to full practice authority (FPA) for nurse practitioners (NPs). Since 2015, the predominant method of granting FPA entails a TTP hour requirement.

Purpose:
Adverse action reports (AARs) and medical malpractice payment reports (MMPRs) of NPs were compared in states with FPA on initial licensure and states with FPA requiring a TTP hour period using data from the National Practitioner Data Bank (NPDB). The relationship of TTP hours to AARs and MMPRs was also evaluated.

Methodology:
A secondary analysis was obtained from a review of retrospective data in the NPDB. States examined were those that grant FPA on initial advanced practice registered nurse licensure and states that require a TTP hour requirement as part of their criteria for granting FPA.

Results:
In a 5-year period, postimplementation of FPA or 5-year postexpiration of the TTP requirement in 23 states, plus the District of Columbia, revealed that states with FPA granted on initial licensure demonstrated a lower incidence of AARs and MMPRs at the 5-year period compared with states that require a TTP hour period. No relationship existed between the amount of TTP hours and the incidence of AARs and MMPRs.

Conclusion:
Transition to practice hours remains a barrier to NPs achieving FPA. It is important for nursing to continue to build the body of evidence that refutes or supports the need for TTP hours.

Implications:
These data can be used when lobbying at the state level in the remaining states seeking FPA.
Rural-Urban Disparities in Mobile Health Application Ownership and Utilization Among Cancer Survivors
Authors: Mahmood Asos , Mahmood Aram , Kedia Satish , Chang Cyril F. 
Published: November 2024

Objective:
Mobile health applications (mHealth apps) can provide health care and health-promoting information while contributing to improving cancer survivors’ quality of life and health outcomes. However, little is known about the rural-urban distribution of mHealth app ownership and utilization. In this study, we explore the characteristics of cancer survivors who own and use mHealth apps and examine rural-urban disparities in mHealth app ownership and utilization among cancer survivors.

Methods:
We utilized data from the “Health Information National Trends Survey–Surveillance, Epidemiology, and End Results” pilot study, fielded among cancer survivors from 3 U.S. cancer registries (Iowa, New Mexico, and California) in 2021. Our sample included 942 cancer survivors who reported owning a smart device (a smartphone and/or a tablet computer). The analyses included computing weighted proportions and fitting a multivariable regression model.

Results:
Overall, 60.3% of cancer survivors reported using mHealth apps, and 16.9% resided in rural areas. Approximately 45.0% of rural cancer survivors reported utilizing mHealth apps (vs 63.5% of urban survivors). Regression analysis revealed that rural cancer survivors had 46.0% lower odds of owning and using mHealth apps compared with their urban counterparts (adjusted odds ratio = 0.54; 95% CI: 0.36, 0.80).

Conclusions:
Rural cancer survivors were less likely to own and use mHealth apps compared with urban survivors. Rural cancer survivors usually face structural and health care system-related barriers to health care access and affordability. Leveraging mHealth technology as a tool could potentially contribute to improving health care delivery for rural cancer survivors, and help address existing structural and informational barriers to access.
Gold standard nephroureterectomy, chemoprophylaxis and surveillance in upper tract urothelial carcinoma
Authors: Basile Giuseppe , Bandini Marco , Li Roger , Poch Michael A. , Necchi Andrea , Spiess Philippe E. 
Published: November 2024

Purpose of review
The purpose of this review is to summarize the most recent evidence on surgical management, strategies to reduce tumor recurrence, and surveillance regimens in patients diagnosed with upper tract urothelial carcinoma (UTUC) and elected for radical treatment.

Recent findings
Minimally invasive surgery is gaining momentum in the surgical management of UTUC. Chemoprophylaxis is still the gold standard to reduce intravesical recurrence after radical nephroureterectomy (RNU). Novel surveillance strategies have been proposed to adapt follow-up regimens to patients’ characteristics.

Summary
Minimally invasive surgery has been associated with comparable oncological outcomes to the open approach while improving postoperative morbidity. In these cases, bladder cuff excision (BCE) is mostly performed by an extravesical approach, that demonstrates a noninferiority compared to the intravesical one in terms of oncological outcomes. Although lymphadenectomy is recommended in patients with high-risk tumors, its benefits are still unclear. Currently, there is a lack of recent prospective trials on chemoprophylaxis to reduce intravesical recurrence post RNU, making single-dose postoperative chemotherapy instillation the standard treatment. Although novel risk stratification models were released by international urological guidelines, their validity is mainly nonevidence-based. Risk-adapted follow-up strategies incorporating cystoscopy and cross-sectional imaging accounting for individual patient factors should be implemented.
The role of MRI in muscle-invasive bladder cancer: an update from the last two years
Authors: Pastorino Giovanni Luigi , Mercinelli Chiara , Necchi Andrea 
Published: November 2024

Purpose of review
Muscle invasive bladder cancer (MIBC) is aggressive and requires radical cystectomy and neoadjuvant therapy, yet over 40% of patients face recurrence. The loss of the bladder also significantly reduces quality of life. Accurate staging, crucial for treatment decisions, is typically done through transurethral resection (TURBT), but inconsistencies in pathology affect diagnosis in 25% of cases. MRI is the most precise imaging method for evaluating local tumor invasiveness. This review discusses recent advances in MRI for staging MIBC and predicting responses to neoadjuvant therapy.

Recent findings
Vesical imaging – reporting and data system (VI-RADS) accuracy may improve if combined with ADC maps and tumor contact length, while a bi-parametric MRI approach without contrast could reduce side effects without losing diagnostic precision, though evidence is mixed. VI-RADS shows promise in predicting neoadjuvant therapy responses, and the new nacVI-RADS score is in development. Non-Gaussian diffusion-weighted imaging techniques and machine learning could enhance accuracy but need more integration with mpMRI. VI-RADS may assist in evaluating responses in bladder-sparing regimens. Urodrill, an MRI-guided biopsy, aims to replace diagnostic TURBT but needs more accuracy data.

Summary
MRI in MIBC is evolving, offering potential for accurate local staging and reduced side effects by avoiding TURBT. Predicting neoadjuvant treatment response could guide personalized treatment and bladder preservation. Larger trials are needed to validate these findings.
Bart syndrome with musculoskeletal deformity: a rare case report
Authors: Pokhrel Sanish , Niraula Zenish , Ghimire Pradip , Ale Magar Sugam , Acharya Ashish , Awal Kiran 
Published: November 2024

Introduction:
Bart syndrome is a rare genetic disorder characterized by epidermolysis bullosa (EB), aplasia cutis congenita, that is congenital local absence of skin and nail abnormalities.

Case Presentation:
The authors herein, present a case of a 14-year-old boy with Bart syndrome. The syndrome was diagnosed clinically. On examination, multiple generalized blisters were present and absence of nails in the toes of both feet and the middle finger of the left hand, which was associated with musculoskeletal deformity.

Discussion:
Bart syndrome, an inherited autosomal dominant disorder, is an exceedingly rare disorder. Musculoskeletal deformity is an uncommon presentation of this syndrome. It is mostly associated with Dystrophic type of EB. It is mostly a clinical diagnosis; however, histopathological study, direct immunofluorescence, and genetic testing helps in diagnosing the type of EB.

Conclusion:
The absence of skin in a localized area at birth is a crucial indicator for diagnosing Bart syndrome at birth, which later heals and can obscure the diagnosis. Early diagnosis and conservative management prevent the disease progression and complications.