bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital Transfers for Digit Replants as Cost Saving and Safe While Access to Replantation Procedures Remains Limited
Authors: Hauc Sacha C. , Ihnat Jacqueline M. , Hu Kevin , Parikh Neil , Rivera Jean Carlo , Alperovich Michael 
Published: September 2024

Background
Finger replantation outcomes are influenced both by injury characteristics and by hospital and patient factors, such as hospital type/location and patient gender or insurance. Finger replantation success rates have been shown to be higher at hospitals with higher volumes of finger replants. This study examines the hospital and patient factors that influence hospital transfer and successful replantation in patients experiencing traumatic finger amputation.

Methods
A total of 5219 patients were identified in the 2008–2015 National Inpatient Sample (NIS) as having experienced traumatic finger amputation with attempted replantation. Hospital transfer and replant outcomes were compared with variables such as patient demographics and hospital characteristics using χ2 tests, t tests, ANOVA, and logistic regression.

Results
Traumatic digit amputation patients were most likely to be transferred to medium or large hospitals in urban areas. Hospital transfer was 1.5 times more likely in White patients than Black or Hispanic patients and 1.6 times more likely in middle income quartile patients than the top income quartile. Postreplant amputation was more likely in patients in the lower three income quartiles, on Medicare, of older age, or with more chronic conditions. Hospital transfer was not associated with changes in the probability of requiring amputation after replantation but was associated with a decreased cost of $5000.

Conclusions
Hospital transfers for finger replants are safe with respect to replant failure rates and cost-effective, saving $5000 per procedure. Gaps in equitable access to care remain, warranting further study to improve health equity.
The Association Between the Origin of the Donation After Circulatory Death Liver Recovery Team and Graft Survival: A National Study
Authors: Ibeabuchi Tobenna , Li Eric , Cywes Claire , Bittermann Therese , Mahmud Nadim , Abt Peter L. 
Published: September 2024

Background.
Transplant centers have traditionally relied upon procurement teams from their own programs (transplant program procurement team [TPT]) to recover donation after circulatory death (DCD) livers and rarely use surgical procurement teams not affiliated with the recipient center (nontransplant program procurement team [NTPT]). However, in the era of wider geographic organ sharing, greater reliance on NTPTs is often necessary.

Methods.
We used national data to study the association between the origin of the donor procurement team (NTPT versus TPT) and the risk of DCD liver allograft failure.

Results.
Five hundred NTPT and 2257 TPT DCD transplants were identified: 1-y graft survival was 88.9 and 88.6%, respectively (P = 0.962). In a multivariable model, the origin of the procurement team was not associated with graft failure NTPT versus TPT (hazard ratio, 0.92; 95% confidence interval, 0.71-1.22; P = 0.57) but rather with known risks for DCD graft loss including donor age, degree of recipient illness, cold ischemic time, and retransplantation. The overall incidence of retransplantation and ischemic cholangiopathy as an indication for retransplantation were similar between NTPT and TPT.

Conclusions.
This data suggests that transplant centers may be able to safely use DCD livers recovered by local surgical teams.
Fostering an aged care organizational culture that supports innovation
Authors: Davy Carol Patricia , Windle Alice , Harvey Gillian 
Published: September 2024

ABSTRACT

Aim:
This study aimed to identify how aged care organizations can foster a culture that supports the implementation of innovation.

Introduction:
The aged care sector must innovate to meet clients’ evolving needs and increased regulatory requirements. Given the need to account for the values, beliefs, expectations, and assumptions held by a diverse range of stakeholders, implementing innovations within aged care can be exceptionally complex. Fostering a supportive organizational culture can facilitate the implementation of these critical innovations.

Methods:
Papers from a large scoping review that identified organizational culture as a barrier and/or enabler to implementing innovations in aged care were imported into NVivo. Data relating to how organizations fostered (or could foster) a culture that supported the implementation of innovations were then extracted, inductively coded, interpreted, and grouped into approaches.

Results:
Of the 193 papers from the original scoping review, 109 were included in this secondary analysis. From these 109 papers, we identified six key approaches: cultivating collaboration; valuing contributions; ensuring alignment between the organizational vision, culture, and innovation; demonstrating organizational commitment; developing and communicating the implementation plan; and accounting for stability.

Conclusions:
Our study outlines effective approaches that can be used by aged care organizations to cultivate a culture that supports the implementation of innovations. However, these approaches should not be viewed in isolation; rather, they are interconnected and mutually reinforcing. Together, these insights offer practical guidance for aged care entities seeking to adapt and evolve through innovation implementation.

Spanish abstract:

http://links.lww.com/IJEBH/A264
Leading the way: implementing aged care innovations
Authors: Davy Carol , Windle Alice , Marshall Amy , Harvey Gillian 
Published: September 2024

ABSTRACT

Objectives:
The objective of this study was to identify the key characteristics of leaders that support the implementation of innovations in aged care settings.

Methods:
We conducted a secondary analysis of papers from a large scoping review that identified how leaders supported the implementation of innovations in aged care. Once imported into NVivo12, the findings were deductively coded using the domains of Bloom's taxonomy of learning. Each parent code was then inductively analyzed to identify key characteristics within each domain.

Results:
Our review identified four types of knowledge, five skills, and six attitudes that leaders should exhibit to better support the implementation of innovations within aged care settings. In addition to our findings regarding Bloom's learning domains, we identified nine leadership behaviors that participants in the included papers perceived as valuable for enhancing the implementation process. Furthermore, we identified four key organizational elements that support leaders in navigating and facilitating the implementation of innovations within aged care settings.

Conclusion:
Our review identified the characteristics that leaders should demonstrate when supporting the implementation of innovations in aged care. Importantly, our findings also emphasized the changing role of leadership from a hierarchical approach to a more collaborative, supportive, and empowering style. The insights identified in this review will help to guide aged care leaders, stressing the significance of adaptable and relational leadership styles that will guide the implementation of innovations within the aged care sector.

Spanish abstract:

http://links.lww.com/IJEBH/A271
MAPK/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy
Authors: Kim Kwang-Soo , Zhang Junyi , Arrieta Víctor A. , Dmello Crismita , Grabis Elena , Habashy Karl , Duffy Joseph , Zhao Junfei , Gould Andrew , Chen Li , Hu Jian , Balyasnikova Irina , Chand Dhan , Levey Dan , Canoll Peter , Zhao Wenting , Sims Peter A. , Rabadan Raul , Pandey Surya , Zhang Bin , Lee-Chang Catalina , Heiland Dieter Henrik , Sonabend Adam M. 
Published: September 2024

AbstractBackgroundGlioblastoma (GB) remains a formidable challenge in neuro-oncology, with immune checkpoint blockade (ICB) showing limited efficacy in unselected patients. We previously recently established that MAPK/ERK signaling is associated with overall survival following anti-PD-1 and anti-CTLA-4 treatment in recurrent GB. However, the causal relationship between MAPK/ERK signaling and susceptibility to ICB, as well as the mechanisms underlying this association, remain poorly understood.MethodWe conductedin vivokinome-wide CRISPR/Cas9 screenings in murine gliomas to identify key regulators of susceptibility to anti-PD-1 and CD8+T cell responses and performed survival studies to validate the most relevant genes. Additionally, paired single cell RNA- sequencing (scRNA-seq) with p-ERK staining, spatial transcriptomics on GB samples, andex-vivoslice culture of a BRAFV600Emutant GB tumor treated with BRAFi/MEKi were used to determine the causal relationship between MAPK signaling, tumor cell immunogenicity, and modulation of microglia phenotype.ResultsCRISPR/Cas9 screens identified the MAPK pathway, particularly the RAF-MEK-ERK pathway, as the most critical modulator of glioma susceptibility to CD8+T cells, and anti-PD-1 across all kinases. Experimentally-induced ERK phosphorylation in gliomas enhanced survival with ICB treatment, led to durable anti-tumoral immunity upon re-challenge and memory T cell infiltration in long-term survivors. Elevated p-ERK in glioma cells correlated with increased interferon responses, antigen presentation and T cell infiltration in GB. Moreover, spatial transcriptomics and scRNA-seq analysis revealed the modulation of interferon responses by the MAPK/ERK pathway in BRAFV600Ehuman GB cells with ERK1/2 knockout and in slice cultures of human BRAFV600EGB tissue. Notably, BRAFi/MEKi treatment disrupted the interaction between tumor cells and tumor-associated macrophages/microglia in slice cultures from BRAFV600Emutant GB.ConclusionOur data indicate that the MAPK/ERK pathway is a critical regulator of GB cell susceptibility to anti-tumoral immunity, modulating interferon responses, and antigen-presentation in glioma cells, as well as tumor cell interaction with microglia. These findings not only elucidate the mechanistic underpinnings of immunotherapy resistance in GB but also highlight the MAPK/ERK pathway as a promising target for enhancing immunotherapeutic efficacy in this challenging malignancy.
Luminal Flow in the Connecting Tubule induces Afferent Arteriole Vasodilation
Authors: Wang Hong , Ortiz Pablo A. , Romero Cesar A. 
Published: September 2024

AbstractBackgroundRenal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF—whether NaCl concentration, independent luminal flow, or the combined total sodium delivery—is still unclear. We hypothesized that increasing luminal flow in the CNT induces CNTGF via O2-generation and ENaC activation.MethodsRabbit afferent arterioles (Af-Arts) with adjacent CNTs were microperfusedex-vivowith variable flow rates and sodium concentrations ranging from <1 mM to 80 mM and from 5 to 40 nL/min flow rates.ResultsPerfusion of the CNT with 5 mM NaCl and increasing flow rates from 5 to 10, 20, and 40 nL/min caused a flow rate-dependent dilation of the Af-Art (p<0.001). Adding the ENaC blocker benzamil inhibited flow-induced Af-Art dilation, indicating a CNTGF response. In contrast, perfusion of the CNT with <1 mM NaCl did not result in flow-induced CNTGF vasodilation (p>0.05). Multiple linear regression modeling (R2=0.51;p<0.001) demonstrated that tubular flow (β=0.163 ± 0.04;p<0.001) and sodium concentration (β=0.14 ± 0.03;p<0.001) are independent variables that induce afferent arteriole vasodilation. Tempol reduced flow-induced CNTGF, and L-NAME did not influence this effect.ConclusionIncreased luminal flow in the CNT induces CNTGF activation via ENaC, partially due to flow-stimulated O2-production and independent of nitric oxide synthase (NOS) activity.
Identification of potent biparatopic antibodies targeting FGFR2 fusion driven cholangiocarcinoma
Authors: Chaturantabut Saireudee , Oliver Sydney , Frederick Dennie T. , Kim Jiwan , Robinson Foxy P. , Sinopoli Alessandro , Song Tian-Yu , Rodriguez Diego J. , Chang Liang , Kesar Devishi , He Yao , Ching Meilani , Dzvurumi Ruvimbo , Atari Adel , Tseng Yuen-Yi , Bardeesy Nabeel , Sellers William R. 
Published: September 2024

AbstractTranslocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, the rate and durability of response are limited due to the emergence of resistance, typically involving acquired FGFR2 kinase domain mutations, and to sub-optimal dosing, relating to drug adverse effects. Here, we report the development of biparatopic antibodies targeting the FGFR2 extracellular domain (ECD), as candidate therapeutics. Biparatopic antibodies can overcome drawbacks of standard bivalent monoparatopic antibodies, which often show poor inhibitory or even agonist activity against oncogenic receptors. We show that oncogenic transformation by FGFR2 fusions requires an intact ECD. Moreover, by systematically generating biparatopic antibodies that target distinct epitope pairs along the FGFR2 ECD, we identified antibodies that effectively block signaling and malignant growth driven by FGFR2-fusions. Importantly, these antibodies demonstrate efficacy in vivo, synergy with FGFR inhibitors, and activity against FGFR2 fusions harboring kinase domain mutations. Thus, biparatopic antibodies may serve as new treatment options for patients with FGFR2-altered cholangiocarcinoma.SummaryWe identify biparatopic FGFR2 antibodies that are effective against FGFR2 fusion driven cholangiocarcinoma.
Feasibility of laminar functional quantitative susceptibility mapping
Authors: Straub Sina , Zhou Xiangzhi , Tao Shengzhen , Westerhold Erin M. , Jin Jin , Middlebrooks Erik H. 
Published: September 2024

AbstractLayer fMRI is an increasingly utilized technique that provides insights into the laminar organization of brain activity. However, both blood-oxygen-level-dependent (BOLD) fMRI and vascular space occupancy data (VASO) have certain limitations, such as bias towards larger cortical veins in BOLD fMRI and high specific absorption rate in VASO. This study aims to explore the feasibility of whole-brain laminar functional quantitative susceptibility mapping (fQSM) compared to laminar BOLD fMRI and VASO at ultra-high field. Data were acquired using 3D EPI techniques. Complex data were denoised with NORDIC and susceptibility maps were computed using 3D path-based unwrapping, the variable-kernel sophisticated harmonic artifact reduction as well as the streaking artifact reduction for QSM algorithms. To assess layer-specific activation, twenty layers were segmented in the somatosensory and motor cortices, obtained from a finger tapping paradigm, and further averaged into six anatomical cortical layers. The magnitude of signal change and z-scores were compared across layers for each technique. fQSM showed the largest activation-dependent mean susceptibility decrease in Layers II/III in M1 and Layers I/ II in S1 with up to -1.3 ppb while BOLD fMRI showed the strongest mean signal increase in Layer I. Our data suggest that fQSM demonstrates less bias towards activation in superficial layers compared to BOLD fMRI. Moreover, activation-based susceptibility change was comparable to VASO data. Studying whole-brain, layer-dependent activation with submillimeter fQSM is feasible, and reduces bias towards venous drainage effects on the cortical surface compared to BOLD fMRI, thereby enabling better localization of laminar activation.
Monitoring of Cell-free Human Papillomavirus DNA in Metastatic or Recurrent Cervical Cancer: Clinical Significance and Treatment Implications
Authors: Yin Zhuomin , Feng Tao , Xu Qing , Dai Wumin , Ni Maowei , Ni Juan , Lou Hanmei 
Published: September 2024

AbstractPurposeMonitoring of circulating human papillomavirus (HPV) cell-free DNA (cfDNA) is a minimally invasive approach for surveillance in HPV-associated cancers, particularly cervical cancer. The aim of this study was to monitor circulating HPV cfDNA levels in patients with recurrent or metastatic cervical cancer during treatment and follow-up to assess the utility of HPV cfDNA as a tumor marker for disease surveillance and in guiding clinical treatment decisions.Experimental DesignIn this prospective pilot observational study, levels of HPV cfDNA in serum samples from 28 patients with recurrent or metastatic HPV+ cervical cancer were measured via digital droplet polymerase chain reaction. Results for HPV cfDNA levels were matched to clinical outcomes and to serum levels of squamous cell carcinoma antigen (SCC-Ag) to assess the clinical potential of HPV cfDNA as a tumor marker.ResultsHPV cfDNA was detected in all 28 patients (100%). Notably, median baseline HPV cfDNA levels varied according to the metastatic pattern in individual patients (P=0.019). Specifically, patients with a combined multiple-metastasis pattern had higher median baseline HPV cfDNA levels than patients with a single metastasis (P=0.003). All participants exhibited changes in HPV cfDNA levels over a median monitoring period of 2 months (range 0.3–16.9) before evaluations for treatment response or disease progression. Among 26 patients initially diagnosed with squamous cell cervical cancer, the positivity rate was 100% for HPV cfDNA and 69.2% for SCC-Ag (P=0.004, 95% confidence interval, 0–0.391). Among 20 patients longitudinally monitored for squamous cell cervical cancer, the concordance with changes in disease status was 90% for HPV cfDNA and 50% for SCC-Ag (P=0.014, 95% confidence interval, 0.022–0.621).ConclusionsHPV cfDNA is a promising tumor marker for HPV+ cervical cancer that offers advantages over SCC-Ag. In the context of precision medicine, HPV cfDNA is poised to play an increasingly pivotal role in monitoring treatment efficacy, providing valuable insights into disease progression, and guiding clinical decisions.
MEK1/2 kinases cooperate with c-Myc:MAX to prevent polycomb repression ofTERTin human pluripotent stem cells
Authors: Kotian Spandana , Rizzardi Lindsay F. , Stern Josh L. 
Published: September 2024

ABSTRACTTelomerase counteracts telomere shortening, enabling human embryonic stem cells (hESC) to undergo long-term proliferation. MAPK signaling plays a major role in regulating the self-renewal of hESC, and previous studies in induced pluripotent stem cells (iPSC) suggested that expression ofTERT, the gene encoding the catalytic subunit of telomerase, relies on MAPK signaling. We examined whether MEK-ERK signaling regulatedTERTtranscription in a model of normal hESC. Kinase inhibitors of MEK1 and MEK2 (MEKi) or ERK1 and ERK2 (ERKi) significantly repressedTERTmRNA levels. Using chromatin immunoprecipitation (ChIP) we observed that MEKi induced the accumulation of the repressive histone mark histone 3 lysine 27 trimethylation (H3K27me3) at theTERTproximal promoter. This increase corresponded with a loss of histone 3 lysine 27 acetylation (H3K27ac) which is associated with transcriptionally active loci. Inhibition of the polycomb repressive complex 2 (PRC2), which deposits H3K27me3, partially rescued the loss ofTERTexpression, indicating that MEK1/2 activity can limit PRC2 activity atTERT. Inhibition of MEK/ERK kinases also repressed expression of c-Myc, a transcription factor reported to regulateTERTin other immortalized cells. Consistent with a key role for c-Myc in regulatingTERT, low doses of a c-Myc:MAX dimerization inhibitor induced a striking and rapid gain of H3K27me3 atTERTand repressedTERTtranscription in hESC. Inhibiting c-Myc:MAX dimerization also resulted in lower MAX recruitment toTERT, suggesting that this complex acts in cis atTERT. Our study using a model of normal human pluripotent stem cells identifies new regulators and mechanisms controlling transcription of an important, developmentally regulated gene involved in telomere protection.
Unlocking precision: How corneal cell area analysis revolutionizes post-transplant stem cell monitoring
Authors: Parkinson Patrick , Makarenko Irina , Baylis Oliver J , Figueiredo Gustavo S , Lako Majlinda , Shukurov Anvar , Figueiredo Francisco C , Wadkin Laura E 
Published: September 2024

AbstractThe corneal epithelium is maintained by limbal stem cells (LSCs). Dysfunction of the LSCs, resulting from chemical and thermal burns, contact lens-related disease, congenial disorders, among other conditions, leads to limbal stem cell deficiency (LSCD), a sight-threatening condition. An effective treatment of LSCD, with 76% of patients reporting regained sight up to 24 months after the operation, consists of transplantingex-vivocultured LSCs from the patient’s other healthy eye (i.e. autologous) or donor (i.e. allogeneic) to the affected eye. The post-operative assessment of corneal recovery is crucial but relies on ponderous and generally subjective visual inspection of a large number of microscopic images of the corneal epithelial cells, relying on the personal experience of the practitioner to interpret imprecise, qualitative diagnostic criteria. From a unique library of 100,000 cornea cell images from 34 patients, we have randomly selected 10 individuals (3,668 images) to demonstrate that the frequency distribution of the epithelial cell areas is a sensitive diagnostic tool of the corneal epithelium status. After a successful operation the distribution of cell areas is rather flat, reflecting an anomalously wide range of cell areas. As the cornea recovers, the frequency distribution becomes narrower with high statistical confidence and eventually approaches that of the healthy cornea. The corneal epithelial cell shape is independent of the cornea status despite a widespread expectation that healthy cells have a hexagonal shape. We also show that the corneal epithelial cell area distribution and its variation with the depth within the cornea are specific to each patient.Significance StatementChemical and thermal cornea burns, contact-lens damage and hereditary factors, among other conditions, cause limbal stem cell deficiency (LSCD), a widespread sight-threatening condition. An efficient LSCD treatment involves a stem cell transplant from the patient’s other healthy eye, in unilateral cases, or a donor, in bilateral cases. Traditional post-operative cornea monitoring is laborious and often subjective as it relies on visual inspection of microscopy corneal epithelial images. We show that the distribution of epithelial cell areas is a sensitive LSCD diagnostic, evolving systematically to a healthy form after a successful treatment. We have developed computer algorithms to implement this quantitative, sensitive and precise approach which can radically improve the quality of both cornea monitoring in disease and response to treatment.