bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time trends in preemptive kidney transplantation in Europe: an ERA registry study
Authors: Kramer Anneke , Boenink Rianne , Mercado Vergara Cynthia G , Bell Samira , Kerschbaum Julia , Rodríguez Arévalo Olga L , Mazuecos Auxiliadora , de Vries Aiko P J , Reisæter Anna V , Wong Esther H S , Lundgren Torbjörn , Valentin María O , Ordoñez Alvarez Flor A , Melilli Edoardo , Finne Patrik , Segelmark Mårten , Couchoud Cécile , Sørensen Søren S , Ferraro Pietro Manuel , Arnol Miha , Arici Mustafa , Ortiz Alberto , Jager Kitty J , Abramowicz Daniel , Stel Vianda S , Hellemans Rachel 
Published: May 2024

ABSTRACT

Background
Preemptive kidney transplantation (PEKT) has better outcomes when compared with transplantation after dialysis. We aimed to examine trends in PEKT between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives.

Methods
Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around PEKT.

Results
Between 2000 and 2019, 20 251 adults underwent PEKT [11 169 from living donors (LDs), 8937 from deceased donors (DDs)]. The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for LD kidney recipients (from 21% to 43%) and DD kidney recipients (from 4% to 11%). Large international differences were found. The increase in PEKT was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donor
or recipient work-up. Suggested initiatives included raising awareness on the possibility of PEKT, earlier start and shorter work-up time for recipient and LD.

Conclusions
Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and DD kidney recipients.
Effective re-induction regimen for children with recurrent medulloblastoma
Authors: O’Halloran Katrina , Phadnis Sheetal , Friedman Gregory K , Metrock Katie , Davidson Tom B , Robison Nathan J , Tamrazi Benita , Cotter Jennifer A , Dhall Girish , Margol Ashley S 
Published: May 2024

Abstract

Background
There is no standard treatment for the recurrence of medulloblastoma, the most common malignant childhood brain tumor, and prognosis remains dismal. In this study, we introduce a regimen that is well-tolerated and effective at inducing remission.

Methods
The primary objectives of this study were to assess tolerability of the regimen and overall response rate (ORR). A retrospective chart review of patients with recurrent medulloblastoma, treated at two institutions with a re-induction regimen of intravenous irinotecan and cyclophosphamide with oral temozolomide and etoposide, was performed. Demographic, clinicopathologic, toxicity, and response data were collected and analyzed.

Results
Nine patients were identified. Median age was 5.75 years. Therapy was well-tolerated with no therapy-limiting toxicities and no toxic deaths. Successful stem cell collection was achieved in all 5 patients in whom it was attempted. ORR after 2 cycles was 78%. Three patients had a complete response, 4 patients had a partial response, 1 patient had stable disease, and 1 patient had progressive disease. Four patients are alive with no evidence of disease (NED), 2 patients are alive with disease, 2 patients have died of disease, and 1 patient died of toxicity related to additional therapy (NED at time of death).

Conclusions
This regimen is well-tolerated and effective. Tumor response was noted in the majority of cases, allowing patients to proceed to additional treatment with no or minimal disease. Further study of this regimen in a clinical trial setting is an important next step.
Pulsed reduced-dose rate re-irradiation for patients with recurrent grade 2 gliomas
Authors: Harari Colin M , Burr Adam R , Morris Brett A , Tomé Wolfgang A , Bayliss Adam , Bhatia Ankush , Grogan Patrick T , Robins H Ian , Howard Steven P 
Published: May 2024

Abstract

Background
Patients with grade 2 glioma exhibit highly variable survival. Re-irradiation for recurrent disease has limited mature clinical data. We report treatment results of pulsed reduced-dose rate (PRDR) radiation for patients with recurrent grade 2 glioma.

Methods
A retrospective analysis of 58 patients treated with PRDR from 2000 to 2021 was performed. Radiation was delivered in 0.2 Gy pulses every 3 minutes encompassing tumor plus margin. Survival outcomes and prognostic factors on outcome were Kaplan–Meier and Cox regression analyses.

Results
The median survival from the date of initial surgery was 8.6 years (95% CI: 5.5–11.8 years). 69% of patients showed malignant transformation to grade 3 (38%) or grade 4 (31%) glioma. Overall survival following PRDR was 12.6 months (95% CI: 8.3–17.0 months) and progression-free survival was 6.2 months (95% CI: 3.8–8.6 months). Overall response rate based on post-PRDR MRI was 36%. In patients who maintained grade 2 histology at recurrence, overall survival from PRDR was 22.0 months with 5 patients remaining disease-free, the longest at 8.2 and 11.4 years. PRDR was generally well tolerated.

Conclusions
To the best of our knowledge, this is the largest reported series of patients with recurrent grade 2 gliomas treated with PRDR radiation for disease recurrence. We demonstrate promising survival and acceptable toxicity profiles following re-irradiation. In the cohort of patients who maintain grade 2 disease, prolonged survival (&gt;5 years) is observed in selected patients. For the entire cohort, 1p19q codeletion, KPS, and longer time from initial diagnosis to PRDR were associated with improved survival.
Crosstalk between Brassinosteroids and Other Phytohormones during Plant Development and Stress Adaptation
Authors: Guo Feimei , Lv Minghui , Zhang Jingjie , Li Jia 
Published: May 2024

Abstract
Brassinosteroids (BRs) are a group of polyhydroxylated phytosterols that play essential roles in regulating plant growth and development as well as stress adaptation. It is worth noting that BRs do not function alone, but rather they crosstalk with other endogenous signaling molecules, including the phytohormones auxin, cytokinins, gibberellins, abscisic acid, ethylene, jasmonates, salicylic acid and strigolactones, forming elaborate signaling networks to modulate plant growth and development. BRs interact with other phytohormones mainly by regulating each others’ homeostasis, transport or signaling pathway at the transcriptional and posttranslational levels. In this review, we focus our attention on current research progress in BR signal transduction and the crosstalk between BRs and other phytohormones.
Persulfidation and phosphorylation of transcription factor SlWRKY6 differentially regulate tomato fruit ripening
Authors: Zhang Min , Hu Kangdi , Ma Lin , Geng Meihui , Zhang Conghe , Yao Gaifang , Zhang Hua 
Published: May 2024

Abstract
Cysteine desulfhydrase catalyses the generation of the signaling molecule hydrogen sulfide (H2S) in plants. In this study, we found that H2S can inhibit tomato (Solanum lycopersicum) fruit ripening and SlWRKY6 undergoes differential protein persulfidation in SlLCD1-overexpressing leaves. Then, further study indicated that SlWRKY6 could be persulfidated by H2S at Cys396. By construction of slwrky6 mutants and SlWRKY6-OE lines, we found that SlWRKY6 positively regulates leaf senescence and fruit ripening by activating the transcription of ripening-related genes STAYGREEN 1 (SlSGR1) and Senescence-Associated Gene 12 (SlSAG12). In addition, SlWRKY6 interacted with kinase SlMAPK4 and was phosphorylated at Ser33. Dual-luciferase transient expression assays and electrophoretic mobility shift assays indicated that SlWRKY6 persulfidation attenuated its transcriptional regulation of target genes SlSGR1 and SlSAG12, whereas SlWRKY6 phosphorylation by SlMAPK4 activated the transcription of target genes to promote fruit ripening. Moreover, we provided evidence that SlWRKY6 persulfidation attenuated its SlMAPK4-mediated phosphorylation to inhibit tomato fruit ripening. By transient expression of SlWRKY6, SlWRKY6C396A, SlWRKY6S33A, and SlWRKY6S33D in slwrky6 fruits, we found that SlWRKY6 persulfidation attenuated the expression of SlSGR1 and SlSAG12 thereby delaying tomato fruit ripening, while SlWRKY6 phosphorylation increased the expression of target genes. As tomato fruits ripened, endogenous H2S production decreased, while SlMAPK4 expression increased. Therefore, our findings reveal a model in which SlWRKY6 persulfidation due to higher endogenous H2S levels in un-ripened fruit inhibits its ability to activate SlSGR1 and SlSAG12 expression, while SlWRKY6 phosphorylation by SlMAPK4 activates its transcriptional activity, thereby promoting tomato fruit ripening.
Oral delivery of nanomedicine for genetic kidney disease
Authors: Huang Yi , Wang Jonathan , Mancino Valeria , Pham Jessica , O’Grady Colette , Li Hui , Jiang Kairui , Chin Deborah , Poon Christopher , Ho Pei-Yin , Gyarmati Georgina , Peti-Peterdi János , Hallows Kenneth R , Chung Eun Ji 
Published: May 2024

Abstract
Chronic and genetic kidney diseases such as autosomal dominant polycystic kidney disease (ADPKD) have few therapeutic options, and clinical trials testing small molecule drugs have been unfavorable due to low kidney bioavailability and adverse side effects. Although nanoparticles can be designed to deliver drugs directly to the diseased site, there are no kidney-targeted nanomedicines clinically available, and most FDA-approved nanoparticles are administered intravenously which is not ideal for chronic diseases. To meet these challenges of chronic diseases, we developed a biomaterials-based strategy using chitosan particles (CP) for oral delivery of therapeutic, kidney-targeting peptide amphiphile micelles (KMs). We hypothesized that encapsuling KMs into CP would enhance the bioavailability of KMs upon oral administration given the high stability of chitosan in acidic conditions and mucoadhesive properties enabling absorption within the intestines. To test this, we evaluated the mechanism of KM access to the kidneys via intravital imaging and investigated the KM biodistribution in a porcine model. Next, we loaded KMs carrying the ADPKD drug metformin into CP (KM-CP-met) and measured in vitro therapeutic effect. Upon oral administration in vivo, KM-CP-met showed significantly greater bioavailability and accumulation in the kidneys as compared to KM only or free drug. As such, KM-CP-met treatment in ADPKD mice (Pkd1fl/fl;Pax8-rtTA;Tet-O-Cre which develops the disease over 120 days and mimics the slow development of ADPKD) showed enhanced therapeutic efficacy without affecting safety despite repeated treatment. Herein, we demonstrate the potential of KM-CP as a nanomedicine strategy for oral delivery for the long-term treatment of chronic kidney diseases.
Is the Coleman–de Luccia Action Minimum?: An AdS/CFT Approach
Authors: Oshita Naritaka , Shoji Yutaro , Yamaguchi Masahide 
Published: May 2024

Abstract
We use the anti-de Sitter/conformal field theory (AdS/CFT) correspondence to find the least bounce action in an AdS false vacuum state, i.e. the most probable decay process of the metastable AdS vacuum within the Euclidean formalism by Callan and Coleman. It was shown that the O(4) symmetric bounce solution leads to the action minimum in the absence of gravity, but it is nontrivial in the presence of gravity. The AdS/CFT duality is used to evade the difficulties particular to a metastable gravitational system. To this end, we show that the Fubini bounce solution in CFT, corresponding to the Coleman–de Luccia (CdL) bounce in AdS, gives the least action among all finite bounce solutions in a conformal scalar field theory. Thus, we prove that the CdL action is the least action among all possible large and thin-wall configurations under certain conditions.
Arthritis in patients with very early systemic sclerosis: a comprehensive clinical and prognostic analysis
Authors: Muraru Sinziana , Mihai Carina , Elhai Muriel , Becker Mike , Jordan Suzana , Garaiman Alexandru , Bruni Cosimo , Petelytska Liubov , Hoffmann-Vold Anna-Maria , Distler Oliver , Dobrota Rucsandra 
Published: May 2024

Abstract

Objective
Arthritis is associated with a worse prognosis in established SSc. However, knowledge about its relevance in very early SSc (veSSc) is scarce. We aimed to assess the prevalence and phenotype of arthritis, as well as its prognostic impact, in patients with veSSc.

Methods
We analysed patients with veSSc, defined as presence of Raynaud’s phenomenon (RP) and/or at least one of: puffy fingers, antinuclear antibodies (ANA), abnormal capillaroscopy, not fulfilling the ACR/EULAR classification criteria for SSc at baseline. We investigated associations between arthritis and clinical parameters, followed by a longitudinal analysis to investigate arthritis as a potential predictor of progression towards established SSc.

Results
We included 159 patients, of whom 108 had at least one follow-up visit. SSc-related arthritis occurred in 22/159 (13.8%) patients at baseline. Arthritis was mostly seronegative, symmetrical, oligo- or polyarticular, non-erosive, and rarely associated with elevation of inflammatory markers. More than half of the patients needed treatment with DMARDs. Anti-centromere antibodies (ACA) were negatively associated with arthritis (odds ratio 0.707, 95% CI 0.513–0.973, P = 0.033). Overall, 43/108 (39.8%) patients with follow-up progressed to established SSc during the observation time. Arthritis was not a significant predictor for progression to established SSc in a multivariable Cox regression.

Conclusion
In this first comprehensive analysis, we found a similar prevalence of arthritis in veSSc as seen in established SSc. Moreover, the use of DMARDs indirectly suggests a relevant disease burden.
Effects of PFAS on human liver transporters: implications for health outcomes
Authors: Vujic Ena , Ferguson Stephen S , Brouwer Kim L R 
Published: May 2024

Abstract
Per- and polyfluoroalkyl substances (PFAS) have become internationally recognized over the past three decades as persistent organic pollutants used in the production of various consumer and industrial goods. Research efforts continue to gauge the risk that historically used, and newly produced, PFAS may cause to human health. Numerous studies report toxic effects of PFAS on the human liver as well as increased serum cholesterol levels in adults. A major concern with PFAS, also dubbed “forever chemicals,” is that they accumulate in the liver and kidney and persist in serum. The mechanisms responsible for their disposition and excretion in humans are poorly understood. A better understanding of the interaction of PFAS with liver transporters, as it pertains to the disposition of PFAS and other xenobiotics, could provide mechanistic insight into human health effects and guide efforts toward risk assessment of compounds in development. This review summarizes the current state of the literature on the emerging relationships (eg, substrates, inhibitors, modulators of gene expression) between PFAS and specific hepatic transporters. The adaptive and toxicological responses of hepatocytes to PFAS that reveal linkages to pathologies and epidemiological findings are highlighted. The evidence suggests that our understanding of the molecular landscape of PFAS must improve to determine their impact on the expression and function of hepatocyte transporters that play a key role in PFAS or other xenobiotic disposition. From here, we can assess what role these changes may have in documented human health outcomes.
Rifaximin plus lactulose versus lactulose alone for reducing the risk of HE recurrence
Authors: Sanyal Arun J. , Kowdley Kris V. , Reau Nancy S. , Pyrsopoulos Nikolaos T. , Allen Christopher , Heimanson Zeev , Bajaj Jasmohan S. 
Published: May 2024

Background:
The aim was to examine rifaximin plus lactulose efficacy in patients with cirrhosis at a risk of developing overt HE who were stratified by important baseline characteristics such as comorbid ascites or diabetes.

Methods:
Pooled post hoc subgroup analysis of adults receiving rifaximin 550 mg twice daily plus lactulose or lactulose alone for 6 months in a phase 3 randomized, double-blind trial and a phase 4 open-label trial was conducted.

Results and Conclusion:
Rifaximin plus lactulose was more efficacious than lactulose alone for reducing the risk of overt HE recurrence and HE-related hospitalization in adults grouped by select baseline disease characteristics.
The relationship between traumatic exposure and pain perception in children: the moderating role of posttraumatic symptoms
Authors: Levy Gigi Einat , Rachmani Moriya , Defrin Ruth 
Published: May 2024

Abstract
Adverse childhood experiences (ACEs) affect approximately half of all children worldwide. These experiences have been linked to increased pain sensitivity in adulthood and a higher likelihood of developing severe chronic pain. However, most studies have assessed the effects of ACEs retrospectively, long after they occurred, leaving room for other factors to influence the observed outcomes. We investigated, for the first time, the association between ACEs and concurrent pain perception among young children who live in a conflict zone and are consistently exposed to potentially traumatic experiences. Participants were 60 elementary school children (ages 8-11 years) living in conflict regions (n = 39) or nonconflict regions (n = 21). Posttraumatic stress symptom (PTSS) severity, traumatic exposure, pressure pain threshold (PPT), and mechanical detection threshold (MDT) were measured. Trauma-exposed children had significantly lower PPT than did controls, but MDT was similar across groups. Pressure pain threshold correlated positively with proximity to the conflict zone and inversely with traumatic exposure magnitude and PTSS severity. In addition, PTSSs moderated the relationship between repeated traumatic exposure and PPT. Children with higher PTSS severity displayed pain hypersensitivity regardless of their traumatic exposure level, whereas in children with lower PTSS severity, greater traumatic exposure correlated with pain hypersensitivity. The results suggest that ACEs among children lead to concurrent pain hypersensitivity and distress and may put them at elevated risk of chronic pain early in life. In addition, our findings emphasize the need for identifying children with various PTSS levels to provide tailored interventions and mitigate the long-term negative effects of ACEs.
What Should Healthcare Systems Consider When Modernizing Call Centers? Early Considerations From the Veterans Health Administration
Authors: Gray Caroline , Lerner Barbara , Egelfeld Jacqueline , Robinson Jada , Urech Tracy , Vashi Anita 
Published: May 2024

SUMMARY

Goal:
Growing numbers of hospitals and payers are using call centers to answer patients’ clinical and administrative questions, schedule appointments, address billing issues, and offer supplementary care during public health emergencies and national disasters. In 2020, the Veterans Health Administration (VA) implemented VA Health Connect, an enterprise-wide initiative to modernize call centers. VA Health Connect is designed to improve the care experience with the convenience, flexibility, and simplicity of a single toll-free number connected to a range of 24/7 virtual services. The services are organized into four areas: administrative guidance for scheduling and general inquiries; pharmacy support for medication matters; clinical triage for evaluation of symptoms and recommended care; and virtual visits with providers for urgent and episodic care. Through a qualitative evaluation of VA Health Connect, we sought to identify the factors that affected the development of this program and to compile considerations to support the implementation of other enterprise-wide initiatives.

Methods:
The evaluation team interviewed 29 clinical and administrative leads from across the VA. These leads were responsible for the modernization of their local service networks. PhD-level qualitative methodologists conducted the interviews, asking participants to reflect on barriers and facilitators to modernization and implementation. The team employed a rapid qualitative analytic approach commonly used in healthcare research to distill robust results.

Principal Findings:
A review of the early implementation of VA Health Connect found: (1) deadlines proved challenging but provided momentum for the initiative; (2) a balance between standardized processes and local adaptations facilitated implementation; (3) attention to staffing, hiring, and training of call center staff before implementation expedited workflows; (4) establishing national and local leadership commitment to the innovation from the onset increased team cohesion and efficacy; and (5) anticipating information technology infrastructure needs prevented delays to modernization and implementation.

Practical Applications:
Our findings suggest that healthcare systems would benefit from anticipating likely obstacles (e.g., delays in software implementations and negotiations with unions), thus providing ample time to secure leadership buy-in and identify local champions, communicating early and often, and supporting flexible implementation to meet local needs. VA leadership can use this evaluation to refine implementation, and it could also have important implications for regulators, federal health exchanges, insurers, and other healthcare systems when determining resource levels for call centers.
Perspective on the Journal of Physician Assistant Education: From Association Newsletter to Academic Peer-Reviewed Journal Celebrating 25 Years
Authors: Pedersen Donald M. , Jones P. Eugene , Asprey David , Honda Trenton 
Published: May 2024

Abstract
For 25 years, the Journal of PA Education (JPAE) and its predecessor publications have been the pre-eminent venues for disseminating and promulgating information and research on the physician assistant (PA) profession. In this article, former and current editors in chief have compiled a detailed history of the journal, its development, and its trajectory into the future, outlining the journey taken by Association of PA Programs/PA Education Association to catalog faculty scholarship through a peer-reviewed journal. Allowing for the referencing of articles and thus adding to the body of knowledge on PAs and PA education, JPAE has not only endured but thrived. This article speaks to the collective effort and excellence of staff, and the many volunteer reviewers, feature editors, and editorial board members who have nurtured JPAE along the way through numerous changes, challenges, and triumphs.