bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Obesity on the Drug–Drug Interaction Between Dolutegravir and Rifampicin or Any Other Strong Inducers
Authors: Berton Mattia , Bettonte Sara , Stader Felix , Battegay Manuel , Marzolini Catia 
Published: July 2023

AbstractBackgroundObesity is increasingly prevalent among people with HIV. Obesity can impact drug pharmacokinetics and consequently the magnitude of drug–drug interactions (DDIs) and, thus, the related recommendations for dose adjustment. Virtual clinical DDI studies were conducted using physiologically based pharmacokinetic (PBPK) modeling to compare the magnitude of the DDI between dolutegravir and rifampicin in nonobese, obese, and morbidly obese individuals.MethodsEach DDI scenario included a cohort of virtual individuals (50% female) between 20 and 50 years of age. Drug models for dolutegravir and rifampicin were verified against clinical observed data. The verified models were used to simulate the concurrent administration of rifampicin (600 mg) at steady state with dolutegravir (50 mg) administered twice daily in normal-weight (BMI 18.5–30 kg/m2), obese (BMI 30–40 kg/m2), and morbidly obese (BMI 40–50 kg/m2) individuals.ResultsRifampicin was predicted to decrease dolutegravir area under the curve (AUC) by 72% in obese and 77% in morbidly obese vs 68% in nonobese individuals; however, dolutegravir trough concentrations were reduced to a similar extent (83% and 85% vs 85%). Twice-daily dolutegravir with rifampicin resulted in trough concentrations always above the protein-adjusted 90% inhibitory concentration for all BMI groups and above the 300 ng/mL threshold in a similar proportion for all BMI groups.ConclusionsThe combined effect of obesity and induction by rifampicin was predicted to further decrease dolutegravir exposure but not the minimal concentration at the end of the dosing interval. Thus, dolutegravir 50 mg twice daily with rifampicin can be used in individuals with a high BMI up to 50 kg/m2.
Nt-acetylation-independent turnover of SQUALENE EPOXIDASE 1 by Arabidopsis DOA10-like E3 ligases
Authors: Etherington Ross D , Bailey Mark , Boyer Jean-Baptiste , Armbruster Laura , Cao Xulyu , Coates Juliet C , Meinnel Thierry , Wirtz Markus , Giglione Carmela , Gibbs Daniel J 
Published: July 2023

Abstract
The acetylation-dependent (Ac/)N-degron pathway degrades proteins through recognition of their acetylated N-termini (Nt) by E3 ligases called Ac/N-recognins. To date, specific Ac/N-recognins have not been defined in plants. Here we used molecular, genetic, and multiomics approaches to characterize potential roles for Arabidopsis (Arabidopsis thaliana) DEGRADATION OF ALPHA2 10 (DOA10)-like E3 ligases in the Nt-acetylation-(NTA)-dependent turnover of proteins at global- and protein-specific scales. Arabidopsis has two endoplasmic reticulum (ER)-localized DOA10-like proteins. AtDOA10A, but not the Brassicaceae-specific AtDOA10B, can compensate for loss of yeast (Saccharomyces cerevisiae) ScDOA10 function. Transcriptome and Nt-acetylome profiling of an Atdoa10a/b RNAi mutant revealed no obvious differences in the global NTA profile compared to wild type, suggesting that AtDOA10s do not regulate the bulk turnover of NTA substrates. Using protein steady-state and cycloheximide-chase degradation assays in yeast and Arabidopsis, we showed that turnover of ER-localized SQUALENE EPOXIDASE 1 (AtSQE1), a critical sterol biosynthesis enzyme, is mediated by AtDOA10s. Degradation of AtSQE1 in planta did not depend on NTA, but Nt-acetyltransferases indirectly impacted its turnover in yeast, indicating kingdom-specific differences in NTA and cellular proteostasis. Our work suggests that, in contrast to yeast and mammals, targeting of Nt-acetylated proteins is not a major function of DOA10-like E3 ligases in Arabidopsis and provides further insight into plant ERAD and the conservation of regulatory mechanisms controlling sterol biosynthesis in eukaryotes.
A cell wall–localized β-1,3-glucanase promotes fiber cell elongation and secondary cell wall deposition
Authors: Fang Shuai , Shang Xiaoguang , He Qingfei , Li Weixi , Song Xiaohui , Zhang Baohong , Guo Wangzhen 
Published: July 2023

Abstract
β-1,3-glucanase functions in plant physiological and developmental processes. However, how β-1,3-glucanase participates in cell wall development remains largely unknown. Here, we answered this question by examining the role of GhGLU18, a β-1,3-glucanase, in cotton (Gossypium hirsutum) fibers, in which the content of β-1,3-glucan changes dynamically from 10% of the cell wall mass at the onset of secondary wall deposition to &lt;1% at maturation. GhGLU18 was specifically expressed in cotton fiber with higher expression in late fiber elongation and secondary cell wall (SCW) synthesis stages. GhGLU18 largely localized to the cell wall and was able to hydrolyze β-1,3-glucan in vitro. Overexpression of GhGLU18 promoted polysaccharide accumulation, cell wall reconstruction, and cellulose synthesis, which led to increased fiber length and strength with thicker cell walls and shorter pitch of the fiber helix. However, GhGLU18-suppressed cotton resulted in opposite phenotypes. Additionally, GhGLU18 was directly activated by GhFSN1 (fiber SCW-related NAC1), a NAC transcription factor reported previously as the master regulator in SCW formation during fiber development. Our results demonstrate that cell wall–localized GhGLU18 promotes fiber elongation and SCW thickening by degrading callose and enhancing polysaccharide metabolism and cell wall synthesis.
Hydrolyzable tannins are incorporated into the endocarp during sclerification of the water caltrop Trapa natans
Authors: Huss Jessica C , Antreich Sebastian J , Felhofer Martin , Mayer Konrad , Eder Michaela , Vieira Dias dos Santos Ana Catarina , Ramer Georg , Lendl Bernhard , Gierlinger Notburga 
Published: July 2023

Abstract
The water caltrop (Trapa natans) develops unique woody fruits with unusually large seeds among aquatic plants. During fruit development, the inner fruit wall (endocarp) sclerifies and forms a protective layer for the seed. Endocarp sclerification also occurs in many land plants with large seeds; however, in T. natans, the processes of fruit formation, endocarp hardening, and seed storage take place entirely underwater. To identify potential chemical and structural adaptations for the aquatic environment, we investigated the cell-wall composition in the endocarp at a young developmental stage, as well as at fruit maturity. Our work shows that hydrolyzable tannins—specifically gallotannins—flood the endocarp tissue during secondary wall formation and are integrated into cell walls along with lignin during maturation. Within the secondary walls of mature tissue, we identified unusually strong spectroscopic features of ester linkages, suggesting that the gallotannins and their derivatives are cross-linked to other wall components via ester bonds, leading to unique cell-wall properties. The synthesis of large amounts of water-soluble, defensive aromatic metabolites during secondary wall formation might be a fast way to defend seeds within the insufficiently lignified endocarp of T. natans.
The optical method based on gas injection overestimates leaf vulnerability to xylem embolism in three woody species
Authors: Petruzzellis Francesco , Di Bonaventura Azzurra , Tordoni Enrico , Tomasella Martina , Natale Sara , Trifilò Patrizia , Tromba Giuliana , Di Lillo Francesca , D’Amico Lorenzo , Bacaro Giovanni , Nardini Andrea 
Published: July 2023

Abstract
Plant hydraulic traits related to leaf drought tolerance, like the water potential at turgor loss point (TLP) and the water potential inducing 50% loss of hydraulic conductance (P50), are extremely useful to predict the potential impacts of drought on plants. While novel techniques have allowed the inclusion of TLP in studies targeting a large group of species, fast and reliable protocols to measure leaf P50 are still lacking. Recently, the optical method coupled with the gas injection (GI) technique has been proposed as a possibility to speed up the P50 estimation. Here, we present a comparison of leaf optical vulnerability curves (OVcs) measured in three woody species, namely Acer campestre (Ac), Ostrya carpinifolia (Oc) and Populus nigra (Pn), based on bench dehydration (BD) or GI of detached branches. For Pn, we also compared optical data with direct micro-computed tomography (micro-CT) imaging in both intact saplings and cut shoots subjected to BD. Based on the BD procedure, Ac, Oc and Pn had P50 values of −2.87, −2.47 and −2.11 MPa, respectively, while the GI procedure overestimated the leaf vulnerability (−2.68, −2.04 and −1.54 MPa for Ac, Oc and Pn, respectively). The overestimation was higher for Oc and Pn than for Ac, likely reflecting the species-specific vessel lengths. According to micro-CT observations performed on Pn, the leaf midrib showed none or very few embolized conduits at −1.2 MPa, consistent with the OVcs obtained with the BD procedure but at odds with that derived on the basis of GI. Overall, our data suggest that coupling the optical method with GI might not be a reliable technique to quantify leaf hydraulic vulnerability since it could be affected by the ‘open-vessel’ artifact. Accurate detection of xylem embolism in the leaf vein network should be based on BD, preferably of intact up-rooted plants.
Implementation and Evaluation of an End-of-Life Standardized Participant Simulation in an Adult/Gerontology Acute Care Nurse Practitioner Program
Authors: Daly Shannon , Roberts Sterling , Winn Sheryl , Greene Lawanda 
Published: July 2023

Abstract
Graduate nursing programs must provide end-of-life (EOL) content to prepare nurse practitioners to manage the holistic needs of patients. This project aimed to measure the End-of-Life Nursing Education Consortium curriculum’s impact on student self-confidence and anxiety levels. A pretest/posttest study design was implemented using an EOL simulation and the Nursing Anxiety and Self-Confidence With Clinical Decision-Making Scale (NASC-CDM©) to compare baseline self-confidence and anxiety levels related to clinical decision-making. Results showed that the simulation increased student self-confidence, but anxiety level remained unchanged. Nurse educators should consider incorporating EOL simulation into graduate curricula to improve student confidence with clinical decision-making.
Clinician's guide to targeted estrogen receptor degradation using PROTAC in patients with estrogen receptor-positive metastatic breast cancer
Authors: Grinshpun Albert 
Published: July 2023

Purpose of review
Metastatic breast cancer (MBC) remains a major clinical challenge, necessitating the development of innovative therapeutic strategies. Estrogen receptor (ER) degradation using proteolysis-targeting chimeras (PROTAC) has emerged as a promising approach for overcoming acquired resistance to endocrine therapy. This review will summarize recent findings, highlighting the role of ER degradation by PROTAC in patients with MBC.

Recent findings
The application of PROTAC technology for ER degradation has demonstrated initial success in preclinical and early clinical studies. PROTACs, consisting of an ER-targeting moiety, an E3 ubiquitin ligase-recruiting moiety, and a linker, facilitate ER ubiquitination and subsequent proteasomal degradation. Yet, significant challenges persist in the clinical translation of ER degradation by PROTAC. These include the optimization of PROTAC design, elucidation of mechanisms underlying resistance to PROTAC-induced ER degradation, and identification of predictive biomarkers for patient stratification. Additionally, addressing potential off-target effects and toxicity profiles remains a critical aspect of developing PROTAC-based therapies.

Summary
Recent data demonstrate the potential of ER degradation by PROTAC as a therapeutic strategy for patients with MBC. Continued research efforts and development of synergistic combinations are crucial for further advancing PROTAC-based therapies and improving outcomes in patients with MBC.
Should Penicillin Allergy Testing Be Included as Part of Preoperative Testing?
Authors: Lozo Svjetlana , Wagner Daniel , Shah Nirav , Goldberg Roger , Gafni-Kane Adam , Solomonides Anthony 
Published: July 2023

ABSTRACT

Introduction:
Penicillin allergy is the most commonly reported drug allergy in the United States. Patients labeled with penicillin allergy are at risk of receiving broad-spectrum antibiotics for surgical site infection prophylaxis, which can lead to increased antibiotic resistance, higher morbidity, suboptimal antibiotic therapy, and higher medical costs. This study aimed to determine the true prevalence of penicillin allergy among surgical patients and to decrease the unnecessary use of broad-spectrum antibiotics.

Methods:
A retrospective chart review was performed of patients who underwent urogynecologic surgery in 2017. In 2018, a quality initiative was started, and all patients reporting penicillin allergies were offered antibiotic allergy testing as part of their preoperative testing.

Results:
In 2017, 15% of patients reported penicillin allergy and 52% of them received surgical prophylaxis with broad-spectrum antibiotics. In 2018, 463 patients underwent surgery, 55 of whom reported penicillin allergy and were offered penicillin allergy testing. 35 (64%) agreed to proceed with testing, and of those tested, 33 (94%) tested negative for penicillin allergy.

Conclusions:
94% of patients with stated penicillin allergy who consented to allergy testing proved to have negative test. Penicillin allergy testing should be considered as part of preoperative management.
The Effect of Video Information Before Insertion of an Implantable Port Catheter on Cancer Patients’ Fear of Pain and Pain Levels
Authors: Işıklı Ayse G. , Soydaş Duygu , Önüt Fatma , Şen Hakan 
Published: July 2023

Background
Implantable port catheters and their needles may cause cancer patients to experience fear of pain.

Objective
The aim of this article was to study the effect of video information provided before implantable port catheter insertion on the fear of pain and on postoperative pain level.

Methods
The study is a randomized controlled trial conducted between July and December 2022 at a university hospital with a total of 84 cancer patients: intervention group (42) and control group (42). Descriptive analyses, χ2 analysis, the Mann-Whitney U test, and Student’s t test were used to assess the data.

Results
In the preoperative period, the mean score of the fear of severe pain subdimension of the patients in the control group was found to be higher than that of the patients in the intervention group (P < .05). When the postoperative pain levels of the patients were evaluated, no difference between the visual analog scale scores of the experimental and control groups was found (P > .05).

Conclusion
Video information provided before the insertion of an implantable port catheter was found to reduce the fear of severe pain in cancer patients, but postoperative pain levels were not affected.

Implications for Practice
The use of audiovisual materials such as videos for multimedia-based information is effective in making remembering the information easy. Video-based information may be more useful in managing fear of pain in patients than traditional verbal information. The findings of this study can serve as a guide for clinical work and for developing targeted measures to reduce fear of pain.
Changes in Facial Symmetry Following Computer-Assisted Secondary Correction of Craniofacial Fractures
Authors: Jiang Taoran , Zhou Sizheng , Yu Zheyuan , Cao Dejun 
Published: July 2023

Objective:
For patients without dysfunctions, the main purpose of secondary correction for craniofacial fractures is restoring facial symmetry. Computer-assisted surgery techniques including virtual surgical planning and intraoperative navigation provide the help to restore the bony symmetry as much as possible. The authors retrospectively quantitatively analyzed patients who received computer-assisted secondary correction for craniofacial fractures on facial symmetry pre and postoperation.

Methods:
This observational study reviewed the medical records of 17 patients requiring secondary correction for craniofacial fractures. Pre and postoperative computed tomography data were used to quantitatively analyze the changes in facial symmetry and enophthalmos.

Result:
All patients enrolled in this study showed mid-facial asymmetry but without dysfunctions except for enophthalmos, and 5 patients had bone defects in the frontal-temporal area. The corrective surgical techniques were different for each patient according to their specific condition. Virtual surgical planning with or without intraoperative navigation was performed for all patients. Compared with the preoperative condition, their facial symmetry was significantly improved. The maximum discrepancy value between the affected side and the mirrored unaffected side decreased from 8.10 ± 2.69 to 3.74 ± 2.02 mm postoperatively, and the mean discrepancy value decreased from 3.58 ± 1.29 to 1.57 ± 0.68 mm. In addition, the Enophthalmos Index decreased from 2.65 to 0.35 mm.

Conclusion:
This observational study objectively demonstrated that computer-assisted secondary correction for craniofacial fractures can significantly improve facial symmetry. And the authors recommend that virtual surgical planning and intraoperative navigation should be a must step in craniofacial fracture correction.
Surgeon Perspectives on Daily Presentation of Ethical Dilemmas: A Qualitative Study
Authors: Char Steven , Prager Kenneth , Dugdale Lydia , Fischkoff Katherine 
Published: July 2023

BACKGROUND:
Surgeons encounter and navigate a unique set of ethical dilemmas. The American College of Surgeons (ACS) previously identified 6 core ethical issues central to the practice of surgery, but there have been no reports of the true range and complexity of ethical dilemmas encountered by surgeons in their daily practice. Qualitative research is well positioned to address this question.

STUDY DESIGN:
We conducted in-depth interviews with attending surgeons across multiple surgical subspecialties at a large, urban, academic medical center asking them to describe the most common ethical dilemmas they encounter in day-to-day practice. Interviews were recorded, transcribed, and coded according to a grounded theory, inductive approach.

RESULTS:
Thirty attending surgeons were interviewed, representing twelve different general surgery subspecialties. The majority of dilemmas identified pertained to 4 of the 6 ACS identified core ethical issues: professional obligations, competition of interests, truth telling, and end-of-life care. No participants described dilemmas relating to the themes of confidentiality or surrogate decision-making. Approximately one-third of participants identified ethical issues not well characterized by the ACS core principles, most often relating to the pressure to provide care that is not medically indicated. There was strong support for a formalized surgical ethics curriculum.

CONCLUSIONS:
Although the ACS-defined core ethical issues in surgery appropriately captured many ethical dilemmas identified by participants, surgeons described several scenarios not well characterized by these themes. A dedicated surgical ethics curriculum may help to better equip surgeons to navigate the ethical dilemmas they are likely to face in practice.
HOMOCYSTEINE POTENTIATES AMYLOID β-INDUCED CEREBRAL ENDOTHELIAL CELL APOPTOSIS, BLOOD BRAIN BARRIER DYSFUNCTION AND ANGIOGENIC IMPAIRMENT
Authors: Carey Ashley , Parodi-Rullan Rebecca , Vazquez-Torres Rafael , Canepa Elisa , Fossati Silvia 
Published: July 2023

AbstractCerebrovascular dysfunction has been implicated as a major contributor to Alzheimer’s Disease (AD) pathology, with cerebral endothelial cell (cEC) stress promoting ischemia, cerebral-blood flow impairments and blood-brain barrier (BBB) permeability. Recent evidence suggests that cardiovascular (CV)/cerebrovascular risk factors, including hyperhomocysteinemia (Hhcy), exacerbate AD pathology and risk. Yet, the underlying molecular mechanisms for this interaction remain unclear. Our lab has demonstrated that amyloid beta 40 (Aβ40) species, and particularly Aβ40-E22Q (vasculotropic Dutch mutant), promote death receptor 4 and 5 (DR4/DR5)-mediated apoptosis in human cECs, barrier permeability and angiogenic impairment. Previous studies show that Hhcy also induces EC dysfunction, but it remains unknown whether Aβ and homocysteine function through common molecular mechanisms. We tested the hypotheses that Hhcy exacerbates Aβ-induced cEC DR4/5-mediated apoptosis, barrier dysfunction, and angiogenesis defects. This study was the first to demonstrate that Hhcy specifically potentiates Aβ40-E22Q-mediated activation of the DR4/5-mediated extrinsic apoptotic pathway in cECs, including DR4/5 expression, caspase 8/9/3 activation, cytochrome-c release and DNA fragmentation. Additionally, we revealed that Hhcy intensifies the deregulation of the same cEC junction proteins mediated by Aβ, precipitating BBB permeability. Furthermore, Hhcy and Aβ40-E22Q, impairing VEGF-A/VEGFR2 signaling and VEGFR2 endosomal trafficking, additively decrease cEC angiogenic capabilities. Overall, these results show that the presence of the CV risk factor Hhcy exacerbates Aβ-induced cEC apoptosis, barrier dysfunction, and angiogenic impairment. This study reveals specific mechanisms through which amyloidosis and Hhcy jointly operate to produce brain EC dysfunction and death, highlighting new potential molecular targets against vascular pathology in comorbid AD/CAA and Hhcy conditions.
Cathelicidin downregulates neurotensin and substance P hippocampal levels
Authors: Flores Ismael Perez , Ariga Suely Kubo , Barbeiro Hermes Vieira , Barbeiro Denise Frediani , Pinheiro da Silva Fabiano 
Published: July 2023

AbstractBackgroundSepsis is a life-threatening condition and septic encephalopathy is an early and frequent manifestation of this disease. Antimicrobial peptides are important components of innate immunity playing a crucial role during bacterial infections. Here, we investigate the protein levels of several neuropeptides in CRAMP-deficient and wild-type mice, in healthy conditions and following experimental sepsis.MethodsMice were submitted to cecal ligation and puncture and the protein levels of neurotensin, substance P, oxytocin and β-endorphin were evaluated in the brain.ResultsWe found that CRAMP-deficient mice produce significantly less neurotensin and substance P than wild-type mice in the hippocampus, both before and 24 hours following experimental sepsis, but not 15 days post-septic shock.ConclusionsThe hippocampus is a complex structure, highly vulnerable during sepsis. The role of antimicrobial peptides and their interplay with neuropeptides should be further evaluated in this scenario.