bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genomic Screen for Yeast Vacuolar Membrane ATPase Mutants
Authors: Sambade Maria , Alba Mercedes , Smardon Anne M , West Robert W , Kane Patricia M 
Published: June 2005

Abstract
V-ATPases acidify multiple organelles, and yeast mutants lacking V-ATPase activity exhibit a distinctive set of growth defects. To better understand the requirements for organelle acidification and the basis of these growth phenotypes, ∼4700 yeast deletion mutants were screened for growth defects at pH 7.5 in 60 mm CaCl2. In addition to 13 of 16 mutants lacking known V-ATPase subunits or assembly factors, 50 additional mutants were identified. Sixteen of these also grew poorly in nonfermentable carbon sources, like the known V-ATPase mutants, and were analyzed further. The cwh36Δ mutant exhibited the strongest phenotype; this mutation proved to disrupt a previously uncharacterized V-ATPase subunit. A small subset of the mutations implicated in vacuolar protein sorting, vps34Δ, vps15Δ, vps45Δ, and vps16Δ, caused both Vma− growth phenotypes and lower V-ATPase activity in isolated vacuoles, as did the shp1Δ mutation, implicated in both protein sorting and regulation of the Glc7p protein phosphatase. These proteins may regulate V-ATPase targeting and/or activity. Eight mutants showed a Vma− growth phenotype but no apparent defect in vacuolar acidification. Like V-ATPase-deficient mutants, most of these mutants rely on calcineurin for growth, particularly at high pH. A requirement for constitutive calcineurin activation may be the predominant physiological basis of the Vma− growth phenotype.
The mei-P26 Gene Encodes a RING Finger B-box Coiled-Coil-NHL Protein That Regulates Seizure Susceptibility in Drosophilia
Authors: Glasscock Edward , Singhania Ayush , Tanouye Mark A 
Published: June 2005

Abstract
Seizure-suppressor mutations provide unique insight into the genes and mechanisms involved in regulating nervous system excitability. Drosophila bang-sensitive (BS) mutants present a useful tool for identifying seizure suppressors since they are a well-characterized epilepsy model. Here we describe the isolation and characterization of a new Drosophila seizure-suppressor mutant that results from disruption of the meiotic gene mei-P26, which belongs to the RBCC-NHL family of proteins. The mei-P26 mutation reduces seizures in easily shocked (eas) and slamdance (sda) epileptic flies following mechanical stimulation and electroconvulsive shock. In addition, mutant mei-P26 flies exhibit seizure thresholds at least threefold greater than those of wild type. The mei-P26 phenotypes appear to result from missense mutation of a critical residue in the NHL protein-protein interaction domain of the protein. These results reveal a surprising role for mei-P26 outside of the germline as a regulator of seizure susceptibility, possibly by affecting synaptic development as a ubiquitin ligase.
Intercalation of Organic Dye Molecules into Double‐stranded DNA. Part 2: The Annelated Quinolizinium Ion as a Structural Motif in DNA Intercalators†
Authors: Ihmels Heiko , Faulhaber Katja , Vedaldi Daniela , Dall'Acqua Francesco , Viola Giampietro 
Published: June 2005

ABSTRACTDNA intercalators represent an important class of compounds with a high potential as DNA‐targeting drugs. In this review it is demonstrated that annelated quinolizinium derivatives such as coralyne and derivatives thereof intercalate into DNA and that this structural motif allows several variations of the substitution pattern without loss of intercalating properties. The commonly applied methods for the evaluation of the DNA association, mainly spectroscopic studies, are pointed out. In addition, studies on the biological activities of annelated quinolizinium derivatives, such as topoisomerase poisoning or cell toxicity, are highlighted.
Photobleaching of Bacteriorhodopsin Solubilized with Triton X‐100
Authors: Sasaki Takanori , Sonoyama Masashi , Demura Makoto , Mitaku Shigeki 
Published: June 2005

ABSTRACTIn the current studies, we examined the effects of hexagonal lattice formation with lipid membranes on the structural stability of native bacteriorhodopsin (bR). Denaturation kinetic measurements for bR solubilized with the mild nonionic detergent Triton X‐100 (TX100) were performed in the dark and under illumination by visible light. The solubilized bR was stable in the dark over a wide concentration range of TX100 (1 to 200 mM). In purple membranes, a bilobed band was observed in visible circular dichroism spectra due to interactions between neighboring chromophores. At all concentrations of TX100, this was replaced by a single positive band. Upon illumination with visible light, TX100‐solubilized bR clearly showed photobleaching to bacterioopsin. These experimental results suggest that photobleaching is due to a lack of intermolecular interactions inside the purple membrane lattice. Extensive kinetic measurements further revealed that the rate constant of photobleaching is strongly dependent on the detergent concentration, although the activation energy for photobleaching does not significantly change with the TX100 concentration. The mechanism of photobleaching for the solubilized bR is discussed with respect to detergent micelle properties.
Outcome of mTHPC Mediated Photodynamic Therapy is Primarily Determined by the Vascular Response
Authors: Triesscheijn Martijn , Ruevekamp Marjan , Aalders Maurice , Baas Paul , Stewart Fiona A. 
Published: June 2005

ABSTRACTWe have previously shown that the efficacy of photodynamic therapy (PDT) using the photosensitizer meso‐tetra‐hydrox‐yphenyl‐chlorin (mTHPC) correlated with plasma drug levels at the time of illumination rather than drug levels in human tumor xenografts or mouse skin. These results suggested that vascular‐mediated effects could be important determinants of PDT response in vivo. In the present study we further investigated the relationship between PDT response, mTHPC pharmacokinetics and the localization and extent of vascular damage induced in human squamous cell carcinoma xenografts (HNXOE). Plasma levels of mTHPC decreased exponentially with time after injection, whereas tumor drug levels remained maximal for at least 48 h. At 3 h after administration mTHPC was localized in the blood vessels, whereas at later times it was distributed throughout the whole tumor. Illumination at 3 h after mTHPC, which resulted in 100% long‐term tumor cure, led to a marked reduction of vascular perfusion and increased tumor hypoxia at 1 h after treatment. Illumination at 48 h resulted in rapid regrowth of most tumors and only 10% cure. This protocol did not affect a significant decrease in vascular perfusion or increase in tumor hypoxia. These data show that optimal responses to mTHPC‐mediated PDT were primarily dependent on the early vascular response, and that plasma drug levels at the time of illumination could predict this relationship.
Choice of Optimal Wavelength for PDT: The Significance of Oxygen Depletion
Authors: Nielsen Kristian P. , Juzeniene Asta , Juzenas Petras , Stamnes Knut , Stamnes Jakob J. , Moan Johan 
Published: June 2005

ABSTRACTWe have investigated the role of tissue oxygenation on light penetration into tissue at different wavelengths. As a field of application we have chosen aminolevulinic acid–photodynamic therapy (ALA‐PDT). To calculate efficiency spectra of PDT on human skin one needs to know the excitation spectrum of the photosensitizer of interest and the relative fluence rate as a function of depth in the tissue. We measured the former and computed the latter with an accurate radiative transfer algorithm. In this way we determined the efficiency spectra as functions of depth for different types of basal cell carcinomas (BCC). Our results suggest that ALA‐PDT works best for nodular BCC at a wavelength of 630 nm, whereas it works best for pigmented superficial BCC at a wavelength of 390 nm. At 630 nm the light penetration into a tumor depends strongly on the oxygenation of the blood. Below a 2 mm thick, well‐oxygenated, nodular BCC, we find the efficiency to be an order of magnitude larger than below a poorly oxygenated tumor. At 390 nm, the light penetration into a tumor does not depend on the oxygenation of the blood.
Decrease in Langerhans Cells and Increase in Lymph Node Dendritic Cells Following Chronic Exposure of Mice to Suberythemal Doses of Solar Simulated Radiation
Authors: McLoone Pauline , Woods Gregory M. , Norval Mary 
Published: June 2005

ABSTRACTExposure of certain strains of mice to ultraviolet radiation (UVR) causes suppression of some innate and adaptive immune responses. One such consequence of acute UVB exposure is a reduction in the number of Langerhans cells (LC) in the epidermis and an increase in dendritic cells (DC) in lymph nodes draining the irradiated skin sites. Exposure to chronic UVB irradiation also has effects on the immune system, but it is unknown what effects are caused by repeated doses of solar simulated radiation (SSR). Consequently, the main aims of the present study were to determine whether repeated exposure to low doses of SSR would lead to similar changes in these cell populations and whether chronic doses of SSR activate a protective photoadaptation mechanism. Groups of C3H/HeN mice were irradiated daily with 3.7 J/cm2 SSR from Cleo Natural lamps for 2, 10, 20, 30 or 60 days. Further groups of mice received an additional dose of 7.4 J/cm2 SSR on days 2, 10, 30 or 60 to test for photoadaptation. The numbers of LC in the epidermis and DC in the lymph nodes draining irradiated skin sites were counted 24 h after the final irradiation. With the exception of mice irradiated for only 2 days, LC were significantly reduced throughout the chronic irradiation protocol, and no recovery occurred. DC numbers were significantly increased in the draining lymph nodes of mice irradiated for 20 days and 60 days.
Retracted: Epigallocatechin‐3‐Gallate Inhibits Photocarcinogenesis Through Inhibition of Angiogenic Factors and Activation of CD8+ T Cells in Tumors
Authors: Mantena Sudheer K. , Roy Anshu M. , Katiyar Santosh K. 
Published: June 2005

ABSTRACTThere has been considerable interest in the use of botanical supplements to protect skin from the adverse effects of solar UV radiation, including photocarcinogenesis. We and others have shown that topical application of (−)‐epigallocatechin‐3‐gallate (EGCG) from green tea prevents photocarcinogenesis in mice; however, the chemopreventive mechanism of EGCG in an in vivo tumor model is not clearly understood. In this study, UV‐B‐induced skin tumors with and without treatment of EGCG (∼1 mg/cm2) and age‐matched skin biopsies from SKH‐1 hairless mice were used to identify potential molecular targets of skin cancer prevention by EGCG. These biopsies were analyzed for various biomarkers of angiogenesis and antitumor immune response using immunostaining, Western blotting and gelatinolytic zymography. We report that compared to non‐EGCG‐treated tumors, topical application of EGCG in UV‐induced tumors resulted in inhibition of protein expression and activity of matrix metalloproteinase (MMP)‐2 and MMP‐9, which play crucial roles in tumor growth and metastasis. In contrast, tissue inhibitor of MMP‐1 (TIMP‐1), which inhibits MMP activity, was increased in tumors. With respect to the tumor vasculature, EGCG decreased the expression of CD31, a cell surface marker of vascular endothelial cells, and inhibited the expression of vascular endothelial growth factor in tumors, which are essential for angiogenesis. EGCG inhibited proliferating cell nuclear antigen in UV‐B‐induced tumors as well. Additionally, higher numbers of cytotoxic T lymphocytes (CD8+ T cells) were detected in EGCG‐treated tumors compared with non‐EGCG‐treated tumors. Together, these in vivo tumor data suggested that inhibition of photocarcinogenesis in mice by EGCG is associated with inhibition of angiogenic factors and induction of antitumor immune reactivity.
Trends in Integration Between Physician Organizations and Pharmacies for Self-Administered Drugs
Authors: Kakani Pragya , Cutler David M. , Rosenthal Meredith B. , Keating Nancy L. 
Published: February 2024

ImportanceIncreasing integration across medical services may have important implications for health care quality and spending. One major but poorly understood dimension of integration is between physician organizations and pharmacies for self-administered drugs or in-house pharmacies.ObjectiveTo describe trends in the use of in-house pharmacies, associated physician organization characteristics, and associated drug prices.Design, Setting, and ParticipantsA cross-sectional study was conducted from calendar years 2011 to 2019. Participants included 20% of beneficiaries enrolled in fee-for-service Medicare Parts A, B, and D. Data analysis was performed from September 15, 2020, to December 20, 2023.ExposuresPrescriptions filled by in-house pharmacies.Main Outcomes and MeasuresThe share of Medicare Part D spending filled by in-house pharmacies by drug class, costliness, and specialty was evaluated. Growth in the number of physician organizations and physicians in organizations with in-house pharmacies was measured in 5 specialties: medical oncology, urology, infectious disease, gastroenterology, and rheumatology. Characteristics of physician organizations with in-house pharmacies and drug prices at in-house vs other pharmacies are described.ResultsAmong 8 020 652 patients (median age, 72 [IQR, 66-81] years; 4 570 114 [57.0%] women), there was substantial growth in the share of Medicare Part D spending on high-cost drugs filled at in-house pharmacies from 2011 to 2019, including oral anticancer treatments (from 10% to 34%), antivirals (from 12% to 20%), and immunosuppressants (from 2% to 9%). By 2019, 63% of medical oncologists, 20% of urologists, 29% of infectious disease specialists, 21% of gastroenterologists, and 22% of rheumatologists were in organizations with specialty-relevant in-house pharmacies. Larger organizations had a greater likelihood of having an in-house pharmacy (0.75 percentage point increase [95% CI, 0.56-0.94] per each additional physician), as did organizations owning hospitals enrolled in the 340B Drug Discount Program (10.91 percentage point increased likelihood [95% CI, 6.33-15.48]). Point-of-sale prices for high-cost drugs were 1.76% [95% CI, 1.66%-1.87%] lower at in-house vs other pharmacies.Conclusions and RelevanceIn this cross-sectional study of physician organization–operated pharmacies, in-house pharmacies were increasingly used from 2011 to 2019, especially for high-cost drugs, potentially associated with organizations’ financial incentives. In-house pharmacies offered high-cost drugs at lower prices, in contrast to findings of integration in other contexts, but their growth highlights a need to understand implications for patient care.
Transgender Patient Preferences When Discussing Gender in Health Care Settings
Authors: Harner Vern , Moore Megan , Casillas Boi , Chrivoli Jess , Lopez Olivares Amaranta , Harrop Erin 
Published: February 2024

ImportanceTransgender (trans) patients report frequent discriminatory and harmful experiences in health care settings; gender-affirming, competent health care improves trans individuals’ health and well-being.ObjectiveTo identify factors influencing trans patients’ decision-making regarding sharing gender-related information with providers (clinicians, health care organizations, health care systems) and trans patient preferences for gender-related questions, as well as the subsequent impact on health care experiences.Design, Setting, and ParticipantsA qualitative, interpretivist phenomenological study was conducted via telephone or video (using Zoom) in English and Spanish from August 10 to September 11, 2020. Participants were recruited via trans-specific social media groups and email listservs. Interviews were transcribed verbatim and analyzed from October 2020 to January 2022 using thematic analysis by a majority trans research team.Main Outcomes and MeasuresSemistructured interviews explored patient health care experiences and preferences.ResultsParticipants included 27 trans and/or nonbinary adults (mean [SD] age, 30.9 [10.4] years; range, 21-69 years) from 13 US states. Four themes were identified: (1) impact of provider behaviors, (2) engaging in relational risk assessment, (3) receiving affirming vs medically competent care, and (4) “how are you going to fit [me] into your system?” The first theme reflected the impact of provider actions, including level of flexibility in care and interpersonal interactions, ability to explain medical relevance of gender-related questions, and preparedness to work with trans patients. Second, respondents weighed a variety of implicit or explicit safety cues when deciding whether and how to share information with providers. Third, participants spoke at length about affirming and medically competent care, noting that they have had to prioritize one over the other. Last, participants reported their needs often being at odds with health care system norms and standards of care.Conclusion and RelevanceIn this qualitative study of trans patient preferences when discussing gender-related information with providers, it was found that equitable, gender-affirming, and competent health care requires flexibility and responsiveness to patient preferences. It requires provider humility and engagement, as well as institutional policies that support competent and gender-affirming spaces. Future research could identify additional roles that providers, administrators, and systems can play in ensuring competent care for trans patients.
Sequence of Epinephrine and Advanced Airway Placement After Out-of-Hospital Cardiac Arrest
Authors: Okubo Masashi , Komukai Sho , Izawa Junichi , Kiyohara Kosuke , Matsuyama Tasuku , Iwami Taku , Kitamura Tetsuhisa 
Published: February 2024

ImportanceWhile epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest (OHCA), the optimal sequence of these interventions remains unclear.ObjectiveTo evaluate the association of the sequence of epinephrine administration and AAM with patient outcomes after OHCA.Design, Setting, and ParticipantsThis cohort study analyzed the nationwide, population-based OHCA registry in Japan and included adults (aged ≥18 years) with OHCA for whom emergency medical services personnel administered epinephrine and/or placed an advanced airway between January 1, 2014, and December 31, 2019. The data analysis was performed between October 1, 2022, and May 12, 2023.ExposureThe sequence of intravenous epinephrine administration and AAM.Main Outcomes and MeasuresThe primary outcome was 1-month survival. Secondary outcomes were 1-month survival with favorable functional status and prehospital return of spontaneous circulation. To control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions, propensity scores and inverse probability of treatment weighting (IPTW) were performed for shockable and nonshockable initial rhythm subcohorts.ResultsOf 259 237 eligible patients (median [IQR] age, 79 [69-86] years), 152 289 (58.7%) were male. A total of 21 592 patients (8.3%) had an initial shockable rhythm, and 237 645 (91.7%) had an initial nonshockable rhythm. Using IPTW, all covariates between the epinephrine-first and AAM-first groups were well balanced, with all standardized mean differences less than 0.100. After IPTW, the epinephrine-first group had a higher likelihood of 1-month survival for both shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms compared with the AAM-first group. For the secondary outcomes, the epinephrine-first group experienced an increased likelihood of favorable functional status and prehospital return of spontaneous circulation for both shockable and nonshockable rhythms compared with the AAM-first group.Conclusions and RelevanceThese findings suggest that for patients with OHCA, administration of epinephrine before placement of an advanced airway may be the optimal treatment sequence for improved patient outcomes.
Deep learning segmentation of organs‐at‐risk with integration into clinical workflow for pediatric brain radiotherapy
Authors: Mekki Lina , Acharya Sahaja , Ladra Matthew , Lee Junghoon 
Published: February 2024

AbstractPurposeRadiation therapy (RT) of pediatric brain cancer is known to be associated with long‐term neurocognitive deficits. Although target and organs‐at‐risk (OARs) are contoured as part of treatment planning, other structures linked to cognitive functions are often not included. This paper introduces a novel automatic segmentation tool specifically designed for the unique challenges posed by pediatric patients undergoing brain RT, as well as its seamless integration into the existing clinical workflow.Methods and MaterialsImages of 47 pediatric brain cancer patients aged 1 to 20 years old and 33 two‐year‐old healthy infants were used to train a vision transformer, UNesT, for the segmentation of five brain OARs. The trained model was then incorporated to clinical workflow via DICOM connections between a treatment planning system (TPS) and a server hosting the trained model such that scans are sent from TPS to the server, automatically segmented, and sent back to TPS for treatment planning.ResultsThe proposed automatic segmentation framework achieved a median dice similarity coefficient of 0.928 (frontal white matter), 0.908 (corpus callosum), 0.933 (hippocampi), 0.819 (temporal lobes), and 0.960 (brainstem) with a mean ± SD run time of 1.8 ± 0.67 s over 20 test cases.ConclusionsThe pediatric brain segmentation tool showed promising performance on five OARs linked to neurocognitive functions and can easily be extended for additional structures. The proposed integration to the clinic enables easy access to the tool from clinical platforms and minimizes disruption to existing workflow while maximizing its benefits.
Semiconductive Biomaterials for Pathological Bone Repair and Regeneration
Authors: Fan Youzhun , Ran Heying , Wang Zhengao , Ning Chengyun , Zhai Jinxia , Yu Peng 
Published: February 2024

AbstractBone implant biomaterials are among the most used materials for clinical application. Despite significant advances in biocompatibility and osteoconductivity, conventional biomaterials lack the ability to cope with the pathological microenvironment (inflammation, infection, residual tumors, etc.) during bone repair. Semiconductor implant materials have unique electrical, optical, ultrasound, and thermal response properties, which facilitate non‐invasively and controllably dynamic repair of pathological bone defects. In this review, the design and synthesis of a new generation of semiconductor‐driven bone implant materials are summarized, the mechanism of action of semiconductive biomaterials' functional interfaces and the dynamic repair process of bone tissues are discussed, and new strategies for the problems encountered during clinical osseointegration is provided. Finally, the review outlooks the future of functional semiconductive implants for bone defect repair.