bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Care Home Managers’ Leadership on the Delivery of Person-Centred Care for People Living with Dementia: A Systematic Review
Authors: Moenke Linda , Handley Melanie , Goodman Claire
Published: May 2023

Background. Care home managers’ leadership is recognised as directly influencing the care received by people living with dementia. What enables care home managers to promote and sustain person-centred care for residents is less well understood. Method. A mixed-methods systematic review synthesised evidence on care home managers’ leadership on the delivery of person-centred care for people living with dementia. Electronic databases (PubMed, Scopus, Cochrane Library, CINAHL, and Google Scholar) were searched between 2009-2021. Thematic synthesis identified commonalities, facilitators, and barriers to managers enabling person-centred care. Results. Twenty-one studies met the inclusion criteria. Approaches demonstrated by care home managers that enabled person-centred care for people living with dementia included valuing and recognising staffs’ work; involving residents and relatives in decision making; providing feedback to staff; promoting a positive work environment and care culture; and involving staff in organisational changes. Barriers to person-centred care were a lack of organisational support for care home managers; staff shortages; managers not having time to work with staff; manager-staff turnover; limited access to dementia training; and a lack of leadership education and training for care home managers. Conclusion. Care home managers are central to the delivery of person-centred care for people living with dementia. The review identified key resources and activities that support this work. The wide variation in leadership approach and a persistent lack of detail about the frequency of educational and organisational support demonstrate a need to explore what enables care home managers to support their staff to deliver person-centred care.
Effect of Different Protocols of Fixed‐Time Artificial Insemination on Mucus, Ovarian Size, and Pregnancy of Mixed‐Breed Cows in the Humid Tropics of Peru
Authors: Diaz-Quevedo Clavel , Ramírez García Alonso , Torres Bernal Lenin , Cáceres Coral Jorge , Ampuero Trigoso Gustavo , Saucedo-Uriarte José Américo
Published: May 2023

The objective of the research was to evaluate three synchronization protocols for fixed‐time artificial insemination (FTAI) inBos indicuswithBos tauruscrossbred cows. Forty‐five cows of 5 ± 1.6 years were selected. The Jsynch treatment consisted of the application of an intravaginal device plus benzoate; on day 8, the device was removed and PGF2α, estradiol cypionate plus eCG was applied, and the FTAI was performed at 48–52 hours after. Conventional treatment consisted of the application of an intravaginal device plus benzoate; on day 8, the device was removed and PGF2αplus eCG was injected, and on day 9, estradiol benzoate was administered, and FTAI was performed at 30 hours. The Ovsynch treatment consisted of the application of GnRH, and on day 8, PGF2αwas applied, on day 9, GnRH was applied again, and on day 10, FTAI plus GnRH was applied. The diagnosis of pregnancy was determined by transrectal ultrasound 45 days after the FTAI. The Jsynch (39.1%) and conventional (39.1%) treatment showed higher pregnancy compared to the Ovsynch treatment (21.7%) of pregnancy. The presence of crystalline mucus at the time of the FTAI was significantly associated with pregnancy. The results of this investigation indicate that it is possible to obtain acceptable pregnancy rates with the FTAI inB. indicuswithB. tauruscrossbred milk‐producing cows, and treatments with progesterone‐releasing devices plus eCG can improve the reproductive performance of cows.
Supplementary Table 6 from Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis
Authors: Lo Emily K.W. , Mears Brian M. , Maurer H. Carlo , Idrizi Adrian , Hansen Kasper D. , Thompson Elizabeth D. , Hruban Ralph H. , Olive Kenneth P. , Feinberg Andrew P.
Published: May 2023

Pairwise jsDMRs
Supplementary figure from ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis
Authors: Deng Chun-Miao , Zhang Guo-Geng , Liu Qin-Wen , Xu Jiao-Jiao , Liu Zhi-Chao , Yang Jing , Xu Tao-Yang , Li Zhi-Gang , Zhang Fan , Li Bin
Published: May 2023

Supplementary figures shows Supplementary figures and figure legends
Supplementary Data from Large B-cell Lymphomas of Immune-Privileged Sites Relapse via Parallel Clonal Evolution from a Common Progenitor B Cell
Authors: Los-de Vries G. Tjitske , Stathi Phylicia , Rutkens Ryanne , Hijmering Nathalie J. , Luijks Jeroen A.C.W. , Groenen Patricia J.T.A. , de Jong Daphne , Ylstra Bauke , Roemer Margaretha G.M.
Published: May 2023

Supplementary Data
Supplementary Table 4 from ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis
Authors: Deng Chun-Miao , Zhang Guo-Geng , Liu Qin-Wen , Xu Jiao-Jiao , Liu Zhi-Chao , Yang Jing , Xu Tao-Yang , Li Zhi-Gang , Zhang Fan , Li Bin
Published: May 2023

Supplementary Table 4 shows DEGs between highly metastasis ESCC sub cell line KYSE150-Luc-LM3 and the parental cell line
Supplementary Figures from Terminally Exhausted CD8+ T Cells Resistant to PD-1 Blockade Promote Generation and Maintenance of Aggressive Cancer Stem Cells
Authors: Chakravarti Mohona , Dhar Sukanya , Bera Saurav , Sinha Abhipsa , Roy Kamalika , Sarkar Anirban , Dasgupta Shayani , Bhuniya Avishek , Saha Akata , Das Juhina , Banerjee Saptak , Vernekar Manisha , Pal Chiranjib , Alam Neyaz , Datta Dipak , Baral Rathindranath , Bose Anamika
Published: May 2023

Contains supplementary figure S1, S2, S3, S4, S5 and S6.
Supplementary Table 2 from ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis
Authors: Deng Chun-Miao , Zhang Guo-Geng , Liu Qin-Wen , Xu Jiao-Jiao , Liu Zhi-Chao , Yang Jing , Xu Tao-Yang , Li Zhi-Gang , Zhang Fan , Li Bin
Published: May 2023

Supplementary Table 2 shows qRT-PCR primers
Supplementary Table 7 from ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis
Authors: Deng Chun-Miao , Zhang Guo-Geng , Liu Qin-Wen , Xu Jiao-Jiao , Liu Zhi-Chao , Yang Jing , Xu Tao-Yang , Li Zhi-Gang , Zhang Fan , Li Bin
Published: May 2023

Supplementary Table 7 shows Human transcription factor in ANO1 interacting proteins detected by IP-MS
Supplementary Table 6 from ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis
Authors: Deng Chun-Miao , Zhang Guo-Geng , Liu Qin-Wen , Xu Jiao-Jiao , Liu Zhi-Chao , Yang Jing , Xu Tao-Yang , Li Zhi-Gang , Zhang Fan , Li Bin
Published: May 2023

Supplementary Table 6 shows DEGs of EC9706 overexpressing ANO1 and control cells
The Tumor Suppressor Functions of Ubiquitin Ligase KPC1: From Cell-Cycle Control to NF-κB Regulator
Authors: Gulei Diana , Drula Rares , Ghiaur Gabriel , Buzoianu Anca Dana , Kravtsova-Ivantsiv Yelena , Tomuleasa Ciprian , Ciechanover Aaron
Published: May 2023

The ubiquitin-proteasome system (UPS) is responsible for up to 90% of intracellular protein degradation. Alterations in UPS are extensively involved in the development and advancement of malignant pathologies. Thus, the components of the UPS can become potential targets for cancer therapeutics. KPC1 is an E3 ubiquitin ligase component of the UPS that regulates key pathways and processes in cancer. KPC1 sustains the ubiquitination of cytoplasmic p27, determining its elimination and transition between cell-cycle phases. KPC1 also regulates NF-κB signaling by inducing ubiquitination of p105 to allow subsequent proteasomal processing to the functional form p50. It has been shown that the KPC1-p50 duo is reduced or absent in multiple malignancies and that therapeutic reinforcement of the functional axis can exhibit significant tumor suppressor activity. Here, we highlight the potential role of KPC1 as a tumor suppressor by fully describing its crucial role in p27 signaling and the canonical NF-κB pathway.
Figure S1-S5 and Table S1 from Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma
Authors: Mender Ilgen , Siteni Silvia , Barron Summer , Flusche Ann Marie , Kubota Naoto , Yu Chunhua , Cornelius Crystal , Tedone Enzo , Maziveyi Mazvita , Grichuk Anthony , Venkateswaran Niranjan , Conacci-Sorrell Maralice , Hoshida Yujin , Kang Rui , Tang Daolin , Gryaznov Sergei , Shay Jerry W.
Published: May 2023

Supplementary Figure Legends
Supplementary Data from Preclinical Profile of BYON3521 Predicts an Effective and Safe MET Antibody–Drug Conjugate
Authors: Groothuis Patrick G. , Jacobs Daniëlle C.H. , Hermens Inge A.T. , Damming Désirée , Berentsen Kim , Mattaar-Hepp Ellen , Stokman Marloes E.M. , Boekel Tinie van , Rouwette Myrthe , van der Vleuten Monique A.J. , Sesink Aloys , Dijcks Fred A. , Coumans Ruud G.E. , Schouten Jan , Glaudemans Dirk H. , Wijk Daniëlle van , Blomenröhr Marion , Kappers Wendela A. , Ubink Ruud , van der Lee Miranda M.C. , Dokter Wim H.A.
Published: May 2023

Supplementary tables and figures
Movie S1 from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability
Authors: Guerra Emanuela , Trerotola Marco , Relli Valeria , Lattanzio Rossano , Tripaldi Romina , Ceci Martina , Boujnah Khouloud , Pantalone Ludovica , Sacchetti Andrea , Havas Kristina M. , Simeone Pasquale , Travali Nicole , Querzoli Patrizia , Pedriali Massimo , Roversi Pietro , Iezzi Manuela , Tinari Nicola , Antolini Laura , Alberti Saverio
Published: May 2023

Supplementary Movie S1
Table S6 from MYC Induces Immunotherapy and IFNγ Resistance Through Downregulation of JAK2
Authors: Markovits Ettai , Harush Ortal , Baruch Erez N. , Shulman Eldad D. , Debby Assaf , Itzhaki Orit , Anafi Liat , Danilevsky Artem , Shomron Noam , Ben-Betzalel Guy , Asher Nethanel , Shapira-Frommer Ronnie , Schachter Jacob , Barshack Iris , Geiger Tamar , Elkon Ran , Besser Michal J. , Markel Gal
Published: May 2023

Differential gene expression analysis between Interferon Resistance Score (IRS) high and low tumors in four melanoma cohorts. Related to Figure 2.
Supplemental Table 4 from mWTX-330, an IL-12 INDUKINE Molecule, Activates and Reshapes Tumor-Infiltrating CD8+ T and NK Cells to Generate Antitumor Immunity
Authors: Nirschl Christopher J. , Brodkin Heather R. , Domonkos Celesztina , Dwyer Connor J. , Hicklin Daniel J. , Ismail Nesreen , Seidel-Dugan Cynthia , Steiner Philipp , Steuert Zoe , Sullivan Jenna M. , Winston William M. , Salmeron Andres
Published: May 2023

Z Scores from EMT-6 Tumor Infiltrating CD8+ T cells from Select Pathways
Supplementary Figure 8 from MYC Induces Immunotherapy and IFNγ Resistance Through Downregulation of JAK2
Authors: Markovits Ettai , Harush Ortal , Baruch Erez N. , Shulman Eldad D. , Debby Assaf , Itzhaki Orit , Anafi Liat , Danilevsky Artem , Shomron Noam , Ben-Betzalel Guy , Asher Nethanel , Shapira-Frommer Ronnie , Schachter Jacob , Barshack Iris , Geiger Tamar , Elkon Ran , Besser Michal J. , Markel Gal
Published: May 2023

Supplementary Figure 8
Supplementary Figure 5 from MYC Induces Immunotherapy and IFNγ Resistance Through Downregulation of JAK2
Authors: Markovits Ettai , Harush Ortal , Baruch Erez N. , Shulman Eldad D. , Debby Assaf , Itzhaki Orit , Anafi Liat , Danilevsky Artem , Shomron Noam , Ben-Betzalel Guy , Asher Nethanel , Shapira-Frommer Ronnie , Schachter Jacob , Barshack Iris , Geiger Tamar , Elkon Ran , Besser Michal J. , Markel Gal
Published: May 2023

Supplementary Figure 5
Supplementary Figure 2 from MYC Induces Immunotherapy and IFNγ Resistance Through Downregulation of JAK2
Authors: Markovits Ettai , Harush Ortal , Baruch Erez N. , Shulman Eldad D. , Debby Assaf , Itzhaki Orit , Anafi Liat , Danilevsky Artem , Shomron Noam , Ben-Betzalel Guy , Asher Nethanel , Shapira-Frommer Ronnie , Schachter Jacob , Barshack Iris , Geiger Tamar , Elkon Ran , Besser Michal J. , Markel Gal
Published: May 2023

Supplementary Figure 2
Data from MYC Induces Immunotherapy and IFNγ Resistance Through Downregulation of JAK2
Authors: Markovits Ettai , Harush Ortal , Baruch Erez N. , Shulman Eldad D. , Debby Assaf , Itzhaki Orit , Anafi Liat , Danilevsky Artem , Shomron Noam , Ben-Betzalel Guy , Asher Nethanel , Shapira-Frommer Ronnie , Schachter Jacob , Barshack Iris , Geiger Tamar , Elkon Ran , Besser Michal J. , Markel Gal
Published: May 2023

Abstract
Immunotherapy has revolutionized the treatment of advanced melanoma. Because the pathways mediating resistance to immunotherapy are largely unknown, we conducted transcriptome profiling of preimmunotherapy tumor biopsies from patients with melanoma that received PD-1 blockade or adoptive cell therapy with tumor-infiltrating lymphocytes. We identified two melanoma-intrinsic, mutually exclusive gene programs, which were controlled by IFNγ and MYC, and the association with immunotherapy outcome. MYC-overexpressing melanoma cells exhibited lower IFNγ responsiveness, which was linked with JAK2 downregulation. Luciferase activity assays, under the control of JAK2 promoter, demonstrated reduced activity in MYC-overexpressing cells, which was partly reversible upon mutagenesis of a MYC E-box binding site in the JAK2 promoter. Moreover, silencing of MYC or its cofactor MAX with siRNA increased JAK2 expression and IFNγ responsiveness of melanomas, while concomitantly enhancing the effector functions of T cells coincubated with MYC-overexpressing cells. Thus, we propose that MYC plays a pivotal role in immunotherapy resistance through downregulation of JAK2.
Supplementary Table S1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Representativeness Table
Figure S1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Figure S1. a) Time To Response (TTR) according to RECIST 1.1. b) Duration of Response (DOR) according to RECIST 1.1. c) Quality of life assessments: Boxplot of EQ-5D VAS evaluation, screening and last known assessment at database lock. d) EQ-5D VAS, change from screening to last known assessment. e) The functional Assessment of Cancer Therapy – General (FACT-G) score sub-scales at screening and at last known assessments
FIGURE 5 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Kaplan–Meier analysis showing. PFS (A) and OS (B), respectively using pretreatment plasma CCL21 (pg/mL) measurements based on their median values. C, Correlation between CCL21 (pg/mL) and CD3+CCR7+CD45RA+ (% counts) matched patient samples (n = 23). D, Flow cytometry–based comparison between short- and long-term survivors for CD3+CCR7+CD45RA+ % (T naïve and T stem cell memory) analysis using pretreatment blood samples (n = 24). Statistical test was unpaired two-tailed t tests, assuming equal variance. E, Kaplan–Meier analysis showing OS using median CD3+CCR7+CD45RA+ % values.
FIGURE 2 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

A and B, Kaplan–Meier analysis showing PFS and OS of patients with a wildtype BAP1 status and UV-damaged uveal melanoma genome. PFS (C) and OS (D) analyses comparing patients with GNAQ- or GNA11-mutated uveal melanoma. E, Volcano plot showing differentially expressed genes between short term (n = 16) and long term (alive patients, n = 4) from bulk RNA-seq. Genes with FDR-adjusted P values <0.05 were considered statistically significant. F, Individual box plots showing relevant gene signatures implicating long-term (alive patients) survival. Statistical tests were carried out using DESeq2 and FDR-adjusted P values were denoted with *, P < 0.05; **, P < 0.01; ***, P < 0.001.
FIGURE 1 from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

A, Kaplan–Meier analysis showing PFS of all patients. B, Kaplan–Meier analysis showing OS of all patients except one. C, Swimmer plot showing time on treatment, time to best response, and duration of response in all patients who received at least one dose of study drug (n  =  29) are shown. D, Kaplan–Meier analysis comparing OS between patients with LDH baseline greater or lower than the upper limit of normal (ULN).
Data from Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
Authors: Sah Vasu R. , Jespersen Henrik , Karlsson Joakim , Nilsson Lisa M. , Bergqvist Mattias , Johansson Iva , Carneiro Ana , Helgadottir Hildur , Levin Max , Ullenhag Gustav , Ståhlberg Anders , Olofsson Bagge Roger , Nilsson Jonas A. , Ny Lars
Published: May 2023

Purpose:
Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.
Patients and Methods:
We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tumor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.
Results:
Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of responding patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling tertiary lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.
Conclusions:
This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.
Significance:
The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomarkers needing validation and become hypothesis generating for experimental research.
Label-Free Characterization of Atherosclerotic Plaques Via High-Resolution Multispectral Fluorescence Lifetime Imaging Microscopy
Authors: Han Jeongmoo , Kim Sunwon , Jung Kim Hyun , Soo Nam Hyeong , Lee Min Woo , Song Joon Woo , Kim Jin Won , Yoo Hongki
Published: May 2023

Background:

Autofluorescence lifetime (AFL) imaging, a robust technique that enables label-free molecular investigation of biological tissues, is being introduced into the field of cardiovascular diagnostics. However, detailed AFL characteristics of coronary arteries remain elusive and there is a lack of methodology enabling such characterization.

Methods:

We developed multispectral fluorescence lifetime imaging microscopy (FLIM) based on analog-mean-delay. Freshly sectioned coronary arteries and atheromas, harvested from 5 swine models, were imaged using FLIM and stained to label lipids, macrophages, collagen, and smooth muscle cells. The components were quantitated from digitized histological images and compared with the corresponding FLIM. Multispectral AFL parameters derived from 2 different spectral bands (390 nm and 450 nm) were analyzed.

Results:

FLIM provided a wide field-of-view, high-resolution AFL imaging of frozen sections. Principal compositions of coronary arteries, such as tunica media, tunica adventitia, elastic laminas, smooth muscle cell–enriched fibrous plaque, lipid-rich core, and foamy macrophages, were well visualized in FLIM images and were found to have each different AFL spectra. In particular, proatherogenic components including lipids and foamy macrophages exhibited significantly different AFL values compared with plaque-stabilizing collagen- or smooth muscle cell–enriched tissues (
P
<0.0001). Pairwise comparisons showed that each composition was distinguishable from another by the difference in multispectral AFL parameters. Pixel-level analysis based on coregistered FLIM-histology dataset showed that each component of atherosclerosis (lipids, macrophages, collagen, and smooth muscle cells) had distinct correlation pattern with AFL parameters. Random forest regressors trained with the dataset allowed automated, simultaneous visualization of the key atherosclerotic components with high accuracy (r>0.87).

Conclusions:

FLIM provided detailed pixel-level AFL investigation of the complex composition of coronary artery and atheroma. Our FLIM strategy enabling an automated, comprehensive visualization of multiple plaque components from unlabeled sections will be highly useful to efficiently evaluate ex vivo samples without the need for histological staining and analysis.
Natural History of Hypertrophic Cardiomyopathy in Noonan Syndrome With Multiple Lentigines
Authors: Monda Emanuele , Prosnitz Aaron , Aiello Rossella , Lioncino Michele , Norrish Gabrielle , Caiazza Martina , Drago Fabrizio , Beattie Meaghan , Tartaglia Marco , Russo Maria Giovanna , Colan Steven D. , Calcagni Giulio , Gelb Bruce D. , Kaski Juan Pablo , Roberts Amy E. , Limongelli Giuseppe
Published: May 2023

BACKGROUND:

We aimed to examine clinical features and outcomes of consecutive molecularly characterized patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.

METHODS:

A retrospective, longitudinal multicenter cohort of consecutive children and adults with a genetic diagnosis of Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy between 2002 and 2019 was assembled. We defined a priori 3 different patterns of left ventricular remodeling during follow-up: (1) an increase in ≥15% of the maximal left ventricular wall thickness (MLVWT), both in mm and
z
-score (progression); (2) a reduction ≥15% of the MLVWT, both in mm and
z
-score (absolute regression); (3) a reduction ≥15% of the MLVWT
z
-score with a stable MLVWT in mm (relative regression). The primary study end point was a composite of cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator-shock.

RESULTS:

The cohort comprised 42 patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy, with a median age at diagnosis of 3.5 (interquartile range, 0.2–12.3) years. Freedom from primary end point was 92.7% (95% CI, 84.7%–100%) 1 year after presentation and 80.9% (95% CI, 70.1%–90.7%) at 5 years. Patients with MLVWT
z
-score >13.7 showed reduced survival compared with those with <13.7. During a median follow-up of 3.7 years (interquartile range, 2.6–7.9), absolute regression was the most common type of left ventricular remodeling (n=9, 31%), followed by progression (n=6, 21%), and relative regression (n=6, 21%).

CONCLUSIONS:

These findings provide insights into the natural history of left ventricular hypertrophy, and can help inform clinicians regarding risk stratification and clinical outcomes in patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.
Comparing Robot Controller Optimization Methods on Evolvable Morphologies
Authors: van Diggelen Fuda , Ferrante Eliseo , Eiben A. E.
Published: May 2023

In this paper, we compare Bayesian Optimization, Differential Evolution, and an Evolution Strategy employed as a gait-learning algorithm in modular robots. The motivational scenario is the joint evolution of morphologies and controllers, where “newborn” robots also undergo a learning process to optimize their inherited controllers (without changing their bodies). This context raises the question: How do gait-learning algorithms compare when applied to various morphologies that are not known in advance (and thus need to be treated as without priors)? To answer this question, we use a test suite of twenty different robot morphologies to evaluate our gait-learners and compare their efficiency, efficacy, and sensitivity to morphological differences. The results indicate that Bayesian Optimization and Differential Evolution deliver the same solution quality (walking speed for the robot) with fewer evaluations than the Evolution Strategy. Furthermore, the Evolution Strategy is more sensitive for morphological differences (its efficacy varies more between different morphologies) and is more subject to luck (repeated runs on the same morphology show greater variance in the outcomes).
The Rules of Engagement: Porphyry’s Attack on Christian Allegory
Authors: Mullins Samuel
Published: May 2023

Book 6 of Eusebius’ Church History contains a fascinating fragment of Porphyry’s Against the Christians in which the latter lambasts Origen’s allegorical reading of the Jewish Scriptures. Though many aspects of this text have received abundant scholarly attention, relatively little has been written on the theory underlying the critique, that is, why exactly Porphyry thought Christian allegories were illegitimate. Furthermore, among the few scholars who have treated this topic at any length, there is no consensus about the precise nature of Porphyry’s objection. In this article I will argue that Porphyry denies the legitimacy of Christian allegories because he thinks the texts they exegete are clear and simple. They are not, for Porphyry, full of the mysteries and enigmas that indicate allegorical exegesis is appropriate. Consequently, Porphyry understands Christian allegories as an attempt to save a text that is plainly immoral rather than genuinely mysterious.
Percentile-Based Relationship between Daily Precipitation and Surface Air Temperature over the Qinghai–Tibet Plateau
Authors: Jiao Yongliang , Li Ren , Wu Tonghua , Zhao Lin , Wu Xiaodong , Ma Junjie , Yao Jimin , Hu Guojie , Xiao Yao , Yang Shuhua , Liu Wenhao , Qiao Yongping , Shi Jianzong , Du Erji , Zhu Xiaofan , Wang Shenning
Published: May 2023

Climate changes significantly impact the hydrological cycle. Precipitation is one of the most important atmospheric inputs to the terrestrial hydrologic system, and its variability considerably influences environmental and socioeconomic development. Atmospheric warming intensifies the hydrological cycle, increasing both atmospheric water vapor concentration and global precipitation. The relationship between heavy precipitation and temperature has been extensively investigated in literature. However, the relationship in different percentile ranges has not been thoroughly analyzed. Moreover, a percentile-based regression provides a simple but effective framework for investigation into other factors (precipitation type) affecting this relationship. Herein, a comprehensive investigation is presented on the temperature dependence of daily precipitation in various percentile ranges over the Qinghai–Tibet Plateau. The results show that 1) most stations exhibit a peaklike scaling structure, while the northeast part and south margin of the plateau exhibit monotonic positive and negative scaling structures, respectively. The scaling structure is associated with the precipitation type, and 2) the positive and negative scaling rates exhibit similar spatial patterns, with stronger (weaker) sensitivity in the south (north) part of the plateau. The overall increase rate of daily precipitation with temperature is scaled by Clausius–Clapeyron relationship. 3) The higher percentile of daily precipitation shows a larger positive scaling rate than the lower percentile. 4) The peak-point temperature is closely related to the local temperature, and the regional peak-point temperature is roughly around 10°C.

Significance Statement

This study aims to better understand the relationship between precipitation and surface air temperature in various percentile ranges over the Qinghai–Tibet Plateau. This is important because percentile-based regression not only accurately describes the response of precipitation to warming temperature but also provides a simple but effective framework for investigating other factors (precipitation type) that may be affecting this relationship. Furthermore, the sensitivity and peak-point temperature are evaluated and compared among different regions and percentile ranges; this study also attempts to outline their influencing factors. To our knowledge, this study is the first integration of percentile-based analysis of the dependence of daily precipitation on surface air temperature.
Controls of Topographic Rossby Wave Properties and Downslope Transport in Dense Overflows
Authors: Han Xianxian , Stewart Andrew L. , Chen Dake , Liu Xiaohui , Lian Tao
Published: May 2023

Antarctic Bottom Water is primarily formed via overflows of dense shelf water (DSW) around the Antarctic continental margins. The dynamics of these overflows therefore influence the global abyssal stratification and circulation. Previous studies indicate that dense overflows can be unstable, energizing topographic Rossby waves (TRW) over the continental slope. However, it remains unclear how the wavelength and frequency of the TRWs are related to the properties of the overflowing DSW and other environmental conditions, and how the TRW properties influence the downslope transport of DSW. This study uses idealized high-resolution numerical simulations to investigate the dynamics of overflow-forced TRWs and the associated downslope transport of DSW. It is shown that the propagation of TRWs is constrained by the geostrophic along-slope flow speed of the DSW and by the dynamics of linear plane waves, allowing the wavelength and frequency of the waves to be predicted a priori. The rate of downslope DSW transport depends nonmonotonically on the slope steepness: steep slopes approximately suppress TRW formation, resulting in steady, frictionally dominated DSW descent. For slopes of intermediate steepness, the overflow becomes unstable and generates TRWs, accompanied by interfacial form stresses that drive DSW downslope relatively rapidly. For gentle slopes, the TRWs lead to the formation of coherent eddies that inhibit downslope DSW transport. These findings may explain the variable properties of TRWs observed in oceanic overflows, and they imply that the rate at which DSW descends to the abyssal ocean depends sensitively on the manifestation of TRWs and/or nonlinear eddies over the continental slope.
Signatures of Oceanic Wind Events in Convection-Resolving WRF Model Simulations
Authors: Thompson Kelsey B. , Mecikalski John R. , Bateman Monte G.
Published: May 2023

Analyses of cloud-top temperature and lightning characteristics of 48 Weather Research and Forecasting (WRF) Model–simulated ocean-based wind events, with 1-min temporal and 0.5-km horizontal resolution, revealed signatures similar to the corresponding 13 observed events detected by buoys and Coastal-Marine Automated Network (C-MAN) stations as shown in prior research on ocean-based wind events by the first author. These events occurred in the eastern Gulf of Mexico and in the Atlantic Ocean from Florida northward through South Carolina. The coldest WRF cloud-top temperature (WCTT) and peak WRF-estimated lightning flash rate values of the model-simulated events, where each event was required to have a negative vertical velocity of at least 10 m s−1 in the lowest 2 km associated with a convective storm, occurred at an average of 4.2 and 1.1 min prior to the events, respectively. With 36 of the events, the peak estimated flash rate occurred within 5 min of the coldest WCTT. Cloud depth typically increased as the WCTT decreased, and the maximum depth occurred at an average of 2.9 min prior to the events. Thermal cooling and precipitation loading provided negative buoyancy needed to help drive the wind events. Environmental characteristics of the model-simulated ocean-based wind events also resembled those associated with land-based wet downbursts, including moist air near the surface, lapse rates near moist adiabatic, and low cloud bases.
Place and transmemory in California Italian American literary narratives: Dorothy Bryant's Miss Giardino
Authors: Ferraro Eveljn
Published: May 2023

In this article, I propose to think of spaces as sites of production and manifestation of memory, which, in turn, constitutes a transnational formation, one that can hardly be discursively fixed. In particular, my analysis of Dorothy Bryant's 1978 novel Miss Giardino uncovers how transmemory, or the intergenerational transmission of memory from diasporic to ethnic subjects, complicates ideas of Italian belonging. I turn to the study of space, with an emphasis on the multiethnic neighborhood of The Mission, in the east-central part of San Francisco, to address the mediation between Italian diasporic past and interethnic present. While acknowledging that forms of inherited memory (or postmemory), such as class memory, affect the social practice of place intergenerationally, I also aim to show that in transmemory spaces are made differently meaningful. Ultimately, reframing spaces of Italian migrations through the lens of transmemory offers a way to move us forward from impasses in Transnational Italian Studies and diaspora debates that assign to memory an overly static and national paradigm.
Ukraine: Meeting the mental health needs of service veterans
Authors: Deahl Martin P , Andreassen Michael
Published: May 2023

The current conflict in Ukraine is a tragedy of epic proportions that without doubt is causing serious psychological damage with inevitable long term consequences affecting combatants, civilians, not to mention displaced refugees. This paper focuses on the mental health needs of service veterans returning home to a country, devastated by the current conflict.
A case study on the performance of repaired sandwich composite aeronautical structures in different failure characteristics under bending loading
Authors: Süsler Sedat , Avşar Yunus Emre , Türkmen Halit S.
Published: May 2023

It is important to develop composite repair methods and investigate their performance against in-service and severe conditions due to high cost of composites, current environmental conscience and difficulties in composite recycling. In this study, the performance of various repair methods applied to two different types of polymer sandwich composite panels made of identical aramid honeycomb core, which are actively used in aerospace structures, is investigated. It is aimed to obtain different failure characteristics and to investigate the effects of these failure modes on the performance of repair methods for two different facesheet types. Three-point bending tests are configured for the flexural performance of repaired sandwich structures in the case of damage modes of core-facesheet adhesive bonded joint delamination and core damage and facesheet failure. The load carrying capacity is measured by calculating the ultimate value of core shear stress and facing stress. The results show that the configured three-point bending procedure is effective to analyse different span regions and to have various failure characteristics. The repaired samples succeed between 80% and 112% in the load capacity. It is proved that repaired specimens have higher load carrying capacity if facesheet based failure due to facing ultimate normal stress is occurred against delamination and core failure due to core shear stress. In addition to this, a modified epoxy filling/patch repair method for sandwich structures made of honeycomb core which can increase the load carrying capacity significantly is presented.
Facilitated ureteroscopy using DJ stent implantation in ureterolithiasis: A retrospective study
Authors: Lidawi Ghalib , Fanne Rami Abu , Majdoub Muhammad , Asali Mohsin , Zeina Abdel-Rauf , Rub Ronen
Published: May 2023

Objective

To investigate the impact of preoperative double J (DJ) stent insertion on outcomes of retrograde semi-rigid ureteroscopy (URS) in patients with upper small and medium sized ureteral stones.

Methods

Between April 2018 and September 2019, we retrospectively reviewed the medical register of Hillel Yaffe tertiary reference Centre (HYMC) for patients who had undergone retrograde semi-rigid URS for urolithiasis. Patients were separated into two groups depending on whether they accepted the DJ stent placement before URS (Group A) or not (Group B). Operating time, stone clearance rate, number of ‘rescue’ DJ stents, duration of ‘rescue’ stents, complication rate and requirement for repeat URS were compared between groups.

Results

318 procedures undertaken in 290 patients were included (Group A, 83 procedures in 80 patiants; Group B, 235 procedures in 210 patients). By comparison with the non-stented group, patients in the preoperative DJ stented group had a higher stone clearance rate, lower complication rate, less need for postoperative ‘rescue’ DJ stent, lower duration of ‘rescue’ stent and lower re-operative URS requirement, including application of a flexible URS.

Conclusion

Facilitated semi-rigid URS with upstream DJ stenting for small and medium size ureteral stones has favourable periprocedural outcomes compared with primary URS.
Simon Clarke’s Marxism and Latin America
Authors: Pascual Rodrigo , Ghiotto Luciana
Published: May 2023

Simon Clarke left an invaluable critical mark on Marxism. Despite his magnanimous work, he is relatively unknown in Latin America because very few texts have been translated into Spanish. We focus on Clarke’s vision and theory of the state, which is of fundamental importance to research in Latin America. First, we focus on his comprehension of the class struggle category to understand the capitalist state’s emergence. Second, we show the importance of his analysis of the subordination of the state and civil society to the rule of money and law. Third, we emphasise his particular way of understanding the social relations of production, which results in his incisive critique of structuralism and the regulation school. Finally, we point out that his understanding of the social relations of production led to a specific way of understanding Marxism that is ‘Simon Clarke’s Marxism’.
Leukocyte-Rich Platelet-Rich Plasma Is Predominantly Anti-inflammatory Compared With Leukocyte-Poor Platelet-Rich Plasma in Patients With Mild-Moderate Knee Osteoarthritis: A Prospective, Descriptive Laboratory Study
Authors: Jayaram Prathap , Mitchell Parker J.T. , Shybut Theodore B. , Moseley Bruce J. , Lee Brendan
Published: May 2023

Background:

Platelet-rich plasma (PRP) has been used extensively in clinical practice to treat patients with symptomatic knee osteoarthritis (OA). Leukocyte-poor PRP (LP-PRP) has been clinically preferred over leukocyte-rich PRP (LR-PRP); however, it is unclear which cytokine mediators of pain and inflammation are present in LR-PRP and LP-PRP from patients with mild to moderate knee OA in order to rationalize a specific formulation.

Hypothesis:

LP-PRP would be predominantly anti-inflammatory and have reduced nociceptive pain mediators compared with LR-PRP from the same individual with mild to moderate knee OA.

Study Design:

Controlled laboratory study.

Methods:

A total of 24 unique samples of PRP were prepared in order to assess 48 samples of LR-PRP and LP-PRP taken from 12 patients (6 male and 6 female) with symptomatic knee OA of Kellgren-Lawrence grade 2 to 3. Patients underwent blood collection for LR-PRP and LP-PRP preparation through a double-spin protocol to obtain baseline whole blood, platelet concentration, and white blood cell subtypes. LR-PRP and LP-PRP from the same patient were produced at the same time and underwent a comprehensive panel through Luminex (multicytokine profiling) to assess key mediators of inflammation: interleukin 1 receptor antagonist (IL-1Ra), interleukin 4, 6, 8, and 10 (IL-4, IL-6, IL-8, and IL-10), IL-1β, tissue necrosis factor α (TNF-α), and matrix metalloproteinase 9 (MMP-9). To assess mediators of nociceptive pain, nerve growth factor (NGF) and tartrate resistant acid phosphatase 5 (TRAP5) were also assessed.

Results:

LR-PRP from patients with mild to moderate knee OA expressed significantly more IL-1Ra, IL-4, IL-8, and MMP-9 compared with LP-PRP formulations from the same patients. No significant differences were found between LR-PRP and LP-PRP in mediators of nociceptive pain—namely, NGF and TRAP5. Other mediators including TNF-α, IL-1β, IL-6, and IL-10 were also found to have no significant expression differences between LR-PRP and LP-PRP.

Conclusion:

LR-PRP expressed significantly more IL-1Ra, IL-4, and IL-8, suggesting that LR-PRP may be more anti-inflammatory than LP-PRP. MMP-9 was expressed in higher concentrations in LR-PRP, suggesting that LR-PRP may be more chondrotoxic than LP-PRP.

Clinical Relevance:

LR-PRP was found to have a robust expression of anti-inflammatory mediators compared with LP-PRP and may be beneficial to patients with long-term knee OA where chronic low-grade inflammation is present. Mechanistic clinical trials are needed to elucidate the key mediators in both LR-PRP and LP-PRP to assess their effect on long-term progression of knee OA.
Hospices and Emergency Preparedness Planning: A Scoping Review of the Literature
Authors: Baker Rogers Janna E.
Published: May 2023

Objective. Palliative and end-of-life care, as provided by hospices, are important elements of a healthcare response to disasters. A scoping review of the literature was conducted to examine and synthesize what is currently known about emergency preparedness planning by hospices. Methods. A literature search of academic and trade publications was conducted through 6 publication databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines when applicable. Publications were selected and findings were organized into themes. Results. A total of 26 articles were included in the literature review. Six themes of Policies and Procedures; Testing/Training/Education; Integration and Coordination; Mitigation; Risk Assessment/Hazard and Vulnerability Analysis; and Regulations were identified. Conclusions. This review demonstrates that hospices have begun to individualize emergency preparedness features that support their unique role. The review supports all-hazards planning for hospices, and emerging from this review is a developing vision for expanded roles of hospices to help communities in times of disaster. Continued research in this specialized area is needed to improve hospices’ emergency preparedness efforts.
An International, Multicenter Evaluation of Comprehensive Medication Management by Pharmacists in ICU Recovery Centers
Authors: Stollings Joanna L. , Poyant Janelle O. , Groth Christine M. , Rappaport Stephen H. , Kruer Rachel M. , Miller Emily , Whitten Jessica A. , Mcintire Allyson M. , McDaniel Cara M. , Betthauser Kevin D. , Mohammad Rima A. , Kenes Michael T. , Korona Rebecca Bookstavar , Barber Alexandra E. , MacTavish Pamela , Dixit Deepali , Yeung Siu Yan A.
Published: May 2023

Background

Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs.

Research Question

What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers?

Study Design and Methods

This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC.

Results

507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients.

Interpretation

A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics.