bluuebunny/crossref_metadata_2025_split huggingface dataset:
A crisis like no other? Unmet needs in healthcare during the first wave of the COVID-19 crisis in Austria
Authors: Schmidt Andrea E , Rodrigues Ricardo , Simmons Cassandra , Steiber Nadia 
Published: October 2022

AbstractBackgroundMany patients experienced restricted access to healthcare during the Coronavirus Disease 2019 (COVID-19) pandemic. This study is among the first to provide systematic evidence on the existence of subjective unmet needs (SUN) in different population groups during the pandemic.MethodsUsing data on individuals aged 20–64 and living in Austria from the AKCOVID survey (June 2020) and the ‘European Social Survey’ (2015), SUN were compared between 2015 and 2020, either related to the pandemic (fear of infection, provider closed or treatment postponed) or not (barriers related to knowledge, affordability, time and reachability). Multinomial logistic regression models identified determinants of SUN during the pandemic, adjusting for socio-demographics, socio-economic status and self-reported health.ResultsShares of the population with SUN in 2020 substantially exceeded SUN in 2015. Excess unmet needs were mostly attributable to the pandemic. Postponed treatments and closed providers were the most important reasons for SUN in June 2020. Older age groups (50–64 years), inactive and retired people were most likely to report pandemic-related SUN. We did not find socio-economic differences in pandemic-related SUN.ConclusionsThe pandemic resulted in a supply-side shock to healthcare, with vulnerabilities emerging especially among older people, people with poor health and/or people no longer active on the labour market. Further research could focus on health system resilience and the possibilities to improve management of healthcare services during pandemics without widening inequalities while maintaining population health.
Telomere-to-telomere genome assembly of bitter melon (Momordica charantia L. var. abbreviata Ser.) reveals fruit development, composition and ripening genetic characteristics
Authors: Fu Anzhen , Zheng Yanyan , Guo Jing , Grierson Donald , Zhao Xiaoyan , Wen Changlong , Liu Ye , Li Jian , Zhang Xuewen , Yu Ying , Ma Hong , Wang Qing , Zuo Jinhua 
Published: October 2022

Abstract
Momordica charantia L. var. abbreviata Ser. (Mca), known as bitter gourd or bitter melon, is a Momordica variety with medicinal value and belongs to the Cucurbitaceae family. In view of the lack of genomic information on bitter gourd and other Momordica species and to promote Mca genomic research, we assembled a 295.6-Mb telomere-to-telomere (T2T) high-quality Mca genome with six gap-free chromosomes after Hi-C correction. This genome is anchored to 11 chromosomes, which is consistent with the karyotype information, and comprises 98 contigs (N50 of 25.4 Mb) and 95 scaffolds (N50 of 25.4 Mb). The Mca genome harbors 19 895 protein-coding genes, of which 45.59% constitute predicted repeat sequences. Synteny analysis revealed variations involved in fruit quality during the divergence of bitter gourd. In addition, assay for transposase-accessible chromatin by high-throughput sequencing and metabolic analysis showed that momordicosides and other substances are characteristic of Mca fruit pulp. A combined transcriptomic and metabolomic analysis revealed the mechanisms of pigment accumulation and cucurbitacin biosynthesis in Mca fruit peels, providing fundamental molecular information for further research on Mca fruit ripening. This report provides a new genetic resource for Momordica genomic studies and contributes additional insights into Cucurbitaceae phylogeny.
Evaluation of ceftazidime/avibactam for treatment of carbapenemase-producing carbapenem-resistant Enterobacterales with OXA-48 and/or NDM genes with or without combination therapy
Authors: Alqahtani Hajar , Alghamdi Ahlam , Alobaidallah Nouf , Alfayez Amal , Almousa Rawan , Albagli Rawan , Shamas Nour , Farahat Fayssal , Mahmoud Ebrahim , Bosaeed Mohammad , Abanamy Reem 
Published: October 2022

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) is an urgent public health threat of significant global concern. Few observational studies have evaluated the clinical outcomes for treatment of CRE harbouring OXA-48 or NDM genes with ceftazidime/avibactam. Previous findings showed lower 30 day mortality with ceftazidime/avibactam ranges between 8.3% and 22%.

Method
This single-centre retrospective cohort study included adult patients aged ≥18 years admitted to King Abdulaziz Medical City (KAMC) who had received ceftazidime/avibactam for at least 72 h for infections caused by CRE with genes encoding for carbapenemase production (CP-CRE).

Results
A total of 211 patients, mostly male (57%), having CP-CRE infections treated with ceftazidime/avibactam were included, with an average age of 62 years. More than 50% of patients were critically ill, for which 46% received invasive ventilation and 36% were on inotropes. The most frequent infectious disease was hospital/ventilator-acquired pneumonia with Klebsiella pneumoniae being the most frequent causative pathogen. The majority of isolates harboured OXA-48 (81%), followed by NDM ± OXA-48 (19%). The overall clinical cure and 30 day mortality was 78% and 21% respectively (stratified per gene: 79% and 21.6% for OXA-48 and 75% and 17.5% for NDM ± OXA-48).

Conclusions
This was the largest study that evaluated clinical outcomes associate with CP-CRE harbouring OXA-48 gene infections treated with ceftazidime/avibactam. Clinical cure and 30 day mortality were consistent with those of previous studies. Findings suggested that combination therapy with ceftazidime/avibactam had no direct impact on clinical outcomes for CP-CRE with OXA-48.
O-GlcNAcylation is a gatekeeper of porcine myogenesis
Authors: Kirkpatrick Laila T , Daughtry Morgan R , El-Kadi Samer , Shi Tim Hao , Gerrard David E 
Published: October 2022

Abstract
Although it has long been known that growth media withdrawal is a prerequisite for myoblast differentiation and fusion, the underpinning molecular mechanism remains somewhat elusive. Using isolated porcine muscle satellite cells (SCs) as the model, we show elevated O-GlcNAcylation by O-GlcNAcase (OGA) inhibition impaired SC differentiation (D5 P &lt; 0.0001) but had unnoticeable impacts on SC proliferation. To explore the mechanism of this phenotype, we examined the expression of the transcription factor myogenin, a master switch of myogenesis, and found its expression was downregulated by elevated O-GlcNAcylation. Because insulin/IGF-1/Akt axis is a strong promoter of myoblast fusion, we measured the phosphorylated Akt and found that hyper O-GlcNAcylation inhibited Akt phosphorylation, implying OGA inhibition may also work through interfering with this critical differentiation-promoting pathway. In contrast, inhibition of O-GlcNAc transferase (OGT) by its specific inhibitor had little impact on either myoblast proliferation or differentiation (P &gt; 0.05). To confirm these in vitro findings, we used chemical-induced muscle injury in the pig as a model to study muscle regenerative myogenesis and showed how O-GlcNAcylation functions in this process. We show a significant decrease in muscle fiber cross sectional area (CSA) when OGA is inhibited (P &lt; 0.05), compared to nondamaged muscle, and a significant decrease compared to control and OGT inhibited muscle (P &lt; 0.05), indicating a significant impairment in porcine muscle regeneration in vivo. Together, the in vitro and in vivo data suggest that O-GlcNAcylation may serve as a nutrient sensor during SC differentiation by gauging cellular nutrient availability and translating these signals into cellular responses. Given the importance of nutrition availability in lean muscle growth, our findings may have significant implications on how muscle growth is regulated in agriculturally important animals.
Circulating Levels of C1q/TNF-Related Protein 3 (CTRP3) and CTRP9 in Gestational Diabetes and Their Association with Insulin Resistance and Inflammatory Cytokines
Authors: Fadaei Reza , Goodarzi Golnoosh , Yarahmadi Sahar , Allahyari Pooneh , Fallah Soudabeh , Moradi Nariman 
Published: October 2022

Abstract

Objective
Gestational diabetes mellitus (GDM) is closely related to obesity, adipose tissue, and adipokines. Adiponectin-homologous adipokines with anti-inflammatory properties, including C1q/TNF-related protein 3 (CTRP3) and CTRP9, regulate glucose and lipid metabolism, which was measured in pregnant women with GDM with the aim to assess their circulating levels and their relation with inflammatory cytokines and other biochemical data.

Methods
Serum levels of CTRP3, CTRP9, adiponectin, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured in 43 subjects with GDM and 42 healthy controls by enzyme-linked immunosorbent assay.

Results
Serum levels of adiponectin and CTRP3 were lower in GDM subjects than in controls, whereas CTRP9, TNF-α, and IL-6 showed higher concentrations in subjects with GDM than in controls. In the subjects with GDM, there was a significant association of CTRP3 with homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, and triglycerides, whereas CTRP9 is associated with TNF-α and HOMA-IR.

Conclusion
The differences in the assessed levels of CTRP3 and CTRP9 suggest a possible relation with the pathogenesis of GDM, in particular insulin resistance, which showed significant association with both adipokines.
Targeting integrin α2 as potential strategy for radiochemosensitization of glioblastoma
Authors: Korovina Irina , Vehlow Anne , Temme Achim , Cordes Nils 
Published: October 2022

AbstractBackgroundGlioblastoma (GBM) is a fast-growing primary brain tumor characterized by high invasiveness and resistance. This results in poor patient survival. Resistance is caused by many factors, including cell-extracellular matrix (ECM) interactions. Here, we addressed the role of adhesion protein integrin α2, which we identified in a high-throughput screen for novel potential targets in GBM cells treated with standard therapy consisting of temozolomide (TMZ) and radiation.MethodsIn our study, we used a range of primary/stem-like and established GBM cell models in vitro and in vivo. To identify regulatory mechanisms, we employed high-throughput kinome profiling, Western blotting, immunofluorescence staining, reporter, and activity assays.ResultsOur data showed that integrin α2 is overexpressed in GBM compared to normal brain and, that its deletion causes radiochemosensitization. Similarly, invasion and adhesion were significantly reduced in TMZ-irradiated GBM cell models. Furthermore, we found that integrin α2-knockdown impairs the proliferation of GBM cells without affecting DNA damage repair. At the mechanistic level, we found that integrin α2 affects the activity of activating transcription factor 1 (ATF1) and modulates the expression of extracellular signal-regulated kinase 1 (ERK1) regulated by extracellular signals. Finally, we demonstrated that integrin α2-deficiency inhibits tumor growth and thereby prolongs the survival of mice with orthotopically growing GBM xenografts.ConclusionsTaken together our data suggest that integrin α2 may be a promising target to overcome GBM resistance to radio- and chemotherapy. Thus, it would be worth evaluating how efficient and safe the adjuvant use of integrin α2 inhibitors is to standard radio(chemo)therapy in GBM.
Punishing Atrocity Crimes in Transitional Contexts: Advancing Discussions on Adequacy of Alternative Criminal Sanctions Using the Case of Colombia
Authors: Mayans-Hermida Beatriz E , Holá Barbora 
Published: October 2022

Abstract
Criminal trials and proportional prison sentences are generally seen as the most suitable way to deal with perpetrators of atrocity crimes. Notwithstanding, traditionally conceived criminal penalties, such as imprisonment, may discourage active responsibility-taking by offenders, disaffect victims by not meeting their needs and impede meaningful engagement between perpetrators and survivors. Arguably, alternative criminal sanctions may be appropriate punishment even for atrocity crimes when tried in transitional societies. Using the case of Colombia, this article analyses the justifications of punishment for atrocities in transitional contexts and discusses the adequacy of alternative criminal sanctions as penalties for atrocity crimes. It concludes that under certain conditions, alternative sanctions can be a viable punishment option that may promote active responsibility-taking and contribute to repairing harm, reintegrating offenders into the community and (re)constructing relationships while serving expressive rationales.
Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment
Authors: Kim Jinyong , Chang Euijin , Park Song Yi , Lee Dae-Won , Kang Chang Kyung , Choe Pyoeng Gyun , Kim Nam Joong , Oh Myoung-don , Park Wan Beom , Lee Kyung-Hun , Im Seock-Ah 
Published: October 2022

Abstract

Background
Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies.

Materials and Methods
In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments.

Results
Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy.

Conclusion
Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.
Epigenetic nature of Arabidopsis thaliana telomeres
Authors: Vaquero-Sedas María I , Vega-Palas Miguel A 
Published: October 2022

Abstract
The epigenetic features of defined chromosomal domains condition their biochemical and functional properties. Therefore, there is considerable interest in studying the epigenetic marks present at relevant chromosomal loci. Telomeric regions, which include telomeres and subtelomeres, have been traditionally considered heterochromatic. However, whereas the heterochromatic nature of subtelomeres has been widely accepted, the epigenetic status of telomeres remains controversial. Here, we studied the epigenetic features of Arabidopsis (Arabidopsis thaliana) telomeres by analyzing multiple genome-wide ChIP-seq experiments. Our analyses revealed that Arabidopsis telomeres are not significantly enriched either in euchromatic marks like H3K4me2, H3K9ac, and H3K27me3 or in heterochromatic marks such as H3K27me1 and H3K9me2. Thus, telomeric regions in Arabidopsis have a bimodal chromatin organization with telomeres lacking significant levels of canonical euchromatic and heterochromatic marks followed by heterochromatic subtelomeres. Since heterochromatin is known to influence telomere function, the heterochromatic modifications present at Arabidopsis subtelomeres could play a relevant role in telomere biology.
Genomic screening reveals ubiquitin-like modifier activating enzyme 1 as a potent and druggable target in c-MYC-high triple negative breast cancer models
Authors: Jacob Sheeba , Turner Tia H , Cai Jinyang , Floros Konstantinos V , Yu Ann K , Coon Colin M , Khatri Rishabh , Alzubi Mohammad A , Jakubik Charles T , Bouck Ynes M , Puchalapalli Madhavi , Shende Mayuri , Dozmorov Mikhail G , Boikos Sosipatros A , Hu Bin , Harrell J Chuck , Benes Cyril H , Koblinski Jennifer E , Costa Carlotta , Faber Anthony C 
Published: October 2022

Abstract
Triple negative breast cancer (TNBC) accounts for over 30% of all breast cancer (BC)-related deaths, despite accounting for only 10% to 15% of total BC cases. Targeted therapy development has largely stalled in TNBC, underlined by a lack of traditionally druggable addictions like receptor tyrosine kinases (RTKs). Here, through full genome CRISPR/Cas9 screening of TNBC models, we have uncovered the sensitivity of TNBCs to the depletion of the ubiquitin-like modifier activating enzyme 1 (UBA1). Targeting UBA1 with the first-in-class UBA1 inhibitor TAK-243 induced unresolvable endoplasmic reticulum (ER)-stress and activating transcription factor 4 (ATF4)-mediated upregulation of proapoptotic NOXA, leading to cell death. c-MYC expression correlates with TAK-243 sensitivity and cooperates with TAK-243 to induce a stress response and cell death. Importantly, there was an order of magnitude greater sensitivity of TNBC lines to TAK-243 compared to normal tissue-derived cells. In five patient derived xenograft models (PDXs) of TNBC, TAK-243 therapy led to tumor inhibition or frank tumor regression. Moreover, in an intracardiac metastatic model of TNBC, TAK-243 markedly reduced metastatic burden, indicating UBA1 is a potential new target in TNBC expressing high levels of c-MYC.
Reciprocity in Low Back Pain Care and Its Role in Power Dynamics: A Give-and-Take Approach
Authors: Mescouto Karime , Tan Meris , Setchell Jenny 
Published: October 2022

Abstract

Objective
The shift toward patient-centered care in physical therapy fostered a deeper consideration of power-sharing in clinical interactions. Elements of reciprocity may enhance such power considerations between physical therapist and patients, but there has been little investigation into how reciprocity is enacted in physical therapy, its value, and how to improve it if required. This study investigates forms of reciprocity during physical therapist–patient interactions in low back pain (LBP) care with the aim of enhancing patient-centered approaches.

Methods
The qualitative design involved (1) ethnographic observations at a fee-for-service practice in Australia, and (2) reflexive discussions between researchers and participating clinicians. To understand reciprocity, the analysis drew from the concepts of “accepting’”(or “blocking”) “offers” that have been previously applied to physical therapy interactions. The analysis is a sub-study using a larger dataset and analyses in which we partnered with physical therapists and people living with LBP.

Results
Forty-nine observations and 13 reflexive discussions were undertaken with 42 people with LBP and 10 physical therapists. Analysis developed 3 themes suggesting that forms of reciprocity depended on physical therapists accepting or blocking patients’ offers, inviting patients to make an offer, and offering personal stories. These elements of reciprocity are relevant to power-sharing during interactions and may impact patient-centered care.

Conclusion
Our results suggest that attending to forms of reciprocity can help physical therapists shift power in clinical interactions. By inviting and accepting “offers,” physical therapists may build collaborative interactions, support individuals to guide the treatment narrative, and shift away from biomedically centered management approaches. Such recommendations create reciprocal environments that might enhance patient-centered care.

Impact
This is one of the few studies to explore how reciprocity is enacted in interactions between physical therapists and s with LBP. Our findings highlight how engaging with the concept of reciprocity could assist with sharing power, improving physical therapist–patient relationships, and enhancing patient-centered care.
Mitochondrial Electron Transport Chain Complex II Dysfunction Causes Premature Aging of Hematopoietic Stem Cells
Authors: Harada Kaito , Yahata Takashi , Onizuka Makoto , Ishii Takamasa , Aziz Ibrahim Abd , Kikkawa Eri , Gondo Yoichi , Ando Kiyoshi 
Published: October 2022

AbstractMitochondria are indispensable in maintaining hematopoietic stem cells (HSCs), and mitochondrial complex II (MCII) has been recognized as a key component of HSCs. However, the physiological role of MCII on long-term hematopoiesis and hematopoietic reconstitution capacity remains unknown. Hence, this study evaluated the impact of MCII dysfunctions on long-term HSC maintenance and hematopoietic homeostasis among conditional transgenic mice with a missense mutation in the succinate dehydrogenase complex subunit C gene (SdhcV69E). HSCs collected from SdhcV69E mice had a higher reactive oxygen species (ROS) accumulation and DNA damage in response to mitochondrial activation. Via the aging stress response, MCII dysfunctions caused decreased white blood cell count with myeloid-skewing property, macrocytic anemia, and thrombocytosis. Moreover, the HSCs of aged SdhcV69E mice exhibited greater ROS accumulation and lower membrane potential. Transplantation-induced replicative stress also caused premature senescent hematopoiesis. Furthermore, accelerated ROS accumulation and profound DNA damage in HSCs were observed in the SdhcV69E-derived cell recipients. The long-term hematopoietic reconstitution capacity was remarkably impaired in HSCs from the SdhcV69E-derived cell recipients. Taken together, MCII plays an essential role in long-term hematopoiesis, and MCII dysfunctions with aging or replicative stresses caused excessive ROS accumulation and DNA damage in HSCs, leading to premature senescence.
VIIShakespeare
Authors: Rendall Edward B M , Smith Peter J , Parsons Elinor , Fairbanks Chloe , Stelzer Emanuel , Bell Shirley , Haworth Ben , Lim Vanessa , O’Brien Sheilagh Ilona , Baratta Luca 
Published: October 2022

AbstractThis chapter has four sections: 1. Editions and Textual Studies; 2. Shakespeare in the Theatre; 3. Shakespeare on Screen; 4. Criticism. Section 1 is by Edward B.M. Rendall; section 2 is by Peter J. Smith; section 3 is by Elinor Parsons; section 4(a) is by Chloe Fairbanks; section 4(b) is by Emanuel Stelzer; section 4(c) is by Shirley Bell; section 4(d) is by Ben Haworth; section 4(e) is by Vanessa Lim; section 4(f) is by Sheilagh Ilona O’Brien; section 4(g) is by Luca Baratta.