bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness of natalizumab on cognition in multiple sclerosis: A cohort study
Authors: Manouchehrinia Ali , Larsson Hanna , Karim Mohammad Ehsanul , Lycke Jan , Olsson Tomas , Kockum Ingrid
Published: February 2023

Background:

Cognitive impairment occurs in 40%–70% of persons with multiple sclerosis (MS).

Objective:

To examine the effectiveness of natalizumab compared with other disease-modifying treatments (DMTs) on improving cognition as measured by the Symbol Digit Modalities Test (SDMT).

Methods:

Data were collected as part of Swedish nationwide phase IV surveillance studies (2007–2020). An increase in SDMT score by ⩾10% of the difference between maximum score possible (110) and the baseline value was defined as cognitive improvement. The likelihood of improvement was compared between natalizumab-treated individuals and individuals treated with other DMTs using mixed effect logistic regression. Trend in odds of improvement was investigated using slope analyses.

Results:

We included 2100 persons with relapsing-remitting MS treated with natalizumab and 2622 persons treated with other DMTs. At 6 months, 45% reached improvement. The natalizumab group showed largest odds of improvement during follow-up (odds ratio: 2.3, 95% confidence interval (CI): 1.5–3.5). The odds of improvement increased by 7% (95% CI: 6–7) per month of natalizumab treatment. The equivalent estimate was 4% (95% CI: 2–5) for other monoclonal antibodies and nonsignificant for oral or platform therapies.

Conclusion:

Treatment with natalizumab or other monoclonal antibodies is associated with a significantly faster likelihood of cognitive improvement than platform or oral DMTs.
Controlling the narrative, examining the self: The unruly femme subjectivity of Fleabag
Authors: Dove-Viebahn Aviva
Published: February 2023

This article challenges conventions of normative femininity and popular feminism by examining the television show Fleabag (2016–2019) and the destabilizing tendencies of its unnamed protagonist (Phoebe Waller-Bridge), who insistently breaks the fourth wall, implying a form of narrative agency. However, her refusal and/or inability to conform to expectations around public decency, feminine norms, and heterosexual romance also betray a lack of narrative control. The show’s unruly framing and its dysfunctional narrator open a dynamic space for explorations of “bad feminism” ( Gay, 2014 ), “fem (me)inine failure” ( Hoskin and Taylor, 2019 ), and “toxic femininity” ( McCann, 2020 ), while foregrounding a kind of femme resistance.
Numerical investigation on particle removal and energy consumption of supplied and recirculated ventilation for industrial workshop
Authors: Lan Chenchao , Diao Yongfa
Published: February 2023

In the weld back-cleaning process, many high-concentration pollutants are produced, which can lead to health problems after prolonged exposure. In this study, a novel recirculating stratified ventilation system is proposed that combines supply and recirculating ventilation. It reduces indoor particulate concentration and exhausts air volume based on the air gouging process in a casting workshop. The influences of the supplied and recirculated air velocities on the particle removal efficiency and energy consumption were investigated and compared with those of a traditional exhaust system. The computational fluid dynamics-discrete phase model coupling method was adopted. First, the feasibility of the model was verified using previously published experimental data. The concentration of the unsteady particles was then simulated with different supplied and recirculated air velocities in the ventilation system. The particles were dispersed owing to the influence of the heat-source temperature. With an increasing supplied air velocity and constant recirculated air velocity, the average particle concentration was decreased. The results show that the particle removal efficiency can be improved by approximately 100%, and 90% of the energy can be saved to achieve the same removal efficiency as a traditional ceiling exhaust system.
Vigilance, risk, and service use among caregivers of people living with dementia
Authors: McCann Brandy Renee , Roberto Karen A , Blieszner Rosemary , Savla Jyoti , Atkinson Emily
Published: February 2023

Objective

The purpose of this investigation was to understand the dynamics among dementia caregiving, vigilance, and home and community-based service use.

Methods

This paper is derived from a larger, mixed-methods study on caregiving. We used a descriptive qualitative approach to analyze interview data of 30 family caregivers of relatives with dementia.

Results

We found five domains of vigilance in which caregivers felt “on duty”: ensuring attentiveness, ensuring safety, ensuring resources, ensuring healthcare, and ensuring closeness. Formal service use did not necessarily give caregivers relief from vigilance, with the language of risk often employed by caregivers.

Conclusion

Because service use could contribute to feelings of vigilance, rather than give caregivers a break from a sense of watchfulness, these findings support calls for dementia-specific training for service providers. In future caregiving research, the relationship between vigilance, caregiver distress, and role captivity should be explored.
and a poem
Authors: Méndez Jason C.
Published: February 2023

“Survival is life after disaster, life in honor of our ancestors, despite the genocidal forces worked against them specifically so we would not exist. – from “The Shape of My Impact,” by Dr. Alexis Pauline Gumbs. This poem explores the practice of mindful living within the context of remembering, bearing witness, and survival (personal and generational). The poem referenced within the title, “and a poem” is, “Remember the wind,” written after Joy Harjo’s poem, “Remember.” “Remember the wind” uses the life cycle of a dandelion to explore the concepts of mindfulness, impermanence and interconnectedness. This poem is an homage to three brilliant Black women, Drs. Dara D. Méndez, Alexis Pauline Gumbs, and Tameka Cage Conley, whose scholarship, creative practice, and troublemaking have taught me how to turn my voice up. To view the original version of this poem, see the supplemental material section of this article online.
How Educational Attainment Moderates the Recursive Relationship Between Policy Orientations and Partisanship
Authors: Zingher Joshua N.
Published: February 2023

Partisanship and policy attitudes are two foundational political dispositions. While scholars recognize both as important, there is a longstanding debate about how these dispositions influence each other. One camp argues that partisanship shapes policy attitudes much more strongly than the reverse, the other claims policy attitudes exert a powerful influence on partisanship. In this paper, I take up this debate and test these claims. I assess whether individuals bring their partisanship in line with their policy orientations with an analysis of 14 ANES and GSS panels. The highly educated have more stable attitudes and are more likely to bring their partisanship and policy attitudes in line with each other. The relationship is weaker among those with only a high school diploma. These results show that policy attitudes exert an underappreciated influence on partisanship. Overall, I find the policy orientations shape partisanship at least as much as the reverse.
Updates on Organoid Model for the Study of Liver Cancer
Authors: El-Khobar Korri E. , Sukowati Caecilia H. C.
Published: February 2023

Liver cancer remains one of the most common cancers worldwide with limited therapy options. The main risk factors for hepatocellular carcinoma (HCC), the most common form of liver cancer, include chronic infection with hepatitis B or hepatitis C viruses, alcohol abuse, and metabolic disease. Current systemic therapies for advanced HCCs have greatly improved in the last decade, but there is still a need to develop more targeted drug therapy for HCCs. The development of liver organoids, a self-organising and self-renewal three-dimensional cell culture model, has greatly improved cancer research, including liver cancer. The generation of liver organoids provides a physiologically relevant model to study cancer drug screening and development, personalized medicine, liver disease modeling, and liver regeneration. However, the advent of organoid development also comes with few shortcomings that must be overcome, including the high cost of the model, the availability of origin tissues, and the need for multilineage liver organoids to replicate the true cellular heterogeneity of the liver. Despite all the limitations, liver organoids provide a reliable in vitro model for translational applications to develop more effective HCC therapy and to understand the underlying pathogenic mechanism in various liver diseases.
Factors Predicting Outcome in Patients With Critical Limb Ischemia After Multidisciplinary Team Treatment: A 5-Year Single-Center Retrospective Review
Authors: Cuschieri Sophia A. , Rao Priyanka D. , Lara Amy , Sommerset Jill , Karmy-Jones Riyad
Published: February 2023

Introduction:

The global burden of peripheral arterial disease and related critical limb ischemia has been increasing, and with it an increased incidence of limb loss and mortality. Multidisciplinary teams appear to have a beneficial impact on managing these complex patients, but measuring success depends on the outcome chosen. Determining the risk/benefit of intervention can be difficult, and there has been increasing emphasis on using frailty measures to predict the likelihood of morbidity and mortality after vascular interventions.

Methods:

We performed a retrospective review of patients referred to a multidisciplinary team over a 5-year period who underwent intervention. Data included the modified Frailty Index (mFI), Society for Vascular Surgery (SVS) WIfI wound score (0-2 vs 3), and pedal acceleration time (PAT) post-procedure. Outcomes analyzed were 1-year amputation-free survival (AFS-1), independence, and major complications.

Results:

There were 81 patients who underwent either open or endovascular revascularization. One-year amputation-free survival was positively correlated with post-procedure PAT (AFS-1 107.3 ± 25.5 vs non-AFS-1 174 ± 93; P = .025) and inversely related to wound score (SVS 3 AFS-1 5/17 [29%] vs SVS 0-2: 46/64 [72%]; P = .025). Independence was linked to wheelchair dependence prior to intervention with 6/16 (38%) patients patients spending more than 50% of their time in a wheelchair being independent versus 56/64 (88%) who were not wheelchair-dependent being independent ( P = .005). An mFI ≥6 was associated with increased incidence of major complications at 1 year (mFI ≥6 11/31 [35%] vs mFI <6 5/50 [10%]; P = .018).

Conclusion:

One-year amputation-free survival was impacted by post-procedural success as measured by PAT, but negatively impacted by severity of wound at presentation. An mFI ≥6 was associated with greater incidence of complications. These findings may impact decision-making in determining the relative risk/benefit of revascularization in CLI. Vascular technologists can have an important role in development of limb salvage teams.
Pedicled Pronator Quadratus Transposition for Functional Opponensplasty: A Cadaveric Anatomical Study for Feasibility
Authors: Cinclair Trey , Urquia Lindsey , Hembd Austin , Lies Shelby
Published: February 2023

Background:

Techniques on opponensplasty for chronic carpal tunnel syndrome have been described previously. A novel pronator quadratus (PQ) transposition for chronic carpal tunnel syndrome is described. In addition, the relationship of the distal perforating branch of the radial artery to the surrounding tissue is detailed to optimize further use of the PQ flap for clinical applications.

Methods:

Ten cadaver hands underwent PQ dissection, and the perforating branch of the radial artery was identified. Measurements were taken from the radiocarpal joint and the radial styloid to the distal perforating branch. Finally, a proposed surgical technique of PQ transposition with proximal radius periosteum to the first metacarpophalangeal joint and anterior interosseous nerve transfer was performed.

Results:

The average distance of the perforating branch from the radiocarpal joint was 10 ± 1.05 mm, and the average distance from the radial styloid was 17.1 ± 1.6 mm. Pronator quadratus transposed with a layer of radius periosteum demonstrated anatomical feasibility.

Conclusions:

The distal perforating branch of the radial artery predictably perfuses the PQ muscle, which may be used in the future as a means of opponensplasty for chronic carpal tunnel syndrome.
Imatinib-induced severe hematological toxicity: Prolonged myelosuppression resulting from extraordinary sensitivity in an old age
Authors: Xu Jia , Ju Bo , Yang Xiao-Dong , Xiu Nuan-Nuan , Zhao Xi-Chen
Published: February 2023

The advent of tyrosine kinase inhibitors (TKIs) has profoundly changed the therapeutic landscape of chronic myeloid leukemia (CML) in the chronic phase (CML-CP). Imatinib is the first-generation, and the first and as yet the most widely used TKI, and the recommended dose is 400 mg/day for treating CML-CP. Most patients tolerate this treatment well, and prolonged hematological toxicities have rarely been reported. In this manuscript, we report a newly diagnosed CML-CP patient who developed prolonged myelosuppression (lasting for more than three months) following only one week of imatinib at 400 mg/day as the solitary treatment. Imatinib was discontinued, and pancytopenia persisted, with a continuous decrease in hemoglobulin levels. After restoration of autologous hematopoiesis, reintroduction of imatinib at 100 mg/day resulted in recurrent myelosuppression, and subsequent treatment with imatinib at 50 mg/day achieved good hematological homeostasis. We hypothesized that extraordinary sensitivity resulted in severe and prolonged myelosuppression.
E-POD investigations of turbulent premixed flame dynamics approaching lean blow-out conditions
Authors: Meloni Roberto , Chiarizia Nicola , Nassini Pier Carlo , Andreini Antonio
Published: February 2023

Thanks to the continuous computational power increase, the use of high-fidelity computational fluid dynamics (CFD) simulations is nowadays customary, especially in the gas turbines design process. The extraordinary temporal and spatial detail of such analyses generate large datasets, which must be carefully studied to correlate different quantities and gain information to characterize the behavior of combustor designs. Several advanced post-processing tools have been proposed; however, the Extended-POD (E-POD) holds the greatest potential for turbulent combustion applications when the mutual influence of different quantities is the main goal of the investigation. The present work investigates the application of the E-POD to an LES model of a perfectly-premixed, swirl-stabilized, methane-air flame approaching Lean-Blow-Out. Leveraging the validation against the experimental data at two different operating conditions on a laboratory test case, the numerical model has been used to collect several quantities of interest for shedding light on the flow-flame interaction near the blow-out. The post-processing algorithm has been used to highlight the differences between two conditions approaching the extinction at distinct air-flow velocities. It has been found that, when the burner is operated with a higher velocity, the flame is subjected to a cyclic low-frequency breakdown around the internal recirculation zone, leading to an ingestion of cold products from the external parts of the combustor toward the center. Although other local effects acting on the flame brush have been found in both conditions, they are related mainly to higher order coherent structures with a lower energy content. As a result, their impact onto flame stability is found to be of secondary importance since their limited interaction with flame stabilization. The work shows that E-POD represents a powerful tool for investigating the key features of flame dynamics even at near-blow-out conditions, constituting a valid algorithm for interpreting the results of CFD analyses on gas turbines combustors.
Governing with care, reciprocity, and relationality: Recognising the connectivity of human and more-than-human wellbeing and the process of decolonisation
Authors: Parsons Meg
Published: February 2023

In this dialogue, wellbeing-led approaches to governance are situated within broader conversations occurring between Indigenous and non-Indigenous scholars about decolonisation, climate change, and practices of cultural resurgence. I highlight how Indigenous peoples around the world are challenging the marginalisation of Indigenous ontologies, epistemologies and practices and seeking to reassert and enact care-filled, kin-centric, and reciprocal relationships with humans and more-than-humans through decolonising governance and management approaches.
German Corona Protest Mobilizers on Telegram and Their Relations to the Far Right: A Network and Topic Analysis
Authors: Zehring Maximilian , Domahidi Emese
Published: February 2023

The Querdenken movement, the leading force behind German corona protests, is suspected of being a gateway to far-right attitudes due to radicalizing inward-oriented communication on Telegram. To investigate potential connections of this movement to the far right and alternative media—and to explore key topics of the Querdenken network over time—we analyzed 6,294,955 messages from 578 public Telegram channels via network analysis and structural topic modeling. This analysis revealed that Querdenken’s subcommunities preferably forward content from far-right and QAnon communities, while far-right and conspiracy theorist alternative media channels act as content distributors for the movement. Four main topics appeared in the Querdenken network with varying prevalence over time and across different communities: promotion, QAnon, right-wing populism, and COVID-19 conspiracy theories. Our results highlight potential directions for future research and practical implications, for example, that political decision makers should account for the increasing influence of the QAnon movement on Querdenken mobilizers’ Telegram activity.
Corporate Social Responsibility (CSR) and Internal Consequences: The Moderating Role of Employees’ Position Levels
Authors: Wong Antony King Fung , Kim Seongseop (Sam)
Published: February 2023

Before understanding customers’ perceptions of hotel CSR, it is important to understand service providers’ responses to hotel CSR because they are the key person to implement the CSR strategy. Therefore, this study investigates the structural relationship among multidimensional CSR performance, attitude, emotions, and resultant behaviors as perceived by hotel employees. In addition, moderating role of employees’ positional levels in the proposed model is evaluated. The findings show that environmental, ethical, and financial/economic domains consisting of hotel CSR performance effectively explain the resultant behaviors that follow. However, social/philanthropic and legal domains do not have considerable effects. The positions held by hotel employees partially moderate the relationships between the proposed constructs. The results of this study add important insights to the existing literature and help hotel practitioners better understand how multidimensional CSR causes positive attitudes, emotions, and behaviors and how the structural model changes depending on the position levels. These results are achieved by using the newly developed hotel CSR measurement scale, which was made through careful and rigorous six-stage procedures.
How YouTubers Make Popular Marketing Videos? Speech Acts, Move Structure, and Audience Response in YouTube Influencer Marketing Videos
Authors: Chen Gong , Li Yi , Sun Ya
Published: February 2023

In recent years, the promotional discourse has grown more versatile due to the emergence of new social media. YouTube influencer marketing is of increasing significance for brands’ promotion, especially in the beauty category. Many studies on the effect of influencer marketing used self-reported surveys, the results of which provide limited help in formulating effective videos. The current study aims to characterize YouTube influencer marketing videos through speech act analysis and genre analysis and then determine the features significantly associated with audience response through correlation analysis. The study collects 12 videos from 8 YouTubers in the beauty category and finds that the overall speech act composition is 56% assertives, 26% expressives, 10.1% commissives, and 7.4% directives. The study also proposes a 10-move structure. Significant positive correlations are reported between audience response and the percentage of directives and three moves, advising YouTubers to utilize more directive speech acts, share more personal experience, and spend more time preparing the audience in the opening of videos soliciting subscription.
Still Stuck: An Examination of the Early Paid Employment Experiences of Young Women With Disabilities
Authors: Hirano Kara A. , Bromley Katherine W. , Lindstrom Lauren E.
Published: February 2023

Young women with disabilities tend to experience poorer postschool employment outcomes than young men with disabilities and their peers without disabilities. Paid work experiences while in high school have been identified as significantly increasing the likelihood of later employment, yet few recent studies have examined the early employment experiences of young women with disabilities. This study reports the characteristics of paid employment experiences of 134 young women with disabilities. Findings indicate that fewer young women in our sample had paid work experience than young women nearly 20 years ago, and that early employment patterns are reflective of gendered employment patterns documented in adulthood. Implications for educators and service providers include collaboration across multiple systems and a need for gender-specific interventions.
Identification and Ranking of the Critical Success Factors for the Achievement of Operational Excellence in the Sudanese Aviation Industry
Authors: Abedelgadir Mohamed Ibrahim Osman , Mohammad Roslina
Published: February 2023

The purpose of this study is to explore the critical success factors (CSFs) for operational excellence by organizations in the Sudanese aviation industry and to determine if it will result in improved organizational performance and competitive advantage. In this study, a comprehensive literature review is done to determine the CSFs and develop an initial CSFs hierarchy model to achieve operational excellence in the Sudanese aviation industry. Analytic hierarchy process (AHP) is used for evaluating and ranking the determined CSFs. The study’s findings propose a conceptual model, using the AHP approach for operational excellence implementation in Sudanese aviation industry. As a result, the CSFs of operational excellence were provided and dissected to reveal its integrated components and the levels of their importance, without any of which the achievement of operational excellence would be impossible. These include leadership, people management, continuous improvement, operational strategy, and asset optimization.
Factors that influence clinical decisions about offering parent coaching for autistic youth served within the Medicaid system
Authors: Straiton Diondra , Frost Kyle , Ingersoll Brooke
Published: February 2023

Background

Parent coaching is an evidence-based practice for young autistic children, but it is underutilized in lower-resourced community settings like the Medicaid system. Clinicians often struggle to implement parent coaching with low-income and marginalized families, but little is known about which factors influence clinician decision-making processes about providing parent coaching to this population.

Method

This qualitative analysis used the framework method and thematic analysis. We used the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to identify factors in the clinical decision-making process that community providers use when offering parent coaching to families of Medicaid-enrolled autistic children. Interviews with 13 providers and a focus group with 13 providers were analyzed.

Results

The following themes emerged: (a) Policies drive provider task priorities and affect competing demands; (b) Providers are more likely to use parent coaching when agency leaders monitor parent coaching benchmarks, though this is rarely done; (c) Logistical factors like scheduling and treatment location affect perceived feasibility of using parent coaching; (d) Previous experience or coursework in parent coaching and/or family systems supports the quality of parent coaching implementation; (e) Provider perceptions of “parent readiness” are initially indicated by overt expressions of parent interest.

Conclusions

In the absence of outer-context and inner-context policies, providers have more decision-making power to offer parent coaching based on their own judgments and preferences, which may result in fewer families being offered parent coaching and increased bias related to which families are offered this service. State-, agency-, and clinician-level recommendations are provided for increasing equitable provision of this evidence-based practice for autism.
Decolonial process tracing: Indigenous rights and pipeline resistance movements
Authors: Awasis Sakihitowin
Published: February 2023

This article explores how decolonial methodologies and Anishinaabe gkendaasowin (ways of knowing) can augment detailed narrative process tracing methodologies used to examine social and political processes. While detailed narrative is most frequently used as a tool of causal inference, focusing on the unfolding of a singular time, I see potential for it to be enriched by Indigenous legal traditions that emphasize epistemic diversity and multiple temporalities. Analyzing how Indigenous rights are leveraged in decision-making processes for the Line 9 and Line 3 pipelines, I show how a decolonial approach to process tracing (DPT) that centers Anishinaabe gkendaasowin can change both the actors and power relations involved. Recognizing that energy decision-making processes take place alongside, outside, and within colonial state institutions, and are embedded in the land as constellations of reciprocal kinship responsibilities, DPT opens space to examine two kinds of Indigenous rights: those acquired through struggle with state institutions, and those inherent to Indigenous communities’ attachment to place. DPT addresses the shortcomings of a focus on linearity by privileging inherent rights that are often excluded from detailed narrative process tracing. To take inherent rights seriously, one must also take more-than-linearity and more-than-humans seriously—and DPT is uniquely positioned to do this. The key features I propose for decolonial process tracing are grounded constellations, multiversality, and multitemporalities. Decolonizing methodologies and Anishinaabeg studies provide direction for more expansive, decolonial process tracing techniques which can in turn help understand the relationship between temporalities, law, and energy governance.
Intrathymic AAV delivery results in therapeutic site-specific integration at TCR loci
Authors: Calabria Andrea , Cipriani Carlo , Spinozzi Giulio , Rudilosso Laura , Esposito Simona , Benedicenti Fabrizio , Albertini Alessandra , Pouzolles Marie , Luoni Mirko , Giannelli Serena , Broccoli Vania , Guilbaud Mickael , Adjali Oumeya , Taylor Naomi , Zimmermann Valérie S. , Montini Eugenio , Cesana Daniela
Published: February 2023

Adeno-associated Viral vectors (AAVs) have been successful exploited in gene therapy applications for the treatment of several genetic disorders. AAV is considered an episomal vector but it has been shown to integrate within the host-cell genome following generation of double-strand DNA breaks or nicks. While AAV integration raises some safety concerns, it can also provide therapeutic benefit; the direct intrathymic injection of an AAV harboring a therapeutic transgene results in integration in T cell progenitors and long-term T cell immunity. To assess the mechanisms of AAV integration, we retrieved and analyzed hundreds of AAV integration sites from lymph node-derived mature T-cells as compared to liver and brain tissue from treated mice. Notably, we found that while AAV integrations in the liver and brain were distributed across the entire mouse genome, >90% of the integrations in T-cells were clustered within the T cell receptor α, β and γ genes. More precisely, the insertion mapped to DNA breaks created by the enzymatic activity of recombination activating genes (RAG) during V(D)J recombination. Our data indicate that RAG activity during T-cell receptor maturation induces a site-specific integration of AAV genomes and opens new therapeutic avenues for achieving long-term AAV-mediated gene transfer in dividing cells.
DRaW: prediction of COVID-19 antivirals by deep learning—an objection on using matrix factorization
Authors: Hashemi S. Morteza , Zabihian Arash , Hooshmand Mohsen , Gharaghani Sajjad
Published: February 2023

Background

Due to the high resource consumption of introducing a new drug, drug repurposing plays an essential role in drug discovery. To do this, researchers examine the current drug-target interaction (DTI) to predict new interactions for the approved drugs. Matrix factorization methods have much attention and utilization in DTIs. However, they suffer from some drawbacks.

Methods

We explain why matrix factorization is not the best for DTI prediction. Then, we propose a deep learning model (DRaW) to predict DTIs without having input data leakage. We compare our model with several matrix factorization methods and a deep model on three COVID-19 datasets. In addition, to ensure the validation of DRaW, we evaluate it on benchmark datasets. Furthermore, as an external validation, we conduct a docking study on the COVID-19 recommended drugs.

Results

In all cases, the results confirm that DRaW outperforms matrix factorization and deep models. The docking results approve the top-ranked recommended drugs for COVID-19.

Conclusions

In this paper, we show that it may not be the best choice to use matrix factorization in the DTI prediction. Matrix factorization methods suffer from some intrinsic issues, e.g., sparsity in the domain of bioinformatics applications and fixed-unchanged size of the matrix-related paradigm. Therefore, we propose an alternative method (DRaW) that uses feature vectors rather than matrix factorization and demonstrates better performance than other famous methods on three COVID-19 and four benchmark datasets.
Reduced numbers of regulatory T cells in chronic heart failure seems not to be restored by cardiac resynchronization therapy
Authors: Martins Sílvia , António Natália , Carvalheiro Tiago , Laranjeira Paula , Rodrigues Ricardo , Gonçalves Lino , Tomaz Cândida , Paiva Artur
Published: February 2023

Background

T cells have been implicated in the development and progression of inflammatory processes in chronic heart failure (CHF). Cardiac resynchronization therapy (CRT) has beneficial effects on symptoms and cardiac remodeling in CHF. However, its impact on the inflammatory immune response remains controversial. We aimed to study the impact of CRT on T cells in heart failure (HF) patients.

Methods

Thirty-nine HF patients were evaluated before CRT (T0) and six months later (T6). Quantification of T cells, their subsets, and their functional characterization, after in vitro stimulation, were evaluated by flow cytometry.

Results

T regulatory (Treg) cells were decreased in CHF patients (healthy group (HG): 1.08 ± 0.50 versus (heart failure patients (HFP)-T0: 0.69 ± 0.40, P = 0.022) and remaining diminished after CRT (HFP-T6: 0.61 ± 0.29, P = 0.003). Responders (R) to CRT presented a higher frequency of T cytotoxic (Tc) cells producing IL-2 at T0 compared with non-responders (NR) (R: 36.52 ± 12.55 versus NR: 24.71 ± 11.66, P = 0.006). After CRT, HF patients presented a higher percentage of Tc cells expressing TNF-α and IFN-γ (HG: 44.50 ± 16.62 versus R: 61.47 ± 20.54, P = 0.014; and HG: 40.62 ± 15.36 versus R: 52.39 ± 18.66, P = 0.049, respectively).

Conclusion

The dynamic of different functional T cell subpopulations is significantly altered in CHF, which results in an exacerbated pro-inflammatory response. Even after CRT, it seems that the inflammatory condition underlying CHF continues to evolve with the progression of the disease. This could be due, at least in part, to the inability to restore Treg cells levels.

Trial registration: Observational and prospective study with no trial registration.
Blood levels of nicotinic acid negatively correlate with hearing ability in healthy older men
Authors: Nakagawa-Nagahama Yoshiko , Igarashi Masaki , Miura Masaomi , Kashiwabara Kosuke , Yaku Keisuke , Fukamizu Yuichiro , Sato Toshiya , Sakurai Takanobu , Nakagawa Takashi , Kadowaki Takashi , Yamauchi Toshimasa
Published: February 2023

Background

Age-related hearing loss (ARHL) is a common phenomenon observed during aging. On the other hand, the decrease in Nicotinamide adenine dinucleotide (NAD +) levels is reported to be closely related to the age-related declines in physiological functions such as ARHL in animal studies. Moreover, preclinical studies confirmed NAD + replenishment effectively prevents the onset of age-related diseases. However, there is a paucity of studies on the relationship between NAD+ metabolism and ARHL in humans.

Methods

This study was analyzed the baseline results of our previous clinical trial, in which nicotinamide mononucleotide or placebo was administered to 42 older men (Igarashi et al., NPJ Aging 8:5, 2022). The correlations between blood levels of NAD+-related metabolites at baseline and pure-tone hearing thresholds at different frequencies (125, 250, 500, 1000, 2000, 4000, and 8000 Hz) in 42 healthy Japanese men aged > 65 years were analyzed using Spearman’s rank correlation. Multiple linear regression analysis was performed with hearing thresholds as the dependent variable and age and NAD+-related metabolite levels as independent variables.

Results

Positive associations were observed between levels of nicotinic acid (NA, a NAD+ precursor in the Preiss-Handler pathway) and right- or left-ear hearing thresholds at frequencies of 1000 Hz (right: r = 0.480, p = 0.001; left: r = 0.422, p = 0.003), 2000 Hz (right: r = 0.507, p < 0.001, left: r = 0.629, p < 0.001), and 4000 Hz (left: r = 0.366, p = 0.029). Age-adjusted multiple linear regression analysis revealed that NA was an independent predictor of elevated hearing thresholds (1000 Hz (right): p = 0.050, regression coefficient (β) = 1610; 1000 Hz (left): p = 0.026, β = 2179; 2000 Hz (right): p = 0.022, β = 2317; 2000 Hz (left): p = 0.002, β = 3257). Weak associations of nicotinic acid riboside (NAR) and nicotinamide (NAM) with hearing ability were observed.

Conclusions

We identified negative correlations between blood concentrations of NA and hearing ability at 1000 and 2000 Hz. NAD+ metabolic pathway might be associated with ARHL onset or progression. Further studies are warranted.

Trial registration

The study was registered at UMIN-CTR (UMIN000036321) on 1st June 2019.

Graphical Abstract
Struggle in the bubble - a prospective study on the effect of remote learning and distance education on confidence in practical surgical skills acquired during COVID-19
Authors: Kneifel Felicia , Morgul Haluk , Katou Shadi , Hölzen Jens P. , Strücker Benjamin , Juratli Mazen , Pascher Andreas , Becker Felix
Published: February 2023

Background

The coronavirus disease (COVID-19) has significantly changed healthcare systems and medical education. Universities were required to develop innovative curricula based on remote and distance education to continue medical education. This prospective questionnaire-based study aimed to investigate the impact of COVID-19-associated remote learning on the surgical training of medical students.

Methods

A 16-item questionnaire-based survey was distributed to medical students at the University Hospital of Münster before and after a surgical skills laboratory (SSL). Two cohorts were included: summer semester 2021 (COV-19), with rigorous social-distancing restrictions requiered SSL to be remotely, and winter semester 2021 (postCOV-19), in which the SSL was provided as a face-to-face, hands-on course.

Results

Both, cohorts showed a significant improvement in self-assessment of pre- and post-course confidence. While no significant difference in the average gain in self-confidence for sterile working was observed between the two cohorts, improvement in self-confidence was significantly higher in the COV-19 cohort regarding skin suturing and knot tying (p < 0.0001). However the average improvement regarding history and physical was significantly higher in the postCOV-19 cohort (p < 0.0001). In subgroup analysis, gender-associated differences varied in the two cohorts and were not related to specific subtasks, while age-stratified analysis revealed superior results for younger students.

Conclusion

The results of our study underline the usability, feasibility, and adequacy of remote learning for the surgical training of medical students. The on-site distance education version, presented in the study, allows the continuing of hands-on experience in a safe environment in compliance with governmental social-distancing restrictions.
How do inpatients’ costs, length of stay, and quality of care vary across age groups after a new case-based payment reform in China? An interrupted time series analysis
Authors: Chen Ya-jing , Zhang Xin-yu , Tang Xue , Yan Jia-qi , Qian Meng-cen , Ying Xiao-hua
Published: February 2023

Context

A patient classification-based payment system called diagnosis-intervention packet (DIP) was piloted in a large city in southeast China in 2018.

Objective

This study evaluates the impact of DIP payment reform on total costs, out-of-pocket (OOP) payments, length of stay (LOS), and quality of care in hospitalised patients of different age.

Methods

An interrupted time series model was employed to examine the monthly trend changes of outcome variables before and after the DIP reform in adult patients, who were stratified into a younger (18–64 years) and an older group (≥ 65 years), further stratified into young-old (65–79 years) and oldest-old (≥ 80 years) groups.

Results

The adjusted monthly trend of costs per case significantly increased in the older adults (0.5%, P = 0.002) and oldest-old group (0.6%, P = 0.015). The adjusted monthly trend of average LOS decreased in the younger and young-old groups (monthly slope change: -0.058 days, P = 0.035; -0.025 days, P = 0.024, respectively), and increased in the oldest-old group (monthly slope change: 0.107 days, P = 0.030) significantly. The changes of adjusted monthly trends of in-hospital mortality rate were not significant in all age groups.

Conclusion

Implementation of the DIP payment reform associated with increase in total costs per case in the older and oldest-old groups, and reduction in LOS in the younger and young-old groups without deteriorating quality of care.
Polycomb group genes are required for neuronal pruning in Drosophila
Authors: Bu Shufeng , Lau Samuel Song Yuan , Yong Wei Lin , Zhang Heng , Thiagarajan Sasinthiran , Bashirullah Arash , Yu Fengwei
Published: February 2023

Background

Pruning that selectively eliminates unnecessary or incorrect neurites is required for proper wiring of the mature nervous system. During Drosophila metamorphosis, dendritic arbourization sensory neurons (ddaCs) and mushroom body (MB) γ neurons can selectively prune their larval dendrites and/or axons in response to the steroid hormone ecdysone. An ecdysone-induced transcriptional cascade plays a key role in initiating neuronal pruning. However, how downstream components of ecdysone signalling are induced remains not entirely understood.

Results

Here, we identify that Scm, a component of Polycomb group (PcG) complexes, is required for dendrite pruning of ddaC neurons. We show that two PcG complexes, PRC1 and PRC2, are important for dendrite pruning. Interestingly, depletion of PRC1 strongly enhances ectopic expression of Abdominal B (Abd-B) and Sex combs reduced, whereas loss of PRC2 causes mild upregulation of Ultrabithorax and Abdominal A in ddaC neurons. Among these Hox genes, overexpression of Abd-B causes the most severe pruning defects, suggesting its dominant effect. Knockdown of the core PRC1 component Polyhomeotic (Ph) or Abd-B overexpression selectively downregulates Mical expression, thereby inhibiting ecdysone signalling. Finally, Ph is also required for axon pruning and Abd-B silencing in MB γ neurons, indicating a conserved function of PRC1 in two types of pruning.

Conclusions

This study demonstrates important roles of PcG and Hox genes in regulating ecdysone signalling and neuronal pruning in Drosophila. Moreover, our findings suggest a non-canonical and PRC2-independent role of PRC1 in Hox gene silencing during neuronal pruning.
Long non-coding RNA CCL14-AS suppresses invasiveness and lymph node metastasis of colorectal cancer cells by regulating MEP1A
Authors: Li Mingzhou , Huang Chengmei , Wu Yuanyuan , Zhu Lina , Zhang Yaxin , Zhou Yi , Li Huali , Liu Zhihao , Pan Xinyan , Wang Xin , Qiu Junfeng , Li Fengtian , Liao Wenting
Published: February 2023

Background

Long non-coding RNAs (lncRNAs) play important roles in the biology of colorectal cancer (CRC). There are several lncRNAs associated with invasion and metastasis have been characterized in CRC. However, studies focusing on the precise molecular mechanisms by which lncRNAs function in lymph node (LN) metastasis in CRC are still limited.

Methods

In this study, by analyzing TCGA dataset, we identified that AC244100.2 (termed CCL14-AS), a novel lncRNA enriched in the cytoplasm, was negatively correlated with LN metastasis and unfavorable prognosis of CRC. In situ hybridization was used to examine CCL14-AS expression in clinical CRC tissues. Various functional experiments including migration assay and wound-healing assay were used to investigate the effects of CCL14-AS on CRC cells migration. The nude mice popliteal lymph node metastasis model assay further confirmed the effects of CCL14-AS in vivo.

Results

CCL14-AS expression was significantly downregulated in CRC tissues compared to adjacent normal tissues. In addition, low CCL14-AS expression was correlated with advanced T classification, LN metastasis, distant metastasis, and shorter disease-free survival of CRC patients. Functionally, CCL14-AS overexpression inhibited the invasiveness of CRC cells in vitro and LN metastasis in nude mice. On the contrary, knockdown of CCL14-AS promoted the invasiveness and LN metastasis abilities of CRC cells. Mechanistically, CCL14-AS downregulated the expression of MEP1A via interacting with MEP1A mRNA and reduced its stability. Overexpression of MEP1A rescued the invasiveness and LN metastasis abilities in CCL14-AS-overexpressing CRC cells. Moreover, the expression levels of CCL14-AS was negatively correlated with that of MEP1A in CRC tissues.

Conclusions

We identified a novel lncRNA, CCL14-AS, as a potential tumor suppressor in CRC. Our findings supported a model in which the CCL14-AS/MEP1A axis serves as critical regulator in CRC progression, suggesting a novel biomarker and therapeutic target in advanced CRC.
[18F] FDG uptake in patients with spondyloarthritis: correlation with serum inflammatory biomarker levels
Authors: Manabe Yuri , Norikane Takashi , Yamamoto Yuka , Murao Mitsumasa , Shimada Hiromi , Wakiya Risa , Nakashima Shusaku , Dobashi Hiroaki , Nishiyama Yoshihiro
Published: February 2023

Background

We aimed to evaluate the correlation between 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake and disease activity assessed by serum inflammatory biomarker levels in patients with spondyloarthritis (SpA).

Methods

A total of 36 SpA patients (24 untreated and 12 treated) were examined using FDG positron emission tomography (PET)/computed tomography and classified into axial SpA (axSpA) and peripheral SpA (pSpA). FDG uptake was evaluated in 23 regions of the body and scored as follows: 0 = less than liver uptake; 1 = more than or equal to liver uptake; and 2 = more than or equal to twice liver uptake. A score of 1 or 2 was considered positive. The number of positive regions and the total score were counted in each patient. The maximum standardized uptake value (SUVmax) was calculated for each region, and maximum SUVmax (MaxSUVmax) was used as a representative value. Correlation of PET findings with serum inflammatory biomarker levels, including C-reactive protein (CRP), erythrocyte sedimentation rate, and matrix metalloproteinase 3 (MMP-3), was analyzed.

Results

All but two patients had at least one positive lesion. PET indices correlated significantly with most of the serum inflammatory biomarker levels in untreated SpA, but not in treated SpA. Further, MaxSUVmax, number of positive regions, and total score correlated significantly with CRP (all P values < 0.001), and the number of positive regions (P = 0.012) and total score (P = 0.007) correlated significantly with MMP-3 in untreated pSpA. PET indices did not correlate with any serum inflammatory biomarker level in untreated axSpA.

Conclusion

FDG uptake in untreated pSpA correlated significantly with serum inflammatory biomarker levels.
Quantum resolution of the cosmological singularity without new physics
Authors: Gielen Steffen , Magueijo João
Published: February 2023

We study a quantum Hot Big Bang in the connection representation, with a matter constant of motion m whose conjugate defines time. Superpositions in m induce a unitary inner product. The wavefunction reveals a resolution of the singularity problem without new physics or supplementary boundary conditions. Backtracking in time, the probability peak eventually halts at a maximum curvature, its height dropping thereafter while a symmetric contracting peak rises. The Big Bang is replaced by a superposition of contracting and expanding regular Universes. We contrast these findings with the situation in the metric representation, where boundary conditions at the singularity are needed for unitary evolution.