bluuebunny/crossref_metadata_2025 huggingface dataset:
Examiner perceptions of the MRCGP recorded consultation assessment for general practice licensing during COVID-19: cross-sectional study
Authors: Botan Vanessa , Laparidou Despina , Phung Viet-Hai , Cheung Peter , Freeman Adrian , Wakeford Richard , Denney Meiling , Law Graham R. , Siriwardena Aloysius Niroshan
Published: January 2023

Background

The Recorded Consultation Assessment (RCA) was developed rapidly during the COVID-19 pandemic to replace the Clinical Skills Assessment (CSA) for UK general practice licensing. Our aim was to evaluate examiner perceptions of the RCA.

Methods

We employed a cross-sectional design using a questionnaire survey of RCA examiners with attitudinal (relating to examiners thoughts and perceptions of the RCA) and free text response options. We conducted statistical descriptive and factor analysis of quantitative data with qualitative thematic analysis of free text responses.

Results

Overall, 182 of 260 (70%) examiners completed the questionnaire. Responders felt that consultations submitted were representative of the work of a typical GP during the pandemic and provided a good sample across the curriculum. They were also generally positive about the logistic, advisory and other support provided as well as the digital platform. Despite responders generally agreeing there was sufficient information available in video or audio consultations to judge candidates’ data gathering, clinical management, and interpersonal skills, they were less confident about their ability to make judgments of candidates’ performance compared with the CSA. The qualitative analysis of free text responses detailed the problems of case selection and content, explained examiners’ difficulties when making judgments, and detailed the generally positive views about support, training and information technology. Responders also provided helpful recommendations for improving the assessment.

Conclusion

The RCA was considered by examiners to be feasible and broadly acceptable, although they experienced challenges from candidate case selection, case content and judgments leading to suggested areas for improvement.
Entity and relation extraction from clinical case reports of COVID-19: a natural language processing approach
Authors: Raza Shaina , Schwartz Brian
Published: January 2023

Background

Extracting relevant information about infectious diseases is an essential task. However, a significant obstacle in supporting public health research is the lack of methods for effectively mining large amounts of health data.

Objective

This study aims to use natural language processing (NLP) to extract the key information (clinical factors, social determinants of health) from published cases in the literature.

Methods

The proposed framework integrates a data layer for preparing a data cohort from clinical case reports; an NLP layer to find the clinical and demographic-named entities and relations in the texts; and an evaluation layer for benchmarking performance and analysis. The focus of this study is to extract valuable information from COVID-19 case reports.

Results

The named entity recognition implementation in the NLP layer achieves a performance gain of about 1–3% compared to benchmark methods. Furthermore, even without extensive data labeling, the relation extraction method outperforms benchmark methods in terms of accuracy (by 1–8% better). A thorough examination reveals the disease’s presence and symptoms prevalence in patients.

Conclusions

A similar approach can be generalized to other infectious diseases. It is worthwhile to use prior knowledge acquired through transfer learning when researching other infectious diseases.
The Swiss Health Insurance Literacy Measure (HILM-CH): Measurement Properties and Cross-Cultural Validation
Authors: Bardy Tess L. C.
Published: January 2023

Background

Most consumers face difficulties when choosing and navigating health insurance plans. Health insurance literacy (HIL) has been discussed as a critical lever to ensure efficient choices and navigation in choice-based health insurance systems. Still, existing evidence about HIL mainly comes from the US, and the only validated scale, the Health Insurance Literacy Measure (HILM), may not be adequate to measure HIL outside US samples. This paper describes the measurement properties of the Swiss Health Insurance Literacy Measure (HILM-CH), the first scale to measure HIL in Switzerland.

Methods

The items of the HILM-CH were adapted from the HILM in German, French, and Italian. A panel of experts refined it to ensure its suitability for the Swiss context. The final version of the HILM-CH contains 21 items, and other relevant measures were administered in the Swiss Health Insurance Literacy Survey to a sample of 6036 insurees. Measurement properties were investigated overall and per linguistic group. Internal reliability was determined using Cronbach’s alphas. Criterion validity was examined through convergent and concurrent validity of the HILM-CH. The construct validity was assessed using factor analysis. Measurement invariance of the HILM-CH between linguistic regions was further evaluated using multiple-group confirmatory factor analyses.

Results

The HILM-CH had acceptable to good reliability (alphas between 0.70 and 0.91). Concurrent and convergent validity showed that HILM-CH is a good measurement of HIL. Factor analysis revealed a four-factor model and showed an acceptable fit to the data (CFI= 0.977; TLI = 0.974; RMSEA = 0.061; SRMR = 0.032). Using the established four-factor model, measurement invariance was established across Switzerland’s German, French, and Italian-speaking regions.

Conclusions

The HILM-CH is a reliable and valid measure of HIL across Switzerland’s German, French, and Italian-speaking regions. It can be used in future research to find associations between HIL and individual characteristics.
Association of Medicaid expansion and 1115 waivers for substance use disorders with hospital provision of opioid use disorder services: a cross sectional study
Authors: Chang Ji Eun , Cronin Cory E. , Lindenfeld Zoe , Pagán José A. , Franz Berkeley
Published: January 2023

Introduction

Opioid-related hospitalizations have risen dramatically, placing hospitals at the frontlines of the opioid epidemic. Medicaid expansion and 1115 waivers for substance use disorders (SUDs) are two key policies aimed at expanding access to care, including opioid use disorder (OUD) services. Yet, little is known about the relationship between these policies and the availability of hospital based OUD programs. The aim of this study is to determine whether state Medicaid expansion and adoption of 1115 waivers for SUDs are associated with hospital provision of OUD programs.

Methods

We conducted a cross-sectional study of a random sample of hospitals (n = 457) from the American Hospital Association’s 2015 American Hospital Directory, compiled with the most recent publicly available community health needs assessment (2015–2018).

Results

Controlling for hospital characteristics, overdose burden, and socio-demographic characteristics, both Medicaid policies were associated with hospital adoption of several OUD programs. Hospitals in Medicaid expansion states had significantly higher odds of implementing any program related to SUDs (OR: 1.740; 95% CI: 1.032–2.934) as well as some specific activities such as programs for OUD treatment (OR: 1.955; 95% CI: 1.245–3.070) and efforts to address social determinants of health (OR: 6.787; 95% CI: 1.308–35.20). State 1115 waivers for SUDs were not significantly associated with any hospital-based SUD activities.

Conclusions

Medicaid expansion was associated with several hospital programs for addressing OUD. The differential availability of hospital-based OUD programs may indicate an added layer of disadvantage for low-income patients with SUD living in non-expansion states.
Barriers and facilitators to implementing evidence-based interventions in the context of a randomized clinical trial in the United States: a qualitative study
Authors: Jaramillo Elise Trott , Willging Cathleen E , Saldana Lisa , Self-Brown Shannon , Weeks Erin A. , Whitaker Daniel J.
Published: January 2023

Background

Evidence-based interventions, which are typically supported by data from randomized controlled trials (RCTs), are highly valued by providers of human services like child welfare. However, implementing such interventions in the context of a randomized clinical trial is a complex process, as conducting an RCT adds extra tasks for providers and complicating factors for provider organizations. Utilizing the Exploration, Preparation, Implementation, and Sustainment Framework, this study examines factors that facilitate or impede success in the implementation of evidence-based interventions in the context of a largescale trial of SafeCare,® a child maltreatment intervention.

Methods

Qualitative data were obtained as part of a larger mixed-methods study involving a cluster randomized trial comparing SafeCare to usual services for caregivers within nine child welfare agencies across four states. Between May and October 2017, individual interviews were conducted with a purposive sample of 21 child welfare administrators and 24 supervisors, and 19 focus groups were conducted with 84 providers. Data were coded iteratively and grouped into themes.

Results

Several interconnected themes centered on facilitators and barriers to SafeCare implementation in the context of a randomized clinical trial. Facilitators included: (1) Benefits afforded through RCT participation; (2) Shared vision and sustained buy-in across system and organizational levels; and (3) Ongoing leadership support for SafeCare and the RCT. Barriers that hindered SafeCare were: (1) Insufficient preparation to incorporate SafeCare into services; (2) Perceived lack of fit, leading to mixed support for SafeCare and the RCT; and (3) Requirements of RCT participation at the provider level.

Conclusions

These data yield insight into an array of stakeholder perspectives on the experience of implementing a new intervention in the context of a largescale trial. This research also sheds light on how the dynamics of conducting an RCT may affect efforts to implement interventions in complex and high-pressure contexts. Findings highlight the importance of aligning knowledge and expectations among researchers, administrators of organizations, and supervisors and providers. Researchers should work to alleviate the burdens of study involvement and promote buy-in among frontline staff not only for the program but also for the research itself.
Whole-exome sequencing identified recurrent and novel variants in benzene-induced leukemia
Authors: Lin Dafeng , Wang Dianpeng , Li Peimao , Deng Lihua , Zhang Zhimin , Zhang Yanfang , Zhang Ming , Zhang Naixing
Published: January 2023

Background

Genome-wide sequencing may extensively identify potential pathogenic variants, which helps to understand mechanisms of tumorigenesis, but such study has not been reported in benzene-induced leukemia (BIL).

Methods

We recruited 10 BIL patients and conducted the whole-exome sequencing on their peripheral blood samples. The obtained sequencing data were screened for potential pathogenic and novel variants, then the variants-located genes were clustered to identify cancer-related pathways. Shared or recurrent variants among the BIL cases were also identified and evaluated for their potential functional impact.

Results

We identified 48,802 variants in exons in total, 97.3% of which were single nucleotide variants. After filtering out variants with minor allele frequency ≥ 1%, we obtained 8667 potentially pathogenic variants, of which 174 were shared by all the BIL cases. The identified variants located in genes that could be significantly enriched into certain cancer-related pathways such as PI3K-AKT signaling pathway and Ras signaling pathway. We also identified 1010 novel variants with no record in the Genome Aggregation Database and in dbSNP, and one of them was shared by 90% cases. The recurrent and novel variant caused a missense mutation in SESN3.

Conclusions

We examined variations of the whole exome in BIL patients for the first time. The commonly shared variants implied a relation with BIL, and the recurrent and novel variant might be specifically related to BIL. The related variants may help unravel the carcinogenic mechanisms of BIL.
Population-based physical activity promotion with a focus on health equity: a review of reviews
Authors: Kohler Simone , Dippon Lea , Helsper Natalie , Rütten Alfred , Abu-Omar Karim , Birkholz Leonie , Pfeifer Klaus , Weber Philipp , Semrau Jana
Published: January 2023

Background

The extent to which people are physically active is dependent upon social gradients. Numerous studies have shown that especially people with social disadvantages do not meet the physical activity (PA) recommendations. A promising strategy to alleviate this issue are approaches that promote PA in the general population. In addition, several researchers have raised concerns that population-based health interventions may increase health inequities. The aim of the current review of reviews was therefore to identify successful population-based PA promotion approaches with a particular focus on health equity.

Methods

Six electronic databases were examined for systematic reviews on population-based PA promotion for the period 2015 to 2021. A reference list and grey literature search were also conducted. Two independent reviewers used inclusion/exclusion criteria to screen titles and abstracts of the potentially relevant literature and conducted a quality assessment for each identified review. All included reviews of population-based approaches for PA promotion with a focus on disadvantaged populations and/or health equity were narratively summarized.

Results

Our search resulted in 4,411 hits. After a systematic review process, six reviews met the inclusion criteria and were included after they were all rated as high quality. We identified that mass-media campaigns, point-of-decision prompts, environmental approaches, policy approaches, and community-based multi-component approaches can promote PA in the general population. Across populations with social disadvantages mass-media campaigns, point-of-decision prompts and policy approaches are likely to be effective as long as they are tailored. Regarding environmental approaches, the results are inconsistent. None of the reviews on community-based multi-component approaches provided evidence on health equity.

Conclusion

There are several effective approaches to promote PA in the general population but evidence regarding health equity is still sparse. Future studies should therefore pay more attention to this missing focus. Furthermore, there is a lack of evidence regarding the type of tailoring and the long-term impact of population-based approaches to PA promotion. However, this requires appropriate funding programmes, complex study designs and evaluation methods.
Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1]
Authors: Schüz Joachim , Ostroumova Evgenia , Kesminiene Ausrele , Davies Louise , Ahn Hyeong Sik , Togawa Kayo , Vaccarella Salvatore
Published: January 2023

Background

Using a toolkit approach, Tsuda et al. critiqued work carried out by or in collaboration with the International Agency for Research on Cancer (IARC/WHO), including the IARC technical publication No. 46 on “Thyroid health monitoring after nuclear accidents” (TM-NUC), the project on nuclear emergency situations and improvement on medical and health surveillance (SHAMISEN), and the IARC-led work on global thyroid cancer incidence patterns as per IARC core mandate.

Main body

We respond on the criticism of the recommendations of the IARC technical publication No. 46, and of global thyroid cancer incidence evaluation.

Conclusion

After nuclear accidents, overdiagnosis can still happen and must be included in informed decision making when providing a system of optimal help for cases of radiation-induced thyroid cancer, to minimize harm to people by helping them avoid diagnostics and treatment they may not need.
Pediatric Gastroenterology and Hepatology in Italy before and after the COVID-19: Lessons learned and management changes by SIGENP
Authors: Dipasquale Valeria , Deganello Saccomani Marco , Di Giorgio Angelo , Oliva Salvatore , Salvatore Silvia , Strisciuglio Caterina , Tambucci Renato , Lionetti Paolo , Romano Claudio
Published: January 2023

﻿Around the world, the 2019 Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised serious public health problems and major medical challenges. The Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) published several papers on ﻿the impact of COVID-19 on the current management, diagnosis, and treatment of acute and chronic gastrointestinal, hepatic, immune-mediated, and functional disorders. The present article summarizes the most relevant SIGENP reports and consensus during and after the peak of the COVID-19 outbreak, including the diagnosis and treatment of inflammatory bowel disease (IBD), indications and timing of digestive endoscopy, and insights into the novel hepatitis.
Tumor necroptosis-mediated shedding of cell surface proteins promotes metastasis of breast cancer by suppressing anti-tumor immunity
Authors: Liu Zhaoshan , Choksi Swati , Kwon Hyung-Joon , Jiao Delong , Liu Chengyu , Liu Zheng-gang
Published: January 2023

Necroptosis is a form of regulated necrosis and is executed by MLKL when MLKL is engaged in triggering the rupture of cell plasma membrane. MLKL activation also leads to the protease, ADAMs-mediated ectodomain shedding of cell surface proteins of necroptotic cells. Tumor necroptosis often happens in advanced solid tumors, and blocking necroptosis by MLKL deletion in breast cancer dramatically reduces tumor metastasis. It has been suggested that tumor necroptosis affects tumor progression through modulating the tumor microenvironment. However, the exact mechanism by which tumor necroptosis promotes tumor metastasis remains elusive. Here, we report that the ectodomain shedding of cell surface proteins of necroptotic cells is critical for the promoting effect of tumor necroptosis in tumor metastasis through inhibiting the anti-tumor activity of T cells. We found that blocking tumor necroptosis by MLKL deletion led to the dramatic reduction of tumor metastasis and significantly elevated anti-tumor activity of tumor-infiltrating and peripheral blood T cells. Importantly, the increased anti-tumor activity of T cells is a key cause for the reduced metastasis as the depletion of CD8+ T cells completely restored the level of metastasis in the Mlkl KO mice. Interestingly, the levels of some soluble cell surface proteins including sE-cadherin that are known to promote metastasis are also dramatically reduced in MLKL null tumors/mice. Administration of ADAMs pan inhibitor reduces the levels of soluble cell surface proteins in WT tumors/mice and leads to the dramatic decrease in metastasis. Finally, we showed the sE-cadherin/KLRG1 inhibitory receptor is the major pathway for necroptosis-mediated suppression of the anti-tumor activity of T cells and the promotion of metastasis. Hence, our study reveals a novel mechanism of tumor necroptosis-mediated promotion of metastasis and suggests that tumor necroptosis and necroptosis-activated ADAMs are potential targets for controlling metastasis.
Auxin-inducible degron 2 system deciphers functions of CTCF domains in transcriptional regulation
Authors: Hyle Judith , Djekidel Mohamed Nadhir , Williams Justin , Wright Shaela , Shao Ying , Xu Beisi , Li Chunliang
Published: January 2023

Background

CTCF is a well-established chromatin architectural protein that also plays various roles in transcriptional regulation. While CTCF biology has been extensively studied, how the domains of CTCF function to regulate transcription remains unknown. Additionally, the original auxin-inducible degron 1 (AID1) system has limitations in investigating the function of CTCF.

Results

We employ an improved auxin-inducible degron technology, AID2, to facilitate the study of acute depletion of CTCF while overcoming the limitations of the previous AID system. As previously observed through the AID1 system and steady-state RNA analysis, the new AID2 system combined with SLAM-seq confirms that CTCF depletion leads to modest nascent and steady-state transcript changes. A CTCF domain sgRNA library screening identifies the zinc finger (ZF) domain as the region within CTCF with the most functional relevance, including ZFs 1 and 10. Removal of ZFs 1 and 10 reveals genomic regions that independently require these ZFs for DNA binding and transcriptional regulation. Notably, loci regulated by either ZF1 or ZF10 exhibit unique CTCF binding motifs specific to each ZF.

Conclusions

By extensively comparing the AID1 and AID2 systems for CTCF degradation in SEM cells, we confirm that AID2 degradation is superior for achieving miniAID-tagged protein degradation without the limitations of the AID1 system. The model we create that combines AID2 depletion of CTCF with exogenous overexpression of CTCF mutants allows us to demonstrate how peripheral ZFs intricately orchestrate transcriptional regulation in a cellular context for the first time.
Multi-centre, randomised, open-label, blinded endpoint assessed, trial of corticosteroids plus intravenous immunoglobulin (IVIG) and aspirin, versus IVIG and aspirin for prevention of coronary artery aneurysms (CAA) in Kawasaki disease (KD): the KD CAA prevention (KD-CAAP) trial protocol
Authors: Eleftheriou Despina , Moraes Yolanda Collaco , Purvis Cara , Pursell Molly , Morillas Marta Merida , Kahn Robin , Mossberg Maria , Kucera Filip , Tulloh Robert , Standing Joseph F. , Swallow Veronica , McCormack Rachael , Herberg Jethro , Levin Michael , Wan Mandy , Klein Nigel , Connon Roisin , Walker Ann Sarah , Brogan Paul
Published: January 2023

Background

Kawasaki disease (KD) is an acute self-limiting inflammatory vasculitis affecting predominantly medium-sized arteries, particularly the coronary arteries. A number of recent studies conducted in different European countries have demonstrated alarmingly high coronary complications despite treatment with intravenous immunoglobulin (IVIG). These high complication rates now emphasize the need for an urgent reappraisal of IVIG as the sole primary therapeutic agent for KD. The Kawasaki disease CAA prevention (KD-CAAP) trial will test the hypothesis that immediate adjunctive corticosteroid treatment to standard of care IVIG and aspirin will reduce coronary artery aneurysm (CAA) rates in unselected KD patients across Europe.

Methods

KD-CAAP is a multicentre, randomised, controlled, open-label, blinded endpoint assessed trial that will be conducted across Europe supported by the conect4children pan-European clinical trials network. Patients with KD who satisfy the eligibility criteria will be randomised (1:1) to receive either oral prednisolone 2 mg/kg/day plus standard of care therapy IVIG (2 g/kg) and aspirin (40 mg/kg/day); or IVIG and aspirin alone. Further management is dictated by temperature and C-reactive protein (CRP) responses. Co-primary outcomes are as follows: (i) any CAA within the 3 months of trial follow-up; (ii) average estimate of maximum coronary Z-score at weeks 1, 2 and 6 adjusting for rescue treatment. Additional outcomes will be assessed including cost effectiveness, quality of life, corticosteroid toxicity and other safety outcomes.

Discussion

Several recent studies have indicated that coronary complications associated with KD across Europe are much higher than early trials of IVIG had initially suggested. KD-CAAP directly addresses this issue by exploring the therapeutic benefit of adjunctive corticosteroids in unselected KD cases. If we find that corticosteroids prevent CAA and are safe, this is a cheap and widely available intervention that could be implemented immediately for the benefit of children.

Trial registration

ISRCTN71987471- March 31, 2020; Eudract 2019–004433-17.
Myeloid/lymphoid neoplasm with eosinophilia and BCR/FGFR1 rearrangement with transformation to cortical T-lymphoblastic lymphoma and erythroid precursors: a case report
Authors: Isaza Alejandro Pineda , Quintero Santiago Castaño , González Lisceth Paola Quintero , Córdoba Fabián Emiliano Ahumada , Olivar Andrés Felipe Arbeláez , Ocaña Juan Carlos Bravo
Published: January 2023

Background

Myeloproliferative neoplasms are a group of diseases with diverse biological and clinical characteristics. As a provisional separate entity, myeloid/lymphoid neoplasms with eosinophilia and genetic rearrangement have been described, which may present an initial clinical behavior of myeloproliferation and be characterized by varied genetic rearrangements. One of these entities is associated with FGFR1 rearrangements, characterized by its low prevalence and few treatment options.

Case presentation

We present the case of a 53-year-old Mestizo male patient of Hispanic origin who initially presented weight loss and fatigue, with a complete blood count showing leukocytosis and eosinophilia, with an initial diagnosis of nonspecific myeloproliferative disorder. In a next-generation sequencing study, BCR::FGFR1 rearrangement was documented, a diagnosis of myeloid/lymphoid neoplasia with eosinophilia and BCR::FGFR1 rearrangement was made, and hydroxyurea therapy was initiated. Subsequently, transformation to cortical T-lymphoblastic leukemia/lymphoma and erythroid precursors was documented, requiring management with chemotherapy.

Conclusions

Myeloid/lymphoid neoplasms with eosinophilia and genetic rearrangements constitute a group of deeply heterogeneous diseases with variable clinical and diagnostic characteristics and whose treatment is not clearly defined.
Effects of down-regulation of ackA expression by CRISPR-dCpf1 on succinic acid production in Actinobacillus succinogenes
Authors: Chen Chunmei , Zheng Pu
Published: January 2023

Succinic acid (SA), a key intermediate in the cellular tricarboxylic acid cycle (TCA), is a 4-carbon dicarboxylic acid of great industrial value. Actinobacillus succinogenes can ferment various carbon sources and accumulate relatively high concentrations of SA, but few reliable genetic engineering tools exist for A. succinogenes and this has hindered strain improvement to increase SA production for industrial application. Two different repressors, endonuclease-deactivated Cas9 (dCas9) from Streptococcus pyogenes and Cpf1 (dCpf1) from Francisella tularensis, were applied to construct a CRISPRi system in A. succinogenes. Codon-optimized Cas9 and native Cpf1 were successfully expressed in A. succinogenes, and the corresponding sgRNA and crRNA expression elements, promoted by the fumarate reductase promoter, frd, were introduced into the CRISPRi plasmid. The highest repression of the ackA gene (encoding acetate kinase) and thereby acetic acid production (~ eightfold) was achieved by the dCpf1-based CRISPRi system, in which the mutation site, E1006A acted at the start of the coding region of ackA, the gene which regulates acetic acid biosynthesis. Compared with the ackA gene knockout mutant, cell growth was moderately improved and SA production increased by 6.3%. Further, the SA titer and productivity in a 3 L fermenter reached 57.06 g/L and 1.87 g/L/h, and there was less acetic acid production. A dCpf1-based CRISPRi-mediated gene repression system was successfully established for the first time, providing a simple and effective tool for studying functional genomics in A. succinogenes and optimizing SA production.
Information embedding in DFRC networks through chirp waveform diversity
Authors: Chalise Batu K. , Amin Moeness G. , Fabrizio Giuseppe A.
Published: January 2023

We consider a dual function radar communications network and propose a waveform diversity-based approach to embed both target and scheduling data in the transmitter pulses. The scheduling data of radar signal bandwidth, carrier frequency, and waveform along with the information on target detection, range, and Doppler are shared among the network radar nodes without a need for designated communication links. Scheduling and target information are encoded to bits and transmitted over the radar coherent processing interval using up- and down-chirps. We derive exact expressions of probability of bit error and false alarm rate for sharing scheduling and target information data between two radar nodes. The effect of different parameters and data sharing on the radar performance is analyzed and validated by computer simulations. Using the cross-ambiguity function, we show the capability of the up- and down- chirp sequence transmission scheme in reducing range sidelobes compared to the conventional transmission of only the up- (or down-) chirps. To overcome the limited data rate associated with only using two chirp waveforms, we consider orthogonal chirp division multiplexing and derive its CAF. We demonstrate the suitability of OCDM for high data rate radar operations by examining the mainlobe width and sidelobe levels of the zero-Doppler and zero-delay cuts of the CAF.
Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients: a randomised, double-blinded, placebo-controlled phase-II trial
Authors: Yulug Burak , Altay Ozlem , Li Xiangyu , Hanoglu Lutfu , Cankaya Seyda , Lam Simon , Velioglu Halil Aziz , Yang Hong , Coskun Ebru , Idil Ezgi , Nogaylar Rahim , Ozsimsek Ahmet , Bayram Cemil , Bolat Ismail , Oner Sena , Tozlu Ozlem Ozdemir , Arslan Mehmet Enes , Hacimuftuoglu Ahmet , Yildirim Serkan , Arif Muhammad , Shoaie Saeed , Zhang Cheng , Nielsen Jens , Turkez Hasan , Borén Jan , Uhlén Mathias , Mardinoglu Adil
Published: January 2023

Background

Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.

Methods

Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.

Results

We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.

Conclusion

Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis.

Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131
A framework towards resilient Mediterranean eco-solutions for small-scale farming systems
Authors: Lamonaca Emilia , Bouzid Amel , Caroprese Mariangela , Ciliberti Maria Giovanna , Cordovil Claudia M.d. S. , Karatzia Maria-Anastasia , Keskin Mahmut , Lazereg Messaoud , Lidga Christina , Panniello Umberto , Saratsis Anastasios , Tappi Marco , Valasi Irene , Yetişgin SezenOcak , Santeramo Fabio Gaetano
Published: January 2023

Background

The impacts of climate change on crop and livestock sectors are well-documented. Climate change and its related events (e.g., high temperatures, extreme events, disease outbreaks) affect livestock production in various ways (e.g., nutrition, housing, health, welfare), and tend to compromise the physical productivity and the economic performances. Understanding animal responses to climate change may help planning strategies to cope with the adverse climatic conditions and also to reduce polluting emissions. Through an interdisciplinary approach, we develop a conceptual framework to assess and develop new organisational models for Mediterranean small-scale farming systems so as to mitigate the impacts of climate change, to improve farm management and farming technologies, and to achieve an effective adaptation to the climate changes. The conceptual framework consists of four phases: (i) community engagement, (ii) strategies development, (iii) data collection and analysis, (iv) business model generation and sustainability assessment. We assess strengths, weaknesses, opportunities, and threats of the eco-solutions by mean of a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis technique.

Results

The proposed eco-solutions are expected to increase the sustainability of agriculture and food production systems by introducing new and efficient uses of natural resources. The proposed models are expected to have an impact not only on the environment (in terms of mitigation), but also on the economic and social performances, as they are expected to foster the responses of small-scale farms to the increasingly frequent effects of climate change (adaptation solutions). Among the positive impacts, we emphasise the importance of more stable revenues, a tendency that would help farmers to raise their revenues. Last but not least, we found that the proposed models are likely to increase the social resilience of the farming systems to the challenges imposed by the climate change.

Conclusions

The eco-solutions can support stakeholders involved in Mediterranean small-scale farming systems by suggesting novel land, crop, and livestock management approaches to optimise revenue flows, business models and climate change mitigation strategies thanks to the adoption of a systemic approach, that is not only focused on specific components of the system but instead based on the linkages between environmental, social, and economic aspects.
High-resolution metagenomic reconstruction of the freshwater spring bloom
Authors: Kavagutti Vinicius S. , Bulzu Paul-Adrian , Chiriac Cecilia M. , Salcher Michaela M. , Mukherjee Indranil , Shabarova Tanja , Grujčić Vesna , Mehrshad Maliheh , Kasalický Vojtěch , Andrei Adrian-Stefan , Jezberová Jitka , Seďa Jaromir , Rychtecký Pavel , Znachor Petr , Šimek Karel , Ghai Rohit
Published: January 2023

Background

The phytoplankton spring bloom in freshwater habitats is a complex, recurring, and dynamic ecological spectacle that unfolds at multiple biological scales. Although enormous taxonomic shifts in microbial assemblages during and after the bloom have been reported, genomic information on the microbial community of the spring bloom remains scarce.

Results

We performed a high-resolution spatio-temporal sampling of the spring bloom in a freshwater reservoir and describe a multitude of previously unknown taxa using metagenome-assembled genomes of eukaryotes, prokaryotes, and viruses in combination with a broad array of methodologies. The recovered genomes reveal multiple distributional dynamics for several bacterial groups with progressively increasing stratification. Analyses of abundances of metagenome-assembled genomes in concert with CARD-FISH revealed remarkably similar in situ doubling time estimates for dominant genome-streamlined microbial lineages. Discordance between quantitations of cryptophytes arising from sequence data and microscopic identification suggested the presence of hidden, yet extremely abundant aplastidic cryptophytes that were confirmed by CARD-FISH analyses. Aplastidic cryptophytes are prevalent throughout the water column but have never been considered in prior models of plankton dynamics. We also recovered the first metagenomic-assembled genomes of freshwater protists (a diatom and a haptophyte) along with thousands of giant viral genomic contigs, some of which appeared similar to viruses infecting haptophytes but owing to lack of known representatives, most remained without any indication of their hosts. The contrasting distribution of giant viruses that are present in the entire water column to that of parasitic perkinsids residing largely in deeper waters allows us to propose giant viruses as the biological agents of top-down control and bloom collapse, likely in combination with bottom-up factors like a nutrient limitation.

Conclusion

We reconstructed thousands of genomes of microbes and viruses from a freshwater spring bloom and show that such large-scale genome recovery allows tracking of planktonic succession in great detail. However, integration of metagenomic information with other methodologies (e.g., microscopy, CARD-FISH) remains critical to reveal diverse phenomena (e.g., distributional patterns, in situ doubling times) and novel participants (e.g., aplastidic cryptophytes) and to further refine existing ecological models (e.g., factors affecting bloom collapse). This work provides a genomic foundation for future approaches towards a fine-scale characterization of the organisms in relation to the rapidly changing environment during the course of the freshwater spring bloom.
Portuguese version of Bern Illegitimates Task Scale: adaptation and evidence of validity
Authors: Neves Paula C. , Andrade Cláudia , Paixão Rui , da Silva José Tomás
Published: January 2023

Background

A new element for job stress called Illegitimate Tasks has been investigated in recent years, along with stress as an offense to self-theory. Illegitimate tasks are those that are either needless or unrelated to the employee's role and can be categorized as unreasonable tasks and unnecessary tasks.

Methods

This study aimed to adapt the Bern Illegitimate Tasks Scale to Portuguese and provide evidence of its validity, through a confirmatory factor analysis with a sample of 472 workers from different sectors.

Results

The internal consistency, of the whole scale, measured by Cronbach’s alpha, was 0.923 and 0.902 and 0.928 for the unnecessary tasks and, for unreasonable tasks subscales respectively. The confirmatory analysis supported a two-factor model and showed good to very good indexes of fit (CFI = 0.985; TLI = 0.997; SRMR = 0.035; RMSEA = 0.171).

Discussion

The Portuguese version of the Bern Illegitimate Tasks Scale presents very good psychometric properties for the intended measurement goals and can now be used in research with Portuguese speaking samples.
Dual signal amplification coupling with DNA-templated silver nanoclusters for sensitive and label-free detection of thrombin
Authors: Zhang Baojun , Ma Weiwei , Guo Jun , Zhao Qiufeng , Zhang Chuangchuang , Zhu Shilong , Xu Haibo , Yin Yanyan
Published: January 2023

Sensitive and reliable determination of thrombin is relevant in the realms of medical and biological research as it serves as an essential biomarker of a number of blood-related illnesses. Herein, we integrate allosteric probe-based specific identification of thrombin and dual signal amplification to present an unique fluorescent technique for label-free and sensitive thrombin detection. Based on DNA polymerase and endonuclease-assisted signal amplification, the method exhibits a high sensitivity with a low limit of detection of 2.3 pM, while maintaining an excellent selectivity and stability. More importantly, the approach is successfully applied in analyzing the effect of nalbuphine on coagulation function of mice. Overall, this approach possesses the advantages of high specificity and sensitivity in label-free detection of thrombin, which is promising in the diagnosis of blood-related diseases.
The usefulness of laparoscopic surgery for inguinal endometriosis
Authors: Mushiake Shu , Kawaguchi Nao , Asakuma Mitsuhiro , Komeda Koji , Shimizu Tetsunosuke , Hirokawa Fumitoshi , Shimomura Tomoo , Lee Sang-Woong
Published: January 2023

Background

Inguinal endometriosis is a rare clinical disease with an unclear etiology and pathogenesis, and its diagnosis requires accurate medical history-taking and histological examination. However, surgical treatment for the condition has not yet been standardized. This report presents two cases of inguinal endometriosis.

Case presentation

The first patient was a 36-year-old woman who complained of pain and swelling in her right inguinal region. Physical examination revealed a soft, tender right inguinal mass. The size of the mass repeatedly increased and decreased during menstruation and did not show swelling with abdominal pressure. Magnetic resonance imaging showed a 3.5 × 2.5 cm mass with high intensity on T2-weighted imaging in the right inguinal canal, and no communication was found between the lesion site and the abdominal cavity. We diagnosed this case as inguinal endometriosis and managed it using an anterior approach and laparoscopic observation. The second patient was a 51-year-old woman who presented with an intermittently painful mass in her right inguinal region. The mass tended to increase in size, with worsening pain before menstruation. Abdominal computed tomography revealed a 2 × 2 cm cystic mass in the right inguinal region. We made a diagnosis of inguinal ectopic endometriosis and decided to operate via the totally extraperitoneal (TEP) method for excision plus transabdominal observation. The postoperative course in both cases was uneventful with no recurrence.

Conclusions

Inguinal endometriosis is a rare entity that should be suspected in patients with cyclical symptoms of inguinal pain and swelling that correlate with their menstrual cycle, which might otherwise be attributed to inguinal hernia. It is crucial to make a preoperative diagnosis based on a careful medical review, physical examination, and imaging studies, and to make an appropriate surgical plan. Particularly, in the case of ectopic inguinal endometriosis involving the canal of Nuck, laparoscopic observation is useful for the intraoperative diagnosis of inguinal endometriosis to help rule out the involvement of other abdominal sites. However, it is important to select and modify the surgical technique to avoid rupturing the endometrisis mass and prevent postoperative recurrence.
Patient dissatisfaction following rhinoplasty: a 10-year experience in Iran
Authors: Ghorbani Farhad , Ahmadi Hanie , Davar Ghazal
Published: January 2023

Background

The nose is one of the most prominent parts of the face and plays a significant role in peoples’ self-satisfaction as well as quality of life. Rhinoplasty is considered as one of the most numerous and delicate cosmetic surgeries all around the world that can be performed for functional issues, esthetic issues, or both. In this study, we aimed to evaluate the dissatisfaction of patients who had undergone rhinoplasty surgery and inform the surgeons to improve the surgical techniques to prevent probable future complaints.

Method

This retrospective cross-sectional study was conducted to report various aspects of dissatisfaction of patients following rhinoplasty. All available files in the Fars Forensic Medicine Department between 2011 and 2020 were reviewed, and the required information was extracted.

Results

Out of 117 patients, 68.4% were females and 31.6% were males. Most of the patients were in the age range of 30–34 years. In terms of educational attainment, the highest frequency is associated with academically educated patients and the lowest with a diploma. The majority of cases filed for litigation less than 6 months after their rhinoplasty. The first rank among the factors of dissatisfaction with surgeries belonged to “respiratory problems” (36.8%) followed by “dissatisfaction with the general shape of the nose” (34.2%).

Conclusion

Our study shows that middle-aged female patients may be more difficult to satisfy. In general, at younger ages, patients complain about esthetics, and with aging, most patients feel dissatisfied with nasal function.
Development of patient- and observer-reported outcome measures to assess COVID-19 signs and symptoms in children and adolescents
Authors: Romano Carla , Mayorga Margaret , Ruiz-Guiñazú Javier , Trudel Géralyn C. , Fehnel Sheri , McQuarrie Kelly , Chan Eric K. H. , Katz Eva G.
Published: January 2023

Background

The Symptoms of Infection with Coronavirus-19 (SIC) is a 30-item patient-reported outcome measure to evaluate the presence and severity of COVID-19 signs/symptoms in adults. This study expanded the context of use of the adult SIC among adolescents aged 12–17 years and supported a pediatric adaptation (the Pediatric SIC [PedSIC]) for caregiver assessment of signs/symptoms in children aged < 12 years.

Methods

Draft versions of the PedSIC and reference materials containing sign/symptom definitions for adolescents, based on an assessment of the reading level of SIC items by a professional linguist, were developed to facilitate accurate completion of the SIC by adolescents and observer-report (PedSIC) by caregivers. For adolescents, reference materials were intended to provide definitions for selected signs/symptoms identified to have a higher reading level. Iterative rounds of cognitive debriefing interviews were conducted from November 2020 to January 2021 to evaluate adolescent understanding of the SIC reference materials and inform refinement of the PedSIC for caregivers of children too young to reliably self-report. Participants were identified via databases of individuals who previously expressed interest in participating in qualitative research and were then screened for eligibility. Recruitment quotas were established to improve sample diversity. Thematic analysis and descriptive statistics were used to assess qualitative and demographic data, respectively.

Results

Nine healthy adolescents (mean [SD, range] age, 14 [1.76, 12–17] years, 56% female, 22% non-White; round 1, n = 6; round 2, n = 3) and 17 caregivers (mean [SD, range] age, 34 [6.28, 26–41] years, 59% female, 35% non-White; round 1, n = 9; round 2, n = 8) were interviewed. Adolescents understood the majority of signs/symptoms (22 of the 30 SIC items) without assistance or use of the reference materials during the cognitive debriefing interview. Definitions were added to the reference materials for 5 additional items, and clarifications provided to existing definitions for 3 items. Seven observer-report (PedSIC) items were modified following feedback from caregivers of healthy young children. Reference materials (similar to those for adolescent use) were developed to support caregiver understanding of the intent of the PedSIC items collecting input from children ages ≥ 5– < 12 years.

Conclusions

Results support using the SIC, PedSIC, and their associated reference materials to evaluate the presence and severity of COVID-19 signs/symptoms in adolescents and children aged < 12 years via caregiver-supported report, respectively.