bluuebunny/crossref_metadata_2025 huggingface dataset:
What are the impacts of setting up new medical schools? A narrative review
Authors: Hashem Ferhana , Marchand Catherine , Peckham Stephen , Peckham Anna
Published: November 2022

Background

The growth of the UK’s population together with an aging society with increasingly complex health and social care needs has placed a greater demand on statutory care services. In view of this emerging landscape, the UK Government has sought to increase its medically trained workforce in order to better respond to the demands placed on the health service. Five universities were announced as homes to new medical schools offering undergraduate places to boost the numbers of doctors training in England. The aim of this narrative review was to explore how new medical schools could improve the health outcomes of the local population and evaluate the potential contribution it may make to the local economy, workforce and to research and innovation.

Methods

A narrative review was undertaken using a systematic approach for the search literature strategy. The articles were evaluated by undertaking a critical assessment evaluating the fitness of a paper for review according to results, methods used to test the hypothesis, conclusions and impact and limitations. Thematic analysis was employed to organise and summarise the findings across a heterogeneous body of literature included in the review. The analysis was developed in an inductive manner and there were not any predefined themes to guide data extraction and analysis.

Results

Thirty-six articles were selected for inclusion for this narrative review. The review identified six key themes: influence of prior rural exposure, medical school environment and rural enrichment programmes, workforce, health outcomes of local populations, social accountability, economic contribution of medical schools to communities and impact on rural research.

Conclusions

The studies included found a wealth of information on a wide-range of topics on the expansion of undergraduate education and its implications on the future medical workforce. It was shown that medical schools can have a positive effect on the health, social, economic and research activity of a region, but this literature tended to be heterogeneous in focus without consideration of the inter-connections between the wider societal and economic impacts arising from long-term sustainable change being brought to a region.
Effect analysis of a virtual simulation experimental platform in teaching pulpotomy
Authors: Lu Jiaxuan , Yang Xin , Zhao Wei , Lin Jiacheng
Published: November 2022

Background

The experimental teaching of pediatric dentistry is a bridge between theoretical study and clinical practice, and virtual simulation technology provides a new method of instruction.

Methods

We built an experimental teaching platform using virtual simulation technology for vital pulpotomy that includes learning and examination modes. A total of 199 students majoring in stomatology in the fourth year at Sun Yat-Sen University were randomly divided into a control group (conventional teaching mode) and an experimental group (virtual simulation experimental teaching model). The teaching effect was evaluated by theoretical and experimental examination.

Results

We found that both the theoretical and experimental scores of the experimental group were higher than those of the control group, and the theoretical scores of the experimental group after exposure to the virtual simulation experimental teaching platform were also higher than those before the class, with significant differences (P < 0.05). Feedback from the experimental group after the class indicated that the platform reinforced their theoretical knowledge and greatly improved their mastery of operational skills.

Conclusions

The application of a virtual simulation experimental teaching platform can effectively improve the teaching of pulpotomy.
Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study
Authors: Wang Hua-Long , Tang Ran , Ren Ru-Jing , Dammer Eric B. , Guo Qi-Hao , Peng Guo-Ping , Cui Hai-Lun , Zhang You-Min , Wang Jin-Tao , Xie Xin-Yi , Huang Qiang , Li Jian-Ping , Yan Fu-Hua , Chen Sheng-Di , He Na-Ying , Wang Gang
Published: November 2022

Background

Language deficits frequently occur during the prodromal stages of Alzheimer’s disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD.

Methods

The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance.

Results

In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks.

Conclusions

PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.
The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis
Authors: Sajadi Manizheh , Fazilti Mohammad , Nazem Habibollah , Mahdevar Mohammad , Ghaedi Kamran
Published: November 2022

Introduction

Transcription factors (TFs) are essential for many biological processes and regulate the expression of several genes. This study’s objective was to analyze the abnormalities in TF expression, their impact on patient prognosis, and related pathways in colorectal cancer (CRC).

Method

The expression alterations of all TFs were investigated using the cancer genome atlas and GSE39582 data. Clinical data were also used to study the association between TFs expression and patient prognosis through the Cox regression test, and a predictive model of CRC patient survival was constructed based on TFs expression. Co-expression network was used to discover TF-related pathways. To validate the findings, the RT-qPCR method was applied to CRC samples and adjacent normal tissue.

Results

The findings revealed that ANKZF1, SALL4, SNAI1, TIGD1, LEF1, FOXS1, SIX4, and ETV5 expression levels increased in both cohorts and were linked to the poor prognosis. NR3C2, KLF4, CASZ1, FOXD2, ATOH1, SALL1, and RORC expression, on the other hand, exhibited a significant decrease, and their increase was related to the good prognosis of patients. The patient mortality risk model based on expression of mentioned TFs revealed that, independent of clinical characteristics, the expression of ANKZF1, LEF1, CASZ1, and ATOH1 could accurately predict patient survival rates. According to the co-expression network, increased transcription factors were linked to metastatic pathways, while decreasing TFs were involved to apoptotic pathways. RT-qPCR findings showed that FOXS1 expression was markedly overexpressed in CRC samples. However, in CRC samples, the expression of CASZ1 decreased.

Conclusion

In CRC, TFs expression of ANKZF1, LEF1, CASZ1 and ATOH1 are deregulated, which are associated with prognosis in patients. According to our findings, changes in the expression of the mentioned TFs have the potential to be considered diagnostic and prognostic biomarkers for CRC patients.
Social and structural determinants of emergency department use among Arab and Jewish patients in Jerusalem
Authors: Unger Shifra , Orr Zvika , Alpert Evan Avraham , Davidovitch Nadav , Shoham-Vardi Ilana
Published: November 2022

Background

A growing body of research demonstrates that economic conditions and racial and ethnic disparities result in excessive overuse of emergency departments (EDs) by a small group of socioeconomically marginalized residents. Knowledge and understanding of these issues on the part of the healthcare team can promote equality by providing structurally competent care. This study aims to identify the major social and structural factors related to patterns of ED visits by Arab and Jewish patients in Israel, where access to health services is covered by universal national health insurance.

Methods

A cross-sectional study was conducted using questionnaires of ED patients in a tertiary care medical center in Jerusalem. The hospital is the largest of the three EDs in Jerusalem with over 90,000 adult patient visits a year. The sample was stratified by ethnicity, including 257 Jewish patients and 170 Arab patients. The outcome variable was repeat visits for the same reason to the ED within 30 days.

Results

There were differences between Jewish and Arab patients’ social and structural characteristics, including health status, socioeconomic status, feeling of safety, and social support. There were also significant differences in some of the characteristics of health service utilization patterns, including ED repeat visits, language barriers when seeking healthcare in the community, and seeking information about medical rights. The variables associated with repeat visits were different between the two groups: among the Arab patients, repeat visits to the ED were associated with concerns about personal safety, whereas among the Jewish patients, they were associated with poverty.

Conclusion

The study illustrates the gaps that exist between the Arab and Jewish population in Israel. The findings demonstrated significant differences between populations in both health status and access to health services. In addition, an association was found in each ethnic group between different structural factors and repeat ED requests. This study supports previous theories and findings of the relationship between structural and social factors and patterns of health services utilization.
Disruptions to U.S. local public health’s role in population-based substance use prevention and response during COVID-19
Authors: Hall Kellie , Higgins Francis , Beach Karla Feeser , Diriba Kabaye , Sladky Mandy , McCall Timothy C.
Published: November 2022

Background

COVID-19 dramatically limited the scale and scope of local health department (LHD) work, redirecting resources to the response. However, the need for essential public health services—including substance use prevention—was not reduced.

Methods

We examined six quantitative data sources, collected between 2016 and 2021, to explore the impact of the COVID-19 pandemic on LHD substance use-related services.

Results

Before the pandemic, the proportion of LHDs providing some level of substance use prevention services was increasing, and many were expanding their level of provision. During the pandemic, 65% of LHDs reduced their level of substance use-related service provision, but the proportion of LHDs providing some level of services remained steady from prior to COVID-19.

Conclusion

We discuss policy recommendations to mitigate the risk of service disruptions during future public health emergencies, including direct and flexible funding for LHDs and federal directives declaring substance use prevention services as essential.
Comprehensive clinical evaluation of TomoEQA for patient-specific pre-treatment quality assurance in helical tomotherapy
Authors: Kim Changhwan , Han Min Cheol , Lee Young Kyu , Shin Han-Back , Kim Hojin , Kim Jin Sung
Published: November 2022

Background

Based on a previous study on the feasibility of TomoEQA, an exit detector-based patient-specific pre-treatment quality assurance (QA) method for helical tomotherapy, an in-depth clinical evaluation was conducted.

Methods

Data of one hundred patients were analyzed to evaluate the clinical usefulness of TomoEQA for patient-specific pre-treatment QA in comparison with the conventional phantom-based method. Additional investigations were also performed under unusual measurement conditions to validate the off-axis region. In addition to the clinical evaluation of TomoEQA, a statistical analysis was conducted to determine the plan parameters that affect the pass/failure results of pre-treatment QA.

Results

The average and standard deviations of the gamma passing rate and point dose error for TomoEQA were comparable to those of the conventional QA method. For TomoEQA, the average values of the gamma passing rate and point dose error were 96.32% (standard deviation (1 sigma) = 3.94; 95% confidence interval (CI), 95.55 to 97.09) and − 1.12% (standard deviation (1 sigma) = 1.04; CI, − 1.32 to − 0.92), respectively. For the conventional QA method, the average values of the gamma passing rate and point dose error were 95.95% (standard deviation (1 sigma) = 4.35; 95% confidence interval (CI), 95.10 to 96.80) and − 1.20% (standard deviation (1 sigma) = 1.61; CI, − 1.52 to − 0.88), respectively. Further experiments on the off-axis region demonstrated that TomoEQA can provide accurate results for 3D dose analysis, which is inherently difficult in the conventional QA method. Through a statistical analysis based on the results of TomoEQA, it was validated that the total fraction (Total Fx), monitor units, beam-on-time, leaf-of-time below 100 ms, and planning target volume diameter were statistically significant for the pass/failure of the pre-treatment QA results.

Conclusions

TomoEQA is a clinically beneficial alternative to the conventional phantom-based QA method.
Hand surgery and hand therapy clinical practice guideline for epidermolysis bullosa
Authors: Box Rachel , Bernardis Catina , Pleshkov Alexander , Jessop Nicky , Miller Catherine , Skye Jennifer , O’Brien Virginia , Veerkamp Matthew , da Rocha Anna Carolina Ferreira , Cornwall Roger
Published: November 2022

What is already known about this topic?

Epidermolysis bullosa (EB) causes blistering and scarring of the hands resulting in contractures fused web spaces and altered function. Surgery is needed to release contractures and web spaces and hand therapy is essential to maintain results, approaches for both differ.

What does this study add?

These guidelines aim to provide information on the surgical and conservative therapeutic hand management of children and adults diagnosed with EB. They are based on available evidence and expert consensus to assist hand surgeons and therapists in decision making, planning and treatment. They highlight the importance of a holistic multidisciplinary team (MDT) approach, where patient priorities are paramount.
Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study
Authors: Briegel Josef , Möhnle Patrick , Keh Didier , Lindner Johanna M. , Vetter Anna C. , Bogatsch Holger , Lange Dorothea , Frank Sandra , Hinske Ludwig C. , Annane Djillali , Vogeser Michael ,   SepNet Critical Care Trials Group, Bauer Michael , Brenner Thorsten , Meybohm Patrick , Weigand Markus , Gründling Matthias , Löffler Markus , Kiehntopf Michael , Bloos Frank , Elke Gunnar , Meersch-Dini Melanie , Putensen Christian , Kaasch Achim , Kluge Stefan
Published: November 2022

Rationale

Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.

Objectives

We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.

Methods

An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality.

Measurements and main results

Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality.

Conclusions

In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death.

Trial registration Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254.
Mapping responsive genomic elements to heat stress in a maize diversity panel
Authors: Liang Zhikai , Myers Zachary A. , Petrella Dominic , Engelhorn Julia , Hartwig Thomas , Springer Nathan M.
Published: November 2022

Background

Many plant species exhibit genetic variation for coping with environmental stress. However, there are still limited approaches to effectively uncover the genomic region that regulates distinct responsive patterns of the gene across multiple varieties within the same species under abiotic stress.

Results

By analyzing the transcriptomes of more than 100 maize inbreds, we reveal many cis- and trans-acting eQTLs that influence the expression response to heat stress. The cis-acting eQTLs in response to heat stress are identified in genes with differential responses to heat stress between genotypes as well as genes that are only expressed under heat stress. The cis-acting variants for heat stress-responsive expression likely result from distinct promoter activities, and the differential heat responses of the alleles are confirmed for selected genes using transient expression assays. Global footprinting of transcription factor binding is performed in control and heat stress conditions to document regions with heat-enriched transcription factor binding occupancies.

Conclusions

Footprints enriched near proximal regions of characterized heat-responsive genes in a large association panel can be utilized for prioritizing functional genomic regions that regulate genotype-specific responses under heat stress.
Does additional extracorporeal shock wave therapy improve the effect of isolated percutaneous radiofrequency coblation in patients with insertional Achilles tendinopathy? Study protocol for a randomized controlled clinical trial
Authors: Song Yu-Jie , Xuan Wen-Kai , Hua Ying-Hui
Published: November 2022

Background

No conclusive evidence recommends a prior treatment for insertional Achilles tendinopathy (IAT). It is theorized that both percutaneous radiofrequency coblation and extracorporeal shockwave therapy (ESWT) relieve pain within the insertion. However, no clinical evidence shows that either treatment promotes the regeneration of the tendon or if the combination of these 2 interventions offers better function and less pain than one therapy.

Methods

The study is a randomized, controlled trial with patients allocated in a 1:1 ratio to one of two parallel groups. Patients with insertional Achilles tendinopathy who are not satisfied with the effect of conservative treatment will be screened. A minimum of 38 patients will be enrolled after deciding to participate in the trial on an informed basis. Then the intervention group and the control group perform radial ESWT and sham-ESWT respectively at 6 months after percutaneous radiofrequency coblation. The primary outcome will be the Victorian Institute of Sports Assessment Achilles (VISA-A) Score. Secondary outcome measures will be Foot and Ankle Outcome Score (FAOS) scale, visual analog scale (VAS), Tegner Score, and MRI ultra-short echo time (UTE) T2* value. The assessments will occur in 6 months, 1 year, and 2 years, post-operatively. The differences between the 2 groups will be conducted as intention-to-treat basis.

Discussion

We aim to investigate if radiofrequency coblation associated with ESWT can provide more encouraging imaging findings as well as functional and clinical outcomes regarding the treatment of the IAT comparing to the single radiofrequency coblation treatment.

Trial registration

ChiCTR1800017898; pre-results. Registered on 20 August 2018.
Cross-cultural adaptation and validation of the Kerlan-Jobe Orthopaedic Clinic shoulder and elbow score in Finnish-speaking overhead athletes
Authors: Sukanen Maria , Pajari Jesse , Äyrämö Sami , Paloneva Juha , Waller Benjamin , Häkkinen Arja , Multanen Juhani
Published: November 2022

Background

The Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score (KJOC) is developed to evaluate the shoulder and elbow function in overhead athletes. To date, the score has not been adapted into Finnish language. The aim of this study was to perform a cross-cultural adaptation of the Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow score (KJOC) into Finnish language and evaluate its validity, reliability, and responsiveness in overhead athletes.

Methods

Forward–backward translation method was followed in the cross-cultural adaptation process. Subsequently, 114 overhead athletes (52 males, 62 females, mean age 18.1 ± 2.8 years) completed the Finnish version of KJOC score, Disabilities of the Arm, Shoulder and Hand (DASH), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) and RAND-36 to assess validity of the KJOC score. To evaluate reliability and responsiveness, the participants filled in the KJOC score 16 days and eight months after the first data collection. Validity, reliability, and responsiveness of the Finnish KJOC score were statistically tested.

Results

Minor modifications were made during the cross-cultural translation and adaptation process, which were related to culture specific terminology in sports and agreed by an expert committee. Construct validity of the KJOC score was moderate to high, based on the correlations with DASH (r = − 0.757); DASH sports module (r = − 0.667); ASES (r = 0.559); and RAND-36 (r = 0.397) questionnaires. Finnish KJOC score showed excellent internal consistency (α = 0.92) and good test–retest reliability (2-way mixed-effects model ICC = 0.77) with acceptable measurement error level (SEM 5.5; MDC 15.1). Ceiling effect was detected for asymptomatic athletes in each item (23.2–61.1%), and for symptomatic athletes in item 5 (47.4%). Responsiveness of the Finnish KJOC score could not be confirmed due to conflicting follow-up results.

Conclusion

The Finnish KJOC score was found to be a valid and reliable questionnaire measuring the self-reported upper arm status in Finnish-speaking overhead athletes.
Spatio-temporal forecasting of future volcanism at Harrat Khaybar, Saudi Arabia
Authors: Alohali Abdullah , Bertin Daniel , de Silva Shanaka , Cronin Shane , Duncan Robert , Qaysi Saleh , Moufti Mohammed R.
Published: November 2022

The 180,000 km2 of Arabian lava fields (“harrats” in Arabic) form one of the largest distributed basaltic provinces in the world. The most recent eruption in 1256 AD, on the outskirts of Medina, as well as shallow dike emplacement in 2009, ~ 200 km northeast of the city, suggest future volcanic threat to this area. Harrat Khaybar (~ 1.7 Ma to present) is one of the largest and most compositionally diverse Arabian lava fields; it is located ~ 137 km northeast of Medina and covers ~ 14,000 km2. Here, we present a new eruption event record and the first estimation of future potential locations and timing of volcanism in Harrat Khaybar. Volcanic vents and eruptive fissures were mapped using remote sensing and field studies, and categorized into a geospatial database, complemented by 16 new 40Ar/39Ar ages. Our analysis reveals that Harrat Khaybar developed over five eruptive phases, where vent locations over time focus towards the central axis forming a broad N-S trend, with a central group concentrated along an axis of the regional Makkah-Madinah-Nafud (MMN) line and wider spatial dispersion between vents outwards from there. For the whole field, we estimate a long-term average recurrence rate of ~ 2.3 eruptions per 10 kyr assuming a Poisson distribution for inter-event times, which indicates that Harrat Khaybar would belong to a global group of highly active distributed volcanic fields. Our analysis also reveals that the field likely had a “flare-up” period between 450 and 300 ka where the vast majority of eruptions occurred, with ~ 18 eruptions per 10 kyr. After this intense period, eruption rates fell to < 2 eruptions per 10 kyr. Based on our findings, we estimate cumulative probabilities of 1.09 and 16.3% as lower and upper bounds of at least one eruption occurring over the next 100 years somewhere in Harrat Khaybar, with the highest probabilities within the central axis region, in particular around Jabal Qidr, Bayda and Abyad.
Adoption of improved cook stoves by households in informal settlements of Woreda 12, Yeka subcity, Addis Ababa
Authors: Kebede Nibretu , Tolossa Degefa , Tefera Tamirat
Published: November 2022

Background

This study analyzed the factors affecting the use of improved cook stoves (ICS) in informal settlements of Addis Ababa based on the data generated from 450 households drawn fromWoreda(Woredais a local term used to describe the lowest administrative unit of Addis Ababa City Administration, Ethiopia.) 12 ofYeka subcity.It examined the interactive effect of households’ socio-economic backgrounds and energy sources on the adoption of ICS. The data were analyzed using descriptive methods and the multinomial logit model.

Results

Demographic and economic factors such as sex of the household head,[Household head is the one who has an income and decision-making power in family affairs (a husband for married people)], family size and family income have no relationships with households’ ICS use while education level, number of years lived in the area, type of home owned, and stove-operating costs have a significant influence on the choice of an ICS. Households that live in a good home (made from wood and cement) used moreMirt(Mirtis an improved firewood stove mainly used to bakeInjeraand bread.) andLakech[Lakechalso calledTikikilis an improved charcoal stove used to cook different kinds of dishes (non-Injera)] stoves than the traditional three-stone stoves. On the other hand, household heads with higher levels of education and who have lived more than 7 years in the area in a better home owned more ICS than the traditional three-stone stoves.

Conclusions

The availability, affordability, durability and simplicity to operate stoves, and subsidies affect the choice of an ICS. Energy sources that are commonly used by households in informal settlements also have a strong influence on the choice of energy-efficient stoves. Compared to ICS, heavy use of traditional three-stone stoves by households that already have access to electricity, directs government policies to focus on providing reliable electric service and subsidize those using ICS.
Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine
Authors: Agrawal Ira , Lim Yong Shan , Ng Shi-Yan , Ling Shuo-Chien
Published: November 2022

Lipids, defined by low solubility in water and high solubility in nonpolar solvents, can be classified into fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols. Lipids not only regulate integrity and fluidity of biological membranes, but also serve as energy storage and bioactive molecules for signaling. Causal mutations in SPTLC1 (serine palmitoyltransferase long chain subunit 1) gene within the lipogenic pathway have been identified in amyotrophic lateral sclerosis (ALS), a paralytic and fatal motor neuron disease. Furthermore, lipid dysmetabolism within the central nervous system and circulation is associated with ALS. Here, we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS pathogenesis. Among the different lipids, accumulation of ceramides, arachidonic acid, and lysophosphatidylcholine is commonly emerging  as detrimental to motor neurons. We end with exploring the potential ALS therapeutics by reducing these toxic lipids.
Methylome and transcriptome data integration reveals potential roles of DNA methylation and candidate biomarkers of cow Streptococcus uberis subclinical mastitis
Authors: Wang Mengqi , Bissonnette Nathalie , Laterrière Mario , Dudemaine Pier-Luc , Gagné David , Roy Jean-Philippe , Zhao Xin , Sirard Marc-André , Ibeagha-Awemu Eveline M.
Published: November 2022

Background

Mastitis caused by different pathogens includingStreptococcus uberis(S. uberis) is responsible for huge economic losses to the dairy industry. In order to investigate the potential genetic and epigenetic regulatory mechanisms of subclinical mastitis due toS. uberis, the DNA methylome (whole genome DNA methylation sequencing) and transcriptome (RNA sequencing) of milk somatic cells from cows with naturally occurringS. uberissubclinical mastitis and healthy control cows (n = 3/group) were studied.

Results

Globally, the DNA methylation levels of CpG sites were low in the promoters and first exons but high in inner exons and introns. The DNA methylation levels at the promoter, first exon and first intron regions were negatively correlated with the expression level of genes at a whole-genome-wide scale. In general, DNA methylation level was lower inS. uberis-positive group (SUG) than in the control group (CTG). A total of 174,342 differentially methylated cytosines (DMCs) (FDR < 0.05) were identified between SUG and CTG, including 132,237, 7412 and 34,693 DMCs in the context of CpG, CHG and CHH (H = A or T or C), respectively. Besides, 101,612 methylation haplotype blocks (MHBs) were identified, including 451 MHBs that were significantly different (dMHB) between the two groups. A total of 2130 differentially expressed (DE) genes (1378 with up-regulated and 752 with down-regulated expression) were found in SUG. Integration of methylome and transcriptome data with MethGET program revealed 1623 genes with significant changes in their methylation levels and/or gene expression changes (MetGDE genes, MethGETP-value < 0.001). Functional enrichment of genes harboring ≥ 15 DMCs, DE genes and MetGDE genes suggest significant involvement of DNA methylation changes in the regulation of the host immune response toS. uberisinfection, especially cytokine activities. Furthermore, discriminant correlation analysis with DIABLO method identified 26 candidate biomarkers, including 6 DE genes, 15 CpG-DMCs and 5 dMHBs that discriminated between SUG and CTG.

Conclusion

The integration of methylome and transcriptome of milk somatic cells suggests the possible involvement of DNA methylation changes in the regulation of the host immune response to subclinical mastitis due toS. uberis. The presented genetic and epigenetic biomarkers could contribute to the design of management strategies of subclinical mastitis and breeding for mastitis resistance.
Nutrient dynamics in coral symbiosis depend on both the relative and absolute abundance of Symbiodiniaceae species
Authors: McIlroy Shelby E. , terHorst Casey P. , Teece Mark , Coffroth Mary Alice
Published: November 2022

Background

Symbionts provide a variety of reproductive, nutritional, and defensive resources to their hosts, but those resources can vary depending on symbiont community composition. As genetic techniques open our eyes to the breadth of symbiont diversity within myriad microbiomes, symbiosis research has begun to consider what ecological mechanisms affect the identity and relative abundance of symbiont species and how this community structure impacts resource exchange among partners. Here, we manipulated the in hospite density and relative ratio of two species of coral endosymbionts (Symbiodinium microadriaticum and Breviolum minutum) and used stable isotope enrichment to trace nutrient exchange with the host, Briareum asbestinum.

Results

The patterns of uptake and translocation of carbon and nitrogen varied with both density and ratio of symbionts. Once a density threshold was reached, carbon acquisition decreased with increasing proportions of S. microadriaticum. In hosts dominated by B. minutum, nitrogen uptake was density independent and intermediate. Conversely, for those corals dominated by S. microadriaticum, nitrogen uptake decreased as densities increased, and as a result, these hosts had the overall highest (at low density) and lowest (at high density) nitrogen enrichment.

Conclusions

Our findings show that the uptake and sharing of nutrients was strongly dependent on both the density of symbionts within the host, as well as which symbiont species was dominant. Together, these complex interactive effects suggest that host regulation and the repression of in hospite symbiont competition can ultimately lead to a more productive mutualism.
The social representation of fintech from the perspective of traditional financial sector professionals: evidence from Brazil
Authors: Joia Luiz Antonio , Proença Rodrigo
Published: November 2022

This study aims to reveal the social representation of fintech from the perspective of traditional financial sector professionals in Brazil—herein used as a proxy for emerging markets—to interpret and compare it with the scientific literature on the concept of fintech. To achieve this, we applied the social representations theory associated with the word evocation test, similarity analysis, and descending hierarchical classification. After analyzing the results, we perceived a partial misalignment between the existing literature on the concept of fintech and the perspective of traditional financial sector professionals concerning this construct. In contrast to the literature surveyed, the respondents lack perception regarding the potential of fintech to constitute disruptive technology for the traditional financial sector—radically transforming or even eliminating it. In addition, traditional financial sector professionals have little insight into the potential of fintech to financially include the low-income population, owing to their lower costs and greater ease of use. Finally, traditional financial sector professionals failed to appreciate the need to develop a legal and regulatory framework for the performance of fintech in emerging markets. This is a subject that has also been scantly addressed by academia.
Reading approaches practiced in EFL classrooms: a narrative review and research agenda
Authors: Ali Zulfiquar , Palpanadan Sarala Thulasi , Asad Muhammad Mujtaba , Churi Prathamesh , Namaziandost Ehsan
Published: November 2022

Reading is an essential skill for students to perform effectively and successfully in any academic setting. This skill is vital for foreign language learners as it provides chances for students to be exposed to English in input-poor settings. English as a foreign language students’ reading skills in diverse contexts remain substandard due to the lack of necessary input and efficient instructional methodologies. Thus, we review the literature on three common reading instructional approaches: the intensive reading (IR) approach, the extensive reading (ER) approach, and the blended IR and ER approach. This review summarizes the existing literature on IR, ER, and blended IR and ER and provides the critical appraisal of existing scholarly literature from several aspects, including reading approach, research design, research context, data analysis method, and the results of various studies of reading approaches. Finally, we present several future research directions in the field of reading research.
Platinum-Free Systemic Therapy in First-Line Metastatic Urothelial Carcinoma: Mirage or Oasis in the Platinum Desert?
Authors: Plimack Elizabeth R. , Zibelman Matthew R.
Published: November 2022

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series was to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

The systemic treatment for metastatic urothelial carcinoma has evolved over the past decade; however, changes in the first-line setting have remained elusive and dependent on platinum-based chemotherapy regimens. Hoimes et al now present an update on the results of cohort A of the EV-103 phase Ib/II trial combining enfortumab vedotin and pembrolizumab in the first-line setting for patients with cisplatin-ineligible metastatic urothelial carcinoma. The efficacy results in this small, phase I cohort demonstrate an impressive response rate with the majority of patients deriving benefit in tumor control. In conjunction with the results from cohort K of EV-103, recently reported at the 2022 ESMO Congress, there is much anticipation regarding this combination as a future standard of care. However, despite this combination not including a traditional cytotoxic chemotherapeutic, it is still associated with potentially life-altering treatment-related toxicity, most notably rash and peripheral neuropathy, along with the risks of immune-related adverse events, which will need to be carefully calibrated for patients.
Effects of Coenzyme Q10 Supplementation on Lipid Profiles in Adults: A Meta-analysis of Randomized Controlled Trials
Authors: Liu Zhihao , Tian Zezhong , Zhao Dan , Liang Ying , Dai Suming , Liu Meitong , Hou Shanshan , Dong Xiaoxi , Zhaxinima  , Yang Yan
Published: November 2022

Context

Previous meta-analyses have suggested that the effects of coenzyme Q10 (CoQ10) on lipid profiles remain debatable. Additionally, no meta-analysis has explored the optimal intake of CoQ10 for attenuating lipid profiles in adults.

Objective

This study conducted a meta-analysis to determine the effects of CoQ10 on lipid profiles and assess their dose–response relationships in adults.

Methods

Databases (Web of Science, PubMed/Medline, Embase, and the Cochrane Library) were systematically searched until August 10, 2022. The random effects model was used to calculate the mean differences (MDs) and 95% CI for changes in circulating lipid profiles. The novel single-stage restricted cubic spline regression model was applied to explore nonlinear dose–response relationships.

Results

Fifty randomized controlled trials with a total of 2794 participants were included in the qualitative synthesis. The pooled analysis revealed that CoQ10 supplementation significantly reduced total cholesterol (TC) (MD −5.53 mg/dL; 95% CI −8.40, −2.66; I2 = 70%), low-density lipoprotein cholesterol (LDL-C) (MD −3.03 mg/dL; 95% CI −5.25, −0.81; I2 = 54%), and triglycerides (TGs) (MD −9.06 mg/dL; 95% CI −14.04, −4.08; I2 = 65%) and increased high-density lipoprotein cholesterol (HDL-C) (MD 0.83 mg/dL; 95% CI 0.01, 1.65; I2 = 82%). The dose–response analysis showed an inverse J-shaped nonlinear pattern between CoQ10 supplementation and TC in which 400-500 mg/day CoQ10 largely reduced TC (χ2 = 48.54, P < .01).

Conclusion

CoQ10 supplementation decreased the TC, LDL-C, and TG levels, and increased HDL-C levels in adults, and the dosage of 400 to 500 mg/day achieved the greatest effect on TC.
Pharmacological inhibition of the acetyltransferase Tip60 mitigates myocardial infarction injury
Authors: Wang Xinrui , Wan Tina C. , Kulik Katherine R. , Lauth Amelia , Smith Brian C. , Lough John W. , Auchampach John A.
Published: November 2022

Pharmacologic strategies that target factors with both pro-apoptotic and anti-proliferative functions in cardiomyocytes (CMs) may be useful for the treatment of ischemic heart disease. One such multifunctional candidate for drug targeting is the acetyltransferase Tip60, which is known to acetylate both histone and non-histone protein targets that have been shown in cancer cells to promote apoptosis and to initiate the DNA damage response, thereby limiting cellular expansion. Using a murine model, we recently published findings demonstrating that CM-specific disruption of the Kat5 gene encoding Tip60 markedly protects against the damaging effects of myocardial infarction (MI). In the experiments described here, in lieu of genetic targeting, we administered TH1834, an experimental drug designed to specifically inhibit the acetyltransferase domain of Tip60. We report that, similar to the effect of disrupting the Kat5 gene, daily systemic administration of TH1834 beginning 3 days after induction of MI and continuing for 2 weeks of a 4-week timeline resulted in improved systolic function, reduced apoptosis and scarring, and increased activation of the CM cell cycle, effects accompanied by reduced expression of genes that promote apoptosis and inhibit the cell cycle and reduced levels of CMs exhibiting phosphorylated Atm. These results support the possibility that drugs that inhibit the acetyltransferase activity of Tip60 may be useful agents for the treatment of ischemic heart disease.
Debt Revenue and the Sustainability of Public Debt
Authors: Reis Ricardo
Published: November 2022

While public debt has risen in the last two decades, the return that it offers to investors has fallen, especially relative to the return on private investment. This creates a revenue for the government as the supplier of the special services offered by public bonds, which include storage of value, safety, liquidity, and reprieve from repression. The present value of this debt revenue is large relative to the stock of public debt, keeping it sustainable even as the present value of primary balances is zero or negative. It gives rise to different policy tradeoffs than the conventional analysis of primary balances and makes different recommendation on the effects of austerity, the optimal amount of debt, or the spillovers between monetary and fiscal policy.
Emerging Market Sovereign Debt in the Aftermath of the Pandemic
Authors: Rogoff Kenneth
Published: November 2022

For emerging markets, fiscal space is a very real constraint that can surface under a variety of circumstances, including rising world interest rates, falling commodity prices, or a global recession. Some emerging markets, and the majority of low-income developing economies, are already in debt distress or default. Near-term, making sure that troubled debtor countries are aware of the full menu of options, including heterodox strategies such as default, is important. Longer-term, a rethink of the Bretton Woods financial institutions to incorporate a greater emphasis on outright grants instead of loans, makes more sense than ever.
Is There Any Future for a US Labor Movement?
Authors: Naidu Suresh
Published: November 2022

A recent flurry of labor movement activity has been driven by younger workers, tight labor markets, and a sympathetic federal government. Nonetheless, US union density remains low, even as unions remain popular. This is because employer opposition and US labor law together imply that workers need to overcome substantial collective action problems at work in order to win union recognition and collective bargaining agreements. These barriers make dense social networks and high levels of social capital at work a prerequisite for unionization. Labor organizing can build this social capital, but faces an uphill battle without policy changes that extend collective bargaining across employers and up the value-chain and make unionization easier. Partnering with labor unions, researchers can study theoretical problems of collective action while also getting a window into what strategies of a renewed labor movement may work.
Iterative reconstruction vs deep learning image reconstruction: comparison of image quality and diagnostic accuracy of arterial stenosis in low-dose lower extremity CT angiography
Authors: Qu Tingting , Guo Yinxia , Li Jianying , Cao Le , Li Yanan , Chen Lihong , Sun Jingtao , Lu Xueni , Guo Jianxin
Published: November 2022

Objective

To compare image quality and diagnostic accuracy of arterial stenosis in low-dose lower-extremity CT angiography (CTA) between adaptive statistical iterative reconstruction-V (ASIR-V) and deep learning image reconstruction (DLIR) algorithms.

Methods

46 patients undergoing low-dose lower-extremity CTA were enrolled. Images were reconstructed using ASIR-V (blending factor of 50% (AV-50) and 100% (AV-100)) and DLIR (medium (DL-M), and high (DL-H)). CT values and standard deviation of the aorta, psoas, popliteal artery, popliteal and ankle muscles were measured. The edge-rise distance and edge-rise slope were calculated. The degrees of granularity and edge blurring were assessed using a 5-point scale. The stenosis degrees were measured on the four reconstructions, and their mean square errors against that of digital subtraction angiography were calculated and compared.

Results

For both ASIR-V and DLIR, higher reconstruction intensity generated lower noise and higher signal-to-noise ratio and contrast-to-noise ratio values. The standard deviation values in AV-100 images were significantly lower than other reconstructions. The two DLIR image groups had higher edge-rise slope and lower edge-rise distance (DL-M:1.79 ± 0.37 mm and DL-H:1.82 ± 0.38 mm vs AV-50:1.96 ± 0.39 mm and AV-100:2.01 ± 0.36 mm, p = 0.014) than ASIR-V images. The overall image quality of DLIR was rated higher than ASIR-V (DL-M:0.83 ± 0.61, DL-H:0.41 ± 0.62, AV-50:1.85 ± 0.60 and AV-100:2.37 ± 0.77, p < 0.001), with DL-H having the highest overall image quality score. For stenosis measurement, DL-H had the lowest mean-square-errors compared to digital subtraction angiography among all reconstruction groups.

Conclusion

DLIR images had higher image quality ratings with lower image noise and sharper vessel walls in low-dose lower-extremity CTA, and DL-H provides the best overall image quality and highest accuracy in diagnosing artery stenoses.

Advances in knowledge:

DLIR provides high-quality images with sharper edges compared to ASIR-V during low-dose CTA of lower extremity arteries, and DLIR (high) provides the best overall image quality and highest accuracy in diagnosing artery stenoses among all reconstruction algorithms (ASIR-V and DLIR). ASIR-V with blending factor of 100% has the strongest noise reduction ability among all reconstruction algorithms (ASIR-V and DLIR); however, it generates the most blurred images.