bluuebunny/crossref_metadata_2025 huggingface dataset:
Proliferation of Bifidobacterium L80 under different proportions of milk protein hydrolysate
Authors: Wang Bing , Yang Yang , Bian Xin , Guan Hua-nan , Liu Lin-lin , Li Xue-xia , Guo Qing-qi , Piekoszewski Wojciech , Chen Feng-lian , Wu Na , Ma Zhan-qian , Shi Yan-guo , Zhang Na
Published: November 2021

The intestinal microecological environment is critical to an infant's growth. For those infants consuming milk power, it is very important to improve the intestinal microecological environment to promote the healthy growth of infants. In this paper, Milk protein hydrolysate (MPH), consisting of different proportions of proteins and small molecule peptides (5:5, 4:6, 3:7, 2:8, 1:9) were added to infant formula powder (IFP). The effects of MFP-enriched IFP addition on proliferation and metabolism of Bifidobacterium L80 were studied. Compared with MPH-free IFP, MFP-enriched IFP with 1:9 of proteins to small molecule peptides significantly enhanced the proliferation of Bifidobacterium L80, resulting in higher cell density, greater viable counts and higher titratable acidity. MFP-enriched IFP increased the content of seven organic acids and H2O2 in the system, and improved the antibacterial activity to E. coli BL21. This study suggested that MPH could be an effective addition to infant formula powder to promote the growth of Bifidobacterium, so to improve the intestinal health of infants.
Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro
Authors: Xu Yu-Jie , He Min-Ke , Liu Shuang , Huang Li-Chang , Bu Xiao-Yun , Kan Anna , Shi Ming
Published: November 2021

Background

The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro.

Methods

The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro.

Results

IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P < 0.0001, 0.011, and 0.0068, respectively) with acceptable sensitivity and specificity. RCAN2 was inversely correlated with NK cell infiltration, and knockdown of RCAN2 promoted proliferation in HCC.

Conclusions

This study revealed the characteristics of the HCC SNV-associated subgroup and screened seven latent markers for their accuracy of prognosis. Additionally, RCAN2 was preliminarily proven to influence proliferation in HCC and it had a close relationship with NK cell infiltration in vitro. With the capability to predict HCC outcomes, the model constructed with seven key differentially expressed genes offers new insights into individual therapy.
Insights from modelling malaria vaccines for policy decisions: the focus on RTS,S
Authors: Galactionova Katya , Smith Thomas A. , Penny Melissa A.
Published: November 2021

Mathematical models are increasingly used to inform decisions throughout product development pathways from pre-clinical studies to country implementation of novel health interventions. This review illustrates the utility of simulation approaches by reviewing the literature on malaria vaccine modelling, with a focus on its link to the development of policy guidance for the first licensed product, RTS,S/AS01. The main contributions of modelling studies have been in inferring the mechanism of action and efficacy profile of RTS,S; to predicting the public health impact; and economic modelling mainly comprising cost-effectiveness analysis. The value of both product-specific and generic modelling of vaccines is highlighted.
Red blood cell blood group A antigen level affects the ability of heparin and PfEMP1 antibodies to disrupt Plasmodium falciparum rosettes
Authors: Hedberg Pontus , Sirel Madle , Moll Kirsten , Kiwuwa Mpungu Steven , Höglund Petter , Ribacke Ulf , Wahlgren Mats
Published: November 2021

Background

The histo-blood group ABO system has been associated with adverse outcomes in COVID-19, thromboembolic diseases and Plasmodium falciparum malaria. An integral part of the severe malaria pathogenesis is rosetting, the adherence of parasite infected red blood cells (RBCs) to uninfected RBCs. Rosetting is influenced by the host’s ABO blood group (Bg) and rosettes formed in BgA have previously been shown to be more resilient to disruption by heparin and shield the parasite derived surface antigens from antibodies. However, data on rosetting in weak BgA subgroups is scarce and based on investigations of relatively few donors.

Methods

An improved high-throughput flow cytometric assay was employed to investigate rosetting characteristics in an extensive panel of RBC donor samples of all four major ABO Bgs, as well as low BgA expressing samples.

Results

All non-O Bgs shield the parasite surface antigens from strain-specific antibodies towards P. falciparum erythrocyte membrane protein 1 (PfEMP1). A positive correlation between A-antigen levels on RBCs and rosette tightness was observed, protecting the rosettes from heparin- and antibody-mediated disruption.

Conclusions

These results provide new insights into how the ABO Bg system affects the disease outcome and cautions against interpreting the results from the heterogeneous BgA phenotype as a single group in epidemiological and experimental studies.

Graphical Abstract
Moderate-intensity treadmill running relieves motion-induced post-traumatic osteoarthritis mice by up-regulating the expression of lncRNA H19
Authors: Zhou Xuchang , Cao Hong , Wang Miao , Zou Jun , Wu Wei
Published: November 2021

Background

The purpose of this study was to explore whether moderate-intensity exercise can alleviate motion-induced post-traumatic osteoarthritis (PTOA) and the expression change of lncRNA H19 during this progression.

Methods

Twenty-week-old male C57BL/6 mice were randomly divided into five groups: model control group (MC group,n = 6), treadmill model group (M group,n = 6), rehabilitation control group (RC group,n = 6), treadmill model + rehabilitation training group (M + R group,n = 6) and treadmill model + convalescent group (M + C group,n = 6). Paraffin sections were used to observe the pathological changes in the mouse knee joint in each group. A micro-CT was used to scan the knee joint to obtain the morphological indexes of the tibial plateau bone. Real-time PCR was used to detect the mRNA levels of inflammatory factors, synthetic and catabolic factors in cartilage.

Results

After high-intensity exercise for 4 weeks, the inflammation and catabolism of the mouse knee cartilage were enhanced, and the anabolism was weakened. Further study showed that these results were partially reversed after 4-week moderate-intensity training. The results of hematoxylin–eosin staining confirmed this finding. Meanwhile, high-intensity exercise reduced the expression of lncRNA H19 in cartilage, while the expression of lncRNA H19 increased after 4 weeks of moderate-intensity exercise.

Conclusion

High-intensity treadmill running can cause injury to the knee cartilage in C57BL/6 mice which leads to PTOA and a decrease of lncRNA H19 expression in cartilage. Moderate-intensity exercise can relieve PTOA and partially reverse lncRNA H19 expression.
Selectively down-regulated PD-L1 by albumin-phenformin nanoparticles mediated mitochondrial dysfunction to stimulate tumor-specific immunological response for enhanced mild-temperature photothermal efficacy
Authors: Zhou Zaigang , Jiang Ning , Chen Jiashe , Zheng Chunjuan , Guo Yuanyuan , Ye Ruirong , Qi Ruogu , Shen Jianliang
Published: November 2021

Background

Mild-temperature photothermal therapy (mild-PTT) has emerged as a highly promising antitumor strategy by triggering immunogenic cell death (ICD) to elicit both innate and adaptive immune responses for tumor control. However, mild-PTT still leads to the risk of tumor recurrence or metastasis because it could hardly completely eradicate tumors due to its impaired immunological efficacy owing to the enhanced PD-L1 expression in tumor cells after treatment.

Results

In this study, we described a hydrogen peroxide (H2O2) responsive manganese dioxide mineralized albumin nanocomposite loading with mitochondria function inhibitor phenformin (PM) and near-infrared photothermal dye indocyanine green (ICG) by modified two-step biomineralization method. In combination with ICG induced mild-PTT and PM mediated mitochondria dysfunction, PD-L1 expression was obviously down-regulated and the generated immunological responses was able to effectively attack the remaining tumor cells. Meanwhile, the risk of tumor metastasis was effectively inhibited by reducing the expression of tumor invasion-related signal molecules (TGF-β and vimentin) after combining treatment.

Conclusion

Such a strategy offers novel insight into the development of nanomedicine for mild-PTT as well as cancer immunotherapy, which can provide protection against tumor relapse post elimination of their initial and metastatic tumors.

Graphical Abstract
The impact of shelf tags with Nutri-Score on consumer purchases: a difference-in-difference analysis of a natural experiment in supermarkets of a major retailer in Belgium
Authors: Vandevijvere Stefanie , Berger Nicolas
Published: November 2021

Background

Delhaize, a major Belgian retailer, started implementing electronic shelf labels (ESL) with Nutri-Score since May 2019. Nutri-Score rates the healthfulness of packaged foods with five colours/letters from red/E (least healthy) to green/A (most healthy). This study evaluated the impact of ESL on consumer purchases, overall, and by food category.

Methods

For 43 intervention stores (implementing ESL in the period 27 May 2019–19 June 2019), a control store, from the same province and retailer-assigned cluster was matched. There were 14 unique control stores. By store, weekly non-food and food sales for 2018 and 2019 were received by Nutri-Score (A/B/C/D/E) and food category according to a retailer-assigned classification system. The primary outcomes were the proportion of food sales for Nutri-Score A,B,C,D,E. Difference-in-differences regression analysis was conducted to estimate the effect of the ESL intervention on proportion of overall food and food category sales for Nutri-Score A,B,C,D,E, using linear mixed models to account for clustering at store-level. We controlled for store characteristics (region, cluster, non-food sales) and week of the year. Analyses were weighted to re-balance discrepancy between the number of intervention and control stores. To account for multiple testing, a Bonferroni adjustment was applied.

Results

Comparing pre- and post-intervention periods, difference-in-differences for the proportion of Nutri-Score B and C product sales were more favourable in intervention than control stores (0.11 ± 0.04%, p = 0.007 and − 0.06 ± 0.03%, p = 0.026 respectively), while difference-in-differences for the proportion of Nutri-Score D product sales were less favourable in intervention than control stores (0.12 ± 0.04%, p = 0.002). For 17/58 food categories (representing 29% of total food sales) a positive impact [increase in healthier (Nutri-Score A, B) and/or decrease in less healthy (Nutri-Score D, E) food sales], and for 16/58 categories (representing 24% of total food sales) a negative impact was found. Positive impacts were found for vegetable, fruit and dairy products and confectionery. Negative impacts were found for bread and bakery products.

Conclusion

The impact of ESL on consumer purchases was mixed. Favourable difference-in-differences were found for Nutri-Score B and C products and unfavourable difference-in-differences for Nutri-Score D products. Shelf labeling on its own is unlikely to significantly influence consumer behaviours.
FUSE binding protein FUBP3 is a potent regulator in Japanese encephalitis virus infection
Authors: Xu Peng , Tong Wei , Chen Young-Mao
Published: November 2021

Background

The JEV genome is a positive-sense RNA with a highly structured capped 5′UTR, 3′UTR and a large open reading frame. 3′UTR is the untranslated region of flavivirus and has various important functions during viral replication, such as translation, replication and encapsidation. During viral replication, the 3′UTR interacts with viral proteins and host proteins and is required for viral RNA replication and translocation.

Methods

The expression level of FUBP3 was knocked down by siRNA and Flag-tagged FUBP3 overexpression plasmid was constructed for overexpression. BHK-21 cells were cultured and infected with JEV to investigate the functional role of FUBP3 in the viral infection cycle. Subcellular localization of FUBP3 and viral replication complexes was observed by dual immunofluorescence staining.

Results

Four host proteins were specifically associated with the 3′UTR of JEV, and FUBP3 was selected to further investigate its potential functional role in the JEV infection cycle. Knockdown of FUBP3 protein resulted in a significant decrease in JEV viral titer, whereas ectopic overexpression of FUBP3 resulted in increased JE viral infectivity. In cells stably knocked down for FUBP3 and then infected with JEV, we found almost no detectable viral NS5 protein. In contrast, when cells stably knocking-down of FUBP3 overexpressed FUBP3, we found a significant increase in viral RNA production over time compared to controls. We also demonstrated that FUBP3 re-localized in the cytoplasm after infection with JEV and co-localized with viral proteins. Exogenous overexpression of FUBP3 was also shown to be located in the JE replication complex and to assist viral replication after JEV infection.

Conclusions

The overall results suggest that FUBP3 regulates RNA replication of JEV and promotes subsequent viral translation and viral particle production.
Scientific evidence based rare disease research discovery with research funding data in knowledge graph
Authors: Zhu Qian , Nguyễn Ðắc-Trung , Sheils Timothy , Alyea Gioconda , Sid Eric , Xu Yanji , Dickens James , Mathé Ewy A. , Pariser Anne
Published: November 2021

Background

Limited knowledge and unclear underlying biology of many rare diseases pose significant challenges to patients, clinicians, and scientists. To address these challenges, there is an urgent need to inspire and encourage scientists to propose and pursue innovative research studies that aim to uncover the genetic and molecular causes of more rare diseases and ultimately to identify effective therapeutic solutions. A clear understanding of current research efforts, knowledge/research gaps, and funding patterns as scientific evidence is crucial to systematically accelerate the pace of research discovery in rare diseases, which is an overarching goal of this study.

Methods

To semantically represent NIH funding data for rare diseases and advance its use of effectively promoting rare disease research, we identified NIH funded projects for rare diseases by mapping GARD diseases to the project based on project titles; subsequently we presented and managed those identified projects in a knowledge graph using Neo4j software, hosted at NCATS, based on a pre-defined data model that captures semantics among the data. With this developed knowledge graph, we were able to perform several case studies to demonstrate scientific evidence generation for supporting rare disease research discovery.

Results

Of 5001 rare diseases belonging to 32 distinct disease categories, we identified 1294 diseases that are mapped to 45,647 distinct, NIH-funded projects obtained from the NIH ExPORTER by implementing semantic annotation of project titles. To capture semantic relationships presenting amongst mapped research funding data, we defined a data model comprised of seven primary classes and corresponding object and data properties. A Neo4j knowledge graph based on this predefined data model has been developed, and we performed multiple case studies over this knowledge graph to demonstrate its use in directing and promoting rare disease research.

Conclusion

We developed an integrative knowledge graph with rare disease funding data and demonstrated its use as a source from where we can effectively identify and generate scientific evidence to support rare disease research. With the success of this preliminary study, we plan to implement advanced computational approaches for analyzing more funding related data, e.g., project abstracts and PubMed article abstracts, and linking to other types of biomedical data to perform more sophisticated research gap analysis and identify opportunities for future research in rare diseases.
Analgesia in pediatric trauma patients in physician-staffed Austrian helicopter rescue: a 12-year registry analysis
Authors: Rugg Christopher , Woyke Simon , Ausserer Julia , Voelckel Wolfgang , Paal Peter , Ströhle Mathias
Published: November 2021

Background

As pediatric patients are typically rare among helicopter emergency medical systems (HEMS), children might be at risk for oligo-analgesia due to the rescuer’s lack of experience and the fear of side effects.

Methods

In this retrospective analysis, data was obtained from the ÖAMTC HEMS digital database including 14 physician staffed helicopter bases in Austria over a 12-year timeframe. Primary missions involving pediatric trauma patients (< 15 years) not mechanically ventilated on-site were included. Analgesia was assessed and compared between the age groups 0–5, 6–10 and 11–14 years.

Results

Of all flight missions, 8.2% were dedicated to children < 15 years. Analgetic drugs were administered in 31.4% of all primary missions (3874 of 12,324), wherefrom 2885 were injured and non-ventilated (0–5 yrs.: n = 443; 6–10 yrs.: n = 902; 11–14 yrs.: n = 1540). The majority of these patients (> 75%) suffered moderate to severe pain, justifying immediate analgesia. HEMS physicians typically chose a monotherapy with an opioid (n = 1277; 44.3%) or Esketamine (n = 1187; 41.1%) followed by the combination of both (n = 324; 11.2%). Opioid use increased (37.2% to 63.4%) and Esketamine use decreased (66.1% to 48.3%) in children < 6 vs. > 10 years. Esketamine was more often administered in extremity (57.3%) than in head (41.5%) or spine injuries (32.3%). An intravenous access was less often established in children < 6 years (74.3% vs. 90.8%; p < 0.001). Despite the use of potent analgesics, 396 missions (13.7%) were performed without technical monitoring. Particularly regarding patient data at handover in hospital, merely < 10% of all missions featured complete documentation. Therefore, sufficient evaluation of the efficacy of pain relief was not possible. Yet, by means of respiratory measures required during transport, severe side effects such as respiratory insufficiency, were barely noted.

Conclusions

In the physician-staffed HEMS setting, pediatric trauma patients liberally receive opioids and Esketamine for analgesia. With regard to severe respiratory insufficiency during transport, the application of these potent analgesics seems safe.
Cardiogenic shock in Taiwan from 2003 to 2017 (CSiT-15 study)
Authors: Chien Shih-Chieh , Hsu Chien-Yi , Liu Hung-Yi , Lin Chao-Feng , Hung Chung-Lieh , Huang Chun-Yao , Chien Li-Nien
Published: November 2021

Background

This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in 2009 and the unavailability of percutaneous ventricular assist devices.

Methods

Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan’s National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels.

Results

In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 105 person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22–25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years.

Conclusions

In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.
On new general versions of Hermite–Hadamard type integral inequalities via fractional integral operators with Mittag-Leffler kernel
Authors: Kavurmacı Önalan Havva , Akdemir Ahmet Ocak , Avcı Ardıç Merve , Baleanu Dumitru
Published: November 2021

The main motivation of this study is to bring together the field of inequalities with fractional integral operators, which are the focus of attention among fractional integral operators with their features and frequency of use. For this purpose, after introducing some basic concepts, a new variant of Hermite–Hadamard (HH-) inequality is obtained for s-convex functions in the second sense. Then, an integral equation, which is important for the main findings, is proved. With the help of this integral equation that includes fractional integral operators with Mittag-Leffler kernel, many HH-type integral inequalities are derived for the functions whose absolute values of the second derivatives are s-convex and s-concave. Some classical inequalities and hypothesis conditions, such as Hölder’s inequality and Young’s inequality, are taken into account in the proof of the findings.
The application of the QALY measure in the assessment of the effects of health interventions on an older population: a systematic scoping review
Authors: Kocot Ewa , Kotarba Paulina , Dubas-Jakóbczyk Katarzyna
Published: November 2021

Background

One of the most commonly used types of evaluation methods is cost-utility analysis (CUA), using the Quality Adjusted Life Year (QALY) indicator as a preference-based measure for assessing effects of a given programme. Such assessments are often translated into health-care provision priorities; therefore, effectively choosing the method of outcome evaluation is crucial for ensuring the best possible allocation of scarce resources. The main objective of this scoping review is to identify what kinds of problems and limitations may occur when the QALY indicator is used to assess the effects of health interventions in the older population.

Methods

To identify literature in a scoping review, the databases MEDLINE via PubMed and Scopus were searched. A manual search on relevant organizations’ and associations’ websites was also conducted (EUnetHTA, ISPOR and national governmental agencies responsible for allocation decisions). No limits concerning publication dates were set. All relevant data were extracted and analyzed, then a narrative summary was prepared.

Results

The database search identified 10,832 relevant items, finally 32 studies were included in the analysis. The main types of issues indicated in the studies were as follows: (1) lower life expectancy in the older population causes lower QALY gains; (2) an equal value of one QALY is used regardless of age; (3) poorer average health state causes lower QALY gains; (4) inadequate instruments to measure quality of life (QoL); (5) attributes of QoL used regardless of age; and (6) no beyond-health QoL aspects taken into account.

Conclusions

This review shows clearly that many problems of different types are connected with using QALY for the older population, but there is no consensus as to whether QALY discriminates against the older population or not – an opinion regarding this issue depends strongly on accepted principles, particularly the approach to equity and how one understands fairness. Health care resources should not be allocated solely on the basis of the health maximization rule because this can lead to discrimination against certain groups (e.g., older, disabled, and/or chronically ill people). To maintain the balance between efficiency and equity, the issues connected with age-based rationing should be widely discussed.
“I had to change my attitude”: narratives of most significant change explore the experience of universal home visits to pregnant women and their spouses in Bauchi State, Nigeria
Authors: Belaid Loubna , Ansari Umaira , Omer Khalid , Gidado Yagana , Baba Muhammed Chadi , Daniel Lois Ezekiel , Andersson Neil , Cockcroft Anne
Published: November 2021

Background

Universal home visits to pregnant women and their spouses in Bauchi State, northern Nigeria, discussed local evidence about maternal and child health risks actionable by households. The expected results chain for improved health behaviours resulting from the visits was based on the CASCADA model, which includes Conscious knowledge, Attitudes, Subjective norms, intention to Change, Agency to change, Discussion of options, and Action to change. Previous quantitative analysis confirmed the impact of the visits on maternal and child outcomes. To explore the mechanisms of the quantitative improvements, we analysed participants’ narratives of changes in their lives they attributed to the visits.

Methods

Local researchers collected stories of change from 23 women and 21 men in households who had received home visits, from eight male and eight female home visitors, and from four government officers attached to the home visits program. We used a deductive thematic analysis based on the CASCADA results chain to analyze stories from women and men in households, and an inductive thematic approach to analyze stories from home visitors and government officials.

Results

The stories from the visited women and men illustrated all steps in the CASCADA results chain. Almost all stories described increases in knowledge. Stories also described marked changes in attitudes and positive deviations from harmful subjective norms. Most stories recounted a change in behaviour attributed to the home visits, and many went on to mention a beneficial outcome of the behaviour change. Men, as well as women, described significant changes. The home visitors’ stories described increases in knowledge, increased self-confidence and status in the community, and, among women, financial empowerment.

Conclusions

The narratives of change gave insights into likely mechanisms of impact of the home visits, at least in the Bauchi setting. The compatibility of our findings with the CASCADA results chain supports the use of this model in designing and analysing similar interventions in other settings. The indication that the home visits changed male engagement has broader relevance and contributes to the ongoing debate about how to increase male involvement in reproductive health.
Compilation and analysis of international from-whom-to-whom financial stock table for Japan, Korea, the United States, and China
Authors: Hagino Satoru , Kim Jiyoung
Published: November 2021

This paper discusses the development of international flow of funds accounts; it compiles and analyzes such accounts with a focus on the global financial crisis. For this purpose, we compile from-whom-to-whom financial stock tables for Japan, Korea, the United States, and China and combine these tables to generate a four-country international from-whom-to-whom financial stock table. Input–output analyses reveal that nonfinancial corporations in the four countries have the largest liability power-of-dispersion and that the Japanese government’s liability power-of-dispersion is large. In contrast, the financial institution sector in Japan has the largest asset power-of-dispersion. In the future, the table could be expanded to include other major Asia–Pacific countries and linked to Euro-area from-whom-to-whom financial stock tables to provide a global from-whom-to-whom financial stock table.
Autonomic vulnerability to biased perception of social inclusion in borderline personality disorder
Authors: Gerra Maria Lidia , Ardizzi Martina , Martorana Silvia , Leoni Veronica , Riva Paolo , Preti Emanuele , Marino Barbara Francesca Marta , Ossola Paolo , Marchesi Carlo , Gallese Vittorio , De Panfilis Chiara
Published: November 2021

Background

Individuals with Borderline Personality Disorder (BPD) feel rejected even when socially included. The pathophysiological mechanisms of this rejection bias are still unknown. Using the Cyberball paradigm, we investigated whether patients with BPD, display altered physiological responses to social inclusion and ostracism, as assessed by changes in Respiratory Sinus Arrhythmia (RSA).

Methods

The sample comprised 30 patients with BPD, 30 with remitted Major Depressive Disorder (rMDD) and 30 Healthy Controls (HC). Self-report ratings of threats toward one’s fundamental need to belong and RSA reactivity were measured immediately after each Cyberball condition.

Results

Participants with BPD showed lower RSA at rest than HC. Only patients with BPD, reported higher threats to fundamental needs and exhibited a further decline in RSA after the Inclusion condition.

Conclusions

Individuals with BPD experience a biased appraisal of social inclusion both at the subjective and physiological level, showing higher feelings of ostracism and a breakdown of autonomic regulation to including social scenarios.
Cone calorimetric fire properties and thermal analysis of polyester-banana peduncle fibre composite fused with bio-fire retardant additive
Authors: Ezeh Ernest Mbamalu
Published: November 2021

Background

Lately, thermoplastic and thermoset polymers are integrated with natural fillers to harvest composites. Due to an excellent property profile, these composites find wide applications in engineering fields. This research work aimed to investigate the parameters that influence the thermal degradation of Polyester-Banana peduncle fibre-reinforced composite incorporated with cow horn ash particle (CHAp) as a fire retardant additive and optimize the total heat produced for the smaller the better. The major instruments used in this study were cone calorimeter and the thermogravimetric analyser.

Result

The parameters considered were time, reinforcement type, and weight per cent of reinforcement material. The composites were made by varying the ratios of CHAp and BPF in the polyester matrix from 0:0, 2.5:2.5, 5:5 and 7.5:7.5 and 10:10 weight per cent. The flammability properties of the developed composites were examined, using a cone calorimeter. The controlling parameters were analysed using the Taguchi robust design method. The ANOVA showed that time had the greatest influence on the total heat release rate (81.72%). The weight per cent reinforcement type (10.37%) and reinforcement type (5.28%) had smaller influences on the heat release rate. The S/N ratio obtained, using optimal testing shows that time had the greatest influence on the total heat release rate, followed by weight per cent of reinforcement type, while reinforcement type had the least influence. The corresponding multiple regression models for total heat released revealed that the total heat release rate increased with an increase in time and reinforcement type and decreased with an increase in weight per cent of the fire retardant additive material.

Conclusion

This work indicated that the parameter design of the Taguchi method provided an efficient methodology for the analyses of the effects of thermal degradation parameters of composites. The controlling parameters of time, the weight of reinforcement material and the type of reinforcement material had significant contributions to the value of heat production during composites thermal decomposition. Time had the greatest contribution, followed by the weight of reinforcement type, and type of reinforcement material.
Correlation and agreement between physical and ultrasound examination after a training session dedicated to the standardization of synovitis assessment in rheumatoid arthritis patients
Authors: Quintana-López Gerardo , Maldonado-Cañón Kevin , Flórez-Suárez Jorge Bruce , Méndez-Patarroyo Paul , Coral-Alvarado Paola , Calvo Enrique
Published: November 2021

Objectives

Assessing disease activity in rheumatoid arthritis (RA) patients requires comprehensive quantification of tender and swollen joints. We aimed to evaluate the correlation and agreement between rheumatologists after a training session dedicated to the standardization of synovitis assessment and compare its performance with a reference imaging modality such as musculoskeletal ultrasonography (MSUS).

Methods

In this cross-sectional study, a total of 28 and 10 joints in RA patients were evaluated by physical examination and ultrasound (US), respectively. After participating in a training session, individual joint assessment for tenderness and swelling was performed by three rheumatologists. MSUS examination was performed separately by an experimented radiologist in a standardized manner, evaluating findings according to the Outcome Measures in Rheumatology Clinical Trial (OMERACT) guidelines.

Results

A total of 80 RA patients were included, with a mean Disease Activity Score based on 28 joints (DAS28)-ESR of 4.02. The interobserver overall agreement and concordance rate in a total of 2240 joints assessed was 81.7% (k = 0.449, p < 0.0001) for tender joints and 66% (k = 0.227, p < 0.0001) for swollen joints. The overall concordance rate was fair (Fleiss' kappa = 0.21, p = 0.027) with an overall agreement of 67.18% yet, more joints were found to be swollen by the US assessment, compared to the physical examination (43% vs 39%).

Conclusion

In our study population, joint tenderness showed better interobserver agreement, correlation, and concordance rate than joint swelling. When comparing the US assessment to the physical examination, a fair overall concordance rate supports the need for the implementation of training sessions dedicated to standardization in rheumatology clinics.
Trends and constraints of utilization of preserved cowpea leaves among households in arid and semi-arid lands in Kenya: a convergent mixed method study
Authors: Owade J. O. , Abong’ G. O. , Okoth M. W. , Mwang’ombe A. W.
Published: November 2021

Background

As much as local communities have employed traditional techniques of preservation to enhance availability and utilization of cowpea leaves, the efficiency of these techniques in achieving food security need to be established. The current study sought to document trends and constraints of utilization of preserved cowpea leaves in the arid and semi-arid lands (ASALs) in order to overcome of seasonal availability of the vegetable.

Method

A mixed method convergent design that included household survey of randomly sampled cowpea producing households and focus group discussion and key informant interviews with stakeholders in the ASAL areas of Kitui and Taita Taveta Counties of Kenya was conducted.

Results

The study found that the utilization of preserved forms of cowpea leaves in the in-season was by 58% of the respondents. Three quarters (73.6%) of the households could not get the vegetables from their own sources during scarcity, whereas 25% did not consume the vegetables at all at such times. The preserved forms of the vegetables was utilized among 24.0% of the households, with significantly (p < 0.05) higher utilization in less arid areas. Households that were involved in commercialization of cowpea leaves and sale of the preserved forms in the open air market had significantly higher likelihood (p < 0.001, OR = 2.47 and p < 0.001, OR = 2.3, respectively) of utilization of the vegetables during scarcity. Emerging themes from the qualitative survey showed that weaknesses in the policy environment, stakeholder interest, marketing and accessibility to proper equipment were the deterrents of traditional preservation of the vegetable.

Conclusion

In conclusion, the preserved forms of cowpea leaves promoted availability of the vegetable especially in the dry seasons. In as much as there is limited practising of preservation of the vegetables, its availability is enhanced through dehydration and other value-addition techniques among a significant number of the households.
Donor Clonal Hematopoiesis and Recipient Outcomes After Transplantation
Authors: Gibson Christopher J. , Kim Haesook T. , Zhao Lin , Murdock H. Moses , Hambley Bryan , Ogata Alana , Madero-Marroquin Rafael , Wang Shiyu , Green Lisa , Fleharty Mark , Dougan Tyler , Cheng Chi-An , Blumenstiel Brendan , Cibulskis Carrie , Tsuji Junko , Duran Madeleine , Gocke Christopher D. , Antin Joseph H. , Nikiforow Sarah , DeZern Amy E. , Chen Yi-Bin , Ho Vincent T. , Jones Richard J. , Lennon Niall J. , Walt David R. , Ritz Jerome , Soiffer Robert J. , Gondek Lukasz P. , Lindsley R. Coleman
Published: November 2021

PURPOSE

Clonal hematopoiesis (CH) can be transmitted from a donor to a recipient during allogeneic hematopoietic cell transplantation. Exclusion of candidate donors with CH is controversial since its impact on recipient outcomes and graft alloimmune function is uncertain.

PATIENTS AND METHODS

We performed targeted error-corrected sequencing on samples from 1,727 donors age 40 years or older and assessed the effect of donor CH on recipient clinical outcomes. We measured long-term engraftment of 102 donor clones and cytokine levels in 256 recipients at 3 and 12 months after transplant.

RESULTS

CH was present in 22.5% of donors, with DNMT3A (14.6%) and TET2 (5.2%) mutations being most common; 85% of donor clones showed long-term engraftment in recipients after transplantation, including clones with a variant allele fraction < 0.01. DNMT3A-CH with a variant allele fraction ≥ 0.01, but not smaller clones, was associated with improved recipient overall (hazard ratio [HR], 0.79; P = .042) and progression-free survival (HR, 0.72; P = .003) after adjustment for significant clinical variables. In patients who received calcineurin-based graft-versus-host disease prophylaxis, donor DNMT3A-CH was associated with reduced relapse (subdistribution HR, 0.59; P = .014), increased chronic graft-versus-host disease (subdistribution HR, 1.36; P = .042), and higher interleukin-12p70 levels in recipients. No recipient of sole DNMT3A or TET2-CH developed donor cell leukemia (DCL). In seven of eight cases, DCL evolved from donor CH with rare TP53 or splicing factor mutations or from donors carrying germline DDX41 mutations.

CONCLUSION

Donor CH is closely associated with clinical outcomes in transplant recipients, with differential impact on graft alloimmune function and potential for leukemic transformation related to mutated gene and somatic clonal abundance. Donor DNMT3A-CH is associated with improved recipient survival because of reduced relapse risk and with an augmented network of inflammatory cytokines in recipients. Risk of DCL in allogeneic hematopoietic cell transplantation is driven by somatic myelodysplastic syndrome–associated mutations or germline predisposition in donors.
Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease
Authors: Krieger Christine C , Sui Xiangliang , Kahaly George J , Neumann Susanne , Gershengorn Marvin C
Published: November 2021

Context

We previously presented evidence that TSH receptor (TSHR)-stimulating autoantibodies (TSAbs) bind to and activate TSHRs but do not bind to IGF1 receptors (IGF1Rs). Nevertheless, we showed that IGF1Rs were involved in thyroid eye disease (TED) pathogenesis because TSAbs activated crosstalk between TSHR and IGF1R. Teprotumumab, originally generated to inhibit IGF1 binding to IGF1R, was recently approved for the treatment of TED (Tepezza).

Objective

To investigate the role of TSHR/IGF1R crosstalk in teprotumumab treatment of TED.

Design

We used orbital fibroblasts from patients with TED (TEDOFs) and measured stimulated hyaluronan (HA) secretion as a measure of orbital fibroblast activation by TED immunoglobulins (TED-Igs) and monoclonal TSAb M22. We previously showed that M22, which does not bind to IGF1R, stimulated HA in a biphasic dose-response with the higher potency phase dependent on TSHR/IGF1R crosstalk and the lower potency phase independent of IGF1R. Stimulation by TED-Igs and M22 was measured in the absence or presence of teprotumumab biosimilar (Tepro) or K1-70, an antibody that inhibits TSHR.

Results

We show: (1) Tepro dose-dependently inhibits stimulation by TED-Igs; (2) Tepro does not bind to TSHRs; (3) Tepro inhibits IGF1R-dependent M22-induced HA production, which is mediated by TSHR/IGF1R crosstalk, but not IGF1R-independent M22 stimulation; and (4) β-arrestin 1 knockdown, which blocks TSHR/IGF1R crosstalk and prevents Tepro inhibition of HA production by M22 and by a pool of TED-Igs.

Conclusion

We conclude that Tepro inhibits HA production by TEDOFs by inhibiting TSHR/IGF1R crosstalk and suggest that inhibition of TSHR/IGF1R crosstalk is the mechanism of its action in treating TED.
Plasma GLP-1 Response to Oral and Intraduodenal Nutrients in Health and Type 2 Diabetes—Impact on Gastric Emptying
Authors: Xie Cong , Huang Weikun , Watson Linda E , Soenen Stijn , Young Richard L , Jones Karen L , Horowitz Michael , Rayner Christopher K , Wu Tongzhi
Published: November 2021

Context

Both gastric emptying and the secretion of glucagon-like peptide-1 (GLP-1) are major determinants of postprandial glycemia in health and type 2 diabetes (T2D). GLP-1 secretion after a meal is dependent on the entry of nutrients into the small intestine, which, in turn, slows gastric emptying.

Objective

To define the relationship between gastric emptying and the GLP-1 response to both oral and small intestinal nutrients in subjects with and without T2D.

Methods

We evaluated: (i) the relationship between gastric emptying (breath test) and postprandial GLP-1 levels after a mashed potato meal in 73 individuals with T2D; (ii) inter-individual variations in GLP-1 response to (a) intraduodenal glucose (4 kcal/min) during euglycemia and hyperglycemia in 11 healthy and 12 T2D, subjects, (b) intraduodenal fat (2 kcal/min) in 15 T2D subjects, and (c) intraduodenal protein (3 kcal/min) in 10 healthy subjects; and (iii) the relationship between gastric emptying (breath test) of 75 g oral glucose and the GLP-1 response to intraduodenal glucose (4 kcal/min) in 21 subjects (9 healthy, 12 T2D).

Results

The GLP-1 response to the mashed potato meal was unrelated to the gastric half-emptying time (T50). The GLP-1 responses to intraduodenal glucose, fat, and protein varied substantially between individuals, but intra-individual variation to glucose was modest. The T50 of oral glucose was related directly to the GLP-1 response to intraduodenal glucose (r = 0.65, P = 0.002).

Conclusion

In a given individual, gastric emptying is not a determinant of the postprandial GLP-1 response. However, the intrinsic gastric emptying rate is determined in part by the responsiveness of GLP-1 to intestinal nutrients.
Postprandial Glycemic Dips Are Associated With Metabolic Disorders and CVD Risk in Euglycemic Individuals
Authors: Sun Ying , Zhao Lei , Teng Di , Shi Xiaoguang , Li Yongze , Shan Zhongyan , Teng Weiping
Published: November 2021

Context

Metabolic disorders and cardiovascular disease (CVD) threaten human health. Many studies have assessed the phenomenon of metabolic disorders and CVD in patients with diabetes. However, in euglycemic individuals, the relationships between glucose regulation, metabolism, and CVD remain unclear.

Objective

This work aimed to explore the associations between postprandial glucose dips, metabolic disorders, and CVD risk.

Methods

We analyzed data from the Thyroid disorders, Iodine status and Diabetes Epidemiological survey (TIDE study), which included 38 878 euglycemic individuals from all 31 provinces of mainland China. The prevalence of metabolic disorders and their related components and CVD risk were calculated according to postprandial glucose dips. Logistic regression models of quartiles of postprandial glucose dips were used to further explore whether the prevalence of these disorders was associated with postprandial glucose dips.

Results

Odds ratios for the fourth vs the first quartile of glucose dips were 0.59 (95% CI, 0.55-0.63) (P < .001) for metabolic disorders, 0.48 (95% CI 0.44-0.53) (P < .001) for metabolic syndrome (MetS), and 0.54 (95% CI, 0.50-0.59) (P < .001) for hyperuricemia. The odds ratio of a 10-year CVD risk greater than 20% for the fourth vs the first glucose dip quartile was 0.67 (95% CI, 0.52-0.85) (P < .001). Models adjusted for body mass index yielded similar results.

Conclusion

Postprandial glucose dips are associated with metabolic disorders, MetS and its related component diseases, and CVD risk. Glucose dips may be a marker of underlying metabolic abnormalities.
Inhibition of TGF-β Signaling Attenuates Disuse-induced Trabecular Bone Loss After Spinal Cord Injury in Male Mice
Authors: Sahbani Karim , Cardozo Christopher P , Bauman William A , Tawfeek Hesham A
Published: November 2021

Bone loss is one of the most common complications of immobilization after spinal cord injury (SCI). Whether transforming growth factor (TGF)-β signaling plays a role in SCI-induced disuse bone loss has not been determined. Thus, 16-week-old male mice underwent sham or spinal cord contusion injury to cause complete hindlimb paralysis. Five days later, 10 mg/kg/day control (IgG) or anti-TGF-β1,2,3 neutralizing antibody (1D11) was administered twice weekly for 4 weeks. Femurs were examined by micro-computed tomography (micro-CT) scanning and histology. Bone marrow (BM) supernatants were analyzed by enzyme-linked immunosorbent assay for levels of procollagen type 1 intact N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase (TRAcP-5b), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and prostaglandin E2 (PGE2). Distal femoral micro-CT analysis showed that SCI-1D11 mice had significantly (P < .05) attenuated loss of trabecular fractional bone volume (123% SCI-1D11 vs 69% SCI-IgG), thickness (98% vs 81%), and connectivity (112% vs 69%) and improved the structure model index (2.1 vs 2.7). Histomorphometry analysis revealed that osteoclast numbers were lower in the SCI-IgG mice than in sham-IgG control. Biochemically, SCI-IgG mice had higher levels of P1NP and PGE2 but similar TRAcP-5b and RANKL/OPG ratio to the sham-IgG group. The SCI-1D11 group exhibited higher levels of P1NP but similar TRAcP-5b, RANKL/OPG ratio, and PGE2 to the sham-1D11 group. Furthermore, 1D11 treatment prevented SCI-induced hyperphosphorylation of tau protein in osteocytes, an event that destabilizes the cytoskeleton. Together, inhibition of TGF-β signaling after SCI protects trabecular bone integrity, likely by balancing bone remodeling, inhibiting PGE2 elevation, and preserving the osteocyte cytoskeleton.