bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroconversion rates following 2 doses of measles- mumps- rubella vaccination given at the ages 12 and 18 months: data for possible additional dose at older age
Authors: Saffar Hana , Mousavi Sayed Jaber , Saffar Hiva , Parsaei Mohammad-Reza , Ghorbani Gholam-Reza , Saffar Mohammad Jafar
Published: January 2022

Background

Despite high rate of vaccination coverage with 2-doses of measles containing vaccine among Iranian children, outbreaks of measles occurred among different age groups and fully vaccinated subjects. Although the main reason for these outbreaks is unknown, however, vaccine failure was supposed to be an important cause. This study was designed to determine the seroconversion rates to measles- mumps- rubella (MMR) vaccine currently in use among Iranian children.

Methods

This prospective study was conducted among healthy children older than 12 months who were candidates of scheduled MMR vaccination. Blood samples were obtained from each mother- infant pair just before vaccination, and from infants 4–6 weeks after MMR1and MMR2immunization. Collected sera were tested for specific lgG antibodies against MMR agents using ELISA method. The proportion of seroprotected subjects among mother- infant pairs before vaccination as well as the prevalence rates of seroconversion after MMR1and MMR2vaccination were calculated. Collected data were analyzed using descriptive statistical methods.

Results

During 22-months study period, 92 mother- infant pairs were participated. Seroimmunity rates against MMR viruses were 85.8%, 84.7% and 86.9% for mothers, and 3.2%, 2.1% and 1.0% for children, respectively. After MMR1vaccination from 52 seronegative children, 80.7%, 78.8% and 75% were seroconverted. These rates increased to 94.8%, 89.7% and 94.8% after the MMR2vaccination. Also, the specific immunity was enhanced among seropositive children.

Conclusion

Majority of the mothers and few infants were immune to MMR viruses prior to MMR1vaccination. Immune responses detected after MMR1injection, and overall seroconversion rates achieved after 2-doses of MMR vaccination were less than expected and inadequate to preserve long-term protection against MMR agents.
Oxidative damage and DNA repair in desiccated recalcitrant embryonic axes of Acer pseudoplatanus L.
Authors: Plitta-Michalak Beata P. , Ramos Alice A. , Pupel Piotr , Michalak Marcin
Published: January 2022

Background

Most plants encounter water stress at one or more different stages of their life cycle. The maintenance of genetic stability is the integral component of desiccation tolerance that defines the storage ability and long-term survival of seeds. Embryonic axes of desiccation-sensitive recalcitrant seeds of Acer pseudoplatnus L. were used to investigate the genotoxic effect of desiccation. Alkaline single-cell gel electrophoresis (comet assay) methodology was optimized and used to provide unique insights into the onset and repair of DNA strand breaks and 8-oxo-7,8-dihydroguanine (8-oxoG) formation during progressive steps of desiccation and rehydration.

Results

The loss of DNA integrity and impairment of damage repair were significant predictors of the viability of embryonic axes. In contrast to the comet assay, automated electrophoresis failed to detect changes in DNA integrity resulting from desiccation. Notably, no significant correlation was observed between hydroxyl radical (٠OH) production and 8-oxoG formation, although the former is regarded to play a major role in guanine oxidation.

Conclusions

The high-throughput comet assay represents a sensitive tool for monitoring discrete changes in DNA integrity and assessing the viability status in plant germplasm processed for long-term storage.
A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation
Authors: Li Bin , Xie Xing
Published: January 2022

Objective

To investigate the effect of A20 and how A20 is regulated in viral myocarditis (VMC).

Methods

BABL/C mice, primary neonatal rat cardiomyocytes and H9c2 cells were infected with Coxsackie virus B3 (CVB3) to establish animal and cellular models of VMC. H&E staining revealed the pathologic condition of myocardium. ELISA measured the serum levels of creatine kinase, creatine kinase isoenzyme and cardiac troponin I. The effects of A20, miR-1a-3p and ADAR1 were investigated using gain and loss of function approaches. ELISA measured the levels of IL-6, IL-18 and TNF-α in serum or cell culture supernatant. TUNEL staining and flow cytometry assessed the apoptosis of myocardium and cardiomyocytes, respectively. RNA-binding protein immunoprecipitation and dual-luciferase reporter assays verified the binding between A20 and miR-1a-3p. Co-immunoprecipitation assay verified the binding between ADAR1 and Dicer.

Results

A20 was underexpressed and miR-1a-3p was overexpressed in the myocardium of VMC mice as well as in CVB3-infected cardiomyocytes. Overexpression of A20 suppressed cardiomyocyte inflammation and apoptosis in vivo and in vitro. miR-1a-3p promoted CVB3-induced inflammation and apoptosis in cardiomyocytes by binding to A20. The expression of miR-1a-3p was regulated by ADAR1. ADAR1 promoted the slicing of miR-1a-3p precursor by binding to Dicer.

Conclusion

A20, regulated by ADAR1/miR-1a-3p, suppresses inflammation and cardiomyocyte apoptosis in VMC.
Comparison and outcomes of emergency department presentations with respiratory disorders among Australian indigenous and non-indigenous patients
Authors: Heraganahally Subash S. , Ghimire Ram H. , Howarth Timothy , Kankanamalage Oshini M. , Palmer Didier , Falhammar Henrik
Published: January 2022

Background

There is sparse evidence in the literature assessing emergency department presentation with respiratory disorders among Indigenous patients. The objective of this study was to evaluate the clinical characteristics and outcomes for Indigenous Australians in comparison to non-Indigenous patients presenting to Emergency Department (ED) with respiratory disorders.

Methods

In this study, two non-contiguous one-month study periods during wet (January) and dry (August) season were reported on, and differences in demographics, respiratory diagnosis, hospital admission, length of hospital stay, re-presentation to hospital after discharge and mortality between Australian Indigenous and non-Indigenous patients was assessed.

Results

There were a total of 528 respiratory ED presentations, 258 (49%) during wet and 270 (51%) in dry season, from 477 patients (52% female and 40% Indigenous). The majority of ED presentations (84%) were self-initiated, with a difference between Indigenous (80%) and non-Indigenous (88%) presentations. Indigenous presentations recorded a greater proportion of transfers from another healthcare facility compared to non-Indigenous presentations (11% vs. 1%). Less than half of presentations (42%) resulted in admission to the ward with no difference by Indigenous status. Lower respiratory tract infections were the most common cause of presentation (41%), followed by airway exacerbation (31%) which was more commonly seen among Indigenous (34%) than non-Indigenous (28%) presentations. Almost 20% of Indigenous patients reported multiple presentations to ED compared to 1% of non-Indigenous patients, though mortality on follow up did not differ (22% for both).

Conclusions

The results of this study may be an avenue to explore possibilities of implementing programs that may be helpful to reduce preventable ED presentation and recurrent hospitalisations among Indigenous population.
Silent voices of the midwives: factors that influence midwives’ achievement of successful neonatal resuscitation in sub-Saharan Africa: a narrative inquiry
Authors: Becker Jan , Becker Chase , Oprescu Florin , Wu Chiung-Jung , Moir James , Shimwela Meshak , Gray Marion
Published: January 2022

Background

In Tanzania, birth asphyxia is a leading cause of neonatal death. The aim of this study was to identify factors that influence successful neonatal resuscitation to inform clinical practice and reduce the incidence of very early neonatal death (death within 24 h of delivery).

Methods

This was a qualitative narrative inquiry study utilizing the 32 consolidated criteria for reporting qualitative research (COREQ). Audio-recorded, semistructured, individual interviews with midwives were conducted. Thematic analysis was applied to identify themes.

Results

Thematic analysis of the midwives’ responses revealed three factors that influence successful resuscitation:

1. Hands-on training (“HOT”) with clinical support during live emergency neonatal resuscitation events, which decreases fear and enables the transfer of clinical skills;

2. Unequivocal commitment to the Golden Minute® and the mindset of the midwife; and.

3. Strategies that reduce barriers.

Immediately after birth, live resuscitation can commence at the mother’s bedside, with actively guided clinical instruction. Confidence and mastery of resuscitation competencies are reinforced as the physiological changes in neonates are immediately visible with bag and mask ventilation.

The proclivity to perform suction initially delays ventilation, and suction is rarely clinically indicated. Keeping skilled midwives in labor wards is important and impacts clinical practice. The midwives interviewed articulated a mindset of unequivocal commitment to the baby for one Golden Minute®. Heavy workload, frequent staff rotation and lack of clean working equipment were other barriers identified that are worthy of future research.

Conclusions

Training in resuscitation skills in a simulated environment alone is not enough to change clinical practice. Active guidance of “HOT” real-life emergency resuscitation events builds confidence, as the visible signs of successful resuscitation impact the midwife’s beliefs and behaviors. Furthermore, a focused commitment by midwives working together to reduce birth asphyxia-related deaths builds hope and collective self-efficacy.
The economic impact of the switch from single- to multi-dose PCV13 vial in Benin
Authors: Ilboudo Patrick G. , Essoh Téné-Alima , Houngnihin Roch A. , Abdoulaye Alfa Daleb , Dick Naomi , Kaucley Landry , Satoulou-Maleyo Alexis
Published: January 2022

Background

Little is known on the economic implications of multi-dose 13 valent pneumococcal conjugate vaccine (PCV13) introduction in expanded program on immunization (EPI). Based on evidence of PCV13’s reduced pressure on vaccine cold chain, Benin, a third world country in West Africa, introduced the multi-dose PCV13 starting in April 2018 in its EPI program in replacement of the single-dose presentation. The objective of this study was to conduct a rapid assessment of the costs and economic impact of switching from single- to multi-dose PCV13 vial in Benin.

Methods

The data collected retrospectively between January 1 and February 16, 2019 using a quantitative questionnaire was analyzed using Excel 2010 and Stata 13. Resources consumed from April 1st to September 30th, 2017 for the single-dose PCV13 and from April 1st to September 30th, 2018 for multi-dose were analyzed. For both presentations, costs analyzed included vaccines, injections supplies, waste management, cold chain, personnel (salaries and per diems), supervision and monitoring, training, social mobilization and overheads. Moreover, additional costs incurred for the introduction of multi-dose PCV13 were also collected. Costs were estimated for each presentation of PCV13 vaccine by calculating the half-year value of recurrent and capital costs, discounted at a rate of 3% for capital items. To enable comparisons, costs pertaining to 2017 were converted to 2018 equivalent values taking inflation in US$ into account.

Results

The economic costs of the single-dose PCV13 exceeded that of the multi-dose: US$ 3,708,795 versus US$ 3,698,795, respectively. Three cost items, including costs of vaccines, injection supplies, and cold chain appeared to be the main drivers of the observed reduction in costs of multi-dose PCV13. Moreover, the cost per infant vaccinated was lower with the single-dose PCV13 than the multi-dose, respectively US$ 6.28 versus US$ 10.92, and costs of vaccines wasted higher for the multi-dose PCV13.

Conclusions

This evaluation seemed to show that the switch from single- to multi-dose PCV13 resulted in reduced economic costs of PCV13. Vaccinating more infants together with a rigorous application of vaccine open vial policy could lead to the change being more cost-effective.
COVID-19 myth-busting: an experimental study
Authors: Challenger Aimée , Sumner Petroc , Bott Lewis
Published: January 2022

Background

COVID-19 misinformation is a danger to public health. A range of formats are used by health campaigns to correct beliefs but data on their effectiveness is limited. We aimed to identify A) whether three commonly used myth-busting formats are effective for correcting COVID-19 myths, immediately and after a delay, and B) which is the most effective.

Methods

We tested whether three common correction formats could reduce beliefs in COVID-19 myths: (i) question-answer, ii) fact-only, (ii) fact-myth. n = 2215 participants (n = 1291 after attrition), UK representative of age and gender, were randomly assigned to one of the three formats. n = 11 myths were acquired from fact-checker websites and piloted to ensure believability. Participants rated myth belief at baseline, were shown correction images (the intervention), and then rated myth beliefs immediately post-intervention and after a delay of at least 6 days. A partial replication, n = 2084 UK representative, was also completed with immediate myth rating only. Analysis used mixed models with participants and myths as random effects.

Results

Myth agreement ratings were significantly lower than baseline for all correction formats, both immediately and after the delay; all β’s > 0.30, p’s < .001. Thus, all formats were effective at lowering beliefs in COVID-19 misinformation.

Correction formats only differed where baseline myth agreement was high, with question-answer and fact-myth more effective than fact-only immediately; β = 0.040, p = .022 (replication set: β = 0.053, p = .0075) and β = − 0.051, p = .0059 (replication set: β = − 0.061, p < .001), respectively. After the delay however, question-answer was more effective than fact-myth, β = 0.040, p =. 031.

Conclusion

Our results imply that COVID-19 myths can be effectively corrected using materials and formats typical of health campaigns. Campaign designers can use our results to choose between correction formats. When myth belief was high, question-answer format was more effective than a fact-only format immediately post-intervention, and after delay, more effective than fact-myth format.
Cardiometabolic health profile of young girls with aesthetic professions
Authors: Lisboa Salime Chedid , Vieira Alexandra , Teodoro Juliana Lopes , Costa Rochelle , Boeno Franccesco Pinto , Farinha Juliano , Bracht Cláudia Gomes , Reischak-Oliveira Álvaro , dos Santos Cunha Giovani
Published: January 2022

Background

In the literature, professions that impose body standards for daily performance are designated as non-conventional professions (i.e. models, athletes, ballet dancers), with great emphasis on the female population. More than a job, it becomes a lifestyle to those inserted in this environment, thus, thousands of children and adolescents seek inclusion and success in these professions due to financial and media gains. Such professions are associated with several health-related risk factors. The purpose of this study was to identify and compare among physical fitness levels, cardiometabolic health markers, mental health and dietary habits in non-conventional professions.

Methods

The sample consisted of 41 female individuals aged between 14 and 24 years, allocated into four groups, control group composed by university students (UG = 11), models (MG = 11), ballet dancers (BG = 11), and athletes’ group (AG = 8). Physical fitness outcomes (cardiorespiratory fitness, flexibility, maximal dynamic strength, muscular endurance and body composition); biochemical outcomes (high-density lipoprotein [HDL], low-density lipoprotein [LDL], total cholesterol [TC], fasting glucose [FG], fasting insulin [FI], C-reactive protein [CRP]), diet quality and mental health were evaluated.

Results

No impairments were observed in the health markers evaluated among groups, both for health-related physical fitness and biochemical outcomes. However, low levels of bone mineral density (BMD) were observed. Even with statistically significant differences between the groups for chronological age (p = 0.002), menarche (p = 0.004), career length (p = 0.001), height (p = 0.001), body mass index (p = 0.018), waist-to-height ratio (p < 0.001), %Fat (p = 0.020), VO2peak(p = 0.020), maximal dynamic strength of knee extensors (p = 0.031) and elbow flexors (p = 0,001) and flexibility (p < 0.001), all these values are within the normal range for health.

Conclusion

The professions analyzed do not seem to interfere in the physical fitness and cardiometabolic health of the girls assessed. However, we identified that exposure to these profession can impair mental health (depressive symptoms in 100% of participants) and body composition (BMD 63% of participants).
Terminology integration and inconsistency identification of adverse event terminology for Japanese medical devices using SPARQL
Authors: Yagahara Ayako , Yokoi Hideto
Published: January 2022

Background

For standardization of terms in the reports of medical device adverse events, 89 Japanese medical device adverse event terminologies were published in March 2015. The 89 terminologies were developed independently by 13 industry associations, suggesting that there may be inconsistencies among the terms proposed. The purpose of this study was to integrate the 89 sets of terminologies and evaluate inconsistencies among them using SPARQL.

Methods

In order to evaluate the inconsistencies among the integrated terminology, the following six items were evaluated: (1) whether the two-layer structure between category term and preferred term is consistent, (2) whether synonyms of a preferred term are involved. Reversing the layer-category order of matching was also performed, (3) whether each preferred term is subordinate to only one category term, (4) whether the definitions of terms are uniquely determined, (5) whether CDRH-NCIt terms corresponding to preferred terms are uniquely determined, (6) whether a term in a medical device problem is used for patient problems.

Results

About 60% of the total number of duplicated terms were found. This is because industry associations that created multiple terminologies adopted the same terms in terminologies of similar medical device groups. In the case that all terms with the same spelling have the same concept, efficient integration can be achieved automatically using RDF. Furthermore, we evaluated six matters of inconsistency in this study, terms that need to be reviewed accounted for about 10% or less than 10% in each item.

Conclusions

The RDF and SPARQL were useful tools to explore inconsistencies of hierarchies, definition statements, and synonyms when integrating terminolgy by term notation, and these had the advantage of reducing the physical and time burden.
The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23
Authors: Navarro-García José Alberto , Salguero-Bodes Rafael , González-Lafuente Laura , Martín-Nunes Laura , Rodríguez-Sánchez Elena , Bada-Bosch Teresa , Hernández Eduardo , Mérida-Herrero Evangelina , Praga Manuel , Solís Jorge , Arribas Fernando , Bueno Héctor , Kuro-O Makoto , Fernández-Velasco María , Ruilope Luis Miguel , Delgado Carmen , Ruiz-Hurtado Gema
Published: January 2022

Background

Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown.

Methods

We carried out a translational approach to study the relationship between the FGF23–Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels.

Results

Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (Itof), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced Itof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes.

Conclusion

The FGF23–Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.

Graphical abstract
Construction of a risk prediction model using m6A RNA methylation regulators in prostate cancer: comprehensive bioinformatic analysis and histological validation
Authors: Quan Yongjun , Zhang Xiaodong , Ping Hao
Published: January 2022

Background

Epigenetic reprogramming reportedly has a crucial role in prostate cancer (PCa) progression. RNA modification is a hot topic in epigenetics, and N6-methyladenosine (m6A) accounts for approximately 60% of RNA chemical modifications. The aim of this study was to evaluate the m6A modification patterns in PCa patients and construct a risk prediction model using m6A RNA regulators.

Materials and methods

Analyses were based on the levels of 25 m6A regulators in The Cancer Genome Atlas (TCGA). Differentially expressed gene (DEG) and survival analyses were performed according to TCGA-PRAD clinicopathologic and follow-up information. To detect the influences of m6A regulators and their DEGs, consensus clustering analysis was performed, and tumor mutational burden (TMB) estimation and tumor microenvironment (TME) cell infiltration were assessed. mRNA levels of representative genes were verified using clinical PCa data.

Results

Diverse expression patterns of m6A regulators between tumor and normal (TN) tissues were detected regarding Gleason score (GS), pathological T stage (pT), TP53 mutation, and survival comparisons, with HNRNPA2B1 and IGFBP3 being intersecting genes. HNRNPA2B1 was upregulated in advanced stages (GS > 7, pT3, HR > 1, and TP53 mutation), as verified using clinical PCa tissue. Three distinct m6A modification patterns were identified through consensus clustering analysis, but no significant difference was found among these groups in recurrence-free survival (RFS) analysis. Six DEGs of m6A clusters (m6Aclusters) were screened through univariate Cox regression analysis. MMAB and PAIAP2 were intersecting genes for the five clinical factors. MMAB, which was upregulated in PCa compared with TN, was verified using clinical PCa samples. Three distinct subgroups were established according to the 6 DEGs. Cluster A involved the most advanced stages and had the poorest RFS. The m6A score (m6Ascore) was calculated based on the 6 genes, and the low m6Ascore group showed poor RFS with a negative association with infiltration for 16 of 23 immune-related cells.

Conclusion

We screened DEGs of m6Aclusters and identified 6 genes (BAIAP2, TEX264, MMAB, JAGN1, TIMM8AP1, and IMP3), with which we constructed a highly predictive model with prognostic value by dividing TCGA-PRAD into three distinct subgroups and performing m6Ascore analysis. This study helps to elucidate the integral effects of m6A modification patterns on PCa progression.
circFARP1 enables cancer-associated fibroblasts to promote gemcitabine resistance in pancreatic cancer via the LIF/STAT3 axis
Authors: Hu Chonghui , Xia Renpeng , Zhang Xiang , Li Tingting , Ye Yuancheng , Li Guolin , He Rihua , Li Zhihua , Lin Qing , Zheng Shangyou , Chen Rufu
Published: January 2022

Background

Cancer-associated fibroblasts (CAFs) are critically involved in gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanism by which CAFs promote chemotherapy resistance remains unexplored. Here, we explored the role of circRNAs in CAF-induced GEM resistance in PDAC.

Methods

circRNA sequencing and quantitative real-time PCR (qRT–PCR) were utilized to screen CAF-specific circRNAs. The effects of CAF circFARP1 expression on GEM resistance in tumor cells were assessed in vitro and in vivo. RNA-seq, RNA pulldown, RNA immunoprecipitation, and luciferase reporter assays were used to screen the downstream target and underlying mechanism of circFARP1.

Results

circFARP1 (hsa_circ_0002557), a CAF-specific circRNA, was positively correlated with GEM chemoresistance and poor survival in an advanced PDAC cohort. Silencing or overexpressing circFARP1 in CAFs altered the ability of CAFs to induce tumor cell stemness and GEM resistance via leukemia inhibitory factor (LIF). Mechanistically, we found that circFARP1 directly binds with caveolin 1 (CAV1) and blocks the interaction of CAV1 and the E3 ubiquitin-protein ligase zinc and ring finger 1 (ZNRF1) to inhibit CAV1 degradation, which enhances LIF secretion. In addition, circFARP1 upregulated LIF expression by sponging miR-660-3p. Moreover, high circFARP1 levels were positively correlated with elevated serum LIF levels in PDAC and poor patient survival. Decreasing circFARP1 levels and neutralizing LIF significantly suppressed PDAC growth and GEM resistance in patient-derived xenograft models.

Conclusions

The circFARP1/CAV1/miR-660-3p/LIF axis is critical for CAF-induced GEM resistance in PDAC. Hence, circFARP1 may be a potential therapeutic target for PDAC.
Peripheral magnetic theta burst stimulation to muscles can effectively reduce spasticity: a randomized controlled trial
Authors: El Nahas Nevine , Kenawy Fatma Fathalla , Abd Eldayem Eman Hamid , Roushdy Tamer M. , Helmy Shahinaz M. , Akl Ahmed Zaki , Ashour Aya Ahmed , Emara Tamer H. , Moawad Marwa Mohamed , Amin Randa M. , Elbokl Ahmed M.
Published: January 2022

Background

Spasticity is a common complication of many neurological diseases and despite contributing much disability; the available therapeutic options are limited. Peripheral magnetic stimulation is one promising option. In this study, we investigated whether peripheral intermittent theta burst stimulation (piTBS) will reduce spasticity when applied directly on spastic muscles.

Methods

In this sham-controlled study, eight successive sessions of piTBS were applied directly to spastic muscles with supra threshold intensity. Assessment was done by modified Ashworth scale (mAS) and estimated Botulinum toxin dose (eBTD) at baseline and after the 8th session in both active and sham groups.

Results

A total of 120 spastic muscles of 36 patients were included in the analysis. Significant reduction of mAS and eBTD was found in the active compared to sham group (p < 0.001). The difference in mAS was also significant when tested in upper limb and lower limb subgroups. The degree of reduction in mAS was positively correlated with the baseline scores in the active group.

Conclusion

piTBS could be a promising method to reduce spasticity and eBTD. It consumes less time than standard high frequency protocols without compromising treatment efficacy.

Trial registration: Clinical trial registry number: PACTR202009622405087. Retrospectively Registered 14th September, 2020.
In situ analysis of hepatitis B virus (HBV) antigen and DNA in HBV-induced hepatocellular carcinoma
Authors: Zheng Ye , Xu Mingzhu , Zeng Dong , Tong Haitao , Shi Yuhan , Feng Yanling , Zhang Xiaonan
Published: January 2022

Aims

Hepatitis B Virus (HBV) infection is the major risk factor for hepatocellular carcinoma (HCC) in East Asia. Here we aimed to further investigate the abundance of viral antigen and DNA within HBV-related HCC and surrounding tissues at histological level.

Method

In addition to routine histopathology, in situ hybridization (ISH) of HBV DNA and immunohistochemistry (IHC) of HBsAg were performed in tissues from 131 HBsAg-positive HCC patients undergoing liver resection. Serum α-fetoprotein together with basic biochemical and immunological parameter was also measured.

Results

Overall, the ISH of HBV DNA and IHC of HBsAg showed 31.3% and 92.9% positive rate respectively (p < 0.0001). The level of correlation between these two markers was much more significant in tumor (p < 0.0001) than in tumor-surrounding tissue (p = 0.01). HBsAg exhibited a much higher positive rate in tumor-adjacent tissue than in tumor tissue (86.6% versus 29.9%, p < 0.0001) with significantly different staining pattern. By contrast, the positive rate of HBV DNA ISH was comparable in tumor and surrounding tissue (17.6% versus 22.9%, p = 0.36). Yet the HBV DNA signal in tumor tissue showed predominant nuclear localization (87.0%) whereas staining pattern in adjacent tissue was mixed (43.3% nuclear localization, p = 0.0015). Finally, no significant association between intra-tumor HBV DNA/HBsAg positivity and major histological markers (microvascular invasion, tumor differentiation, etc.) or recurrence after surgery was observed.

Conclusions

These data confirmed the largely integrated state of HBV DNA, weaker expression and altered localization of surface antigen in tumor compared with surrounding tissue. The strikingly different prevalence and localization of HBsAg and HBV DNA reflected the complex and heterogeneous mechanisms leading to HBV-induced tumorigenesis.
HairNet: a deep learning model to score leaf hairiness, a key phenotype for cotton fibre yield, value and insect resistance
Authors: Rolland Vivien , Farazi Moshiur R. , Conaty Warren C. , Cameron Deon , Liu Shiming , Petersson Lars , Stiller Warwick N.
Published: January 2022

Background

Leaf hairiness (pubescence) is an important plant phenotype which regulates leaf transpiration, affects sunlight penetration, and provides increased resistance or susceptibility against certain insects. Cotton accounts for 80% of global natural fibre production, and in this crop leaf hairiness also affects fibre yield and value. Currently, this key phenotype is measured visually which is slow, laborious and operator-biased. Here, we propose a simple, high-throughput and low-cost imaging method combined with a deep-learning model, HairNet, to classify leaf images with great accuracy.

Results

A dataset of$$\sim $$∼ 13,600 leaf images from 27 genotypes of Cotton was generated. Images were collected from leaves at two different positions in the canopy (leaf 3 & leaf 4), from genotypes grown in two consecutive years and in two growth environments (glasshouse & field). This dataset was used to build a 4-part deep learning model called HairNet. On the whole dataset, HairNet achieved accuracies of 89% per image and 95% per leaf. The impact of leaf selection, year and environment on HairNet accuracy was then investigated using subsets of the whole dataset. It was found that as long as examples of the year and environment tested were present in the training population, HairNet achieved very high accuracy per image (86–96%) and per leaf (90–99%). Leaf selection had no effect on HairNet accuracy, making it a robust model.

Conclusions

HairNet classifies images of cotton leaves according to their hairiness with very high accuracy. The simple imaging methodology presented in this study and the high accuracy on a single image per leaf achieved by HairNet demonstrates that it is implementable at scale. We propose that HairNet replaces the current visual scoring of this trait. The HairNet code and dataset can be used as a baseline to measure this trait in other species or to score other microscopic but important phenotypes.
Is postoperative cognitive decline after cardiac surgery associated with plasma beta amyloid 1–42 levels?
Authors: Požgain Zrinka , Dulić Grgur , Kondža Goran , Bogović Siniša , Šerić Ivan , Hil Dejan , Trogrlić Bojan , Bednjanić Ana , Perković-Kovačević Marina , Šahinović Ines
Published: January 2022

Background

Postoperative cognitive decline following cardiac surgery is one of the frequently reported complications affecting postoperative outcome, characterized by impairment of memory or concentration. The aetiology is considered multifactorial and the research conducted so far has presented contradictory results. The proposed mechanisms to explain the cognitive decline associated with cardiac surgery include the neurotoxic accumulation of β-amyloid (Aβ) proteins similar to Alzheimer's disease. The comparison of coronary artery bypass grafting procedures concerning postoperative cognitive decline and plasmatic Aβ1-42 concentrations has not yet been conducted.

Methods

The research was designed as a controlled clinical study of patients with coronary artery disease undergoing surgical myocardial revascularization with or without the use of a cardiopulmonary bypass machine. All patients completed a battery of neuropsychological tests and plasmatic Aβ1-42 concentrations were collected.

Results

The neuropsychological test results postoperatively were significantly worse in the cardiopulmonary bypass group and the patients had larger shifts in the Aβ1-42 preoperative and postoperative values than the group in which off-pump coronary artery bypass was performed.

Conclusions

The conducted research confirmed the earlier suspected association of plasmatic Aβ1-42 concentration to postoperative cognitive decline and the results further showed that there were less changes and lower concentrations in the off-pump coronary artery bypass group, which correlated to less neurocognitive decline. There is a lot of clinical contribution acquired by this research, not only in everyday decision making and using amyloid proteins as biomarkers, but also in the development and application of non-pharmacological and pharmacological neuroprotective strategies.
Omega-6 sparing effects of parenteral lipid emulsions—an updated systematic review and meta-analysis on clinical outcomes in critically ill patients
Authors: Notz Quirin , Lee Zheng-Yii , Menger Johannes , Elke Gunnar , Hill Aileen , Kranke Peter , Roeder Daniel , Lotz Christopher , Meybohm Patrick , Heyland Daren K. , Stoppe Christian
Published: January 2022

Background

Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients.

Methods

A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed.

Results

1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10;p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] − 6.88; 95% CI − 11.27, − 2.49;p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD − 3.53; 95% CI − 6.16, − 0.90;p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95;p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care.

Conclusion

Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact.

Trial registrationPROSPERO international prospective database of systematic reviews (CRD42021259238).

Graphical abstract
Genome-wide analysis and functional annotation of chromatin-enriched noncoding RNAs in rice during somatic cell regeneration
Authors: Zhang Yu-Chan , Zhou Yan-Fei , Cheng Yu , Huang Jia-Hui , Lian Jian-Ping , Yang Lu , He Rui-Rui , Lei Meng-Qi , Liu Yu-Wei , Yuan Chao , Zhao Wen-Long , Xiao Shi , Chen Yue-Qin
Published: January 2022

Background

Plants have the remarkable ability to generate callus, a pluripotent cell mass that acquires competence for subsequent tissue regeneration. Global chromatin remodeling is required for this cell fate transition, but how the process is regulated is not fully understood. Chromatin-enriched noncoding RNAs (cheRNAs) are thought to play important roles in maintaining chromatin state. However, whether cheRNAs participate in somatic cell regeneration in plants has not yet been clarified.

Results

To uncover the characteristics and functions of cheRNAs during somatic cell reprogramming in plants, we systematically investigate cheRNAs during callus induction, proliferation and regeneration in rice. We identify 2284 cheRNAs, most of which are novel long non-coding RNAs or small nucleolar RNAs. These cheRNAs, which are highly conserved across plant species, shuttle between chromatin and the nucleoplasm during somatic cell regeneration. They positively regulate the expression of neighboring genes via specific RNA motifs, which may interact with DNA motifs around cheRNA loci. Large-scale mutant analysis shows that cheRNAs are associated with plant size and seed morphology. Further detailed functional investigation of two che-lncRNAs demonstrates that their loss of function impairs cell dedifferentiation and plant regeneration, highlighting the functions of cheRNAs in regulating the expression of neighboring genes via specific motifs. These findings supportcis- regulatory roles of cheRNAs in influencing a variety of rice traits.

Conclusions

cheRNAs are a distinct subclass of regulatory non-coding RNAs that are required for somatic cell regeneration and regulate rice traits. Targeting cheRNAs has great potential for crop trait improvement and breeding in future.
Phase I/II trial of meclofenamate in progressive MGMT-methylated glioblastoma under temozolomide second-line therapy—the MecMeth/NOA-24 trial
Authors: Zeyen Thomas , Potthoff Anna-Laura , Nemeth Robert , Heiland Dieter H. , Burger Michael C. , Steinbach Joachim P. , Hau Peter , Tabatabai Ghazaleh , Glas Martin , Schlegel Uwe , Grauer Oliver , Krex Dietmar , Schnell Oliver , Goldbrunner Roland , Sabel Michael , Thon Niklas , Delev Daniel , Clusmann Hans , Seidel Clemens , Güresir Erdem , Schmid Matthias , Schuss Patrick , Giordano Frank A. , Radbruch Alexander , Becker Albert , Weller Johannes , Schaub Christina , Vatter Hartmut , Schilling Judith , Winkler Frank , Herrlinger Ulrich , Schneider Matthias
Published: January 2022

Background

Glioblastoma is the most frequent and malignant primary brain tumor. Even in the subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and favorable response to first-line therapy, survival after relapse is short (12 months). Standard therapy for recurrent MGMT-methylated glioblastoma is not standardized and may consist of re-resection, re-irradiation, and chemotherapy with temozolomide (TMZ), lomustine (CCNU), or a combination thereof. Preclinical results show that meclofenamate (MFA), originally developed as a nonsteroidal anti-inflammatory drug (NSAID) and registered in the USA, sensitizes glioblastoma cells to temozolomide-induced toxicity via inhibition of gap junction-mediated intercellular cytosolic traffic and demolishment of tumor microtube (TM)-based network morphology.

Methods

In this study, combined MFA/TMZ therapy will be administered (orally) in patients with first relapse of MGMT-methylated glioblastoma. A phase I component (6–12 patients, 2 dose levels of MFA + standard dose TMZ) evaluates safety and feasibility and determines the dose for the randomized phase II component (2 × 30 patients) with progression-free survival as the primary endpoint.

Discussion

This study is set up to assess toxicity and first indications of efficacy of MFA repurposed in the setting of a very difficult-to-treat recurrent tumor. The trial is a logical next step after the identification of the role of resistance-providing TMs in glioblastoma, and results will be crucial for further trials targeting TMs. In case of favorable results, MFA may constitute the first clinically feasible TM-targeted drug and therefore might bridge the idea of a TM-targeted therapeutic approach from basic insights into clinical reality.

Trial registration

EudraCT 2021-000708-39. Registered on 08 February 2021
Effects of electrode size and placement on comfort and efficiency during low-intensity neuromuscular electrical stimulation of quadriceps, hamstrings and gluteal muscles
Authors: Flodin J. , Juthberg R. , Ackermann P. W.
Published: January 2022

Background

Neuromuscular electrical stimulation (NMES) may prevent muscle atrophy, accelerate rehabilitation and enhance blood circulation. Yet, one major drawback is that patient compliance is impeded by the discomfort experienced. It is well-known that the size and placement of electrodes affect the comfort and effect during high-intensity NMES. However, during low-intensity NMES the effects of electrode size/placement are mostly unknown. Therefore, the purpose of this study was to investigate how electrode size and pragmatic placement affect comfort and effect of low-intensity NMES in the thigh and gluteal muscles.

Methods

On 15 healthy participants, NMES-intensity (mA) was increased until visible muscle contraction, applied with three electrode sizes (2 × 2 cm, 5 × 5 cm, 5 × 9 cm), in three different configurations on quadriceps and hamstrings (short-transverse (ST), long-transverse (LT), longitudinal (L)) and two configurations on gluteus maximus (short-longitudinal (SL) and long-longitudinal (LL)). Current–density (mA/cm2) required for contraction was calculated for each electrode size. Comfort was assessed with a numerical rating scale (NRS, 0–10). Significance was set to p < 0.05 and values were expressed as median (inter-quartile range).

Results

On quadriceps the LT-placement exhibited significantly better comfort and lower current intensity than the ST- and L-placements. On hamstrings the L-placement resulted in the best comfort together with the lowest intensity. On gluteus maximus the LL-placement demonstrated better comfort and required less intensity than SL-placement. On all muscles, the 5 × 5 cm and 5 × 9 cm electrodes were significantly more comfortable and required less current–density for contraction than the 2 × 2 cm electrode.

Conclusion

During low-intensity NMES-treatment, an optimized electrode size and practical placement on each individual muscle of quadriceps, hamstrings and gluteals is crucial for comfort and intensity needed for muscle contraction.
A deep learning model for early risk prediction of heart failure with preserved ejection fraction by DNA methylation profiles combined with clinical features
Authors: Zhao Xuetong , Sui Yang , Ruan Xiuyan , Wang Xinyue , He Kunlun , Dong Wei , Qu Hongzhu , Fang Xiangdong
Published: January 2022

Background

Heart failure with preserved ejection fraction (HFpEF), affected collectively by genetic and environmental factors, is the common subtype of chronic heart failure. Although the available risk assessment methods for HFpEF have achieved some progress, they were based on clinical or genetic features alone. Here, we have developed a deep learning framework, HFmeRisk, using both 5 clinical features and 25 DNA methylation loci to predict the early risk of HFpEF in the Framingham Heart Study Cohort.

Results

The framework incorporates Least Absolute Shrinkage and Selection Operator and Extreme Gradient Boosting-based feature selection, as well as a Factorization-Machine based neural network-based recommender system. Model discrimination and calibration were assessed using the AUC and Hosmer–Lemeshow test. HFmeRisk, including 25 CpGs and 5 clinical features, have achieved the AUC of 0.90 (95% confidence interval 0.88–0.92) and Hosmer–Lemeshow statistic was 6.17 (P = 0.632), which outperformed models with clinical characteristics or DNA methylation levels alone, published chronic heart failure risk prediction models and other benchmark machine learning models. Out of them, the DNA methylation levels of two CpGs were significantly correlated with the paired transcriptome levels (R < −0.3, P < 0.05). Besides, DNA methylation locus in HFmeRisk were associated with intercellular signaling and interaction, amino acid metabolism, transport and activation and the clinical variables were all related with the mechanism of occurrence of HFpEF. Together, these findings give new evidence into the HFmeRisk model.

Conclusion

Our study proposes an early risk assessment framework for HFpEF integrating both clinical and epigenetic features, providing a promising path for clinical decision making.
Managing pregnancy in a spinal muscular atrophy type III patient in Indonesia: a case report
Authors: Setyaningrum Cempaka Thursina Srie , Harahap Indra Sari Kusuma , Nurputra Dian Kesumapramudya , Rachman Irwan Taufiqur , Harahap Nur Imma Fatimah
Published: January 2022

Background

Spinal muscular atrophy is a genetic disorder characterized by degeneration of lower motor neurons, leading to progressive muscular atrophy and even paralysis. Spinal muscular atrophy usually associated with a defect of the survival motor neuron 1 (SMN-1) gene. Classification of spinal muscular atrophy is based on the age of onset and maximum motor function milestone achieved. Although spinal muscular atrophy can be screened for in newborns, and even confirmed earlier genetically, this remains difficult in Third World countries such as Indonesia.

Case presentation

A 28-year-old Asian woman in the first trimester of her second pregnancy, was referred to the neurology department from the obstetric department. Her milestone history showed she was developmentally delayed and the ability to walk independently was reached at 26 months old. At 8 years old, she started to stumble and lose balance while walking. At this age, spinal muscular atrophy was suspected because of her clinical presentations, without any molecular genetic testing. She was married at the age of 25 years and was soon pregnant with her first child. At the gestational age of 32 weeks, her first pregnancy was ended by an emergency caesarean section because of premature rupture of the membranes. In this second pregnancy, she was referred early to the general hospital from the district hospital to receive multidisciplinary care. She and her first daughter underwent genetic testing for spinal muscular atrophy, which has been readily available in our institution since 2018, to confirm the diagnosis and prepare for genetic counseling.

Conclusions

Managing pregnancy in a patient with spinal muscular atrophy should be performed collaboratively. In this case, genetic testing of spinal muscular atrophy and the collaborative management of this patient allowed the clinical decision making and genetic counseling throughout her pregnancy and delivery.