bluuebunny/crossref_metadata_2025 huggingface dataset:
The miR528-D3 Module Regulates Plant Height in Rice by Modulating the Gibberellin and Abscisic Acid Metabolisms
Authors: Zhao Juan , Liu Xing , Wang Mei , Xie Lingjuan , Wu Zhengxin , Yu Jiuming , Wang Yuchen , Zhang Zhiqiao , Jia Yufang , Liu Qingpo
Published: May 2022

Plant height, as one of the important agronomic traits of rice, is closely related to yield. In recent years, plant height-related genes have been characterized and identified, among which the DWARF3 (D3) gene is one of the target genes of miR528, and regulates rice plant height and tillering mainly by affecting strigolactone (SL) signal transduction. However, it remains unknown whether the miR528 and D3 interaction functions in controlling plant height, and the underlying regulatory mechanism in rice. In this study, we found that the plant height, internode length, and cell length of internodes of d3 mutants and miR528-overexpressing (OE-miR528) lines were greatly shorter than WT, D3-overexpressing (OE-D3), and miR528 target mimicry (OE-MIM528) transgenic plants. Knockout of D3 gene (d3 mutants) or miR528-overexpressing (OE-miR528) triggers a substantial reduction of gibberellin (GA) content, but a significant increase of abscisic acid (ABA) accumulation than in WT. The d3 and OE-miR528 transgenic plants were much more sensitive to GA, but less sensitive to ABA than WT. Moreover, the expression level of GA biosynthesis-related key genes, including OsCPS1, OsCPS2, OsKO2 and OsKAO was remarkably higher in OE-D3 plants, while the NECD2 expression, a key gene involved in ABA biosynthesis, was significantly higher in d3 mutants than in WT and OE-D3 plants. The results indicate that the miR528-D3 module negatively regulates plant height in rice by modulating the GA and ABA homeostasis, thereby further affecting the elongation of internodes, and resulting in lower plant height, which adds a new regulatory role to the D3-mediated plant height controlling in rice.
Alanine-specific appetite in slow growing chickens is associated with impaired glucose transport and TCA cycle
Authors: Niknafs Shahram , Fortes Marina R. S. , Cho Sungbo , Black John L. , Roura Eugeni
Published: May 2022

Background

The rate of protein accretion and growth affect amino acid requirements in young animals. Differences in amino acid metabolism contribute to individual variations in growth rate. This study aimed at determining how amino acid needs may change with growth rates in broiler chickens. Experiment 1 consisted of testing amino acid choices in two chicken groups with extreme growth rates (the slowest –SG- or fastest –FG- growing birds in a flock). Essential (EAA) (methionine, lysine and threonine) or non-essential (NEAA) (alanine, aspartic acid and asparagine) amino acids were added to a standard control feed (13.2 MJ/kg; 21.6% crude protein). The chickens were offered simultaneous access to the control feed and a feed supplemented with one of the two amino acid mixes added at 73% above standard dietary levels. Experiment 2 consisted of the selection of the bottom 5 SG and top 5 FG chickens from a flock of 580 to study differences in amino acid metabolism using the proventriculus representing gut sensing mechanism. In this experiment, transcriptomic, proteomic, and genomic analyses were used to compare the two groups of chickens.

Results

SG preferred NEAA, while they rejected EAA supplemented feeds (P < 0.05). However, FG rejected NEAA (P < 0.05), and they were indifferent to EAA supplemented feed (P > 0.05). Transcriptomic and proteomic analyses identified 909 differentially expressed genes and 146 differentially abundant proteins associated with differences in growth rate (P < 0.05). The integration of gene expression and protein abundance patterns showed the downregulation of sensing and transport of alanine and glucose associated with increased alanine catabolism to pyruvate in SG chickens.

Conclusion

Dietary preferences for NEAA in the SG group are associated with a potential cytosolic depletion of alanine following an upregulation of the catabolism into TCA cycle intermediates.
The effects of dual antiplatelet therapy (DAPT) adherence on survival in patients undergoing revascularization and the determinants of DAPT adherence
Authors: Zhang Shuqi , Chourase Mithlesh , Sharma Nupur , Saunik Sujata , Duggal Mona , Danaei Goodarz , Duggal Bhanu
Published: May 2022

Background

The prevalence and burden of coronary heart disease (CHD) has increased substantially in India, accompanied with increasing need for percutaneous coronary interventions (PCI). Although a large government-funded insurance scheme in Maharashtra, India covered the cost of PCI for low-income patients, the high cost of post-PCI treatment, especially Dual Antiplatelet Therapy (DAPT), still caused many patients to prematurely discontinue the secondary prevention. Our study aimed to investigate the effectiveness of DAPT adherence on all-cause mortality among post-PCI patients and explore the potential determinants of DAPT adherence in India.

Method

We collected clinical data of 4,595 patients undergoing PCI in 110 participating medical centers in Maharashtra, India from 2012 to 2015 by electronic medical records. We surveyed 2527 adult patients who were under the insurance scheme by telephone interview, usually between 6 to 12 months after their revascularization. Patients reporting DAPT continuation in the telephone survey were categorized as DAPT adherence. The outcome of the interest was all-cause mortality within 1 year after the index procedure. Multivariate Cox proportional hazard (PH) model with adjustment of potential confounders and standardization were used to explore the effects of DAPT adherence on all-cause mortality. We further used a multivariate logistic model to investigate the potential determinants of DAPT adherence.

Results

Out of the 2527 patients interviewed, 2064 patients were included in the analysis, of whom 470 (22.8%) discontinued DAPT prematurely within a year. After adjustment for baseline confounders, DAPT adherence was associated with lower one-year all-cause mortality compared to premature discontinuation (less than 6-month), with an adjusted hazard ratio (HR) of 0.52 (95% Confidence Interval (CI) = (0.36, 0.67)). We also found younger patients (OR per year was 0.99 (0.97, 1.00)) and male (vs. female, OR of 1.30 (0.99, 1.70)) had higher adherence to DAPT at one year as did patients taking antihypertensive medications (vs. non medication, OR of 1.57 (1.25, 1.95)).

Conclusion

These findings suggest the protective effects of DAPT adherence on 1-year mortality among post-PCI patients in a low-income setting and indicate younger age, male sex and use of other preventive treatments were predictors of higher DAPT adherence.
Description of organizational and clinician characteristics of primary dementia care in Canada: a multi-method study
Authors: Henein Mary , Arsenault-Lapierre Geneviève , Sourial Nadia , Godard-Sebillotte Claire , Bergman Howard , Vedel Isabelle ,   Research on Organization of Healthcare Services for Alzheimer’s (ROSA) Team
Published: May 2022

Background

Organizational and clinician characteristics are important considerations for the implementation of evidence-based recommendations into primary care practice. The introduction of Canadian dementia practice guidelines and Alzheimer strategies offers a unique context to study which of the organizational and clinician characteristics align with good quality care in primary care practices.

Methods

To evaluate the quality of dementia care, we carried out a retrospective chart review in randomly selected patients with a diagnosis of dementia and who had a visit during a 9-month period in 33 primary care practices. We collected data on indicators that were based on existing Canadian evidence-based recommendations to measure a quality of dementia care score. In addition, four questionnaires were administered: two questionnaires to evaluate the organizational characteristics of the practices (dementia-specific and general organization) and two to evaluate the clinician characteristics (one for family physicians and one for nurses). Primary care practices were stratified into tertiles based on their average quality of dementia care score (low, moderate, high). The differences between the groups organizational and clinician questionnaires scores were analyzed descriptively and visually.

Results

The mean overall scores for each questionnaire were higher in the high quality of dementia care group. When looking at the breakdown of the overall score into each characteristic, the high-quality group had a higher average score for the dementia-specific organizational characteristics of “access to and coordination with home and community services”, “financial support”, “training”, “coordination and continuity within the practice”, and “caregiver support and involvement”. The characteristic “Leadership” showed a higher average score for the moderate and high-quality groups than the low-quality group. In both clinician questionnaires, the high group scored better in “attitudes towards the Alzheimer’s plan” than the other two groups.

Conclusions

These results suggest that investing in organizational characteristics specifically aimed at dementia care is a promising avenue to improve quality of dementia care in primary care. These results may be useful to enhance the implementation of evidence-based practices and improve the quality of dementia care.
Correlation analysis of physical fitness and its impact on falls in 2130 community- dwelling older adults: a retrospective cross-sectional study
Authors: Lin Wang-Sheng , Hsu Nai-Wei , Lee Meng-Jer , Lin You-Yuan , Tsai Chih-Chun , Pan Po-Jung
Published: May 2022

Background

As the community-dwelling population ages in Taiwan, concerns regarding long-term care have grown more urgent. Physical fitness plays a key role in enabling community-dwelling older adults to independently complete daily tasks and avoid falling accidents. However, the effect of physical fitness on falls and other fitness-related factors remains poorly understood.

Methods

In this retrospective cross-sectional study, 2130 community-dwelling older adults were recruited from a rural region of Taiwan. Each of these participants completed a demographics interview and frailty questionnaire and reported their history of falls. We evaluated each participant’s height and body weight measurements, calf circumference, bone mass density, and results on the grip strength, single-leg standing, chair sit-and-reach, 8-ft up-and-go, 30-second chair stand, 2-minute step, 30-second arm curl, 6-m walk, and back scratch tests to determine their overall physical fitness, which consisted of their body composition, muscular strength and endurance, flexibility, and cardiopulmonary fitness.

Results

The prevalence of falls in the preceding year among the older adults surveyed was 20.8%, and the resultant hospitalization rate was 10.9%. The older adults who were more physically active in the past week, had regular exercise habits, lived with family, and had no history of hospitalization due to falls, exhibited greater performance on the physical fitness tests. Three time fallers exhibited lower levels of overall physical fitness than did those who had not fallen. The nonfallers outperformed the fallers in grip strength (participants who had not fallen and those who had fallen once, twice, or three times in the preceding year: 24.66 ± 0.19 vs. 23.66 ± 0.35 vs. 20.62 ± 0.71 vs. 22.20 ± 0.90 kg) and single-leg standing duration (19.38 ± 0.39 vs. 16.33 ± 0.78 vs. 13.95 ± 1.67 vs. 12.34 ± 1.82 seconds).

Conclusions

Exercise habits, living status, hospitalization due to falls, and amount of exercise were all associated with physical fitness in community-dwelling older adults. The results of all of the assessments indicated that the participants who had fallen three times exhibited lower levels of physical fitness than did those who had not fallen in the previous year. Physical measurements, including grip strength and single-leg standing duration, are associated with an individual’s risk of falling, which indicates that they should be considered in the development of geriatric physical fitness and fall-prevention programs.
Adapting strategies for effective and efficient pediatric HIV case finding in low prevalence countries: risk screening tool for testing children presenting at high-risk entry points in Ethiopia
Authors: Teferi Wondimu , Gutreuter Steve , Bekele Alemayehu , Ahmed Jelaludin , Ayalew Jemal , Gross Jessica , Kumsa Hanna , Antefe Tenagnework , Mengistu Semegnew , Mirkovic Kelsey , Dziuban Eric J. , Ross Christine , Belay Zena , Tilahun Tsegaye , Kassa Desta , Hrapcak Susan
Published: May 2022

Background

Implementing effective and efficient case-finding strategies is crucial to increasing pediatric antiretroviral therapy coverage. In Ethiopia, universal HIV testing is conducted for children presenting at high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC); however, low positivity rates observed at inpatient, malnutrition and OVC entry points warrant re-assessing current case-finding strategies. The aim of this study is to develop HIV risk screening tool applicable for testing children presenting at inpatient, malnutrition and OVC entry points in low-HIV prevalence settings.

Methods

The study was conducted from May 2017–March 2018 at 29 public health facilities in Amhara and Addis Ababa regions of Ethiopia. All children 2–14 years presenting to five high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC) were enrolled after consent. Data were collected from registers, medical records, and caregiver interviews. Screening tools were constructed using predictors of HIV positivity as screening items by applying both logistic regression and an unweighted method. Sensitivity, specificity and number needed to test (NNT) to identify one new child living with HIV (CLHIV) were estimated for each tool.

Results

The screening tools had similar sensitivity of 95%. However, the specificities of tools produced by logistic regression methods (61.4 and 65.6%) which are practically applicable were higher than those achieved by the unweighted method (53.6). Applying these tools could result in 58‒63% reduction in the NNT compared to universal testing approach while maintaining the overall number of CLHIV identified.

Conclusion

The screening tools developed using logistic regression method could significantly improve HIV testing efficiency among children presenting to malnutrition, inpatient, and OVC entry points in Ethiopia while maintaining case identification. These tools are simplified to practically implement and can potentially be validated for use at various entry points. HIV programs in low-prevalence countries can also further investigate and optimize these tools in their settings.
Digital screening for postnatal depression: mixed methods proof-of-concept study
Authors: Eisner Emily , Lewis Shôn , Stockton-Powdrell Charlotte , Agass Ria , Whelan Pauline , Tower Clare
Published: May 2022

Background

Depression during the postnatal year is prevalent in mothers (17%) and fathers (9%), and suicide is the leading cause of maternal death in this period. Lifelong costs and consequences of untreated postnatal depression (PND) are high due to impacts on infants as well as parents. We aimed to improve access to PND treatment using digital screening. We developed a smartphone app (ClinTouch DAWN-P) that allows parents to monitor their mood daily with the Edinburgh Postnatal Depression Scale (EPDS), uploading responses in real-time to a secure server. We evaluated the app’s feasibility, acceptability, validity and safety in a proof-of-concept study.

Methods

Pregnant women (≥ 36 weeks gestation) and partners were recruited from antenatal services and invited to complete daily EPDS assessments via the ClinTouch DAWN-P app until 6 weeks postpartum. Participants completed standard paper-based EPDS at two time points for validity comparisons. We examined app acceptability and usability at 6 weeks postpartum with qualitative interviews, examined using framework analysis, and the abridged Mobile App Rating Scale (convergent mixed methods design).

Results

Most (96%) eligible pregnant women approached were keen to try the app. Participating mothers (n = 15) and partners/fathers (n = 8) found the app easy to use, and 91% continued to use it for the full study period. Overall, 67% of daily app-based assessments were completed, with a history of depression predicting lower app usage. Participants suggested modifications to the app and its deployment to improve usability (e.g., extending the response window and including feedback and parenting advice). The validity of app-based responses was confirmed by high agreement with standard EPDS. App-based and paper-based ratings showed perfect agreement in identifying cases of likely PND. There were no serious adverse events relating to app use.

Conclusions

Digital PND screening appears feasible, acceptable, valid and safe. It also benefits from being remotely delivered: we enrolled all participants remotely during the first COVID-19 lockdown. Use of digital screening could address known shortcomings of conventional health visitor-delivered screening such as limited staff time, parental unwillingness to disclose difficulties to a professional, lack of partner/father screening, and language barriers.

Trial registration

The study was prospectively registered (Clinicaltrials.gov:NCT04279093).
Relationship between physical activity and mental health in women after childbirth: a cross-sectional exploratory study
Authors: Tomioka Yumi
Published: May 2022

Background

Physical activity (PA) is recommended for women after childbirth. However, it is unknown whether PA, such as housework and child-rearing, is associated with mental health. This study aimed to measure daily PA in women 2 months postpartum as well as investigate the relationship between daily PA and mental health.

Methods

In this cross-sectional quantitative exploratory study conducted between September 2017 and May 2018, 110 women were approached for participation. Mental health was evaluated using the General Health Questionnaire-28, and PA measurements were performed using accelerometers that the participants wore for 2 days. Welch’s t-test and linear regression analysis were performed to assess the relationship between PA and mental health.

Results

This study included 99 participants. The mean amount of daily activities from housework and child-rearing was 3.21 ± 1.14 metabolic equivalent of tasks (METs)-h/day and that of time spent sitting was at least 7.5 h/12.5 h. PA time spent in light child-rearing and housework activities was significantly longer among multiparous women than among primiparous women (t =  − 3.41). PA time comprising the duration of moderate (3 METs) or more vigorous PA was 73 min/day. No significant relationship between mental health and PA was observed. However, the amount of daily activities tended to increase with an improvement in mental health. The amount of daily activities exceeded 3 METs-h/day regardless of the mental health status.

Conclusions

No significant relationship was found between the amount of daily activities and mental health. The former increased as the latter improved. The amount of daily activities met the standard recommended by the World Health Organization, regardless of the mental health status.
When to add anti-angiogenesis drugs to EGFR-mutated metastatic non–small cell lung cancer patients: a real-world study from Taiwan
Authors: Chen Chieh-Lung , Wang Sing-Ting , Liao Wei-Chih , Chen Chia-Hung , Tu Chih-Yen , Chen Hung-Jen , Hsia Te-Chun , Cheng Wen-Chien
Published: May 2022

Background

The addition of anti-angiogenesis drugs to epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) or chemotherapy in patients with EGFR-mutant non–small cell lung cancer (NSCLC) can improve disease control. We conducted a study to evaluate the efficacy of combination therapeutic strategies and identify patients who could benefit from combination therapy.

Methods

This study enrolled patients with stage IV EGFR-mutant NSCLC treated with first-line EGFR-TKIs between January 2014 and December 2020. We divided patients into three groups: patients who received an anti-angiogenesis drug as first-line combination therapy, those who received an anti-angiogenesis drug as further-line combination therapy, and those with no anti-angiogenesis therapy.

Results

A total of 204 patients were enrolled in the final analysis. Progression-free survival (PFS) in patients receiving first-line anti-angiogenesis plus EGFR-TKI combination therapy was longer (18.2 months) than those treated with first-line EGFR-TKI monotherapy (10.0 months for both, p < 0.001). No difference in overall survival (OS) was observed among these three groups (30.5 vs. 42.6 vs. 33.7 months, p = 0.326). Multivariate Cox regression analysis revealed L858R mutation, pleural liver, and bone metastasis as independent prognostic factors for poor OS. However, the addition of anti-angiogenesis therapy to patients with these poor prognostic factors improved OS to levels similar to those without these poor prognostic factors.

Conclusion

First-line combination EGFR-TKI plus anti-angiogenesis therapy improves PFS in patients with stage IV EGFR-mutant NSCLC. Adding an anti-angiogenesis drug at any line to patients harboring L858R mutation with pleural, liver, or bone metastases can provide survival benefits.
Intracranial extension of an intramuscular haemangioma of superior rectus: case report and literature review
Authors: Al-Johani Saud , Al-Romaih Arwa
Published: May 2022

Background

Intramuscular haemangiomas are rare, benign vascular tumours that represent < 1% of all haemangiomas. When involving the extraocular muscles, haemangiomas are extremely rare, with only nine cases reported in the literature; to date there are no reported cases of extraocular muscle haemangiomas extending into the brain.

Case presentation

A 6-year-old boy with a two-week history of a painless swelling and erythema on the upper eyelid. On examination, the patient had restricted extraocular motility in all directions of gaze. In addition, the eye appeared proptotic, with chemosis and hyperaemia of the conjunctiva. Visual acuity and intraocular pressure were normal. Orbital computed tomography imaging showed a mass in the left superior rectus, with heterogeneous enhancement following contrast administration. Incisional biopsy revealed an intramuscular haemangioma of the superior rectus muscle with capillary-type vessels. The patient received an intralesional steroid, which improved the condition for a few months; however, the lesion later recurred and included an intracranial extension.

Conclusion

This case represents the first reported case of intracranial extension of intramuscular haemangioma of extraocular muscle.
Impact of agitation/activation strategies on the antibiofilm potential of sodium hypochlorite/etidronate mixture in vitro
Authors: Cai Ming , Cai Yanling , Yang Ruiqi , Xu Zhezhen , Neelakantan Prasanna , Wei Xi
Published: May 2022

Background

To investigate the effect of a rotary agitation method or ultrasonically activated irrigation on the antibiofilm effect of a mixture of sodium hypochlorite (NaOCl) and etidronate (1-hydroxyethylidene-1,1-bisphosphonate, HEBP) using a dual-species biofilm model in root canal system.

Methods

Mature dual-species biofilms of Enterococcus faecalis and Streptococcus gordonii were formed in root canals of mandibular premolars. Teeth were randomly allotted (n = 12) to group 1, XP-endo Finisher (XPF); group 2, ultrasonically activated irrigation (UAI); group 3, syringe-and-needle irrigation (SNI). In all groups, canals were instrumented with a rotary instrument (XP-endo Shaper) prior to irrigant agitation/activation. A mixture containing 2.5% NaOCl and 9% HEBP was used throughout the experiment. Bacterial counts from the canal were determined using qPCR before preparation (S1), after preparation (S2), and after final irrigation agitation/activation (S3). Bacterial viability within the dentinal tubules in the coronal, middle and apical root-thirds was quantified using confocal microscopy after Live/Dead staining. The bacterial counts and viability were compared between groups using one-way ANOVA and post-hoc Tukey’s tests. Paired t-test was used to compare the bacterial counts within groups.

Results

Instrumentation alone could significantly reduce the microbial counts in all the groups (P < 0.0001). Subsequent agitation/activation resulted in significant microbial reduction only in XPF and UAI (P < 0.05), both of which reduced significantly more microbial counts than SNI (P < 0.05). Live/Dead staining revealed that XPF and UAI showed significantly greater percentage of dead bacteria within the dentinal tubules than SNI in the coronal third (P < 0.05); UAI resulted in the significantly highest percentage of dead bacteria in the middle third (P < 0.05); while there was no significant difference between the groups in the apical third (P > 0.05).

Conclusions

When using the sodium hypochlorite/etidronate mixture for irrigation, final irrigant agitation/activation with XP-endo Finisher or ultrasonic can improve disinfection of the main root canal space and the dentinal tubules in the coronal third, while ultrasonically activated irrigation appears to exhibit better disinfection within dentinal tubules in the middle third.
Molecular characteristics and genetic evolutionary analyses of circulating parvoviruses derived from cats in Beijing
Authors: Tang Yashu , Tang Na , Zhu Jingru , Wang Min , Liu Yang , Lyu Yanli
Published: May 2022

Background

Feline parvovirus (FPV) is a member of the family Parvoviridae, which is a major enteric pathogen of cats worldwide. This study aimed to investigate the prevalence of feline parvovirus in Beijing of China and analyze the genetic features of detected viruses.

Results

In this study, a total of 60 (8.5%) parvovirus-positive samples were detected from 702 cat fecal samples using parvovirus-specific PCR. The complete VP2 genes were amplified from all these samples. Among them, 55 (91.7%) sequences were characterized as FPV, and the other five (8.3%) were typed as canine parvovirus type 2 (CPV-2) variants, comprised of four CPV-2c and a new CPV-2b strain. In order to investigate the origin of CPV-2 variants in cats, we amplified full-length VP2 genes from seven fecal samples of dogs infected with CPV-2, which were further classified as CPV-2c. The sequences of new CPV-2b/MT270586 and CPV-2c/MT270587 detected from feline samples shared 100% identity with previous canine isolates KT156833 and MF467242 respectively, suggesting the CPV-2 variants circulating in cats might be derived from dogs. Sequence analysis indicated new mutations, Ala91Ser and Ser192Phe, in the FPV sequences, while obtained CPV-2c carried mutations reported in Asian CPV variants, showing they share a common evolutionary pattern with the Asian 2c strains. Interestingly, the FPV sequence (MT270571), displaying four CPV-specific residues, was found to be a putative recombinant sequence between CPV-2c and FPV. Phylogenetic analysis of the VP2 gene showed that amino acid and nucleotide mutations promoted the evolution of FPV and CPV lineages.

Conclusions

Our findings will be helpful to further understand the circulation and evolution of feline and canine parvovirus in Beijing.
Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study
Authors: Eyileten Ceren , Wicik Zofia , Keshwani Disha , Aziz Faisal , Aberer Felix , Pferschy Peter N. , Tripolt Norbert J. , Sourij Caren , Prietl Barbara , Prüller Florian , von Lewinski Dirk , De Rosa Salvatore , Siller-Matula Jolanta M. , Postula Marek , Sourij Harald
Published: May 2022

Background

In patients with type 2 diabetes mellitus (T2DM) an association between severe hypoglycaemic episodes and the risk of cardiovascular (CV) morbidity and mortality has been previously established.

Methods

We aimed to investigate the influence of hypoglycaemia on several diabetes-related and platelet-related miRNAs selected based on bioinformatic analysis and literature search, including hsa-miR-16, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a, miR-223, miR-126. Selected miRNAs were validated by qRT-PCR in 14 patients with T2DM on metformin monotherapy, without established CV disease and antiplatelet therapy during a stepwise hypoglycaemic clamp experiment and a follow-up 7 days after the clamp event. In order to identify which pathways and phenotypes are associated with validated miRNAs we performed target prediction on genes expressed with high confidence in platelets.

Results

Circulating levels of miR-106a-5p, miR-15b, miR-15a, miR-16-5p, miR-223 and miR-126 were increased after euglycaemic clamp followed by hypoglycaemic clamp, each with its distinctive time trend. On the contrary, miR-129-2-3p, miR-92a-3p and miR-34a-3p remained unchanged. MiR-16-5p was negatively correlated with interleukin (IL)-6, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) (p = 0.002, p < 0.001, p = 0.016, respectively), whereas miR-126 was positively correlated with VCAM (p < 0.001). There were negative correlations between miR-16-5p, miR-126 and coagulation factors, including factor VIII and von Willebrand factor (vWF). Among all studied miRNAs, miR-126, miR-129-2-3p and miR-15b showed correlation with platelet function. Bioinformatic analysis of platelet-related targets of analyzed miRNAs showed strong enrichment of IL-2 signaling. We also observed significant enrichment of pathways and diseases related to cancer, CV diseases, hyperglycemia, and neurological diseases.

Conclusions

Hypoglycaemia can significantly influence the expression of platelet-enriched miRNAs, with a time trend paralleling the time course of platelet activation. This suggests miRNAs could be exploited as biomarkers for platelet activation in response to hypoglycaemia, as they are probably released by platelets upon activation by hypoglycaemic episodes. Should they hold their promise in clinical endpoint studies, platelet-derived miRNAs might become helpful markers of CV risk in subjects with diabetes.

Trial registration The study was registered at clinical trials.gov; Impact of Hypoglycaemia in Patients With DIAbetes Mellitus Type 2 on PLATElet Activation (Diaplate), trial number: NCT03460899
Cardiac repolarization abnormalities in children with familial Mediterranean fever
Authors: Farag Yomna , Sayed Shaimaa , Mostafa Fatma Alzhraa , Marzouk Huda , Mohamed Raghda H. , Sobhy Rodina
Published: May 2022

Background

Familial Mediterranean fever (FMF) is an autoinflammatory disease that can have conduction disturbances and cardiac rhythm disorders as manifestations of cardiac involvement. The aim of the study is to assess the susceptibility of children with FMF to cardiac repolarization abnormalities and therefore arrhythmia in children with FMF.

Methods

A cross sectional study conducted on 60 children had FMF and 40 age and sex matched healthy controls. Cardiac repolarization markers, cardiac dimensions and functions were assessed by electrocardiogram (ECG) and conventional echocardiography in patients and controls.

Results

The mean ± SD age of the patients was 10.43 ± 3.472 years, corrected QT (QTc) and the ratio of peak to end T wave (Tpe) over QTc interval (Tpe /QTc) increased significantly in FMF patients more than healthy control (p value 0.023 and 0.022 respectively). P wave dispersion (Pd) was significantly higher in FMF patients with amyloidosis (p value 0.030). No significant difference was found in cardiac dimensions and functions between the two groups. We found a statistically negative correlation between Pd and age of patients at time of study, age of disease onset and age at diagnosis. On the other hand, we found a statistically significant positive correlation between Pd with number of attacks per year and disease severity score. Furthermore, Tpe/QTc ratio correlated with FMF 50 score, QTc correlated with 24 hours proteinuria. QT, JT intervals correlated with fibrinogen.

Conclusions

FMF Patients may have increased risk of arrhythmia and should be monitored on regular basis. Compliance to colchicine therapy and better disease control might play a role in decreasing this risk.
CCR5 activation and endocytosis in circulating tumor-derived cells isolated from the blood of breast cancer patients provide information about clinical outcome
Authors: Raghavakaimal Ashvathi , Cristofanilli Massimo , Tang Cha-Mei , Alpaugh R. K. , Gardner Kirby P. , Chumsri Saranya , Adams Daniel L.
Published: May 2022

Background

CCR5 is a motility chemokine receptor implicated in tumor progression, whose activation and subsequent endocytosis may identify highly aggressive breast cancer cell subtypes likely to spread into the circulatory system.

Methods

The MDA-MB-231 cell line was used to model and visualize CCR5 activation by stimulation with RANTES, in an effort to quantify CCR5 endocytosis from the cell surface to the perinuclear space. CCR5 expression was then examined in tumor-associated cells (TACs), consisting of circulating tumor cells and circulating stromal cells, isolated from the peripheral blood of 54 metastatic breast cancer (mBC) patients to evaluate these CCR5 pooling patterns as they relate to progression and survival over 2 years.

Results

In MB231 experiments, it was observed that CCR5 formed ~ 1 micron clusters identified as “CCR5 pools” on the surface of the cell, which in the presence of RANTES were endocytosed and translocated to the cell cytoplasm. When TACs from patients were analyzed, CCR5 pools were observed on the cell surface and translocating to the nuclear area, with CCR5 also having a positive statistical correlation between increased numbers of TACs and increased CCR5 pools on the cells. Further, it was determined that patients with very high numbers of CCR5 (> 10 CCR5 pools), specifically in the circulating stromal cells, were associated with worse progression-free survival (hazard ratio = 4.5, p = 0.002) and worse overall survival (hazard ratio = 3.7, p = 0.014).

Conclusions

Using a liquid biopsy approach, we evaluated two populations of tumor-associated cells emanating from primary tumors, with data suggesting that upregulation of the motility chemokine CCR5 in TACs provides clinically relevant opportunities for treating and tracking drug targetable receptors in mBC.
Comprehensive assessment of differential ChIP-seq tools guides optimal algorithm selection
Authors: Eder Thomas , Grebien Florian
Published: May 2022

Background

The analysis of chromatin binding patterns of proteins in different biological states is a main application of chromatin immunoprecipitation followed by sequencing (ChIP-seq). A large number of algorithms and computational tools for quantitative comparison of ChIP-seq datasets exist, but their performance is strongly dependent on the parameters of the biological system under investigation. Thus, a systematic assessment of available computational tools for differential ChIP-seq analysis is required to guide the optimal selection of analysis tools based on the present biological scenario.

Results

We created standardized reference datasets by in silico simulation and sub-sampling of genuine ChIP-seq data to represent different biological scenarios and binding profiles. Using these data, we evaluated the performance of 33 computational tools and approaches for differential ChIP-seq analysis. Tool performance was strongly dependent on peak size and shape as well as on the scenario of biological regulation.

Conclusions

Our analysis provides unbiased guidelines for the optimized choice of software tools in differential ChIP-seq analysis.
Are preoperative oral antibiotics effective in reducing the incidence of anastomotic leakage after colorectal cancer surgery? Study protocol for a prospective, multicentre, randomized controlled study
Authors: Gao Rui Qi , Wang Wei Dong , Yu Peng Fei , Mo Zhen Chang , Dong Dan Hong , Yang Xi Sheng , Li Xiao Hua , Ji Gang
Published: May 2022

Introduction

The optimal preoperative preparation for elective colorectal cancer surgery has been debated in academic circles for decades. Previously, several expert teams have conducted studies on whether preoperative mechanical bowel preparation and oral antibiotics can effectively reduce the incidence of postoperative complications, such as surgical site infections and anastomotic leakage. Most of the results of these studies have suggested that preoperative mechanical bowel preparation for elective colon surgery has no significant effect on the occurrence of surgical site infections and anastomotic leakage.

Methods/design

This study will examine whether oral antibiotic bowel preparation (OABP) influences the incidence of anastomotic leakage after surgery in a prospective, multicentre, randomized controlled trial that will enrol 1500 patients who require colon surgery. The primary endpoint, incidence of anastomotic leakage, is based on 2.3% in the OABP ± mechanical bowel preparation (MBP) group in the study by Morris et al. Patients will be randomized (1:1) into two groups: the test group will be given antibiotics (both neomycin 1 g and metronidazole 0.9 g) the day before surgery, and the control group will not receive any special intestinal preparation before surgery, including oral antibiotics or mechanical intestinal preparation. All study-related clinical data, such as general patient information, past medical history, laboratory examination, imaging results, and surgery details, will be recorded before surgery and during the time of hospitalization. The occurrence of postoperative fistulas, including anastomotic leakage, will be recorded as the main severe postoperative adverse event and will represent the primary endpoint.

Ethics and dissemination

Ethics approval was obtained from the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200173). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Protocol was revised on November 22, 2021, version 4.0.

Trial registration

ChiCTR2000035550. Registered on 13 Aug 2020.
The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants
Authors: Morowitz Michael J. , Katheria Anup C. , Polin Richard A. , Pace Elizabeth , Huang David T. , Chang Chung-Chou H. , Yabes Johathan G.
Published: May 2022

Background

Early-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2–3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants.

Methods

The NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants’ index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity.

Discussion

The NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery.

Trial registration

Trial registration data: June 25, 2019 NCT03997266.
Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)—study protocol for a phase 2, randomized, placebo controlled trial
Authors: Waibel M. , Thomas H. E. , Wentworth J. M. , Couper J. J. , MacIsaac R. J. , Cameron F. J. , So M. , Krishnamurthy B. , Doyle M. C. , Kay T. W.
Published: May 2022

Background

Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening.

The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function.

Methods

This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10–30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses.

Discussion

This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D.

Trial registration

ANZCTR ACTRN12620000239965. Registered on 26 February 2020. ClinicalTrials.gov NCT04774224. Registered on 01 March 2021
The role of non-Helicobacter pylori bacteria in the pathogenesis of gastroduodenal diseases
Authors: Waskito Langgeng Agung , Rezkitha Yudith Annisa Ayu , Vilaichone Ratha-korn , Sugihartono Titong , Mustika Syifa , Dewa Nyoman Wibawa I , Yamaoka Yoshio , Miftahussurur Muhammad
Published: May 2022

Over the past decade, the development of next-generation sequencing for human microbiota has led to remarkable discoveries. The characterization of gastric microbiota has enabled the examination of genera associated with several diseases, including gastritis, precancerous lesions, and gastric cancer. Helicobacter pylori (H. pylori) is well known to cause gastric dysbiosis by reducing diversity, because this bacterium is the predominant bacterium. However, as the diseases developed into more severe stages, such as atrophic gastritis, premalignant lesion, and gastric adenocarcinoma, the dominance of H. pylori began to be displaced by other bacteria, including Streptococcus, Prevotella, Achromobacter, Citrobacter, Clostridium, Rhodococcus, Lactobacillus, and Phyllobacterium. Moreover, a massive reduction in H. pylori in cancer sites was observed as compared with noncancer tissue in the same individual. In addition, several cases of H. pylori-negative gastritis were found. Among these individuals, there was an enrichment of Paludibacter, Dialister, Streptococcus, Haemophilus parainfluenzae, and Treponema. These remarkable findings suggest the major role of gastric microbiota in the development of gastroduodenal diseases and led us to the hypothesis that H. pylori might not be the only gastric pathogen. The gastric microbiota point of view of disease development should lead to a more comprehensive consideration of this relationship.
The effects of nano-curcumin supplementation on adipokines levels in obese and overweight patients with migraine: a double blind clinical trial study
Authors: Sedighiyan Mohsen , Abdolahi Mina , Jafari Elham , Vahabi Zahra , Sohrabi Athar Sara , Hadavi Shima , Narimani Zamanabadi Mahnaz , Yekaninejad Mir-Saeed , Djalali Mahmoud
Published: May 2022

Objective

The present study aimed to investigate the effects of nano-curcumin supplementation on adipokines levels and clinical signs in obese and overweight patients with migraine.

Results

Forty-four patients with episodic migraine participated in this clinical trial and were divided into two groups nano-curcumin (80 mg/day) and the control group over 2-month period. At the baseline and the end of the research, the serum levels of MCP-1, Resistin, and Visfatin were measured using the ELISA method. In addition, the headache attack frequencies, severity, and duration of pain were recorded. The results of the present study showed that nano-curcumin can significantly reduce MCP-1 serum levels in the nano-curcumin supplemented group (P = 0.015, size effect = 13.4%). In the case of resistin and visfatin, nano-curcumin supplementation exerted no statistically significant changes in serum levels (P > 0.05). Nano-curcumin also significantly reduced the attack frequencies, severity, and duration of headaches (P < 0.05). These findings indicate that targeting curcumin can be a promising approach to migraine management. However, further comprehensive human trials are needed to confirm these findings.

Trial Registration

This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20160626028637N2 on the date 2020-07-10.
$M_{\varphi}M_{\psi}$-convexity and separation theorems
Authors: Bombardelli Mea , Varošanec Sanja
Published: May 2022

A characterization of pairs of functions that can be separated by an $M_{\varphi}M_{\psi}$

M
φ

M
ψ

-convex function and related results are obtained. Also, a Hyers–Ulam stability result for $M_{\varphi}M_{\psi}$

M
φ

M
ψ

-convex functions is given.
Some inequalities and numerical results estimating error of approximation for tensor product kind bivariate quantum beta-type operators and pertaining to GBS variant
Authors: Özkan Esma Yıldız
Published: May 2022

In this study, we investigate some inequalities estimating the error of approximation for new defined tensor product kind quantum beta-type operators on rectangular regions, and we give an inequality in weighted mean. Moreover, we introduce generalized Boolean sum (GBS) operators pertaining to tensor product kind bivariate quantum beta-type operators, and we also give inequalities estimating the error of approximation for GBS variant concerning the mixed modulus of continuity for Bögel continuous and Bögel differentiable functions, respectively. Finally, we present some applications illustrating numerical results of approximation errors with the help of Maple software.