bluuebunny/crossref_metadata_2025 huggingface dataset:
A mixed methods multiple case study to evaluate the implementation of a care pathway for colorectal cancer surgery using extended normalization process theory
Authors: van Zelm R. , Coeckelberghs E. , Sermeus W. , Wolthuis A. , Bruyneel L. , Panella M. , Vanhaecht K.
Published: January 2021

Background

Specific factors that facilitate or prevent the implementation of enhanced recovery protocols for colorectal cancer surgery have been described in previous qualitative studies. This study aims to perform a concurrent qualitative and quantitative evaluation of factors associated with successful implementation of a care pathway (CP) for patients undergoing surgery for colorectal cancer.

Methods

This comparative mixed methods multiple case study was based on a sample of 10 hospitals in 4 European countries that implemented a specific CP and performed pre- and post-implementation measurements. In-depth post-implementation interviews were conducted with healthcare professionals who were directly involved. Primary outcomes included protocol adherence and improvement rate. Secondary outcomes included length of stay (LOS) and self-rated protocol adherence. The hospitals were ranked based on these quantitative findings, and those with the highest and lowest scores were included in this study. Qualitative data were summarized on a per-case basis using extended Normalization Process Theory (eNPT) as theoretical framework. The data were then combined and analyzed using joint display methodology.

Results

Data from 381 patients and 30 healthcare professionals were included. Mean protocol adherence rate increased from 56 to 62% and mean LOS decreased by 2.1 days. Both measures varied greatly between hospitals. The two highest-ranking hospitals and the three lowest-ranking hospitals were included as cases. Factors which could explain the differences in pre- and post-implementation performance included the degree to which the CP was integrated into daily practice, the level of experience and support for CP methodology provided to the improvement team, the intrinsic motivation of the team, shared goals and the degree of management support, alignment of CP development and hospital strategy, and participation of relevant disciplines, most notably, physicians.

Conclusions

Overall improvement was achieved but was highly variable among the 5 hospitals evaluated. Specific factors involved in the implementation process that may be contributing to these differences were conceptualized using eNPT. Multidisciplinary teams intending to implement a CP should invest in shared goals and teamwork and focus on integration of the CP into daily processes. Support from hospital management directed specifically at quality improvement including audit may likewise facilitate the implementation process.

Trial registration

NCT02965794.

US National Library of Medicine, ClinicalTrials.gov. Registered 4 August 2014.
'Generation Pup' – protocol for a longitudinal study of dog behaviour and health
Authors: Murray Jane Katherine , Kinsman Rachel Heather , Lord Michelle Susannah , Da Costa Rosa Elizabete Pinto , Woodward Joshua Luke , Owczarczak-Garstecka Sara Cecylia , Tasker Séverine , Knowles Toby Grahame , Casey Rachel Alison
Published: January 2021

Background

Despite extensive research, many questions remain unanswered about common problems that impact dog welfare, particularly where there are multiple contributing factors that can occur months or years before the problem becomes apparent. The Generation Pup study is the first longitudinal study of dogs that recruits pure- and mixed-breed puppies, aiming to investigate the relative influence of environmental and genetic factors on a range of health and behaviour outcomes, (including separation related behaviour, aggression to familiar/unfamiliar people or dogs and obesity). This paper describes the study protocol in detail.

Methods

Prior to commencing recruitment of puppies, the study infrastructure was developed, and subject specialists were consulted to inform data collection methodology. Questionnaire content and timepoint(s) for data collection for outcomes and potential predictors were chosen with the aim of providing the best opportunity of achieving the aims of the study, subject to time and funding constraints. Recruitment of puppies (< 16 weeks, or < 21 weeks of age if entering the United Kingdom or Republic of Ireland through quarantine) is underway. By 23 January 2020, 3726 puppies had been registered, with registration continuing until 10,000 puppies are recruited. Data collection encompasses owner-completed questionnaires issued at set timepoints throughout the dog’s life, covering aspects such as training, diet, exercise, canine behaviour, preventative health care, clinical signs and veterinary intervention. Owners can elect to submit additional data (health cards completed by veterinary professionals, canine biological samples) and/or provide consent for access to veterinary clinical notes. Incidence and breed associations will be calculated for conditions for which there is currently limited information (e.g. separation related behaviour). Multivariable statistical analysis will be conducted on a range of outcomes that occur throughout different life stages, with the aim of identifying modifiable risk factors that can be used to improve canine health and welfare.

Discussion

The Generation Pup project is designed to identify associations between early-life environment, genotypic make-up and outcomes at different life stages. Modifiable risk factors can be used to improve canine health and welfare. Research collaboration with subject specialists is welcomed and already underway within the fields of orthopaedic research, epilepsy, epigenetics and canine impulsivity.
Genetic association between CDKN2B/CDKN2B-AS1 gene polymorphisms with primary glaucoma in a North Indian cohort: an original study and an updated meta-analysis
Authors: Thakur Nanamika , Kupani Manu , Mannan Rashim , Pruthi Archna , Mehrotra Sanjana
Published: January 2021

Background

Variants in CDKN2B/CDKN2B-AS1 have been reported to modulate glaucoma risk in several GWAS across different populations. CDKN2B/CDKN2A encodes tumor suppressor proteins p16INK4A/p15INK4B which influences cell proliferation/senescence in RGCs, the degeneration of which is a risk factor for glaucoma. CDKN2B-AS1 codes a long non-coding RNA in antisense direction and is involved in influencing nearby CDKN2A/CDKN2B via regulatory mechanisms.

Methods

Current study investigated four SNPs (rs2157719, rs3217992, rs4977756, rs1063192) of aforementioned genes in a case–control study in a North Indian cohort. Genotyping was done with Taqman chemistry. In addition, an updated meta-analysis was performed.

Results

Two SNPs, rs3217992 and rs2157719 were found to be significantly associated with the disease. The frequency of ‘T’ allele of rs3217992 was significantly lower in cases (POAG/PACG) [p = 0.045; OR = 0.80(CI = 0.65–0.99) and p = 0.024; OR = 0.73(CI = 0.55–0.96)], respectively than in controls. Genetic model analysis revealed that TT + CT genotype confers 0.73-fold protection against POAG [p = 0.047; OR = 0.73(CI = 0.54–0.99)] and trend assumed additive model gives 0.53 times higher protection against PACG progression. However the association of rs3217992 with POAG and PACG did not remain significant after Bonferroni correction. For rs2157719, the ‘C’ allele was found to be less prevalent among cases (POAG/PACG) with respect to controls. Cochran Armitage trend test assuming additive model revealed 0.77 and 0.64-fold protection against POAG and PACG respectively. Bonferroni correction (pcorr = 0.003) was applied and the association of rs2157719 remained significant in PACG cases but not among POAG cases (p = 0.024). The ‘CC’ genotype also confers protection against primary glaucoma (POAG/PACG) among males and female subjects. The frequency rs1063192 and rs4977756 did not vary significantly among subjects, however the haplotype ‘CATA’ was found to be associated with increased glaucoma risk. An updated meta-analysis conducted on pooled studies on POAG cases and controls revealed significant association between rs1063192, rs2157719, rs4977756 and POAG except rs3217992.

Conclusion

The study concludes significant association between INK4 variants and primary glaucoma in the targeted North Indian Punjabi cohort. We believe that deep-sequencing of INK4 locus may help in identifying novel variants modifying susceptibility to glaucoma. Functional studies can further delineate the role of CDKN2B and CDKN2B-AS1 in primary glaucoma for therapeutic intervention.
Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid
Authors: de la Torre Paz , Fernández-de la Torre Miguel , Flores Ana I.
Published: January 2021

Background

Successful pregnancy is supported by a healthy maternal–fetal interface (i.e., the decidual tissues) which holds the conceptus and safeguards it against stressors from the beginning of pregnancy. Any disturbance of this interface can presumably lead to the loss of pregnancy. The use of the immunosuppressive drug mycophenolic acid (MPA) should be discontinued in pregnancy given its abortive and embryotoxic effects. Direct teratogenic effects have been observed in mammalian embryos cultured in MPA, but the underlying mechanisms of abortion by MPA are less understood.

Methods

Decidual stromal cells isolated from human placentas are cultured in the presence of clinically relevant doses of MPA. Data regarding the effects of MPA on the proliferation and viability of decidua cultures are first analysed and then, molecular pathways contributing to these effects are unravelled.

Results

MPA treatment of decidual stromal cells results in loss of proliferation capacity and a decrease in the viability of decidua cultures. The molecular pathways involved in the effects of MPA on decidual stromal cells are a reduction in pre-rRNA synthesis and subsequent disruption of the nucleolus. The nucleolar stress stabilizes p53, which in turn, leads to a p21–mediated cell cycle arrest in late S and G2 phases, preventing the progression of the decidua cells into the mitosis. Furthermore, MPA does not induce apoptosis but activate mechanisms of autophagy and senescence in decidual stromal cells.

Conclusion

The irreversible growth arrest of decidua cells, whose role in the maintenance of the pregnancy microenvironment is known, may be one cause of miscarriage in MPA treated pregnant women.
Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial
Authors: Tuttolomondo Antonino , Cirrincione Anna , Casuccio Alessandra , Del Cuore Alessandro , Daidone Mario , Di Chiara Tiziana , Di Raimondo Domenico , Corte Vittoriano Della , Maida Carlo , Simonetta Irene , Scaglione Stefania , Pinto Antonio
Published: January 2021

Background

Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage.

Aims

We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes.

Methods

Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose­ lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels.

Results

At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy.

Conclusions

Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.
Rhamnolipid the Glycolipid Biosurfactant: Emerging trends and promising strategies in the field of biotechnology and biomedicine
Authors: Thakur Priyanka , Saini Neeraj K. , Thakur Vijay Kumar , Gupta Vijai Kumar , Saini Reena V. , Saini Adesh K.
Published: January 2021

Rhamnolipids (RLs) are surface-active compounds and belong to the class of glycolipid biosurfactants, mainly produced from Pseudomonas aeruginosa. Due to their non-toxicity, high biodegradability, low surface tension and minimum inhibitory concentration values, they have gained attention in various sectors like food, healthcare, pharmaceutical and petrochemicals. The ecofriendly biological properties of rhamnolipids make them potent materials to be used in therapeutic applications. RLs are also known to induce apoptosis and thus, able to inhibit proliferation of cancer cells. RLs can also act as immunomodulators to regulate the humoral and cellular immune systems. Regarding their antimicrobial property, they lower the surface hydrophobicity, destruct the cytoplasmic membrane and lower the critical micelle concentration to kill the bacterial cells either alone or in combination with nisin possibly due to their role in modulating outer membrane protein. RLs are also involved in the synthesis of nanoparticles for in vivo drug delivery. In relation to economic benefits, the post-harvest decay of food can be decreased by RLs because they prevent the mycelium growth, spore germination of fungi and inhibit the emergence of biofilm formation on food. The present review focuses on the potential uses of RLs in cosmetic, pharmaceutical, food and health-care industries as the potent therapeutic agents.
Invited commentary: The Covid-19 pandemic in the United States
Authors: Holtzman Neil A. (Tony)
Published: January 2021

Despite being the wealthiest and one of the most technologically advanced countries in the world, the United States has the greatest number of Covid-19 cases and deaths. What accounts for this failure? The dismantling of the country’s public health infrastructure has crippled contact tracing and exacerbated inequality as a disproportionate number of poor people and people of color have fallen ill with Covid-19. Inadequate regulation of the private for-profit sector has adversely affected the efficiency and quality of testing for the virus, and the prescription of costly drugs whose benefit and safety in treating infected patients have not been established. More stringent regulation of the commercial sector has led to the development of efficacious vaccines in a remarkably short time. Still, questions remain about the vaccines’ effectiveness in the real world, and their safety.
Correction to: Beyond the map: evidencing the spatial dimension of health inequalities
Authors: Fayet Yohan , Praud Delphine , Fervers Béatrice , Ray-Coquard Isabelle , Blay Jean-Yves , Ducimetiere Françoise , Fagherazzi Guy , Faure Elodie
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Short- and medium-term outcomes of intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: a propensity score-matched study
Authors: Liao Chun-Kai , Chern Yih-Jong , Lin Yueh-Chen , Hsu Yu-Jen , Chiang Jy-Ming , Tsai Wen-Sy , Hsieh Pao-Shiu , Hung Hsin-Yuan , Yeh Chien-Yuh , You Jeng-Fu
Published: January 2021

Backgrounds

Though better short-term outcomes were frequently reported, differences in specimen parameters and the rate of subsequent peritoneal recurrence between intracorporeal anastomosis (IA) and extracorporeal anastomoses (EA) for laparoscopic right hemicolectomy have not been analyzed. We aimed to compare the pathologic differences and oncological outcomes between these two approaches.

Methods

We retrospectively analyzed 217 consecutive patients who underwent laparoscopic right hemicolectomies from September 2016 to April 2018 and classified them into IA and EA groups, based on the approach used. Propensity score matching analysis was performed, after which 101 patients were included in each group with the patients matched for demographics, tumor stage, and localization.

Results

The IA group had a longer operative time, shorter length of stay, shorter time to first flatus and tolerating a soft diet, and better pain scale scores at postoperative day 3. No inter-group differences in conversion, postoperative complication, mortality, or readmission rates were found. The IA group had a longer resected colon length (23.67 vs. 19.75 cm,p= 0.010) and nearest resected margin (7.51 vs. 5.40 cm,p= 0.010) for cancer near the hepatic flexure. There are comparable 3-year overall survival (87.7% vs. 89.6%,p= 0.604) and disease-free survival (75.0% vs. 75.7%,p= 0.842) between the IA and EA groups. The rate of peritoneal recurrence was similar between the two groups (5.9% vs. 7.9%,p= 0.580).

Conclusions

The overall survival, disease-free survival, and the rate of peritoneal recurrence were comparable between the IA and EA procedures. IA ensures better recovery and comparable complications to EA and achieved a more precise tumor excision; thus, IA can be considered a safe procedure for patients with right-sided colon lesions.
Measuring freezing of gait during daily-life: an open-source, wearable sensors approach
Authors: Mancini Martina , Shah Vrutangkumar V. , Stuart Samuel , Curtze Carolin , Horak Fay B. , Safarpour Delaram , Nutt John G.
Published: January 2021

Background

Although a growing number of studies focus on the measurement and detection of freezing of gait (FoG) in laboratory settings, only a few studies have attempted to measure FoG during daily life with body-worn sensors. Here, we presented a novel algorithm to detect FoG in a group of people with Parkinson’s disease (PD) in the laboratory (Study I) and extended the algorithm in a second cohort of people with PD at home during daily life (Study II).

Methods

In Study I, we described of our novel FoG detection algorithm based on five inertial sensors attached to the feet, shins and lumbar region while walking in 40 participants with PD. We compared the performance of the algorithm with two expert clinical raters who scored the number of FoG episodes from video recordings of walking and turning based on duration of the episodes: very short (< 1 s), short (2–5 s), and long (> 5 s). In Study II, a different cohort of 48 people with PD (with and without FoG) wore 3 wearable sensors on their feet and lumbar region for 7 days. Our primary outcome measures for freezing were the % time spent freezing and its variability.

Results

We showed moderate to good agreement in the number of FoG episodes detected in the laboratory (Study I) between clinical raters and the algorithm (if wearable sensors were placed on the feet) for short and long FoG episodes, but not for very short FoG episodes. When extending this methodology to unsupervised home monitoring (Study II), we found that percent time spent freezing and the variability of time spent freezing differentiated between people with and without FoG (p < 0.05), and that short FoG episodes account for 69% of the total FoG episodes.

Conclusion

Our findings showed that objective measures of freezing in PD using inertial sensors on the feet in the laboratory are matching well with clinical scores. Although results found during daily life are promising, they need to be validated. Objective measures of FoG with wearable technology during community-living would be useful for managing this distressing feature of mobility disability in PD.
Neutralization assay with SARS-CoV-1 and SARS-CoV-2 spike pseudotyped murine leukemia virions
Authors: Zheng Yue , Larragoite Erin T. , Williams Elizabeth S. C. P. , Lama Juan , Cisneros Isabel , Delgado Julio C. , Slev Patricia , Rychert Jenna , Innis Emily A. , Coiras Mayte , Rondina Matthew T. , Spivak Adam M. , Planelles Vicente
Published: January 2021

Background

Virus neutralization by antibodies is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal murine leukemia virus genome encoding firefly luciferase. This assay design is intended for use in laboratories with biocontainment level 2 and therefore circumvents the need for the biocontainment level 3 that would be required for replication-competent SARS-CoV-2 virus. To validate the pseudovirion assay, we set up comparisons with other available antibody tests including those from Abbott, Euroimmun and Siemens, using archived, known samples.

Results

11 out of 12 SARS-CoV-2-infected patient serum samples showed neutralizing activity against SARS-CoV-2-spike pseudotyped MLV viruses, with neutralizing titers-50 (NT50) that ranged from 1:25 to 1:1,417. Five historical samples from patients hospitalized for severe influenza infection in 2016 tested negative in the neutralization assay (NT50 < 25). Three serum samples with high neutralizing activity against SARS-CoV-2/MLV pseudoviruses showed no detectable neutralizing activity (NT50 < 25) against SARS-CoV-1/MLV pseudovirions. We also compared the semiquantitative Siemens SARS-CoV-2 IgG test, which measures binding of IgG to recombinantly expressed receptor binding domain of SARS-CoV-2 spike glycoprotein with the neutralization titers obtained in the pseudovirion assay and the results show high concordance between the two tests (R2 = 0.9344).

Conclusions

SARS-CoV-2 spike/MLV pseudovirions provide a practical means of assessing neutralizing activity of antibodies in serum or plasma from infected patients under laboratory conditions consistent with biocontainment level 2. This assay offers promise also in evaluating immunogenicity of spike glycoprotein-based candidate vaccines in the near future.
Effects of a psychological nursing intervention on prevention of anxiety and depression in the postpartum period: a randomized controlled trial
Authors: Liu Hongling , Yang Yang
Published: January 2021

Background

Anxiety and postpartum depression are the most common psychological problems in women after delivery. Cognitive behavior intervention has been reported to have an effect in the therapy of postpartum depression. This research aimed to investigate whether cognitive behavior intervention could prevent the pathogenesis of postpartum depression in primiparous women.

Methods

In this randomized controlled trial, primiparous women who were prone to postpartum depression were recruited. Participates in the control group received routine postpartum care and those in the intervention group received both routine postpartum care and cognitive behavior intervention. Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Edinburgh Postpartum Depression Scale (EPDS) and Pittsburgh Sleep Quality Index (PSQI) were evaluated before and after the intervention.

Results

In the intervention group, the post-intervention scores of HAMA, HAMD, EPDS and PSQI were all significantly lower than the baseline scores (p = 0.034, p = 0.038, p = 0.004, p = 0.014, respectively). The proportion of participants with postpartum depression in the intervention group (11.5%) was significantly lower than the control group (24.3%) after the 6-week intervention. Participants in the intervention group were significantly more satisfied with the care than those in the control group (p = 0.032).

Conclusion

This research provided evidence that cognitive behavioral intervention in postpartum period could alleviate anxiety and depression in primiparous women, and inhibit the pathogenesis of postpartum depression.

Trial registry This clinical trial was registered in the Chinese Clinical Trial Registry (ChiCTR2000040076).
Bibliometric analysis of peer-reviewed literature on antimicrobial stewardship from 1990 to 2019
Authors: Sweileh Waleed M.
Published: January 2021

Background

The World Health Organization recommended the implementation of antimicrobial stewardship (AMS) in the clinical settings to minimize the development and spread of antimicrobial resistance (AMR). The current study aimed to assess global research activity on AMS as one measure for efforts dedicated to contain AMR.

Method

A bibliometric method was applied using Scopus. A validated search query was implemented. Bibliometric indicators and mapping were generated. The study period was from 1990 to 2019. The search query utilized the keywords “antimicrobial stewardship” or “antibiotic stewardship” in the titles or abstracts. In addition, documents with the term “restrict” or “restriction” if used with the terms “antimicrobial” or “antibiotic” were retrieved.

Results

The search query returned 4402 documents. The keyword “antimicrobial stewardship” returned 2849 documents while the keyword “antibiotic stewardship” returned 1718 documents. The terms restrict/restriction and antimicrobial/antibiotics returned 209 documents. The number of publications and cumulative citations showed a steep and parallel increase in the last decade. The region of the Americas returned the most while the Eastern Mediterranean region returned the least. The United States (n = 1834, 41.7%) ranked first. Main research themes in the retrieved literature were the (1) impact of AMS on hospital length stay, (2) role of pharmacists, and (3) development of resistance of various pathogens. Clostridium difficile (n = 94) and Staphylococcus aureus (n = 76) were among the most frequently encountered author keywords. The Infection Control and Hospital Epidemiology journal ranked first (n = 245, 5.6%, h-index = 134) while documents published in the Clinical Infectious Diseases journal (h-index = 321) received the highest number of citations per document (70.7). At the institutional level, the US Centers for Disease Prevention and Control (n = 93, 2.1%) ranked first followed by the Imperial College London (n = 86, 2.0%). The main funding sponsors were the National Institute of Health. Pfizer, Merck, and Bayer pharmaceutical companies played a key role in funding AMS research. International research collaboration between developed (n = 3693, 83.9%) and developing countries (n = 759, 17.2%).

Conclusion

The fight against AMR is a global responsibility and implementation of AMS need to be carried out across the globe. International research collaboration between developing and developed countries should be encouraged.
A cross-sectional comparison of breastfeeding knowledge, attitudes, and perceived partners’ support among expectant couples in Mekelle, Ethiopia
Authors: Gebremariam Kidane Tadesse , Zelenko Oksana , Mulugeta Afework , Gallegos Danielle
Published: January 2021

Background

Breastfeeding is considered the biological norm and essential to reduce infant morbidity and mortality. Mothers are responsible for breastfeeding but the support of others, including their partners is an influential determinant. The aim of this study was to compare antenatal breastfeeding knowledge, attitudes, and perceived breastfeeding support of expectant couples in Mekelle, Ethiopia.

Methods

As part of a randomised controlled trial of an mHealth intervention, 128 couples in their third trimester from three selected health centres in Mekelle city were recruited to participate between September and October 2018. Couples who each had a personal mobile phone, read and spoke Tigrigna, and lived together were included. Baseline data on breastfeeding knowledge, attitudes, and perceived support (breastfeeding savvy, help, appreciation, presence and responsiveness) were collected using previously validated tools through interview by health workers.

Results

Compared to mothers, male partners were more likely to indicate their intention to provide breastfeeding appreciation (p = 0.02), breastfeeding presence (p = 0.002), and breastfeeding responsiveness (p = 0.04). The mothers’ prenatal perception of their partners’ intended breastfeeding support was lower than fathers’ perceptions to support their partners. Multiparous mothers had more positive perceptions regarding their partners’ breastfeeding savvy (p = 0.03), and breastfeeding help (p = 0.02) compared to primiparous mothers.

Conclusions

Fathers in Ethiopia are potentially strong supporters of breastfeeding practice. Future breastfeeding interventions should promote the involvement of fathers in breastfeeding and encourage mothers to increase their partners’ involvement in breastfeeding.
The role of activating transcription factor 6 in hydroxycamptothecin-induced fibroblast autophagy and apoptosis
Authors: Tao Jin , Chen Hui , Li Xiaolei , Wang Jingcheng
Published: January 2021

Background

The over-proliferation of fibroblasts is considered to be the main cause of scar adhesion after joint surgery. Hydroxycamptothecin (HCPT), though as a potent antineoplastic drug, shows preventive effects on scar adhesion. This study aimed to investigate the role of activating transcription factor 6 (ATF-6) in the HCPT-induced inhibition of fibroblast viability.

Methods

The cell counting kit-8 (CCK-8) assay, western blot analysis, lentivirus-mediated gene silencing, transmission electron microscopy (TEM) analysis, immunofluorescent staining for autophagy-related protein light chain 3 (LC3) were used to explore the effect of HCPT on triggering fibroblast apoptosis and inhibiting fibroblast proliferation, and the involvement of possible signaling pathways.

Results

It was found that HCPT exacerbated fibroblast apoptosis and repressed its proliferation. Subsequently, endoplasmic reticulum stress (ERS)-related proteins were determined by western blot prior to ATF6 p50 was screened out and reexamined after it was silenced. As a result, ATF6-mediated ERS played a role in HCPT-induced fibroblast apoptosis. Autophagy-related proteins and autophagosomes were detected after the HCPT administration using western blot and TEM analyses, respectively. Autophagy was activated after the HCPT treatment. With the co-treatment of autophagy inhibitor 3-methyladenine (3-MA), both the western blot analysis and the CCK-8 assay showed inhibited autophagy, which indicated that the effect of HCPT on fibroblast proliferation was partially reversed. Besides, the LC3 immunofluorescence staining revealed suppressed autophagy after silencing ATF6 p50.

Conclusion

Our results demonstrate that HCPT acts as a facilitator of fibroblast apoptosis and inhibitor of fibroblast proliferation for curbing the postoperative scar adhesion, in which the ATF6-mediated ERS pathway and autophagy are involved.
Retrospective study on effectiveness of Activ L total disc replacement
Authors: Sun Wenzhi , Wang Peng , Hu Hailiang , Kong Chao , Hai Yong , Lu Shibao
Published: January 2021

Background

The effectiveness of lumbar total disc replacement (TDR) with different prostheses for sagittal alignment has been reported previously. However, there are only few reports on Activ L TDR and no specific evidence regarding whether sagittal alignment affects the clinical outcomes.

Methods

Eighty-seven patients who underwent mono- or bi-segmental lumbar TDR with Activ L were studied. The films of the upright anteroposterior and lateral spine in neutral, flexion, and extension positions were obtained before surgery and at 1 month and 1 and 3 years after surgery. The radiographic parameters such as lumbar lordosis (LL), index level lordosis (IL), pelvic incidence (PI), pelvic tilt (PT), segmental lordosis (SL), and sacral slope (SS) were measured based on the lateral upright radiographs. Clinical outcomes were evaluated using the Oswestry Disability Index (ODI) and visual analog scale (VAS) pre- and post-operatively.

Results

Eighty-seven patients with complete radiographic data were available for a 3-year follow-up period. Of these, 66 received a single-level TDR, and 21 received a 2-level TDR. At 1 month, the mean LL was similar to the pre-operative data and then was significantly increased to 45.1° at 3 years. On average, the IL tended to significantly increase, while the mean SL at L–5 was increased from 16.5° pre-operatively to 21.0° at 3 years. The mean SL at L1–2, L2–3, L3–4, and L5–S1; PI; PT; and SS showed no obvious difference after 3 years. In contrast, VAS and ODI scores showed significant improvement after surgery.

Conclusions

Activ L TDR showed a favorable effect on sagittal alignment, enhancing the IL while preserving the LL and SS. However, satisfactory clinical results for over a 3-year follow-up were not affected by sagittal alignment.
Brachial-ankle pulse wave velocity is associated with the risk of osteoporosis: a cross-sectional evidence from a Chinese community-based cohort
Authors: Tang Kun , Zhang Qiao , Peng Nianchun , Hu Ying , Xu Shujing , Zhang Miao , Wang Rui , Shi Lixin
Published: January 2021

Background

Association of arterial stiffness and osteoporosis has been well documented in elderly population. However, it is not clear whether they co-progress from the early stages through common mechanisms. The object of this study was to evaluate possible associations between arterial stiffness and osteoporosis by measuring brachial-ankle pulse wave velocity (baPWV) and the Osteoporosis Self-Assessment Tool for Asia (OSTA) index among a healthy population of Chinese aged 40 years and older. Whether baPWV can be used as a predictor of osteoporosis on OSTA was further assessed.

Methods

This study was cross-sectional in design. Of 3984 adults aged 40 years and older in the Yunyan district of Guiyang (Guizhou, China) who underwent both OSTA and baPWV measurements within 1 month, 1407 were deemed eligible for inclusion (women, 1088; men, 319).

Results

The mean baPWV was 1475 ± 302 cm/s (range,766–3459 cm/s). baPWV in 110 individuals with high risk of osteoporosis (OSTA index < − 4) was higher than that of individuals with non-high risk (1733 ± 461 cm/s vs. 1447 ± 304 cm/s, P < 0.001). OSTA index was negatively correlated with baPWV(ρ = − 0.296, P < 0.001) after adjusting for age, sex, body mass index, waist circumference, diastolic blood pressure, and creatinine clearance rate. baPWV was an independent predictor for the presence of high risk of osteoporosis (β = − 0.001, P < 0.001) and was consistent across age and sex subgroups, and the optimal baPWV cutoff value for predicting the presence of high risk of osteoporosis and fracture was 1693 cm/s. The AUC was 0.722 (95% confidence interval [CI], 0.667–0.777; P < 0.001, sensitivity of 52.8% and specificity of 83.6%).

Conclusions

We conclude that arterial stiffness measured by baPWV is well correlated with the severity of osteoporosis evaluated by OSTA. baPWV index may be a valuable tool for identifying individuals with risk of developing osteoporosis.
Compacting a synthetic yeast chromosome arm
Authors: Luo Zhouqing , Yu Kang , Xie Shangqian , Monti Marco , Schindler Daniel , Fang Yuan , Zhao Shijun , Liang Zhenzhen , Jiang Shuangying , Luan Meiwei , Xiao Chuanle , Cai Yizhi , Dai Junbiao
Published: January 2021

Background

Redundancy is a common feature of genomes, presumably to ensure robust growth under different and changing conditions. Genome compaction, removing sequences nonessential for given conditions, provides a novel way to understand the core principles of life. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system is a unique feature implanted in the synthetic yeast genome (Sc2.0), which is proposed as an effective tool for genome minimization. As the Sc2.0 project is nearing its completion, we have begun to explore the application of the SCRaMbLE system in genome compaction.

Results

We develop a method termed SCRaMbLE-based genome compaction (SGC) and demonstrate that a synthetic chromosome arm (synXIIL) can be efficiently reduced. The pre-introduced episomal essential gene array significantly enhances the compacting ability of SGC, not only by enabling the deletion of nonessential genes located in essential gene containing loxPsym units but also by allowing more chromosomal sequences to be removed in a single SGC process. Further compaction is achieved through iterative SGC, revealing that at least 39 out of 65 nonessential genes in synXIIL can be removed collectively without affecting cell viability at 30 °C in rich medium. Approximately 40% of the synthetic sequence, encoding 28 genes, is found to be dispensable for cell growth at 30 °C in rich medium and several genes whose functions are needed under specified conditions are identified.

Conclusions

We develop iterative SGC with the aid of eArray as a generic yet effective tool to compact the synthetic yeast genome.
Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer
Authors: Oka Miho , Xu Liu , Suzuki Toshihiro , Yoshikawa Toshiaki , Sakamoto Hiromi , Uemura Hayato , Yoshizawa Akiyasu C. , Suzuki Yutaka , Nakatsura Tetsuya , Ishihama Yasushi , Suzuki Ayako , Seki Masahide
Published: January 2021

Background

Long-read sequencing of full-length cDNAs enables the detection of structures of aberrant splicing isoforms in cancer cells. These isoforms are occasionally translated, presented by HLA molecules, and recognized as neoantigens. This study used a long-read sequencer (MinION) to construct a comprehensive catalog of aberrant splicing isoforms in non-small-cell lung cancers, by which novel isoforms and potential neoantigens are identified.

Results

Full-length cDNA sequencing is performed using 22 cell lines, and a total of 2021 novel splicing isoforms are identified. The protein expression of some of these isoforms is then validated by proteome analysis. Ablations of a nonsense-mediated mRNA decay (NMD) factor, UPF1, and a splicing factor, SF3B1, are found to increase the proportion of aberrant transcripts. NetMHC evaluation of the binding affinities to each type of HLA molecule reveals that some of the isoforms potentially generate neoantigen candidates. We also identify aberrant splicing isoforms in seven non-small-cell lung cancer specimens. An enzyme-linked immune absorbent spot assay indicates that approximately half the peptide candidates have the potential to activate T cell responses through their interaction with HLA molecules. Finally, we estimate the number of isoforms in The Cancer Genome Atlas (TCGA) datasets by referring to the constructed catalog and found that disruption of NMD factors is significantly correlated with the number of splicing isoforms found in the TCGA-Lung Adenocarcinoma data collection.

Conclusions

Our results indicate that long-read sequencing of full-length cDNAs is essential for the precise identification of aberrant transcript structures in cancer cells.
Combined low-dose everolimus and low-dose tacrolimus after Alemtuzumab induction therapy: a randomized prospective trial in lung transplantation
Authors: Benazzo Alberto , Cho Ara , Nechay Anna , Schwarz Stefan , Frommlet Florian , Wekerle Thomas , Hoetzenecker Konrad , Jaksch Peter
Published: January 2021

Background

Long-term outcomes of lung transplantation are severely affected by comorbidities and development of chronic rejection. Among the comorbidities, kidney insufficiency is one of the most frequent and it is mainly caused by the cumulative effect of calcineurin inhibitors (CNIs). Currently, the most used immunosuppression protocols worldwide include induction therapy and a triple-drug maintenance immunosuppression, with one calcineurin inhibitor, one anti-proliferative drug, and steroids. Our center has pioneered the use of alemtuzumab as induction therapy, showing promising results in terms of short- and long-term outcomes. The use of alemtuzumab followed by a low-dose double drug maintenance immunosuppression, in fact, led to better kidney function along with excellent results in terms of acute rejection, chronic lung allograft dysfunction, and survival (Benazzo et al., PLoS One 14(1):e0210443, 2019). The hypothesis driving the proposed clinical trial is that de novo introduction of low-dose everolimus early after transplantation could further improve kidney function via a further reduction of tacrolimus. Based on evidences from kidney transplantation, moreover, alemtuzumab induction therapy followed by a low-dose everolimus and low-dose tacrolimus may have a permissive action on regulatory immune cells thus stimulating allograft acceptance.

Methods

A randomized prospective clinical trial has been set up to answer the research hypothesis. One hundred ten patients will be randomized in two groups. Treatment group will receive the new maintenance immunosuppression protocol based on low-dose tacrolimus and low-dose everolimus and the control group will receive our standard immunosuppression protocol. Both groups will receive alemtuzumab induction therapy. The primary endpoint of the study is to analyze the effect of the new low-dose immunosuppression protocol on kidney function in terms of eGFR change. The study will have a duration of 24 months from the time of randomization. Immunomodulatory status of the patients will be assessed with flow cytometry and gene expression analysis.

Discussion

For the first time in the field of lung transplantation, this trial proposes the combined use of significantly reduced tacrolimus and everolimus after alemtuzumab induction. The new protocol may have a twofold advantage: (1) further reduction of nephrotoxic tacrolimus and (2) permissive influence on regulatory cells development with further reduction of rejection episodes.

Trial registration

EUDRACT Nr 2018-001680-24. Registered on 15 May 2018
A randomised controlled trial comparing palate surgery at 6 months versus 12 months of age (the TOPS trial): a statistical analysis plan
Authors:   On behalf of the TOPS trial management group, Conroy Elizabeth J. , Cooper Rachael , Shaw William , Persson Christina , Willadsen Elisabeth , Munro Kevin J. , Williamson Paula R. , Semb Gunvor , Walsh Tanya , Gamble Carrol
Published: January 2021

Background

Cleft palate is among the most common birth abnormalities. The success of primary surgery in the early months of life is crucial for successful feeding, hearing, dental development, and facial growth. Over recent decades, age at palatal surgery in infancy has reduced. The Timing Of Primary Surgery for cleft palate (TOPS) trial aims to determine whether, in infants with cleft palate, it is better to perform primary surgery at age 6 or 12 months (corrected for gestational age).

Methods/design

The TOPS trial is an international, two-arm, parallel group, randomised controlled trial. The primary outcome is insufficient velopharyngeal function at 5 years of age. Secondary outcomes, measured at 12 months, 3 years, and 5 years of age, include measures of speech development, safety of the procedure, hearing level, middle ear function, dentofacial development, and growth. The analysis approaches for primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The TOPS protocol has been published previously.

Discussion

This paper provides details of the planned statistical analyses for the TOPS trial and will reduce the risk of outcome reporting bias and data-driven results.

Trial registration

ClinicalTrials.gov NCT00993551. Registered on 9 October 2009.
Plant nutrient quality impacts survival and reproductive fitness of the dengue vector Aedes aegypti
Authors: Nyasembe Vincent Odhiambo , Tchouassi David Poumo , Muturi Martha Njeri , Pirk Christian W. W. , Sole Catherine L. , Torto Baldwyn
Published: January 2021

Background

In a recent study using DNA barcoding, we identified the plants fed upon by four Afro-tropical mosquito species that vector dengue, malaria, and Rift Valley fever. Herein, we have expanded on this study by investigating the role of three of the plants, Pithecellobium dulce (Fabaceae), Leonotis nepetifolia (Lamiaceae), and Opuntia ficus-indica (Cactaceae), on the survival, fecundity, and egg viability of the dengue vector Aedes aegypti.

Methods

We tested these effects using females that received (i) an initial three rations of blood meals and (ii) no blood meal at all. Two controls were included: age-matched females fed on glucose solution with or without an initial blood meal and those fed exclusively on blood meals. Data were collected daily over a 30-day period. The amino acid contents of Ae. aegypti guts and their respective diets were detected by coupled liquid chromatography-mass spectrometry.

Results

Females fed on P. dulce and an exclusively blood meal diet had a shorter survival than those fed on glucose. On the other hand, females fed on L. nepetifolia survived longer than those fed exclusively on blood meals, whereas those fed on O. ficus-indica had the shortest survival time. With an initial blood meal, females fed on L. nepetifolia laid 1.6-fold more eggs while those fed on the other diets laid fewer eggs compared to those fed exclusively on blood meals. Hatching rates of the eggs laid varied with the diet. Mass spectroscopic analysis of gut contents of mosquitoes exposed to the different diets showed qualitative and quantitative differences in their amino acid levels.

Conclusion

Our findings highlight the central role of plant nutrients in the reproductive fitness of dengue vectors, which may impact their disease transmission potential.

Graphical Abstract