bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in psychosocial status of adolescents during COVID-19: a six-country cross-sectional survey in Asia Pacific
Authors: Wang Jun , Aaron Alec , Baidya Anurima , Chan Christabel , Wetzler Erica , Savage Kevin , Joseph Michael , Kang Yunhee
Published: November 2021

Background

School closures and family economic instability caused by the COVID-19 lockdown measures have threatened the mental health and academic progress of adolescents. Through secondary data analysis of World Vision Asia Pacific Region’s COVID-19 response-assessments in May–June 2020, this study examined whether adolescents’ study, physical, and leisure activities, psychosocial status, and sources of COVID-19 information differed by gender.

Methods

The assessments used cross-sectional surveys of adolescents in poor communities served by World Vision (n = 5552 males and n = 6680 females) aged 10–18 years old in six countries. The study households of adolescents were selected either by random sampling or non-probability convenience sampling and assessed using telephone or in-person interviews. Multivariate logistic regression analyses examined the relationship between gender and psychosocial status; daily activities (e.g., play, study); and sources of information about COVID-19.

Results

Participation in remote education was low (range: 0.5–20.7% across countries), with gender difference found only in Vietnam. Compared to males, female adolescents were less likely to play physically with a range of AOR: 0.36–0.55 (n = 5 countries) or play video games with a range of AOR: 0.55–0.72 (n = 2 countries). Female adolescents were more likely to feel isolated or stressed (India, AOR = 1.13, 95%CI:1.00, 1.26); feel unsafe (the Philippines, AOR = 2.22, 95%CI:1.14, 4.33; Vietnam, AOR = 1.31, 95%CI:1.03, 1.47); be concerned about education (India, AOR = 1.24, 95%CI:1.09, 1.41; Myanmar, AOR = 1.59, 95%CI:1.05, 2.40); or be concerned about household income (India, AOR = 1.13, 95%CI:1.00, 1.28; Vietnam, AOR = 1.31, 95%CI:1.09, 1.58). Female adolescents were also less likely to obtain COVID-19 related information through internet/social media (Bangladesh, AOR = 0.51, 95%CI:0.41, 0.64; India, AOR = 0.84, 95%CI:0.73, 0.96; and Myanmar, AOR = 0.65, 95%CI:0.43, 0.97) and mobile call or short message (India, AOR = 0.88, 95%CI:0.80, 0.98) but more likely to get the information from friends (Vietnam, AOR = 1.18, 95%CI:1.02, 1.36) and family (Bangladesh, AOR = 1.44, 95% CI:1.21, 1.70; India, AOR = 1.29, 95% CI:1.15, 1.45).

Conclusions

An understanding of gender differences in the impacts of COVID-19 on adolescents' schooling, physical, and mental health can inform adolescent protection interventions. Psychosocial support during response and recovery phases needs to pay special attention to gender differences, since female adolescents’ psychosocial status is at higher risk when facing the challenges of this pandemic.
Modeling of lung phenotype of Hermansky–Pudlak syndrome type I using patient-specific iPSCs
Authors: Suezawa Takahiro , Kanagaki Shuhei , Korogi Yohei , Nakao Kazuhisa , Hirai Toyohiro , Murakami Koji , Hagiwara Masatoshi , Gotoh Shimpei
Published: November 2021

Background

Somatic cells differentiated from patient-specific human induced pluripotent stem cells (iPSCs) could be a useful tool in human cell-based disease research. Hermansky–Pudlak syndrome (HPS) is an autosomal recessive genetic disorder characterized by oculocutaneous albinism and a platelet dysfunction. HPS patients often suffer from lethal HPS associated interstitial pneumonia (HPSIP). Lung transplantation has been the only treatment for HPSIP. Lysosome-related organelles are impaired in HPS, thereby disrupting alveolar type 2 (AT2) cells with lamellar bodies. HPSIP lungs are characterized by enlarged lamellar bodies. Despite species differences between human and mouse in HPSIP, most studies have been conducted in mice since culturing human AT2 cells is difficult.

Methods

We generated patient-specific iPSCs from patient-derived fibroblasts with the most common bi-allelic variant, c.1472_1487dup16, in HPS1 for modeling severe phenotypes of HPSIP. We then corrected the variant of patient-specific iPSCs using CRISPR-based microhomology-mediated end joining to obtain isogenic controls. The iPSCs were then differentiated into lung epithelial cells using two different lung organoid models, lung bud organoids (LBOs) and alveolar organoids (AOs), and explored the phenotypes contributing to the pathogenesis of HPSIP using transcriptomic and proteomic analyses.

Results

The LBOs derived from patient-specific iPSCs successfully recapitulated the abnormalities in morphology and size. Proteomic analysis of AOs involving iPSC-derived AT2 cells and primary lung fibroblasts revealed mitochondrial dysfunction in HPS1 patient-specific alveolar epithelial cells. Further, giant lamellar bodies were recapitulated in patient-specific AT2 cells.

Conclusions

The HPS1 patient-specific iPSCs and their gene-corrected counterparts generated in this study could be a new research tool for understanding the pathogenesis of HPSIP caused by HPS1 deficiency in humans.
Codon pair optimization (CPO): a software tool for synthetic gene design based on codon pair bias to improve the expression of recombinant proteins in Pichia pastoris
Authors: Huang Yide , Lin Ting , Lu Lingfang , Cai Fan , Lin Jie , Jiang Yu′e , Lin Yao
Published: November 2021

Background

Codon optimization is a common method to improve protein expression levels in Pichia pastoris and the current strategy is to replace rare codons with preferred codons to match the codon usage bias. However, codon-pair contexts have a profound effect on translation efficiency by influencing both translational elongation rates and accuracy. Until now, it remains untested whether optimized genes based on codon pair bias results in higher protein expression levels compared to codon usage bias.

Results

In this study, an algorithm based on dynamic programming was introduced to develop codon pair optimization (CPO) which is a software tool to provide simple and efficient codon pair optimization for synthetic gene design in Pichia pastoris. Two reporters (MT1-MMP E2C6 and ADAM17 A9B8 scFvs) were employed to test the effects of codon pair bias and CPO optimization on their protein expression levels. Four variants of MT1-MMP E2C6 and ADAM17 A9B8 for each were generated, one variant with the best codon-pair context, one with the worst codon-pair context, one with unbiased codon-pair context, and another optimized based on codon usage. The expression levels of variants with the worst codon-pair context were almost undetectable by Western blot and the variants with the best codon-pair context were expressed well. The expression levels on MT1-MMP E2C6 and ADAM17 A9B8 were more than five times and seven times higher in the optimized sequences based on codon-pair context compared to that based on codon usage, respectively. The results indicated that the codon-pair context-based codon optimization is more effective in enhancing expression of protein in Pichia pastoris.

Conclusions

Codon-pair context plays an important role on the protein expression in Pichia pastoris. The codon pair optimization (CPO) software developed in this study efficiently improved the protein expression levels of exogenous genes in Pichia pastoris, suggesting gene design based on codon pair bias is an alternative strategy for high expression of recombinant proteins in Pichia pastoris.
Optimising co-design with ethnic minority consumers
Authors: Chauhan Ashfaq , Leefe Jessica , Shé Éidín Ní , Harrison Reema
Published: November 2021

Co-design as a participatory method aims to improve health service design and implementation. It is being used more frequently by researchers and practitioners in various health and social care settings. Co-design has the potential for achieving positive outcomes for the end users involved in the process; however, involvement of diverse ethnic minority population in the process remains limited. While the need to engage with diverse voices is identified, there is less information available on how to achieve meaningful engagement with these groups. Ethnic minorities are super-diverse population and the diversity between and within these groups need consideration for optimising their participation in co-design. Based on our experience of working with diverse ethnic minority groups towards the co-design of consumer engagement strategies to improve patient safety in cancer services as part of the two nationally-funded research projects in Australia, we outline reflections and practical techniques to optimise co-design with people from diverse ethnic backgrounds. We identify three key aspects of the co-design process pertinent to the involvement of this population; 1) starting at the pre-commencement stage to ensure diverse, seldom heard consumers are invited to and included in co-design work, 2) considering logistics and adequate resources to provide appropriate support to address needs before, during and beyond the co-design process, and 3) supporting and enabling a diversity of contributions via the co-design process.
α-Fe2O3@Pt heterostructure particles to enable sonodynamic therapy with self-supplied O2 and imaging-guidance
Authors: Zhang Tian , Zheng Qiang , Fu Yike , Xie Congkun , Fan Gonglin , Wang Yifan , Wu Yongjun , Cai Xiujun , Han Gaorong , Li Xiang
Published: November 2021

Sonodynamic therapy (SDT), presenting spatial and temporal control of ROS generation triggered by ultrasound field, has attracted considerable attention in tumor treatment. However, its therapeutic efficacy is severely hindered by the intrinsic hypoxia of solid tumor and the lack of smart design in material band structure. Here in study, fine α-Fe2O3 nanoparticles armored with Pt nanocrystals (α-Fe2O3@Pt) was investigated as an alternative SDT agent with ingenious bandgap and structural design. The Schottky barrier, due to its unique heterostructure, suppresses the recombination of sono-induced electrons and holes, enabling superior ROS generation. More importantly, the composite nanoparticles may effectively trigger a reoxygenation phenomenon to supply sufficient content of oxygen, favoring the ROS induction under the hypoxic condition and its extra role played for ultrasound imaging. In consequence, α-Fe2O3@Pt appears to enable effective tumor inhibition with imaging guidance, both in vitro and in vivo. This study has therefore demonstrated a highly potential platform for ultrasound-driven tumor theranostic, which may spark a series of further explorations in therapeutic systems with more rational material design.

Graphical Abstract
Evaluation of the clinical value of carbon nanoparticles in endoscopic thyroidectomy and prophylactic central neck dissection through total mammary areolas approach for thyroid cancer
Authors: He Jie , Zhang Chaojie , Zhang Zeyu , Xia Fada
Published: November 2021

Background

Carbon nanoparticles (CNs) are tracers used in thyroid surgery of patients with thyroid cancer (TC) to help remove lymph nodes and protect the parathyroid gland. The facilitative effect of carbon nanoparticles in endoscopic thyroidectomy and prophylactic central neck dissection (pCND) has not been reported.

Methods

The protective effect on parathyroid gland (PG) function and the numbers of identified parathyroid glands and central lymph nodes in endoscopic thyroid surgery through the total mammary areolas approach were compared between the CN and control groups.

Results

All endoscopic thyroidectomies were successfully completed. No difference was found in either group regarding the general characteristics or operative complications. The mean number of superior PGs and inferior PGs identified in situ or in the dissected central lymph tissues was not different between the groups. The mean number of lymph nodes removed by unilateral CND was greater in the CN group than in the control group. However, there was no difference in the number of harvested lymph nodes when excluding the LNs less than 5 mm, which exhibit an extremely low metastatic rate.

Conclusion

Carbon nanoparticles do not improve the protective effect on the parathyroid gland, especially the inferior glands, in endoscopic thyroid surgery through the total mammary areolas approach. There is no need to use CNs to facilitate the lymph node harvest in endoscopic prophylactic unilateral CND.
The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis
Authors: Mu Yu , Zhao Linxian , He Hongyu , Zhao Huimin , Li Jiannan
Published: November 2021

Background

Protective ileostomy is always applied to avoid clinically significant anastomotic leakage and other postoperative complications for patients receiving laparoscopic rectal cancer surgery. However, whether it is necessary to perform the ileostomy is still controversial. This meta-analysis aims to analyze the efficacy of ileostomy on laparoscopic rectal cancer surgery.

Methods

Cochrane Library, EMBASE, Web of Science, and PubMed were applied for systematic search of all relevant literature, updated to May 07, 2021. Studies compared patients with and without ileostomy for laparoscopic rectal cancer surgery. We applied Review Manager software to perform this meta-analysis. The quality of the non-randomized controlled trials was assessed using the Newcastle-Ottawa scale (NOS), and the randomized studies were assessed using the Jadad scale.

Results

We collected a total of 1203 references, and seven studies were included using the research methods. The clinically significant anastomotic leakage rate was significantly lower in ileostomy group (27/567, 4.76%) than that in non-ileostomy group (54/525, 10.29%) (RR = 0.47, 95% CI 0.30–0.73, P for overall effect = 0.0009, P for heterogeneity = 0.18, I2 = 32%). However, the postoperative hospital stay, reoperation, wound infection, and operation time showed no significant difference between the ileostomy and non-ileostomy groups.

Conclusion

The results demonstrated that protective ileostomy could decrease the clinically significant anastomotic leakage rate for patients undergoing laparoscopic rectal cancer surgery. However, ileostomy has no effect on postoperative hospital stay, reoperation, wound infection, and operation time. The efficacy of ileostomy after laparoscopic rectal cancer surgery: a meta-analysis.
Corpus luteum number and the maternal renin-angiotensin-aldosterone system as determinants of utero-placental (vascular) development: the Rotterdam Periconceptional Cohort
Authors: Wiegel Rosalieke E. , Karsten Maud J. H. , Reijnders Igna F. , van Rossem Lenie , Willemsen Sten P. , Mulders Annemarie G. M. G. J. , Koning Anton H. J. , Steegers Eric A. P. , Danser A. H. Jan , Steegers-Theunissen Régine P. M.
Published: November 2021

Background

Pregnancies with > 1 corpus luteum (CL) display a hyperdynamic circulation and an increased risk of small-for-gestational age deliveries. Among the factors released by the CL is prorenin, the inactive precursor of renin. Since the renin-angiotensin-aldosterone system (RAAS) is involved in early hemodynamic pregnancy adaptation, we linked both CL number and first-trimester concentrations of prorenin (as an indicator of RAAS activity) and the aldosterone/renin ratio (as an indicator of angiotensin-independent aldosterone effectiveness) to non-invasive markers of utero-placental (vascular) development, measured longitudinally from the first trimester onwards.

Methods

A total of 201 women, who conceived naturally or after in-vitro fertilization treatment (with 0 (n = 8), 1 (n = 143), or > 1 (n = 51) CL), were selected from the Rotterdam Periconceptional Cohort. Maternal RAAS components were determined at 11 weeks gestation. Placental volume and utero-placental vascular volume were measured from transvaginal 3D ultrasound scans at 7, 9 and 11 weeks gestation, pulsatility and resistance indices of the uterine arteries were assessed by pulsed wave Doppler ultrasounds at 7, 9, 11, 13, 22 and 32 weeks gestation. At birth placental weight was obtained using standardized procedures.

Results

Pregnancies without a CL show lower uterine artery indices throughout gestation than 1 CL and > 1 CL pregnancies, while parameters of placental development are comparable among the CL groups. After adjustment for patient- and treatment-related factors, first-trimester prorenin concentrations are positively associated with uterine artery pulsatility and resistance indices (β 0.06, 95% CI 0.01;0.12, p = 0.04 and β 0.10, 95% CI 0.01;0.20, p = 0.04, respectively), while high prorenin concentrations are negatively associated with first-trimester utero-placental vascular volume (β -0.23, 95% CI -0.44;-0.02, p = 0.04) and placental weight (β -93.8, 95%CI -160.3;-27.4, p = 0.006). In contrast, the aldosterone/renin ratio is positively associated with first-trimester placental volume (β 0.12, 95% CI 0.01;0.24, p = 0.04).

Conclusions

The absence of a CL, resulting in low prorenin concentrations, associates with low uterine artery pulsatility and resistance, while high prorenin concentrations associate with a low utero-placental vascular volume and weight. These data support a scenario in which excess prorenin, by upregulating angiotensin II, increases uterine resistance, thereby preventing normal placental (vascular) development, and increasing the risk of small-for-gestational age deliveries. Simultaneously, high aldosterone concentrations, by ensuring volume expansion, exert the opposite.
A systematic review of the validity, reliability, and feasibility of measurement tools used to assess the physical activity and sedentary behaviour of pre-school aged children
Authors: Phillips Sophie M. , Summerbell Carolyn , Hobbs Matthew , Hesketh Kathryn R. , Saxena Sonia , Muir Cassey , Hillier-Brown Frances C.
Published: November 2021

Physical activity (PA) and sedentary behaviour (SB) of pre-school aged children are associated with important health and developmental outcomes. Accurate measurement of these behaviours in young children is critical for research and practice in this area. The aim of this review was to examine the validity, reliability, and feasibility of measurement tools used to assess PA and SB of pre-school aged children.

Searches of electronic databases, and manual searching, were conducted to identify articles that examined the measurement properties (validity, reliability or feasibility) of measurement tools used to examine PA and/or SB of pre-school aged children (3–7 years old). Following screening, data were extracted and risk of bias assessment completed on all included articles.

A total of 69 articles, describing 75 individual studies were included. Studies assessed measurement tools for PA (n = 27), SB (n = 5), and both PA and SB (n = 43). Outcome measures of PA and SB differed between studies (e.g. moderate to vigorous activity, step count, posture allocation). Most studies examined the measurement properties of one measurement tool only (n = 65). Measurement tools examined included: calorimetry, direct observation, combined heart rate and accelerometry, heart rate monitors, accelerometers, pedometers, and proxy report (parent, carer or teacher reported) measures (questionnaires or diaries). Studies most frequently assessed the validity (criterion and convergent) (n = 65), face and content validity (n = 2), test-retest reliability (n = 10) and intra-instrument reliability (n = 1) of the measurement tools. Feasibility data was abstracted from 41 studies.

Multiple measurement tools used to measure PA and SB in pre-school aged children showed some degree of validity, reliability and feasibility, but often for different purposes. Accelerometers, including the Actigraph (in particular GT3X versions), Actical, ActivPAL and Fitbit (Flex and Zip), and proxy reported measurement tools used in combination may be useful for a range of outcome measures, to measure intensity alongside contextual information.
MPS1 is involved in the HPV16-E7-mediated centrosomes amplification
Authors: Alfaro-Mora Yair , Domínguez-Gómez Guadalupe , Cáceres-Gutiérrez Rodrigo E. , Tolentino-García Laura , Herrera Luis A. , Castro-Hernández Clementina , Bermúdez-Cruz Rosa María , Díaz-Chávez José
Published: November 2021

Background

It has been reported that the oncoprotein E7 from human papillomavirus type 16 (HPV16-E7) can induce the excessive synthesis of centrosomes through the increase in the expression of PLK4, which is a transcriptional target of E2F1. On the other hand, it has been reported that increasing MPS1 protein stability can also generate an excessive synthesis of centrosomes. In this work, we analyzed the possible role of MPS1 in the amplification of centrosomes mediated by HPV16-E7.

Results

Employing qRT-PCR, Western Blot, and Immunofluorescence techniques, we found that E7 induces an increase in the MPS1 transcript and protein levels in the U2OS cell line, as well as protein stabilization. Besides, we observed that inhibiting the expression of MPS1 in E7 protein-expressing cells leads to a significant reduction in the number of centrosomes.

Conclusions

These results indicate that the presence of the MPS1 protein is necessary for E7 protein to increase the number of centrosomes, and possible implications are discussed.
The Italian National Registry for FSHD: an enhanced data integration and an analytics framework towards Smart Health Care and Precision Medicine for a rare disease
Authors: Bettio Cinzia , Salsi Valentina , Orsini Mirko , Calanchi Enrico , Magnotta Luca , Gagliardelli Luca , Kinoshita June , Bergamaschi Sonia , Tupler Rossella
Published: November 2021

Background

The Italian Clinical network for FSHD (ICNF) has established the Italian National Registry for FSHD (INRF), collecting data from patients affected by Facioscapulohumeral dystrophy (FSHD) and their relatives. The INRF has gathered data from molecular analysis, clinical evaluation, anamnestic information, and family history from more than 3500 participants.

Methods

A data management framework, called Mediator Environment for Multiple Information Sources (MOMIS) FSHD Web Platform, has been developed to provide charts, maps and search tools customized for specific needs. Patients’ samples and their clinical information derives from the Italian Clinical network for FSHD (ICNF), a consortium consisting of fourteen neuromuscular clinics distributed across Italy. The tools used to collect, integrate, and visualize clinical, molecular and natural history information about patients affected by FSHD and their relatives are described.

Results

The INRF collected the molecular data regarding FSHD diagnosis conducted on 7197 subjects and identified 3362 individuals carrying a D4Z4 Reduced Allele (DRA): 1634 were unrelated index cases. In 1032 cases the molecular testing has been extended to 3747 relatives, 1728 carrying a DRA. Since 2009 molecular analysis has been accompanied by clinical evaluation based standardized evaluation protocols. In the period 2009–2020, 3577 clinical forms have been collected, 2059 follow the Comprehensive Clinical Evaluation form (CCEF). The integration of standardized clinical information and molecular data has made possible to demonstrate the wide phenotypic variability of FSHD. The MOMIS (Mediator Environment for Multiple Information Sources) data integration framework allowed performing genotype–phenotype correlation studies, and generated information of medical importance either for clinical practice or genetic counseling.

Conclusion

The platform implemented for the FSHD Registry data collection based on OpenClinica meets the requirement to integrate patient/disease information, as well as the need to adapt dynamically to security and privacy concerns. Our results indicate that the quality of data collection in a multi-integrated approach is fundamental for clinical and epidemiological research in a rare disease and may have great value in allowing us to redefine diagnostic criteria and disease markers for FSHD. By extending the use of the MOMIS data integration framework to other countries and the longitudinal systematic collection of standardized clinical data will facilitate the understanding of disease natural history and offer valuable inputs towards trial readiness. This approach is of high significance to FSHD medical community and also to rare disease research in general.
Biological and prognostic value of ETV5 in high-grade serous ovarian cancer
Authors: Zhang Lu , Fu Ruiting , Liu Ping , Wang Lijun , Liang Weihua , Zou Hong , Jia Wei , Tao Lin
Published: November 2021

Background

ETS transcription factors are known to act as either positive or negative regulators of the expression of genes involved in various biological processes. It was reported that ETS variant transcription factor 5 (ETV5), a key member of the ETS family, mainly plays a role as an potential oncogene in various malignant tumors. However, the role and mechanism of ETV5 in high-grade serous ovarian cancer (HGSOC) have not been elucidated.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect ETV5 messenger ribonucleic acid (mRNA) expression in 87 HGSOC tissues and 35 normal fallopian tube tissues. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of ETV5 in six ovarian cancer (OC) and human embryonic cell lines. Knockdown or overexpression of ETV5 in HGSOC cell lines, Cell Counting Kit-8, colony formation, and transwell assays were used to detect HGSOC cell proliferation, invasion, and migration capabilities. The chi-square test was used to analyze the clinicopathological characteristics of HGSOC patients. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to analyze the correlation between ETV5 expression and HGSOC patient prognosis. Univariate and multivariate analyses using the Cox regression model were conducted to determine the independent significance of relevant clinical covariates.

Results

Bioinformatic analysis demonstrated that ETV5 expression was significantly upregulated in OC (p < 0.05). qRT-PCR showed that ETV5 was significantly overexpressed in HGSOC tissues than in fallopian tube tissues (p < 0.05). qRT-PCR and western blotting assays demonstrated that ETV5 was relatively highly expressed in OC cell lines. ETV5 overexpression was positively associated with poor survival in HGSOC patients, therefore making it a high-risk factor for HGSOC progression. Furthermore, ETV5 promoted the proliferation, migration, and invasion capabilities of HGSOC cells.

Conclusion

ETV5 has a carcinogenic effect in HGSOC and can be used as a clinically effective biomarker to determine the prognosis of HGSOC patients.
The glucose infusion rate of parenteral nutrition in the first week of life in preterm infants: an observational study
Authors: Angelika Dina , Etika Risa , Utomo Martono Tri , Mirha Setya , Handayani Kartika Darma , Ugrasena I. Dewa Gede
Published: November 2021

Background

Most preterm infants require a continuous glucose infusion in the early postnatal period due to the interruption of the transplacental glucose supply after birth to promote better neurodevelopmental outcomes.

Aims

To investigate the glucose infusion rate (GIR) on parenteral nutrition (PN) in the first week of life administered in preterm infants and its effect on neonatal morbidity and mortality.

Methods

This study included 97 infants aged < 37 gestational weeks and weighed < 2500 g at birth. Infants recruited in this study were classified into 3 groups based on the GIR usage in parenteral nutrition as follows: GIR usage of 5- < 7 g/kg/day (Group I), GIR usage of 7–13 g/kg/day (Group II), and GIR usage of > 13–15 g/kg/day (Group III). Univariate and multivariate logistic regression analyzes were carried out to investigate whether the GIR usage in the three groups was associated with selected neonatal morbidities and mortality. Neonatal morbidities analyzed included respiratory distress syndrome (RDS), necrotizing enterocolitis, sepsis, retinopathy of prematurity, pulmonary hypertension, hypoglycemia, and hyperglycemia.

Result

Of 97 preterm infants included, 51.5% infants had a gestational age of 34- < 37 weeks, and 54.6% infants had a birth weight of 1500- < 2500 g. The multivariate logistic regression analysis showed that the GIR usage of 5- < 7 g/kg/day was an independent variable that significantly increased the risk of hypoglycemia (Adjusted Odds Ratio [AOR] = 4.000, 95% Confidence Interval [CI] = 1.384–11.565, P = 0.010) and reduced the risk of sepsis (AOR = 0.096, 95% CI = 0.012–0.757, P = 0.026). The GIR usage in all three groups did not increase the risk of mortality. For neonatal morbidity analyzed in this study, RDS (AOR = 5.404, 95%CI = 1.421–20.548, P = 0.013) was an independent risk factor of mortality.

Conclusion

The GIR usage of < 7 g/kg/day in PN in the first week of life administered to preterm infants was an independent variable in increasing hypoglycemia, but in contrast, reducing the risk of sepsis.
Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer: the BULLSEYE trial
Authors: Privé Bastiaan M. , Janssen Marcel J. R. , van Oort Inge M. , Muselaers Constantijn H. J. , Jonker Marianne A. , van Gemert Willemijn A. , de Groot Michel , Westdorp Harm , Mehra Niven , Verzijlbergen J. Fred , Scheenen Tom W. J. , Zámecnik Patrik , Barentsz Jelle O. , Gotthardt Martin , Noordzij Walter , Vogel Wouter V. , Bergman Andries M. , van der Poel Henk G. , Vis André N. , Oprea-Lager Daniela E. , Gerritsen Winald R. , Witjes J. Alfred , Nagarajah James
Published: November 2021

Background

The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial.

Changes in methods and materials

Two important changes were made to the original protocol: (1) the study will now use 177Lu-PSMA-617 instead of 177Lu-PSMA-I&T and (2) responding patients with residual disease on 18F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177Lu-PSMA-617 will also receive an interim 18F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; “Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer” and is now partly supported by Advanced Accelerator Applications, a Novartis Company.

Conclusions

We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177Lu-PSMA-I&T under the previous protocol will be replaced.

Trial registration

ClinicalTrials.gov NCT04443062. First posted: June 23, 2020.
Immune cell profiles in synovial fluid after anterior cruciate ligament and meniscus injuries
Authors: Kim-Wang Sophia Y. , Holt Abigail G. , McGowan Alyssa M. , Danyluk Stephanie T. , Goode Adam P. , Lau Brian C. , Toth Alison P. , Wittstein Jocelyn R. , DeFrate Louis E. , Yi John S. , McNulty Amy L.
Published: November 2021

Background

Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, the contributing factors remain unclear. In this study, we characterized the immune cell profiles of normal and injured joints at the time of ACL and meniscal surgeries.

Methods

Twenty-nine patients (14 meniscus-injured and 15 ACL-injured) undergoing ACL and/or meniscus surgery but with a normal contralateral knee were recruited. During surgery, synovial fluid was aspirated from both normal and injured knees. Synovial fluid cells were pelleted, washed, and stained with an antibody cocktail consisting of fluorescent antibodies for cell surface proteins. Analysis of immune cells in the synovial fluid was performed by polychromatic flow cytometry. A broad spectrum immune cell panel was used in the first 10 subjects. Based on these results, a T cell-specific panel was used in the subsequent 19 subjects.

Results

Using the broad spectrum immune cell panel, we detected significantly more total viable cells and CD3 T cells in the injured compared to the paired normal knees. In addition, there were significantly more injured knees with T cells above a 500-cell threshold. Within the injured knees, CD4 and CD8 T cells were able to be differentiated into subsets. The frequency of total CD4 T cells was significantly different among injury types, but no statistical differences were detected among CD4 and CD8 T cell subsets by injury type.

Conclusions

Our findings provide foundational data showing that ACL and meniscus injuries induce an immune cell-rich microenvironment that consists primarily of T cells with multiple T helper phenotypes. Future studies investigating the relationship between immune cells and joint degeneration may provide an enhanced understanding of the pathophysiology of PTOA following joint injury.
Role of FBXW2 in explant cultures of bovine periosteum-derived cells
Authors: Akiyama Mari
Published: November 2021

Objective

Bone regeneration is a potential technique for treating osteoporosis. A previous study reported that F-box and WD-40 domain-containing protein 2 (FBXW2) localized with osteocalcin in bovine periosteum after 5 weeks of explant culture. However, the osteoblastic functions of FBXW2 remain unclear. In this study, double-fluorescent immunostaining was used to investigate the potential role of FBXW2 and its relationship with osteocalcin.

Results

At day 0, FBXW2 was expressed in the cambium layer between the bone and periosteum, while osteocalcin was expressed in bone. After explant culture, changes in the periosteum were observed from weeks 1 to 7. At week 1, partial FBXW2 expression was seen with a small amount of osteocalcin. At week 2, a layer of FBXW2 was observed. From weeks 3 to 7, tube-like structures of FBXW and osteocalcin were observed, and periosteum-derived cells were released from the periosteum in areas where no FBXW2 was observed. Bovine periosteum-derived cells can form a three-dimensional cell pellet, because multilayered cell sheets are formed inside of the periosteum in vitro. It is shown that in results FBXW2 is produced in periosteal explants near sites where initial osteogenic activity is observed, suggesting that it may be involved in periosteal osteogenesis.
RETRACTED ARTICLE: Recognition method of radar intra-pulse modulation type based on signal square spectrum bandwidth ratio
Authors: Li Dongmei , Xu Zhiyuan , Gu Lei , Zhu Lanxiang
Published: November 2021

The twenty-first century is the era of electronic warfare and information warfare. The focus is of the battle between all parties. CEEMD can link the time domain and frequency domain, describe the two-dimensional time–frequency characteristics of the signal, and draw the time–frequency diagram of the signal, so as to reduce the noise signal and improve the signal-to-noise ratio of the signal. The purpose of this paper was to study how to adjust the signal square spectrum bandwidth ratio in the subject of identifying the intra-pulse modulation of radar, so as to solve the problem of identifying the type of radar intra-pulse modulation. The experimental results in this paper show that the decomposition result of EEMD is incomplete and the signal reconstruction error is larger. Compared with the previous two methods, not only the CEEMD method can effectively suppress modal aliasing, but also the decomposition result is complete; the signal reconstruction error is very small, and the decomposition results close to ideal value. The interleaving filter with a bandwidth ratio of 1:2 can divide the 100 GHz channel spacing into asymmetric output spectra with bandwidths greater than 60 GHz and 30 GHz, which effectively improves the current mix of 10 Gb/s and 40 Gb/s The bandwidth utilization of the system illustrates the success of the simulation experiment.
Systematic review and meta-analysis of the safety of chloroquine and hydroxychloroquine from randomized controlled trials on malarial and non-malarial conditions
Authors: Souza Botelho Mayra , Bolfi Fernanda , Leite Renata Giacomini Occhiuto Ferreira , Leite Mauro Salles Ferreira , Banzato Luisa Rocco , Soares Luiza Teixeira , Olivatti Thaina Oliveira Felicio , Mangolim Amanda Sampaio , Oliveira Flávia Ramos Kazan , Abbade Luciana Patrícia Fernandes , Abbade Joelcio Francisco , de Barros Almeida Ricardo Augusto Monteiro , Simões Corrêa Galendi Julia , Thabane Lehana , dos Santos Nunes-Nogueira Vania
Published: November 2021

Background

Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained.

Objectives

The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs).

Methods

The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used a random-effects model to pool results across studies and Peto’s one-step odds ratio (OR) for event rates below 1%. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence.

Results

One hundred and six RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95% confidence interval [CI]: 0.76–1.26, 33 trials, 15,942 participants, moderate certainty of evidence). However, there was a moderate certainty of evidence that CQ/HCQ increases the incidence of cardiac complications (RR: 1.62, 95% CI: 1.10–2.38, 16 trials, 9908 participants). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1.63, 95% CI: − 0.4–6.57, 5 trials, 344 participants, very low certainty of evidence).

Conclusions

CQ and HCQ probably do not increase SAEs, with low frequency of these adverse events on malarial and non-malarial conditions. However, they may increase cardiac complications especially in patients with COVID-19. No clear effect of their use on the incidence of retinopathy was observed.

Systematic review registration

PROSPERO CRD42020177818
Barriers and enablers to physical activity in patients during hospital stay: a scoping review
Authors: Geelen Sven Jacobus Gertruda , van Dijk - Huisman Hanneke Corine , de Bie Robert Adriaan , Veenhof Cindy , Engelbert Raoul , van der Schaaf Marike , Lenssen Antoine François
Published: November 2021

Background

Low levels of physical activity are common during the hospital stay and have been associated with negative health outcomes. Understanding barriers and enablers to physical activity during a hospital stay can improve the development and implementation of tailored interventions aimed at improving physical activity. Previous studies have identified many barriers and enablers, but a comprehensive overview is lacking. This study aimed to identify and categorize all published patient- and healthcare professional-reported barriers and enablers to physical activity during a hospital stay for acute care, using the Theoretical Domains Framework (TDF).

Methods

We conducted a scoping review of Dutch and English articles using MEDLINE, CINAHL Plus, EMBASE, PsycINFO, and Cochrane Library (inception to September 2020), which included quantitative, qualitative, and mixed-methods studies reporting barriers and enablers to physical activity during a hospital stay for acute care, as perceived by patients or healthcare professionals. Two reviewers systematically extracted, coded, and categorized all barriers and enablers into TDF domains.

Results

Fifty-six articles were included in this review (32 qualitative, 7 quantitative, and 17 mixed-methods). In total, 264 barriers and 228 enablers were reported by patients, and 415 barriers and 409 enablers by healthcare professionals. Patient-reported barriers were most frequently assigned to the TDF domains Environmental Context & Resources (ECR, n = 148), Social Influences (n = 32), and Beliefs about Consequences (n = 25), while most enablers were assigned to ECR (n = 67), Social Influences (n = 54), and Goals (n = 32). Barriers reported by healthcare professionals were most frequently assigned to ECR (n = 210), Memory, Attention and Decision Process (n = 45), and Social/Professional Role & Identity (n = 31), while most healthcare professional-reported enablers were assigned to the TDF domains ECR (n = 143), Social Influences (n = 76), and Behavioural Regulation (n = 54).

Conclusions

Our scoping review presents a comprehensive overview of all barriers and enablers to physical activity during a hospital stay and highlights the prominent role of the TDF domains ECR and Social Influences in hospitalized patients’ physical activity behavior. This TDF-based overview provides a theoretical foundation to guide clinicians and researchers in future intervention development and implementation.

Scoping review registration

No protocol was registered for this review.
The effect of eye protection on SARS-CoV-2 transmission: a systematic review
Authors: Byambasuren Oyungerel , Beller Elaine , Clark Justin , Collignon Peter , Glasziou Paul
Published: November 2021

Background

The effect of eye protection to prevent SARS-CoV-2 infection in the real-world remains uncertain. We aimed to synthesize all available research on the potential impact of eye protection on transmission of SARS-CoV-2.

Methods

We searched PROSPERO, PubMed, Embase, The Cochrane Library for clinical trials and comparative observational studies in CENTRAL, and Europe PMC for pre-prints. We included studies that reported sufficient data to estimate the effect of any form of eye protection including face shields and variants, goggles, and glasses, on subsequent confirmed infection with SARS-CoV-2.

Results

We screened 898 articles and included 6 reports of 5 observational studies from 4 countries (USA, India, Columbia, and United Kingdom) that tested face shields, goggles, and wraparound eyewear on 7567 healthcare workers. The three before-and-after and one retrospective cohort studies showed statistically significant and substantial reductions in SARS-CoV-2 infections favouring eye protection with odds ratios ranging from 0.04 to 0.6, corresponding to relative risk reductions of 96% to 40%. These reductions were not explained by changes in the community rates. However, the one case–control study reported odds ratio favouring no eye protection (OR 1.7, 95% CI 0.99, 3.0). The high heterogeneity between studies precluded any meaningful meta-analysis. None of the studies adjusted for potential confounders such as other protective behaviours, thus increasing the risk of bias, and decreasing the certainty of evidence to very low.

Conclusions

Current studies suggest that eye protection may play a role in prevention of SARS-CoV-2 infection in healthcare workers. However, robust comparative trials are needed to clearly determine effectiveness of eye protections and wearability issues in both healthcare and general populations.
Strain-level analysis reveals the vertical microbial transmission during the life cycle of bumblebee
Authors: Su Qinzhi , Wang Qinglin , Mu Xiaohuan , Chen Hao , Meng Yujie , Zhang Xue , Zheng Li , Hu Xiaosong , Zhai Yifan , Zheng Hao
Published: November 2021

Background

Microbial acquisition and development of the gut microbiota impact the establishment of a healthy host-microbes symbiosis. Compared with other animals, the eusocial bumblebees and honeybees possess a simple, recurring, and similar set of gut microbiota. However, all bee gut phylotypes have high strain-level diversity. Gut communities of different bee species are composed of host-specific groups of strains. The variable genomic regions among strains of the same species often confer critical functional differences, such as carbon source utilization, essential for the natural selection of specific strains. The annual bumblebee colony founded by solitary queens enables tracking the transmission routes of gut bacteria during development stages.

Results

Here, we first showed the changes in the microbiome of individual bumblebees across their holometabolous life cycle. Some core gut bacteria persist throughout different stages of development. Gut microbiota of newly emerged workers always resembles those of their queens, suggesting a vertical transmission of strains from queens to the newborn workers. We then follow the dynamic changes in the gut community by comparing strain-level metagenomic profiles of queen-worker pairs longitudinally collected across different stages of the nest development. Species composition of both queen and worker shifts with the colony’s growth, and the queen-to-worker vertical inheritance of specific strains was identified. Finally, comparative metagenome analysis showed clear host-specificity for microbes across different bee hosts. Species from honeybees often possess a higher level of strain variation, and they also exhibited more complex gene repertoires linked to polysaccharide digestion. Our results demonstrate bacterial transmission events in bumblebee, highlighting the role of social interactions in driving the microbiota composition.

Conclusions

By the community-wide metagenomic analysis based on the custom genomic database of bee gut bacteria, we reveal strain transmission events at high resolution and the dynamic changes in community structure along with the colony development. The social annual life cycle of bumblebees is key for the acquisition and development of the gut microbiota. Further studies using the bumblebee model will advance our understanding of the microbiome transmission and the underlying mechanisms, such as strain competition and niche selection.