bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticles functionalized with stem cell secretome and CXCR4-overexpressing endothelial membrane for targeted osteoporosis therapy
Authors: Zhang Chi , Zhang Wei , Zhu Dashuai , Li Zhenhua , Wang Zhenzhen , Li Junlang , Mei Xuan , Xu Wei , Cheng Ke , Zhong Biao
Published: January 2022

Background

Osteoporosis is a chronic condition affecting patients’ morbidity and mortality and represents a big socioeconomic burden. Because stem cells can proliferate and differentiate into bone-forming cells, stem cell therapy for osteoporosis has been widely studied. However, cells as a live drug face multiple challenges because of their instability during preservation and transportation. In addition, cell therapy has potential adverse effects such as embolism, tumorigenicity, and immunogenicity.

Results

Herein, we sought to use cell-mimicking and targeted therapeutic nanoparticles to replace stem cells. We fabricated nanoparticles (NPs) using polylactic-co-glycolic acid (PLGA) loaded with the secretome (Sec) from mesenchymal stem cells (MSCs) to form MSC-Sec NPs. Furthermore, we cloaked the nanoparticles with the membranes from C–X–C chemokine receptor type 4 (CXCR4)-expressing human microvascular endothelial cells (HMECs) to generate MSC-Sec/CXCR4 NP. CXCR4 can target the nanoparticles to the bone microenvironment under osteoporosis based on the CXCR4/SDF-1 axis.

Conclusions

In a rat model of osteoporosis, MSC-Sec/CXCR4 NP were found to accumulate in bone, and such treatment inhibited osteoclast differentiation while promoting osteogenic proliferation. In addition, our results showed that MSC-Sec/CXCR4 NPs reduce OVX-induced bone mass attenuation in OVX rats.

Graphical Abstract
Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection
Authors: Pi Jiang , Zhang Zhiyi , Yang Enzhuo , Chen Lingming , Zeng Lingchan , Chen Yiwei , Wang Richard , Huang Dan , Fan Shuhao , Lin Wensen , Shen Hongbo , Xu Jun-Fa , Zeng Gucheng , Shen Ling
Published: January 2022

Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a top killer among infectious diseases. While Bacillus Calmette-Guerin (BCG) is the sole TB vaccine, the clumped-clustered features of BCG in intradermal immunization appear to limit both the BCG protection efficacy and the BCG vaccination safety. We hypothesize that engineering of clumped-clustered BCG into nanoscale particles would improve safety and also facilitate the antigen-presenting-cell (APC)’s uptake and the following processing/presentation for better anti-TB protective immunity. Here, we engineered BCG protoplasts into nanoscale membraned BCG particles, termed as “BCG-Nanocage” to enhance the anti-TB vaccination efficiency and safety. BCG-Nanocage could readily be ingested/taken by APC macrophages selectively; BCG-Nanocage-ingested macrophages exhibited better viability and developed similar antimicrobial responses with BCG-infected macrophages. BCG-Nanocage, like live BCG bacilli, exhibited the robust capability to activate and expand innate-like T effector cell populations of Vγ2+ T, CD4+ T and CD8+ T cells of rhesus macaques in the ex vivo PBMC culture. BCG-Nanocage immunization of rhesus macaques elicited similar or stronger memory-like immune responses of Vγ2Vδ2 T cells, as well as Vγ2Vδ2 T and CD4+/CD8+ T effectors compared to live BCG vaccination. BCG-Nanocage- immunized macaques developed rapidly-sustained pulmonary responses of Vγ2Vδ2 T cells upon Mtb challenge. Furthermore, BCG- and BCG-Nanocage- immunized macaques, but not saline controls, exhibited undetectable Mtb infection loads or TB lesions in the Mtb-challenged lung lobe and hilar lymph node at endpoint after challenge. Thus, the current study well justifies a large pre-clinical investigation to assess BCG-Nanocage for safe and efficacious anti-TB vaccination, which is expected to further develop novel vaccines or adjuvants.

Graphical Abstract
Implementing healthy food environment policies in New Zealand: nine years of inaction
Authors: Mackay Sally , Gerritsen Sarah , Sing Fiona , Vandevijvere Stefanie , Swinburn Boyd
Published: January 2022

Background

The INFORMAS [International Network for Food and Obesity/Non-communicable Diseases (NCDs) Research, Monitoring and Action Support] Healthy Food Environment Policy Index (Food-EPI) was developed to evaluate the degree of implementation of widely recommended food environment policies by national governments against international best practice, and has been applied in New Zealand in 2014, 2017 and 2020. This paper outlines the 2020 Food-EPI process and compares policy implementation and recommendations with the 2014 and 2017 Food-EPI.

Methods

In March–April 2020, a national panel of over 50 public health experts participated in Food-EPI. Experts rated the extent of implementation of 47 “good practice” policy and infrastructure support indicators compared to international best practice, using an extensive evidence document verified by government officials. Experts then proposed and prioritized concrete actions needed to address the critical implementation gaps identified. Progress on policy implementation and recommendations made over the three Food-EPIs was compared.

Results

In 2020, 60% of the indicators were rated as having “low” or “very little, if any” implementation compared to international benchmarks: less progress than 2017 (47%) and similar to 2014 (61%). Of the nine priority actions proposed in 2014, there was only noticeable action on one (Health Star Ratings). The majority of actions were therefore proposed again in 2017 and 2020. In 2020 the proposed actions were broader, reflecting the need for multisectoral action to improve the food environment, and the need for a mandatory approach in all policy areas.

Conclusions

There has been little to no progress in the past three terms of government (9 years) on the implementation of policies and infrastructure support for healthy food environments, with implementation overall regressing between 2017 and 2020. The proposed actions in 2020 have reflected a growing movement to locate nutrition within the wider context of planetary health and with recognition of the social determinants of health and nutrition, resulting in recommendations that will require the involvement of many government entities to overcome the existing policy inertia. The increase in food insecurity due to COVID-19 lockdowns may provide the impetus to stimulate action on food polices.
The qualitative experience of telehealth access and clinical encounters in Australian healthcare during COVID-19: implications for policy
Authors: White Jennifer , Byles Julie , Walley Tom
Published: January 2022

Background

Adaptive models of healthcare delivery, such as telehealth consultations, have rapidly been adopted to ensure ongoing delivery of essential healthcare services during the COVID-19 pandemic. However, there remain gaps in our understanding of how clinicians have adapted to telehealth. This study aims to explore the telehealth experiences of specialists, based at a tertiary hospital in the Hunter Region, and general practitioners (GP), including barriers, enablers and opportunities.

Methods

An interpretative qualitative study involving in-depth interviews explored the telehealth experiences of specialists, based at a tertiary hospital in the Hunter Region of Australia, and GPs, including barriers, enablers and opportunities. Data were analysed using an inductive thematic approach with constant comparison.

Results

Individual interviews were conducted with 10 specialists and five GPs. Key themes were identified: (1) transition to telehealth has been valuable but challenging; (2) persisting telehealth process barriers need to be addressed; (3) establishing when face-to-face consults are essential; (4) changes in workload pressures and potential for double-up; (5) essential modification of work practices; and (6) exploring what is needed going forward.

Conclusions

While there is a need to rationalize and optimize health access during a pandemic, we suggest that more needs to be done to improve telehealth going forward. Our results have important policy implications. Specifically, there is a need to effectively train clinicians to competently utilize and be confident using this telehealth and to educate patients on necessary skills and etiquette.
Optimal strategies to screen health care workers for COVID-19 in the US: a cost-effectiveness analysis
Authors: Maya Sigal , Padda Guntas , Close Victoria , Wilson Trevor , Ahmed Fareeda , Marseille Elliot , Kahn James G.
Published: January 2022

Background

Transmission of SARS-CoV-2 in health care facilities poses a challenge against pandemic control. Health care workers (HCWs) have frequent and high-risk interactions with COVID-19 patients. We undertook a cost-effectiveness analysis to determine optimal testing strategies for screening HCWs to inform strategic decision-making in health care settings.

Methods

We modeled the number of new infections, quality-adjusted life years lost, and net costs related to six testing strategies including no test. We applied our model to four strata of HCWs, defined by the presence and timing of symptoms. We conducted sensitivity analyses to account for uncertainty in inputs.

Results

When screening recently symptomatic HCWs, conducting only a PCR test is preferable; it saves costs and improves health outcomes in the first week post-symptom onset, and costs $83,000 per quality-adjusted life year gained in the second week post-symptom onset. When screening HCWs in the late clinical disease stage, none of the testing approaches is cost-effective and thus no testing is preferable, yielding $11 and 0.003 new infections per 10 HCWs. For screening asymptomatic HCWs, antigen testing is preferable to PCR testing due to its lower cost.

Conclusions

Both PCR and antigen testing are beneficial strategies to identify infected HCWs and reduce transmission of SARS-CoV-2 in health care settings. IgG tests’ value depends on test timing and immunity characteristics, however it is not cost-effective in a low prevalence setting. As the context of the pandemic evolves, our study provides insight to health-care decision makers to keep the health care workforce safe and transmissions low.
Incidental germline findings during molecular profiling of tumor tissues for precision oncology: molecular survey and methodological obstacles
Authors: Lebedeva Alexandra , Shaykhutdinova Yulia , Seriak Daria , Ignatova Ekaterina , Rozhavskaya Ekaterina , Vardhan Divyasphoorthi , Manicka Sofia , Sharova Margarita , Grigoreva Tatiana , Baranova Ancha , Mileyko Vladislav , Ivanov Maxim
Published: January 2022

Background

A fraction of patients referred for complex molecular profiling of biopsied tumors may harbor germline variants in genes associated with the development of hereditary cancer syndromes (HCS). Neither the bioinformatic analysis nor the reporting of such incidental germline findings are standardized.

Methods

Data from Next-Generation Sequencing (NGS) of biopsied tumor samples referred for complex molecular profiling were analyzed for germline variants in HCS-associated genes. Analysis of variant origin was performed employing bioinformatic algorithms followed by manual curation. When possible, the origin of the variant was validated by Sanger sequencing of the sample of normal tissue. The variants’ pathogenicity was assessed according to ACMG/AMP.

Results

Tumors were sampled from 183 patients (Males: 75 [41.0%]; Females: 108 [59.0%]; mean [SD] age, 57.7 [13.3] years) and analysed by targeted NGS. The most common tumor types were colorectal (19%), pancreatic (13%), and lung cancer (10%). A total of 56 sequence variants in genes associated with HCS were detected in 40 patients. Of them, 17 variants found in 14 patients were predicted to be of germline origin, with 6 variants interpreted as pathogenic (PV) or likely pathogenic (LPV), and 9 as variants of uncertain significance (VUS). For the 41 out of 42 (97%) missense variants in HCS-associated genes, the results of computational prediction of variant origin were concordant with that of experimental examination. We estimate that Sanger sequencing of a sample of normal tissue would be required for ~ 1–7% of the total assessed cases with PV or LPV, when necessity to follow with genetic counselling referral in ~ 2–15% of total assessed cases (PV, LPV or VUS found in HCS genes).

Conclusion

Incidental findings of pathogenic germline variants are common in data from cancer patients referred for complex molecular profiling. We propose an algorithm for the management of patients with newly detected variants in genes associated with HCS.
Development of a radiomics model to diagnose pheochromocytoma preoperatively: a multicenter study with prospective validation
Authors: Kong Jianqiu , Zheng Junjiong , Wu Jieying , Wu Shaoxu , Cai Jinhua , Diao Xiayao , Xie Weibin , Chen Xiong , Yu Hao , Huang Lifang , Fang Hongpeng , Fan Xinxiang , Qin Haide , Li Yong , Wu Zhuo , Huang Jian , Lin Tianxin
Published: January 2022

Background

Preoperative diagnosis of pheochromocytoma (PHEO) accurately impacts preoperative preparation and surgical outcome in PHEO patients. Highly reliable model to diagnose PHEO is lacking. We aimed to develop a magnetic resonance imaging (MRI)-based radiomic-clinical model to distinguish PHEO from adrenal lesions.

Methods

In total, 305 patients with 309 adrenal lesions were included and divided into different sets. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction, feature selection, and radiomics signature building. In addition, a nomogram incorporating the obtained radiomics signature and selected clinical predictors was developed by using multivariable logistic regression analysis. The performance of the radiomic-clinical model was assessed with respect to its discrimination, calibration, and clinical usefulness.

Results

Seven radiomics features were selected among the 1301 features obtained as they could differentiate PHEOs from other adrenal lesions in the training (area under the curve [AUC], 0.887), internal validation (AUC, 0.880), and external validation cohorts (AUC, 0.807). Predictors contained in the individualized prediction nomogram included the radiomics signature and symptom number (symptoms include headache, palpitation, and diaphoresis). The training set yielded an AUC of 0.893 for the nomogram, which was confirmed in the internal and external validation sets with AUCs of 0.906 and 0.844, respectively. Decision curve analyses indicated the nomogram was clinically useful. In addition, 25 patients with 25 lesions were recruited for prospective validation, which yielded an AUC of 0.917 for the nomogram.

Conclusion

We propose a radiomic-based nomogram incorporating clinically useful signatures as an easy-to-use, predictive and individualized tool for PHEO diagnosis.
Understanding the impacts of child marriage on the health and well-being of adolescent girls and young women residing in urban areas in Egypt
Authors: Elnakib Shatha , Elsallab May , Wanis Maha Abdel , Elshiwy Shadia , Krishnapalan Nishan Prasana , Naja Nada Aghar
Published: January 2022

Background

Egypt has made progress in delaying age at marriage, but child marriage continues to be practiced in many places across the country. This study investigates the impacts of child marriage on the health and wellbeing of girls residing in urban Egypt using a multi-method approach.

Methods

The quantitative component leveraged data from the 2014 Egypt Demographic and Health Survey and focused on (1) reproductive health, (2) maternal health and (3) social outcomes among a subsample of ever-married urban women ages 20–24 (N = 1041). Simple and multivariable logistic regressions were used to estimate prevalence odds ratios and 95% confidence intervals for associations between child marriage and the three sets of outcomes. The qualitative component drew from 11 focus groups, 23 in-depth interviews, and 13 key informant interviews conducted in three urban sites in Egypt. The data was thematically analyzed using a combination of inductive and deductive coding.

Results

The prevalence of marriage under age 18 was 13.22%. Child marriage was significantly associated with ever use of contraception (Adjusted Odds Ratio (AOR) 2.95 95% CI 1.67–5.19), multiple births (AOR 12.93 95% CI 5.45–30.72), rapid repeat childbirth (AOR 2.20 95% CI 1.34–3.63), and pregnancy termination (AOR 1.89 95% CI 1.11–3.23). Many of these associations disappeared after adjusting for marriage duration. Girls married under age 18 had larger spousal age gaps (AOR 2.06; 95% CI 1.24–3.41) and higher odds of FGM (AOR 2.14; 95% CI 1.11–4.13). They were significantly more likely to report receiving no ANC care (AOR 0.39; 95% CI 0.19–0.80), and less likely to deliver through C-section (AOR: 0.53; 95% CI 0.34–0.83). Consequences emerging from the qualitative data centered around five themes: (1) Access to and use of sexual and reproductive health services; (2) exposure to FGM; (3) marriage and birth registration; (4) marital relations; and (5) relationship with in-laws.

Conclusion

Findings provide important insights into the practice of child marriage in urban areas in Egypt and illustrate a range of adverse consequences associated with the practice.
Interviewing adolescent girls about sexual and reproductive health: a qualitative study exploring how best to ask questions in structured follow-up interviews in a randomized controlled trial in Zambia
Authors: Isaksen Katja , Sandøy Ingvild , Zulu Joseph , Melberg Andrea , Kabombwe Sheena , Mudenda Mweetwa , Musonda Patrick , Svanemyr Joar
Published: January 2022

Background

Numerous studies have documented inconsistent reporting of sexual behaviour by adolescents. The validity and reliability of self-reported data on issues considered sensitive, incriminating or embarrassing, is prone to social-desirability bias. Some studies have found that Audio Computer-Assisted Self Interviewing (ACASI) that removes the personal interaction involved in face-to-face interviews, decreases item non-response and increases reporting of sensitive behaviours, but others have found inconsistent or contradictory results. To reduce social desirability bias in the reporting of sensitive behaviours, face-to-face interviews were combined with ACASI in a cluster randomized trial involving adolescents in Zambia.

Methods

To explore adolescent girls’ experiences and opinions of being interviewed about sexual and reproductive health, we combined Focus Group Discussions with girl participants and individual semi-structured interviews with teachers. This study was done after the participants had been interviewed for the 6th time since recruitment. Young, female research assistants who had conducted interviews for the trial were also interviewed for this study.

Results

Respondents explained often feeling shy, embarrassed or uncomfortable when asked questions about sex, pregnancy and abortion face-to-face. Questions on sexual activity elicited feelings of shame, and teachers, research assistants and girls alike noted that direct questions about sexual activities limit what the participant girls may be willing to share. Responding to more indirect questions in relation to the context of a romantic relationship was slightly easier. Efforts by interviewers to signal that they did not judge the participants for their behavior and increased familiarity with the interviewer reduced discomfort over time. Although some appreciated the opportunity to respond to questions on their own, the privacy offered by ACASI also provided an opportunity to give false answers. Answering on tablets could be challenging, but participants were reluctant to ask for assistance for fear of being judged as not conversant with technology.

Conclusion

Strategies to avoid using overly direct language and descriptive words, asking questions within the context of a romantic relationship and a focus on establishing familiarity and trust can reduce reporting bias. For the use of ACASI, considerations must be given to the context and characteristics of the study population.
Raltegravir 1200 mg once daily as maintenance therapy in virologically suppressed HIV-1 infected adults: QDISS open-label trial
Authors: Hall Nolwenn , Allavena Clotilde , Katlama Christine , Jobert Alexandra , Molina Jean-Michel , Cua Eric , Bani-Sadr Firouzé , Hocqueloux Laurent , Duvivier Claudine , Merrien Dominique , Hikombo Hitoto , André-Garnier Elisabeth , Gaultier Aurélie , Raffi François ,   the QDISS Study Group, Bollengier Olivier , Guimard Thomas , Leautez Sophie , Blanchi Sophie , Becker Agathe , Cotte Laurent , Ferry Tristan , Perpoint Thomas , Trabaud Marie-Anne , Biron Laetitia , Ferré Virginie , Flet Laurent , Reliquet Véronique , Rodalec Audrey , Volteau Christèle , Breaud Sophie , Puglièse Pascal , Rosenthal Eric , De Dieuleveult Barbara , Prazuck Thierry , Bachelard Antoine , Legac Sylvie , Yazdanpanah Yazdan , Ghosn Jade , Kalambay Myriam , Slama Laurence , Viard Jean-Paul , Lourenco Jérémy , Ktorza Nadine , Palich Romain , Schneider Luminita , Aslan Alexandre , Tateo Mariagrazia , Zeggagh Jeremy , Brodard Véronique , Hentzien Maxime , Kmiec Isabelle , N’Guyen Yohan , Ajana Faïza , Bocket Laurence , Huleux Thomas , Meybeck Agnes
Published: January 2022

Background

Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy.

Methods

The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm.

Results

Of 100 participants 91% maintained viral suppression (95% CI: 83.6–95.8) at week 24 and 89% (81.2–94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3–4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol (p = 0.023) and LDL-cholesterol (p = 0.009) decreased, lifestyle and ease subscale significantly improved (p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p = 0.007).

Conclusion

RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes.

Trial registration: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.
Cold case: The disappearance of Egypt bee virus, a fourth distinct master strain of deformed wing virus linked to honeybee mortality in 1970’s Egypt
Authors: de Miranda Joachim R. , Brettell Laura E. , Chejanovsky Nor , Childers Anna K. , Dalmon Anne , Deboutte Ward , de Graaf Dirk C. , Doublet Vincent , Gebremedhn Haftom , Genersch Elke , Gisder Sebastian , Granberg Fredrik , Haddad Nizar J. , Kaden Rene , Manley Robyn , Matthijnssens Jelle , Meeus Ivan , Migdadi Hussein , Milbrath Meghan O. , Mondet Fanny , Remnant Emily J. , Roberts John M. K. , Ryabov Eugene V. , Sela Noa , Smagghe Guy , Somanathan Hema , Wilfert Lena , Wright Owen N. , Martin Stephen J. , Ball Brenda V.
Published: January 2022

In 1977, a sample of diseased adult honeybees (Apis mellifera) from Egypt was found to contain large amounts of a previously unknown virus, Egypt bee virus, which was subsequently shown to be serologically related to deformed wing virus (DWV). By sequencing the original isolate, we demonstrate that Egypt bee virus is in fact a fourth unique, major variant of DWV (DWV-D): more closely related to DWV-C than to either DWV-A or DWV-B. DWV-A and DWV-B are the most common DWV variants worldwide due to their close relationship and transmission byVarroa destructor. However, we could not find any trace of DWV-D in several hundred RNA sequencing libraries from a worldwide selection of honeybee, varroa and bumblebee samples. This means that DWV-D has either become extinct, been replaced by other DWV variants better adapted to varroa-mediated transmission, or persists only in a narrow geographic or host range, isolated from common bee and beekeeping trade routes.
Pericyte, but not astrocyte, hypoxia inducible factor-1 (HIF-1) drives hypoxia-induced vascular permeability in vivo
Authors: Baumann Julia , Tsao Chih-Chieh , Patkar Shalmali , Huang Sheng-Fu , Francia Simona , Magnussen Synnøve Norvoll , Gassmann Max , Vogel Johannes , Köster-Hegmann Christina , Ogunshola Omolara O.
Published: January 2022

Background

Ways to prevent disease-induced vascular modifications that accelerate brain damage remain largely elusive. Improved understanding of perivascular cell signalling could provide unparalleled insight as these cells impact vascular stability and functionality of the neurovascular unit as a whole. Identifying key drivers of astrocyte and pericyte responses that modify cell–cell interactions and crosstalk during injury is key. At the cellular level, injury-induced outcomes are closely entwined with activation of the hypoxia-inducible factor-1 (HIF-1) pathway. Studies clearly suggest that endothelial HIF-1 signalling increases blood–brain barrier permeability but the influence of perivascular HIF-1 induction on outcome is unknown. Using novel mouse lines with astrocyte and pericyte targeted HIF-1 loss of function, we herein show that vascular stability in vivo is differentially impacted by perivascular hypoxia-induced HIF-1 stabilization.

Methods

To facilitate HIF-1 deletion in adult mice without developmental complications, novel Cre-inducible astrocyte-targeted (GFAP-CreERT2; HIF-1αfl/fland GLAST-CreERT2; HIF-1αfl/fl) and pericyte-targeted (SMMHC-CreERT2; HIF-1αfl/fl) transgenic animals were generated. Mice in their home cages were exposed to either normoxia (21% O2) or hypoxia (8% O2) for 96 h in an oxygen-controlled humidified glove box. All lines were similarly responsive to hypoxic challenge and post-Cre activation showed significantly reduced HIF-1 target gene levels in the individual cells as predicted.

Results

Unexpectedly, hypoxia-induced vascular remodelling was unaffected by HIF-1 loss of function in the two astrocyte lines but effectively blocked in the pericyte line. In correlation, hypoxia-induced barrier permeability and water accumulation were abrogated only in pericyte targeted HIF-1 loss of function mice. In contrast to expectation, brain and serum levels of hypoxia-induced VEGF, TGF-β and MMPs (genes known to mediate vascular remodelling) were unaffected by HIF-1 deletion in all lines. However, in agreement with the permeability data, immunofluorescence and electron microscopy showed clear prevention of hypoxia-induced tight junction disruption in the pericyte loss of function line.

Conclusion

This study shows that pericyte but not astrocyte HIF-1 stabilization modulates endothelial tight junction functionality and thereby plays a pivotal role in hypoxia-induced vascular dysfunction. Whether the cells respond similarly or differentially to other injury stimuli will be of significant relevance.
Establishing a novel community-focussed lactation support service: a descriptive case series
Authors: Griffin Samantha , Watt Jo , Wedekind Sophie , Bramer Solange , Hazemi-Jebelli Yasmin , Boyle Robert , Weaver Gillian , Shenker Natalie S.
Published: January 2022

Background

Although breastfeeding is widely acknowledged as protecting both infant and maternal health postnatally, a partial or complete shortfall of maternal milk can occur for a range of reasons. In this eventuality, the currently available options for feeding infants are screened donor human milk (DHM), infant formula or unscreened shared human milk. In the UK, DHM has only been widely available in specific clinical contexts for the last 40 years, mainly to reduce the risk of necrotising enterocolitis in extremely preterm infants alongside optimal support for maternal lactation and breastfeeding. The Hearts Milk Bank (HMB) was established in 2017 as an independent, non-profit human milk bank that aimed to ensure equitable, assured access to screened DHM for neonatal units. As a result of the generosity of mothers, a surplus of DHM rapidly became available and together with lactation support, has since been provided to families with a healthcare referral. This programme has now been formalised for families facing lactational challenges, and DHM stocks are permanently maintained to meet their needs.

Case series

This case series describes the clinical paths of four families who accessed lactation support and DHM from the HMB, along with a description of the process for community provision. To date, the HMB has supported over 300 families. Working collaboratively with key stakeholders, the HMB team has developed a prioritisation strategy based on utilitarian ethical models, protocols that ensure safe handling and appropriateness of use, broader donor recruitment parameters that maintain safety with a pragmatic approach for full term healthy infants, and a process to ensure parents or carers have access to the knowledge needed to give informed consent and use DHM appropriately.

Conclusions

Stakeholders, including parents, healthcare professionals, and milk banks, will need to discuss priorities for both DHM use and research gaps that can underpin the equitable expansion of services, in partnership with National Health Service (NHS) teams and third-sector organisations that support breastfeeding and maternal mental health.
Real-time monitoring of Ralstonia solanacearum infection progress in tomato and Arabidopsis using bioluminescence imaging technology
Authors: Xu Cuihong , Zhong Lingkun , Huang Zeming , Li Chenying , Lian Jiazhang , Zheng Xuefang , Liang Yan
Published: January 2022

Background

Ralstonia solanacearum, one of the most devastating bacterial plant pathogens, is the causal agent of bacterial wilt. Recently, several studies on resistance to bacterial wilt have been conducted using the Arabidopsis-R. solanacearumsystem. However, the progress ofR. solanacearuminfection in Arabidopsis is still unclear.

Results

We generated a bioluminescentR. solanacearumby expressing plasmid-basedluxCDABE. Expression ofluxCDABE did not alter the bacterial growth and pathogenicity. The light intensity of bioluminescentR. solanacearumwas linearly related to bacterial concentrations from 104to 108 CFU·mL−1. After root inoculation with bioluminescentR. solanacearumstrain, light signals in tomato and Arabidopsis were found to be transported from roots to stems via the vasculature. Quantification of light intensity from the bioluminescent strain accurately reported the difference in disease resistance between Arabidopsis wild type and resistant mutants.

Conclusions

BioluminescentR. solanacearumstrain spatially and quantitatively measured bacterial growth in tomato and Arabidopsis, and offered a tool for the high-throughput study ofR. solanacearum-Arabidopsis interaction in the future.
Scale-up of prevention programmes: sustained state-wide use of programme delivery software is explained by normalised self-organised adoption and non-adoption
Authors: Goldberg Eileen , Conte Kathleen , Loblay Victoria , Groen Sisse , Persson Lina , Innes-Hughes Christine , Mitchell Jo , Milat Andrew , Williams Mandy , Green Amanda , Hawe Penelope
Published: January 2022

Background

Population-level health promotion is often conceived as a tension between “top-down” and “bottom-up” strategy and action. We report behind-the-scenes insights from Australia’s largest ever investment in the “top-down” approach, the $45m state-wide scale-up of two childhood obesity programmes. We used Normalisation Process Theory (NPT) as a template to interpret the organisational embedding of the purpose-built software designed to facilitate the initiative. The use of the technology was mandatory for evaluation, i.e. for reporting the proportion of schools and childcare centres which complied with recommended health practices (the implementation targets). Additionally, the software was recommended as a device to guide the implementation process. We set out to study its use in practice.

Methods

Short-term, high-intensity ethnography with all 14 programme delivery teams across New South Wales was conducted, cross-sectionally, 4 years after scale-up began. The four key mechanisms of NPT (coherence/sensemaking, cognitive participation/engagement, collective action and reflexive monitoring) were used to describe the ways the technology had normalised (embedded).

Results

Some teams and practitioners embraced how the software offered a way of working systematically with sites to encourage uptake of recommended practices, while others rejected it as a form of “mechanisation”. Conscious choices had to be made at an individual and team level about the practice style offered by the technology—thus prompting personal sensemaking, re-organisation of work, awareness of choices by others and reflexivity about professional values. Local organisational arrangements allowed technology users to enter data and assist the work of non-users—collective action that legitimised opposite behaviours. Thus, the technology and the programme delivery style it represented were normalised by pathways of adoption and non-adoption. Normalised use and non-use were accepted and different choices made by local programme managers were respected. State-wide, implementation targets are being reported as met.

Conclusion

We observed a form of self-organisation where individual practitioners and teams are finding their own place in a new system, consistent with complexity-based understandings of fostering scale-up in health care. Self-organisation could be facilitated with further cross-team interaction to continuously renew and revise sensemaking processes and support diverse adoption choices across different contexts.
A new 1.375-approximation algorithm for sorting by transpositions
Authors: Silva Luiz Augusto G. , Kowada Luis Antonio B. , Rocco Noraí Romeu , Walter Maria Emília M. T.
Published: January 2022

Background

sorting by transpositions(SBT) is a classical problem in genome rearrangements. In 2012, SBT was proven to be$$\mathcal {NP}$$NP-hard and the best approximation algorithm with a 1.375 ratio was proposed in 2006 by Elias and Hartman (EH algorithm). Their algorithm employssimplification, a technique used to transform an input permutation$$\pi$$πinto asimple permutation$${\hat{\pi }}$$π^, presumably easier to handle with. The permutation$${\hat{\pi }}$$π^is obtained by inserting new symbols into$$\pi$$πin a way that the lower bound of the transposition distance of$$\pi$$πis kept on$${\hat{\pi }}$$π^. The simplification is guaranteed to keep the lower bound, not the transposition distance. A sequence of operations sorting$${\hat{\pi }}$$π^can be mimicked to sort$$\pi$$π.

Results and conclusions

First, using an algebraic approach, we propose a new upper bound for the transposition distance, which holds for all$$S_n$$Sn. Next, motivated by a problem identified in the EH algorithm, which causes it, in scenarios involving how the input permutation is simplified, to require one extra transposition above the 1.375-approximation ratio, we propose a new approximation algorithm to solve SBT ensuring the 1.375-approximation ratio for all$$S_n$$Sn. We implemented our algorithm and EH’s. Regarding the implementation of the EH algorithm, two other issues were identified and needed to be fixed. We tested both algorithms against all permutations of sizen,$$2\le n \le 12$$2≤n≤12. The results show that the EH algorithm exceeds the approximation ratio of 1.375 for permutations with a size greater than 7. The percentage of computed distances that are equal to transposition distance, computed by the implemented algorithms are also compared with others available in the literature. Finally, we investigate the performance of both implementations on longer permutations of maximum length 500. From the experiments, we conclude that maximum and the average distances computed by our algorithm are a little better than the ones computed by the EH algorithm and the running times of both algorithms are similar, despite the time complexity of our algorithm being higher.
Impact of tourniquet during total knee arthroplasty when tranexamic acid was used: a meta-analysis of randomized controlled trials
Authors: Sun Changjiao , Zhang Xiaofei , Ma Qi , Tu Yan , Cai Xu , Zhou Yonggang
Published: January 2022

Introduction

The efficacy of tourniquet use during primary total knee arthroplasty (TKA) is thought to reduce intraoperative blood loss, improve surgical exposure, and optimize cement fixation. Tranexamic acid (TXA) use can decrease postsurgical blood loss and transfusion requirements. This review aimed to appraise the effects of tourniquet use in TKA for patients with tranexamic acid use.

Methods

A meta-analysis was conducted to identify relevant randomized controlled trials involving TXA plus a tourniquet (TXA-T group) and use of TXA plus no tourniquet (TXA-NT group) in TKA. Web of Science, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CNKI, and Wanfang database were searched from 2010 through October 2021.

Results

We identified 1720 TKAs (1690 patients) assessed in 14 randomized controlled trials. Compared with the TXA-NT group, the TXA-T group resulted in less intra-operative blood loss (P < 0.00001) and decreased duration of surgery (P < 0.00001), however more hidden blood loss (P = 0.0004) and less knee range of motion (P < 0.00001). No significant differences were found between two groups in terms of decrease in hemoglobin (P = 0.84), total blood loss (P = 0.79), transfusion rate (P = 0.18), drainage volume (P = 0.06), Visual Analogue Scale (VAS) at either the day of surgery (P = 0.2), 1 day (P = 0.25), 2 day (P = 0.39), 3 day (P = 0.21), 5 day (P = 0.21), 7 day (P = 0.06) or 1 month after surgery (P = 0.16), Hospital for Special Surgery (HSS) score at either 7 day (P = 0.10), 1 month (P = 0.08), 3 month (P = 0.22) or 6 month after the surgery (P = 0.92), Knee circumference (P = 0.28), length of hospital (P = 0.12), and complications such as intramuscular venous thrombosis (P = 0.81), deep venous thrombosis (P = 0.10), superficial infection (P = 0.45), deep wound infection (P = 0.64), and delayed wound healing (P = 0.65).

Conclusion

No big differences could be found by using or not tourniquet when use the TXA, though some benefits are related to operation time and less intra-operative blood loss by using tourniquet and TXA, Using the tourniquet was related to more hidden blood loss and less knee range of motion. More adequately powered and better-designed randomized controlled trials (RCTs) studies with long-term follow-up are required to validate this study.
Why the patients with Hirayama disease have abnormal cervical sagittal alignment? A radiological measurement analysis of posterior cervical extensors
Authors: Tian Ye , Xie Lin , Jiang Jianyuan , Wang Hongli
Published: January 2022

Purpose

To explore the relationship between the strength of posterior cervical extensors (PCEs) and cervical sagittal alignment in Hirayama disease (HD) patients.

Methods

We analyzed the (magnetic resonance imaging) MRI T2WI and X-rays of 60 HD patients who visited Huashan Hospital from June 2017 to February 2020. Symptoms of these patients include adolescent onset, manifestation of unilateral upper limb muscle weakness and muscle atrophy of the forearm and hand. MRI images were used to measure (the cross-sectional area) CSA of cervical PCEs. The ratio of muscle CSA to vertebral body areas at the same level is defined as R-CSA. Cervical sagittal alignment includes the C2–7 Cobb angle, T1 slope and C2–7 sagittal vertical axis (SVA). The geometric center of the C3–6 vertebral body was determined using the line connecting the C2 inferior endplate and the C7 upper endplate. When located behind the line, it is defined as a “local kyphotic deformity.” The number of vertebral bodies involved in kyphotic deformity was determined by measuring the local kyphosis angle (LKA). Spearman correlation analysis (α = 0.05) was used to determine the relationship between R-CSA and sagittal parameters. ROC curves were used to analyze the sensitivity and specificity of relevant variables.

Results

Spearman correlation test revealed that R-CSA negatively correlated with T1S (S = 0.34, r = 0.34, p = 0.01) and LKA (S = 0.44, r = 0.5, p = 0.01), but did not correlate with the C2-C7 Cobb angle (S = 0.20, p = 0.12) or C2-C7 SVA (S =  − 0.17, p = 0.46). (p < 0.05). ROC curve analysis showed that the areas under the curve (AUCs) of the T1 slope and LKA was 0.6696 and 0.7646, respectively. T1 slope, cutoff value: 17.2°; sensitivity: 0.5806; specificity: 0.7241; p < 0.05. LKA: cutoff value: − 14°; sensitivity: 1; specificity: 0.5333; p < 0.05.

Conclusions

In patients with Hirayama disease, the strength of posterior cervical extensors and cervical sagittal alignment are closely related. The local kyphosis angle can be used as a reference for the strength of posterior cervical extensors. These results indicate the weakness of PCEs, which may predispose the cervical spine of HD patients to a less stable situation. Therefore, patients with Hirayama disease should strengthen the exercise of the PCEs.
Efficacy and safety of radiofrequency treatment for improving knee pain and function in knee osteoarthritis: a meta-analysis of randomized controlled trials
Authors: Liu Jian , Wang Ting , Zhu Zhen-Hua
Published: January 2022

Background

The clinical utility of radiofrequency (RF) in patients with knee osteoarthritis (OA) remains unclear. We conducted a meta-analysis to systematically evaluate the efficacy and safety of RF treatment in patients with knee OA.

Methods

Searches of the PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data databases were performed through August 30, 2021. The major outcomes from published randomized controlled trials (RCTs) involving patients with knee OA were compared between RF and control groups, including Visual Analogue Scale (VAS) or Numerical Rating Scale (NRS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS), Global Perceived Effect (GPE) scale, and adverse effects at available follow-up times.

Results

Fifteen RCTs involving 1009 patients were included in this meta-analysis, and the results demonstrated that RF treatment correlated with improvements in pain relief (VAS/NRS score, all P < 0.001) and knee function (WOMAC, all P < 0.001) at 1–2, 4, 12, and 24 weeks after treatment as well as patients’ degree of satisfaction with treatment effectiveness (GPE scale, 12 weeks, P < 0.001). OKSs did not differ significantly between the two groups. Moreover, treatment with RF did not significantly increase adverse effects. Subgroup analysis of knee pain indicated that the efficacy of RF treatment targeting the genicular nerve was significantly better than intra-articular RF at 12 weeks after treatment (P = 0.03).

Conclusions

This meta-analysis showed that RF is an efficacious and safe treatment for relieving knee pain and improving knee function in patients with knee OA.
Function, strength, and muscle activation of the shoulder complex in Crossfit practitioners with and without pain: a cross-sectional observational study
Authors: Silva Elisa Raulino , Maffulli Nicola , Migliorini Filippo , Santos Gilmar Moraes , de Menezes Fábio Sprada , Okubo Rodrigo
Published: January 2022

Background

The shoulder joint is the most commonly injured joint in CrossFit practitioners, because of the high intensity and loads associated with this sport. Despite the large number of clinical cases, there is a shortage of studies that investigate influence of biomechanical aspects of upper limbs' injuries on CrossFit practitioners. This study hypothesized that there would be a difference in function, strength, and muscle activation between Crossfit practitioners with and without shoulder pain.

Methods

We divided 79 Crossfit practitioners into two groups according to whether they reported pain (n = 29) or no pain (n = 50) in the shoulder during Crossfit training. Muscle function, strength, and activation were assessed using the Disability Arm, Shoulder and Hand function questionnaire, Upper Quarter Y Balance Test and Closed Kinetic Chain Upper Extremity Stability Test shoulder tests, isometric muscle strength assessment by manual dynamometry and muscle activation by surface electromyography and pain report.

Results

The function based on questionnaire was associated with pain (p = 0.004). We observed a statistically significant difference between the two groups only in the surface electromyography activity of the lower trapezius, and in the variables of shoulder pain and function (p = 0.038).

Conclusion

Crossfit practitioners with shoulder pain occurring during training showed good function and stability of the shoulder joint, but there was a reduction in the activation of stabilizing muscles, especially the lower trapezius.

Trial registration Registro Brasileiro de Ensaios Clinico (Brasilian National Registry) with the ID: RBR-2gycyv.
Application of a new integrated low-profile anterior plate and cage system in single-level cervical spondylosis: a preliminary retrospective study
Authors: Wei Leixin , Xu Chen , Dong Minjie , Dou Yibo , Tian Ye , Wu Huiqiao , Wu Xiaodong , Wang Xinwei , Chen Huajiang , Shen Xiaolong , Cao Peng , Yuan Wen
Published: January 2022

Background

Although ACDF has been widely used in treating cervical spondylosis and related diseases, the complications along with this anterior surgical technique have hindered its application and affected the postoperative outcome of the patients. Here, we investigated the clinical and radiological outcomes of a new integrated low-profile anterior plate and cage system for anterior cervical discectomy and fusion (ACDF) in treating cervical spondylosis.

Methods

A total of 96 cervical spondylosis patients who underwent single-level ACDF between 2018 to 2020 in our institute were enrolled. There were 28 patients using the new implants and 68 patients using the zero-profile (Zero-P) implants. The Japanese Orthopedic Association (JOA) score and the visual analog scale (VAS) were used to evaluate the clinical outcomes. The cervical and segmental Cobb angle and range of motion (ROM) were used to assessed the radiological outcomes. Incidence of complications were also recorded. All data were recorded at pre-operation, 6-month and 12-month post-operation.

Results

All patients were followed-up for at least 1-year, the mean follow-up time was over one year. The fusion rate was similar in the two groups. There was no significant difference in the postoperative JOA score recovery rate, postoperative VAS score of neck and arm pain, postoperative ROM, and incidence of complications between two groups (P > 0.05). However, postoperative cervical and segmental Cobb angle were better maintained in the new low-profile implant group compared to Zero-P group.

Conclusions

The clinical outcomes of the new low-profile implant were satisfactory and comparable to that of zero-profile system. It may have advantages in improving and maintaining the cervical lordosis, and can be an alternative device for single-level cervical spondylosis treated with ACDF.