bluuebunny/crossref_metadata_2025 huggingface dataset:
Displacement current guided control of electromagnetically induced transparency in nano-discretized terahertz metamaterials
Authors: Yang Maosheng , Liang Lanju , Wang Tongling , Lu Yuying , Li Peipei , Du Binbin , Ma Qilin , Liu Dandan , Zhang Tan , Fang Jie , Yan Xin , Yao Haiyun , Zhang Gang , Yang Qilin , Wang Yaru , Wang Meng , Dai Zijie , Zhang Jingjing , Ye Yunxia , Song Xiaoxian , Zhang Haiting , Ren Xundong , Yao Jianquan
Published: September 2022

It is difficult for nano-scale optical devices to resonate with terahertz waves. By using a nano-discretized metamaterial (NDMM), we converted a gap-localized electromagnetic response into terahertz spectroscopy. A switch of an electromagnetically induced transparency (EIT) analog is acquired by a displacement current in NDMMs and is strongly dependent on the discretization of the nanogap. By controlling the distance of the nanogap, the switch of the EIT can be determined, which, in turn, is linked to the polarization of the electric field. If the electric field is perpendicular to the nanogap, the switch of the EIT can be tuned. While the electric field is parallel to the nanogap, the EIT would exist on all occasions, no matter how the nanogap changes. The proposed NDMMs may ultra-sensitively detect the vibrations of the nano-world using the spectroscopic information of terahertz (THz) response.
High-sensitivity and wide-bandwidth fiber-coupled diamond magnetometer with surface coating
Authors: Zhang Shao-Chun , Lin Hao-Bin , Dong Yang , Du Bo , Gao Xue-Dong , Yu Cui , Feng Zhi-Hong , Chen Xiang-Dong , Guo Guang-Can , Sun Fang-Wen
Published: September 2022

Mapping magnetic fields from different materials and structures can provide a powerful means for broad applications of activity probe and feature analysis. Here, we present a high-sensitivity and wide-bandwidth fiber-based quantum magnetometer at the scale of a few hundred micrometers. We propose a fiber-coupled diamond magnetometer. Tracking a pulsed optically detected magnetic resonance spectrum allows a magnetic field sensitivity of

103
  
pT
/

Hz

and a bandwidth of 2.6 kHz. Additionally, with an approach of coating the diamond surface with silver reflective film, both the fluorescence collection and excitation efficiency are significantly enhanced, and the sensitivity and bandwidth are expected to be further improved to

50
  
pT
/

Hz

and 4.1 kHz, respectively. Finally, this fiber-based quantum magnetometer is applied as a probe to successfully map the magnetic field induced by the current-carrying copper-wire mesh. Such a stable and compact magnetometer can provide a powerful tool in many areas of physical, chemical, and biological researches.
An economic evaluation of an online computer-tailored smoking cessation intervention that includes message frame-tailoring: A randomized controlled trial
Authors: Altendorf Maria B. , van Weert Julia C. M. , Hoving Ciska , Smit Eline S.
Published: September 2022

Evidence of economic evaluations of behaviour change interventions is scarce, but needed to guide policy makers’ decision-making. This study economically evaluated 4 versions of an innovative online computer-tailored smoking cessation intervention. The economic evaluation from a societal perspective was embedded in a randomized controlled trial among 532 smokers using a 2 (message frame-tailoring, i.e. how messages are presented: autonomy-supportive vs controlling) x 2 (content-tailoring, i.e. what content is presented: tailored vs. generic) design. Both kinds of tailoring, content-tailoring and message frame-tailoring, were based on a set of questions asked at baseline. Self-reported costs, prolonged smoking abstinence (cost-effectiveness) and quality of life (cost-utility) were assessed during a 6-month-follow-up. For cost-effectiveness analysis, costs per abstinent smoker were calculated. For cost-utility analysis, costs per QALY (i.e. quality-adjusted life year) gained were calculated. A willingness-to-pay (WTP) threshold of €20.000 was used. Bootstrapping and sensitivity analysis were conducted. Cost-effectiveness analysis showed that up to a WTP of €2.000, the combination of message frame- and content-tailoring dominated all study groups. From a WTP of €2.005, the content-tailored group dominated all study groups. Cost-utility analysis revealed that the combination of message frame-tailoring and content-tailoring had the highest probability of being the most efficient study group at all levels of the WTP. The combination of message frame-tailoring and content-tailoring in online smoking cessation programmes seemed to have high potential for cost-effectiveness (smoking abstinence) and cost-utility (quality of life), thus providing good value for money. Yet, when the WTP for each abstinent smoker is high (i.e., €2.005 or higher), the addition of message frame-tailoring might not be worth the effort and content-tailoring only is preferred.
Repair of mismatched templates during Rad51-dependent Break-Induced Replication
Authors: Choi Jihyun , Kong Muwen , Gallagher Danielle N. , Li Kevin , Bronk Gabriel , Cao Yiting , Greene Eric C. , Haber James E.
Published: September 2022

Using budding yeast, we have studied Rad51-dependent break-induced replication (BIR), where the invading 3’ end of a site-specific double-strand break (DSB) and a donor template share 108 bp of homology that can be easily altered. BIR still occurs about 10% as often when every 6th base is mismatched as with a perfectly matched donor. Here we explore the tolerance of mismatches in more detail, by examining donor templates that each carry 10 mismatches, each with different spatial arrangements. Although 2 of the 6 arrangements we tested were nearly as efficient as the evenly-spaced reference, 4 were significantly less efficient. A donor with all 10 mismatches clustered at the 3’ invading end of the DSB was not impaired compared to arrangements where mismatches were clustered at the 5’ end. Our data suggest that the efficiency of strand invasion is principally dictated by thermodynamic considerations, i.e., by the total number of base pairs that can be formed; but mismatch position-specific effects are also important. We also addressed an apparent difference between in vitro and in vivo strand exchange assays, where in vitro studies had suggested that at a single contiguous stretch of 8 consecutive bases was needed to be paired for stable strand pairing, while in vivo assays using 108-bp substrates found significant recombination even when every 6th base was mismatched. Now, using substrates of either 90 or 108 nt–the latter being the size of the in vivo templates–we find that in vitro D-loop results are very similar to the in vivo results. However, there are still notable differences between in vivo and in vitro assays that are especially evident with unevenly-distributed mismatches. Mismatches in the donor template are incorporated into the BIR product in a strongly polar fashion up to ~40 nucleotides from the 3’ end. Mismatch incorporation depends on the 3’→ 5’ proofreading exonuclease activity of DNA polymerase δ, with little contribution from Msh2/Mlh1 mismatch repair proteins, or from Rad1-Rad10 flap nuclease or the Mph1 helicase. Surprisingly, the probability of a mismatch 27 nt from the 3’ end being replaced by donor sequence was the same whether the preceding 26 nucleotides were mismatched every 6th base or fully homologous. These data suggest that DNA polymerase δ “chews back” the 3’ end of the invading strand without any mismatch-dependent cues from the strand invasion structure. However, there appears to be an alternative way to incorporate a mismatch at the first base at the 3’ end of the donor.
Clinical and laboratory factors associated with neonatal sepsis mortality at a major Vietnamese children’s hospital
Authors: Toan Nguyen Duc , Darton Thomas C. , Huong Nguyen Hoang Thien , Nhat Le Thanh Hoang , Nguyen To Nguyen Thi , Tuyen Ha Thanh , Thinh Le Quoc , Mau Nguyen Kien , Tam Pham Thi Thanh , Phuong Cam Ngoc , Nhan Le Nguyen Thanh , Minh Ngo Ngoc Quang , Xuan Ngo Minh , Thuong Tang Chi , Hung Nguyen Thanh , Boinett Christine , Reece Stephen , Karkey Abhilasha , Day Jeremy N. , Baker Stephen
Published: September 2022

Sepsis is a major cause of neonatal mortality and children born in low- and middle-income countries (LMICs) are at greater risk of severe neonatal infections than those in higher-income countries. Despite this disparity, there are limited contemporaneous data linking the clinical features of neonatal sepsis with outcome in LMICs. Here, we aimed to identify factors associated with mortality from neonatal sepsis in Vietnam. We conducted a prospective, observational study to describe the clinical features, laboratory characteristics, and mortality rate of neonatal sepsis at a major children’s hospital in Ho Chi Minh City. All in-patient neonates clinically diagnosed with probable or culture-confirmed sepsis meeting inclusion criteria from January 2017 to June 2018 were enrolled. We performed univariable analysis and logistic regression to identify factors independently associated with mortality. 524 neonates were recruited. Most cases were defined as late-onset neonatal sepsis and were hospital-acquired (91.4% and 73.3%, respectively). The median (IQR) duration of hospital stay was 23 (13–41) days, 344/524 (65.6%) had a positive blood culture (of which 393 non-contaminant organisms were isolated), and 69/524 (13.2%) patients died. Coagulase-negative staphylococci (232/405; 57.3%), Klebsiella spp. (28/405; 6.9%), and Escherichia coli (27/405; 6.7%) were the most isolated organisms. Sclerema (OR = 11.4), leukopenia <4,000/mm3 (OR = 7.8), thrombocytopenia <100,000/mm3 (OR = 3.7), base excess < –20 mEq/L (OR = 3.6), serum lactate >4 mmol/L (OR = 3.4), extremely low birth weight (OR = 3.2), and hyperglycaemia >180 mg/dL (OR = 2.6) were all significantly (p<0.05) associated with mortality. The identified risk factors can be adopted as prognostic factors for the diagnosis and treatment of neonatal sepsis and enable early risk stratification and interventions appropriate to reduce neonatal sepsis in LMIC settings.
Southwestern national park service employee risk, knowledge, and concern for triatomine exposure: A qualitative analysis using a novel knowledge, attitudes, and practices survey
Authors: Alvarado Antonio , Mader Emily M. , Buttke Danielle , Harrington Laura C.
Published: September 2022

Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is a neglected parasitic infection in the United States (US). In the Southwestern US, National Park Service (NPS) employees are a unique population with potential exposure to CD. This population lives in close contact with several species of sylvatic triatomine bugs, the vectors of T. cruzi, that may enter residential buildings at night. Despite the higher potential risk of CD transmission for southwestern NPS employees, the socio-cultural factors that impact autochthonous CD transmission in the US remain unknown. To address this gap, we investigated how NPS employee knowledge and attitudes impact their triatomine preventive behaviors. We distributed a 42-item online questionnaire to NPS employees at four national parks in Arizona and Texas. We detected high self-reported bite exposure in NPS housing, despite moderate- to high-frequency of prevention behaviors. Specific behaviors, such as often or always repairing window screens, were associated with a decreased risk of putative triatomine bug exposure. Additionally, NPS employees had low knowledge of CD. For those with greater knowledge of CD, it was not associated with increased frequency of prevention behavior. We found that increased CD anxiety was associated with increased personal agency to reduce the risk of CD. These results demonstrate the influence of knowledge and attitudes regarding CD on triatomine prevention behavior within a potential high-risk population in the US, and the importance of utilizing strategies beyond provision of education to influence behaviors.
The Eucalyptus grandis chloroplast proteome: Seasonal variations in leaf development
Authors: Baldassi Amanda Cristina , Balbuena Tiago Santana
Published: September 2022

Chloroplast metabolism is very sensitive to environmental fluctuations and is intimately related to plant leaf development. Characterization of the chloroplast proteome dynamics can contribute to a better understanding on plant adaptation to different climate scenarios and leaf development processes. Herein, we carried out a discovery-driven analysis of the Eucalyptus grandis chloroplast proteome during leaf maturation and throughout different seasons of the year. The chloroplast proteome from young leaves differed the most from all assessed samples. Most upregulated proteins identified in mature and young leaves were those related to catabolic-redox signaling and biogenesis processes, respectively. Seasonal dynamics revealed unique proteome features in the fall and spring periods. The most abundant chloroplast protein in humid (wet) seasons (spring and summer) was a small subunit of RuBisCO, while in the dry periods (fall and winter) the proteins that showed the most pronounced accumulation were associated with photo-oxidative damage, Calvin cycle, shikimate pathway, and detoxification. Our investigation of the chloroplast proteome dynamics during leaf development revealed significant alterations in relation to the maturation event. Our findings also suggest that transition seasons induced the most pronounced chloroplast proteome changes over the year. This study contributes to a more comprehensive understanding on the subcellular mechanisms that lead to plant leaf adaptation and ultimately gives more insights into Eucalyptus grandis phenology.
Long term follow up of direct oral anticoagulants and warfarin therapy on stroke, with all-cause mortality as a competing risk, in people with atrial fibrillation: Sentinel network database study
Authors: de Lusignan Simon , Hobbs F. D. Richard , Liyanage Harshana , Sherlock Julian , Ferreira Filipa , Tripathy Manasa , Heiss Christian , Feher Michael , Joy Mark P.
Published: September 2022

Background

We investigated differences in risk of stroke, with all-cause mortality as a competing risk, in people newly diagnosed with atrial fibrillation (AF) who were commenced on either direct oral anticoagulants (DOACs) or warfarin treatment.

Methods and results

We conducted a retrospective cohort study of the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database (a network of 500 English general practices). We compared long term exposure to DOAC (n = 5,168) and warfarin (n = 7,451) in new cases of AF not previously treated with oral anticoagulants. Analyses included: survival analysis, estimating cause specific hazard ratios (CSHR), Fine-Gray analysis for factors affecting cumulative incidence of events occurring over time and a cumulative risk regression with time varying effects.We found no difference in CSHR between stroke 1.08 (0.72–1.63, p = 0.69) and all-cause mortality 0.93 (0.81–1.08, p = 0.37), or between the anticoagulant groups. Fine-Gray analysis produced similar results 1.07 (0.71–1.6 p = 0.75) for stroke and 0.93 (0.8–1.07, p = 0.3) mortality. The cumulative risk of mortality with DOAC was significantly elevated in early follow-up (67 days), with cumulative risk decreasing until 1,537 days and all-cause mortality risk significantly decreased coefficient estimate:: -0.23 (-0.38–0.01, p = 0.001); which persisted over seven years of follow-up.

Conclusions

In this large, contemporary, real world primary care study with longer follow-up, we found no overall difference in the hazard of stroke between warfarin and DOAC treatment for AF. However, there was a significant time-varying effect between anti-coagulant regimen on all-cause mortality, with DOACs showing better survival. This is a key methodological observation for future follow-up studies, and reassuring for patients and health care professionals for longer duration of therapy
The impact of an integrated, interprofessional knowledge translation intervention on access to inpatient rehabilitation for persons with cognitive impairment
Authors: Linkewich Elizabeth , Rios Jorge , Allen Kay-Ann , Avery Lisa , Dawson Deirdre R. , Donald Michelle , Egan Mary , Hunt Anne , Jutzi Katelyn , McEwen Sara
Published: September 2022

Introduction

Stroke rehabilitation teams’ skills and knowledge in treating persons with cognitive impairment (CI) contribute to their reduced access to inpatient rehabilitation. This study examined stroke inpatient rehabilitation referral acceptance rates for persons with CI before and after the implementation of a multi-faceted integrated knowledge translation (KT) intervention aimed at improving clinicians’ skills in a cognitive-strategy based approach, Cognitive Orientation to daily Occupational Performance (CO-OP), CO-OP KT.

Methods

CO-OP KT was implemented at five inpatient rehabilitation centres, using an interrupted time series design and data from an electronic referral and database system called E-Stroke. CO-OP KT included a 2-day workshop, 4 months of implementation support, health system support, and a sustainability plan. A mixed effects model was used to model monthly acceptance rates for 12 months prior to the intervention and 6 months post.

Results

The dataset was comprised of 2604 pre-intervention referrals and 1354 post. In the mixed effects model, those with CI had a lower pre-intervention acceptance rate than those without. Post-intervention the model showed the acceptance rate for those with CI increased by 8.6% (p = 0.02), whereas those with no CI showed a non-significant increase of less than 1%.

Conclusions

Proportionally more persons with CI gained access to inpatient stroke rehabilitation following an integrated KT intervention.
Economic development, weather shocks and child marriage in South Asia: A machine learning approach
Authors: Dietrich Stephan , Meysonnat Aline , Rosales Francisco , Cebotari Victor , Gassmann Franziska
Published: September 2022

Globally, 21 percent of young women are married before their 18th birthday. Despite some progress in addressing child marriage, it remains a widespread practice, in particular in South Asia. While household predictors of child marriage have been studied extensively in the literature, the evidence base on macro-economic factors contributing to child marriage and models that predict where child marriage cases are most likely to occur remains limited. In this paper we aim to fill this gap and explore region-level indicators to predict the persistence of child marriage in four countries in South Asia, namely Bangladesh, India, Nepal and Pakistan. We apply machine learning techniques to child marriage data and develop a prediction model that relies largely on regional and local inputs such as droughts, floods, population growth and nightlight data to model the incidence of child marriages. We find that our gradient boosting model is able to identify a large proportion of the true child marriage cases and correctly classifies 77% of the true marriage cases, with a higher accuracy in Bangladesh (92% of the cases) and a lower accuracy in Nepal (70% of cases). In addition, all countries contain in their top 10 variables for classification nighttime light growth, a shock index of drought over the previous and the last two years and the regional level of education, suggesting that income shocks, regional economic activity and regional education levels play a significant role in predicting child marriage. Given the accuracy of the model to predict child marriage, our model is a valuable tool to support policy design in countries where household-level data remains limited.
‘‘Ask the way from those who have walked it before”—Grandmothers’ roles in health-related decision making and HIV pre-exposure prophylaxis use among pregnant and breastfeeding women in sub-Saharan Africa
Authors: Reddy Krishnaveni , Kemigisha Doreen , Chitukuta Miria , Dadabhai Sufia , Mathebula Florence , Tenza Siyanda , Palanee-Phillips Thesla , Ryan Julia , Macagna Nicole , Musara Petina , van der Straten Ariane
Published: September 2022

HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa and vertical transmission rates remain high despite established strategies for HIV prevention. During the MTN-041/MAMMA study, we explored the influence of grandmothers (mothers and mothers-in-law of pregnant and breastfeeding women) in eastern and southern Africa on the health-related decisions of pregnant and breastfeeding women and their potential to support use of HIV prevention products. To do this we used structured questionnaires and focus group discussions with three stakeholder groups: 1) grandmothers, 2) HIV-uninfected currently or recently pregnant or breastfeeding women and 3) male partners of currently or recently pregnant or breastfeeding women. A total of 23 focus group discussions comprising 68 grandmothers, 65 pregnant or breastfeeding women and 63 male partners were completed across four study sites. Grandmothers were described as important sources of information during pregnancy and breastfeeding playing both supportive and influencer roles due to personal maternal experience and generational knowledge. While pregnant and breastfeeding women were not keen to involve grandmothers in HIV prevention decision making, they were accepting of grandmothers’ involvement in a supportive role. Grandmothers expressed willingness to support pre-exposure prophylaxis use and agreed with the other two stakeholder groups that this decision should be made by women themselves or together with partners. These novel data indicate potential for grandmothers’ health related supportive roles to be extended to support decision-making and adherence to biomedical HIV prevention options, and possibly contribute to the decline in HIV acquisition among pregnant and breastfeeding women in these communities.
An Overview of Cancer in the First 315,000 All of Us Participants
Authors: Aschebrook-Kilfoy Briseis , Zakin Paul , Craver Andrew , Shah Sameep , Kibriya Muhammad G. , Stepniak Elizabeth , Ramirez Andrea , Clark Cheryl , Cohn Elizabeth , Ohno-Machado Lucila , Cicek Mine , Boerwinkle Eric , Schully Sheri D. , Mockrin Stephen , Gebo Kelly , Mayo Kelsey , Ratsimbazafy Francis , Sanders Alan , Shah Raj C. , Argos Maria , Ho Joyce , Kim Karen , Daviglus Martha , Greenland Philip , Ahsan Habibul ,   On behalf of the All of Us Research Program Investigators
Published: September 2022

Introduction

The NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program’s focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered.

Materials and methods

This work was performed on data collected from the All of Us Research Program’s 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed.

Results and discussion

Data collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data.

Conclusions

This study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future.
Iterative phase contrast CT reconstruction with novel tomographic operator and data-driven prior
Authors: van Gogh Stefano , Mukherjee Subhadip , Xu Jinqiu , Wang Zhentian , Rawlik Michał , Varga Zsuzsanna , Alaifari Rima , Schönlieb Carola-Bibiane , Stampanoni Marco
Published: September 2022

Breast cancer remains the most prevalent malignancy in women in many countries around the world, thus calling for better imaging technologies to improve screening and diagnosis. Grating interferometry (GI)-based phase contrast X-ray CT is a promising technique which could make the transition to clinical practice and improve breast cancer diagnosis by combining the high three-dimensional resolution of conventional CT with higher soft-tissue contrast. Unfortunately though, obtaining high-quality images is challenging. Grating fabrication defects and photon starvation lead to high noise amplitudes in the measured data. Moreover, the highly ill-conditioned differential nature of the GI-CT forward operator renders the inversion from corrupted data even more cumbersome. In this paper, we propose a novel regularized iterative reconstruction algorithm with an improved tomographic operator and a powerful data-driven regularizer to tackle this challenging inverse problem. Our algorithm combines the L-BFGS optimization scheme with a data-driven prior parameterized by a deep neural network. Importantly, we propose a novel regularization strategy to ensure that the trained network is non-expansive, which is critical for the convergence and stability analysis we provide. We empirically show that the proposed method achieves high quality images, both on simulated data as well as on real measurements.
Interventional embolization combined with surgical resection for treatment of extracranial AVM of the head and neck: A monocentric retrospective analysis
Authors: Lilje Daniel , Wiesmann Martin , Hasan Dimah , Ridwan Hani , Hölzle Frank , Nikoubashman Omid
Published: September 2022

Objectives

The aim of this study was to demonstrate the efficacy and feasibility of treating patients with extracranial arteriovenous malformations (AVM) of the head and neck with interventional embolization followed by surgical resection.

Methods

We reviewed the charts of all patients between 2012 and 2021 with extracranial AVM of the head and neck scheduled for interdisciplinary treatment according to University Hospital RWTH Aachen’s protocol and conducted standardized interviews using a newly developed questionnaire. Interview results, as well as clinical examination and radiographic outcome results were analyzed to help determine the efficacy of our treatment approach.

Results

We included 10 patients (8 female, 2 male), with a mean age of 33.5 (11–61) years who were scheduled for treatment of the AVM with interventional embolization followed by surgical resection. In 6 of the 10 patients (60%) the lesion was located in extracranial soft tissue only. In one patient (10%), the lesion was located in bone tissue only. A combined intraosseous and oral soft tissue lesion was seen in the remaining 3 patients (30%). Radiographic resolution was achieved in 62.5% of cases and a significant decrease of symptoms was identified (p = 0.002). None of the patients reported dissatisfaction and no major complications occurred.

Conclusion

An interdisciplinary treatment approach combining neuroradiological interventions with surgical resection appears to be an effective treatment with an acceptable complication rate. Patients treated according to our protocol showed a high satisfaction rate, regardless of the radiographic outcome. Standardized follow-up allows for early detection of recurrences and helps with subjective patient satisfaction.
The relationship between myodural bridges, hyperplasia of the suboccipital musculature, and intracranial pressure
Authors: Li Chan , Yue Chen , Liu Zhao-Chang , Gong Jin , Wei Xiao-Song , Yang Heng , Gilmore Campbell , Yu Sheng-Bo , Hack Gary D. , Sui Hong-Jin
Published: September 2022

During mammalian evolution, the Myodural Bridges (MDB) have been shown to be highly conserved anatomical structures. However, the putative physiological function of these structures remains unclear. The MDB functionally connects the suboccipital musculature to the cervical spinal dura mater, while passing through the posterior atlanto-occipital and atlanto-axial interspaces. MDB transmits the tensile forces generated by the suboccipital muscles to the cervical dura mater. Moreover, head movements have been shown to be an important contributor to human CSF circulation. In the present study, a 16-week administration of a Myostatin-specific inhibitor, ACE-031, was injected into the suboccipital musculature of rats to establish an experimental animal model of hyperplasia of the suboccipital musculature. Using an optic fiber pressure measurement instrument, the present authors observed a significant increase in intracranial pressure (ICP) while utilizing the hyperplasia model. In contrast, surgically severing the MDB connections resulted in a significant decrease in intracranial pressure. Thus, these results indicated that muscular activation of the MDB may affect CSF circulation, suggesting a potential functional role of the MDB, and providing a new research perspective on CSF dynamics.
Characterization and optimization of polymer-polymer aqueous two-phase systems for the isolation and purification of CaCo2 cell-derived exosomes
Authors: Torres-Bautista Abril , Torres-Acosta Mario A. , González-Valdez José
Published: September 2022

Exosomes are cell-derived vesicles that present attractive characteristics such as nano size and unique structure for their use as drug delivery systems for drug therapy, biomarkers for prognostic, diagnostic and personalized treatments. So far, one of the major challenges for therapeutic applications of exosomes is the development of optimized isolation methods. In this context, aqueous two-phase systems (ATPS) have been used as an alternative method to isolate biological molecules and particles with promising expectations for exosomes. In this work, fractionation of exosomes obtained from CaCo2 cell line and culture media contaminants were individually performed in 20 polymer-polymer ATPS. The effect of design parameters such as polymer composition, molecular weight, and tie-line length (TLL) on polyethylene glycol (PEG)-Dextran, Dextran-Ficoll and PEG-Ficoll systems was studied. After partition analysis, 4 of the 20 systems presented the best exosome fractionation from contaminants under initial conditions, which were optimized via salt addition (NaCl) to a final concentration of 25 mM, to improve collection efficiency. The PEG 10,000 gmol-1 –Dextran 10,000 gmol-1 system at TLL 25% w/w with NaCl, showed the best potential isolation efficiency. Following this proposed strategy, an exosome purification factor of 2 in the top PEG-rich phase can be expected furtherly demonstrating that ATPS have the potential for the selective recovery of these promising nanovesicles.
Variation in clinical target volume delineation in postoperative radiotherapy for biliary tract cancer
Authors: Koo Taeryool , Cheong Kwang-Ho , Kim Kyubo , Park Hae Jin , Park Younghee , Koh Hyeon Kang , Kim Byoung Hyuck , Kim Eunji , Kim Kyung Su , Choi Jin Hwa
Published: September 2022

We aimed to evaluate the inter-clinician variability in the clinical target volume (CTV) for postoperative radiotherapy (PORT) for biliary tract cancer (BTC) including extrahepatic bile duct cancer (EBDC) and gallbladder cancer (GBC). Nine experienced radiation oncologists delineated PORT CTVs for distal EBDC (pT2N1), proximal EBDC (pT2bN1) and GBC (pT2bN1) patients. The expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE) was used to quantify expert agreements. We generated volumes with a confidence level of 80% to compare the maximum distance to each CTV in six directions. The degree of agreement was moderate; overall kappa values were 0.573 for distal EBDC, 0.513 for proximal EBDC, and 0.511 for GBC. In the distal EBDC, a larger variation was noted in the right, post, and inferior direction. In the proximal EBDC, all borders except the right and left direction showed a larger variation. In the GBC, a larger variation was found in the anterior, posterior, and inferior direction. The posterior and inferior borders were the common area having discrepancies, associated with the insufficient coverage of the paraaortic node. A consensus guideline is needed to reduce inter-clinician variability in the CTVs and adequate coverage of regional lymph node area.
Comparison of baseline lymphoma and HIV characteristics in Malawi before and after implementation of universal antiretroviral therapy
Authors: Gondwe Yolanda , Kudowa Evaristar , Tomoka Tamiwe , Kasonkanji Edwards D. , Kaimila Bongani , Zuze Takondwa , Mumba Noel , Kimani Stephen , Mulenga Maurice , Chimzimu Fred , Kampani Coxcilly , Randall Cara , Lilly Amy , Gopal Satish , Fedoriw Yuri , Painschab Matthew
Published: September 2022

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016–2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting.

Trial registration: ClinicalTrials.gov identifier: NCT02835911.
Mansonone G and its derivatives exhibit membrane permeabilizing activities against bacteria
Authors: Htoo Htut Htut , Tuyet Nhung Ngo Thi , Nakprasit Kittiporn , Aonbangkhen Chanat , Chaikeeratisak Vorrapon , Chavasiri Warinthorn , Nonejuie Poochit
Published: September 2022

In an era where the rate of bacteria evolving to be resistant to clinically-used antibiotics far exceeds that of antibiotic discovery, the search for new sources of antibacterial agents has expanded tremendously. In recent years, interest in plant-based natural products as promising sources of antibacterial agents has taken an upward trend. Mansonones, botanically-derived naphthoqionones, having many uses in Asian traditional medicine–including anti-infective roles–have sparked interest as a possible source of antibacterial agents. Here, we show that mansonone G, extracted from Mansonia gagei Drumm. heartwoods, possessed antibacterial activities towards Bacillus subtilis, Staphylococcus aureus and Escherichia coli lptD4213, inhibiting the growth of the bacteria at 15.6 μM, 62.5 μM and 125 μM, respectively. Fourteen derivatives of mansonone G were synthesized successfully and were found to have a similar antibacterial spectrum to that of the parent compound, with some derivatives possessing improved antibacterial activities. Bacterial cytological profiling analysis showed that mansonone G harbors membrane permeabilizing activities against B. subtilis and E. coli lptD4213. Temporal analysis of SYTOX Green staining among individual cells showed that mansonone G rapidly permeabilized bacterial membrane within 10 min, with SYTOX Green intensity reaching 13-fold above that of the control. Collectively, these findings highlight the importance of mansonone G and its derivatives as potential antibacterial agents, paving the way for further modifications in order to improve their antibacterial spectrum.
Melatonin supplementation alleviates cellular damage and physical performance decline induced by an intensive training period in professional soccer players
Authors: Farjallah Mohamed Amine , Ghattassi Kais , Kamoun Anis , Graja Ahmed , Ben Mahmoud Lobna , Driss Tarak , Jamoussi Kamel , Sahnoun Zouheir , Souissi Nizar , Zmijewski Piotr , Hammouda Omar
Published: September 2022

Melatonin has been proved to have positive effects on cellular damage and metabolic regulation. The aim of the study was to determine the effect of melatonin supplementation during an intensive training period on physical performance decline, oxidative stress and cellular damage state. The investigation was conducted on 20 soccer players who participated in an exhaustive six-day training schedule associated with daily 5 mg oral melatonin or placebo ingestion. Resting blood samples and physical performance were measured before and after the training period. The mixed 2-way ANOVA (group x training camp) showed that compared to placebo, melatonin intake prevented an increase in advanced oxidation protein products (p>0.05) and increased the antioxidant enzyme activity (i.e., superoxide dismutase; p<0.001). In addition, melatonin prevented an increase of biomarkers of renal function (e.g., creatinine; p>0.05) and biomarkers of muscle (e.g., creatine kinase; p>0.05) and liver (e.g., gamma-glutamyltransferase; p>0.05) damage. Furthermore, melatonin alleviated the deterioration in physical performance (countermovement jump, five-jump test and 20-m sprint; p>0.05). In conclusion, the obtained data showed increased oxidative stress and renal, muscle and liver damage in professional soccer players during an exhaustive training schedule. Melatonin intake during the training period exerts beneficial effects on physical performance and protects tissues against the deleterious effects of reactive oxygen species and cellular damage.
Mucosal expression of Ca and P transporters and claudins in the small intestine of broilers is altered by dietary Ca:P in a limestone particle size dependent manner
Authors: Hu Y. X. , van Baal J. , Hendriks W. H. , Duijster M. , van Krimpen M. M. , Bikker P.
Published: September 2022

High calcium (Ca) intake and fine limestone reduces precaecal phosphorus (P) absorption independently of P solubility in broilers. This study aimed to determine whether dietary total Ca: total P ratio (Ca:P) and limestone particle size (LPS) affect gene expression of P transporters in the small intestine. A total of 384 one-day-old Ross 308 male broiler chickens received diets low (0.50), medium (1.00) or high (1.75) in Ca:P containing either fine (160 μm) or coarse (1062 μm) limestone, in a 3×2 factorial arrangement. Expression of Ca- and P-related genes were determined using real-time quantitative PCR (RT-qPCR) in duodenum and jejunum. Increasing dietary Ca:P decreased duodenal calcium-sensing receptor (CaSR), calbindin-D28k (CaBP-D28k), plasma membrane Ca-ATPase 1 (PMCA1) and sodium-coupled P cotransporter type IIb (NaPi-IIb), but not transient receptor potential canonical 1 (TRPC1) mRNA. This effect was greater with fine limestone when Ca:P increased from low to medium, but greater with coarse limestone when increased from medium to high. A similar inhibitory effect was observed for jejunal CaBP-D28k expression where increasing dietary Ca:P and fine limestone decreased CaSR mRNA, while dietary Ca:P decreased TRPC1 mRNA only for coarse limestone. It also decreased jejunal NaPi-IIb mRNA irrespective of LPS. Dietary treatments did not affect jejunal PMCA1 mRNA expression or that of inorganic phosphate transporter 1 and 2 and xenotropic and polytropic retrovirus receptor 1 in both intestinal segments. Dietary Ca increase reduced mucosal claudin-2 mRNA in both segments, and jejunal zonula occludens-1 (ZO-1) mRNA only for coarse limestone. In conclusion, increasing dietary Ca:P reduced expression of duodenal P transporters (NaPi-IIb) in a LPS dependent manner, hence Ca induced reduction in intestinal P absorption is mediated by decreasing P transporters expression. Dietary Ca reduces Ca digestibility by downregulating mRNA expression of both Ca permeable claudin-2 and Ca transporters (CaBP-D28k, PMCA1).
Health insurance literacy in the Netherlands: The translation and validation of the United States’ Health Insurance Literacy Measure (HILM)
Authors: Holst Laurens , Victoor Aafke , Brabers Anne , Rademakers Jany , de Jong Judith
Published: September 2022

An important criterion for the proper functioning of a managed competition healthcare system, such as operates in the Netherlands, is that all citizens can make well-informed decisions regarding their health insurance policy. In order to achieve this, citizens need certain health insurance literacy skills. It is not known how far citizens in the Netherlands have these skills. The aim of this study is to provide a reliable instrument that measures the health insurance literacy of citizens in the Netherlands. It would be based upon an existing instrument developed in the US. We translated the US Health Insurance Literacy Measure (HILM) into Dutch. Furthermore, we established the psychometric properties of the Dutch version (HILM-NL), and we validated the HILM-NL in a general population sample by sending surveys to members of the Nivel Dutch Health Care Consumer Panel (DHCCP) in February and March 2020. The response rates were respectively 54% (n = 806) and 56% (n = 595). No insurmountable difficulties with equivalence were encountered throughout the translation process. The HILM-NL showed an acceptable level of internal consistency, good test-retest reliability, and a good construct validity. The HILM-NL is a reliable instrument for measuring health insurance literacy among citizens in the Netherlands. With this instrument, it is better possible both to assess how these citizens choose and use a health insurance policy, and also the difficulties they face. It enables citizens in the Netherlands to be supported better in making well-informed decisions on health insurance.
Overview of systematic reviews: Management of common Traumatic Brain Injury-related complications
Authors: Vasudevan Vandana , Amatya Bhasker , Khan Fary
Published: September 2022

Background

Many clinical interventions are trialled to manage medical complications following Traumatic Brain Injury (TBI). However, published evidence for the effects of those clinical interventions is limited. This article is an overview of common complications and their management from published systematic reviews in TBI.

Methods and findings

A health science electronic database search for published systematic reviews for management of common complications in TBI was conducted in the last decade till 31stJanuary 2021. Methodological quality and evidence were critically appraised using the Grading of Recommendations, Assessment, Development and Evaluations and Revised-Assessment of Multiple Systematic review tools. Overall, only six systematic reviews complied with search criteria, these evaluated fatigue, spasticity and post traumatic seizures (29 RCTs, 13 cohort studies, n = 5639 participants). No systematic reviews for other common TBI-related complications met criteria for this review. The included reviews varied from ‘moderate to high’ in methodological quality. The findings suggest beneficial treatment effect of anti-epileptic drugs (phenytoin/levetiracetam) compared with placebo in reducing early seizure incidence, but no significant benefit of phenytoin over levetiracetam, valproate, or neuroprotective agent for early or late posttraumatic seizures. There was ‘limited’ evidence for spasticity-related interventions, and ‘insufficient’ evidence of cardiorespiratory training on fatigue levels.

Conclusions

Despite the high prevalence and associated functional impact of TBI-related complications, there is limited evidence to guide treating clinicians for management of common TBI complications. More robust studies are needed to build evidence in this population.
In planta transcriptomics reveals conflicts between pattern-triggered immunity and the AlgU sigma factor regulon
Authors: Wang Haibi , Smith Amy , Lovelace Amelia , Kvitko Brian H.
Published: September 2022

In previous work, we determined the transcriptomic impacts of flg22 pre-induced Pattern Triggered Immunity (PTI) inArabidopsis thalianaon the pathogenPseudomonas syringaepv.tomatoDC3000 (Pto). During PTI exposure we observed expression patterns inPtoreminiscent of those previously observed in aPto algUmutant. AlgU is a conserved extracytoplasmic function sigma factor which has been observed to regulate over 950 genes inPtoin growth media. We sought to identify the AlgU regulon when the bacteria are inside the plant host and which PTI-regulated genes overlapped with AlgU-regulated genes. In this study, we analyzed transcriptomic data from RNA-sequencing to identify the AlgU regulon (while in the host) and its relationship with PTI. Our results showed that the upregulation of 224 genes while inside the plant host require AlgU, while another 154 genes are downregulated dependent on AlgU inArabidopsisduring early infection. Both stress response and virulence-associated genes were upregulated in a manner dependent on AlgU, while the flagellar motility genes are downregulated in a manner dependent on AlgU. Under the pre-induced PTI condition, more than half of these AlgU-regulated genes have lost induction/suppression in contrast to mock treated plants, and almost all function groups regulated by AlgU were affected by PTI.