Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis.

Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type I interferon signaling platform. Here, we determined cryoelectron microscopy (cryo-EM) structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs at resolutions sufficient to build and refine atomic models. The structures identify the filament-forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.

Gate-tunable contact-induced Fermi-level shift in semimetal.

Low-dimensional semimetal­semiconductor (Sm-S) van der Waals (vdW) heterostructures have shown their potentials in nanoelectronics and nano-optoelectronics recently. It is an important scientific issue to study the interfacial charge transfer as well as the corresponding Fermi-level shift in Sm-S systems. Here we investigated the gate-tunable contact-induced Fermi-level shift (CIFS) behavior in a semimetal single-walled carbon nanotube (SWCNT) that formed a heterojunction with a transition-metal dichalcogenide (TMD) flake. A resistivity comparison methodology and a Fermi-level catch-up model have been developed to measure and analyze the CIFS, whose value is determined by the resistivity difference between the naked SWCNT segment and the segment in contact with the TMD. Moreover, the relative Fermi-level positions of SWCNT and two-dimensional (2D) semiconductors can be efficiently reflected by the gate-tunable resistivity difference. The work function change of the semimetal, as a result of CIFS, will naturally introduce a modified form of the Schottky­Mott rule, so that a modified Schottky barrier height can be obtained for the Sm-S junction. The methodology and physical model should be useful for low-dimensional reconfigurable nanodevices based on Sm-S building blocks.

Multiphoton simultaneous multislice imaging.

PURPOSE: To develop multiphoton excitation techniques for simultaneous multislice (SMS) imaging and evaluate their performance and specific absorption rate (SAR) benefit. To improve multiphoton SMS reconstruction quality with a novel CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) design. THEORY AND METHODS: When a conventional single-slice RF field is applied together with an oscillating gradient field, the two can combine to generate multiphoton excitation at multiple discrete spatial locations. Because the conventional RF is reused at multiple spatial locations, multiphoton excitation offers reduced SAR for SMS applications. CAIPIRINHA shifts are often used to improve parallel-imaging acceleration. Interestingly, CAIPIRINHA-type shifts can be obtained for multiphoton SMS by updating the oscillating gradient phase at every phase encode. In this work, both a gradient-echo and a spin-echo sequence with multiphoton CAIPIRINHA-SMS excitation pulses are implemented for in vivo human imaging at 3 T. RESULTS: For three slices, multiphoton SMS provides a 51% reduction in SAR compared with conventional superposition SMS, whereas for five slices, SAR is reduced by 66%. Multiphoton SMS outperforms PINS (power independent of number of slices) and MultiPINS in terms of SAR reduction especially when the pulse duration is short, slices are thin, and/or the slice spacing is large. A custom CAIPIRINHA phase-encoding design for multiphoton SMS significantly improves reconstruction quality. CONCLUSION: Multiphoton SMS excitation can be obtained by combining conventional single-slice RF pulses with an oscillating gradient and offers significant SAR benefits compared with conventional superposition SMS. A novel CAIPIRINHA design allows higher multiband factors for multiphoton SMS imaging.

Pilot Randomized Controlled Trial of Game Plan for PrEP: A Brief, Web and Text Message Intervention to Help Sexual Minority Men Adhere to PrEP and Reduce Their Alcohol Use.

Suboptimal adherence to oral PrEP medications, particularly among younger sexual minority men (SMM), continues to be a key barrier to achieving more substantial declines in new HIV infections. Although variety of interventions, including web and text-message-based applications, have successfully addressed PrEP adherence, very few have addressed the potential influence of alcohol. This pilot study explored whether the Game Plan for PrEP, a brief, web-based and text messaging intervention, helped promote PrEP persistence and adherence and reduced condomless sex and alcohol use. Seventy-three heavy-drinking SMM on PrEP were recruited online from states with Ending the HIV Epidemic jurisdictions and randomly assigned 1:1 to receive either the Game Plan for PrEP intervention or an attention-matched control. We collected online surveys assessing primary outcomes at one, three, and six months post-enrollment. As secondary outcomes, we also collected dried blood spot samples at baseline, three, and six months to analyze for biomarkers of PrEP and alcohol use. Our results showed that the odds of stopping PrEP or experiencing a clinically meaningful lapse in PrEP adherence (≥ 4 consecutive missed doses) were not different across the two conditions. We also did not find evidence of any differences in condomless sex or drinking outcomes across conditions, although participants in both conditions reported drinking less often over time. These findings were consistent across both self-reported outcomes and biomarkers. Overall, we did not find evidence that our brief, web and text messaging intervention encouraged more optimal PrEP coverage or moderate their alcohol use.

Feasibility of text message follow-up for pediatric asthma care after an emergency department visit.

Background: Many children seen in the Emergency Department (ED) for asthma do not follow-up with their primary care provider. Text messaging via short message service (SMS) is a ubiquitous, but untested means of providing post-ED asthma follow-up care.Objective: To evaluate responses to an asthma assessment survey via SMS following an ED visit and estimate the likelihood of response by sociodemographic and clinical characteristics. Methods: We recruited 173 parents of children 2-17 years-old presenting for ED asthma care to receive a follow-up text (participation rate: 85%). One month later, parents received via SMS a 22-item survey that assessed asthma morbidity. We assessed response rates overall and by various sociodemographic and clinical characteristics, including age, parental education, and indicators of asthma severity.Results: Overall, 55% of parents (n = 95) responded to the SMS survey. In multivariable logistic regression (MLR), parents who graduated high school had a four-fold higher response rate compared to parents with less than a high school degree (OR: 4.05 (1.62, 10.13)). More parents of children with oral steroid use in the prior 12 months responded to survey items (OR: 2.53 (1.2, 5.31)). Reported asthma characteristics included: 48% uncontrolled, 22% unimproved/worse, 21% with sleep disruption, and 10% who were hospitalized for asthma.Conclusions: Text messaging may be a viable strategy to improve post-ED asthma assessment and to identify children with persistent symptoms in need of enhanced care or modification of care plans.

Text message questionnaires for Patient-Reported Outcome Measures after Cesarean section-A feasibility study.

BACKGROUND: Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed assessment on the timing of severe pain, opioid consumption, influence on activities such as mobilization, breastfeeding, and caring for the infant are difficult to conduct, especially after discharge. Short message services (SMS)-based questionnaires may offer a low-cost way of providing such data but with the risk of insufficient response rates. We assessed the feasibility of collecting detailed, prospective data on postoperative pain and recovery during the initial hours and days following cesarean section using SMS-based questionnaires. METHODS: Prospective Danish single-center cohort study involving elective cesarean sections under spinal anesthesia with fentanyl and bupivacaine. The postoperative pain regimen consisted of paracetamol, NSAID and oral morphine by request. Patients received an SMS-based questionnaire at 6, 12, 18, 24, and 48 h postoperatively, as well as on days 7 and 30. PRIMARY OUTCOME: Response rate and time from receiving the SMS to completion of the questionnaires. SECONDARY OUTCOMES: Opioid consumption and Patient Reported Outcomes Measures on pain and recovery. RESULTS: From December 2022 to June 2023; 100 patients were included. The response rate was 78% at 6 h postoperatively, decreasing to 63% at 24 h. The median response time from receiving to answering the SMS-based questionnaire at 6 h after cesarean section was 23 min (IQR 2-72), decreasing to 20 min (IQR 2-78) after 24 h. Severe pain, corresponding to a Numeric Rating Scale (NRS) score >6, was reported by 57% (95% CI 65-84) at 6 h, decreasing to 28% (95% CI 34-58) at 24 h. Median opioid consumption within the first 24 h was 30 mg (IQR 20-50). CONCLUSION: SMS-based questionnaires on Patient Reported Outcome Measures are a feasible and cost-effective way of prospectively collecting frequent data with acceptable response rates, even shortly after cesarean section. Secondarily 66% of patients reported severe pain during the first 24 h following cesarean section, with the highest pain scores within the initial 12 h. Future studies should focus on optimizing pain-management within this timeframe.

Effectiveness of a culturally tailored text messaging program for promoting cervical cancer screening in accra, Ghana: a quasi-experimental trial.

INTRODUCTION: Despite breakthroughs in cervical cancer detection, resource-constrained countries continue to have a disproportionately high incidence and death rate. Mhealth has been identified as an important tool for increasing cervical cancer screening rates in Sub-Saharan Africa. We determined whether sending Ghanaian women culturally tailored one-way mobile phone SMS text messages about cervical cancer would encourage the uptake of the human papillomavirus (HPV) test. METHODS: From August to November 2016, 88 women aged 18 to 39 living or working in an urban community (Accra, Ghana) participated in a quasi-experimental study. For 8 weeks, 32 SMS messages regarding cervical cancer were developed and sent to the personal phones of intervention arm participants (n = 42). Women in the control group (n = 46) received SMS texts with general health and lifestyle advice. Fischer's exact tests were performed to assess cervical cancer screening uptake and associated reasons for non-uptake between the intervention and control groups (p < 0.05). RESULTS: At the baseline, women differed in terms of ethnicity and wealth. After the intervention, participants' self-reported risk factors for cervical cancer, such as early menarche, usual source of medical treatment, family history of cancer, smoking, and alcohol history, changed. None of the women in the intervention group sought cervical cancer screening after the intervention, but only one (2.2%) of the control arm participants did. Almost all the women (> 95%) agreed that an HPV test was essential and that regular healthcare check-ups could help prevent cervical cancer. Some women believed that avoiding particular foods could help prevent cervical cancer (23.8% intervention vs. 58.7% control, p < 0.001). Time constraints and out-of-pocket expenses were significant barriers to cervical cancer screening. CONCLUSION: A one-way SMS delivered to urban women did not increase cervical cancer screening attendance. The time spent in screening facilities and the lack of coverage by the National Health Insurance Scheme limited screening uptake. We urge for the establishment of screening centers in all healthcare facilities, as well as the inclusion of cervical cancer screening in healthcare programs through cost-sharing.

SMS-based interventions for improving child and adolescent vaccine coverage and timeliness: a systematic review.

BACKGROUND: The aim of this review was to investigate the impact of short message service (SMS)-based interventions on childhood and adolescent vaccine coverage and timeliness. METHODS: A pre-defined search strategy was used to identify all relevant publications up until July 2022 from electronic databases. Reports of randomised trials written in English and involving children and adolescents less than 18 years old were included. The review was conducted in accordance with PRISMA guidelines. RESULTS: Thirty randomised trials were identified. Most trials were conducted in high-income countries. There was marked heterogeneity between studies. SMS-based interventions were associated with small to moderate improvements in vaccine coverage and timeliness compared to no SMS reminder. Reminders with embedded education or which were combined with monetary incentives performed better than simple reminders in some settings. CONCLUSION: Some SMS-based interventions appear effective for improving child vaccine coverage and timeliness in some settings. Future studies should focus on identifying which features of SMS-based strategies, including the message content and timing, are determinants of effectiveness.

Employing Bayesian analysis to establish a cut-off point and assess stigma prevalence in substance use disorder: a comprehensive study of the Chinese version of the Substance Use Stigma Mechanism Scale.

PURPOSE: In China, individuals with substance use disorders (SUD) face severe stigma, but reliable stigma assessment tool is lacking. Therefore, this study aimed to validate the Chinese version of the Substance Use Stigma Mechanism Scale (SU-SMS-C) and set its cut-off point. METHODS: We recruited 1005 individuals with SUDs from Chinese rehabilitation centers. These participants completed a battery of questionnaires that included the SU-SMS-C, The Multidimensional Scale of Perceived Social Support (MSPSS), Center for Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale (GSES), and Perceived Devaluation and Discrimination (PDD). Confirmatory factor analysis was used to assess the construct validity of the scale. Additionally, the Naive Bayes classifier was used to establish the cut-off point for the SU-SMS-C. We additionally explored the correlation between patient demographic characteristics and stigma. RESULTS: A confirmatory factor analysis was utilized, revealing a second-order five-factor model. Based on the Naive Bayes classifier, the area under the receiver operating characteristic (AUCROC) of 0.746, the cut-off point for the SU-SMS-C was established at 44.5. The prevalence of stigma observed in the study population was 49.05%. Significant disparities were observed in the distribution of stigma across genders, with males experiencing more pronounced stigma than females. Moreover, patients consuming different primary substances reported diverse levels of stigma. Notably, those primarily using heroin endured a higher degree of stigma than users of other substances. CONCLUSION: The study is the first to identify a cut-off point for the SU-SMS-C by Naive Bayes classifier, bridging a major gap in stigma measurement research. SU-SMS-C may help treat and manage SUDs by reducing stigma.

The Use of Mobile Technologies to Promote Physical Activity and Reduce Sedentary Behaviors in the Middle East and North Africa Region: Systematic Review and Meta-Analysis.

BACKGROUND: The Middle East and North Africa (MENA) region faces unique challenges in promoting physical activity and reducing sedentary behaviors, as the prevalence of insufficient physical activity is higher than the global average. Mobile technologies present a promising approach to delivering behavioral interventions; however, little is known about the effectiveness and user perspectives on these technologies in the MENA region. OBJECTIVE: This study aims to evaluate the effectiveness of mobile interventions targeting physical activity and sedentary behaviors in the MENA region and explore users' perspectives on these interventions as well as any other outcomes that might influence users' adoption and use of mobile technologies (eg, appropriateness and cultural fit). METHODS: A systematic search of 5 databases (MEDLINE, Embase, CINAHL, Scopus, and Global Index Medicus) was performed. Any primary studies (participants of all ages regardless of medical condition) conducted in the MENA region that investigated the use of mobile technologies and reported any measures of physical activity, sedentary behaviors, or user perceptions were included. We conducted a narrative synthesis of all studies and a meta-analysis of randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs; quality assessment of the rest of the included studies was completed using the relevant Joanna Briggs Institute critical appraisal tools. RESULTS: In total, 27 articles describing 22 interventions (n=10, 37% RCTs) and 4 (15%) nonexperimental studies were included (n=6141, 46% women). Half (11/22, 50%) of the interventions included mobile apps, whereas the other half examined SMS. The main app functions were goal setting and self-monitoring of activity, whereas SMS interventions were primarily used to deliver educational content. Users in experimental studies described several benefits of the interventions (eg, gaining knowledge and receiving reminders to be active). Engagement with the interventions was poorly reported; few studies (8/27, 30%) examined users' perspectives on the appropriateness or cultural fit of the interventions. Nonexperimental studies examined users' perspectives on mobile apps and fitness trackers, reporting several barriers to their use, such as perceived lack of usefulness, loss of interest, and technical issues. The meta-analysis of RCTs showed a positive effect of mobile interventions on physical activity outcomes (standardized mean difference=0.45, 95% CI 0.17-0.73); several sensitivity analyses showed similar results. The trim-and-fill method showed possible publication bias. Only 20% (2/10) of the RCTs measured sedentary behaviors; both reported positive changes. CONCLUSIONS: The use of mobile interventions for physical activity and sedentary behaviors in the MENA region is in its early stages, with preliminary evidence of effectiveness. Policy makers and researchers should invest in high-quality studies to evaluate long-term effectiveness, intervention engagement, and implementation outcomes, which can inform the design of culturally and socially appropriate interventions for countries in the MENA region. TRIAL REGISTRATION: PROSPERO CRD42023392699; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392699.

Evaluation of an SMS Based Alcohol Intervention for Same Sex Attracted Women: A Randomized Controlled Trial to Examine Feasibility, Acceptability, and Efficacy.

PURPOSE: The purpose of this randomized controlled trial (Trial registration ID: redacted) was to examine the feasibility, acceptability, and efficacy of the Step One program, an SMS-based alcohol intervention for same-sex attracted women (SSAW). METHODS: Ninety-seven SSAW who scored ≥8 on the Alcohol Use Disorders Identification Test (AUDIT) were randomly allocated to receive the Step One program (n = 47; mean age = 36.79) or a weekly message containing a link to a website with health information and support services for LGBT individuals (n = 50; mean age = 34.08). Participants completed questionnaires on alcohol use, wellbeing, and help-seeking at baseline (T1), intervention completion (T2; 4 wk after baseline) and 12 wk post-intervention (T3). In addition, participants in the intervention condition completed feasibility and accessibility measures at T2, and a subsample (n = 10) was interviewed about acceptability at T3. RESULTS: Across conditions, participants significantly reduced their alcohol intake and improved their wellbeing and help-seeking over time. However, there were no significant differences between the intervention and control condition. Furthermore, frequency of help-seeking was low; only four intervention group participants and three control group participants began accessing support between T1 and T3. Overall, our findings indicate the intervention would benefit from revision prior to implementation. CONCLUSIONS: Our approach was consistent with best practice in the development of an ecologically valid intervention; however, this intervention, in its current form, lacks the complexity desired by its users to optimally facilitate alcohol reduction among SSAW. Keywords: Alcohol intervention; Intervention mapping framework; Randomized controlled trial (RCT); Same-sex attracted women; Short-message service (SMS).

Spectral Characteristics and Displacement Sensing of U-Shaped Single-Mode-Multimode-Single-Mode Fiber Structure.

The U-shaped fiber configuration represents the elementary form of micro-displacement sensing, characterized by its exceptional freedom and flexibility. The study proposes the U-shaped bent single-mode-multimode-single-mode (SMS) fiber structure that integrates the multimode interference (MMI) effect for enhanced mode dispersion and the Mach-Zönder interference (MZI) effect for spectral sensitivity improvement. The transmission spectral properties of the U-shaped SMS fiber structure with a bent radius over 1 cm are experimentally measured as the change in displacement varied within the range of 5 mm in this work. As the radius decreases, the spectrum shows redshift, which is related to the central wavelength of the peak or dips-a smaller wavelength results in a stronger redshift for the same displacement change. The average sensitivity of micro-displacement measurement within a range of 5 mm is 5.41 pm/µm, and the linearity is 99.62%. The maximum sensitivity of U-shaped SMS fiber structure is 34.46 pm/µm, with the minimum displacement change of approximately 5.804 nm. The transmission spectral properties of the U-shaped SMS fiber structure within the ranges of 50 µm, 500 µm, and 5 mm are experimentally measured in this work. This experiment observed a relatively uniform spectral drift pattern in a large range of micro-displacement sensing. The measurement range is limited by the limited spectral range of the light source and the discontinuous variation in the effective refractive index. This provides an experimental reference for further understanding the characteristics of U-shaped fiber structures and applying its application in micro-displacement sensing.

Chemical Epigenetic Regulation Secondary Metabolites Derived from Aspergillus sydowii DL1045 with Inhibitory Activities for Protein Tyrosine Phosphatases.

Protein tyrosine phosphatases (PTPs) are ubiquitous in living organisms and are promising drug targets for cancer, diabetes/obesity, and autoimmune disorders. In this study, a histone deacetylase inhibitor called suberoylanilide hydroxamic acid (SAHA) was added to a culture of marine fungi (Aspergillus sydowii DL1045) to identify potential drug candidates related to PTP inhibition. Then, the profile of the induced metabolites was characterized using an integrated metabolomics strategy. In total, 46% of the total SMs were regulated secondary metabolites (SMs), among which 20 newly biosynthesized metabolites (10% of the total SMs) were identified only in chemical epigenetic regulation (CER) broth. One was identified as a novel compound, and fourteen compounds were identified from Aspergillus sydowii first. SAHA derivatives were also biotransformed by A. sydowii DL1045, and five of these derivatives were identified. Based on the bioassay, some of the newly synthesized metabolites exhibited inhibitory effects on PTPs. The novel compound sydowimide A (A11) inhibited Src homology region 2 domain-containing phosphatase-1 (SHP1), T-cell protein tyrosine phosphatase (TCPTP) and leukocyte common antigen (CD45), with IC50 values of 1.5, 2.4 and 18.83 µM, respectively. Diorcinol (A3) displayed the strongest inhibitory effect on SHP1, with an IC50 value of 0.96 µM. The structure-activity relationship analysis and docking studies of A3 analogs indicated that the substitution of the carboxyl group reduced the activity of A3. Research has demonstrated that CER positively impacts changes in the secondary metabolic patterns of A. sydowii DL1045. The compounds produced through this approach will provide valuable insights for the creation and advancement of novel drug candidates related to PTP inhibition.

Text messages to improve young child diets: Results from a cluster-randomized controlled trial in Kanchanpur, Nepal.

The objective of this study was to test whether adding a text message campaign about the importance of eating eggs and other nutrition-related behaviours to an on-going package of large-scale, diverse social and behaviour change interventions would improve four types of nutrition-related knowledge and behaviour outcomes: child diets (egg consumption as the primary outcome), maternal diets, maternal nutrition knowledge, and maternal participation in additional interventions. The cluster-randomized controlled trial involved a repeat cross-sectional design, recruiting families with children 12-23 months of age at baseline and endline in one plains district of Nepal. Throughout the 1000-day period, 51 text messages were sent to each household at specific time points to reinforce ideal diets and other nutrition-related practices and promote engagement with community health workers and other intervention platforms. The primary outcome was egg consumption and dietary diversity among young children. We found no population-level effect. Some evidence supports that for those who received and opened the SMS intervention, it improved child egg consumption (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.03-1.93), child minimum dietary diversity (OR: 1.36, 95% CI: 1.07-1.73), child dietary diversity scores (ß: 0.15, 95% CI: 0.01-0.24), as well as maternal IYCF knowledge (ß: 0.21, 95% CI: 0.08-0.35), participation in health mothers' group meetings (OR: 3.03, 95% CI: 1.91-4.84) and Bhanchhin Aama listenership (OR: 1.36, 95% CI: 1.07-1.73). This study highlights the importance of more research to understand the effectiveness of emerging digital interventions for behaviour change among specific populations, to facilitate nuanced targeting to those who can best benefit from these investments. Registered at clinicaltrials.gov with identifier NCT03926689.

Whole-Cerebrum distortion-free three-dimensional pseudo-continuous arterial spin labeling at 7T.

Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave = 0.4 mT/m, Gratio = 14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R = 2 × 2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2 × 2 × 4 mm3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.

Noninvasive Prenatal Screening for Common Fetal Aneuploidies Using Single-Molecule Sequencing.

Amplification biases caused by next-generation sequencing (NGS) for noninvasive prenatal screening (NIPS) may be reduced using single-molecule sequencing (SMS), during which PCR is omitted. Therefore, the performance of SMS-based NIPS was evaluated. We used SMS-based NIPS to screen for common fetal aneuploidies in 477 pregnant women. The sensitivity, specificity, positive predictive value, and negative predictive value were estimated. The GC-induced bias was compared between the SMS- and NGS-based NIPS methods. Notably, a sensitivity of 100% was achieved for fetal trisomy 13 (T13), trisomy 18 (T18), and trisomy 21 (T21). The positive predictive value was 46.15% for T13, 96.77% for T18, and 99.07% for T21. The overall specificity was 100% (334/334). Compared with NGS, SMS (without PCR) had less GC bias, a better distinction between T21 or T18 and euploidies, and better diagnostic performance. Overall, our results suggest that SMS improves the performance of NIPS for common fetal aneuploidies by reducing the GC bias introduced during library preparation and sequencing.

Measuring brain beats: Cardiac-aligned fast functional magnetic resonance imaging signals.

Blood and cerebrospinal fluid (CSF) pulse and flow throughout the brain, driven by the cardiac cycle. These fluid dynamics, which are essential to healthy brain function, are characterized by several noninvasive magnetic resonance imaging (MRI) methods. Recent developments in fast MRI, specifically simultaneous multislice acquisition methods, provide a new opportunity to rapidly and broadly assess cardiac-driven flow, including CSF spaces, surface vessels and parenchymal vessels. We use these techniques to assess blood and CSF flow dynamics in brief (3.5 min) scans on a conventional 3 T MRI scanner in five subjects. Cardiac pulses are measured with a photoplethysmography (PPG) on the index finger, along with functional MRI (fMRI) signals in the brain. We, retrospectively, align the fMRI signals to the heartbeat. Highly reliable cardiac-gated fMRI temporal signals are observed in CSF and blood on the timescale of one heartbeat (test-retest reliability within subjects R2  > 50%). In blood vessels, a local minimum is observed following systole. In CSF spaces, the ventricles and subarachnoid spaces have a local maximum following systole instead. Slower resting-state scans with slice timing, retrospectively, aligned to the cardiac pulse, reveal similar cardiac-gated responses. The cardiac-gated measurements estimate the amplitude and phase of fMRI pulsations in the CSF relative to those in the arteries, an estimate of the local intracranial impedance. Cardiac aligned fMRI signals can provide new insights about fluid dynamics or diagnostics for diseases where these dynamics are important.

Simultaneous multislice imaging with slice-specific z-shim.

PURPOSE: To implement slice-specific z-shim in simultaneous multislice (SMS) imaging in order to minimize signal losses in slice-accelerated T2 *-weighted acquisitions, such as for spinal cord functional neuroimaging. METHODS: The RF envelopes of the individual slice bands are temporally shifted on the plateau of the slice-selection gradient pulse before being combined to the multiband RF envelope. Thus, optimum z-shims can be realized for each slice of an SMS excitation, which is in contrast to conventional z-shimming. EPI with 2-fold SMS acceleration was performed on a 3T whole-body MR system in phantoms and the cervical spinal cord of healthy volunteers (i) without z-shim, (ii) with conventional z-shim using the average value of the slices of the SMS excitation, and (iii) with optimal, slice-specific z-shims for each slice using envelope shifts. RESULTS: Phantom experiments demonstrate the equivalence of the envelope shift and conventional z-shimming for non-SMS excitations. With SMS, the best image quality is obtained with "mixed" z-shim, where only the z-shim differences of the slices of an SMS excitation are implemented by an envelope shift while their mean z-shim is applied conventionally with a gradient pulse after the echoes acquired for N/2 ghost correction. In phantoms and in vivo, this setup outperforms the approaches without slice-specific z-shim with respect to signal amplitude and temporal SNR at the expense of slight TE differences (<1 ms) between the slices. CONCLUSION: With RF envelope shifts, slice-specific z-shims can be combined with SMS imaging, which could improve slice-accelerated functional neuroimaging in the spinal cord.

Simultaneous multislice EPI prospective motion correction by real-time receiver phase correction and coil sensitivity map interpolation.

PURPOSE: To improve the image reconstruction for prospective motion correction (PMC) of simultaneous multislice (SMS) EPI of the brain, an update of receiver phase and resampling of coil sensitivities are proposed and evaluated. METHODS: A camera-based system was used to track head motion (3 translations and 3 rotations) and dynamically update the scan position and orientation. We derived the change in receiver phase associated with a shifted field of view (FOV) and applied it in real-time to each k-space line of the EPI readout trains. Second, for the SMS reconstruction, we adapted resampled coil sensitivity profiles reflecting the movement of slices. Single-shot gradient-echo SMS-EPI scans were performed in phantoms and human subjects for validation. RESULTS: Brain SMS-EPI scans in the presence of motion with PMC and no phase correction for scan plane shift showed noticeable artifacts. These artifacts were visually and quantitatively attenuated when corrections were enabled. Correcting misaligned coil sensitivity maps improved the temporal SNR (tSNR) of time series by 24% (p = 0.0007) for scans with large movements (up to ˜35 mm and 30°). Correcting the receiver phase improved the tSNR of a scan with minimal head movement by 50% from 50 to 75 for a United Kingdom biobank protocol. CONCLUSION: Reconstruction-induced motion artifacts in single-shot SMS-EPI scans acquired with PMC can be removed by dynamically adjusting the receiver phase of each line across EPI readout trains and updating coil sensitivity profiles during reconstruction. The method may be a valuable tool for SMS-EPI scans in the presence of subject motion.

A randomized controlled trial of post-donation communication materials to increase donor return following a vasovagal reaction.

BACKGROUND: Vasovagal reactions (VVRs) are one of the primary reasons for people to stop donating blood. The aim of this study was to evaluate the impact of newly developed online communications on the rate of return of whole-blood (WB) and plasma donors who experienced a VVR. STUDY DESIGN AND METHODS: First-time and experienced WB and plasma donors who had a VVR without a loss of consciousness in the previous 3 days were randomly allocated to receive (a) an SMS sent 1-4 days post-VVR (n = 2303), (b) an email sent 6-10 days post-VVR (n = 2360), (c) both the SMS and the email (n = 2248), or (d) business-as-usual donor retention communications (control; n = 2557). Donation data were extracted to determine subsequent donation attempts. RESULTS: For return within 3 months, WB donors in the Email Only condition had significantly increased odds of returning (OR: 1.26, 95%CI: 1.01-1.56). Subgroup analysis within WB donors showed increased odds of return for women sent the SMS and Email (OR: 1.50, 95%CI: 1.14-1.96) or the Email Only (OR: 1.44, 95%CI: 1.10-1.89), and for first-time donors sent the Email Only (OR: 1.48, 95%CI: 1.07-2.05). At 6 months, only first-time WB donors in the Email Only condition had significantly increased odds of returning (OR: 1.30, 95%CI: 1.01-1.69). No significant effects of the intervention were found for immediate or intermediate return for plasma donors. DISCUSSION: Sending an email addressing common donor concerns regarding VVRs increases WB donor retention, but additional strategies are needed for the effects to last and to retain plasma donors.