bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fused ultrasound and electromyography-driven neuromuscular model to improve plantarflexion moment prediction across walking speeds
Authors: Zhang Qiang , Fragnito Natalie , Franz Jason R. , Sharma Nitin 
Published: August 2022

Abstract
Background
Improving the prediction ability of a human-machine interface (HMI) is critical to accomplish a bio-inspired or model-based control strategy for rehabilitation interventions, which are of increased interest to assist limb function post neurological injuries. A fundamental role of the HMI is to accurately predict human intent by mapping signals from a mechanical sensor or surface electromyography (sEMG) sensor. These sensors are limited to measuring the resulting limb force or movement or the neural signal evoking the force. As the intermediate mapping in the HMI also depends on muscle contractility, a motivation exists to include architectural features of the muscle as surrogates of dynamic muscle movement, thus further improving the HMI’s prediction accuracy.

Objective
The purpose of this study is to investigate a non-invasive sEMG and ultrasound (US) imaging-driven Hill-type neuromuscular model (HNM) for net ankle joint plantarflexion moment prediction. We hypothesize that the fusion of signals from sEMG and US imaging results in a more accurate net plantarflexion moment prediction than sole sEMG or US imaging.

Methods
Ten young non-disabled participants walked on a treadmill at speeds of 0.50, 0.75, 1.00, 1.25, and 1.50 m/s. The proposed HNM consists of two muscle-tendon units. The muscle activation for each unit was calculated as a weighted summation of the normalized sEMG signal and normalized muscle thickness signal from US imaging. The HNM calibration was performed under both single-speed mode and inter-speed mode, and then the calibrated HNM was validated across all walking speeds.

Results
On average, the normalized moment prediction root mean square error was reduced by 14.58 % ($$p=0.012$$

p
=
0.012

) and 36.79 % ($$p<0.001$$

p
<
0.001

) with the proposed HNM when compared to sEMG-driven and US imaging-driven HNMs, respectively. Also, the calibrated models with data from the inter-speed mode were more robust than those from single-speed modes for the moment prediction.

Conclusions
The proposed sEMG-US imaging-driven HNM can significantly improve the net plantarflexion moment prediction accuracy across multiple walking speeds. The findings imply that the proposed HNM can be potentially used in bio-inspired control strategies for rehabilitative devices due to its superior prediction.
Motorless cadence control of standard and low duty cycle-patterned neural stimulation intensity extends muscle-driven cycling output after paralysis
Authors: Gelenitis Kristen , Foglyano Kevin , Lombardo Lisa , McDaniel John , Triolo Ronald 
Published: August 2022

Abstract
Background
Stimulation-driven exercise is often limited by rapid fatigue of the activated muscles. Selective neural stimulation patterns that decrease activated fiber overlap and/or duty cycle improve cycling exercise duration and intensity. However, unequal outputs from independently activated fiber populations may cause large discrepancies in power production and crank angle velocity among pedal revolutions. Enforcing a constant cadence through feedback control of stimulus levels may address this issue and further improve endurance by targeting a submaximal but higher than steady-state exercise intensity.

Methods
Seven participants with paralysis cycled using standard cadence-controlled stimulation (S-Cont). Four of those participants also cycled with a low duty cycle (carousel) cadence-controlled stimulation scheme (C-Cont). S-Cont and C-Cont patterns were compared with conventional maximal stimulation (S-Max). Outcome measures include total work (W), end power (Pend), power fluctuation (PFI), charge accumulation (Q) and efficiency (η). Physiological measurements of muscle oxygenation (SmO2) and heart rate were also collected with select participants.

Results
At least one cadence-controlled stimulation pattern (S-Cont or C-Cont) improved Pend over S-Max in all participants and increased W in three participants. Both controlled patterns increased Q and η and reduced PFI compared with S-Max and prior open-loop studies. S-Cont stimulation also delayed declines in SmO2 and increased heart rate in one participant compared with S-Max.

Conclusions
Cadence-controlled selective stimulation improves cycling endurance and increases efficiency over conventional stimulation by incorporating fiber groups only as needed to maintain a desired exercise intensity. Closed-loop carousel stimulation also successfully reduces power fluctuations relative to previous open-loop efforts, which will enable neuroprosthesis recipients to better take advantage of duty cycle reducing patterns.
The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice
Authors: Sobolewski Marissa , Conrad Katherine , Marvin Elena , Eckard Matthew , Goeke Calla M. , Merrill Alyssa K. , Welle Kevin , Jackson Brian P. , Gelein Robert , Chalupa David , Oberdörster Günter , Cory-Slechta Deborah A. 
Published: August 2022

Abstract
Background
Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain metal dyshomeostasis, including significant increases in brain Fe. Since Fe is redox active and neurotoxic to brain in excess, this study examined the extent to which postnatal Fe inhalation exposure, might contribute to the observed neurotoxicity of UFPs. Mice were exposed to 1 µg/m3 Fe oxide nanoparticles alone, or in conjunction with sulfur dioxide (Fe (1 µg/m3) + SO2 (SO2 at 1.31 mg/m3, 500 ppb) from postnatal days 4–7 and 10–13 for 4 h/day.

Results
Overarching results included the observations that Fe + SO2 produced greater neurotoxicity than did Fe alone, that females appeared to show greater vulnerability to these exposures than did males, and that profiles of effects differed by sex. Consistent with metal dyshomeostasis, both Fe only and Fe + SO2 exposures altered correlations of Fe and of sulfur (S) with other metals in a sex and tissue-specific manner. Specifically, altered metal levels in lung, but particularly in frontal cortex were found, with reductions produced by Fe in females, but increases produced by Fe + SO2 in males. At PND14, marked changes in brain frontal cortex and striatal neurotransmitter systems were observed, particularly in response to combined Fe + SO2 as compared to Fe only, in glutamatergic and dopaminergic functions that were of opposite directions by sex. Changes in markers of trans-sulfuration in frontal cortex likewise differed in females as compared to males. Residual neurotransmitter changes were limited at PND60. Increases in serum glutathione and Il-1a were female-specific effects of combined Fe + SO2.

Conclusions
Collectively, these findings suggest a role for the Fe contamination in air pollution in the observed neurotoxicity of ambient UFPs and that such involvement may be different by chemical mixture. Translation of such results to humans requires verification, and, if found, would suggest a need for regulation of Fe in air for public health protection.
Effects of lactation room quality on working mothers’ feelings and thoughts related to breastfeeding and work: a randomized controlled trial and a field experiment
Authors: van Dellen Sjoukje A. , Wisse Barbara , Mobach Mark P. 
Published: August 2022

Abstract
Background
The challenging combination of breastfeeding and work is one of the main reasons for early breastfeeding cessation. Although the availability of a lactation room (defined as a private space designated for milk expression or breastfeeding) is important in enabling the combination of breastfeeding and work, little is known about the effects of lactation room quality on mothers’ feelings and thoughts related to breastfeeding and work. We hypothesized that a high-quality lactation room (designed using the Theory of Supportive Design) would cause mothers to experience less stress, have more positive thoughts about milk expression at work, perceive more organizational support, and report more subjective well-being, than a low-quality lactation room.

Methods
In an online randomized controlled trial (Study 1), Dutch mothers (N = 267) were shown either a high-quality or a low-quality lactation room (using pictures and descriptions for the manipulation) and were then asked about their feelings and thoughts. In a subsequent field experiment (Study 2) we modified the lactations rooms in a large organization in Groningen, the Netherlands, to manipulate lactation room quality, and asked mothers (N = 61) who used either a high-quality or low-quality lactation room to fill out surveys to assess the dependent variables.

Results
The online study showed that mothers exposed to the high-quality lactation room anticipated less stress, more positive cognitions about milk expression at work, more perceived organizational support, and more subjective well-being than mothers exposed to the low-quality lactation room (p <  0.05). Moreover, the effect of lactation room quality on perceived organizational support was especially pronounced for mothers who were higher in environmental sensitivity. The field experiment showed that use of the high-quality room led to less reported stress than use of the low-quality room (p <  0.05). We also found that mothers who were higher in environmental sensitivity perceived more control over milk expression at work and experienced more subjective well-being in the high-quality condition than in the low-quality condition (p <  0.05).

Conclusion
The current studies show that not only the availability, but also the quality of lactation rooms is important in facilitating the combination of breastfeeding and work.
Vitamin B12 in Leber hereditary optic neuropathy mutation carriers: a prospective cohort study
Authors: Zibold Julia , von Livonius Bettina , Kolarova Hana , Rudolph Günter , Priglinger Claudia S. , Klopstock Thomas , Catarino Claudia B. 
Published: August 2022

Abstract
Background
Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, frequently resulting in acute or subacute severe bilateral central vision loss. Vitamin B12 deficiency is also a known cause of optic neuropathy through mitochondrial dysfunction. Here we evaluated the prevalence and clinical significance of vitamin B12 deficiency in a large cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral center.

Methods
From the Munich LHON prospective cohort study, participants included all LHON patients and asymptomatic LHON mutation carriers, who were recruited between February 2014 and March 2020 and consented to participate. Neurological, general, and ophthalmological examinations were regularly performed, as were laboratory tests. Vitamin B12 deficiency was diagnosed if serum vitamin B12 was below 201 pg/mL, or if 201–339 pg/mL plus low serum holotranscobalamin or elevated serum methylmalonic acid or elevated total plasma homocysteine.

Results
We analyzed 244 subjects, including 147 symptomatic LHON patients (74% males) and 97 asymptomatic mutation carriers (31% males). Median age at study baseline was 34 years (range 5–82 years). The prevalence of vitamin B12 deficiency was higher for LHON mutation carriers than for the general population in all age categories. This was statistically significant for the LHON mutation carriers under 65 years (21% vs. 5–7%, p = 0.002). While vitamin B12 deficiency prevalence was not statistically different between LHON patients and asymptomatic mutation carriers, its clinical correlates, e.g., macrocytosis and polyneuropathy, were more frequent in the subgroup of LHON patients. Excessive alcohol consumption was a significant predictor of vitamin B12 deficiency (p < 0.05).

Conclusions
The high prevalence of vitamin B12 deficiency in LHON mutation carriers, both asymptomatic mutation carriers and LHON patients, highlights the need for regular vitamin B12 screening in this population, in order to ensure early treatment, aiming for better outcomes. Our study is not conclusive regarding vitamin B12 deficiency as determinant for disease conversion in LHON, and further research is warranted to disentangle the role of vitamin B12 in the pathophysiology and prognosis of LHON.
Single-cell diploid Hi-C reveals the role of spatial aggregations in complex rearrangements and KMT2A fusions in leukemia
Authors: Xing Zhihao , Mai Huirong , Liu Xiaorong , Fu Xiaoying , Zhang Xingliang , Xie Lichun , Chen Yunsheng , Shlien Adam , Wen Feiqiu 
Published: August 2022

Abstract
Background
Simple translocations and complex rearrangements are formed through illegitimate ligations of double-strand breaks of fusion partners and lead to generation of oncogenic fusion genes that affect cellular function. The contact first hypothesis states that fusion partners tend to colocalize prior to fusion in normal cells. Here we test this hypothesis at the single-cell level and explore the underlying mechanism.

Results
By analyzing published single-cell diploid Hi-C datasets, we find partner genes fused in leukemia exhibit smaller spatial distances than those fused in solid tumor and control gene pairs. Intriguingly, multiple partners tend to colocalize with KMT2A in the same cell. 3D genome architecture has little association with lineage decision of KMT2A fusion types in leukemia. Besides simple translocations, complex rearrangement-related KMT2A fusion genes (CRGs) also show closer proximity and belong to a genome-wide mutual proximity network. We find CRGs are co-expressed, co-localized, and enriched in the targets of the transcriptional factor RUNX1, suggesting they may be involved in RUNX1-mediated transcription factories. Knockdown of RUNX1 leads to significantly fewer contacts among CRGs. We also find CRGs are enriched in active transcriptional regions and loop anchors, and exhibit high levels of TOP2-mediated DNA breakages. Inhibition of transcription leads to reduced DNA breakages of CRGs.

Conclusions
Our results demonstrate KMT2A partners and CRGs may form dynamic and multipartite spatial clusters in individual cells that may be involved in RUNX1-mediated transcription factories, wherein massive DNA damages and illegitimate ligations of genes may occur, leading to complex rearrangements and KMT2A fusions in leukemia.
Successes and lessons learned in database development for national multi-site cancer care delivery research trials: the Alliance for Clinical Trials in Oncology experience
Authors: Zahrieh David , Hillman Shauna L. , Tan Angelina D. , Frank Jennifer L. , Dockter Travis , Meyers Bobbi Jo , Cherevko Cassie L. , Peil Elizabeth S. , McCue Shaylene , Kour Oudom , Gunn Heather J. , Neuman Heather B. , Chang George J. , Paskett Electra D. , Mandrekar Sumithra J. , Dueck Amylou C. 
Published: August 2022

Abstract
Introduction
Alliance for Clinical Trials in Oncology (Alliance) coordinated trials utilize Medidata Rave® (Rave) as the primary clinical data capture system. A growing number of innovative and complex cancer care delivery research (CCDR) trials are being conducted within the Alliance with the aims of studying and improving cancer-related care. Because these trials encompass patients, providers, practices, and their interactions, a defining characteristic of CCDR trials is multilevel data collection in pragmatic settings. Consequently, CCDR trials necessitated innovative strategies for database development, centralized data management, and data monitoring in the presence of these real-world multilevel relationships. Having real trial experience in working with community and academic centers, and having recently implemented five CCDR trials in Rave, we are committed to sharing our strategies and lessons learned in implementing such pragmatic trials in oncology.

Methods
Five Alliance CCDR trials are used to describe our approach to analyzing the database development needs and the novel strategies applied to overcome the unanticipated challenges we encountered. The strategies applied are organized into 3 categories: multilevel (clinic, clinic stakeholder, patient) enrollment, multilevel quantitative and qualitative data capture, including nontraditional data capture mechanisms being applied, and multilevel data monitoring.

Results
A notable lesson learned in each category was (1) to seek long-term solutions when developing the functionality to push patient and non-patient enrollments to their respective Rave study database that affords flexibility if new participant types are later added; (2) to be open to different data collection modalities, particularly if such modalities remove barriers to participation, recognizing that additional resources are needed to develop the infrastructure to exchange data between that modality and Rave; and (3) to facilitate multilevel data monitoring, orient site coordinators to the their trial’s multiple study databases, each corresponding to a level in the hierarchy, and remind them to establish the link between patient and non-patient participants in the site-facing NCI web-based enrollment system.

Conclusion
Although the challenges due to multilevel data collection in pragmatic settings were surmountable, our shared experience can inform and foster collaborations to collectively build on our past successes and improve on our past failures to address the gaps.
Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials
Authors: Williams Thomas , Alexander Sarah , Blackstone James , De Angelis Floriana , John Nevin , Doshi Anisha , Beveridge Judy , Braisher Marie , Gray Emma , Chataway Jeremy ,   on behalf of the MS-SMART and MS-STAT2 Investigators
Published: August 2022

Abstract
Background
Slower than planned recruitment is a major factor contributing to the delay or failure of randomised controlled trials to report on time. There is a limited evidence base regarding the optimisation of recruitment strategies. Here we performed an observational review of our experience in recruitment for two large randomised controlled trials for people with secondary progressive multiple sclerosis. We aimed to explicitly determine those factors which can facilitate trial recruitment in progressive neurodegenerative disease.

Methods
Recruitment data from the sequential MS-SMART [NCT01910259] and MS-STAT2 [NCT03387670] UK randomised controlled trials was reviewed from the largest recruiting site, University College London (UCL). The trial population was similar which allowed comparison over the two recruitment periods of 2015–2016 and 2018–2021. This included sources of referral, progress through stages of recruitment, reasons for participant ineligibility and the impact of publicity events upon recruitment.

Results
In MS-SMART, 18% of patients contacted were enrolled, compared to 27% for MS-STAT2. Online registration of interest portals provided the greatest number of referrals (76% in MS-SMART, and 51% in MS-STAT2), with publicity in national media outlets producing a demonstrable increase in the number of potential participants. The introduction of an online self-screening questionnaire for MS-STAT2 resulted in 67% of potential participants (3080 of 4605) automatically determining their own ineligibility. In both studies, however, around 60% of those directly telephoned to discuss the study were not eligible, with difficulties related to travel to trial visits, or excluded medication, being the most common issues. Eighty-four percent of those deemed potentially eligible following telephone calls were enrolled in the MS-STAT2 study, compared to only 55% for MS-SMART.

Conclusions
Through a detailed review of recruiting participants at the largest centre into two large randomised controlled trials with similar entry criteria, we have identified a number of approaches that may improve recruitment efficiency. We highlight here the importance of mandatory online self-screening questionnaires, a coordinated publicity campaign, and simple interventions such as eligibility checklists and appointment reminders. Recruitment approaches should be further assessed through a studies within a trial (SWAT) design.

Trial registration
MS-SMART: NCT01910259; registered July 2013 and MS-STAT2: NCT03387670; registered Jan 2018
Enhanced rare disease mapping for phenome-wide genetic association in the UK Biobank
Authors: Patrick Matthew T. , Bardhi Redina , Zhou Wei , Elder James T. , Gudjonsson Johann E. , Tsoi Lam C. 
Published: August 2022

Abstract
Background
Rare diseases collectively affect up to 10% of the population, but often lack effective treatment, and typically little is known about their pathophysiology. Major challenges include suboptimal phenotype mapping and limited statistical power. Population biobanks, such as the UK Biobank, recruit many individuals who can be affected by rare diseases; however, investigation into their utility for rare disease research remains limited. We hypothesized the UK Biobank can be used as a unique population assay for rare diseases in the general population.

Methods
We constructed a consensus mapping between ICD-10 codes and ORPHA codes for rare diseases, then identified individuals with each rare condition in the UK Biobank, and investigated their age at recruitment, sex bias, and comorbidity distributions. Using exome sequencing data from 167,246 individuals of European ancestry, we performed genetic association controlling for case/control imbalance (SAIGE) to identify potential rare pathogenic variants for each disease.

Results
Using our mapping approach, we identified and characterized 420 rare diseases affecting 23,575 individuals in the UK Biobank. Significant genetic associations included JAK2 V617F for immune thrombocytopenic purpura (p = 1.24 × 10−13) and a novel CALR loss of function variant for essential thrombocythemia (p = 1.59 × 10−13). We constructed an interactive resource highlighting demographic information (http://www-personal.umich.edu/~mattpat/rareDiseases.html) and demonstrate transferability by applying our mapping to a medical claims database.

Conclusions
Enhanced disease mapping and increased power from population biobanks can elucidate the demographics and genetic associations for rare diseases.