bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal Speech Biomarkers for Remote Monitoring of ALS Disease Progression
Authors: Neumann Michael , Kothare Hardik , Ramanarayanan Vikram 
Published: June 2024

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that severely impacts affected persons’ speech and motor functions, yet early detection and tracking of disease progression remain challenging. The current gold standard for monitoring ALS progression, the ALS functional rating scale - revised (ALSFRS-R), is based on subjective ratings of symptom severity, and may not capture subtle but clinically meaningful changes due to a lack of granularity. Multimodal speech measures which can be automatically collected from patients in a remote fashion allow us to bridge this gap because they are continuous-valued and therefore, potentially more granular at capturing disease progression. Here we investigate the responsiveness and sensitivity of multimodal speech measures in persons with ALS (pALS) collected via a remote patient monitoring platform in an effort to quantify how long it takes to detect a clinically-meaningful change associated with disease progression. We recorded audio and video from 278 participants and automatically extracted multimodal speech biomarkers (acoustic, orofacial, linguistic) from the data. We find that the timing alignment of pALS speech relative to a canonical elicitation of the same prompt and the number of words used to describe a picture are the most responsive measures at detecting such change in both pALS with bulbar (n= 36) and non-bulbar onset (n= 107). Interestingly, the responsiveness of these measures is stable even at small sample sizes. We further found that certain speech measures are sensitive enough to track bulbar decline even when there is no patient-reported clinical change, i.e. the ALSFRS-R speech score remains unchanged at 3 out of a total possible score of 4. The findings of this study have the potential to facilitate improved, accelerated and cost-effective clinical trials and care.
Beta Burst-Driven Adaptive Deep Brain Stimulation Improves Gait Impairment and Freezing of Gait in Parkinson’s Disease
Authors: Wilkins K.B. , Petrucci M.N. , Lambert E.F. , Melbourne J.A. , Gala A.S. , Akella P. , Parisi L. , Cui C. , Kehnemouyi Y.M. , Hoffman S.L. , Aditham S. , Diep C. , Dorris H.J. , Parker J.E. , Herron J.A. , Bronte-Stewart H.M 
Published: June 2024

AbstractBackgroundFreezing of gait (FOG) is a debilitating symptom of Parkinson’s disease (PD) that is often refractory to medication. Pathological prolonged beta bursts within the subthalamic nucleus (STN) are associated with both worse impairment and freezing behavior in PD, which are improved with deep brain stimulation (DBS). The goal of the current study was to investigate the feasibility, safety, and tolerability of beta burst-driven adaptive DBS (aDBS) for FOG in PD.MethodsSeven individuals with PD were implanted with the investigational Summit™ RC+S DBS system (Medtronic, PLC) with leads placed bilaterally in the STN. A PC-in-the-loop architecture was used to adjust stimulation amplitude in real-time based on the observed beta burst durations in the STN. Participants performed either a harnessed stepping-in-place task or a free walking turning and barrier course, as well as clinical motor assessments and instrumented measures of bradykinesia, OFF stimulation, on aDBS, continuous DBS (cDBS), or random intermittent DBS (iDBS).ResultsBeta burst driven aDBS was successfully implemented and deemed safe and tolerable in all seven participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved from OFF to aDBS and showed similar efficacy as cDBS. Similar improvements were also seen for overall clinical motor impairment, including tremor, as well as quantitative metrics of bradykinesia.ConclusionBeta burst driven adaptive DBS was feasible, safe, and tolerable in individuals with PD with gait impairment and FOG.
Pseudoscience in Cancer Services; a survey of National Health Service Trusts in England
Authors: Rose Leslie B 
Published: June 2024

AbstractBackgroundScientifically implausible treatments are offered by some hospital cancer departments. Examples are reiki, aromatherapy, and reflexology. Salaried practitioners are employed to deliver these therapies, which are provided as palliative care, although they lack evidence of effectiveness. Such practices seem to conflict with efforts to make health care evidence based.AimTo estimate the extent of certain pseudoscientific practices in NHS Trusts, and to evaluate the rationale for such provision.DesignRelevant documents were requested from NHS Trusts under the Freedom of Information Act 2000 (FOIA). Main outcome measures were: number of trusts offering pseudoscientific practices in cancer departments, time to full FOIA response, presence and content of practice governance documents, and presence and quality of evidence for practices.Setting/ParticipantsCancer care departments in NHS hospitals in England. No patient participants were involved in the survey.Results13.6% of eligible NHS trusts were offering pseudoscientific clinical practices. No trust provided a valid business case, or any robust evidence for the practices. The governance documents included claims about chakras, meridians, and invisible “energy”. Ten trusts required that informed consent be obtained from patients. This could not have been obtained because information given was misleading.ConclusionsPseudoscientific practices are embedded in the NHS in England, and governance documents show poor understanding of clinical evidence.
Subnational tailoring of malaria interventions to prioritize the malaria response in Guinea
Authors: Diallo Ousmane Oumou , Diallo Abdourahamane , Toh Kok Ben , Diakité Nouman , Dioubaté Mohamed , Runge Manuela , Symons Tasmin , Diallo Elhadj Marouf , Gerardin Jaline , Galatas Beatriz , Camara Alioune 
Published: June 2024

AbstractBackgroundIn the context of high malaria burden yet limited resources, Guinea’s national malaria program adopted an innovative subnational tailoring (SNT) approach, including engagement of stakeholders, data review, and data analytics, to update their malaria operational plan for 2024-2026 and identify the most appropriate interventions for each district considering the resources available.MethodsGuinea’s malaria program triggered the SNT exercise with a list of decisions that could be informed with local data. The program established an SNT team, which determined intervention targeting criteria; identified, assembled, and reviewed relevant data sources; stratified malaria risk and its determinants to inform geographical targeting for each intervention; and used mathematical modeling to predict the impact of different intervention mix scenarios. The SNT analysis was performed at the district level, excluding the urban area of Conakry.ResultsMalaria incidence, malaria prevalence, and all-cause under-5 mortality were used for the epidemiological stratification of Guinea. Additional indicators relevant for decisions-making including seasonality patterns, insecticide resistance or malaria interventions and vaccine coverage were also stratified. Stratified layers were used to inform the targeting criteria for each intervention to identify districts to prioritize for indoor residual spray, dual-action insecticide-treated nets, seasonal malaria chemoprevention (SMC) including number of cycles for each eligible district, malaria vaccine, and perennial malaria chemoprevention. Results of the SNT analysis were used to mobilize funding from the Global Fund for scale-up of dual-action nets and expansion of SMC.ConclusionsSNT allowed Guinea’s national malaria program to adapt their intervention strategy at the health district level, an unprecedented approach in the country. The use of local data to inform eligibility and prioritization allowed the program to identify the optimal mix of interventions for each district and to successfully mobilize resources to support their plans.
Establishment of Reference Values of Markers of Non-Thyroidal Illness Syndrome on a State-of-the-Art Fully Automated ABEI-Based Chemiluminescence System
Authors: Ijaz Aamir , Anjum Muhammad Usman , Ahmed Farhan , Paracha Shamila Najeeb , Habib Farzana , Shaukat Muhammad Bilal , Najeeb Sara , Hafeez Najma 
Published: June 2024

AbstractBackgroundNon-Thyroidal Illness Syndrome (NTIS), previously called Euthyroid Sick Syndrome has always been a diagnostic dilemma for Chemical Pathologists and treating physicians. Combination of four test i.e. Reverse Triiodothyronine (rT3), Free Triiodothyronine (fT3), Free Thyroxine (fT4) and Thyroid Stimulating Hormone (TSH) can be helpful to diagnose NTIS in critically ill patients. We need, however, to determine the reference values found in a reference population, free of any thyroidal as well as non-thyroidal illness.Methods and MaterialsInitially, 266 adult volunteers were included in the study from Mohi Uddin Islamic Medical College Mirpur AJ&K (MIMC) and Mohi Uddin Teaching Hospital Mirpur AJ&K (MOTH) after taking written informed consent. About 124 volunteers were selected (males 61; females 63) after exclusion of the volunteers with one or more of the exclusion criteria. Blood specimens were collected and analyzed for rT3, fT3, fT4 and TSH using Maglumi X8 (S nibe, China), an ABEI (N-(aminobutil)-N-(ethyl)-isoluminol) based analyzer at Pathology Laboratory MOTH.ResultsReference values of rT3, fT3, fT4 and TSH were found to be 13.3 – 19.8 ng/dL (0.2 – 0.30 nmol/L); 2.65 - 4.15 pg/mL (4.08 - 6.39 pmol/L);10.6 - 16.2 pg/mL (13.64–20.84 pmol/L) and 0.43 - 3.98 μIU/mL (0.43 – 3.98 mIU/L), respectively.ConclusionReference values determined in our own population should be used when diagnosing and monitoring NTIS and other thyroid disorders
Could the Inflation Reduction Act Maximum Fair Price Hurt Patients?
Authors: Rivera Esteban , Sydor Anne M. , Popovian Robert 
Published: June 2024

ABSTRACTBackgroundThe Inflation Reduction Act’s Medicare Drug Price Negotiation Program allows the federal government to negotiate caps for select medications. These price caps may reduce revenue for the pharmacy benefit managers (PBMs) that negotiate the actual price paid for medicines in the US. To offset the resulting pressure on their profit margins, it is possible that PBMs would, in turn, increase patient’s out-of-pocket costs for medicines with capped prices. The model presented here evaluates how such increased out-of-pocket costs for the anticoagulants Eliquis (apixaban) and Xarelto (rivaroxaban) could impact patients financially and clinically.MethodsCopay distributions for all 2023 prescription fills for Eliquis and Xarelto managed by the three largest PBMs were used to approximate current copay costs. Increased out-of-pocket costs were modeled as a shift of all Eliquis and Xarelto prescriptions to the highest copay tier. The known linear relationship between copay costs and treatment abandonment was used to calculate the potential resulting increase in treatment abandonment. Known rates of morbidity and mortality due to abandoning anticoagulants were used to estimate resulting increases in morbidity and mortality.ResultsIf the three largest PBMs all shifted costs onto patients by moving all Eliquis and Xarelto prescriptions to the highest formulary tier, Tier 6, patients’ copay amount would increase by $235 to $482 million for Eliquis and $105 to $206 million for Xarelto. Such an increase could lead to 169,000 to 228,000 patients abandoning Eliquis and 71,000 to 93,000 abandoning Xarelto. The resulting morbidity and mortality could include up to an additional 145,000 major cardiovascular events and up to 97,000 more deaths.ConclusionThe Medicare Price Negotiation Program could impact patients negatively if it causes PBMs to increase patients’ out-of-pocket costs for medicines. Policymakers should closely monitor changes in overall affordability, including all patient out-of-pocket expenditures, for medications in the program. Preemptive measures to ensure that the most vulnerable citizens are not placed in precarious situations leading to poorer health outcomes should be considered.
A qualitative study on factors influencing health workers’ uptake of a pilot surgical antibiotic prophylaxis stewardship programme in selected Georgian hospitals
Authors: Narayan Sideeka , Warsi Sahil Khan , Kachkachishvili Iago , Kontselidze Osiko , Jibuti Mariam , Esebua Nino , Papiashvili Ana , Wong Danilo Lo Fo , Kandelaki Ketevan 
Published: June 2024

AbstractAntimicrobial misuse in surgical antibiotic prophylaxis (SAP) can include the inappropriate use of broad-spectrum antibiotics or prolonged dosing. In 2021, a pilot antimicrobial stewardship programme (ASP) was launched in Georgia, which involved developing and adapting SAP guidelines, establishing an interprofessional SAP prescribing approach, collecting surgical site infection (SSI) data via routinely collected data and telephonic patient follow-ups, and providing surgical unit staff with prescribing feedback and training on antimicrobial resistance (AMR) and antimicrobial stewardship (AMS). ASP introduction was staggered across ten hospitals over three years.This study explored behavioural determinants of surgical teams’ ASP uptake in five hospitals where the ASP was introduced or about to be introduced. Findings primarily concerned epidemiologists’ and nurses’ ASP-related behaviour. Those at ASP non-introduced hospitals were less involved in the SAP prescribing process, had lower AMR awareness, and lacked professional development opportunities. Those at ASP-introduced hospitals exhibited higher AMR knowledge and felt ASP participation boosted confidence, facilitated work, and furnished key professional development.Results indicate interprofessional collaboration on SAP prescribing supported ASP uptake across teams, and investment in health worker training and administrative encouragement ensured effective ASP participation and implementation. Findings highlight the crucial role of epidemiologists in SAP and illustrate a need for developing Georgian nurses’ AMR competencies as a vehicle to address public AMR knowledge gaps. Longer-term ASP uptake will need to consider the regulatory context in which hospitals lack access to national-level SSI data and feedback on SSI reporting but are fined for reporting non-compliance.Despite resource limitations and a small sample size, the study engaged all pilot ASP health workers. Respondents’ inexperience of qualitative research participation and ensuant hesitation limited exploration of motivational factors supporting health workers’ ASP uptake, which could be explored in further research.
TheO-Fucosyltransferase SPINDLY Attenuates Auxin-Induced Fruit Growth by Inhibiting ARF6 and ARF8 binding to Coactivator Mediator Complex inArabidopsis
Authors: Wang Yan , Kelley Seamus , Zentella Rodolfo , Hu Jianhong , Wei Hua , Wang Lei , Shabanowitz Jeffrey , Hunt Donald F. , Sun Tai-ping 
Published: June 2024

ABSTRACTThe phytohormone auxin plays a pivotal role in promoting fruit initiation and growth upon fertilization in flowering plants. Upregulation of auxin signaling by genetic mutations or exogenous auxin treatment can induce seedless fruit formation from unpollinated ovaries, termed parthenocarpy. Recent studies suggested that the class A AUXIN RESPONSE FACTOR6 (ARF6) and ARF8 inArabidopsisplay dual functions by first inhibiting fruit initiation when complexed with unidentified corepressor IAA protein(s) before pollination, and later promoting fruit growth after fertilization as ARF dimers. However, whether and how posttranslational modification(s) regulate ARF6- and ARF8-mediated fruit growth were unknown. In this study, we reveal that both ARF6 and ARF8 areO-fucosylated in their middle region (MR) by SPINDLY (SPY), a novel nucleocytoplasmic proteinO-fucosyltransferase, which catalyzes the addition of a fucose moiety to specific Ser/Thr residues of target proteins. Epistasis, biochemical and transcriptome analyses indicated that ARF6 and ARF8 are downstream of SPY, but ARF8 plays a more predominant role in parthenocarpic fruit growth. Intriguingly, two ARF6/8-interacting proteins, the co-repressor IAA9 and MED8, a subunit of the coactivator Mediator complex, were alsoO-fucosylated by SPY. Biochemical assays demonstrated that SPY-mediatedO-fucosylation of these proteins reduced ARF-MED8 interaction, which led to enhanced transcription repression activity of the ARF6/8-IAA9 complex but impaired transactivation activities of ARF6/8. Our study unveils the role of proteinO-fucosylation by SPY in attenuating auxin-triggered fruit growth through modulation of activities of key transcription factors, a co-repressor and the coactivator MED complex.
Optimization of an improved, time-saving, and scalable, protocol for the extraction of DNA from diverse viromes
Authors: Shamash Michael , Kapoor Saniya , Maurice Corinne F. 
Published: June 2024

AbstractIntroductionThe virome, composed of viruses inhabiting diverse ecosystems, significantly influences microbial community dynamics and host health. The phenol-chloroform DNA extraction protocol for viromes, though effective, is time-intensive and requires the use of multiple toxic chemicals.MethodsThis study introduces a streamlined, scalable protocol for DNA extraction using a commercially-available kit as an alternative, assessing its performance against the phenol-chloroform method across human fecal, mouse fecal, and soil samples.ResultsNo significant differences in virome diversity or community composition were seen between methods. Most viral operational taxonomic units (vOTUs) were common to both methods, with only a small percentage unique to either approach. Alpha- and beta-diversity analyses showed no significant impact of the extraction method on virome composition, confirming the kit’s efficacy and versatility.ConclusionsWhile the kit approach offers benefits like reduced toxicity and increased throughput, it has limitations such as higher costs and potential issues reliably capturing low-abundance taxa. This protocol provides a viable option for large-scale virome studies, although the phenol-chloroform approach may still be preferable for specific sample types.
Speech-reception-threshold estimation via EEG-based continuous speech envelope reconstruction
Authors: Borges Heidi B. , Zaar Johannes , Alickovic Emina , Christensen Christian B. , Kidmose Preben 
Published: June 2024

AbstractThis study investigates the potential of speech-reception-threshold (SRT) estimation through electroencephalography (EEG) based envelope reconstruction techniques with continuous speech. Additionally, we investigate the influence of the stimuli’s signal-to-noise ratio (SNR) on the temporal response function (TRF). Twenty young normal-hearing participants listened to audiobook excerpts with varying background noise levels while EEG was recorded. A linear decoder was trained to reconstruct the speech envelope from the EEG data. The reconstruction accuracy was calculated as the Pearson’s correlation between the reconstructed and actual speech envelopes. An EEG SRT estimate (SRTneuro) was obtained as the midpoint of a sigmoid function fitted to the reconstruction accuracy versus SNR data points. Additionally, the TRF was estimated at each SNR level, followed by a statistical analysis to reveal significant effects of SNR levels on the latencies and amplitudes of the most prominent components. The SRTneurowas within 3 dB of the behavioral SRT for all participants. The TRF analysis showed a significant latency decrease for N1 and P2 and a significant amplitude magnitude increase for N1 and P2 with increasing SNR. The results suggest that both envelope reconstruction accuracy and the TRF components are influenced by changes in SNR, indicating they may be linked to the same underlying neural process.
Responses to ligand binding in the bacterial DNA sliding clamp β-clamp manifest in dynamic allosteric effects
Authors: Simonsen Signe , Prestel Andreas , Østerlund Eva C. , Otterlei Marit , Jørgensen Thomas J.D. , Kragelund Birthe B. 
Published: June 2024

AbstractThe homo-dimeric, ring-shaped bacterial DNA sliding clamp, β-clamp, is a central hub in DNA replication and repair. It interacts with a plethora of proteins via short linear motifs, which bind to the same hydrophobic binding pocket on β-clamp. Although the structure, functions and interactions of β-clamp have been amply studied, less focus has been on understanding its dynamics and how this is influenced by ligand binding. In this work, we have made a backbone nuclear magnetic resonance (NMR) assignment of the 83 kDa dimeric β-clamp and used NMR in combination with hydrogen-deuterium exchange mass spectrometry to scrutinize the dynamics of β-clamp and how different ligands affect this. We found that binding of a small peptide from the polymerase III α subunit affects the dynamics and stability of β-clamp. This effect not only appears locally around the binding pocket, but also globally through dynamic allosteric connections to distant regions of the protein, including the dimer interface. This dissipated dynamic effect is likely a consequence of the binding pocket architecture and may reflect a common mechanism of structural plasticity, where different ligands impose differential responses in the structure and dynamics of β-clamp.HighlightsNMR spectroscopy of β-clamp revealed its inherent dynamicsA peptide ligand from polymerase III stabilizes β-clamp from global unfoldingPeptide binding causes allosteric effects that manifest in changes in dynamicsDynamic changes occur distant to the binding pocket in the dimer interfaceAllostery may be a mechanism for differential responses to interaction partnersGraphical abstract