Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron supplementation in anemic Zanzibari toddlers is associated with greater loss in erythrocyte iron isotope enrichment.

BACKGROUND Heavy parasitic loads increase the risk of iron (Fe) deficiency anemia, which remains prevalent globally. Where parasites are common, understanding the influence of parasitic infections on Fe incorporation and erythropoiesis in toddlers is especially important. OBJECTIVES The aim of this study was to identify the impacts of malarial and helminth infections on red blood cell (RBC) Fe incorporation and subsequent changes in RBC Fe isotope enrichment for 84 days postdosing in toddlers at high risk for parasitic infections. METHODS Fe incorporation was measured in a group of Zanzibari toddlers (n = 71; 16-25 months) using a stable Fe isotopic method. At study entry, an oral stable Fe isotope was administered. Blood was collected 14 (D14) and 84 (D84) days postdosing for the assessment of Fe status indicators and RBC isotopic enrichment. Blood and stool samples were collected and screened for malaria and helminth parasites. Factors associated with changes in RBC Fe isotope enrichment were identified using regression models. RESULTS Toddlers who had larger weight-for-age z-scores, lower total body Fe, and helminth infections (n = 26) exhibited higher RBC Fe incorporation. RBC Fe isotope enrichment decreased from D14 to D84 by -2.75 percentage points (P < 0.0001; n = 66). Greater loss in RBC Fe isotope enrichment from D14 to D84 was observed in those who received Fe supplementation, those with either helminths or both malarial and helminth infections, and in those with greater RBC Fe incorporation on D14. CONCLUSIONS Toddlers who received Fe supplementation exhibited significantly greater losses of RBC Fe isotope enrichment over time. We speculate this greater loss of RBC Fe enrichment is indicative of increased erythropoiesis due to the provision of Fe among anemic or helminth-infected toddlers.
Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial

ABSTRACT Background Infantile beriberi–related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown. Objectives We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers. Methods In this double-blind, 4–parallel arm randomized controlled dose–response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed. Results In total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other. Conclusions A supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288.
Distinct transcriptional profiles of Leptospira borgpetersenii serovar Hardjo strains JB197 and HB203 cultured at different temperatures

Background Leptospirosis is a zoonotic, bacterial disease, posing significant health risks to humans, livestock, and companion animals around the world. Symptoms range from asymptomatic to multi-organ failure in severe cases. Complex species-specific interactions exist between animal hosts and the infecting species, serovar, and strain of pathogen. Leptospira borgpetersenii serovar Hardjo strains HB203 and JB197 have a high level of genetic homology but cause different clinical presentation in the hamster model of infection; HB203 colonizes the kidney and presents with chronic shedding while JB197 causes severe organ failure and mortality. This study examines the transcriptome of L. borgpetersenii and characterizes differential gene expression profiles of strains HB203 and JB197 cultured at temperatures during routine laboratory conditions (29°C) and encountered during host infection (37°C). Methodology/Principal findings L. borgpetersenii serovar Hardjo strains JB197 and HB203 were isolated from the kidneys of experimentally infected hamsters and maintained at 29°C and 37°C. RNAseq revealed distinct gene expression profiles; 440 genes were differentially expressed (DE) between JB197 and HB203 at 29°C, and 179 genes were DE between strains at 37°C. Comparison of JB197 cultured at 29°C and 37°C identified 135 DE genes while 41 genes were DE in HB203 with those same culture conditions. The consistent differential expression of ligB, which encodes the outer membrane virulence factor LigB, was validated by immunoblotting and 2D-DIGE. Differential expression of lipopolysaccharide was also observed between JB197 and HB203. Conclusions/Significance Investigation of the L. borgpetersenii JB197 and HB203 transcriptome provides unique insight into the mechanistic differences between acute and chronic disease. Characterizing the nuances of strain to strain differences and investigating the environmental sensitivity of Leptospira to temperature is critical to the development and progress of leptospirosis prevention and treatment technologies, and is an important consideration when serovars are selected and propagated for use as bacterin vaccines as well as for the identification of novel therapeutic targets.
Health care resource utilization and cost burden of hemophilia B in the United States.

Hemophilia B is a rare congenital blood disorder characterized by factor IX deficiency. Clinical profiles of hemophilia B range from mild to severe forms of the disease. The objective of this study was to characterize the economic burden associated with differing clinical profiles of hemophilia B from a US health system perspective. Using the IBM MarketScan database (June 2011-February 2019), a claims-based algorithm was developed to identify 4 distinct profiles (mild, moderate, moderate-severe, and severe) in adult males with hemophilia B based on the frequency of hemorrhage events and factor IX replacement claims. Mean annual health care resource use (HRU) and costs were statistically compared between patients with hemophilia B (N = 454) and 1:1 demographic-matched controls (N = 454), both overall and with stratification by clinical profile. Compared with matched controls, patients with hemophilia B had a significantly higher comorbidity burden (Charlson Comorbidity Index, mean ± standard deviation [SD]: 0.9 ± 1.7 vs 0.3 ± 0.9, P < .001). Across all clinical profiles, patients with hemophilia B had significantly higher HRU vs matched controls (mean ± SD: 0.3 ± 0.6 vs 0.1 ± 0.3 inpatient admissions; 0.6 ± 1.2 vs 0.2 ± 0.6 emergency department visits; 17.7 ± 22.9 vs 8.0 ± 11.0 outpatient visits; all P < .001). Annual total health care costs per patient among patients with hemophilia B were more than 25-fold higher vs matched controls (mean ± SD: $201 635 ± $411 530 vs $7879 ± $29 040, respectively, P < .001). Annual total health care costs per patient increased with increasing severity (mean ± SD: mild, $80 811 ± $284 313; moderate, $137 455 ± $222 021; moderate-severe, $251 619 ± $576 886; severe, $632 088 ± $501 270). The findings of this study highlight the substantial burden of illness associated with hemophilia B.
The role of characterisation in everyday voice engagement and AVATAR therapy dialogue

Abstract Background Voices are commonly experienced as communication with a personified ‘other’ with ascribed attitudes, intentionality and personality (their own ‘character’). Phenomenological work exploring voice characterisation informs a new wave of relational therapies. To date, no study has investigated the role of characterisation in behavioural engagement with voices or within psychological therapy for distressing voices. Methods Baseline characterisation (the degree to which the voice is an identifiable and characterful entity) of the dominant voice was rated (high, medium or low) using a newly developed coding framework, for n = 60 people prior to starting AVATAR therapy. Associations between degree of characterisation and (i) everyday behavioural engagement with voices (The Beliefs about Voices Questionnaire-Revised; n = 60); and (ii) interaction within avatar dialogue [Session 4 Time in Conversation (participant–avatar); n = 45 therapy completers] were explored. Results Thirty-three per cent reported high voice characterisation, 42% medium and 25% low. There was a significant association between characterisation and behavioural engagement [H(2) = 7.65, p = 0.022, ɛ2 = 0.130] and duration of participant–avatar conversation [F(2,42) = 6.483, p = 0.004, η2 = 0.236]. High characterisation was associated with increased behavioural engagement compared with medium (p = 0.004, r = 0.34; moderate effect) and low (p = 0.027, r = 0.25; small−moderate effect) with a similar pattern observed for the avatar dialogue [high v. medium: p = 0.008, Hedges’ g = 1.02 (large effect); high v. low: p = 0.023, Hedges' g = 1.03 (large effect)]. No differences were observed between medium and low characterisation. Discussion Complex voice characterisation is associated with how individuals interact with their voice(s) in and out of therapy. Clinical implications and future directions for AVATAR therapy and other relational therapies are discussed.
Is OCT a Viable Tool to Monitor Disease-Modifying Treatments in RRMS Yet?

Optical coherence tomography (OCT) is considered a key research tool to monitor neurodegenerative processes in CNS disorders. This is particularly applicable to multiple sclerosis (MS), in which retinal changes (peripapillary retinal nerve fiber layer and ganglion cell–inner plexiform layer [GCIPL] thicknesses) tend to reflect MRI markers of CNS damage and atrophy, especially in eyes not affected by previous optic neuritis.1
New Glance at the Role of TM6SF2 in Lipid Metabolism and Liver Cancer

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver diseases. NAFLD can progress to more severe conditions, such as non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC), which confer increased morbidity and mortality. However, many individuals with NAFLD do not progress to these more severe conditions. Such variations in the susceptibility of NAFLD progression suggest that it is likely affected by multiple factors, in particular, genetic factors.
Value of handgrip strength to predict clinical outcomes and therapeutic response in malnourished medical inpatients: Secondary analysis of a randomized controlled trial.

BACKGROUND Disease-related malnutrition is associated with loss of muscle mass and impaired functional status. Handgrip strength (HGS) has been proposed as an easy-to-use tool to assess muscle strength in clinical practice. OBJECTIVES We investigated the prognostic implications of HGS in patients at nutritional risk with regard to clinical outcomes and response to nutritional support. METHODS This was a secondary analysis of the randomized controlled, multicenter, Effect of Early Nutritional Support on Frailty, Functional Outcome, and Recovery of Malnourished Medical Inpatients Trial, which compared the effects of individualized nutritional support with usual hospital food in medical inpatients at nutritional risk. Our primary endpoint was 30-d all-cause mortality. The association between sex-specific HGS and clinical outcomes was investigated using multivariable regression analyses, adjusted for randomization, age, weight, height, nutritional risk, admission diagnosis, comorbidities, interaction terms, and study center. We used interaction terms to investigate possible effect modification regarding the nutritional support intervention. RESULTS Mean ± SD HGS in the 1809 patients with available handgrip measurement was 17.0 ± 7.1 kg for females and 28.9 ± 11.3 kg for males. Each decrease of 10 kg in HGS was associated with increased risk of 30-d mortality (female: adjusted OR: 2.11; 95% CI: 1.23, 3.62, P = 0.007; male: adjusted OR: 1.44; 95% CI: 1.07, 1.93, P = 0.015) and 180-d mortality (female: adjusted OR: 1.45; 95% CI: 1.0, 2.10, P = 0.048; male: adjusted OR: 1.55; 95% CI: 1.28, 1.89, P < 0.001). Individualized nutritional support was most effective in reducing mortality in patients with low HGS (adjusted OR: 0.29; 95% CI: 0.10, 0.82 in patients in the ≤10th percentile compared with OR: 0.98; 95% CI: 0.66, 1.48 in patients in the >10th percentile; P for interaction = 0.026). CONCLUSIONS In medical inpatients at nutritional risk, HGS provided significant prognostic information about expected mortality and complication risks and helps to identify which patients benefit most from nutritional support. HGS may thus improve individualization of nutritional therapy.This trial was registered at clinicaltrials.gov as NCT02517476.
Availability of Services and Caregiver Burden: Supporting Individuals With Neurogenetic Conditions During the COVID-19 Pandemic

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers’ reported impact on their dependent’s services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden. Two online questionnaires were completed by caregivers participating in Simons Searchlight in April and May 2020. Surveys were completed by caregivers of children or dependent adults with neurodevelopmental genetic conditions in Simons Searchlight. Caregivers reported that the impact of the COVID-19 pandemic moderately or severely disrupted services, therapies, or medical supports. The majority of caregivers were responsible for providing some aspect of therapy. Caregivers reported “feeling stressed but able to deal with problems as they arise,” and reported lower anxiety at follow-up. Caregivers reported that telehealth services were not meeting the needs of those with complex medical needs. Future surveys will assess if and how medical systems, educational programs, therapists, and caregivers adapt to the challenges arising during the COVID-19 pandemic.
Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection

ABSTRACT Objectives In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. Material and methods A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. Results A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. Conclusions Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.
Inflammatory bowel disease-related economic costs due to presenteeism and absenteeism

Abstract Background Inflammatory bowel disease (IBD), consisting of Crohn’s disease and ulcerative colitis, can be a lifelong burden generating high costs to an economic system. Data regarding the cost of workplace presenteeism and absenteeism in workers with IBD are limited. Our objective was to assess these costs in employed adults. Methods A structured questionnaire, hospital records and national registers were combined to assess the economic costs involved with workplace presenteeism and absenteeism in employed patients. Our final sample comprised 320 IBD patients. The costs were calculated as productivity-loss costs by using a Human Capital Approach. Results Due to IBD, the mean annual economic costs of workplace presenteeism were €643.90/patient, and mean annual absenteeism costs were €740.90/patient. Women had higher costs (€955/patient/year) from absenteeism compared to men (€531/patient/year) especially when working blue-collar jobs. These findings were also evident in presenteeism. CD and UC patients had similar total costs due to presenteeism and absenteeism. The use of biologics did not have a major impact on these costs. Conclusion IBD patients had moderate economic costs from workplace presenteeism and absenteeism. Interestingly, women, working blue-collar jobs, had higher costs than men.
Bilingualism in Parkinson’s disease: Relationship to cognition and quality of life

ABSTRACT Some studies have found that bilingualism promotes cognitive reserve. Objective: We aimed to determine whether bilingualism, defined as regularly (i.e. daily) using at least two languages at least since early adulthood, is associated with cognitive advantages in Parkinson’s disease (PD) or whether the possible benefits of bilingualism are lost in the context of PD, possibly affecting quality of life (QoL) and independence. Method: Participants with idiopathic PD (n = 140, mean age = 67.9 [SD = 6.4], 78% men) completed standard neuropsychological tasks evaluating attention/working memory, language, executive function, memory, and visuospatial ability, as well as measures of wellbeing and functional independence. Results: Bilinguals with PD (n = 21) performed worse than monolinguals with PD (n = 92) on attention/working memory and language measures. The between-group differences in attention/working memory were restricted to verbally-based measures. When measured along a continuum, a higher degree of bilingualism was correlated with lower scores on measures of attention/working memory and language. There were no group differences in self- or informant-reported cognitive decline, PD health-related QoL, or functional independence. Conclusions: Bilingualism in PD was not associated with better cognitive performance. Lower scores on language-based measures may reflect a distributed fund of linguistic information across more than one language, lower language proficiency in English, and/or other cultural artifacts. Furthermore, using normative data specific to the dominant language spoken or conducting neuropsychological testing in participants’ self-reported most proficient language may enhance additional studies addressing this topic. Future research may also examine the roles of bilingualism over time and across other neurodegenerative diseases with and without EF impairment to illuminate further the impact of bilingualism on cognition and QoL, and shape culturally and linguistically diverse research and clinical care.
Electrical tunability of terahertz nonlinearity in graphene

We turn graphene from an inert electronic material to the most nonlinear material for the terahertz range using a small voltage. Graphene is conceivably the most nonlinear optoelectronic material we know. Its nonlinear optical coefficients in the terahertz frequency range surpass those of other materials by many orders of magnitude. Here, we show that the terahertz nonlinearity of graphene, both for ultrashort single-cycle and quasi-monochromatic multicycle input terahertz signals, can be efficiently controlled using electrical gating, with gating voltages as low as a few volts. For example, optimal electrical gating enhances the power conversion efficiency in terahertz third-harmonic generation in graphene by about two orders of magnitude. Our experimental results are in quantitative agreement with a physical model of the graphene nonlinearity, describing the time-dependent thermodynamic balance maintained within the electronic population of graphene during interaction with ultrafast electric fields. Our results can serve as a basis for straightforward and accurate design of devices and applications for efficient electronic signal processing in graphene at ultrahigh frequencies.
Evaluation of biological contaminants in foods by hyperspectral imaging: A review

ABSTRACT Responding to the ever-growing concern about safe foods and security, the food industries are forced to seek an emerging technology capable of detecting and quantifying contaminations, especially those of biological origin. Among the different emerging technologies, hyperspectral imaging is considered a good alternative as it can be easily applied at all steps of the food production process and is a non-destructive technique. This paper reviews targeted analytical applications of hyperspectral imaging in monitoring biological contaminants in food. First, traditional techniques for detection of biological contaminants in foods are presented, where disadvantages for practical applications are highlighted and explained in detail. Second, prominent applications of hyperspectral imaging from the last decade to food safety and quality assessment are reviewed, specifically focusing on both deteriorative and pathogenic microorganisms, microbial toxins, and parasites; whether acting individually or collectively in spoiling food products and/or represent a health risk to the consumers. Finally, relevant current and future challenges, advantages and disadvantages of hyperspectral imaging applications are briefly examined.