Miracle-dz/UniFAR-FTUs huggingface dataset:
Developmental plasticity of mitochondrial aerobic metabolism, growth and survival by prenatal glucocorticoids and thyroid hormones: an experimental test in wild great tits.

Developmental plasticity is partly mediated by transgenerational effects, including those mediated by the maternal endocrine system. Glucocorticoid and thyroid hormones may play central roles in developmental programming through their action on metabolism and growth. However, the mechanisms by which they affect growth and development remain understudied. One hypothesis is that maternal hormones directly affect the production and availability of energy-carrying molecules (e.g. ATP) by their action on mitochondrial function. To test this hypothesis, we experimentally increased glucocorticoid and thyroid hormones in wild great tit eggs (Parus major) to investigate their impact on offspring mitochondrial aerobic metabolism (measured in blood cells), and subsequent growth and survival. We show that prenatal glucocorticoid supplementation affected offspring cellular aerobic metabolism by decreasing mitochondrial density, maximal mitochondrial respiration and oxidative phosphorylation, while increasing the proportion of the maximum capacity being used under endogenous conditions. Prenatal glucocorticoid supplementation only had mild effects on offspring body mass, size and condition during the rearing period, but led to a sex-specific (females only) decrease in body mass a few months after fledging. Contrary to our expectations, thyroid hormones supplementation did not affect offspring growth or mitochondrial metabolism. Recapture probabilities as juveniles or adults were not significantly affected by prenatal hormonal treatments. Our results demonstrate that prenatal glucocorticoids can affect post-natal mitochondrial density and aerobic metabolism. The weak effects on growth and apparent survival suggest that nestlings were mostly able to compensate for the transient decrease in mitochondrial aerobic metabolism induced by prenatal glucocorticoids.
Human blood biocompatibility and immunogenicity of scFvD2B PEGylated gold nanoparticles

Single chain variable D2B antibody fragments (scFvD2Bs) exhibit high affinity binding to prostate specific membrane antigens overexpressed in metastatic prostate cancer (PC). Conjugation of scFvD2B to gold nanoparticles (AuNPs) would enhance its stability and plasma half-life circulation to shuttle theranostic agents in PC. In this study, we synthesized PEGylated scFvD2B-AuNPs (AuNPs-scFvD2B-PEG) and tested their integrity, biocompatibility, and immunogenicity in freshly withdrawn human blood. Prior to blood incubation, Zeta potential measurements, UV–Vis spectroscopy, and dynamic light scattering (DLS) were used to assess the physicochemical properties of our nano-complexes in the presence or absence of PEGylation. A surface plasmon resonance band shift of 2 and 4 nm confirmed the successful coating for AuNPs-scFvD2B and AuNPs-scFvD2B-PEG, respectively. Likewise, DLS revealed a size increase of ∼3 nm for AuNPs-scFvD2B and ∼19 nm for AuNPs-scFvD2B-PEG. Zeta potential increased from −34 to −19 mV for AuNPs-scFvD2B and reached −3 mV upon PEGylation. Similar assessment measures were applied post-incubation in human blood with additional immunogenicity tests, such as hemolysis assay, neutrophil function test, and pyridine formazan extraction. Interestingly, grafting PEG chains on AuNPs-scFvD2B precluded the binding of blood plasma proteins and reduced neutrophil activation level compared with naked AuNPs-citrate counterparts. Most likely, a hydrated negative PEG cloud shielded the NPs rendering blood compatiblility with less than 10% hemolysis. In conclusion, the biocompatible AuNPs-scFvD2B-PEG presents promising characteristics for PC targeted therapy, with minimal protein adsorption affinity, low immunorecognition, and reduced hemolytic activity.
Expansion of Cancer Risk Profile for BRCA1 and BRCA2 Pathogenic Variants

Key Points Question Which cancer types and their clinical characteristics are associated with pathogenic variants in BRCA1 and BRCA2 in addition to breast, ovarian, prostate, and pancreatic cancers? Findings In this case-control study of 63 828 patients with 14 common cancer types and 37 086 controls, pathogenic variants in BRCA1 were associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer. Meaning The study results suggest that the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than that determined from previous analyses, potentially indicating the broader clinical relevance of BRCA1/2 genetic testing.
Mixed Case Palletizing with Industrial Robots

The automated building of customer order pallets in a retail, food or beverage distribution center is still a challenging and complex task. Over the past 15 years many companies have tried to develop different solutions to tackle this labor intensive job. In this article a detailed overview of existing implementations will be presented and compared with the development results of the activities from KUKA, Grenzebach and Swisslog under the leadership of the author of this paper. The final paper will contain examples of the two global soft drink producers in the world and a short overview of the current development project from Swisslog at the German drugstore chain dm.
[The six dimensions of positive health valued by different stakeholders within mental health care].

BACKGROUND In recent years a new concept of health, 'positive health', has been developed, which focusses on a person's resilience instead of merely the absence of disease. A previous survey among a variety of stakeholders in general health care showed that there are differences in how dimensions of positive health are valued. Patients valued the spiritual and societal participation dimension higher than physicians and policymakers. AIM To investigate how the six dimensions of positive health are valued by patients, health care professionals and policymakers in mental health care in the Netherlands, and to test whether these values differ from such stakeholders in general healthcare. METHOD In a cross-sectional survey patients (N= 458), healthcare professionals (N=250) and policy makers (N=47) of two mental health care institutions in the Netherlands filled in an online survey. The results were compared to the results of the study by Huber e.a. (2016) by ANCOVA, paired T-tests and cohens' d. RESULTS Respondents valued all dimensions equally high. No significant differences between groups were found, except for a significant difference on daily functioning. Patients rated this dimension significantly higher than other stakeholders. The equal significance of the six dimensions is in contrast with the findings of a previous survey among stakeholders in general health care. CONCLUSION In contrast to stakeholders in general health care, those in mental health care valued all dimensions of health of equal and high importance. Only daily functioning was rated lower by professionals and policymakers than by patients.
Broadening Neurologic Manifestations in Adult Patients With Dravet Syndrome

Dravet syndrome (DS), originally described by Charlotte Dravet in 1978,1 is a rare neurologic disorder characterized by a refractory, developmental, and epileptic encephalopathy with onset in the first year of life.2 The reported incidence is between 1 in 15,000 and 1 in 41,000 children.3,4 It is caused by a heterozygous pathogenic variant in the SCN1A gene that codes for the alpha subunit of the voltage-gated sodium channel Nav1.1. 5 Children with DS have refractory seizures and developmental delay with impaired intellectual development, and because DS is a chronic, refractory, lifelong disorder that persists into adulthood, adult neurologists eventually care for people with DS.6 The neurologic manifestations of DS in adults, however, are not well-studied.
Tagetes lucida Cav. essential oil and the mixture of its main compounds are antibacterial and modulate antibiotic resistance in multi‐resistant pathogenic bacteria

We evaluated an essential oil (EO) of Tagetes lucida Cav. and the mixture of its main compounds against multi‐drug resistant bacteria. We found that EO and the partially reconstituted blend of its main components have antibacterial activity and inhibit antibiotic resistance (ampicillin, chloramphenicol, nalidixic acid, vancomycin and imipenem) in strains of Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa HIM‐MR01. The T. lucida EO alone or added to the antibiotics showed antimicrobial activity against S. aureus and P. aeruginosa. The EO main bioactive compounds were methyl eugenol (relative abundance in EO: 46·15%), estragole (32·93%), linalool (2·48%) and geraniol (0·33%). The mixture (PREO) of those compounds at those proportions inhibited the growth of P. aeruginosa in 45% at 683·62 µg ml−1 and that of S. aureus in 51·7% at 39·04 µg ml−1. The PREO had higher antibacterial and modulatory activities than the original EO. In conclusion, we overcame the unpredictability of EO activity (due to their natural variability) by determining which EO components inhibited bacteria and then producing a PREO to generate a reproducible mixture with predictable antibacterial and modulation of resistance activities. Thus, the PREO, and its components, show potential as alternatives to manage multidrug‐resistant pathogens.
Myeloarchitectonic plasticity in elite golf players' brains

Human neuroimaging studies have demonstrated that exercise influences the cortical structural plasticity as indexed by gray or white matter volume. It remains elusive, however, whether exercise affects cortical changes at the finer‐grained myelination structure level. To answer this question, we scanned 28 elite golf players in comparison with control participants, using a novel neuroimaging technique—quantitative magnetic resonance imaging (qMRI). The data showed myeloarchitectonic plasticity in the left temporal pole of the golf players: the microstructure of this brain region of the golf players was better proliferated than that of control participants. In addition, this myeloarchitectonic plasticity was positively related to golfing proficiency. Our study has manifested that myeloarchitectonic plasticity could be induced by exercise, and thus, shed light on the potential benefits of exercise on brain health and cognitive enhancement.
Targeting Anxiety to Improve Sleep Disturbance: A Randomized Clinical Trial of App-Based Mindfulness Training

ABSTRACT Objective Sleep disturbance is experienced by nearly 20% of Americans and is highly comorbid with anxiety. Sleep disturbances may predict the development of anxiety disorders. Mindfulness training (MT) has shown efficacy for anxiety yet remains limited by in-person-based delivery. Digitally delivered MT may target habitual worry processes, yet its effects on sleep have not been studied. This study tested if app-based MT for anxiety could reduce worry and improve sleep and examined the underlying mechanisms. Methods Individuals reporting worry interfering with sleep were randomized to treatment as usual (TAU; n = 40) or TAU + app-based MT (n = 40). Treatment-related changes in worry-related sleep disturbances (WRSDs), worry, nonreactivity, and anxiety were evaluated via self-report questionnaires at 1 and 2 months after treatment initiation. Fitbit devices were used to record total sleep time and estimate sleep efficiency. At 2 months, TAU received access to app-based MT, and both groups were reassessed at 4 months. Results In a modified intent-to-treat analysis, WRSD scores decreased by 27% in TAU + MT (n = 36) and 6% in TAU (n = 35) at 2 months (median [IQR] change = 11 [4.3] versus 15 [5.0], p = .001). These WRSD reductions were mediated by decreased worry, particularly improved nonreactivity (p values < .001). At 4 months, TAU reported a significant 29% reduction after beginning app-based MT at 2 months and TAU + MT maintained its gains. No significant between-group differences in average estimated total sleep time or sleep efficiency were found after 2 months of using the app. Conclusions Few mindfulness-related apps have been evaluated for clinical efficacy and/or mechanism. Results from this study demonstrate a mechanistic link between MT and increased emotional nonreactivity, decreased worry, and reduction in reported sleep disturbances, suggesting that app-based MT may be a viable option to help individuals who report that worry interferes with their sleep. Trial Registration: ClinicalTrials.gov identifier: NCT03684057.
Genotype-phenotype and outcome associations in patients with Fanconi anemia: the National Cancer Institute cohort

Fanconi anemia (FA) is caused by pathogenic variants in the FA/BRCA DNA repair pathway genes, and is characterized by congenital abnormalities, bone marrow failure and an increased risk of cancer. We conducted a genotype-phenotype and outcomes study of 203 patients with FA in our cohort. We compared across the genes, FA/BRCA DNA repair pathways (upstream, ID complex and downstream), and type of pathogenic variants (hypomorphic or null). We explored differences between the patients evaluated in our clinic (clinic cohort) and those who provided data remotely (field cohort). Patients with variants in the upstream complex pathway had less severe phenotype, lacking VACTERL-H (Vertebral, Anal, Cardiac, Tracheo-esophageal fistula, Esophageal/duodenal atresia, Renal, Limb, Hydrocephalus) association and/or PHENOS (Pigmentation, small Head, small Eyes, Neurologic, Otologic, Short stature) features. ID complex was associated with VACTERL-H. The clinic cohort had more PHENOS features than the field cohort. PHENOS was associated with increased risk of bone marrow failure, and VACTERL-H with hypothyroidism. The cumulative incidences of severe bone marrow failure, solid tumors and leukemia as the first event were 70%, 20% and 6.5%, respectively. Head and neck and gynecological cancers were the most common solid tumors, with a further increased risk after hematopoietic cell transplantation. Among patients with FANCA, variants in exons 27-30 were associated with a higher frequency of solid tumors. Overall the median survival was 37 years; patients with leukemia or FANCD1/BRCA2 variants had the poorest survival. Patients with variants in the upstream complex had better survival than those with variants in ID or the downstream complex (P=0.001 and P=0.016, respectively). FA is phenotypically and genotypically heterogeneous; detailed characterization provides new insights towards understanding this complex syndrome and guiding its clinical management.
Comparison of efficacy of diode laser in patients of facial hirsutism with normal dehydroepiandrosterone sulfate and dihydrotestosterone versus deranged dehydroepiandrosterone sulfate and dihydrotestosterone level—A longitudinal study

Hirsutism is defined as an excessive terminal hair growth in female over male pattern distribution areas. Traditional methods of hair removal have been replaced by lasers. The aim of the study was to observe the effect of diode laser in hirsutism patient with normal and deranged dehydroepiandrosterone sulfate (DHEAS) and dihydrotestosterone (DHT) level. Fifty patients of facial hirsutism with skin type IV and V were enrolled. Eighteen patients with deranged DHEAS and DHT level were allocated in group A whereas 16 patients with normal level were allocated in group B. Three sittings of diode laser was done in all subjects with varying session within a period of 6 months. At first follow‐up visit, the percentage of hair reduction was fair in 62.5% of patients in group B and 16.7% of patients in group A, whereas at second follow‐up visit, it was good in 56.3% of patients in group B and 11.1% of patients in group A. Increase in vellus hair and reduction in percentage of terminal hair were more significant in group B. Hair free interval and satisfaction level was significantly higher in group B. Diode laser is effective mode of treatment in hirsutism patient irrespective of hormone level. But, the effect is observed to be more efficacious in patients with normal DHEAS and DHT level.
Which anchorage device is the best during retraction of anterior teeth? An overview of systematic reviews

Objective To evaluate the available evidence regarding the clinical effectiveness of different types of anchorage devices. Methods A comprehensive literature search of different electronic databases was conducted for systematic reviews investigating different anchorage methods published up to April 15, 2021. Any ongoing systematic reviews were searched using PROSPERO, and a grey literature search was undertaken using Google Scholar and OpenGrey. No language restriction was applied. Screening, quality assessment, and data extraction were performed independently by two authors. Information was categorized and narratively synthesized for the key findings from moderate- and high-quality reviews. Results Fourteen systematic reviews were included (11 were of moderate/high quality). Skeletal anchorage with miniscrews was associated with less anchorage loss (and sometimes with anchorage gain). Similarly, skeletal anchorage was more effective in retracting anterior teeth and intruding incisors and molars, resulting in minor vertical skeletal changes and improvements in the soft tissue profile. However, insufficient evidence was obtained for the preference of any anchorage method in terms of the duration of treatment, number of appointments, quality of treatment, patient perception, or adverse effects. The effectiveness of skeletal anchorage can be enhanced when directly loaded, used in the mandible rather than the maxilla, used buccally rather than palatally, using dual rather than single miniscrews, used for en-masse retraction, and in adults. Conclusions The level of evidence regarding anchorage effectiveness is moderate. Nevertheless, compared to conventional anchorage, skeletal anchorage can be used with more anchorage preservation. Further high-quality randomized clinical trials are required to confirm these findings.
Comparison of concurrent chemoradiotherapy with radiotherapy alone for locally advanced esophageal squamous cell cancer in elderly patients: A randomized, multicenter, phase II clinical trial

This randomized, multicenter, phase II clinical trial was performed to compare the safety and efficacy of concurrent chemoradiotherapy using S‐1 (CCRT) with radiotherapy alone (RT) for elderly patients with locally advanced esophageal squamous cell carcinoma (ESCC). All eligible patients were randomly assigned to the CCRT group or the RT group at a 1:1 ratio. The CCRT group received 50.4 Gy radiotherapy concurrent with S‐1 and the RT group received 59.4 Gy radiotherapy alone. The primary endpoints were toxicity and the overall response rate (ORR), and the secondary endpoints were overall survival (OS) and progression‐free survival (PFS). In total, 157 elderly patients with ESCC were recruited from December 2016 to March 2020. By June 2021, the median follow‐up duration had reached 38 months. No grade 5 toxicities occurred in either group and the overall rate of severe toxicities (≥grade 3) was higher in the CCRT group (19.2% vs 7.6%; P = .037), particularly neutropenia (7.7% vs 1.3%; P = .06). The CCRT group presented a significantly higher ORR (83.3% vs 68.4%; P = .009) and prolonged PFS (25.7 vs 13.9 months; P = .026) than the RT group. The median OS was 27.3 months in the CCRT group and 19.1 months in the RT group (P = .59). For patients older than 70 years with locally advanced ESCC, concurrent chemoradiotherapy with S‐1 had tolerable adverse effects and improved ORR and PFS compared to radiotherapy alone.
Evaluation of low power and high speed CMOS current comparators

Over the past few decades, CMOS current comparators have been used in a wide range of applications, including analogue circuits, MVL (multiple-valued logic) circuits, and various electronic products. A current comparator is generally used in an ADC (analog-to-digital) converter of sensors and similar devices, and several techniques and approaches have been implemented to design the current comparator to improve performance. To this end, this paper presents a bibliographical survey of recently-published research on different current comparator topologies for low-power and high-speed applications. Moreover, several aspects of the CMOS current comparator are discussed regarding the design implementation, parameters, and performance comparison in terms of the power dissipation and operational speed. This review will serve as a comparative study and reference for researchers working on CMOS current comparators in low-power and high-speed applications.
Analog Frontend Circuits for Avalanche Photodiodes

The aims of this work is to design low noise electronics for optical sensing and X‐ray spectroscopy using Sheffield‐grown Avalanche photodiodes(APD). A transimpedance amplifier(TIA) for a 2.0 μm LIDAR system is designed and tested as part of a project funded by ESA. Numerical analysis is provided for the TIA in addition to SPICE and experimental analysis. Characterisation of the TIA shows that a noise equivalent power of less than 100 fW/√Hz can be achieved with an optimised InAs APD. Preliminary results of a TIA‐InAs module at 2.0 μm is presented. A low noise charge sensitive preamplifier(CSP) with a novel local feedback is designed and characterised. The CSP shows a better noise performance than commercially available CSP such as the CoolFet 250. The CSP is also characterised for APD dark current of up 4 μA and the CSP is found to behave well for such relatively high dark current. Discrepancies between the SPICE model and measured characteristic of the CSP’s input JFET is presented and discussed. The first ever Aluminium Indium Phosphide (AlInP) APD X‐ray spectroscopy measurement is presented in this work. AlInP is the widest band material that can be grown latticematched on a GaAs substrate. Due to its wide bandgap, AlInP can offer reverse dark current of less than 2 pA at gain of 100 for a 200um device, making it desirable for room temperature operation. An energy resolution of 647 eV is obtained for AlInP APD coupled to the CSP and exposed to 55Fe X‐rays. Using the CSP presented in this work, previously reported GaAs/AlGaAs APD is characterised and compared with results obtained using a commercial CSP. A 21% improvement in X‐ray energy resolution is reported, despite degradation in the APD.
Toward improved urban earthquake monitoring through deep-learning-based noise suppression

Earthquake monitoring in urban settings is essential but challenging, due to the strong anthropogenic noise inherent to urban seismic recordings. Here, we develop a deep-learning-based denoising algorithm, UrbanDenoiser, to filter out urban seismological noise. UrbanDenoiser strongly suppresses noise relative to the signals, because it was trained using waveform datasets containing rich noise sources from the urban Long Beach dense array and high signal-to-noise ratio (SNR) earthquake signals from the rural San Jacinto dense array. Application to the dense array data and an earthquake sequence in an urban area shows that UrbanDenoiser can increase signal quality and recover signals at an SNR level down to ~0 dB. Earthquake location using our denoised Long Beach data does not support the presence of mantle seismicity beneath Los Angeles but suggests a fault model featuring shallow creep, intermediate locking, and localized stress concentration at the base of the seismogenic zone.