Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase I Study of Combination Olaparib and Radium-223 in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Bone Metastases (COMRADE).

Given that radium-223 is a radiopharmaceutical that induces DNA damage, and olaparib is a PARP inhibitor that interferes with DNA repair mechanisms, we hypothesized their synergy in mCRPC. We sought to demonstrate the safety and efficacy of olaparib + radium-223. We conducted a multicenter phase 1 3+3 dose escalation study of olaparib with fixed dose radium-223 in patients with mCRPC with bone metastases. The primary objective was to establish the RP2D of olaparib, with secondary objectives of safety, PSA response, alkaline phosphatase response, radiographic progression-free survival (rPFS), overall survival (OS), and efficacy by homologous recombination repair (HRR) gene status. Twelve patients were enrolled; all patients received a prior androgen receptor signaling inhibitor (ARSI) (100%) and 3 patients (25%) prior docetaxel. Dose-limiting toxicities (DLTs) included cytopenias, fatigue, and nausea. No DLTs were seen in the observation period however delayed toxicities guided the RP2D. The RP2D of olaparib was 200 mg orally twice daily with radium-223. The most common treatment-related adverse events were fatigue (92%) and anemia (58%). The rPFS at 6 months was 58% (95% CI 27-80%). Nine patients were evaluable for HRR gene status; one had a BRCA2 alteration (rPFS 11.8 months) and one had a CDK12 alteration (rPFS 3.1 months). Olaparib can be safely combined with radium-223 at the RP2D 200mg PO BID with fixed dose radium-223. Early clinical benefit was observed and will be investigated in a phase 2 study.
2-phosphor-converted white light-emitting diodes using oxynitride/nitride phosphors

Green α-sialon:Yb2+ and red Sr2Si5N8:Eu2+ oxynitride/nitride phosphors have been demonstrated as potential downconversion luminescent materials for white light-emitting diodes (LEDs). In this letter, the authors attempt to fabricate white LEDs by combining α-sialon:Yb2+ and Sr2Si5N8:Eu2+ with a blue LED die and report their optical properties. These two phosphors lend themselves for use in 2-phosphor-converted white LEDs with promising properties: a wide range of tunable correlated color temperature (2700–6700K), acceptable color rendering index (82–83), and luminous efficacy (17–23lm∕W). These LEDs are acceptable for general lighting.
Ultrastructural Analysis of Differences in the Growth and Maturation of Staphylococcus pseudintermedius Biofilm on Biotic and Abiotic Surfaces

Biofilm has been recognized as an important source of antimicrobial resistance. These sessile microbial colonies tend to attach and grow on every surface, biotic and abiotic, and they account for approximately 80% of chronic and recurrent infections. ABSTRACT Biofilms are extremely complex yet systematic microbial structures. Studies comparing the differences in their growth on living and nonliving surfaces by electron microscopy are limited. Therefore, the purpose of this study was to ultrastructurally investigate the differences in the growth and development of Staphylococcal biofilm on polycarbonate filters and canine skin explants. Using scanning and transmission electron microscopy (SEM and TEM), Staphylococcus pseudintermedius was incubated for 6, 12, 24, 48, and 72 h. It was observed that similar amounts of exopolymeric substance (EPS) were deposited on the biofilm on both surfaces, but the biofilm on the skin explants was primarily flat, whereas the biofilm on the membrane developed a multilayered plateaued look. Microcolony formation was only observed on the membrane filter during the early stages of biofilm development. On the membrane biofilms, EPS was observed to be deposited in a distinctive pattern. EPS deposition on the membrane surface was observed to peak before it declined, but on the explant, a constant increase was observed at all time points. Cell exposure to the environment on both the membrane filters and explants differed depending on the stage of biofilm formation. On both the membranes and the skin explants, there was a perceptible difference between the biofilm growth patterns and speeds. The results of this study suggest that data extrapolated from studies on biofilm bactericidal compounds performed on abiotic surfaces (such as polycarbonate filters) may not be entirely applicable to biofilm growing on biotic surfaces (e.g., skin) due to ultrastructural variations revealed in this study. IMPORTANCE Biofilm has been recognized as an important source of antimicrobial resistance. These sessile microbial colonies tend to attach and grow on every surface, biotic and abiotic, and they account for approximately 80% of chronic and recurrent infections. Biofilms are not all alike; they have different structures and microbial compositions. This high variability allows for differences in the production of exopolymer substances, affecting antimicrobial penetration. No studies have been published that simultaneously compare the structure of biofilms grown on abiotic (in vitro) and biotic (ex vivo) surfaces. To identify treatment alternatives, it is essential to understand the differences between biofilms. The results of the study show how biofilm structures and compositions are dependent on the substrate on which they grow.
New method for measurement of the total energy density of sound waves

The total energy of a sound field in reverberation chambers is usually sampled by an array of microphones. Each measures the time average of the squared sound pressure at its location. This is equivalent to sampling the time average of the potential energy density of the sound field. It would be advantageous to measure as well the time‐averaged squared particle velocity. This would yield the kinetic‐energy density, which added to the potential‐energy density would then yield the total‐energy density. A principal advantage of the total energy density is that its spatial variance is in general appreciably less than the potential variance. We find this from an analysis of the variances for the eigenmodes of rectangular chambers having reflecting (rigid) walls. A microphone for total energy density can be made from a spatial array of four elements arranged at the corners of a tetrahedron. Electret microphones seem to be particularly suitable for the elements. The total energy density can be computed from the .
Total Breast Reconstruction with Lipofilling after Traditional Mastectomy without the Use of Tissue Expanders

Background: Lipofilling can be used to reconstruct a breast without additional implants or autologous composite grafts. However, methods to maximize retention of the transferred fat remain under debate. Here, the authors present their experience of breast reconstruction with lipofilling without concomitant use of tissue expanders. Methods: Patients who had completed breast reconstruction with lipofilling between June of 2010 and June of 2016 were reviewed. Those with obtainable follow-up magnetic resonance imaging scans were included in this cross-sectional study. The hospital records were reviewed for details of the lipofilling operations. Magnetic resonance imaging scans were evaluated for the volume retention and quality of the transferred fat. The patients were asked to assess the appearance and sensitivity of the reconstructed breast, the recovery time, and any adverse effects at the fat donor area. Results: Thirty-eight women with 41 reconstructed breasts were included in the study. The median age at follow-up was 62 years (range, 48 to 78 years). They had undergone a median of four (range, two to six) lipofilling procedures with a median total volume 690 mL (range, 369 to 1350 mL). After a median follow-up of 2.1 years (range, 0.4 to 6.8 years), the median proportion of transferred fat retained was 58% (range, 14% to 119%), representing a reconstructed breast volume of 76% (range, 17% to 100%) of the contralateral breast. Oil cysts larger than 10 mm were detected in 7%. Most patients reported being satisfied with the reconstructed breast and experienced few side effects. Conclusions: Breast reconstruction with lipofilling can be performed with an acceptable number of procedures and no preoperative skin expansion. It extends the option of autologous breast reconstruction to women unsuited for major reconstructive procedures. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Bottom-Up Construction of the Interaction between Janus Particles

While the interaction between two uniformly charged spheres—viz colloids—is well-known, the interaction between nonuniformly charged spheres such as Janus particles is not. Specifically, the Derjaguin approximation relates the potential energy between two spherical particles with the interaction energy Vpl per unit area between two planar surfaces. The formalism has been extended to obtain a quadrature expression for the screened electrostatic interaction between Janus colloids with variable relative orientations. The interaction is decomposed into three zones in the parametric space, distinguished by their azimuthal symmetry. Different specific situations are examined to estimate the contributions of these zones to the total energy. The effective potential Vpl is renormalized such that the resulting potential energy is identical with the actual one for the most preferable relative orientations between the Janus particles. The potential energy as a function of the separation distance and the mutual orientation of a pair of particles compares favorably between the analytical (but approximate) form and the rigorous point-wise computational model used earlier. Coarse-grained models of Janus particles can thus implement this potential model efficiently without loss of generality.
Optimization of cancer immunotherapy on the basis of programmed death ligand‐1 distribution and function

Programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) immune checkpoint blockade as a breakthrough in cancer immunotherapy has shown unprecedented positive outcomes in the clinic. However, the overall effectiveness of PD‐L1 antibody is less than expected. An increasing number of studies have demonstrated that PD‐L1 is widely distributed and expressed not only on the cell membrane but also on the inside of the cells as well as on the extracellular vesicles secreted by tumour cells. Both endogenous and exogenous PD‐L1 play significant roles in influencing the therapeutic effect of anti‐tumour immunity. Herein, we mainly focused on the distribution and function of PD‐L1 and further summarized the potential targeted therapeutic strategies. More importantly, in addition to taking the overall expression abundance of PD‐L1 as a predictive indicator for selecting corresponding PD‐1/PD‐L1 monoclonal antibodies (mAbs), we also proposed that personalized combination therapies based on the different distribution of PD‐L1 are worth attention to achieve more efficient and effective therapeutic outcomes in cancer patients.
Understanding the Roles of Host Defense Peptides in Immune Modulation: From Antimicrobial Action to Potential as Adjuvants

Host defense peptides are expressed in various immune cells, including phagocytic cells and epithelial cells. These peptides selectively alter innate immune pathways in response to infections by pathogens, such as bacteria, fungi, and viruses, and modify the subsequent adaptive immune environment. Consequently, they play a wide range of roles in both innate and adaptive immune responses. These peptides are of increasing importance due to their broad-spectrum antimicrobial activity and their functions as mediators linking innate and adaptive immune responses. This review focuses on the pleiotropic biological functions and related mechanisms of action of human host defense peptides and discusses their potential clinical applications.
Latent anxiety and depression dimensions differ amongst patients with eating disorders: A Swedish nationwide investigation

Anxiety and depression symptoms are common in individuals with eating disorders. To study these co‐occurrences, we need high‐quality self‐report questionnaires. The 19‐item self‐rated Comprehensive Psychopathological Rating Scale for Affective Syndromes (CPRS‐S‐A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions.
FINANCIAL DECISION MAKING AND WEALTH LOSS IN OLDER ADULTS WITH EARLY MEMORY LOSS: THE WALLET STUDY

ABSTRACT Risk perception refers to people’s subjective judgments about the possibility of negative occurrences and the extent to which they are concerned with them. Previous studies have found that older adults who were exposed to ongoing terror threats developed later-life and terror risk perceptions. These studies showed that high risk perception has negative psychological and physiological consequences. This study aimed to identify the factors associated with the development of both later-life risk perception and terror risk perception in later life. Data were collected via an online survey with 306 Internet users aged 50 years and over, half resided in a high-risk zone while the remainder lived in a low-risk zone. The Perceived Risk Scale, measures of depressive symptoms, life satisfaction, social support, spirituality, internet use, and personal background were applied. Low self-rated health was associated with terror and later-life risk perceptions, regardless of the risk zone. After controlling for personal background, only depressive symptoms significantly correlated with high risk perceptions. These findings suggest that older adults with poorer self-rated health, secular beliefs, and elevated depressive symptoms may be susceptible to developing high risk perceptions. Clinicians should encourage older adults to identify preserving resources to improve adjustment to late life stressors.
Oxidative stress—A key determinant of complications and negative outcome in hepatitis E virus infected pregnancies: A comprehensive account involving cases from northeast India

Regulated oxidative stress (OS) is important during pregnancy. Sporadic studies suggest the significance of deregulated OS in hepatitis E virus (HEV) infected pregnancy, but with limited reactive oxygen species (ROS) or antioxidant markers. The present novel study, therefore, aimed to evaluate the significance of ROS‐antioxidant imbalance and resulting altered OS in HEV infected pregnancy complications like preterm delivery (PTD) and outcome. Difference in serum levels of ROS and antioxidant panel of markers were evaluated by ELISA for HEV immunoglobulin M RNA positive genotype 1 cases (including acute [acute viral hepatitis, AVH] and fulminant [fulminant hepatic failure, FHF] cases) and healthy term delivery subjects, and analyzed statistically. Direct ROS marker H2O2 levels and indirect OS marker for DNA damage 8‐hydroxy‐2′‐deoxyguanosine was significantly increased in HEV‐cases compared to controls, and was associated and prognostic factor for PTD and fetal death in HEV cases. A comparatively lower total serum antioxidant capacity was observed in the FHF cases compared to the control subjects and the AVH cases. Glutathione (GSH) levels and superoxide dismutase (SOD) activity were significantly associated with PTD in the FHF sub‐cohorts (p = 0.017) and AVH sub‐cohorts (p < 0.001), respectively, and was associated with poor prognosis in HEV cases. The serum H2O2 levels were found to be negatively correlated with SOD activity (p = 0.016) and GSH levels (p = 0.001) in the HEV‐AVH cases; and positively correlated with the viral load in HEV cases (p = 0.023). The ROS‐antioxidant imbalance resulting OS plays a detrimental associative role in HEV infected pregnancy complications like PTD and adverse pregnancy outcomes; and holds therapeutic significance.
Genome Sequences of Alkalihalobacillus clausii, Bacillus safensis, Escherichia coli, and Pasteurella multocida Isolates from the Rumen, Nasopharynx, Vagina, and Uterus of Healthy Beef Cattle

Here, we present the first draft genome sequences of 10 bacterial strains that were isolated from the rumen, nasopharynx, vagina, or uterus of healthy beef cattle. These genomes are from one Alkalihalobacillus clausii isolate, three Bacillus safensis isolates, five Escherichia coli isolates, and one Pasteurella multocida isolate. ABSTRACT Here, we present the first draft genome sequences of 10 bacterial strains that were isolated from the rumen, nasopharynx, vagina, or uterus of healthy beef cattle. These genomes are from one Alkalihalobacillus clausii isolate, three Bacillus safensis isolates, five Escherichia coli isolates, and one Pasteurella multocida isolate.
Low-intensity swimming with blood flow restriction over 5 weeks increases VO2peak: A randomized controlled trial using Bayesian informative prior distribution

ABSTRACT Peak oxygen uptake (VO2peak) and speed at first (LT1, minimal lactate equivalent) and second lactate threshold (LT2 = LT1 +1.5 mmol·L−1) are crucial swimming performance surrogates. The present randomized controlled study investigated the effects of blood flow restriction (BFR) during low-intensity swimming (LiT) on VO2peak, LT1, and LT2. Eighteen male swimmers (22.7 ±3.0 yrs; 69.9 ±8.5 kg; 1.8 ±0.1 m) were either assigned to the BFR or control (noBFR) group. While BFR was applied during LiT, noBFR completed the identical LIT without BFR application. BFR of the upper limb was applied via customized pneumatic cuffs (75% of occlusion pressure: 135 ±10 mmHg; 8 cm cuff width). BFR training took place three times a week over 5 weeks (accumulated weekly net BFR training: 60 min·week−1; occlusion per session: 2-times 10 min·session−1) and was used exclusively at low intensities. VO2peak, LT1, and LT2 diagnostics were employed. Bayesian credible intervals revealed notable VO2peak improvements by +0.29 L·min−1 kg−1 (95% credible interval: −0.26 to +0.85 L·min−1 kg−1) when comparing BFR vs. noBFR. Speed at LT1 −0.01 m·s−1 (−0.04 to +0.02 m·s−1) and LT2 −0.01 m·s−1 (−0.03 to +0.02 m·s−1) did not change meaningfully when BFR was employed. Fifteen sessions of LIT swimming (macrocycle of 5 h over 5 weeks) with a weekly volume of 60 min with BFR application adds additional impact on VO2peak improvement compared to noBFR LIT swimming. Occasional BFR applications should be considered as a promising means to improve relevant performance surrogates in trained swimmers. Highlights Low-intensity swimming with blood flow restricted (BFR) induced superior peak oxygen consumption adaptations compared to non-restricted swimming training over a 5-week lasting training period BFR and non-BFR swimming training-induced similar adaptations regarding swimming speed at first and second lactate threshold In conclusion, BFR served as a feasible, promising and beneficial complementary training stimuli to traditional swimming training regarding oxygen consumption adaptations.
Influence of mid-afternoon nap duration and sleep parameters on memory encoding, mood, processing speed, and vigilance

Abstract Study Objectives To determine how mid-afternoon naps of differing durations benefit memory encoding, vigilance, speed of processing (SOP), mood, and sleepiness; to evaluate if these benefits extend past 3 hr post-awakening and to examine how sleep macrostructure during naps modulate these benefits. Methods Following short habitual sleep, 32 young adults underwent four experimental conditions in randomized order: wake; naps of 10 min, 30 min, and 60 min duration verified with polysomnography. A 10-min test battery was delivered at a pre-nap baseline, and at 5 min, 30 min, 60 min, and 240 min post-nap. Participants encoded pictures 90 min post-nap and were tested for recognition 210 min later. Results Naps ranging from 10 to 60 min increased positive mood and alleviated self-reported sleepiness up to 240 min post-nap. Compared to waking, only naps of 30 min improved memory encoding. Improvements in vigilance were moderate, and benefits for SOP were not observed. Sleep inertia was observed for the 30 min to 60 min naps but was resolved within 30 min after waking. We found no significant associations between sleep macrostructure and memory benefits. Conclusions With short habitual sleep, naps ranging from 10 to 60 min had clear and lasting benefits for positive mood and self-reported sleepiness/alertness. Cognitive improvements were moderate, with only the 30 min nap showing benefits for memory encoding. While there is no clear “winning” nap duration, a 30 min nap appears to have the best trade-off between practicability and benefit. Clinical Trial ID Effects of Varying Duration of Naps on Cognitive Performance and Memory Encoding, https://www.clinicaltrials. gov/ct2/show/NCT04984824, NCT04984824.
Chronology of the Solar System’s Oldest Solids

Determining the origins of our solar system and, by proxy, other planetary systems, depends on knowing accurately and precisely the timing and tempo of the transformation of the disk of gas and dust to the solids that formed the planets. Relative ages based on the short-lived nuclide 26Al indicate that high-temperature calcium-aluminum inclusions (CAIs) formed before lower temperature chondrules but these ages are heavily dependant on a model of homogeneous distribution of 26Al within the protoplanetary disk. The competing X-wind model argues for heterogeneous distribution of 26Al due to its formation by intra-solar system irradiation such that this system would have no chronological significance. We report a207Pb-206Pb isochron age of 4565.45 ± 0.45 Myr for chondrules from the CV chondrite Allende, an age that is 1.66 ± 0.48 Myr younger than the accepted Pb-Pb age for CAIs from this chondrite group. This age offset is in excellent agreement with the relative ages determined using the 26Al-26Mg system, an observation that supports a supernova origin for 26Al and, importantly, the chronological significance of the 26Al-26Mg system in general. This is consistent with an early and brief CAI-forming event followed by recurrent chondrule formation throughout the life span of the protoplanetary disk. The paucity of old chondrules in chondrite meteorites may reflect their early incorporation into the parent bodies of differentiated meteorites after CAIs were effectively removed from the innermost regions of the protoplanetary disk. Lastly, the agreement between the absolute and relative chronology of CAIs and chondrules requires a solar system age younger than ~4567.5 Myr