Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined Effects of Synaptic and Axonal Integrity on Longitudinal Gray Matter Atrophy in Cognitively Unimpaired Adults

Background and Objectives Synaptic dysfunction and degeneration is a predominant feature of brain aging, and synaptic preservation buffers against Alzheimer disease (AD) protein-related brain atrophy. We tested whether CSF synaptic protein concentrations similarly moderate the effects of axonal injury, indexed by CSF neurofilament light [NfL]), on brain atrophy in clinically normal adults. Methods Clinically normal older adults enrolled in the observational Hillblom Aging Network study at the UCSF Memory and Aging Center completed baseline lumbar puncture and longitudinal brain MRI (mean scan [follow-up] = 2.6 [3.7 years]). CSF was assayed for synaptic proteins (synaptotagmin-1, synaptosomal-associated protein 25 [SNAP-25], neurogranin, growth-associated protein 43 [GAP-43]), axonal injury (NfL), and core AD biomarkers (ptau181/Aβ42 ratio; reflecting AD proteinopathy). Ten bilateral temporoparietal gray matter region of interest (ROIs) shown to be sensitive to clinical AD were summed to generate a composite temporoparietal ROI. Linear mixed-effects models tested statistical moderation of baseline synaptic proteins on baseline NfL-related temporoparietal trajectories, controlling for ptau181/Aβ42 ratios. Results Forty-six clinically normal older adults (mean age = 70 years; 43% female) were included. Synaptic proteins exhibited small to medium correlations with NfL (r range: 0.10–0.36). Higher baseline NfL, but not ptau181/Aβ42 ratios, predicted steeper temporoparietal atrophy (NfL × time: β = −0.08, p < 0.001; ptau181/Aβ42 × time: β = −0.02, p = 0.31). SNAP-25, neurogranin, and GAP-43 significantly moderated NfL-related atrophy trajectories (−0.07 ≤ β's ≥ −0.06, p's < 0.05) such that NfL was associated with temporoparietal atrophy at high (more abnormal) but not low (more normal) synaptic protein concentrations. At high NfL concentrations, atrophy trajectories were 1.5–4.5 times weaker when synaptic protein concentrations were low (β range: −0.21 to −0.07) than high (β range: −0.33 to −0.30). Discussion The association between baseline CSF NfL and longitudinal temporoparietal atrophy is accelerated by synaptic dysfunction and buffered by synaptic integrity. Beyond AD proteins, concurrent examination of in vivo axonal and synaptic biomarkers may improve detection of neural alterations that precede overt structural changes in AD-sensitive brain regions.
Modeling mRNA Translation With Ribosome Abortions

We derive a deterministic mathematical model for the flow of ribosomes along a mRNA called the ribosome flow model with extended objects and abortions (RFMEOA). This model incorporates important cellular features such as every ribosome covers several codons and they may detach from various regions along the track due to more realistic biological situations including phenomena of ribosome-ribosome collisions. We prove that the ribosome density profile along the mRNA in the RFMEOA and in particular, the protein production rate converge to a unique steady-state. Simulations of the RFMEOA demonstrate a surprising result that an increase in the initiation rate may sometimes lead to a decrease in the production rate. We believe that this model could be helpful to provide insight into the effects of premature termination on the protein expression and be useful for understanding and re-engineering the translation process.
Factors Associated With Ultrasound Color Doppler Twinkling by Breast Biopsy Markers: In Vitro and Ex Vivo Evaluation of 35 Commercially Available Markers.

Background: Targeted axillary lymph node dissection after neoadjuvant systemic therapy (NST) for breast cancer depends on identifying marked metastatic lymph nodes. However, ultrasound visualization of biopsy markers is challenging. Objective: To identify biopsy markers that demonstrate actionable twinkling in cadaveric breast, and to assess the association of actionable twinkling with markers' surface roughness. Methods: Commercial breast biopsy markers were evaluated for twinkling artifact in various experimental conditions relating to scanning medium (solid gel phantom, ultrasound coupling gel, cadaveric breast), transducer (ML6-15, 9L, C1-6), and embedding material (present vs absent). Markers were assigned twinkling scores from 0 (confident in no twinkling) to 4 (confident in exuberant twinkling); score ≥3 represented actionable twinkling (sufficient confidence to rely solely on twinkling for target localization). Markers were hierarchically advanced to evaluation with increasingly complex media if showing at least minimal twinkling for a given medium. A 3D-coherence optical profiler measured marker surface roughness. Mixed-effects proportional odds regression models assessed associations between twinkling scores and transducer and embedding material; Wilcoxon rank sum test evaluated associations between actionable twinkling and surface roughness. Results: Thirty-five markers (21 with embedding material) were evaluated. Ten markers without embedding material advanced to evaluation in cadaveric breast. Higher twinkling scores were associated with presence of embedding material [odds ratio (OR)=5.05 in solid gel phantom, 9.84 in coupling gel] and transducer (using C1-6 as reference, OR in solid gel phantom, ultrasound coupling gel, and cadaveric breast of 0.83, 0.36, and 0.04 for 9L, and 0.18, 0.17, and 0.04 for ML6-15; post-hoc P between 9L and ML6-15 of <.001, .02, and .04). In cadaveric breast, three markers [Cork, Q, MRI (Flex)] exhibited actionable twinkling for ≥2 transducers; surface roughness was significantly higher for markers with than without actionable twinkling for C1-6 (median values: 0.97 vs 0.35, P=.02) and 9L (1.75 vs 0.36; P=.002) transducers. Conclusion: Certain breast biopsy markers exhibited actionable twinkling in cadaveric breast. Twinkling was observed with greater confidence for C1-6 and 9L than ML6-15 transducer. Actionable twinkling was associated with higher marker surface roughness. Clinical Impact: Use of twinkling for marker detection could impact preoperative or intraoperative localization after NST.
Activation of the pattern recognition receptor NOD1 in periodontitis impairs the osteogenic capacity of human periodontal ligament stem cells via p38/MAPK signalling

Nucleotide oligomerization domain receptor 1 (NOD1) mediates host recognition of pathogenic bacteria in periodontium. However, the specific role of NOD1 in regulating osteogenesis is unclear. Therefore, this study focused on the activation status of NOD1 in periodontitis and its effect on the osteogenic capacity of human periodontal ligament stem cells (hPDLSCs) as well as the underlying mechanism.
Beta‐lactam resistance and the effectiveness of antimicrobial peptides against KPC‐producing bacteria

Bacterial resistance is a problem that is giving serious cause for concern because bacterial strains such as Acinetobacter baumannii and Pseudomonas aeruginosa are difficult to treat and highly opportunistic. These bacteria easily acquire resistance genes even from other species, which confers greater persistence and tolerance towards conventional antibiotics. These bacteria have the highest death rate in hospitalized intensive care patients, so strong measures must be taken. In this review, we focus on the use of antimicrobial peptides (AMPs) as an alternative to traditional drugs, due to their rapid action and lower risk of generating resistance by microorganisms. We also present an overview of beta‐lactams and explicitly explain the activity of AMPs against carbapenemase‐producing bacteria as potential alternative agents for infection control.
STEEP AND BREAKING DEEP WATER WAVES

Many naval applications require a further basic understanding of surface wave hydrodynamics up to and beyond the onset of breaking, and of the energy and momentum transfer processes which take place during and after breaking. In the present paper is described a technique for the computation of steep asymmetric wave motions up to the incipient of onset stages of breaking. Comparisons are made with related computational schemes and then the method is used for a study of limiting wave conditions and the onset of breaking. The computations are compared with recent measurements made at NRL and elsewhere of the limiting heights of deep water waves and the losses in potential energy density and momentum flux which accompany the breaking process. An estimate of the limiting wave height at breaking in deep water from the computational results is in good agreement with experiments described here. The potential energy and momentum flux loss rates of plunging breakers are about twice those of spilling breakers in deep water.
Comparing Non-Communicable Disease Risk Factors in Asian Migrants and Native Koreans among the Asian Population

Assessing the health of international migrants is crucial in the Republic of Korea, Asia, and even worldwide. We compared the risk factors for non-communicable diseases among Asian migrants in Korea and the Korean population. This cross-sectional (2015) and longitudinal (2009-2015) observational study comprised a population-wide analysis spanning 2009 to 2015. Asian migrants (n=987,214) in Korea and Korean nationals (n=1,693,281) aged ≥20 were included. The Asian migrants were classified as Chinese, Japanese, Filipino, Vietnamese, and other. The prevalence of risk factors for non-communicable diseases (current smoking, obesity, diabetes mellitus, and hypertension) were analyzed. Regarding the age-adjusted prevalence, direct age standardization was conducted separately by sex using 10-year age bands; the World Standard Population was used as the standard population. Among the participants aged ≥20, the age-adjusted prevalence of current smoking was higher among Chinese and other Asian migrant men than among Korean men and women (p<0.001 and p<0.001, respectively). The age-adjusted prevalence of obesity was higher among Chinese, Filipino, and other Asian migrant women than in Korean women (p<0.001, p=0.002, and p<0.001, respectively). Among the participants aged 20-49, the age-adjusted prevalence of diabetes mellitus and hypertension was higher in Filipino migrant women than in Korean women (p=0.009 and p<0.001, respectively). Current rates of smoking and obesity were worse among Asian migrants of specific nationalities than among native Koreans. The health inequalities among Filipino migrant women in Korea, especially those aged 20-49, should be addressed.
Dietary energy:protein ratio influences the efficiency of utilisation of dietary protein by growing turkeys

ABSTRACT 1. The following experiment was designed to confirm that the efficiency of dietary protein utilisation (ep) can be reduced when the AMEn to digestible crude protein (DCP) ratio of the feed falls below a critical level. In addition, whether the efficiency would be improved at high DCP contents through the addition of oil or starch was determined. 2. A 14d trial (starting at 21 d of age), using BUT 6 turkeys, was designed to measure the effects on ep of four feeds (12.1 MJ AMEn/kg) with AMEn:DCP ratios ranging from 45 to 72 MJ AMEn/kg, and two additional feeds with the same DCP as the highest protein feed, one with an AMEn:DCP ratio of 59, through the addition of canola oil, and the other with a ratio of 51 MJ/kg supplemented with both starch and oil. Twenty birds constituted each experimental unit, with two replications of each sex being used per dietary treatment. 3. Ten birds per sex were sampled at the start of the trial and a further five per pen at the end for carcass analysis. Each carcass including feathers was ground and subsampled for water, protein and lipid determination. 4. A split-line regression described ep on the four feeds unsupplemented with additional energy (R2 = 0.81) with breakpoint at 60.6 MJ AME/kg DCP, maximum ep at 0.736 g/g, and a slope of 0.017. No improvement in ep resulted from supplementing the high protein feed with oil or a mixture of oil and starch, but feed intake and protein and lipid retention increased significantly (P < 0.05). 5. The argument that insufficient energy is available to enable high protein feeds to be utilised efficiently was not corroborated by the evidence from this trial.
Initial United Kingdom experience of endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography

Backgrounds/Aims Gallstone disease is a recognized complication of bariatric surgery. Subsequent management of choledocholithiasis may be challenging due to altered anatomy which may include Roux-en-Y gastric bypass (RYGB). We conducted a retrospective service evaluation study to assess the safety and efficacy of endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) in patients with RYGB anatomy. Methods All the patients who underwent EDGE for endoscopic retrograde cholangiopancreatography after RYGB at two tertiary care centers in the United Kingdom between January 2020 and October 2021 were included in the study. Clinical and demographic details were recorded for all patients. The primary outcome measures were technical and clinical success. Adverse events were recorded. Hot Axios lumen apposing metal stents measuring 20 mm in diameter and 10 mm in length were used in all the patients for creation of a gastro-gastric or gastro-jejunal fistula. Results A total of 14 patients underwent EDGE during the study period. The majority of the patients were female (85.7%) and the mean age of patients was 65.8 ± 9.8 years. Technical success was achieved in all but one patient at the first attempt (92.8%) and clinical success was achieved in 100% of the patients. Complications arose in 3 patients with 1 patient experiencing persistent fistula and weight gain. Conclusions In patients with RYGB anatomy, EDGE facilitated biliary access has a high rate of clinical success with an acceptable safety profile. Adverse events are uncommon and can be managed endoscopically.
BESS: BDP Estimation Based Slow Start Algorithm for MPTCP in mmWave-LTE Networks

In recent years, millimeter wave (mmWave) communications, considered as a compelling technology to achieve throughput improvement target of the fifth generation (5G) mobile networks, is quickly attracting attention in both scientific and industrial communities. To enhance reliability of mmWave link, mmWave-LTE networks with MPTCP could be used as an effective solution due to its path diversity. However, the poor performance of MPTCP is found in mmWave-LTE networks based on previous studies. In this paper, we identify the reason of the preceding problem which is the congestion window overgrowth in Slow Start phase, and propose a BDP Estimation Based Slow Start (BESS) algorithm for MPTCP to address this problem. Our simulations show that with the control of BESS, MPTCP can sufficiently use the bandwidth of mmWave networks, and improve networks robustness when mmWave link is switched from LOS to NLOS condition.
Integrating appraisal processes in the study demands-resources framework – a diary study

ABSTRACT Background and Objectives: Students face various demands that can lead to health complaints. Hindering demands appear to be especially harmful. Since the perception of demands differs between persons, their individual appraisal determines stress perception. However, individual appraisal processes are largely neglected in research. Therefore, this study builds on the study demands-resources model in examining the dynamics of students’ demand-appraisal processes and their effects on well-being. Design: During ten days in a four-week period, 247 students participated in a diary study. Methods: We analyzed our data via multilevel path analysis. Results: Our analyses revealed that the student’s appraisal of the same demands varied across days and depended on available resources, i.e., the received support quality on the respective day. Appraising demands as hindering was positively linked to the perception of stress on the same day. Daily perception of stress was positively linked to person-level strain and health complaints after four weeks. Conclusions: The results highlight the importance of assessing the individual appraisal of demands rather than pre-categorizing demands. Furthermore, our findings identify social support as a crucial resource in reducing hindering appraisal; hence, it should be included in student-focused stress-management interventions. Limitations and further implications are also discussed.
Plasma and Liver Pharmacokinetics of the N-Acetylgalactosamine Short Interfering RNA JNJ-73763989 in Recombinant Adeno-Associated–Hepatitis B Virus–Infected Mice

JNJ-73763989 is an N-acetylgalactosamine conjugated short interfering RNA combination product consisting of two triggers in clinical development for chronic hepatitis B virus (HBV) infection treatment that induces a selective degradation of all HBV mRNA transcripts. Our aim is to characterize the plasma and liver pharmacokinetics (PK) of JNJ-73763989 after intravenous and subcutaneous administration in recombinant adeno-associated (rAAV) HBV infected mice. Forty-two male rAAV-HBV infected C57Bl/6 mice received JNJ-73763989 doses of 10 mg/kg i.v. or 1, 3 and 10 mg/kg s.c. Plasma and liver concentrations were analyzed simultaneously using nonlinear mixed-effects modeling with the NONMEM 7.4. A population PK model consisting of a two-compartment disposition model with transporter-mediated drug disposition, including internalization to the liver compartment, linear elimination from plasma and liver, and first-order absorption following subcutaneous administration, was suitable to describe both plasma and liver PK. After subcutaneous dosing, absolute bioavailability was complete and flip-flop kinetics were observed. JNJ-73763989 distributes from plasma to liver via transporter-mediated liver internalization in less than 24 hours, with sustained (>42 days) liver exposure. The saturation of transporter-mediated liver internalization was hypothesized to be due to asialoglycoprotein receptor saturation. Increasing the dose decreased the relative liver uptake efficiency in mice for intravenously and, to a lesser extent, subcutaneously administered JNJ-73763989. Lower dose levels administered subcutaneously in mice can maximize the proportion of the dose reaching the liver. SIGNIFICANCE STATEMENT Pharmacokinetic modeling of JNJ-73763989 liver and plasma concentration-time data in mice indicated that the proportion of JNJ-73763989 reaching the liver may be increased by administering lower subcutaneous doses compared to higher intravenous doses. Model-based simulations can be applied to optimize the dose and regimen combination.
Exon 2‐mediated deletion of Trem2 does not worsen metabolic function in diet‐induced obese mice

Triggering receptor expressed on myeloid cells 2 (Trem2) is highly expressed on myeloid cells and is involved in cellular lipid homeostasis and inflammatory processes. Trem2 deletion in mice (Trem2−/−) evokes adipose tissue dysfunction, but its role in worsening obesity‐induced metabolic dysfunction has not been resolved. Here we aimed to determine the causal role of Trem2 in regulating glucose homeostasis and insulin sensitivity in mice. Nine‐week‐old male and female littermate wild‐type (WT) and Trem2−/− mice were fed a low‐ or high‐fat diet for 18 weeks and phenotyped for metabolic function. Diet‐induced weight gain was similar between genotypes, irrespective of sex. Consistent with previous reports, we find that loss of Trem2 causes massive adipocyte hypertrophy and an attenuation in the lipid‐associated macrophage transcriptional response to obesity. In contrast to published data, we find that loss of Trem2 does not worsen metabolic function in obese mice. No differences in intraperitoneal glucose tolerance (ipGTT), oral GTT or mixed meal substrate control, including postprandial glucose, non‐esterified fatty acids, insulin or triglycerides, were found between WT and Trem2−/− animals. Similarly, no phenotypic differences existed when animals were challenged with stressors on metabolic demand (i.e. acute exercise or environmental temperature modulation). Collectively, we report a disassociation between adipose tissue remodelling caused by loss of Trem2 and whole‐body metabolic homeostasis in obese mice. The complementary nature of experiments conducted gives credence to the conclusion that loss of Trem2 is unlikely to worsen glucose homeostasis in mice.
In situ hybridization to detect DNA amplification in extracellular vesicles

Abstract EVs have emerged as an important component in tumour initiation, progression and metastasis. Although notable progresses have been made, the detection of EV cargoes remain significantly challenging for researchers to practically use; faster and more convenient methods are required to validate the EV cargoes, especially as biomarkers. Here we show, the possibility of examining embedded EVs as substrates to be used for detecting DNA amplification through ultrasensitive in situ hybridization (ISH). This methodology allows the visualization of DNA targets in a more direct manner, without time consuming optimization steps or particular expertise. Additionally, formalin‐fixed paraffin‐embedded (FFPE) blocks of EVs allows long‐term preservation of samples, permitting future studies. We report here: (i) the successful isolation of EVs from liposarcoma tissues; (ii) the EV embedding in FFPE blocks (iii) the successful selective, specific ultrasensitive ISH examination of EVs derived from tissues, cell line, and sera; (iv) and the detection of MDM2 DNA amplification in EVs from liposarcoma tissues, cell lines and sera. Ultrasensitive ISH on EVs would enable cargo study while the application of ISH to serum EVs, could represent a possible novel methodology for diagnostic confirmation. Modification of probes may enable researchers to detect targets and specific DNA alterations directly in tumour EVs, thereby facilitating detection, diagnosis, and improved understanding of tumour biology relevant to many cancer types.
Association between kinetic of Anti-Neutrophil Cytoplasmic Antibody (ANCA), renal survival and relapse risk in ANCA-glomerulonephritis.

BACKGROUND Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies focused on its association with renal prognosis. Thus, we aimed to investigate the relationship between i) ANCA specificity and evolutive profile, and ii) renal outcomes. METHODS This multicentric retrospective study included patients diagnosed with ANCA-GN since 01/01/2000. Patients without ANCA at diagnosis and with fewer than 3 ANCA determinations during follow-up were excluded. We analyzed eGFR variation, renal-free and relapse-free survival according to three ANCA profiles (negative, recurrent, persistent) and to ANCA specificity (MPO or PR3). RESULTS Over a follow-up of 56 [34-101] months, a median of 19 [13-25] ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free (p = 0.019) survival and tended to have a lower renal survival (p = 0.053) compared to those with negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (p = 0.015) and those with recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (p = 0.013) compared to other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a two-fold increase of eGFR at 2-year (OR = 6.79, 95% CI [1.78, 31.4], p = 0.008). CONCLUSION ANCA kinetic after ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus, ANCA kinetic may help identify patients with a smoldering disease.