Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-scale top-down strategy to generate viable genome-reduced phages

Abstract Efforts have been made to reduce the genomes of living cells, but phage genome reduction remains challenging. It is of great interest to investigate whether genome reduction can make phages obtain new infectious properties. We developed a CRISPR/Cas9-based iterative phage genome reduction (CiPGr) approach and applied this to four distinct phages, thereby obtaining heterogeneous genome-reduced mutants. We isolated and sequenced 200 mutants with loss of up to 8–23% (3.3–35 kbp) of the original sequences. This allowed the identification of non-essential genes for phage propagation, although loss of these genes is mostly detrimental to phage fitness to various degrees. Notwithstanding this, mutants with higher infectious efficiency than their parental strains were characterized, indicating a trade-off between genome reduction and infectious fitness for phages. In conclusion, this study provides a foundation for future work to leverage the information generated by CiPGr in phage synthetic biology research.
Willingness of intensive care unit patients’ family members to donate organs: A cross-sectional study

The large gap between the demand for, and the supply of organs worldwide makes promoting organ donation an important global social issue. Even after someone has signed a consent form or registered for organ donation, ethically, the hospital still requires a family member’s written permission before organ donation can proceed. As a result, a family member rather than the patient makes the final decision. This study investigated the willingness of the family members of hypothetical patients in intensive care units (ICUs) suffering from an irreversible condition to sign an organ donation consent form. A cross-sectional survey was conducted among family members of ICU patients recruited from one medical center in southern Taiwan from April to October 2014, which followed the STROBE guidelines. Of 110 ICU family members, 71 (64.5%) were willing to donate the organs of hypothetical patients with irreversible conditions. Based on logistic regression, family support, attitude, and knowledge of organ donation significantly predicted 34% of the variance in willingness to sign consent. Attitude toward organ donation and behavioral knowledge of organ donation correlated significantly with a willingness to sign a consent form. This study found that family support and organ donation attitudes were important factors in predicting the willingness to sign a consent form for the organ donation of hypothetical patients. The study provides evidence that nurses and healthcare staff need to consider family support and educate families on organ donation to encourage potential donors to accept and agree to organ donation.
Young men’s perceptions and attitudes towards two fertility awareness interventions and preferences for future initiatives

Abstract This study explored young Danish men’s perceptions and attitudes towards two fertility awareness (FA) interventions (a podcast episode and an informational poster) and their preferences for how fertility awareness and prevention efforts should be targeted and communicated to young men in the future. Focus groups were held with 13 young men who were between the ages of 25–35 and in a committed relationship over Zoom in January 2021. Data were analysed using qualitative content analysis. Young men preferred FA interventions to be factual as in the informational poster and to include personal stories that could serve as conversation starters as in the podcast. According to the young men, FA interventions should communicate using positive language and humour and not be negative or shaming. They preferred intervention formats like TV-programmes, podcasts, and social media. The participants also suggested fertility information should be included in sexual education in high school and vocational education. This research suggests that future FA campaigns should be developed in cooperation with the target group together with clinicians, and concurrent studies using different intervention formats should be performed. In all probability, a mix of different interventions is necessary to attain the desired effect to ensure long-lasting fertility awareness.
Secondary glaucoma following vitreo-retinal surgeries

Vitreoretinal surgeries either in the form of external compression by buckles or by increasing the intraocular volume by tamponades can cause a significant rise in intraocular pressure (IOP), causing glaucoma to be one of the most common consequences of vitreoretinal surgeries despite improved surgical techniques. Identifying the mechanism that causes the raised IOP is crucial as the management of glaucoma can differ accordingly. Intravitreal (IVT) injections in the form of IVT steroids or anti-vascular endothelial growth factor (anti-VEGF) injections can also cause a significant rise in the IOP and effect, especially the glaucomatous eyes, which are already predisposed. Not just the overlapping clinical features make the diagnosis confusing but also associated scarring of the conjunctiva, and the presence of episcleral hardware in some cases due to scleral buckle make the surgical management of glaucoma in these eyes very challenging. In this review, we describe in detail the various mechanisms causing secondary glaucoma post vitreoretinal surgeries with a focus on how to distinguish between them. We also discuss the possible consequences of anti-VEGF agents on IOP, various surgical challenges, and modifications with newer surgical options in the management of this refractory glaucoma.
Early experience with low-pass filtered images facilitates visual category learning in a neural network model

Humans are born with very low contrast sensitivity, meaning that inputs to the infant visual system are both blurry and low contrast. Is this solely a byproduct of maturational processes or is there a functional advantage for beginning life with poor visual acuity? We addressed the impact of poor vision during early learning by exploring whether reduced visual acuity facilitated the acquisition of basic-level categories in a convolutional neural network model (CNN), as well as whether any such benefit transferred to subordinate-level category learning. Using the ecoset dataset to simulate basic-level category learning, we manipulated model training curricula along three dimensions: presence of blurred inputs early in training, rate of blur reduction over time, and grayscale versus color inputs. First, a training regime where blur was initially high and was gradually reduced over time—as in human development—improved basic-level categorization performance in a CNN relative to a regime in which non-blurred inputs were used throughout training. Second, when basic-level models were fine-tuned on a task including both basic-level and subordinate-level categories (using the ImageNet dataset), models initially trained with blurred inputs showed a greater performance benefit as compared to models trained exclusively on non-blurred inputs, suggesting that the benefit of blurring generalized from basic-level to subordinate-level categorization. Third, analogous to the low sensitivity to color that infants experience during the first 4–6 months of development, these advantages were observed only when grayscale images were used as inputs. We conclude that poor visual acuity in human newborns may confer functional advantages, including, as demonstrated here, more rapid and accurate acquisition of visual object categories at multiple levels.
Nonlinear Dielectric Response in the Vicinity of the “Inverse Melting” Point of Rochelle Salt

The linear, and the second- and third-order nonlinear susceptibilities were measured in order to verify conclusions stemming from the theory of the ferroelectric effect in Rochelle salt proposed by Mitsui (Phys. Rev. 111, 1259 (1958)) and concerning the behavior of the susceptibilities in the vicinity of the phase transition points. Particular attention is focused on the nontrivial “inverse melting” point. Our experimental results comply with the theoretical predictions.
Atypical chronic myeloid leukemia and myelodysplastic/myeloproliferative neoplasm, not otherwise specified: 2023 update on diagnosis, risk stratification, and management

Atypical chronic myeloid leukemia (aCML) and myelodysplastic/myeloproliferative (MDS/MPN) neoplasms, not otherwise specified (NOS), are MDS/MPN overlap neoplasms characterized by leukocytosis, in the absence of monocytosis and eosinophilia, with <20% blasts in the blood and bone marrow.
Role of Chromogranin A in the Diagnosis and Follow-up of Neuroendocrine Tumors

Objective The aim of this study was to assess the utility of serum chromogranin A (CgA) along the clinical pathway of patients with neuroendocrine tumors (NETs). Methods A retrospective review of medical records was conducted of patients with NET who had at least 1 measurement of CgA between January 2015 and April 2021 at a large metropolitan Australian hospital. Chromogranin A was classified as increased or decreased if there was at least a 25% change in sequential levels and was compared with disease response by anatomical or functional imaging if within 6 weeks (considered concurrent). Results Of 102 patients with NETs, 67 had at least 1 serum CgA level: 50 had been ordered during diagnostic workup, of which 33 were elevated (sensitivity: 66%; 95% confidence interval, 51%–79%). Of 129 CgA results concurrent with imaging, the sensitivity for detecting progressive disease was 28% (95% confidence interval, 15%–44%). Conclusions Our findings support previous concerns that CgA adds little value in clinical decision-making.
1550 nm VCSEL-based 0.48 Tb/s transmission scheme employing PAM-4 and WDM for active optical cables

With this paper we investigate the system-level performance of VCSELs, parameterized with true experimental LI-VI data and dynamic characteristics of state-of-the-art VCSELs with 3 dB modulation bandwidth at 15 GHz, and propose their deployment as high-speed multi-level optical sources in a mid-range active optical cable (AOC) model for performance prediction of a rack-to-rack interconnection. The AOC architecture combines a 6-element 1550 nm VCSEL array, each directly modulated with 40 Gbaud PAM-4 data, with a wavelength division multiplexer (WDM), in order to implement a parallel link with aggregate traffic of 0.48 Tb/s. Transmission reach exceeded 300 m by deploying a two-tap feed forward equalizer filter at the electrical VCSEL driver. Bit Error Rate (BER) measurements and analysis were carried out in MATLAB. In practice, the thermal behavior and basic operational characteristics of the VCSELs fabricated by the Technische Universität München (TUM) were used to study the thermal performance and operational range of the complete AOC model. The VCSELs were initially operated at 20°C and BER measurements showed power penalties of 1.7 dB and 3.5 dB at 300 m and 500 m of transmission distance respectively for all 6 data channels. System performance was also investigated for elevated operating temperatures of the VCSEL module and the additional system degradation and BER penalties introduced by operation at 50°C and 65°C were also investigated for transmission distances of 300 m and 500 m.
Genesis of a functional astrocyte syncytium in the developing mouse hippocampus

Astrocytes are increasingly shown to operate as an isopotential syncytium in brain function. Protoplasmic astrocytes acquire this ability to functionally go beyond the single‐cell level by evolving into a spongiform morphology, cytoplasmically connecting into a syncytium, and expressing a high density of K+ conductance. However, none of these cellular/functional features exist in neonatal newborn astrocytes, which imposes a basic question of when a functional syncytium evolves in the developing brain. Our results show that the spongiform morphology of individual astrocytes and their spatial organization all reach stationary levels by postnatal day (P) 15 in the hippocampal CA1 region. Functionally, astrocytes begin to uniformly express a mature level of passive K+ conductance by P11. We next used syncytial isopotentiality measurement to monitor the maturation of the astrocyte syncytium. In uncoupled P1 astrocytes, the substitution of endogenous K+ by a Na+‐electrode solution ([Na+]p) resulted in the total elimination of the physiological membrane potential (VM), and outward K+ conductance as predicted by the Goldman‐Hodgkin‐Katz (GHK) equation. As more astrocytes are coupled to each other through gap junctions during development, the [Na+]p‐induced loss of physiological VM and the outward K+ conductance is progressively compensated by the neighboring astrocytes. By P15, a stably established syncytial isopotentiality (−73 mV), and a fully compensated outward K+ conductance appeared in all [Na+]p‐recorded astrocytes. Thus, in view of the developmental timeframe wherein a singular syncytium is anatomically and functionally established for intra‐syncytium K+ equilibration, an astrocyte syncytium becomes fully operational at P15 in the mouse hippocampus.
A simple investigation of the Granger-causality test in integrated-cointegrated VAR systems

The size and power of various generalization tests for the Granger-causality in integrated-cointegrated VAR systems are considered. By using Monte Carlo methods, properties of eight versions of the test are studied in two different forms, the standard form and the modified form by Dolado & Lütkepohl (1996) in a study confined to properties of the Wald test only. In their study as well as in ours, both the standard and the modified Wald tests are shown to perform badly especially in small samples. We find, however, that the corrected LR tests exhibit correct size even in small samples. The power of the test is higher when the true VAR(2) model is estimated, and the modified test loses information by estimating the extra coefficients. The same is true when considering the power results in the VAR(3) model, and the power of the tests is somewhat lower than those in the VAR(2).
Whole-genome characterization of myoepithelial carcinomas of the soft tissue

Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors. Both patients developed metastatic disease, and P2 died of disease. P1 tumor showed a rhabdoid cytomorphology and a complete loss of INI1 (SMARCB1) expression, associated with a homozygous SMARCB1 deletion. The tumor from P2 showed a clear cell/small cell morphology, retained INI1 expression and strong S100 positivity. By WES and WGS, tumors from both patients displayed low tumor mutation burdens, and no targetable alterations in cancer genes were detected. P2's tumor harbored an EWSR1::KLF15 rearrangement, whereas the tumor from P1 showed a novel ASCC2::GGNBP2 fusion. WGS evidenced a complex genomic event involving mainly Chromosomes 17 and 22 in the tumor from P1, which was consistent with chromoplexy. These findings are consistent with previous reports of EWSR1 rearrangements (50% of cases) in MECs and provide a genetic basis for the loss of SMARCB1 protein expression observed through immunohistochemistry in 10% of 40% of MEC cases. The lack of additional driver mutations in these tumors supports the hypothesis that these alterations are the key molecular events in MEC evolution. Furthermore, the presence of complex structural variant patterns, invisible to WES, highlights the novel biological insights that can be gained through the application of WGS to rare cancers.
Extracellular vesicles and insulin‐mediated vascular function in metabolic syndrome

Metabolic Syndrome (MetS) raises cardiovascular disease risk. Extracellular vesicles (EVs) have emerged as important mediators of insulin sensitivity, although few studies on vascular function exist in humans. We determined the effect of insulin on EVs in relation to vascular function. Adults with MetS (n = 51, n = 9 M, 54.8 ± 1.0 years, 36.4 ± 0.7 kg/m2, ATPIII: 3.5 ± 0.1 a.u., VO2max: 22.1 ± 0.6 ml/kg/min) were enrolled in this cross‐sectional study. Peripheral insulin sensitivity (M‐value) was determined during a euglycemic clamp (40 mU/m2/min, 90 mg/dl), and blood was collected for EVs (CD105+, CD45+, CD41+, TX+, and CD31+; spectral flow cytometry), inflammation, insulin, and substrates. Central hemodynamics (applanation tonometry) was determined at 0 and 120 min via aortic waveforms. Pressure myography was used to assess insulin‐induced arterial vasodilation from mouse 3rd order mesenteric arteries (100–200 μm in diameter) at 0.2, 2 and 20 nM of insulin with EVs from healthy and MetS adults. Adults with MetS had low peripheral insulin sensitivity (2.6 ± 0.2 mg/kg/min) and high HOMA‐IR (4.7 ± 0.4 a.u.) plus Adipose‐IR (13.0 ± 1.3 a.u.). Insulin decreased total/particle counts (p < 0.001), CD45+ EVs (p = 0.002), AIx75 (p = 0.005) and Pb (p = 0.04), FFA (p < 0.001), total adiponectin (p = 0.006), ICAM (p = 0.002), and VCAM (p = 0.03). Higher M‐value related to lower fasted total EVs (r = −0.40, p = 0.004) while higher Adipose‐IR associated with higher fasted EVs (r = 0.42, p = 0.004) independent of VAT. Fasting CD105+ and CD45+ derived total EVs correlated with fasting AIx75 (r = 0.29, p < 0.05) and Pb (r = 0.30, p < 0.05). EVs from MetS participants blunted insulin‐induced vasodilation in mesenteric arteries compared with increases from healthy controls across insulin doses (all p < 0.005). These data highlight EVs as potentially novel mediators of vascular insulin sensitivity and disease risk.
Toxic effect of carpet dust on the biochemical indices and histological structure of the lung in rats: the potential role of cytochrome P450 2E1 and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways

Abstract Background: Carpet dust exposure in the carpet industry causes various respiratory hazards that lead to permanent loss of lung function. This study investigated the potentially toxic effects of knotted and tufted carpet dust on rat lungs and the possible involvement of cytochrome P450 2E1 (CYP2E1) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathways in the induced toxicity, as well as histological changes in the lung induced by carpet dust. Methods: This study divided 48 adult rats into six groups: group I was the control group, group II (vehicle group) received phosphate buffer saline (50 µL/rat), groups III and IV received knotted dust (2.5 and 5 mg/kg, respectively), and groups V and VI received tufted dust (2.5 and 5 mg/kg, respectively). All treatments were intranasally administered once a day for 7 days. Results: Both dust types significantly decreased the lung content of GSH compared with the control. Significantly elevated malondialdehyde (MDA) and nitric oxide (NO) lung contents were observed with an increased CYP2E1, interleukin (IL)-6, nuclear factor kappa B (NF-κβ), and ERK/MAPK. The histological lung structure was moderately affected with a moderately increased number of CD68-positive macrophages in the lung parenchyma of knotted dust-exposed rats, whereas tufted dust exposure severely affected the lung tissue with significantly increased CD68-positive macrophages. Conclusions: Carpet dust exposure could induce oxidative stress and inflammatory response in the lung tissue via induction of CYP2E1 that stimulates ERK/MAPK signalling pathway proteins, resulting in elevated MDA, NO and IL-6 levels in the lung tissue with suppressed GSH content. Tufted dust could possess a more toxic response than knotted ones.
Estimation procedures for Maxwell distribution under type-I progressive hybrid censoring scheme

The Maxwell (or Maxwell–Boltzmann) distribution was invented to solve the problems relating to physics and chemistry. It has also proved its strength of analysing the lifetime data. For this distribution, we consider point and interval estimation procedures in the presence of type-I progressively hybrid censored data. We obtain maximum likelihood estimator of the parameter and provide asymptotic and bootstrap confidence intervals of it. The Bayes estimates and Bayesian credible and highest posterior density intervals are obtained using inverted gamma prior. The expression of the expected number of failures in life testing experiment is also derived. The results are illustrated through the simulation study and analysis of a real data set is presented.
High‐dose insulin should be used before vasopressors/inotropes in calcium‐channel blocker toxicity

High‐dose insulin (HDI) therapy with adapted glucose supplementation to maintain euglycaemia has been suggested to treat calcium‐channel blocker (CCB) poisonings. Its underlying mechanisms of action are now well documented. We present a narrative review of the published experimental studies, case reports and experts' opinions to support the effectiveness and safety of HDI in the treatment of CCB poisoning. Our review strongly encourages the use of HDI as first‐line therapy in CCB‐poisoned patients in the presence of cardiovascular compromise, especially if cardiac function impairment has been diagnosed, before, but without delaying, the administration of vasopressors/inotropic drugs.
Regional shape alteration of left thalamus associated with late chronotype in young adults

ABSTRACT Chronotype reflects individual differences in circadian rhythms and influences individual psychology and behavior. Previous studies found altered subcortical structures are closely related to individual chronotypes. However, these studies have been conducted mainly using voxel-based morphometry and traditional volume measurement methods with certain limitations. This study aimed to investigate subcortical aberrant volume and shape patterns in late chronotypes (LC) young adults compared to early chronotypes (EC) young adults. Magnetic resonance imaging (MRI) scanning and chronotype assessment were performed once for all participants, including 49 LC young adults and 49 matched EC young adults. The morningness and eveningness preferences were assessed using the Chronotype Questionnaire. A vertex-wise shape analysis was conducted to analyze structural MRI data. There were no significant differences in brain tissue volume and subcortical structural volume between groups. LC young adults showed significant regional shape atrophy in the left ventral posterior thalamus compared to EC individuals. A significant correlation was found between the regional shape atrophy of left ventral posterior thalamus and the score of Chronotype Questionnaire in LC young adults. Regional shape alteration of left thalamus was closely related to the chronotype, and LC may be a potential risk factor for sleep-related behavioral and mental problems in young adults. However, the predominantly female sample and the failure to investigate the effect of chronotype on the subcortical structure-function network are limitations of this study. Further prospective studies are needed to investigate the temporal characteristics of thalamic shape changes and consequent behavioral and psychiatric problems in adults with LC.