Miracle-dz/UniFAR-FTUs huggingface dataset:
A multidimensional analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in the bone marrow of pediatric acute myeloid leukemia

Pediatric cancers are characterized by a relatively low mutational burden and therefore, children are thought to be poor candidates for T cell-engaging immunotherapies. Here, we performed a multidimensional characterization of the tumor immune microenvironment in newly diagnosed children with acute myeloid leukemia (AML) and non-leukemic controls. We identified a subset of pediatric AML patients with remarkably high levels of T cell infiltration and a relatively low abundance of anti-inflammatory macrophages. In addition, we detected large T cell networks that colocalized with B cells in the bone marrow of immune-infiltrated samples, resembling tertiary lymphoid structures as described in solid tumors. Using spatial transcriptomics, we dissected the composition of these structures and revealed unique hotspots of anti-tumor immunity. This work raises the possibility that a subset of pediatric AML patients may benefit from T cell-engaging immunotherapies and encourages further study of these lymphoid structures in the context of immunotherapy in AML.
ON MAXIMAL FUNCTION AND FRACTIONAL INTEGRAL, ASSOCIATED WITH THE BESSEL DIFFERENTIAL OPERATOR

In this paper we consider the generalized shift operator, generated by Bessel differ- ential operator B, by means of which maximal functions (B-maximal functions) and frac- tional integrals (B-fractional integrals) are investigated. The Lp(B)-boundedness result for the B-maximal function and (Lp(B),Lq(B))-boundedness result for the B-fractional integral are obtained.
Measurements of the aero-acoustic properties of the vocal folds and vocal tract during phonation into controlled acoustic loads

The aeroacoustic properties of the vocal folds and tract are difficult to measure directly. Here, they were measured using broad- and narrow-band excitation at the mouth during phonation into various acoustic loads, including a non-resonant load provided by an acoustically infinite waveguide with cross section comparable with that of the tract. The tract is treated as a duct terminated by the larynx. Mechanical properties of the walls and terminations were determined using a microphone array (Dickens et al. 2007). The vocal fold response was monitored with an electroglottograph and wall motion was measured electromechanically. The impedance spectra show negative resistance bands at frequencies near those of phonation, consistent with regeneration at the folds. The walls give inertances consistent with thicknesses of order 1 cm and compliances consistent with distributed stiffnesses of about 100 kN/m3 (Hanna et al. 2012). The duct resonant properties are consistent with losses several times higher than the.
Meta-analysis of the Effect of Medication on Falls in the Elderly

The objective of this study was to carry out a systematic quality review and meta- analysis of all literature published in years 1981-1997 which studied the effect of drugs in the elderly and which had analyzable data on major groups of drugs. The sources of data were reports of surveys, case-control, prospective and retrospective studies, published in English. Identified studies were assessed for (i) ecological, (ii) methodological and (iii) statistical features. The drugs were classified into four main groups, namely (a) antidepressants (b) antipsychotics, (c) diuretics, and (d) hypnosedatives. Increasing risk of falls were related in order to diuretics, hypnosedatives, antidepressants and antipsychotics: the odd ratios with antipsychotics was 42% higher than with diuretics. The conclusion was that, clinically, the following classes of drugs show a significant positive relationship with falls: antipsychotics, antidepressants and hypnosedatives. The relationship with diuretics and falls is less clear; at best, it has a weak relationship with falls.
RNA Polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation

The controlled release of promoter-proximal paused RNA polymerase II (Pol II) into productive elongation is a major step in gene regulation. However, functional analysis of Pol II pausing is difficult because factors that regulate pause release are almost all essential. In this study, we identified heterozygous loss-of-function mutations in SUPT5H, which encodes SPT5, in individuals with beta-thalassemia unlinked to HBB mutations. During erythropoiesis in healthy human cells, cell cycle genes were highly paused at the transition from progenitors to precursors. When the pathogenic mutations were recapitulated by SUPT5H editing, Pol II pause release was globally disrupted, and the transition from progenitors to precursors was delayed, marked by a transient lag in erythroid-specific gene expression and cell cycle kinetics. Despite this delay, cells terminally differentiate, and cell cycle phase distributions normalize. Therefore, hindering pause release perturbs proliferation and differentiation dynamics at a key transition during erythropoiesis, revealing a role for Pol II pausing in the temporal coordination between the cell cycle and differentiation.
Universally torsionless and trace modules

We study, over an arbitrary ring R, a class of right modules intermediate between the projective and the flat content modules. Over the ring of rational integers these modules are the locally free abelian groups. Over any commutative ring they are the modules which remain torsionless under all scalar extensions. They each possess a certain separability property exactly when R is left semihereditary. We define M to be universally torsionless if the natural map M 0 A Hom(M*, A) is monic for all left modules A. We give various equivalent conditions for M to be universally torsionless, one of which is that M is a trace module, i.e. that x E M.M*(x) for all x E M. We show the countably generated such modules are projective. Chase showed that rings over which products of projective or flat modules are also, respectively, projective or flat have other interesting properties and that they are characterized by certain left ideal theoretical conditions. We show similar results hold when the trace or content properties are preserved by products.
Visual impairment and blindness due to retinitis pigmentosa in India: 15-year follow-up of the Andhra Pradesh Eye Disease Study cohort

Purpose: To assess the incidence, visual impairment, and blindness due to retinitis pigmentosa (RP) in a rural southern Indian cohort. Methods: This is a population-based longitudinal cohort study of participants with RP from the Andhra Pradesh Eye Disease Study (APEDS) cohorts I and III, respectively. The study included participants with RP of APEDS I who were followed until APEDS III. Their demographic data along with ocular features, fundus photographs, and visual fields (Humphrey) were collected. Descriptive statistics using mean ± standard deviation with interquartile range (IQR) were calculated. The main outcome measures were RP incidence, visual impairment, and blindness as per the World Health Organization (WHO) definitions. Results: At baseline (APEDS I), 7771 participants residing in three rural areas were examined. There were nine participants with RP with a mean age at baseline of 47.33 ± 10.89 years (IQR: 39–55). There was a male preponderance (6:3), and the mean best-corrected visual acuity (BCVA) of 18 eyes from nine participants with RP was 1.2 ± 0.72 logarithm of minimum angle of resolution (logMAR; IQR: 0.7–1.6). Over a mean follow-up duration of 15 years, 5395/7771 (69.4%) were re-examined, which included seven RP participants from APEDS 1. Additionally, two new participants with RP were identified; so, the overall incidence was 370/ million in 15 years (24.7/million per year). The mean BCVA of 14 eyes of seven participants with RP who were re-examined in APEDS III was 2.17 ± 0.56 logMAR (IQR: 1.8–2.6), and five of these seven participants with RP developed incident blindness during the follow-up period. Conclusion: RP is a prevalent disease in southern India that warrants appropriate strategies to prevent this condition.
Long-term Prognostic Impact of Metachronous Rectal Cancer in Patients With Familial Adenomatous Polyposis: A Single-center Retrospective Study.

AIM To evaluate the risk factors and long-term prognosis of metachronous rectal cancer in the remnant rectum of patients with familial adenomatous polyposis (FAP). PATIENTS AND METHODS Sixty-five patients (49 families) who underwent prophylactic surgery, including bowel resection, for FAP between January 1976 and August 2022 at Hamamatsu University Hospital were included and divided into two groups based on the presence of metachronous rectal cancer. Risk factors for metachronous rectal cancer development were analysed in cases treated with total colectomy with ileorectal anastomosis (IRA) and stapled total proctocolectomy with ileal pouch anal anastomosis (IPAA) (IRA, n=22; stapled IPAA n=20; total, n=42). RESULTS The median surveillance period was 169 months. Twelve patients developed metachronous rectal cancer (IRA, n=5; stapled IPAA, n=7), of which six with advanced cancer died. Patients who temporarily dropped out of surveillance were significantly more likely to have metachronous rectal cancer (metachronous vs. non-metachronous rectal cancer: 33.3% vs. 1.9%, p<0.01). The mean duration of surveillance suspension was 87.8 months. Cox regression analysis revealed that temporary surveillance drop-out independently affected the risk (p=0.04). The overall survival associated with metachronous rectal cancer was 83.3% at 1 year and 41.7% at 5 years. Overall survival was significantly worse in advanced cancer than in early cancer cases (p<0.01). CONCLUSION Temporary drop-out from surveillance was a risk factor for metachronous rectal cancer development, and advanced cancer had a poor prognosis. Continuous surveillance of patients with FAP, without temporary drop-out, is strongly recommended.
Muscle shape changes in Parkinson's disease impair function during rapid contractions

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized, among the others, by muscle weakness. PD patients reach lower values of peak torque during maximal voluntary contractions but also slower rates of torque development (RTD) during explosive contractions. The aim of this study was to better understand how an impairment in structural/mechanical (peripheral) factors could explain the difficulty of PD patients to raise torque rapidly.
Counterstreaming magnetized plasmas with kappa distributions – II. Perpendicular wave propagation

The analysis of the stability and the dispersion properties of a counterstreaming plasma system with kappa distributions are extended here with the investigation of perpendicular instabilities. Purely growing filamentation (Weibel-like) modes propagating perpendicular to the background magnetic field can be excited in streaming plasmas with or without an excess of parallel temperature. In this case, however, the effect of suprathermal tails of kappa populations is opposite to that obtained for parallel waves: the growth rates can be higher and the instability faster than for Maxwellian plasmas. The unstable wavenumbers also extend to a markedly larger broadband making this instability more likely to occur in space plasmas with anisotropic distributions of kappa-type. The filamentation instability of counterstreaming magnetized plasmas could provide a plausible mechanism for the origin of two-dimensional transverse magnetic fluctuations detected at different altitudes in the solar wind.
Evaluation of FAS and eNOS expression in COVID-19 placenta: histopathological and immunohistochemical study.

OBJECTIVE In this study, the effects of cell adhesion, inflammation and apoptotic changes on fetal development in cases of COVID-19 placenta were investigated. PATIENTS AND METHODS Placenta tissue samples from 15 COVID-19 and 15 healthy pregnant women were taken after delivery. Tissue samples were fixed in formaldehyde, then blocked with paraffin wax and 4-6 µm thick sections were cut and stained with Harris Hematoxylene-Eosin. Sections were stained with FAS antibody and endothelial nitric oxide synthase (eNOS) antibody. RESULTS In COVID-19 placenta section, deterioration of the root villus basement membrane structure in the maternal region, decidua cells and syncytial cell degeneration, significant increase in fibrinoid tissue, endothelial dysfunction in free villi and intense congestion in blood vessels, increase in syncytial nodes and bridges were observed. In terms of inflammation, eNOS expression was increased in Hoffbauer cells, dilated blood vessels endothelial cells in chorionic villi, and surrounding inflammatory cells. Positive FAS expression was also increased in the basement membranes of root and free villi, syncytial bridge and nodes, and endothelial cells. CONCLUSIONS The effect of COVID-19 caused an increase in eNOS activity and acceleration of the proapoptotic process and the deterioration of cell-membrane adhesion.
Epidemiology of secondary infection after snakebites in center-west Brazil

Background Snakebites represent a significant health problem in tropical countries, with an annual incidence of 2.7 million cases worldwide. The incidence of secondary infections after snake bites is also high and is usually caused by bacteria from the oral cavity of snakes. Morganella morganii has been identified as an important cause of infections and has been guiding antibiotic therapy in several regions of Brazil and the world. Methodology/Principal findings We performed a retrospective cross-sectional evaluation of snakebites in hospitalized patients between January 2018 and November 2019 and selected those with secondary infection in their medical records. During the period, 326 cases of snakebites were treated, and 155 (47.5%) of them eventually had secondary infections. However, only seven patients underwent culture of soft tissue fragments, in which three cases were negative culture results, while Aeromonas hydrophila was identified in four cases. Of these, 75% were resistant to ampicillin/sulbactam, 50% had intermediate sensitivity to imipenem, and 25% had intermediate sensitivity to piperacillin/tazobactam. Trimethoprim/sulfamethoxazole (TMP-SMX) was not tested on any strain. Of the 155 cases that progressed to secondary infections, 48.4% (75) were empirically treated with amoxicillin/clavulanate, 41.9% (65) with TMP-SMX, and 32 (22%) of these 144 cases required a change to a second regimen, and 10 of these 32 patients required a third therapeutic regimen. Conclusion Wild animals act as reservoirs of resistant bacteria because their oral cavity favors biofilm formation, which explains the finding of A. hydrophila with a reduced sensitivity profile in this study. This fact is essential for the appropriate choice of empirical antibiotic therapy.
Redesign of explicit and implicit discrete time model reference adaptive control schemes

The design of MRAC for achieving independent tracking and regulation objectives with a unique equilibrium point in the controller parameter space is presented. The corresponding schemes can use either an explicit reference model or an implicit reference model. The design is done from a stability point of view by extending an appropriate control configuration used for the case of known plant parameters. The result of the design is a simple control scheme using a linear constant feedforward controller and a non-linear feedback controller. The stability of the system and boundness of various variables do not require any positivity condition. The performances of the control structure in tracking and regulation are evaluated by simulations.
STING directly recruits WIPI2 for autophagosome formation during STING‐induced autophagy

The cGAS‐STING pathway plays an important role in host defense by sensing pathogen DNA, inducing type I IFNs, and initiating autophagy. However, the molecular mechanism of autophagosome formation in cGAS‐STING pathway‐induced autophagy is still unclear. Here, we report that STING directly interacts with WIPI2, which is the key protein for LC3 lipidation in autophagy. Binding to WIPI2 is necessary for STING‐induced autophagosome formation but does not affect STING activation and intracellular trafficking. In addition, the specific interaction between STING and the PI3P‐binding motif of WIPI2 leads to the competition of WIPI2 binding between STING and PI3P, and mutual inhibition between STING‐induced autophagy and canonical PI3P‐dependent autophagy. Furthermore, we show that the STING‐WIPI2 interaction is required for the clearance of cytoplasmic DNA and the attenuation of cGAS‐STING signaling. Thus, the direct interaction between STING and WIPI2 enables STING to bypass the canonical upstream machinery to induce LC3 lipidation and autophagosome formation.
Survival and predictors of breast cancer mortality in South Ethiopia: A retrospective cohort study

Background Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in over 100 countries. In March 2021, the World Health Organization called on the global community to decrease mortality by 2.5% per year. Despite the high burden of the disease, the survival status and the predictors for mortality are not yet fully determined in many countries in Sub-Saharan Africa, including Ethiopia. Here, we report the survival status and predictors of mortality among breast cancer patients in South Ethiopia as crucial baseline data to be used for the design and monitoring of interventions to improve early detection, diagnosis, and treatment capacity. Methods A hospital-based retrospective cohort study was conducted among 302 female breast cancer patients diagnosed from 2013 to 2018 by reviewing their medical records and telephone interviews. The median survival time was estimated using the Kaplan-Meier survival analysis method. A log-rank test was used to compare the observed differences in survival time among different groups. The Cox proportional hazards regression model was used to identify predictors of mortality. Results are presented using the crude and adjusted as hazard ratios along with their corresponding 95% confidence intervals. Sensitivity analysis was performed with the assumption that loss to follow-up patients might die 3 months after the last hospital visit. Results The study participants were followed for a total of 4,685.62 person-months. The median survival time was 50.81 months, which declined to 30.57 months in the worst-case analysis. About 83.4% of patients had advanced-stage disease at presentation. The overall survival probability of patients at two and three years was 73.2% and 63.0% respectively. Independent predictors of mortality were: patients residing in rural areas (adjusted hazard ratio = 2.71, 95% CI: 1.44, 5.09), travel time to a health facility ≥7 hours (adjusted hazard ratio = 3.42, 95% CI: 1.05, 11.10), those who presented within 7–23 months after the onset of symptoms (adjusted hazard ratio = 2.63, 95% CI: 1.22, 5.64), those who presented more than 23 months after the onset of symptoms (adjusted hazard ratio = 2.37, 95% CI: 1.00, 5.59), advanced stage at presentation (adjusted hazard ratio = 3.01, 95% CI: 1.05, 8.59), and patients who never received chemotherapy (adjusted hazard ratio = 6.69, 95% CI: 2.20, 20.30). Conclusion Beyond three years after diagnosis, patients from southern Ethiopia had a survival rate of less than 60% despite treatment at a tertiary health facility. It is imperative to improve the early detection, diagnosis, and treatment capacities for breast cancer patients to prevent premature death in these women.
Optical cavity squeezing of multiwave mixing via dark states

We theoretically demonstrate the influence of dark states on single-mode and two-mode optical squeezing in a four-level atomic–cavity coupling system through fifth- and third-order cascade nonlinearity. We first show the cone emissions of self-diffraction and phase-conjugate spontaneous parametric (SP) four-wave mixing processes. Then, we inject a coherent or Einstein–Podolsky–Rosen field into the SP-MWM channels to investigate the corresponding squeezing. The investigations have potential applications in quantum information processing.
Determining the Delamanid Pharmacokinetics/Pharmacodynamics Susceptibility Breakpoint Using Monte Carlo Experiments

Antimicrobial susceptibility testing, based on clinical breakpoints that incorporate pharmacokinetics/pharmacodynamics (PK/PD) and clinical outcomes, is becoming a new standard in guiding individual patient therapy as well as for drug resistance surveillance. However, for most antituberculosis drugs, breakpoints are instead defined by the epidemiological cutoff values of the MIC of phenotypically wild-type strains irrespective of PK/PD or dose. ABSTRACT Antimicrobial susceptibility testing, based on clinical breakpoints that incorporate pharmacokinetics/pharmacodynamics (PK/PD) and clinical outcomes, is becoming a new standard in guiding individual patient therapy as well as for drug resistance surveillance. However, for most antituberculosis drugs, breakpoints are instead defined by the epidemiological cutoff values of the MIC of phenotypically wild-type strains irrespective of PK/PD or dose. In this study, we determined the PK/PD breakpoint for delamanid by estimating the probability of target attainment for the approved dose administered at 100 mg twice daily using Monte Carlo experiments. We used the PK/PD targets (0- to 24-h area under the concentration-time curve to MIC) identified in a murine chronic tuberculosis model, hollow fiber system model of tuberculosis, early bactericidal activity studies of patients with drug-susceptible tuberculosis, and population pharmacokinetics in patients with tuberculosis. At the MIC of 0.016 mg/L, determined using Middlebrook 7H11 agar, the probability of target attainment was 100% in the 10,000 simulated subjects. The probability of target attainment fell to 25%, 40%, and 68% for PK/PD targets derived from the mouse model, the hollow fiber system model of tuberculosis, and patients, respectively, at the MIC of 0.031 mg/L. This indicates that an MIC of 0.016 mg/L is the delamanid PK/PD breakpoint for delamanid at 100 mg twice daily. Our study demonstrated that it is feasible to use PK/PD approaches to define a breakpoint for an antituberculosis drug.
Anisotropy effects in homogenized magnetodielectric photonic crystals

Exact analytic formulas for calculating the effective permittivity, permeability, and crossed magnetoelectric tensors for photonic crystals in the long-wavelength limit are presented. The formulas are valid for arbitrary Bravais lattice and form of inclusions, which can be dielectric, magnetic, or chiral. We have applied them to study the optical anisotropy of homogenized magnetodielectric three-dimensional photonic crystals, which can be induced by the type of Bravais lattice or the form of the inclusion even in the case when the photonic crystal is composed of isotropic materials. It is established that the electromagnetic modes, propagating in such anisotropic magnetodielectric metamaterials, are extraordinary, unlike the modes in homogenized nonmagnetic dielectric composites, where at least one mode is ordinary.