Miracle-dz/UniFAR-FTUs huggingface dataset:
Monkeypox: a review of epidemiological modelling studies and how modelling has led to mechanistic insight

Abstract Human monkeypox (mpox) virus is a viral zoonosis that belongs to the Orthopoxvirus genus of the Poxviridae family, which presents with similar symptoms as those seen in human smallpox patients. Mpox is an increasing concern globally, with over 80,000 cases in non-endemic countries as of December 2022. In this review, we provide a brief history and ecology of mpox, its basic virology, and the key differences in mpox viral fitness traits before and after 2022. We summarize and critique current knowledge from epidemiological mathematical models, within-host models, and between-host transmission models using the One Health approach, where we distinguish between models that focus on immunity from vaccination, geography, climatic variables, as well as animal models. We report various epidemiological parameters, such as the reproduction number, R 0, in a condensed format to facilitate comparison between studies. We focus on how mathematical modelling studies have led to novel mechanistic insight into mpox transmission and pathogenesis. As mpox is predicted to lead to further infection peaks in many historically non-endemic countries, mathematical modelling studies of mpox can provide rapid actionable insights into viral dynamics to guide public health measures and mitigation strategies.
The Climatology of Synoptic-Scale Ascent over Western North America: A Perspective on Storm Tracks

AbstractThe position and variability of storm tracks across western North America are examined during the October–April cool seasons spanning 1989–2010. The location and intensity of storms are represented by strong synoptic-scale ascent, which is diagnosed by the alternative balance omega equation applied to ECMWF Re-Analysis Interim data. This dynamically filtered method removes poorly resolved updrafts arising from subsynoptic-scale phenomena such as convection and mountain waves. The resulting vertical motions are illustrated for the case of a strong storm traversing the western United States.Summary statistics of synoptic-scale ascent are compiled over months, seasons, and the entire 21-yr period. Locations exhibiting high mean values of ascent are deemed to represent storm tracks. The climatological-mean storm track exhibits a sinusoidal shape across the eastern Pacific and western North America. The composite evolution of strong storms moving along specific segments of the storm track show regional.
Solving racial/ethnic disparities associated with Medicare Part D Star Ratings

Abstract Objective Medicare Part D Star Ratings are instrumental in shaping healthcare quality improvement efforts. However, the calculation metrics for medication performance measures for this program have been associated with racial/ethnic disparities. In this study, we aimed to explore whether an alternative program, named Star Plus by us that included all medication performance measures developed by Pharmacy Quality Alliance and applicable to our study population, would reduce such disparities among Medicare beneficiaries with diabetes, hypertension, and/or hyperlipidemia. Method We conducted an analysis of a 10% random sample of Medicare A/B/D claims linked to the Area Health Resources File. Multivariate logistic regressions with minority dummy variables were used to examine racial/ethnic disparities in measure calculations of Star Ratings and Star Plus, respectively. Results Adjusted results indicated that relative to non-Hispanic Whites (Whites), racial/ethnic minorities had significantly lower odds of being included in the Star Ratings measure calculations: the odds ratios (ORs) for Blacks, Hispanics, Asians, and Others were 0.68 (95% confidence interval [CI] = 0.66–0.71), 0.73 (CI = 0.69–0.78), 0.88 (CI = 0.82–0.93), and 0.92 (CI = 0.88–0.97), respectively. In contrast, every beneficiary in the sample was included in Star Plus. Further, racial/ethnic minorities had significantly higher increase in the odds of being included in measure calculation in Star Plus than Star Ratings. The ORs for Blacks, Hispanics, Asians, and Others were 1.47 (CI = 1.41–1.52), 1.37 (CI = 1.29–1.45), 1.14 (CI = 1.07–1.22), and 1.09 (CI = 1.03–1.14), respectively. Conclusions Our study demonstrated that racial/ethnic disparities may be eliminated by including additional medication performance measures to Star Ratings.
Technical advancement and practical considerations of LC-MS/MS-based methods for host cell protein identification and quantitation to support process development

ABSTRACT Host cell proteins (HCPs) are process-related impurities derived from the manufacturing of recombinant biotherapeutics. Residual HCP in drug products, ranging from 1 to 100 ppm (ng HCP/mg product) or even below sub-ppm level, may affect product quality, stability, efficacy, or safety. Therefore, removal of HCPs to appropriate levels is critical for the bioprocess development of biotherapeutics. Liquid chromatography-mass spectrometry (LC-MS) analysis has become an important tool to identify, quantify, and monitor the clearance of individual HCPs. This review covers the technical advancement of sample preparation strategies, new LC-MS-based techniques, and data analysis approaches to robustly and sensitively measure HCPs while overcoming the high dynamic range analytical challenges. We also discuss our strategy for LC-MS-based HCP workflows to enable fast support of process development throughout the product life cycle, and provide insights into developing specific analytical strategies leveraging LC-MS tools to control HCPs in process and mitigate their potential risks to drug quality, stability, and patient safety.
Concurrent oral delivery of non-oncology drugs through solid self-emulsifying system for repurposing in hepatocellular carcinoma

Abstract Objective The present study aimed to identify a safe and effective non-oncology drug cocktail as an alternative to toxic chemotherapeutics for hepatocellular carcinoma (HCC) treatment. The assessment of cytotoxicity of cocktail (as co-adjuvant) in combination with chemotherapeutic docetaxel (DTX) is also aimed. Further, we aimed to develop an oral solid self-emulsifying drug delivery system (S-SEDDS) for the simultaneous delivery of identified drugs. Significance The identified non-oncology drug cocktail could overcome the shortage of anticancer therapeutics and help to reduce cancer-related mortality. Moreover, the developed S-SEDDS could be an ideal system for concurrent oral delivery of non-oncology drug combinations. Methods The non-oncology drugs (alone and in combinations) were screened in vitro for anticancer effect (against HepG2 cells) using (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide; MTT) dye assay, and cell cycle arresting and apoptotic behaviors using the fluorescence-activated cell sorting (FACS) technique. The S-SEDDS is composed of drugs such as ketoconazole (KCZ), disulfiram (DSR), tadalafil (TLF), and excipients like span-80, tween-80, soybean oil, Leciva S-95, Poloxamer F108 (PF-108), and Neusilin® US2 (adsorbent carrier), which was developed and characterized. Results The cocktail composed of KCZ, DSR, and TLF has showed substantial cytotoxicity (at the lowest concentration of 3.3 pmol), HepG2 cell arrest at G0/G1 and S phases, and substantial cell death via apoptosis. The DTX inclusion into this cocktail has further resulted in increased cytotoxicity, cell arrest at the G2/M phase, and cell necrosis. The optimized blank liquid SEDDS that remains transparent without phase separation for more than 6 months is used for the preparation of drug-loaded liquid SEDDS (DL-SEDDS). The optimized DL-SEDDS with low viscosity, good dispersibility, considerable drug retention upon dilution, and smaller particle size is further converted into drug-loaded solid SEDDS (DS-SEDDS). The final DS-SEDDS demonstrated acceptable flowability and compression characteristics, significant drug retention (more than 93%), particle size in nano range (less than 500 nm), and nearly spherical morphology following dilutions. The DS-SEDDS showed substantially increased cytotoxicity and Caco-2 cell permeability than plain drugs. Furthermore, DS-SEDDS containing only non-oncology drugs caused lower in vivo toxicity (only 6% body weight loss) than DS-SEDDS containing non-oncology drugs with DTX (about 10% weight loss). Conclusion The current study revealed a non-oncology drug combination effective against HCC. Further, it is concluded that the developed S-SEDDS containing non-oncology drug combination alone and in combination with DTX could be a promising alternative to toxic chemotherapeutics for the effective oral treatment of hepatic cancer.
Psychiatric Admissions in a Large Hospital in Madrid during COVID-19 Lockdown: Was There a Change in Patient Profile?

Introduction. COVID-19 led to a reorganization of health care in Madrid. The objective of this study is to describe the sociodemographic and clinical profile of psychiatric patients admitted to Gregorio Marañón Hospital during lockdown. Methods. A retrospective cross-sectional study was con-ducted and data were collected from all admissions to our psychiatric unit from March 15 to May 30, 2019 and 2020. A protocol was developed including clinical and sociodemo-graphic variables and a series of variables referring to the year prior to admission. In addition to descriptive statistics, we used Student's t test to compare quantitative variables and χ (2) for qualitative variables. Results. In 2020, the attended population increased by 312.5%, while admissions increased only 2.5%. Socioeconomic status was significantly lower in 2020 (χ (2)=18.041; p=0.001). The number of previous hospi-talizations was significantly higher in 2019 patients (t=2,147; p=0.032), but the variables that measured only the previ-ous year reflected more time of psychopathology (χ (2)=7.407; p=0.025) and hospitalization (χ (2)=16,765; p = 0.000) in 2020, as well as more dysfunctional family relationships (χ (2)=33.819; p=0.000) and less autonomy (χ (2)=6.387; p=0.041). The in-dex admission was significantly shorter in 2020 (t=2.977; p=0.003). There were also significant differences in the reason for admission, diagnosis, and substance use. Conclusions. There was a decrease in attendance to emer-gency services and the need for hospital admissions and an increase in the proportion of admissions in people with an unfavorable social and family background and with psychot-ic and bipolar disorders.
Association of sulfonylureas with the risk of dementia: A population‐based cohort study

Sulfonylureas are oral glucose‐lowering medications positioned as a second‐line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase‐4 (DPP4) inhibitor use.
Maternal and neonatal outcomes after benzodiazepine and benzodiazepine agonist exposure during pregnancy in women with mental disorders

To compare the gestational age of neonates in utero exposed to benzodiazepines (BDZs) with nonexposed controls. Secondary objectives were birth weight, presence of congenital malformations, APGAR score and the need for >3 months (prolonged) maternal psychiatric care.
Perceived Anxiety in Family Caregivers of Individuals with Autism Spectrum Disorder, Down Syndrome and Williams Syndrome during the Lockdown of the First COVID-19 Wave in Spain

Background. The lockdown during the first wave of COV- ID-19 in Spain has been related to higher levels of anxiety in the general population. However, the emotional impact on Spanish caregivers of individuals with neurodevelopmental disorders (NDD) has not been studied so far. Methods. An online questionnaire was distributed to Spanish organisations providing support to individuals with NDD and their families. Data from caregivers of individuals with autism spectrum disorder (ASD) (N = 17), Down syn-drome (DS) (N = 25) and Williams syndrome (WS) (N = 18) were analysed. Results. All caregivers reported concerns directly related to the pandemic and lockdown situation. Caregivers of indi-viduals with ASD showed higher level of concern about the possibility of family conflict. All three groups reported higher levels of anxiety during the lockdown. Anxiety was predicted by previous anxiety disorder and the child's diagnosis. Conclusions. Predictors of anxiety in caregivers of indi-viduals with NDD differ from those previously reported in the general Spanish population. The results suggest that confine-ment in Spain was especially demanding for families of indi-viduals with ASD. Public policies should consider the particular needs of people with NND and their caregivers to minimise the negative consequences of the ongoing pandemic.
The Use of TOVS Cloud-Cleared Radiances in the NCEP SSI Analysis System

Abstract With improved assimilation techniques, it is now possible to directly assimilate cloud-cleared radiances, rather than temperature and moisture retrievals, in objective analyses. The direct use of the cloud-cleared radiances became the operational technique for using satellite sounding data at the National Centers for Environmental Prediction (NCEP) in October 1995. The methodology for using the data (including bias correction, ozone analysis, skin temperature analysis, and quality control) are described in this paper. The impact of the direct use of the radiances compared to the previously operational use of satellite sounding data shows considerable improvement in NCEP’s forecast skill, especially in the Southern Hemisphere. It is anticipated that additional positive impacts will occur with application of the technique to other remotely sensed data.
The safety of trial of labor after cesarean section (TOLAC) versus elective repeat cesarean section (ERCS): a systematic review and meta-analysis

Abstract Objective Women’s choice of birth following a cesarean delivery either includes a trial of elective repeat cesarean section (ERCS) or a trial of labor after cesarean (TOLAC). No comprehensive overview or systematic summary is currently available. Methods EMBASE, PubMed, and the Cochrane Library databases were searched from inception to 1 February 2020. Studies reporting the safety of TOLAC and ERCS in pregnant women with prior cesarean delivery were included. Statistical analysis was performed using RevMan 5.3 and Stata 15.0. Odds ratios (ORs) and 95% confidence intervals (CIs) were adopted as the effective measures. Results A total of 13 studies covering 676,532 cases were included in this meta-analysis. The results demonstrated that the rates of uterine rupture (OR = 3.35, 95%CI [1.57, 7.15], I2 = 81%), neonatal asphyxia (OR = 2.32, 95%CI [1.76, 3.08], I2 = 0%) and perinatal death (OR = 1.71, 95%CI [1.29, 2.25], I2 = 0%) were higher in the TOLAC group compared with the ERCS group. The rates of peripartum hysterectomy (OR = 0.70, 95%CI [0.44, 1.11], I2 = 62%), blood transfusion (OR = 1.24, 95%CI [0.72, 2.12], I2 = 95%), and puerperal infection (OR = 1.11, 95%CI [0.77, 1.60], I2 = 95%) showed no significant differences between the two groups. Conclusion TOLAC is associated with a higher risk of uterine rupture, neonatal asphyxia, and perinatal death compared with ERCS. Nevertheless, it should be noted that the risks of all complications were small in both groups. This information is important for healthcare providers and women choosing the delivery type.
Hereditary hemochromatosis beyond hyperferritinemia: Clinical and laboratory investigation of the patient’s profile submitted to phlebotomy in two reference centers in southern Brazil

Abstract Hereditary Hemochromatosis is a disorder characterized by iron deposition in several organs and hyperferritinemia. The most studied variants are linked to the HFE gene. In Brazil, surveys that characterize this population are scarce, with no sampling in the state of Rio Grande do Sul. Our objective is to carry out a data collection focusing on the profile of this population and the influence of the most frequently HFE variants. Two centers were enrolled: Hospital de Clínicas de Porto Alegre and Hospital São Vicente de Paulo. Patients with hyperferritinemia and undergoing phlebotomy were invited. Clinical data were collected, including HFE investigation. Among the descriptive data, the allele frequency of the C282Y variant (0.252) stands out, which differs from the national scenario. Systemic arterial hypertension was the most cited comorbidity. Differences between centers were observed, highlighting higher frequency of H63D cases in HSVP (p<0.01). Genotypes were stratified according to deleterious effect of C282Y variant. Higher transferrin saturation and number of phlebotomies were observed in the C282Y/C282Y cases (p<0.001). Positive family history for hyperferritinemia was more prevalent in compound heterozygotes (p<0.01). The results presented confirm the importance of encouraging such studies and reiterate the need for greater attention to this population.
Quantitative Interpretation of Laser Ceilometer Intensity Profiles

Abstract The authors have used a commercially available laser ceilometer to measure vertical profiles of the optical extinction in rain. This application requires special signal processing to correct the raw data for the effects of receiver noise, high-pass filtering, and the incomplete overlap of the transmitted beam with the receiver field of view at close range. The calibration constant of the ceilometer, denoted by C, is determined from the profile of the corrected returned power in conditions of moderate attenuation in which the power is completely extinguished over a distance on the order of 1 km. In this determination, the value of the backscatter-to-extinction ratio k of the scattering medium must be specified and an allowance made for the effects of multiple scattering. These requirements impose an uncertainty on C that can amount to ±50%. An alternative to determining the calibration constant is explained, which does not require specifying k, although it assumes that k is constant with height. U.
Extragalactic ultra-high energy cosmic rays. I. Contribution from hot spots in FR-II radio galaxies.

The hot spots of Fanaroff-Riley class II radio galaxies, considered as working surfaces of highly collimated plasma jets, are proposed to be the dominant sources of the cosmic rays at energies above 1 EeV a . We apply the model of first order Fermi acceleration at strong, nonrelativistic shock waves to the hot spot region. The strength of the model has been demonstrated by Biermann & Strittmatter (1987) and by Meisenheimer et al. (1989), who explain their radio-to-optical spectra and infer the physical conditions of the radiating plasma. Using synchrotron radiating electrons as a trace, we can calculate the spectrum and the maximum energy of protons accelerated under the same conditions. For simplicity, we disregard heavy nuclei, but their probable role is discussed
Neuropilin-1 interacts with VE-cadherin and TGFBR2 to stabilize adherens junctions and prevent activation of endothelium under flow

Linear and disturbed flow differentially regulate gene expression, with disturbed flow priming endothelial cells (ECs) for a proinflammatory, atheroprone expression profile and phenotype. Here, we investigated the role of the transmembrane protein neuropilin-1 (NRP1) in ECs exposed to flow using cultured ECs, mice with an endothelium-specific knockout of NRP1, and a mouse model of atherosclerosis. We demonstrated that NRP1 was a constituent of adherens junctions that interacted with VE-cadherin and promoted its association with p120 catenin, stabilizing adherens junctions and inducing cytoskeletal remodeling in alignment with the direction of flow. We also showed that NRP1 interacted with transforming growth factor–β (TGF-β) receptor II (TGFBR2) and reduced the plasma membrane localization of TGFBR2 and TGF-β signaling. NRP1 knockdown increased the abundance of proinflammatory cytokines and adhesion molecules, resulting in increased leukocyte rolling and atherosclerotic plaque size. These findings describe a role for NRP1 in promoting endothelial function and reveal a mechanism by which NRP1 reduction in ECs may contribute to vascular disease by modulating adherens junction signaling and promoting TGF-β signaling and inflammation. Description The barrier function and quiescence of the endothelium are supported by transmembrane protein NRP1. Maintaining a quiescent endothelium Atherosclerosis causes disturbed blood flow that activates inflammatory pathways in endothelial cells, which attracts leukocytes to plaques and exacerbates disease progression. Bosseboeuf et al. investigated the role of the transmembrane protein NRP1 in the response of the endothelium to flow. Under normal flow patterns, NRP1 stabilized protein complexes at cell-cell junctions called adherens junctions and suppressed endothelial inflammation. In mice, NRP1 deficiency was associated with greater numbers of rolling leukocytes on endothelial cells in vitro and in vivo and larger plaque sizes in a model of atherosclerosis. Thus, NRP1 maintains the endothelium in a quiescent state and may limit inflammation in the endothelium under the disturbed blood flow patterns that are characteristic of atherosclerosis. —WW
Temporal avoidance as a means of reducing competition between sympatric species

Human activity has modified the availability of natural resources and the abundance of species that rely on them, potentially changing interspecific competition dynamics. Here, we use large-scale automated data collection to quantify spatio-temporal competition among species with contrasting population trends. We focus on the spatial and temporal foraging behaviour of subordinate marsh tits Poecile palustris among groups of socially and numerically dominant blue tits Cyanistes caeruleus and great tits Parus major. The three species exploit similar food resources in mixed groups during autumn–winter. Using 421 077 winter recordings of individually marked birds at 65 automated feeding stations in Wytham Woods (Oxfordshire, UK), we found that marsh tits were less likely to join larger groups of heterospecifics, and they accessed food less frequently in larger groups than in smaller ones. Marsh tit numbers within groups declined throughout the diurnal and winter periods, while the number of blue and great tits increased. However, sites that attracted larger groups of these heterospecifics also attracted more marsh tits. The results suggest that subordinate species exhibit temporal avoidance of socially and numerically dominant heterospecifics, but have limited ability for spatial avoidance, indicating that behavioural plasticity enables only a partial reduction of interspecific competition.