Miracle-dz/UniFAR-FTUs huggingface dataset:
Unexpected phenotypic and molecular changes of combined glucocerebrosidase and acid sphingomyelinase deficiency

ABSTRACT Heterozygous variants in GBA1, encoding glucocerebrosidase (GCase), are the most common genetic risk factor for Parkinson's disease (PD). Moreover, sporadic PD patients also have a substantial reduction of GCase activity. Genetic variants of SMPD1 are also overrepresented in PD cohorts, whereas a reduction of its encoded enzyme (acid sphingomyelinase or ASM) activity is linked to an earlier age of PD onset. Despite both converging on the ceramide pathway, how the combined deficiencies of both enzymes might interact to modulate PD has yet to be explored. Therefore, we created a double-knockout (DKO) zebrafish line for both gba1 (or gba) and smpd1 to test for an interaction in vivo, hypothesising an exacerbation of phenotypes in the DKO line compared to those for single mutants. Unexpectedly, DKO zebrafish maintained conventional swimming behaviour and had normalised neuronal gene expression signatures compared to those of single mutants. We further identified rescue of mitochondrial Complexes I and IV in DKO zebrafish. Despite having an unexpected rescue effect, our results confirm ASM as a modifier of GBA1 deficiency in vivo. Our study highlights the need for validating how genetic variants and enzymatic deficiencies may interact in vivo.
The Relationship Between Patient Safety Culture and the Intentions of the Nursing Staff to Report a Near-Miss Event During the COVID-19 Crisis

Background: Reporting a near-miss event has been associated with better patient safety culture. Purpose: To examine the relationship between patient safety culture and nurses' intention to report a near-miss event during COVID-19, and factors predicting that intention. Methods: This mixed-methods study was conducted in a tertiary medical center during the fourth COVID-19 waves in 2020-2021 among 199 nurses working in COVID-19–dedicated departments. Results: Mean perception of patient safety culture was low overall. Although 77.4% of nurses intended to report a near-miss event, only 20.1% actually did. Five factors predicted nurses' intention to report a near-miss event; the model explains 20% of the variance. Poor departmental organization can adversely affect the intention to report a near-miss event. Conclusions: Organizational learning, teamwork between hospital departments, transfers between departments, and departmental disorganization can affect intention to report a near-miss event and adversely affect patient safety culture during a health crisis.
Abnormal characteristic static and dynamic functional network connectivity in idiopathic normal pressure hydrocephalus

Abstract Aims Idiopathic Normal pressure hydrocephalus (iNPH) is a neurodegenerative disease characterized by gait disturbance, dementia, and urinary dysfunction. The neural network mechanisms underlying this phenomenon is currently unknown. Methods To investigate the resting‐state functional connectivity (rs‐FC) abnormalities of iNPH‐related brain connectivity from static and dynamic perspectives and the correlation of these abnormalities with clinical symptoms before and 3‐month after shunt. We investigated both static and dynamic functional network connectivity (sFNC and dFNC, respectively) in 33 iNPH patients and 23 healthy controls (HCs). Results The sFNC and dFNC of networks were generally decreased in iNPH patients. The reduction in sFNC within the default mode network (DMN) and between the somatomotor network (SMN) and visual network (VN) were related to symptoms. The temporal properties of dFNC and its temporal variability in state‐4 were sensitive to the identification of iNPH and were correlated with symptoms. The temporal variability in the dorsal attention network (DAN) increased, and the average instantaneous FC was altered among networks in iNPH. These features were partially associated with clinical symptoms. Conclusion The dFNC may be a more sensitive biomarker for altered network function in iNPH, providing us with extra information on the mechanisms of iNPH.
Monkeypox (Mpox) outbreak during COVID‐19 pandemic—Past and the future

Monkeypox infection (Mpox) is caused by the Orthopoxvirus (OPXV) genus of the Poxviridae family, closely resembling its more famous sibling smallpox. Recently World Health Organization (WHO), have renamed monkeypox as Mpox citing racial concerns, so we will be referring to monkeypox as Mpox. There has been a recent outbreak in May 2022 when Mpox cases were identified in all six WHO regions. On July 23, 2022, WHO declared it a public health emergency. Before the current outbreak, Mpox had been reported in people from several parts of central and west African countries; and almost all Mpox cases in people outside of Africa were linked to international travel to countries where the disease commonly occurs or through imported animals. With the waning of smallpox vaccine‐induced immunity, Mpox can spread in the global population. Though the virus generally does not cause high mortality in immunocompetent individuals, however, severe disease and mortality may result if the virus spreads to immunocompromised individuals, children, elderly individuals, pregnant women, and individuals living with comorbidities such as diabetes. The current transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. It was found that 98% of the persons with infection were either gay or bisexual men, with 41% suffering from HIV infection. The reasons behind this current epidemiological behavior have to be studied further to formulate a hypothesis that, is it the homosexuals who need to be more concerned or is it a global concern, and is monkeypox changing its behaviour to a sexually transmitted infection? The rash, along with associated lymphadenopathy, is a clue toward Mpox infection, but polymerase chain reaction is needed for the confirmative diagnosis. With the discovery of a vaccine, repurposed antivirals, and precautionary steps to prevent the spread of infection, it might help in the containment of the virus. In addition, what we already know about Mpox has to be re‐evaluated, because most of the information gathered is from low‐resource settings in Africa. The world at large and health care agencies specifically needs to galvanize a well‐funded global plan and research initiatives to contain the spread of Mpox. In this article, we have attempted to make the readers aware of the biology, etiopathogenesis including the changes at the cellular level the virus is causing, the changing trends of the virus transmission, and the clinical manifestations. We have also attempted to elaborate on the potential challenges and the need for early diagnosis and containment of this Mpox outbreak. This could be achieved by effectieve use of vaccination and taking social safety measures, especially by the communities at risk.
Evaluation of a docetaxel-cisplatin-fluorouracil-Au complex in human oral carcinoma cell line

Abstract Higher tobacco and alcohol use have led to a consistent increase in head and neck cancer incidence rates. Currently employed chemotherapeutic and surgical treatment are associated with significant drawbacks. Herein, we evaluated the anti-tumour effect of gold nanoparticles as a vehicle for the delivery of a triple chemotherapy drug formulation and elucidated the potential underlying mechanism. The hydrodynamic size of docetaxel, cisplatin, and 5-fluorouracil physically co-adsorbed on Au nanoparticles was 56 ± 0.8 nm, showing a negative zeta potential. Fourier transform infra-red spectroscopy data confirmed that the triple chemotherapy drug successfully interacted with the gold nano-carrier. Au nanoparticles exhibited high loading efficacy of docetaxel (61%), cisplatin (75%), and 5-fluorouracil (90%), with a controlled drug release profile at 24 h. The triple chemotherapy drug formulation was tested in human oral cavity cancer cell line (KB). Cytotoxicity achieved through a synergistic effect between the treatments led to apoptosis, with a lower half-maximal inhibitory concentration indicating higher cytotoxicity than that of plain docetaxel-cisplatin-fluorouracil. Taken together, we demonstrated that the docetaxel-cisplatin-fluorouracil-gold complex exhibited excellent cytotoxicity in KB cells, superior to that docetaxel-cisplatin-fluorouracil. HIGHLIGHTS The docetaxel-cisplatin-fluorouracil-Au complex showed a controlled drug-release profile at 24 h. The docetaxel-cisplatin-fluorouracil-Au complex exhibited enhanced internalisation efficiency in cells. Au nanoparticles were biocompatible, with no change in apoptosis among cell line. Spherical Au nanoparticles allowed a high volume of incorporated docetaxel, cisplatin, and 5-fluorouracil to steadily attach onto cells.
Factors Affecting Completion of Human Papillomavirus Vaccination Series by Gender in a Predominantly Hispanic Border Town Community

No statistically significant human papillomavirus vaccine series completion rates, by sex, were found in a US-Mexico border community. Objectives The human papillomavirus (HPV) vaccine is recommended for females and males aged 9 to 45. Nationally, the HPV vaccination rates are lower for males than females; however, this has not been studied in a US-Mexico border community. Our study aims to report the HPV vaccination completion by gender and determine which sociodemographic factors influence vaccination. Methods This cross-sectional study was conducted among uninsured and underinsured individuals aged between 9 and 26 years served through a community-based HPV vaccine program in El Paso, TX. Data collected included demographic information, psychosocial variables, and vaccine administration data. Descriptive statistics were used to summarize demographic data. Unadjusted t test/Fisher exact test and multivariable relative risk regression were run on significant variables to determine the association with vaccine completion by gender. Results Most participants were female (63.4%), and an overall vaccine series completion was 30.67%. We found no significant difference in HPV vaccine completion rates by gender. Males who resided in the United States for more than a decade were 31% more likely to complete the vaccine series, and females who had 9 to 13 years of education had lower odds of vaccine completion. Knowledge significantly increased after the intervention for both genders (p = .002). There was no significant change in psychosocial variables from the preintervention to the immediate postintervention survey. Conclusions Our multicomponent, culturally tailored intervention may equally impact male and female participants and encourages all genders to complete their HPV vaccine series. Additional studies with a larger male sample are needed.
The mechanosensitive ion channel ASIC2 mediates both proprioceptive sensing and spinal alignment

By translating mechanical forces into molecular signals, proprioceptive neurons provide the CNS with information on muscle length and tension, which is necessary to control posture and movement. However, the identities of the molecular players that mediate proprioceptive sensing are largely unknown. Here, we confirm the expression of the mechanosensitive ion channel ASIC2 in proprioceptive sensory neurons. By combining in vivo proprioception‐related functional tests with ex vivo electrophysiological analyses of muscle spindles, we showed that mice lacking Asic2 display impairments in muscle spindle responses to stretch and motor coordination tasks. Finally, analysis of skeletons of Asic2 loss‐of‐function mice revealed a specific effect on spinal alignment. Overall, we identify ASIC2 as a key component in proprioceptive sensing and a regulator of spine alignment.
Bartonella Prevalence and Genome Sequences in Rodents in Some Regions of Xinjiang, China

Rodent-borne Bartonella species have been associated with zoonotic diseases. Bartonella species such as Bartonella elizabethae, Bartonella grahamii, and Bartonella tribocorum can cause disease in humans. Humans can be infected by blood-sucking arthropods through the scratches and bites of an infected reservoir host or via contact with infectious rodents. ABSTRACT In this study, we investigated Bartonella infection and its genetic diversity in rodents in Beitun, Xinjiang Uygur Autonomous Region, China. Small mammals were captured using snap traps at four sampling sites in 2018. Spleen and liver tissues were collected and cultured to isolate Bartonella strains. Whole-genome sequencing was performed on the strains identified as Bartonella by gltA gene PCR, and the average nucleotide identity (ANI) of the genomes was calculated by using FastANI v1.33. Phylogenetic trees were constructed for the samples positive for Bartonella spp. by the gltA PCR assay based on 1,290-bp gltA genes, 2,903-bp rpoB genes, and core-genome single nucleotide polymorphisms (SNPs). Among 66 rodents, 11 were positive for Bartonella, with an infection rate of 16.67%. The rodent infection rates in different tissues (χ2 = 2.133; P = 0.242), species (χ2 = 9.631; P = 0.141), and habitats (χ2 = 4.309; P = 0.312) did not show statistical differences. Bartonella spp. isolated from the rodents were phylogenetically divided into six clades (two different Bartonella species were detected in two rodents). By comparing phylogenetic trees based on gltA genes, rpoB genes, and SNPs, we found that the topological structures of several evolutionary trees are different. However, the Bartonella strains isolated in this study were clustered into six clusters in different phylogenetic trees. Broad distributions and high genetic diversity of Bartonella strains were observed among rodents in Beitun, Xinjiang. IMPORTANCE Rodent-borne Bartonella species have been associated with zoonotic diseases. Bartonella species such as Bartonella elizabethae, Bartonella grahamii, and Bartonella tribocorum can cause disease in humans. Humans can be infected by blood-sucking arthropods through the scratches and bites of an infected reservoir host or via contact with infectious rodents. Xinjiang is one of the provinces with the most abundant species of Bartonella in China, but there are few reports about the prevalence of Bartonella in the Beitun area. This research aims to investigate the occurrence and prevalence of Bartonella infection in rodents at these sampling sites and provide a basis for the prevention and control of rodent Bartonella species in Beitun and the surrounding areas of Xinjiang.
On the Failure of Standard Emission Measure Analysis for Solar Extreme-Ultraviolet and Ultraviolet Irradiance Spectra

We perform emission measure analysis of new and accurate UV (λ > 1200 Å) and extreme-ultraviolet (EUV) (λ ≤ 1200 Å) irradiance (“Sun-as-a-star”) emission-line spectra of the Sun. Our data consist of (1) daily averaged UV irradiances from the SOLSTICE on the UARS spacecraft and (2) EUV irradiances obtained on the same date from a m spectrograph flown on a sounding rocket. Both instruments have a spectral resolution of roughly 1 Å. The absolute uncertainties in these data are at most ±15% ( ± 2 σ), one of the highest photometric accuracies yet achieved. We find large, highly significant and systematic discrepancies in the emission measure analysis of transition region lines which can only be accounted for by a breakdown of one or more standard assumptions. All strong lines above 1000 Å, which are from the Li and Na isoelectronic sequences, are too strong by factors of between 2.5 and 7 compared with their counterparts in the EUV region. Previous studies were tantalizingly close to finding these discrepancies, but those data lacked the wavelength coverage and relative photometric precision necessary for definitive conclusions. We argue that either dynamical effects, inaccurate treatments of atomic processes, and/or Lyman continuum absorption are the culprits. However, we favor the former explanation. In any event, this study should have implications for models of the solar transition region, for observing programs with the CDS and SUMER instruments on SOHO, and for analysis of UV spectra for stars across the cool half of the H-R diagram. Finally, the discrepancy is not seen for the “coronal” Li-like ions.
The Frequency of CYP2C19 Loss-of-Function Variants in Patients with Non-Cardioembolic Ischemic Stroke or Transient Ischemic Attack in the Dutch Population

Introduction: The CYP2C19 enzyme converts clopidogrel into an active metabolite. Carriers of CYP2C19 loss-of-function (LOF) variants with a history of ischemic stroke or transient ischemic attack (TIA) using clopidogrel may have a higher risk of recurrent stroke. To study the implications of genetic CYP2C19 heterogeneity in treatment of cerebral ischemia, knowledge about the prevalence of CYP2C19 LOF variants within the population is important. We investigated the frequency of CYP2C19 LOF variants in patients with non-cardioembolic ischemic stroke or TIA in the Dutch population. Methods: We performed a single-center observational study with a cross-sectional design in a Dutch thrombectomy-capable stroke center. We included all patients presenting with non-cardioembolic ischemic stroke or TIA. We determined the frequency of CYP2C19 LOF variants in the full cohort. Additionally, we compared the frequency of CYP2C19 LOF variants in two subgroups: patients with first-ever non-cardioembolic ischemic stroke or TIA versus patients with recurrent ischemic stroke or TIA using clopidogrel because of a history of ischemic stroke or TIA. Results: We enrolled 410 patients between January 1, 2021, and July 1, 2021. 109 (26.6%) patients were carriers of CYP2C19 LOF variants. We found no difference in the frequency of CYP2C19 LOF variants between patients with first-ever ischemic stroke or TIA versus patients with recurrent ischemic stroke or TIA using clopidogrel (25.9 vs. 31.9%, respectively, p = 0.31). Discussion and Conclusion: About a quarter of patients with non-cardioembolic ischemic stroke or TIA in the Dutch population carry a CYP2C19 LOF variant. This is lower than estimates found in studies with Asian populations but similar to estimates found among Caucasian patients in other parts of the world.
Association of Posttraumatic Epilepsy With Long-term Functional Outcomes in Individuals With Severe Traumatic Brain Injury

Background and Objective Nearly one-third of patients with severe traumatic brain injury (TBI) develop posttraumatic epilepsy (PTE). The relationship between PTE and long-term outcomes is unknown. We tested whether, after controlling for injury severity and age, PTE is associated with worse functional outcomes after severe TBI. Methods We performed a retrospective analysis of a prospective database of patients with severe TBI treated from 2002 through 2018 at a single level 1 trauma center. Glasgow Outcome Scale (GOS) was collected at 3, 6, 12, and 24 months postinjury. We used repeated-measures logistic regression predicting GOS, dichotomized as favorable (GOS 4–5) and unfavorable (GOS 1–3), and a separate logistic model predicting mortality at 2 years. We used predictors as defined by the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) base model (i.e., age, pupil reactivity, and GCS motor score), PTE status, and time. Results Of 392 patients who survived to discharge, 98 (25%) developed PTE. The proportion of patients with favorable outcomes at 3 months did not differ between those with and without PTE (23% [95% Confidence Interval [CI]: 15%–34%] vs 32% [95% CI: 27%–39%]; p = 0.11) but was significantly lower at 6 (33% [95% CI: 23%–44%] vs 46%; [95% CI: 39%–52%] p = 0.03), 12 (41% [95% CI: 30%–52%] vs 54% [95% CI: 47%–61%]; p = 0.03), and 24 months (40% [95% CI: 47%–61%] vs 55% [95% CI: 47%–63%]; p = 0.04). This was driven by higher rates of GOS 2 (vegetative) and 3 (severe disability) outcomes in the PTE group. By 2 years, the incidence of GOS 2 or 3 was double in the PTE group (46% [95% CI: 34%–59%]) compared with that in the non-PTE group (21% [95% CI: 16%–28%]; p < 0.001), while mortality was similar (14% [95% CI: 7%–25%] vs 23% [95% CI: 17%–30%]; p = 0.28). In multivariate analysis, patients with PTE had lower odds of favorable outcome (odds radio [OR] 0.1; 95% CI: 0.1–0.4; p < 0.001), but not mortality (OR 0.9; 95% CI: 0.1–1.9; p = 0.46). Discussion Posttraumatic epilepsy is associated with impaired recovery from severe TBI and poor functional outcomes. Early screening and treatment of PTE may improve patient outcomes.
An Absence of Persistent Postural Stability Deficits Following a Sport Concussion in Collegiate Athletes

Objective: The purpose of our study was to determine whether persistent postural stability deficits exist in athletes following sport concussion (SC) in comparison with preinjury (baseline) values using Sample Entropy (SampEn). Setting: Sports medicine clinic. Patients or Other Participants: Participants consisted of 71 collegiate athletes (44 male, 27 female) with an average age of 19.9 ± 0.96 years who had a history of 1 concussion that occurred during their time as a collegiate athlete. Design: In our prospective, cohort design participants completed the Sensory Organization Test (SOT) at baseline, upon reporting symptom-free following a diagnosed SC, and upon establishing a new baseline prior to the start of the subsequent sport season. Main Outcome Measures: The SOT's condition scores were calculated and analyzed in alignment with the manufacturer's instructions. SampEn was calculated in the anterior-posterior (AP) and medial-lateral (ML) directions from the center-of-pressure oscillations over the 20-second time series for each SOT condition. The SOT and SampEn outcome scores for each condition were analyzed with repeated-measures analyses of variance. Results: Significant main effects were observed for the SOT's conditions 3 (F1.6, 114.8 = 7.83, P = .001, η2 = 0.10 [0.02-0.20]), 5 (F1.8, 126.8 = 11.53, P < .001, η2 = 0.14 [0.04-0.25]), and 6 (F1.9, 134.5 = 25.11, P < .001, η2 = 0.26 [0.14-0.37]), with significant improvements across time. Significant main effects were also observed for SampEn in the AP direction for conditions 3 (F2, 140 = 7.59, P = .001, η2 = 0.10 [0.02-0.19]) and 6 (F2, 140 = 6.22, P = .003, η2 = 0.08 [0.011-0.170]), with significant improvements across time. Conclusions: Following a diagnosed SC, our results suggest that collegiate athletes returned if not exceeded baseline values at the symptom-free and new baseline assessments. The application of linear and nonlinear measures of postural stability following a SC yielded similar outcomes in conjunction with a baseline assessment. Our findings support the clinical utility of the baseline SC assessment when evaluating persisting balance deficits when using linear or nonlinear measures.