Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone morphogenetic protein 4 is involved in cadmium-associated bone damage

Abstract Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl2) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.
Outbreak of Burkholderia stabilis Infections Associated with Contaminated Nonsterile, Multiuse Ultrasound Gel — 10 States, May–September 2021

In July 2021, the Virginia Department of Health notified CDC of a cluster of eight invasive infections with Burkholderia stabilis, a bacterium in the Burkholderia cepacia complex (BCC), among hospitalized patients at hospital A. Most patients had undergone ultrasound-guided procedures during their admission. Culture of MediChoice M500812 nonsterile ultrasound gel used in hospital A revealed contamination of unopened product with B. stabilis that matched the whole genome sequencing (WGS) of B. stabilis strains found among patients. CDC and hospital A, in collaboration with partner health care facilities, state and local health departments, and the Food and Drug Administration (FDA), identified 119 B. stabilis infections in 10 U.S. states, leading to the national recall of all ultrasound gel products produced by Eco-Med Pharmaceutical (Eco-Med), the manufacturer of MediChoice M500812. Additional investigation of health care facility practices revealed frequent use of nonsterile ultrasound gel to assist with visualization in preparation for or during invasive, percutaneous procedures (e.g., intravenous catheter insertion). This practice could have allowed introduction of contaminated ultrasound gel into sterile body sites when gel and associated viable bacteria were not completely removed from skin, leading to invasive infections. This outbreak highlights the importance of appropriate use of ultrasound gel within health care settings to help prevent patient infections, including the use of only sterile, single-use ultrasound gel for ultrasonography when subsequent percutaneous procedures might be performed.
A critical thermal transition driving spring phenology of Northern Hemisphere conifers

Despite growing interest in predicting plant phenological shifts, advanced spring phenology by global climate change remains debated. Evidence documenting either small or large advancement of spring phenology to rising temperature over the spatio‐temporal scales implies a potential existence of a thermal threshold in the responses of forests to global warming. We collected a unique data set of xylem cell‐wall‐thickening onset dates in 20 coniferous species covering a broad mean annual temperature (MAT) gradient (−3.05 to 22.9°C) across the Northern Hemisphere (latitudes 23°–66° N). Along the MAT gradient, we identified a threshold temperature (using segmented regression) of 4.9 ± 1.1°C, above which the response of xylem phenology to rising temperatures significantly decline. This threshold separates the Northern Hemisphere conifers into cold and warm thermal niches, with MAT and spring forcing being the primary drivers for the onset dates (estimated by linear and Bayesian mixed‐effect models), respectively. The identified thermal threshold should be integrated into the Earth‐System‐Models for a better understanding of spring phenology in response to global warming and an improved prediction of global climate‐carbon feedbacks.
Evaluation of antifungal susceptibility and clinical characteristics in fungal keratitis in a tertiary care center in North India

Purpose: To study the antifungal susceptibility of common corneal pathogenic fungi to antifungal agents in the North Indian population. Methods: Prospective study of the antifungal sensitivity testing (natamycin, amphotericin B, voriconazole, itraconazole, fluconazole, posaconazole, caspofungin, micafungin) of fungal isolates from 50 cases of culture positive fungal keratitis by using E test method. Details noted included demographic data, visual acuity, clinical details, grade of keratitis, healing time, and success in medical management. Results: Of 50 patients with fungal keratitis (mean age: 40.28 ± 16.77 years), 12 eyes healed within 3 weeks, 14 had a delayed healing response, and 24 had chronic keratitis. Among the 15 cases of Fusarium isolates, 93.3% were sensitive to natamycin, while 40% to amphotericin B; 66.6% to voriconazole, 13.4% to itraconazole and fluconazole each. 80% of Fusarium cases (n = 12) showed susceptibility to posaconazole. Among Aspergillus flavus isolates, 53.4% (n = 8) were sensitive to natamycin, with only 40% (n = 7) showing sensitivity to amphotericin B and good susceptibility to azoles. MIC against susceptible Fusarium spp. for natamycin was 3–16 μg/mL, amphotericin B: 1–8 μg/mL, voriconazole: 0.5–1.5 μg/mL, itraconazole: 0.5–12 μg/mL, posaconazole: 0.094–1.5 μg/mL. MIC against Aspergillus flavus was natamycin: 8–32 μg/mL, amphotericin B: 0.5–16 μg/mL, voriconazole: 0.025–4 μg/mL, itraconazole: 0.125–8 μg/mL, posaconazole: 0.047–0.25 μg/mL; against Aspergillus niger isolates, to natamycin was 6 μg/mL (n=1), amphotericin B 8–12 μg/mL (n = 3), voriconazole: 0.125–0.19 μg/mL (n = 3), itraconazole: 0.38–0.75 μg/mL, posaconazole: 0.064–0.19 μg/mL and against Aspergillus fumigatus (n = 1), was natamycin4 μg/mL, amphotericin B - 8 μg/mL, voriconazole 0.25 μg/mL, itraconazole 1 μg/mL, and posaconazole 0.19 μg/mL. MIC against susceptible Acremonium spp. for natamycin was 1.5–16 μg/mL, amphotericin B: 0.5–8 μg/mL, voriconazole: 0.19–3 μg/mL, itraconazole: 0.125 μg/mL, posaconazole: 0.125–0.5 μg/mL and against susceptible Curvularia was natamycin 0.75–4 μg/mL, amphotericin B 0.5–1 μg/mL, voriconazole 0.125–0.19 μg/mL, itraconazole 0.047–0.094 μg/mL, posaconazole 0.047–0.094 μg/mL. MIC against Mucor spp. + Rhizopus spp. (n = 1) was natamycin: 8 μg/mL, amphotericin B: 0.75 μg/mL, posaconazole: 1.5 μg/mL. MIC against of Alternaria (n = 1) was voriconazole: 0.19 μg/mL, posaconazole: 0.094 μg/mL. MIC against Penicillium (n=1) was natamycin: 8 μg/mL, voriconazole: 0.25 μg/mL, itraconazole: 0.5 μg/mL, and Posaconazole: 0.125 μg/mL. Conclusion: Our observations highlight the variations in susceptibility to antifungal agents. Posaconazole seems to be effective with low MIC against common corneal pathogenic fungal isolates.
The gut microbiota is important for the maintenance of blood–cerebrospinal fluid barrier integrity

The gut microbiota communicates with the brain through several pathways including the vagus nerve, immune system, microbial metabolites and through the endocrine system. Pathways along the humoral/immune gut microbiota–brain axis are composed of a series of vascular and epithelial barriers including the intestinal epithelial barrier, gut–vascular barrier, blood–brain barrier and blood–cerebrospinal fluid barrier. Of these barriers, the relationship between the gut microbiota and blood–cerebrospinal fluid barrier is yet to be fully defined. Here, using a germ‐free mouse model, we aimed to assess the relationship between the gut microbiota and the integrity of the blood–cerebrospinal fluid barrier, which is localized to the choroid plexus epithelium. Using confocal microscopy, we visualized the tight junction protein zonula occludens‐1, an integral aspect of choroid plexus integrity, as well as the choroid plexus fenestrated capillaries. Quantification of tight junction proteins via network analysis led to the observation that there was a decrease in the zonula occludens‐1 network organization in germ‐free mice; however, we did not observe any differences in capillary structure. Taken together, these data indicate that the blood–cerebrospinal fluid barrier is another barrier along the gut microbiota–brain axis. Future studies are required to elucidate its relative contribution in signalling from microbiota to the brain.
The effect of different thickness scleral lens on corneal parameters in eyes with keratoconus

Purpose: To investigate the impact of different-thickness scleral lenses (SLs) on corneal thickness, curvature, and fluid reservoir thickness in keratoconic eyes. Methods: Schiempflug imaging and AS-OCT was captured before and immediately following 6 h of SL wear. Different-thickness lenses were used while keeping the other parameters the same. The timing of the measurement for day 1 and day 2 was matched to allow for the control of the confounding influence of diurnal variation. Results: Immediately after 6 h of lens wear, no statistically significant difference (P > 0.05) was noted in corneal edema in any region and quadrants between thin- and thick-lens wearers. The calculated percentage of corneal edema was also within the range of overnight closed eye physiological swelling. Pentacam measured higher central corneal thickness compared to AS-OCT in both baselines and after 6 h of lens wear. The current investigation reported minimal but not statistically significant (P > 0.05) flattening in anterior and steepening in posterior curvature parameters in both thin and thick SLs. The mean reduction in the fluid reservoir thickness was 80.00 ± 3.99 and 79.36 ± 3.84 microns after 6 h of thin- and thick-lens wear, respectively, which was not statistically significant (P > 0.05). A statistically significant positive correlation (r = 0.67, P = 0.02) was found between lens thickness and change in anterior steep k with thick-lens wear. Conclusion: Central lens thickness of 200–400 μm did not cause any significant change in corneal curvature and fluid reservoir thickness and did not induce clinically significant corneal edema after short-term SL wear.
Serum proteomic profiling reveals MTA2 and AGO2 as potential prognostic biomarkers associated with disease activity and adverse outcomes in multiple myeloma

Multiple myeloma (MM) is an incurable plasma cell malignancy accounting for approximately 10% of hematological malignancies. Identification of reliable biomarkers for better diagnosis and prognosis remains a major challenge. This study aimed to identify potential serum prognostic biomarkers corresponding to MM disease activity and evaluate their impact on patient outcomes. Serum proteomic profiles of patients with MM and age-matched controls were performed using LC–MS/MS. In the verification and validation phases, the concentration of the candidate biomarkers was measured using an ELISA technique. In addition, the association of the proposed biomarkers with clinical outcomes was assessed. We identified 23 upregulated and 15 downregulated proteins differentially expressed in newly diagnosed and relapsed/refractory MM patients compared with MM patients who achieved at least a very good partial response to treatment (≥VGPR). The top two candidate proteins, metastasis-associated protein-2 (MTA2) and argonaute-2 (AGO2), were selected for further verification and validation studies. Both MTA2 and AGO2 showed significantly higher levels in the disease-active states than in the remission states (p < 0.001). Regardless of the patient treatment profile, high MTA2 levels were associated with shorter progression-free survival (p = 0.044; HR = 2.48; 95% CI, 1.02 to 6.02). Conversely, high AGO2 levels were associated with IgG and kappa light-chains isotypes and an occurrence of bone involvement features (p < 0.05) and were associated with prolonged time to response (p = 0.045; HR = 3.00; 95% CI, 1.03 to 8.76). Moreover, the analytic results using a publicly available NCBI GEO dataset revealed that AGO2 overexpression was associated with shorter overall survival among patients with MM (p = 0.032, HR = 1.60, 95% CI, 1.04 to 2.46). In conclusion, MTA2 and AGO2 proteins were first identified as potential biomarkers that reflect disease activity, provide prognostic values and could serve as non-invasive indicators for disease monitoring and outcome predicting among patients with MM.
EVOLVING SPHERES OF SHEAR-FREE ANISOTROPIC FLUID

The fluid models mentioned in the title are studied in a modified approach, based on two formulas for the mass function. All characteristics of the fluid are expressed through a master potential, satisfying an ordinary second-order differential equation. Different constraints are imposed on this core of relations, finding new solutions and deriving the classical results for perfect fluids as particular cases. All charged anisotropic solutions, all conformally flat and all uniform density solutions are found. A large class of solutions with linear equation among the two pressures is derived, including the case of vanishing tangential pressure. The mechanism responsible for the appearance of equation of state is elucidated.
Post‐pancreatitis diabetes mellitus is common in chronic pancreatitis and is associated with adverse outcomes

Abstract Background Post‐pancreatitis diabetes mellitus (PPDM) is a common consequence of chronic pancreatitis (CP). We aimed to determine the incidence and predictors of PPDM after CP onset, as well as complications and antidiabetic therapy requirements, in a high‐volume tertiary center. Methods We did a cohort study with retrospectively collected data from patients with definite CP seen at the Karolinska University Hospital between January 1999 and December 2020. Cause‐specific Cox regression analysis was used to assess PPDM predictors. To estimate risk of complications and need for therapy the Fine‐Gray subdistribution hazard model was employed, accounting for death as a competing risk. Results We identified 481 patients with CP. The cumulative incidence of PPDM was 5.1%, 13.2%, 27.5% and 38.9% at 5, 10, 15 and 20 years, respectively. Compared to CP patients without diabetes, patients with PPDM were predominantly male (55% vs. 75%), had more frequently alcoholic etiology (44% vs. 62%) and previous acute pancreatitis. The only independent predictor of PPDM was presence of pancreatic calcifications (aHR = 2.45, 95% CI 1.30–4.63). Patients with PPDM had higher rates of microangiopathy (aSHR = 1.59, 95% CI 1.02–2.52) and infection (aSHR = 4.53, 95% CI 2.60–9.09) compared to CP patients who had type 2 diabetes (T2DM). The rate of insulin use was three‐fold higher, whereas metformin use rate was two‐fold higher in the same comparison. Conclusions Patients with PPDM have a higher frequency of clinically significant complications and were more commonly prescribed insulin and metformin, suggesting a more aggressive phenotype than that of T2DM. Greater PPDM awareness is needed to optimize disease management.
Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis

Background: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy–related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. Methods: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. Results: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%–84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%–70%]; I2=82%), encephalopathy 54% ([95% CI, 39%–68%]; I2=43%), seizures 37% ([95% CI, 27%–49%]; I2=65%), headache 31% ([95% CI, 22%–42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%–100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%–99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%–66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%–68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%–73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%–53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. Conclusions: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.
The unforeseen future: Impacts of the COVID‐19 pandemic on home video‐EEG telemetry

The coronavirus disease 2019 (COVID‐19) pandemic had widespread impact on health care systems globally—particularly services arranged around elective admission and attendance such as epilepsy monitoring units and home video‐EEG telemetry (HVET). Here, we review the ongoing impacts of the pandemic on HVET services among several different providers who used different initial models of HVET. We discuss the features of HVET that led to success in providing continued diagnostic services to patients with epilepsy and related disorders and through retrospective audit of our services demonstrate the high diagnostic yield of HVET. We reflect on this unforeseen future and its implications for other diagnostic techniques and approaches.
Key concepts for informed health choices. 2.1: comparisons of treatments should be fair

As explained in previous essays in this series, it is impossible to know what the effects of a treatment are without comparing it to what would have happened without the treatment. Predicting what the likely effects of a treatment will be depends on treatment comparisons – typically comparisons between groups of people who are treated differently. The trustworthiness of estimates of treatment effects from treatment comparisons depends on the extent to which the design, conduct, analysis, reporting and interpretation of the comparisons have minimised the risk of systematic errors (biases) that distort effect estimates away from the actual effects. Because it is generally not possible to know the degree to which an effect estimate is biased, judgements must be made about the risk of bias using criteria that assess sources of bias. In this essay, we explain seven sources of bias that should be considered when making judgements about the trustworthiness of treatment comparisons:
Food insufficiency, adverse childhood experiences and mental health: results of the Singapore Mental Health Study 2016

Abstract Objective: This study aimed to investigate the prevalence and correlates of food insufficiency and its association with mental disorders and adverse childhood experiences (ACE) in Singapore. Design: This analysis utilised data from the Singapore Mental Health Study (SMHS 2016). Setting: SMHS 2016 was a population-based, psychiatric epidemiological study conducted among Singapore residents. Participants: Interviews were conducted with 6126 respondents. Respondents were included if they were aged 18 years and above, Singapore citizens or permanent residents and able to speak in English, Chinese or Malay. Results: The prevalence of food insufficiency was 2·0 % (95 % CI (1·6, 2·5)) among adult Singapore residents. Relative to respondents who did not endorse any ACE, those with ACE (OR: 2·9, 95 % CI (1·2, 6·6)) had higher odds of food insufficiency. In addition, there were significant associations between lifetime mental disorders and food insufficiency. Bipolar disorder (OR: 2·7, 95 % CI (1·2, 6·0)), generalised anxiety disorder (OR: 4·5, 95 % CI (1·5, 13·5)) and suicidal behaviour (OR: 2·37, 95 % CI (1·04, 5·41)) were shown to be significantly associated with higher odds of food insufficiency. Conclusions: The prevalence of food insufficiency is low in Singapore. However, this study identifies a vulnerable group of food-insufficient adults that is significantly associated with mental disorders, including suicidality. Government-funded food assistance programmes and multi-agency efforts to deal with the social determinants of food insufficiency, such as income sufficiency and early detection and intervention of mental distress, are key to ensuring a sustainable and equitable food system.
From bones to bytes: Do manipulable 3D models have added value in osteology education compared to static images?

Over the past few years, anatomy education has been revolutionized through digital media, resulting in innovative computer‐based 3D models to supplement or even replace traditional learning materials. However, the added value of these models in terms of learning performance remains unclear. Multiple mechanisms may contribute to the inconclusive findings. This study focusses on the impact of active manipulation on learning performance and the influence that posttest design features may have on the outcome measurement.
Association of Remdesivir Treatment With Mortality Among Hospitalized Adults With COVID-19 in the United States

Key Points Question Is remdesivir treatment associated with reduced risk of inpatient mortality among US patients hospitalized with COVID-19? Findings In this retrospective cohort study of 24 856 patients with COVID-19 and 24 856 propensity score–matched control patients using US-based health insurance claims and hospital chargemaster data, remdesivir treatment was associated with significant 17% lower risk of inpatient mortality among patients hospitalized with COVID-19. Meaning Results of this study complement those from randomized clinical trials and suggest that remdesivir treatment was associated with significantly reduced inpatient mortality among patients hospitalized with COVID-19.