Miracle-dz/UniFAR-FTUs huggingface dataset:
Singapore's health outcomes after critical illness in kids: A study protocol exploring health outcomes of families 6 months after critical illness.

AIM To explore and understand the impact of paediatric intensive care unit (PICU) admission on longitudinal health outcomes, experiences and support needs of children and their parents in the first 6 months after PICU discharge and to examine the role of ethnicity. DESIGN This study uses a prospective, longitudinal design. METHODS The sample will include children (N = 110) and at least one parent (N = 110) admitted to the PICU (KKH-AM start-up fund, October 2020). Quantitative study: Participants will be recruited at PICU admission. Data will be collected at five time points: during PICU admission (T0), at PICU discharge (T1), 1 month (T2), 3 months (T3) and 6 months (T4) after PICU discharge. Questionnaires will assess physical and cognitive outcomes of the child survivor. Emotional and social health outcomes will be assessed for both the child and the parents. Qualitative study: At least 12 parents will take part in a semi-structured interview conducted at both 1 and 6 months after PICU to explore their experiences and support needs after PICU discharge. All interviews will be audio-recorded with verbatim transcription. We will use framework analysis for qualitative data analysis. DISCUSSION Understanding of Singapore health outcomes after critical illness in kids (SHACK) and their families is limited. There is an urgent need to comprehensively understand the health trajectory and consequences of the PICU child survivors and their families. This research will be the first to explore the health outcomes, needs and experiences after paediatric critical illness in Asia. IMPACT This study will provide an understanding of the health outcomes and trajectory of children and parents in the first 6 months after PICU discharge and examine the association between race and outcomes after PICU discharge. Identification of modifiable pre-disposing risk factors during the PICU admission will inform future interventions to improve long-term outcomes of children and parents following paediatric critical illness. TRIAL REGISTRATION Clinicaltrial.gov: ClinicalTrials.gov Identifier: NCT04637113.
Microcatheter Stabilization Technique Using Partially Inflated Balloon for Coil Embolization of Paraclinoid Aneurysms

Purpose Coil embolization of paraclinoid aneurysms should be simple, safe, and effective considering the benign nature of the aneurysm. Here, we present a microcatheter stabilization technique using a partially inflated balloon for the treatment of paraclinoid aneurysms. Materials and Methods This retrospective study included 58 patients who underwent balloon-assisted coiling (BAC) for unruptured paraclinoid aneurysms at a tertiary neuro-intervention center between January 2019 and March 2020. We applied a technique to stabilize the microcatheter’s position using the modified BAC technique in paraclinoid aneurysms showing various projections around the ophthalmic curve of the internal carotid artery. The basic concept of the technique is to place a partially inflated balloon just distal to the aneurysm neck and support the distal curve of the microcatheter using the proximal bottom of the balloon. Immediate radiological outcomes were analyzed, and clinical outcomes were evaluated with modified Rankin Scale (mRS) scores. Results The BAC was successfully performed in 51 of 58 patients (88%). We treated the remaining 7 patients by switching to stent-assisted coiling. We obtained a 37% mean packing density resulting in favorable occlusion in all 58 aneurysms (complete occlusion in 35 and residual neck in 23). There were no intraprocedural thromboembolic or hemorrhagic events except one that revealed an asymptomatic infarction after the procedure (1.7%). Magnetic resonance angiography follow-up was performed in 37 patients at an average of 11.8 months, in which 11 minor recurrences (29.7%) were found. There was no major recurrence nor retreatment. The mRS score was 0 in all patients during a mean follow-up of 17.7 months (range, 12–25 months). Conclusion The modified balloon-assisted coiling technique using a partially inflated balloon was safe and effective and could serve as an option for treating paraclinoid aneurysms.
Prevalence and sociodemographic correlates of medication intake adherence among primary health-care users in Albania.

Background Evidence about the magnitude and determinants of medication intake adherence among patients and the general population in Southeastern Europe is scant. Aims To assess the prevalence and sociodemographic correlates of medication intake adherence among adult primary health-care (PHC) users in Albania. Methods A cross-sectional study was conducted in 2018-2019 in a representative sample of 1553 adult PHC users (response: 94%) selected probabilistically from 5 major regions of Albania. There were 849 (55%) women and 704 (45%) men, with a mean age 54.6 (16.4) years. A structured interviewer-administered questionnaire inquired about medication intake adherence prescribed by family physicians, and sociodemographic characteristics. Binary logistic regression was used to assess the sociodemographic correlates of medication intake adherence. Results Three hundred (19.8%) participants did not take the prescribed medication. In multivariable-adjusted logistic model, significant correlates of nonintake of medication included rural residence, low educational level, unemployment and low economic level. Among these 300 participants, 273 (91%) considered the high cost of the drugs as a reason for not taking the medication. Conclusion We found a high prevalence of nonintake of medication prescribed by family physicians. Decision-makers and policy-makers in Albania and elsewhere should consider the provision of essential drugs free of charge or at low cost to low socioeconomic groups and other vulnerable and marginalized population categories, because the costs of noncompliance will eventually be higher.
Diagnostic and Therapeutic Delays in Patients With Hepatocellular Carcinoma.

BACKGROUND Delays in diagnosis and treatment have been reported for many cancers, with resultant stage migration and worse survival; however, few data exist in patients with hepatocellular carcinoma (HCC). These data are of particular importance in light of the COVID-19 pandemic, which has caused disruptions in healthcare processes and may continue to impact cancer care for the foreseeable future. The aim of our study was to characterize the prevalence and clinical significance of diagnostic and treatment delays in patients with HCC. METHODS We performed a retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and July 2017 at 2 US health systems. Diagnostic and treatment delays were defined as >90 days between presentation and HCC diagnosis and between diagnosis and treatment, respectively. We used multivariable logistic regression to identify factors associated with diagnostic and treatment delays and Cox proportional hazard models to identify correlates of overall survival. RESULTS Of 925 patients with HCC, 39.0% were diagnosed via screening, 33.1% incidentally, and 27.9% symptomatically. Median time from presentation to diagnosis was 37 days (interquartile range, 18-94 days), with 120 patients (13.0%) experiencing diagnostic delays. Median time from HCC diagnosis to treatment was 46 days (interquartile range, 29-74 days), with 17.2% of patients experiencing treatment delays. Most (72.5%) diagnostic delays were related to provider-level factors (eg, monitoring indeterminate nodules), whereas nearly half (46.2%) of treatment delays were related to patient-related factors (eg, missed appointments). In multivariable analyses, treatment delays were not associated with increased mortality (hazard ratio, 0.90; 95% CI, 0.60-1.35); these results were consistent across subgroup analyses by Barcelona Clinic Liver Cancer stage and treatment modality. CONCLUSIONS Diagnostic and therapeutic delays exceeding 3 months are common in patients with HCC; however, observed treatment delays do not seem to significantly impact overall survival.
Biochemical characterization of a recombinant acid phosphatase from Acinetobacter baumannii

Genomic sequence analysis of Acinetobacter baumannii revealed the presence of a putative Acid Phosphatase (AcpA; EC 3.1.3.2). A plasmid construct was made, and recombinant protein (rAcpA) was expressed in E. coli. PAGE analysis (carried out under denaturing/reducing conditions) of nickel-affinity purified protein revealed the presence of a near-homogeneous band of approximately 37 kDa. The identity of the 37 kDa species was verified as rAcpA by proteomic analysis with a molecular mass of 34.6 kDa from the deduced sequence. The dependence of substrate hydrolysis on pH was broad with an optimum observed at 6.0. Kinetic analysis revealed relatively high affinity for PNPP (Km = 90 μM) with Vmax, kcat, and Kcat/Km values of 19.2 pmoles s-1, 4.80 s-1(calculated on the basis of 37 kDa), and 5.30 x 104 M-1s-1, respectively. Sensitivity to a variety of reagents, i.e., detergents, reducing, and chelating agents as well as classic acid phosphatase inhibitors was examined in addition to assessment of hydrolysis of a number of phosphorylated compounds. Removal of phosphate from different phosphorylated compounds is supportive of broad, i.e., ‘nonspecific’ substrate specificity; although, the enzyme appears to prefer phosphotyrosine and/or peptides containing phosphotyrosine in comparison to serine and threonine. Examination of the primary sequence indicated the absence of signature sequences characteristic of Type A, B, and C nonspecific bacterial acid phosphatases.
The higBA-Type Toxin-Antitoxin System in IncC Plasmids Is a Mobilizable Ciprofloxacin-Inducible System

Toxin-antitoxin (TA) systems play vital roles in maintaining plasmids in bacteria. Plasmids with incompatibility group C are large plasmids that disseminate via conjugation and carry high-profile antibiotic resistance genes. ABSTRACT A putative type II toxin-antitoxin (TA) module almost exclusively associated with conjugative IncC plasmids is homologous to the higBA family of TA systems found in chromosomes and plasmids of several species of bacteria. Despite the clinical significance and strong association with high-profile antimicrobial resistance (AMR) genes, the TA system of IncC plasmids remains largely uncharacterized. In this study, we present evidence that IncC plasmids encode a bona fide HigB-like toxin that strongly inhibits bacterial growth and results in cell elongation in Escherichia coli. IncC HigB toxin acts as a ribosome-dependent endoribonuclease that significantly reduces the transcript abundance of a subset of adenine-rich mRNA transcripts. A glycine residue at amino acid position 64 is highly conserved in HigB toxins from different bacterial species, and its replacement with valine (G64V) abolishes the toxicity and the mRNA cleavage activity of the IncC HigB toxin. The IncC plasmid higBA TA system functions as an effective addiction module that maintains plasmid stability in an antibiotic-free environment. This higBA addiction module is the only TA system that we identified in the IncC backbone and appears essential for the stable maintenance of IncC plasmids. We also observed that exposure to subinhibitory concentrations of ciprofloxacin, a DNA-damaging fluoroquinolone antibiotic, results in elevated higBA expression, which raises interesting questions about its regulatory mechanisms. A better understanding of this higBA-type TA module potentially allows for its subversion as part of an AMR eradication strategy. IMPORTANCE Toxin-antitoxin (TA) systems play vital roles in maintaining plasmids in bacteria. Plasmids with incompatibility group C are large plasmids that disseminate via conjugation and carry high-profile antibiotic resistance genes. We present experimental evidence that IncC plasmids carry a TA system that functions as an effective addiction module and maintains plasmid stability in an antibiotic-free environment. The toxin of IncC plasmids acts as an endoribonuclease that targets a subset of mRNA transcripts. Overexpressing the IncC toxin gene strongly inhibits bacterial growth and results in cell elongation in Escherichia coli hosts. We also identify a conserved amino acid residue in the toxin protein that is essential for its toxicity and show that the expression of this TA system is activated by a DNA-damaging antibiotic, ciprofloxacin. This mobile TA system may contribute to managing bacterial stress associated with DNA-damaging antibiotics.
Isolation and Genomic Analysis of the Phage vB_PaeP_fHoPae04 Infecting Pseudomonas aeruginosa

Here, we report the genomic sequence of Pseudomonas aeruginosa phage vB_PaeP_fHoPae04, isolated from hospital wastewater in Helsinki, Finland. The phage genome is 45,491 bp long, has a G+C content of 52.2%, and contains 70 protein-coding genes and 3 tRNA genes. ABSTRACT Here, we report the genomic sequence of Pseudomonas aeruginosa phage vB_PaeP_fHoPae04, isolated from hospital wastewater in Helsinki, Finland. The phage genome is 45,491 bp long, has a G+C content of 52.2%, and contains 70 protein-coding genes and 3 tRNA genes.
Heart failure as a complication of COVID-19 infection: systematic review and meta-analysis

Abstract Background/objectives The prevalence and prognostic implications of heart failure (HF), as a complication of COVID-19 infection remains unclear. We performed a systematic review and metanalysis aimed to evaluate the pooled incidence of acute HF as a cardiac complication of COVID-19 disease and to estimate the related mortality risk in these patients. Methods Data were obtained searching MEDLINE, Scopus and Web of Science for all investigations published any time to 26 December 2020. If statistical heterogeneity was 50%, the results were derived from the fixed-effects model otherwise the random-effects model. Results Overall, 1064 patients [mean age 66 years, 618 males] were included in the final analysis reviewing six investigations. The cumulative in-hospital rate of COVID-19 patients complicated by acute HF ranged between 6.9 and 63.4% among the studies reviewed. A random effect model revealed a pooled incidence of COVID-19 patients complicated by acute HF in 20.2% of cases (95% CI: 11.1–33.9%, p < 0.0001 I2 = 94.4%). A second pooled analysis, based on a random-effect model, confirmed a significant increased risk of death in COVID-19 patients complicated by acute HF during the infection (OR 9.36, 95% CI 4.76–18.4, p < 0.0001, I2 = 56.6%). Meta-regression analysis, using age as moderator variable, failed in founding a statistically significant relationship with the incidence of acute HF onset as a complication of COVID-19 disease (p = 0.062) or the mortality risk among the same subjects (p = 0.053). Conclusions Acute HF represents a frequent complication of COVID-19 infection associated with a higher risk of mortality in the short-term period.
Naturally-derived protein extract from Gryllus bimaculatus improves antioxidant properties and promotes osteogenic differentiation of hBMSCs

Naturally-derived proteins or peptides are promising biopolymers for tissue engineering applications owing to their health-promoting activity. Herein, we extracted proteins (~90%) from two-spotted cricket (Gryllus bimaculatus) and evaluated their osteoinductive potential in human bone marrow-derived mesenchymal stem cells (hBMSCs) under in vitro conditions. The extracted protein isolate was analyzed for the amino acid composition and the mass distribution of the constituent peptide fraction. Fourier transform infrared (FTIR) spectroscopy was used to determine the presence of biologically significant functional groups. The cricket protein isolate (CPI) exhibited characteristic protein peaks in the FTIR spectrum. Notably, an enhanced cell viability was observed in the presence of the extracted proteins, showing their biocompatibility. The CPI also exhibited antioxidant properties in a concentration-dependent manner. More significant mineralization was observed in the CPI-treated cells than in the control, suggesting their osteoinductive potential. The upregulation of the osteogenic marker genes (Runx2, ALP, OCN, and BSP) in CPI treated media compared with the control supports their osteoinductive nature. Therefore, cricket-derived protein isolates could be used as functional protein isolate for tissue engineering applications, especially for bone regeneration.
Prospective Evaluation of Health Care Provider and Patient Assessments in Chemotherapy-Induced Peripheral Neurotoxicity

Background and Objective There is no agreement on the gold standard for detection and grading of chemotherapy-induced peripheral neurotoxicity (CIPN) in clinical trials. The objective is to perform an observational prospective study to assess and compare patient-based and physician-based methods for detection and grading of CIPN. Methods Consecutive patients, aged 18 years or older, candidates for neurotoxic chemotherapy, were enrolled in the United States, European Union, or Australia. A trained investigator performed physician-based scales (Total Neuropathy Score–clinical [TNSc], used to calculate Total Neuropathy Score–nurse [TNSn]) and supervised the patient-completed questionnaire (Functional Assessment of Cancer Treatment/Gynecologic Oncology Group–Neurotoxicity [FACT/GOG-NTX]). Evaluations were performed before and at the end of chemotherapy. On participants without neuropathy at baseline, we assessed the association between TNSc, TNSn, and FACT/GOG-NTX. Considering a previously established minimal clinically important difference (MCID) for FACT/GOG-NTX, we identified participants with and without a clinically important deterioration according to this scale. Then, we calculated the MCID for TNSc and TNSn as the difference in the mean change score of these scales between the 2 groups. Results Data from 254 participants were available: 180 (71%) had normal neurologic status at baseline. At the end of the study, 88% of participants developed any grade of neuropathy. TNSc, TNSn, and FACT/GOG-NTX showed good responsiveness (standardized mean change from baseline to end of chemotherapy >1 for all scales). On the 153 participants without neuropathy at baseline and treated with a known neurotoxic chemotherapy regimen, we verified a moderate correlation in both TNSc and TNSn scores with FACT/GOG-NTX (Spearman correlation index r = 0.6). On the same sample, considering as clinically important a change in the FACT/GOG-NTX score of at least 3.3 points, the MCID was 3.7 for TNSc and 2.8 for the TNSn. Conclusions MCID for TNSc and TNSn were calculated and the TNSn can be considered a reliable alternative objective clinical assessment if a more extended neurologic examination is not possible. The FACT/GOG-NTX score can be reduced to 7 items and these items correlate well with the TNSc and TNSn. Classification of Evidence This study provides Class III evidence that a patient-completed questionnaire and nurse-assessed scale correlate with a physician-assessed scale.
Thiol–disulfide homeostasis and ischemia‐modified albumin as a marker of oxidative stress in patients with sarcopenia

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength. Chronic inflammatory conditions and increased oxidative stress are in the pathogenesis of sarcopenia. Our aim was to evaluate the relationship between sarcopenia and thiol–disulfide homeostasis and ischemia‐modified albumin levels as an oxidative stress marker.
Warming and elevated CO2 alter tamarack C fluxes, growth and mortality: evidence for heat stress-related C starvation in the absence of water stress.

Climate warming is increasing the frequency of climate-induced tree mortality events. While drought combined with heat is considered the primary cause of this mortality, little is known about whether moderately, high temperatures alone can induce mortality, or whether rising CO2 would prevent mortality at high growth temperatures. We grew tamarack (Larix laricina) under ambient (400 ppm) and elevated (750 ppm) CO2 concentrations combined with ambient, ambient +4°C, and ambient +8°C growth temperatures to investigate whether high growth temperatures lead to carbon limitations and mortality. Growth at +8°C led to 40% mortality in the ambient CO2 (8TAC) treatment, but no mortality in the elevated CO2 treatment. Thermal acclimation of respiration led to similar leaf carbon balances across the warming treatments, despite a lack of photosynthetic acclimation. Photosynthesis was stimulated under elevated CO2, increasing seedling growth, but not leaf carbon concentrations. However, growth and foliar carbon concentrations were lowest in the +8°C treatments, even with elevated CO2. Dying 8TAC seedlings had lower needle carbon concentrations and lower ratios of photosynthesis to respiration than healthy 8TAC seedlings, indicating that carbon limitations were likely the cause of seedling mortality under high growth temperatures.
Ultrahigh specific strength in a magnesium alloy strengthened by spinodal decomposition

Spinodal decomposition is discovered to be an effective way to strengthen magnesium alloy. Strengthening of magnesium (Mg) is known to occur through dislocation accumulation, grain refinement, deformation twinning, and texture control or dislocation pinning by solute atoms or nano-sized precipitates. These modes generate yield strengths comparable to other engineering alloys such as certain grades of aluminum but below that of high-strength aluminum and titanium alloys and steels. Here, we report a spinodal strengthened ultralightweight Mg alloy with specific yield strengths surpassing almost every other engineering alloy. We provide compelling morphological, chemical, structural, and thermodynamic evidence for the spinodal decomposition and show that the lattice mismatch at the diffuse transition region between the spinodal zones and matrix is the dominating factor for enhancing yield strength in this class of alloy.
Diffusion tensor imaging reveals greater microstructure damage in lesional tissue that shrinks into cerebrospinal fluid in multiple sclerosis

Atrophied T2 lesion volume (LV), reflecting the complete transformation of lesions into cerebrospinal fluid (CSF), has been associated with disease progression in multiple sclerosis (MS). The underlying damage leading to lesion destruction remains poorly understood. The objective of this study was to use diffusion tensor imaging (DTI) to investigate the extent of microstructural tissue damage at baseline in lesions that subsequently transform into CSF.