Miracle-dz/UniFAR-FTUs huggingface dataset:
Outgrowth endothelial progenitor cells restore cerebral barrier function following ischaemic damage: The impact of NOX2 inhibition

Disruption of blood–brain barrier (BBB), formed mainly by human brain microvascular endothelial cells (HBMECs), constitutes the major cause of mortality following ischaemic stroke. This study investigates whether OECs (outgrowth endothelial cells) can restore BBB integrity and function following ischaemic damage and how inhibition of NOX2, a main source of vascular oxidative stress, affects the characteristics of BBB established with OECs and HBMECs in ischaemic settings. In vitro models of human BBB were constructed by co‐culture of pericytes and astrocytes with either OECs or HBMECs before exposure to oxygen–glucose deprivation (OGD) alone or followed by reperfusion (OGD + R) in the absence or presence of NOX2 inhibitor, gp91ds‐tat. The function and integrity of BBB were assessed by measurements of paracellular flux of sodium fluorescein (NaF) and transendothelial electrical resistance (TEER), respectively. Treatment with OECs during OGD + R effectively restored BBB integrity and function. Compared to HBMECs, OECs possessed lower NADPH oxidase activity, superoxide anion levels and had greater total antioxidant capacity during OGD and OGD + R. Inhibition of NADPH oxidase during OGD and OGD + R restored the integrity and function of BBB established by HBMECs. This was evidenced by reductions in NADPH oxidase activity and superoxide anion levels. In contrast, treatment with gp91ds‐tat aggravated ischaemic injury‐induced BBB damage constructed by OECs. In conclusion, OECs are more resistant to ischaemic conditions and can effectively repair cerebral barrier following ischaemic damage. Suppression of oxidative stress through specific targeting of NOX2 requires close attention while using OECs as therapeutics.
Evaluation of Natural Language Processing for the Identification of Crohn Disease–Related Variables in Spanish Electronic Health Records: A Validation Study for the PREMONITION-CD Project

Background The exploration of clinically relevant information in the free text of electronic health records (EHRs) holds the potential to positively impact clinical practice as well as knowledge regarding Crohn disease (CD), an inflammatory bowel disease that may affect any segment of the gastrointestinal tract. The EHRead technology, a clinical natural language processing (cNLP) system, was designed to detect and extract clinical information from narratives in the clinical notes contained in EHRs. Objective The aim of this study is to validate the performance of the EHRead technology in identifying information of patients with CD. Methods We used the EHRead technology to explore and extract CD-related clinical information from EHRs. To validate this tool, we compared the output of the EHRead technology with a manually curated gold standard to assess the quality of our cNLP system in detecting records containing any reference to CD and its related variables. Results The validation metrics for the main variable (CD) were a precision of 0.88, a recall of 0.98, and an F1 score of 0.93. Regarding the secondary variables, we obtained a precision of 0.91, a recall of 0.71, and an F1 score of 0.80 for CD flare, while for the variable vedolizumab (treatment), a precision, recall, and F1 score of 0.86, 0.94, and 0.90 were obtained, respectively. Conclusions This evaluation demonstrates the ability of the EHRead technology to identify patients with CD and their related variables from the free text of EHRs. To the best of our knowledge, this study is the first to use a cNLP system for the identification of CD in EHRs written in Spanish.
Misplaced Intuitions in Interventions to Reduce Attractiveness-Based Discrimination

Individuals and organizations are increasing efforts to address discrimination. Nonexperts may lack awareness of, or are resistant to, scientifically informed strategies for reducing discrimination, instead relying on intuition. Five studies investigated the accuracy of nonexperts’ intuitions about reducing discrimination concerning physical attractiveness. In Studies 1a to 1c (N = 902), participants predicted the effectiveness of six interventions to reduce attractiveness-based favoritism on a judgment task. Studies 2a and 2b (N = 6,292) investigated the effectiveness of these interventions. Although two interventions reduced discrimination, intuitions were poorly aligned with actual results; fewer than 1% of participants identified the combination of interventions that did, versus did not, impact judgment, and responses were more likely to be below than above chance when predicting each intervention’s effectiveness. Although follow-up work should investigate the accuracy of intuition in other forms of discrimination, these results further stress the need for greater development and adoption of evidence-based strategies for combating discrimination.
Pregnancy outcomes in female cancer survivors after hematopoietic stem cell transplantation.

OBJECTIVE This study was conducted to retrospectively investigate the pregnancy outcomes of patients who underwent stem cell transplantation (SCT). We also aimed at determining the reasons for avoiding pregnancy despite prolonged remission. PATIENTS AND METHODS The study population consisted of patients who became pregnant after autologous or allogeneic SCT at Dr. Abdurrahman Yurtarslan Oncology Hospital between 2009 and 2020 for hematologic diseases. Data from 83 patients who had undergone allogeneic or autologous SCT were available for analysis. A total of 18 pregnancies occurred in 14 of these patients. To compare pregnancy outcomes, pregnant patients who received care at Etlik Zübeyde Hanım Maternity Hospital were selected as the control group. RESULTS No pregnancy occurred in 69 of the patients whose data were analyzed. Of these 69 patients, 48 (69.6%) did not want to become pregnant. The most common reason for not wanting a pregnancy was due to the fact that the patient was not married [21 patients (30.4%)]. The pregnancy rate was higher in the HL group than in other hematologic malignancies [8 patients (57.1%)]. Twelve (85.7%) of the patients who became pregnant did so after autologous SCT and 2 (14.3%) after allogeneic SCT. The cumulative incidence of obstetric complications was higher in pregnancies after SCT than in the control group, and the prevalence of low birth weight was observed more frequently. CONCLUSIONS Patients who became pregnant after SCT have a higher rate of pregnancy complications. However, these patients achieve similar live birth rates as the healthy population. Many patients have concerns about pregnancy and should be counseled appropriately.
The glue that keeps everybody together: Peer support in mothers of young children with special health care needs

Abstract Background The first years following diagnosis may be particularly challenging for parents and peer support from other parents of children with special health care needs may buffer their stress. Methods This qualitative interview study sought to explore the impact of early access to parental peer support and whether it leads to positive adaptation and improved family well‐being. Results Five mothers of young children with special health care needs from peer support organizations in two northern US states participated in interviews by telephone or Zoom. Themes of interest included professional scrutiny, going through the motions, someone who understands, learning and sharing, and one size does not fit all. Although most participants attributed positive changes in their emotional well‐being to the support they received, they were wary of extending the impact of peer support to their child and family. Conclusions Implications for practice include embedding peer support programmes in neonatal care units and children's hospitals, as well as the addition of mindfulness practices to facilitate parental adaptation to disability and promote family well‐being.
Features of Odontogenic Sinusitis Associated With Dental Implants

With the increase in dental implants for tooth loss, odontogenic sinusitis following maxillary dental implants is frequently encountered in otorhinolaryngology practice. The authors aimed to reveal the association between implant extrusion into maxillary sinus, along with implant‐related complications in patients diagnosed with implant‐related odontogenic sinusitis (IR‐ODS).
Tool evaluation for the detection of variably sized indels from next generation whole genome and targeted sequencing data

Insertions and deletions (indels) in human genomes are associated with a wide range of phenotypes, including various clinical disorders. High-throughput, next generation sequencing (NGS) technologies enable the detection of short genetic variants, such as single nucleotide variants (SNVs) and indels. However, the variant calling accuracy for indels remains considerably lower than for SNVs. Here we present a comparative study of the performance of variant calling tools for indel calling, evaluated with a wide repertoire of NGS datasets. While there is no single optimal tool to suit all circumstances, our results demonstrate that the choice of variant calling tool greatly impacts the precision and recall of indel calling. Furthermore, to reliably detect indels, it is essential to choose NGS technologies that offer a long read length and high coverage coupled with specific variant calling tools.
Hypomethylating agent and venetoclax in patients with chronic myelomonocytic leukemia: Is the combination indeed better?

REFERENCES 1. Branch DR. Unraveling the IVIG mystique. Transfusion. 2013;53(2): 242-244. 2. Galeotti C, Kaveri SV, Bayry J. IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol. 2017;29(11): 491-498. 3. Pendergrast J, Armali C, Callum J, et al. A prospective observational study of the incidence, natural history, and risk factors for intravenous immunoglobulin-mediated hemolysis. Transfusion. 2021;61(4):10531063. 4. Bruggeman CW, Nagelkerke SQ, Lau W, et al. Treatment-associated hemolysis in Kawasaki disease: association with blood-group antibody titers in IVIG products. Blood Adv. 2020;4(14):3416-3426. 5. Michelis FV, Branch DR, Scovell I, et al. Acute hemolysis after intravenous immunoglobulin amid host factors of ABO-mismatched bone marrow transplantation, inflammation, and activated mononuclear phagocytes. Transfusion. 2014;54(3):681-690. 6. Mohamed M. Intravenous immunoglobulin-associated hemolysis: risk factors, challenges, and solutions. Int J Clin Transfus Med. 2016;4:121-131. 7. Lakkaraja M, Jin JC, Manotas K, et al. Blood group a mothers are more likely to develop anemia during antenatal intravenous immunoglboulin treatment of fetal and neonatal alloimmune thrombocytopenia. Transfusion. 2016;56(10):2449-2454. 8. Wallenhorst C, Patel A, Shebl A, et al. Anti-a/B isoagglutinin reduction in an intravenous immunoglobulin product and risk of hemolytic anemia: a hospital-based cohort study. Transfusion. 2020;60(7):13811390. 9. Gerber S, Gaida A, Spiegl N, et al. Reduction of Isoagglutinin in intravenous immunoglobulin (IVIG) using blood group Aand B-specific Immunoaffinity chromatography: industry-scale assessment. BioDrugs. 2016;30(5):441-451. 10. Nguyen AA, Habiballah SB, Platt CD, et al. Immunoglobulins in the treatment of COVID-19 infection: proceed with caution! Clin Immunol. 2020;216:108459. Received: 20 January 2022 Revised: 11 February 2022 Accepted: 16 February 2022 DOI: 10.1002/ajh.26504
Exposure to immediate-release tramadol in children 6 years and under – a nationwide French poison control center study

Abstract Introduction Data regarding immediate-release (IR)-tramadol exposures in children remain sparse. We aimed to investigate the incidence of IR-tramadol exposures in ≤6-year-old children, to describe the characteristics and resulting outcome of ingestions involving IR-tramadol alone, and to estimate a clinically relevant toxic dose in this population. Methods Retrospective analysis of IR-tramadol exposures in ≤6-year-old children, collected by the French Poison Control Centers (PCCs) in 2003–2019. The incidence was estimated using IR-tramadol prescription data from the Health Improvement Network database (the French version of THIN). The Poison severity score (PSS) was used to grade severity. Results We found 1260 IR-tramadol exposures in ≤6-year-old children. The number of cases per 100,000 IR-tramadol-treated patients increased over time (p < .0001). One hundred forty-five cases involving IR-tramadol alone were analyzed. The median age was 3.0 years (IQR: 1.9, 4.0), the M/F ratio was 1.5 and the median dose was 5.0 mg/kg (IQR 3.3–11.1). Half of the children (49.7%) remained asymptomatic (PSS0) while 29.6% and 14.5% developed minor (PSS1) or moderate-to-severe (PSS2–PSS3) neurological symptoms, respectively. Twelve children developed respiratory depression. No seizures and no fatality were reported. All symptomatic children recovered within 24 h. The ingested IR-tramadol dose was positively correlated with the PSS (p < .0001). Using a receiver operating characteristic (ROC) curve approach (area under the curve, 0.92; p < .001), ingestion of ≥7.4 mg/kg IR-tramadol was appropriate to recommend hospital referral (sensitivity, 100% [95% confidence interval (CI), 85–100]; specificity, 73% [95% CI, 64–80]; predictive positive value, 39% [95% CI, 35–57]; negative predictive value, 100% [95% CI, 96–100]). Children who ingested <7.4 mg/kg IR-tramadol developed no (n = 68) or minor (n = 22) neurological symptoms. Conclusions Despite increasing tramadol prescriptions in adults during the study period in France, oral exposure to IR-tramadol in ≤6-year-old children was rare but possibly responsible for severe toxicity. Children with no underlying disease and concomitant medication ingesting <7.4 mg/kg IR-tramadol alone could be observed at home. However, given the observed variability in the onset of seizures after tramadol ingestion, which can occur at ingested tramadol doses below 7.4 mg and even at therapeutic doses, parents or guardians should be specifically warned about the risk of seizures.
Fontan‐associated liver disease

1Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA 2Division of Abdominal Imaging, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA 3Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA 4Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
Motor point stimulation induces more robust F‐waves than peripheral nerve stimulation

The F‐wave is a motor response induced by electrical stimulation of peripheral nerves via the antidromic firing of motor nerves, which reflects the motoneuron excitability. To induce F‐waves, transcutaneous peripheral nerve stimulation (PNS) is used, which activates nerve branches via transcutaneous electrodes over the nerve branches. An alternative method to activate peripheral nerves, that is, motor point stimulation (MPS), which delivers electrical stimulation over the muscle belly, has not been used to induce F‐waves. In our previous studies, we observed that MPS induced F‐wave‐like responses, that is, motor responses at the latency of F‐waves at a supramaximal stimulation. Here, we further investigated the F‐wave‐like responses induced by MPS in comparison with PNS in the soleus muscle. Thirteen individuals participated in this study. We applied MPS and PNS on the participant's left soleus muscle. Using a monopolar double‐pulse stimulation, the amplitude of the second H‐reflex induced by PNS decreased, whereas the amplitude of the motor response at the F‐wave latency induced by MPS did not decrease. These results suggest that the motor response at the F‐wave latency induced by MPS was not an H‐reflex but an F‐wave. We also found that the F‐wave induced by MPS had a greater amplitude and higher persistence and caused less pain when compared with the F‐waves induced using PNS. We conclude that MPS evokes antidromic firing inducing F‐waves more consistently compared with PNS.
Gut microbiota-drug interactions in cancer pharmacotherapies: implications for efficacy and adverse effects

ABSTRACT Introduction The gut microbiota is involved in host physiology and health. Reciprocal microbiota-drug interactions are increasingly recognized as underlying some individual differences in therapy response and adverse events. Cancer pharmacotherapies are characterized by a high degree of interpatient variability in efficacy and side effect profile and recently, the microbiota has emerged as a factor that may underlie these differences. Areas covered The effects of cancer pharmacotherapy on microbiota composition and function are reviewed with consideration of the relationship between baseline microbiota composition, microbiota modification, antibiotics exposure, and cancer therapy efficacy. We assess the evidence implicating the microbiota in cancer therapy-related adverse events including impaired gut function, cognition, and pain perception. Finally, potential mechanisms underlying microbiota-cancer drug interactions are described, including direct microbial metabolism, and microbial modulation of liver metabolism and immune function. This review focused on preclinical and clinical studies conducted in the last 5 years. Expert opinion Preclinical and clinical research supports a role for baseline microbiota in cancer therapy efficacy, with emerging evidence that the microbiota modification may assist in side effect management. Future efforts should focus on exploiting this knowledge toward the development of microbiota-targeted therapies. Finally, a focus on specific drug-microbiota-cancer interactions is warranted.
Site of death among individuals with and without dementia in 2016–2018

Individuals living with dementia often have limited capacity to express their care preferences at the final stage of life, and therefore, are at risk of receiving end-of-life care that may not align with their preferences. While most people prefer to be at home in their final days of life, research has shown that individuals with dementia are less likely to die in a home or community setting compared to those without dementia. Studies also suggest that the percentage of individuals with dementia who died in a home or community setting has been increasing over time. This study sought to update the literature by examining the association between dementia status and site of death, and by comparing the trends in site of death between decedents with and without dementia using recent national data.
Oxidative stress and inflammation parameters-novel biomarkers for idiopathic pulmonary fibrosis.

OBJECTIVE The pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) are not well elucidated. It is assumed that oxidative stress and inflammation are the key underlying culprits for its onset and progression. To gain deeper insight into these processes, we have evaluated several oxidative stress parameters, inflammation markers [i.e., high sensitivity C-reactive protein (hsCRP), serum amyloid A1 (SAA1)], soluble programmed cell death-ligand 1 (sPD-L1), and 25-hydroxyvitamin D [25(OH)D] in IPF patients. PATIENTS AND METHODS Biochemistry analyses were done in 30 consecutive IPF patients and 30 age and gender-matched healthy control group (CG). RESULTS IPF patients had significantly higher advanced oxidation protein products (p<0.001), pro-oxidant-antioxidant balance (p=0.010), total oxidative status (p<0.001), and ischemia modified albumin (p<0.001) compared to CG. Lower total antioxidant status and total sulfhydryl groups (tSGH) and significantly higher sPD-L1, hsCRP (p<0.001 for all), SAA1 proteins (p=0.014) and [25(OH)D] severe deficiency [11.0 (9.6-15.1) nmol/L] in IPF patients compared to CG were observed. Paraoxonase 1 activity and hsCRP level were lower, while tSHG and sPD-L1 were higher in IPF patients with more severe disease (i.e., II+III stage compared to I stage, p<0.05 for all). CONCLUSIONS IPF patients are in a state of profound oxidative stress compared to healthy people. The inflammatory component of the disease was confirmed by higher hsCRP and SAA1, but lower [25(OH)D] in IPF than in healthy people. Also, higher levels of sPD-L1 in patients with IPF compared to healthy individuals suggest that sPD-L1 may have a significant role in immune response in IPF.
Hippocampal neurons maintain a large PtdIns(4)P pool that results in faster PtdIns(4,5)P2 synthesis

Is phosphoinositide metabolism cell-type specific? By comparing the amount and rate of synthesis between hippocampal neurons, astrocytes, and the tsA201 cell line, de la Cruz et al. show that central neurons have a larger PtdIns(4)P pool and are faster at synthesizing PtdIns(4,5)P2.
Combination therapy based on targeted nano drug co-delivery systems for liver fibrosis treatment: a review

Abstract Liver fibrosis is the hallmark of liver disease and occurs prior to the stages of cirrhosis and hepatocellular carcinoma. Any type of liver damage or inflammation can result in fibrosis. Fibrosis does not develop overnight, but rather as a result of the long-term action of injury factors. At present, however, there are no good treatment methods or specific drugs other than removing the pathogenic factors. Drug application is still limited, which means that drugs with good performance in vitro cannot achieve good therapeutic effects in vivo, owing to various factors such as poor drug targeting, large side effects and strong hydrophobicity. Hepatic stellate cells (HSCs) are the primary effector cells in liver fibrosis. The nano-drug delivery system is a new and safe drug delivery system that has many advantages which are widely used in the field of liver fibrosis. Drug resistance and side effects can be reduced when two or more drugs are used in combination drug delivery. Combination therapy of drugs with different targets has emerged as a novel approach to treating liver fibrosis, and the nano co-delivery system enhances the benefits of combination therapy. While nano co-delivery systems can maximise benefits while avoiding drug side effects, this is precisely the advantage of the nano co-delivery system. This review briefly described the pathogenesis and current treatment strategies, the different co-delivery systems of combination drugs in the nano delivery system, and targeting strategies for nano delivery systems on liver fibrosis therapy. Due to their superior performance, nano delivery systems and targeting drug delivery systems have received a lot of attention in the new drug delivery system. The new delivery systems offer a new pathway in the treatment of liver fibrosis, and it is believed that it can be a new treatment for fibrosis in the future. Nano co-delivery system of combination drugs and targeting strategies has proven the effectiveness of anti-fibrosis at the experimental level.
Mitochondrial Diversity of the Asian Tiger Mosquito Aedes albopictus (Diptera: Culicidae) in Peninsular Malaysia

Abstract Aedes albopictus is one of the main mosquito vectors responsible for transmitting arboviruses to humans and animals. The ability of this mosquito to support virus transmission has been linked to vector competence, which is partly attributed to the genetic disparities in Ae. albopictus population. At present, little is known about the biologically important traits of Ae. albopictus in Malaysia. Thus, the study aims to determine the genetic variation of Ae. albopictus based on the mitochondria-encoded sequences of cytochrome oxidase subunit I (COI). A statistical parsimony network of 253 taxa aligned as 321 characters of the COI gene revealed 42 haplotypes (H1–H42), of which H1 was the most widespread haplotype in Peninsular Malaysia. Three highly divergent haplotypes (H21, H30, and H31) were detected from the northern population. Overall, haplotype and nucleotide diversities were 0.576 and 0.003, respectively, with low genetic differentiation (FST = 0.039) and high gene flow (Nm = 12.21) across all populations.