Miracle-dz/UniFAR-FTUs huggingface dataset:
Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes

OBJECTIVE Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as “level 2 hypoglycemia. ” In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association. RESEARCH DESIGN AND METHODS Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). RESULTS For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c. CONCLUSIONS IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.
Traditional Human Immunodeficiency Virus treatment and family and social influence as barriers to accessing HIV care services in Belu, Indonesia

Access to HIV care services, including antiretroviral therapy (ART), is essential for improving health outcomes of people living with HIV (PLHIV) and reducing HIV transmission and AIDS-related deaths. As a part of a qualitative study in Belu, this paper describes the use of traditional medicines for HIV treatment and family and social influence as barriers to access to HIV care services among PLHIV. One-on-one in-depth interviews were employed to collect data from 46 PLHIV (26 women and 20 men) and 10 healthcare professionals. They were recruited using the snowball sampling technique. The study information sheets were initially posted on information boards in healthcare facilities. Potential participants who contacted to confirm their participation were recruited for an interview and then asked for help to distribute the information sheets to their eligible colleagues who might be willing to participate. Data analysis was performed using NVivo 12 software and guided by a qualitative data analysis framework. The findings showed that the use of traditional medicines, a well-known cultural practice in Belu, was a barrier to access to HIV care services among PLHIV. The influence of family in determining the use of traditional medicines for HIV treatment, supported by the lack of knowledge of ART, effectiveness of traditional medicines in treating other health issues, and social influence of relatives, neighbours, and friends, were also significant barriers to PLHIV’s access to HIV care services. The findings indicate the need for dissemination of HIV care-related information for PLHIV, family, and community members to increase their knowledge of the service, ART and its function, and to support and improve access to HIV care services especially ART by PLHIV.
Mechanisms of immune effector cell‐associated neurotoxicity syndrome after CAR‐T treatment

Abstract Chimeric antigen receptor T‐cell (CAR‐T) treatment has revolutionized the landscape of cancer therapy with significant efficacy on hematologic malignancy, especially in relapsed and refractory B cell malignancies. However, unexpected serious toxicities such as cytokine release syndrome (CRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS) still hamper its broad application. Clinical trials using CAR‐T cells targeting specific antigens on tumor cell surface have provided valuable information about the characteristics of ICANS. With unclear mechanism of ICANS after CAR‐T treatment, unremitting efforts have been devoted to further exploration. Clinical findings from patients with ICANS strongly indicated existence of overactivated peripheral immune response followed by endothelial activation‐induced blood–brain barrier (BBB) dysfunction, which triggers subsequent central nervous system (CNS) inflammation and neurotoxicity. Several animal models have been built but failed to fully replicate the whole spectrum of ICANS in human. Hopefully, novel and powerful technologies like single‐cell analysis may help decipher the precise cellular response within CNS from a different perspective when ICANS happens. Moreover, multidisciplinary cooperation among the subjects of immunology, hematology, and neurology will facilitate better understanding about the complex immune interaction between the peripheral, protective barriers, and CNS in ICANS. This review elaborates recent findings about ICANS after CAR‐T treatment from bed to bench, and discusses the potential cellular and molecular mechanisms that may promote effective management in the future. This article is categorized under: Cancer > Biomedical Engineering Immune System Diseases > Molecular and Cellular Physiology Neurological Diseases > Molecular and Cellular Physiology
Conserved requirement of autophagy-related effectors during coronavirus replication

ABSTRACT The recurrence of zoonotic transmission events highlights the need for novel treatment strategies against emerging coronaviruses (CoVs), namely SARS-CoV, MERS-CoV and most notably SARS-CoV-2. Our recently performed genome-wide CRISPR knockout screen revealed a list of conserved pan-coronavirus as well as MERS-CoV or HCoV-229E-specific host dependency factors (HDF) essential during the viral life cycle. Intriguingly, we identified the macroautophagy/autophagy pathway-regulating immunophilins FKBP8, TMEM41B, and MINAR1 as conserved MERS-CoV, HCoV-229E, SARS-CoV, and SARS-CoV-2 host factors, which further constitute potential targets for therapeutic intervention by clinically approved drugs.
“I Have to Fight to Get Out”: African American Women Intimate Partner Violence Survivors’ Construction of Agency

African American women survivors of intimate partner violence are disproportionately murdered and help-seeking is a critical variable to examine as it relates to it. There is an urgent need to develop culturally salient interventions that center African American women’s ways of knowing. An initial step to doing so is identifying how they employ their sense of individual agency during help-seeking. This paper reflects findings from a study designed to do just that. We conducted 30 in-depth, semi-structured interviews with women who self-identified as African American. Constructivist grounded theory methodology was employed. Constructed agency emerged from the data. This nascent theory explicates four phases of African American women survivors’ help-seeking: resistance, persistence, rejection, and resignation. Constructed agency provides practitioners and researchers with a theoretical model to examine African American women’s nuanced help-seeking efforts when seeking informal supports and interventions from formal providers.
Scalar Pulse Width Modulation Strategies For Matrix Converters

This paper describes three different scalar pulse width modulation (PWM) techniques for matrix converters to be compared to two other scalar techniques proposed here. Before exposing all the techniques, a mathematical review of the matrix converters is done to aid the comprehension of this converter. These new techniques use, for synthesizing an output reference voltage, only two input voltages in each switching period. As consequence, the losses of the switching process are expected to be lower than the losses of the other techniques. All techniques presented, but one, have unity displacement factor (DF). To verify the characteristics of these new methods, some simulation results are presented and compared with some simulation results presented by the other methods.
Selecting ideal drugs for encapsulation in thermosensitive liposomes and other triggered nanoparticles

Abstract Objective Thermosensitive liposomes (TSL) and other triggered drug delivery systems (DDS) are promising therapeutic strategies for targeted drug delivery. However, successful designs with candidate drugs depend on many variables, including nanoparticle formulation, drug properties, and cancer cell properties. We developed a computational model based on experimental data to predict the potential efficacies of drugs when used with triggered DDS, such as TSL. Methods A computer model based on the Krogh cylinder was developed to predict uptake and cell survival with four anthracyclines when delivered by intravascular triggered DDS (e.g., TSL): doxorubicin (DOX), idarubicin (IDA), pirarubicin (PIR), and aclarubicin (ACLA). We simulated three tumor types derived from SVR angiosarcoma, LLC lung cancer, or SCC-1 oral carcinoma cells. In vitro cellular drug uptake and cytotoxicity data were obtained experimentally and incorporated into the model. Results For all three cell lines, ACLA and IDA had the fastest cell uptake, with slower uptake for DOX and PIR. Cytotoxicity was highest for IDA and lowest for ACLA. The computer model predicted the highest tumor drug uptake for ACLA and IDA, resulting from their rapid cell uptake. Overall, IDA was most effective and produced the lowest tumor survival fraction, with DOX being the second best. Perivascular drug penetration was reduced for drugs with rapid cell uptake, potentially limiting delivery to cancer cells distant from the vasculature. Conclusion Combining simple in vitro experiments with a computer model could provide a powerful screening tool to evaluate the potential efficacy of candidate investigative drugs preceding TSL encapsulation and in vivo studies.
Nitrogen removal by a strengthened comprehensive floating bed with embedded pellets made by a newly isolated Pseudomonas sp. Y1

ABSTRACT A newly heterotrophic nitrification aerobic denitrification(HN-AD) bacterium Pseudomonas sp. Y1 with highly nitrogen removal ability was isolated from the activated sludge, TN removal rate of which was 99.73%. In this study, two types of different ecology floating bed systems were designed to achieve efficient nitrogen removal in the urban eutrophic landscape water body, one is the comprehensive ecological floating bed(CEFB) system with only Lythrum salicari and the other is the strengthened comprehensive ecological floating bed (SCEFB) system with both Lythrum and embedded pellets made by Y1. The TN removal rates of the CEFB system were 33.82%, 83.84% and 88.91% at 8±1℃, 15±1℃ and 25±1℃, respectively, while the TN removal rates of the SCEFB system increased by nearly 40%, 16% and 11% at the same environment, respectively. The result shows that the SCEFB system can purify the simulated water from surface water body class V to class IV. Thus it has a broad application prospect in the urban eutrophic landscape water body. GRAPHICAL ABSTRACT
A dual‐mode waveguide filter based on stereometamaterial CSRR resonator

This paper represents a new dual‐mode waveguide filter based on a stereometamaterial resonator. A novel resonator is proposed in the paper consisting of two stacked complementary split ring resonators (CSRR) where one of them is twisted in its plane. This resonator provides a transmission zero, which can be easily adjusted in both of the upper and lower stopbands of the filter. By cascading the four of the proposed resonator, an eight order symmetric filter with four transmission zeros are designed. The filter parameters are optimized using the genetic algorithm (GA). This filter is fabricated and the experimental results are in a good agreement with the simulation data. Besides the flexibility in the design, the most important characteristic of the proposed structure is its compactness compared to similar structures.
Postnatal microcephaly and retinal involvement expand the phenotype of RPL10 ‐related disorder

Hemizygous missense variants in the RPL10 gene encoding a ribosomal unit are responsible for an X‐linked syndrome presenting with intellectual disability (ID), autism spectrum disorder, epilepsy, dysmorphic features, and multiple congenital anomalies. Among 15 individuals with RPL10‐related disorder reported so far, only one patient had retinitis pigmentosa and microcephaly was observed in approximately half of the cases. By exome sequencing, three Italian and one Spanish male children, from three independent families, were found to carry the same hemizygous novel missense variant p.(Arg32Leu) in RPL10, inherited by their unaffected mother in all cases. The variant, not reported in gnomAD, is located in the 28S rRNA binding region, affecting an evolutionary conserved residue and predicted to disrupt the salt‐bridge between Arg32 and Asp28. In addition to features consistent with RPL10‐related disorder, all four boys had retinal degeneration and postnatal microcephaly. Pathogenic variants in genes responsible for inherited retinal degenerations were ruled out in all the probands. A novel missense RPL10 variant was detected in four probands with a recurrent phenotype including ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies. The presented individuals suggest that retinopathy and postnatal microcephaly are clinical clues of RPL10‐related disorder, and at least the retinal defect might be more specific for the p.(Arg32Leu) RPL10 variant, suggesting a specific genotype/phenotype correlation.
Anti‐HBc‐nonreactive occult hepatitis B infections with HBV genotypes B and C in vaccinated immunocompetent adults

Absence of anti‐HBc reactivity with detectable anti‐HBs was observed in blood donors with occult hepatitis B virus (HBV) infection (OBI). The prevalence and mechanisms underlying this uncommon condition were investigated over time in Chinese blood donors with OBI. Isolated anti‐HBs OBI status was identified from 466,911 donors from Dalian, China, and monitored in follow‐up (range: 2.6–84.3 months). HBV vaccination status was documented, and infecting viral strains were characterized. Of 451 confirmed OBIs (1:1035), 43 (9.5%; 1:10,858) had isolated anti‐HBs as only serological marker. Isolated anti‐HBs OBIs differed from anti‐HBc‐reactive OBIs by significantly younger age (median 24 years), higher HBV DNA (median: 20 IU/ml) and anti‐HBs (median 60.5 IU/L) levels, paucity of mutations in HBV Core and S proteins, and high vaccination rate (72%). Vaccinated isolated anti‐HBs OBIs (n = 31) differed from unvaccinated (n = 11) by significantly younger age (22 vs 38 years), higher anti‐HBs level at index (48% vs 9% with anti‐HBs >100 IU/L) and higher frequency of anti‐HBs immune response (44% vs 20%). Of 15 vaccinated and 5 unvaccinated OBIs follow‐up, 65% (8 vaccinated and 5 unvaccinated) became HBV DNA negative suggesting aborted recent infection, while 35% (7 vaccinated) had low persistent viraemia 2 to 65 months post index. In conclusion, isolated anti‐HBs OBI in Chinese blood donors appears associated with young, vaccinated, adults exposed to HBV who predominantly develop low level aborted infection revealed by transient HBV DNA and immune anti‐HBs response. However, a subset of individuals still experienced low but persistent viral replication whose clinical outcome remains uncertain.
Synaptic components are required for glioblastoma progression in Drosophila

Glioblastoma (GB) is the most aggressive, lethal and frequent primary brain tumor. It originates from glial cells and is characterized by rapid expansion through infiltration. GB cells interact with the microenvironment and healthy surrounding tissues, mostly neurons and vessels. GB cells project tumor microtubes (TMs) contact with neurons, and exchange signaling molecules related to Wingless/WNT, JNK, Insulin or Neuroligin-3 pathways. This cell to cell communication promotes GB expansion and neurodegeneration. Moreover, healthy neurons form glutamatergic functional synapses with GB cells which facilitate GB expansion and premature death in mouse GB xerograph models. Targeting signaling and synaptic components of GB progression may become a suitable strategy against glioblastoma. In a Drosophila GB model, we have determined the post-synaptic nature of GB cells with respect to neurons, and the contribution of post-synaptic genes expressed in GB cells to tumor progression. In addition, we document the presence of intratumoral synapses between GB cells, and the functional contribution of pre-synaptic genes to GB calcium dependent activity and expansion. Finally, we explore the relevance of synaptic genes in GB cells to the lifespan reduction caused by GB advance. Our results indicate that both presynaptic and postsynaptic proteins play a role in GB progression and lethality.
Durability of switched therapy after failure of WHO-recommended antiretroviral therapy regimens in a resource-limited setting

Objective: The study investigated the durability of switched therapy and factors associated with the viral rebound among patients on second-line antiretroviral therapy (ART) in Uganda. Design: A retrospective dynamic cohort of adults initiated on second-line ART after virological failure to first-line ART. Methods: Patients on second-line treatment for at least 6 months between 2007 and 2017 were included. Patients were followed, until they experienced a viral rebound (viral load ≥200 copies/ml). Cumulative probability of viral rebounds and factors associated with viral rebound were determined using Kaplan–Meier methods and Cox proportional hazard models. Results: One thousand, one hundred and one participants were enrolled of which 64% were women, the median age was 37 years [interquartile range (IQR) 31–43]. The preswitch median CD4+ cell count and viral load were 128 cells/μl (IQR 58–244) and 45 978 copies/ml (IQR 13 827–139 583), respectively. During the 4190.37 person-years, the incidence rate of viral rebound was 83.29 [95% confidence interval (CI) 74.99–92.49] per 1000 person-years. The probability of viral rebound at 5 and 10 years was 0.29 (95% CI 0.26–0.32) and 0.62 (95% CI 0.55–0.69), respectively. The median rebound-free survival was 8.7 years. Young adults (18–24 years) [adjusted hazard ratio (aHR) 2.49, 95% CI 1.32–4.67], preswitch viral load at least 100 000 copies/ml (aHR 1.53, 95% CI 1.22–1.92), and atazanavir/ritonavir (ATV/r)-based second-line (aHR 1.73, 95% CI 1.29–2.32) were associated with an increased risk of viral rebound. Conclusion: Switched therapies are durable for 8 years after failure of recommended regimens. A high preswitch viral load, ATV/r-based regimens, and young adulthood are risk factors for viral rebound, which underscores the need for more durable regimens and differentiated care services.
The pleiotropic roles of SPT5 in transcription

ABSTRACT Initially discovered by genetic screens in budding yeast, SPT5 and its partner SPT4 form a stable complex known as DSIF in metazoa, which plays pleiotropic roles in multiple steps of transcription. SPT5 is the most conserved transcription elongation factor, being found in all three domains of life; however, its structure has evolved to include new domains and associated posttranslational modifications. These gained features have expanded transcriptional functions of SPT5, likely to meet the demand for increasingly complex regulation of transcription in higher organisms. This review discusses the pleiotropic roles of SPT5 in transcription, including RNA polymerase II (Pol II) stabilization, enhancer activation, Pol II pausing and its release, elongation, and termination, with a focus on the most recent progress of SPT5 functions in regulating metazoan transcription.
Drug-drug interactions between psychotropic medications and oral contraceptives

ABSTRACT Introduction This is a comprehensive overview of pharmacokinetic drug-drug interactions (DDIs) involving oral contraceptives (OCs) and psychotropic medications. Areas covered Medline and Embase from inception to April 2021 were searched for DDIs between OCs and psychotropic medications. They included case reports/series and cross-sectional, cross-over, placebo-controlled studies of patient cohorts and healthy females. We classified DDIs as: combined hormonal contraceptives (CHCs) acting as victim drugs (i.e. affected by psychotropic co-medications), CHCs as perpetrators, (i.e. affecting the activity of psychotropic co-medications), progestin-derivatives as victim drugs and progestin-derivatives affecting psychotropic co-medications. Alteration ratios reflecting changes in pharmacokinetic parameters before and after the DDI were estimated to approximate the extent of the DDI. Expert opinion Women taking antiepileptic agents with strong to moderate enzyme-inducing properties (carbamazepine, phenobarbital, phenytoin) or those with moderate to mild enzyme-inducing properties (cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, rufinamide, topiramate) should avoid OCs. Daily doses of cytochrome P450 1A2 substrates including clozapine may need to be reduced by 50% in women taking concomitant CHCs. Compared to CHCs, the propensity of progestin-only pills for DDIs has been investigated less. We provide a summary table for clinicians containing recommendations based on literature and package inserts; whenever evidence was available, we provided dose-correction factors.
Prehospital Tranexamic Acid in Major Pediatric Trauma Within a Physician-Led Emergency Medical Services System: A Multicenter Retrospective Study

Objectives: Describe prehospital tranexamic acid (TXA) use and appropriateness within a major trauma pediatric population, and identify the factors associated with its use. Design: Multicenter, retrospective study, 2014–2020. Setting: Data were extracted from a multicenter French trauma registry including nine trauma centers within a physician-led prehospital emergency medical services (EMS) system. Patients: Patients less than 18 years old were included. Those who did not receive prehospital intervention by a mobile medical team and those with missing data on TXA administration were excluded. Interventions: None. Measurements and Main Results: Nine-hundred thirty-four patients (median [interquartile range] age: 14 yr [9–16 yr]) were included, and 68.6% n = 639) were male. Most patients were involved in a road collision (70.2%, n = 656) and suffered a blunt trauma (96.5%; n = 900). Patients receiving TXA (36.6%; n = 342) were older (15 [13–17] vs 12 yr [6–16 yr]) compared with those who did not. Patient severity was higher in the TXA group (Injury Severity Score 14 [9–25] vs 6 [2–13]; p < 0.001). The median dosage was 16 mg/kg (13–19 mg/kg). TXA administration was found in 51.8% cases (n = 256) among patients with criteria for appropriate use. Conversely, 32.4% of patients (n = 11) with an isolated severe traumatic brain injury (TBI) also received TXA. Age (odds ratio [OR], 1.2; 95% CI, 1.1–1.2), A and B prehospital severity grade (OR, 7.1; 95% CI, 4.1–12.3 and OR, 4.5; 95% CI, 2.9–6.9 respectively), and year of inclusion (OR, 1.2; 95% CI, 1.1–1.3) were associated with prehospital TXA administration. Conclusions: In our physician-led prehospital EMS system, TXA is used in a third of severely injured children despite the lack of high-level of evidence. Only half of the population with greater than or equal to one criteria for appropriate TXA use received it. Conversely, TXA was administered in a third of isolated severe TBI. Further research is warranted to clarify TXA indications and to evaluate its impact on mortality and its safety profile to oversee its prescription.