Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma

Simple Summary Multiple myeloma (MM) is an incurable hematological malignancy characterized by an increase in abnormal plasma cells. Disease progression, drug resistance, and immunosuppression in MM are associated with immune-related molecules, such as immune checkpoint and co-stimulatory molecules, present in the tumor microenvironment. Novel agents targeting these cell-surface molecules are currently under development, including monoclonal antibodies, bispecific monoclonal antibodies, and chimera antigen receptor T-cell therapies. In this review, we focus on the signaling lymphocytic activation molecule family receptors and provide an overview of their biological functions and novel therapies in MM. Abstract The signaling lymphocytic activation molecule (SLAM) family receptors are expressed on various immune cells and malignant plasma cells in multiple myeloma (MM) patients. In immune cells, most SLAM family molecules bind to themselves to transmit co-stimulatory signals through the recruiting adaptor proteins SLAM-associated protein (SAP) or Ewing’s sarcoma-associated transcript 2 (EAT-2), which target immunoreceptor tyrosine-based switch motifs in the cytoplasmic regions of the receptors. Notably, SLAMF2, SLAMF3, SLAMF6, and SLAMF7 are strongly and constitutively expressed on MM cells that do not express the adaptor proteins SAP and EAT-2. This review summarizes recent studies on the expression and biological functions of SLAM family receptors during the malignant progression of MM and the resulting preclinical and clinical research involving four SLAM family receptors. A better understanding of the relationship between SLAM family receptors and MM disease progression may lead to the development of novel immunotherapies for relapse prevention.
The prevalence and associated factors of adverse pregnancy outcomes among Afghan women in Iran; Findings from community-based survey

Backgrounds An estimated 2.5 million Afghans are living in the Iran and almost half of them are young women at the childbearing ages. Although the evidence indicates lower rates of antenatal care and higher incidence of pregnancy complications in Afghan compared to Iranian women, the underlying reasons are not well defined. Therefore, in the present study, we aimed to explore the prevalence and associated sociodemographic factors of adverse pregnancy outcomes and examine the impact of intimate partner violence, food insecurity, poor mental health, and housing issues on pregnancy outcome in Afghan women living in Iran. Methods In July 2019, we enrolled 424 Afghan women aged 18–44 years old using the time-location sampling at three community health centers in the south region of Tehran province. The data was collected through face to face interviews using the researcher-developed questionnaire. Using bivariate and multivariate analysis, the impact of poor antenatal care, intimate partner violence, food insecurity, and poor mental health was assessed on the incidence of adverse pregnancy outcome. Results More than half (56.6%) of Afghan women reported at least one pregnancy complication in their recent pregnancy. The results showed that undocumented, illiterate, and unemployed Afghan women with lower socioeconomic status are more likely to experience adverse pregnancy outcomes. Furthermore, we observed lower prevalence of adverse pregnancy outcomes among documented immigrants with health insurance compared to those with no health insurance. It is also been found that the food insecurity [Adjusted OR = 3.35, 95% CI (1.34–8.36)], poor antenatal care [Adjusted OR = 10.50, 95% CI (5.40–20.39)], intimate partner violence [Adjusted OR = 2.72, 95% CI (1.10–6.77)], and poor mental health [Adjusted OR = 4.77, 95% CI (2.54–8.94)] could adversely impact the pregnancy outcome and we observed higher incidence of adverse outcomes among those suffering from these situations. Conclusion To our knowledge, this is the first study that explored the prevalence and associated factors of adverse pregnancy outcomes and the impact of intimate partner violence, food insecurity, poor mental health on pregnancy outcome among Afghan women in Iran. Enhancing the psychosocial support and empowering Afghan women through expanding the social network and safety net should be a priority for the central government and international parties. Psychological counseling should be incorporated into routine maternity care for Afghan refugees. Access to free antenatal care is a right for all Afghan women and it should be facilitated by universal health insurance for all Afghans regardless of their legal status.
Association of digoxin with mortality in patients with advanced chronic kidney disease: A population-based cohort study

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate—eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23–2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75–1.86), ischemic stroke (sHR 1.42; 95% CI 0.85–2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78–1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.
Observation of an extremely constricted cathodic arc attachment to electrodes of high intensity discharge lamps

Usually two modes of arc attachment to cathodes for high intensity discharge (HID) lamps are observed, the spot mode for high pressure, low currents and large electrode diameters and the diffuse mode for the opposite conditions. Recently, a very constricted attachment to cathodes was observed both in real HID lamps and in Bochum’s model lamp. In the model lamp, the extremely constricted arc attachment was observed in argon and xenon atmosphere at a pressure p = 0.26 MPa and for currents I = 1–6 A. Whereas the global electrode temperature and the cathode fall of the diffuse and the spot mode differ only slightly, the extremely constricted arc attachment (so-called ‘super spot mode’) is associated with a significantly decreased global electrode temperature at similar parameters. The reduction in electrode temperature implies low cathode falls and low electrode losses, respectively. Scanning electron micrographs show that the surface structure of the electrodes has substantial influence on the mode of cathodic arc attachment.
Assessing Health-Related Quality of Life Among Survivors of Testicular Cancer: A Systematic Review

This study aimed to determine if the current health-related quality of life (HRQoL) tools created for survivors of testicular cancer are collecting the highest quality of data via a two-step methodological critique of both the seminal studies that produced a survivor of testicular cancer HRQoL tool (Phase 1) and the actual tool itself (Phase 2). It is the goal of this current article to present and discuss Phase 1. A systematic review aimed to assess the methodological quality of studies conducted to create instruments used to measure survivors of testicular cancer HRQoL. Five reviewers independently assessed each study with the 20-item Appraisal Tool for Cross-Sectional Studies (AXIS). Inter-rater agreement and Fleiss’ kappa was also assessed to ensure consistency in reported scores. Assessments for the EORTC QLQ-TC 26 and CAYA-T studies were low (AXIS 52.5%; IRA 95%; κ = 0.779) and fair (AXIS 65%; IRA 80%; κ = 0.599), respectively. Critical appraisal of the scales included issues within the three core AXIS domains. Primary concerns related to sampling methodology and the lack of a qualitative component of their core conceptual development phase. Both reviewed seminal studies have significant methodological concerns that question the tools’ quality. Next steps include extensive appraisal of the psychometric properties of the EORTC QLQ TC-26 and the CAYA-T to complete the comprehensive review. Accurate and reliable data are necessary to understand survivor of testicular cancer HRQoL and assist in building the bridge of communication between health care professionals and survivors to help to improve patient outcomes.
Electrocardiographic features and their echocardiographic correlates in peripartum cardiomyopathy: results from the ESC EORP PPCM registry

In peripartum cardiomyopathy (PPCM), electrocardiography (ECG) and its relationship to echocardiography have not yet been investigated in large multi‐centre and multi‐ethnic studies. We aimed to identify ECG abnormalities associated with PPCM, including regional and ethnic differences, and their correlation with echocardiographic features.
Survey-derived best management practices for backyard beekeepers improve colony health and reduce mortality

Honey bee colony losses in the US have exceeded acceptable levels for at least a decade, leaving beekeepers in need of management practices to improve colony health and survival. Here, an empirical Best Management Practice (BMP) regimen was tested, comprised of the top four management practices associated with reduced colony mortality in backyard beekeeping operations according to Bee Informed Partnership Loss and Management survey results. Seven study locations were established across the US, and each location consisted of ten colonies treated according to empirical BMPs and ten according to average beekeeping practice. After 3 years, colonies treated according to empirical BMPs experienced reduced Varroa infestation, viral infection, and mortality compared to colonies managed with Average practices. In addition, BMP colonies produced more new colonies via splits. The colonies under Average practices were given chemical Varroa treatments only once per year, and thus spent more months above economic threshold of 3.0 mites/100 bees. Increased time spent above the economic threshold was significantly correlated to both increased viral infection and colony mortality. This study demonstrates the cumulative effects of management and colony health stressors over months and years, especially the dire importance of regular Varroa monitoring and management.
Development of a Multiplex Real-Time PCR Assay for Predicting Macrolide and Tetracycline Resistance Associated with Bacterial Pathogens of Bovine Respiratory Disease

Antimicrobial resistance (AMR) in bovine respiratory disease (BRD) is an emerging concern that may threaten both animal and public health. Rapid and accurate detection of AMR is essential for prudent drug therapy selection during BRD outbreaks. This study aimed to develop a multiplex quantitative real-time polymerase chain reaction assay (qPCR) to provide culture-independent information regarding the phenotypic AMR status of BRD cases and an alternative to the gold-standard, culture-dependent test. Bovine clinical samples (297 lung and 111 nasal) collected in Nebraska were subjected to qPCR quantification of macrolide (MAC) and tetracycline (TET) resistance genes and gold-standard determinations of AMR of BRD pathogens. Receiver operating characteristic curve analysis was used to classify AMR based on the qPCR results. For lung tissues, the qPCR method showed good agreement with the gold-standard test for both MACs and TETs, with a sensitivity of 67–81% and a specificity higher than 80%. For nasal swabs, qPCR results passed validation criteria only for TET resistance detection, with a sensitivity of 88%, a specificity of 80% and moderate agreement. The culture-independent assay developed here provides the potential for more rapid AMR characterization of BRD cases directly from clinical samples at equivalent accuracy and higher time efficiency compared with the gold-standard, culture-based test.
Completion of the AAV Structural Atlas: Serotype Capsid Structures Reveals Clade-Specific Features

The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting.
Distinct Gene Expression Signatures Characterize Strong Clinical Responders Versus Nonresponders to Canakinumab in Children With Systemic Juvenile Idiopathic Arthritis

Canakinumab is a human anti–interleukin‐1β (anti–IL‐1β) blocking agent that effectively neutralizes IL‐1β–mediated signaling for treatment of systemic juvenile idiopathic arthritis (JIA). While many patients have dramatic clinical response to IL‐1 blockade, approximately one‐third fail to respond, but there are currently no validated clinical or immunologic predictors of response. We undertook this study to characterize distinct gene signatures for treatment response and nonresponse to canakinumab in systemic JIA patients.
Rotational temperature measurements in atmospheric pulsed dielectric barrier discharge - gas temperature and molecular fraction effects

This study was dedicated to the correlation between the rotational temperature and the plasma gas temperature in a non-thermal atmospheric plasma obtained by a dielectric barrier discharge. Different parameters were modified (e.g. gas temperature, molecular fraction) in argon water gas mixtures. The rotational temperature of OH(A) was spectroscopically measured. It is shown that in mixtures mainly composed of atomic species, namely rare gases, the OH(A) rotational temperature is strongly correlated with a gas temperature streamer. In mixed (atomic and molecular) plasmas it seems that the rotational temperature can constitute an approach to the translational energy of heavy particles in the streamer areas.
PRIASE 2021 guidelines for reporting animal studies in Endodontology: a consensus-based development.

Animal testing is crucial in situations when research on humans is not allowed because of unknown health risks and ethical concerns. The current project aims to develop reporting guidelines exclusively for animal studies in Endodontology, using an established consensus-based methodology. The guidelines have been named: Preferred Reporting Items for Animal Studies in Endodontology (PRIASE) 2021. Nine individuals (PD, VN, AK, PM, MN, JF, EP, JJ, SJ), including the project leaders (PD, VN) formed a steering committee. The steering committee developed a novel checklist by adapting and integrating their animal testing and peer-review experience with the Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines and also the Clinical and Laboratory Images in Publications (CLIP) principles. A PRIASE Delphi Group (PDG) and PRIASE Online Meeting Group (POMG) were also formed. Thirty-one PDG members participated in the online Delphi process and achieved consensus on the checklist items and flowchart that were used to formulate the PRIASE guidelines. The novel PRIASE 2021 guidelines were discussed with the POMG on 9th September 2020 via a Zoom online video call attended by 21 individuals from across the globe, and seven steering committee members. Following the discussions, the guidelines were modified and then piloted by several authors whilst writing a manuscript involving research on animals. The PRIASE 2021 guidelines are a checklist consisting of 11 domains and 43 individual items together with a flowchart. The PRIASE 2021 guidelines are focused on improving the methodological principles, reproducibility and quality of animal studies in order to enhance their reliability as well as repeatability to estimate the effects of endodontic treatments and usefulness for guiding future clinical studies on humans.
Efficacy of Advance Care Planning Videos for Patients: A Randomized Controlled Trial in Cancer, Heart, and Kidney Failure Outpatient Settings

Background Patient videos about advance care planning (ACP; hereafter “Videos”), were developed to support uptake of provincial policy and address the complexity of patients’ decision-making process. We evaluate self-administered ACP Videos, compare the studies’ choice of outcomes, show correlations between the patients’ ACP actions, and discuss implications for health care policy. Objective To test the efficacy of the Videos on patients’ ACP/goals of care designation conversations with a health care provider. Design, Setting, and Participants Using a 2-arm, 1:1 randomized controlled trial, we recruited outpatients with a diagnosis of kidney failure, heart failure, metastatic lung, gastrointestinal, or gynecological cancer from 22 sites. Analysis followed the intention-to-treat principle. Interventions Videos describing the ACP process and illustrating the resuscitative, medical, and comfort levels of care. Main Outcomes and Measures The primary outcome was the proportion of participants who reported having an ACP/goals of care designation (GCD) conversation with a health care provider by 3 mo. Outcomes were measured using the Behaviours in Advance Care Planning and Actions Survey, an online survey capturing ACP attitudes, processes, and actions. Results We analyzed 241 and 217 participants at baseline and 3 mo, respectively. The proportion of participants who had an ACP/GCD conversation with a health care provider by 3 mo was significantly different between study arms (46% intervention; 32% control; adjusted odds ratio, 1.83; P = 0.032). Adjusted for the quality of conversations, there was no significant difference. Conclusions Videos as stand-alone tools do not engage individuals in high-quality ACP. Pragmatic trials are necessary to evaluate their impact on downstream outcomes when integrated into intentional, comprehensive conversations with a health care provider. Considering the strong correlation between 2 activities (physicians discussing options, patients telling health care providers preferences), policy should focus on empowering patients to initiate these conversations.
A Bispecific Single-Domain Antibody Boosts Autologous Vγ9Vδ2-T Cell Responses Toward CD1d in Chronic Lymphocytic Leukemia

Purpose: Although considerable progress has been made with autologous T cell–based therapy in B-cell malignancies, application in chronic lymphocytic leukemia (CLL) lags behind due to disappointing response rates as well as substantial toxicity that is of particular concern in the elderly CLL population. Vγ9Vδ2-T cells form a conserved T-cell subset with strong intrinsic immunotherapeutic potential, largely because of their capacity to be triggered by phosphoantigens that can be overproduced by CLL and other malignant cells. Specific activation of Vγ9Vδ2-T cells by a bispecific antibody may improve the efficacy and toxicity of autologous T-cell–based therapy in CLL. Experimental Design: We evaluated CD1d expression in a cohort of 78 untreated patients with CLL and generated and functionally characterized a CD1d-specific Vγ9Vδ2-T cell engager based on single-domain antibodies (VHH). Results: CD1d was expressed by CLL in the majority of patients, particularly in patients with advanced disease. The CD1d-specific Vγ9Vδ2-T cell engager induced robust activation and degranulation of Vγ9Vδ2-T cells, enabling Vγ9Vδ2-T cells from patients with CLL to lyse autologous leukemic cells at low effector-to-target ratios. Expression of CD1d on CLL cells is upregulated by all-trans retinoic acid, and sensitizes the malignant cells to bispecific VHH-induced lysis. Furthermore, we provide evidence that the Vγ9Vδ2-T cell receptor retains responsiveness to phosphoantigens when the bispecific VHH is bound, and aminobisphosphonates can therefore enhance bispecific Vγ9Vδ2-T cell engager–mediated tumor-specific killing. Conclusions: Collectively, our data demonstrate the immunotherapeutic potential of this novel CD1d-specific Vγ9Vδ2-T cell engager in CLL.
Hard ticks (Acari: Ixodidae) infesting domestic animals in Egypt: diagnostic characters and a taxonomic key to the collected species

Ticks are important vectors of emerging health problems in humans and animals. We conducted several field surveillances to investigate the fauna of hard ticks on domestic animals in seven governorates of Egypt during 2018–2019. A total of 3265 individual tick specimens were collected and identified to the species level; the specimens belong to 11 species within three genera (Amblyomma, Hyalomma, and Rhipicephalus). Tick infestation was highest in dromedary camels (70%), followed by dogs (52.5%), cattle (50%), buffaloes (38%), and horses (12%). Ten species were collected from dromedary camels, 2 from cattle, and one species from dogs, buffaloes, and horses. Diagnostic characters with high‐quality photographic images of the 11 tick species were provided. New measurements of the body regions such as spiracles and body grooves were also obtained to provide further details on morphological variations among the diverse tick species. This study provided detailed descriptions of the genital apertures of five Hyalomma species. Morphological variations of male Hyalomma impeltatum, and genital apertures of female Hyalomma dromedarii and Hyalomma excavatum were also examined in this study. Finally, we provided additional details on local geographic distributions, hosts, endemicity status, and disease relationships of the eleven tick species.