bluuebunny/crossref_metadata_2025 huggingface dataset:
P038 Ultrasound scanning in gum clinics – is it feasible; is it valuable?
Authors: Suchak Tara , Taher Marjan , Schweitzer Margaritha Von
Published: May 2024

Introduction

With increasing financial constraint and commissioning pressures, GUM providers need to develop services to improve clinical care and cut costs. In order to provide fully integrated sexual health provision we introduced trans-vaginal ultrasound scanning to assess IUD/IUS position and placement as well as scanning for deep implants in August 2016 at a central London clinic.

Methods

A member of staff trained in ultrasound was identified and a suitable portable machine sourced. From 11th August 2016, the new service was advertised to clinics within the trust and patients could be referred for assessment of coil/implant presence and position both for booked ‘sessions’ and on an ad hoc basis.

Results

To 3rdMarch 2017, 127 TV scans have been performed. The indication for scanning was: 70 (55%) post insertion of inter-uterine contraception; 21 (17%) for lost threads; 9 (7%) bleeding problems and 27 (21%) other reasons.

5% (6/127) devices were identified as incorrectly positioned and could be changed at the scanning appointment. Only 1 patient required onward referral for a departmental ultrasound scan.

Discussion

Ultrasound scanning in GUM clinics is feasible and has proven to be a valuable addition to current services offered. Consequently referrals for hospital based ultrasound scans have decreased, resulting in shorter waiting times for patients as well as providing a ‘one stop shop’ for patients.
P041 Disintegrating sexual and reproductive healthcare? our patients’ views
Authors: Bull Lauren , Rayment Michael , Jones Rachael , Cohen CE
Published: May 2024

Introduction

The drive for integrated sexual and reproductive health services has improved access for women. However, councils in our area indicate Level 3 services will only provide initial contraceptive scripts, redirecting women to primary care services thereafter. We canvassed service users’ opinions.

Method

Women dispensed with pill/patch/ring/injection prescriptions during February 2017 were invited to complete an anonymous online survey.

Results

The response rate was 46% (92 responses over four weeks). Half lived locally. A majority were aged 18–34 years (77, 84%), of white ethnicity (73, 80%) and in full-time employment (78; 84%). Most were GP registered (77, 84%). Most were pill users (62, 67%). Over half sought a repeat prescription (52, 57%), 24 (26%) were new starters and 18 (20%) requested a sexual health screen.

Two thirds (63, 69%) walked-in without an appointment. One third (32, 35%) stated they couldn’t be seen at their GP. Ease of access was the main driver for attendance (76, 77%). Other key reasons for choosing our service: access to their method of choice (50, 54%); professional advice about methods (34, 37%); to ask sexual health advice (18, 20%); to receive STI screening (21, 23%). 78 women (87%) cited they had concerns about the council’s proposal, with 69 (85%) stating access to primary care concerned them.

Discussion

This survey highlights the value to patients of easy access to skilled professionals who provide comprehensive sexual and reproductive healthcare. Significant concerns were raised about this proposal, which ignores both the need and value women place on integrated services like ours.
P043 Contraceptive use in HIV positive women. are effective methods being offered?
Authors: Bell Laura , Wilson Yvonne , Dinsmore Wallace , Donnelly Claire , Emerson Carol , McCarty Emma , Walker Eoin , Quah Say
Published: May 2024

Introduction

British HIV Association (BHIVA) guidelines recommend that consistent condom use should be encouraged along with additional methods of contraception for women living with HIV. Highly active antiretroviral therapy (HAART) may reduce the efficacy of hormonal contraceptive.

Methods

A retrospective chart review was carried out of all women under the age of 45 regularly attending the clinic (attended twice in the past year). Charts were reviewed to establish if the method of contraception used was discussed and documented within the past year, which method was being used and if there were any drug interactions.

Results

A total of 145 female patients were identified. The method of contraception used was documented in 75%, as shown in the table. Of the women reporting no contraceptive use 14 were not sexually active. 124 (86%) patients were prescribed HAART. Of those patients who were prescribed HAART and hormonal methods of contraception, 2 potential drug interactions were identified of which 1 had been discussed with patient. From 2014–2016 29 patients became pregnant (those diagnosed through antenatal services were excluded) of which 19 where prescribed HAART.

Discussion

Contraceptive methods should be discussed with HIV positive patients along with advice on consistent use of condoms in patients using hormonal methods of contraception and HAART. This will help prevent unplanned pregnancies as well as HIV transmission.

Abstract P043 Table 1

Contraceptive use in HIV positive women

Method of ContraceptionCondomsNoneIUSIUDHysterectomy/SterilisedCOCPOPImplantDMPANot documentedNumber of Patients4636836421237
Impact of Attitude, Emotion, Interaction, and Perception on Learner Satisfaction in Online Learning with Mediating Effect of Motivation During COVID-19
Authors: Mukherjee Debarshi , Saha Mahasweta , Chakraborty Subhayan , Jena Lokesh Kumar , Hasan Khandakar Kamrul , Debnath Ranjit , Mitra Sudakshina
Published: May 2024

Switching from traditional to online learning during the COVID-19 pandemic bore the associated opportunities and challenges. The study presents the clout of Perception, Emotion, Attitude, Teacher-Student, and Peer interaction on Learner Satisfaction (LS) partially mediated by motivation among business management students of Russia, India, and Bangladesh. The psychological framework used in the study, followed by Structural Equation Modelling, displayed a significant association between all exogenous and endogenous variables. The responses from the 1008 students during the pandemic corroborate two critical learning theories, i.e. Social Constructivism and Media Richness Theory, by confirming a significant and positive relationship between attitude and motivation. The learners’ perception of the content and administration is pivotal for LS. Whereas peer learning was an important aspect in Russia and India, assisted learning was preferred by the students of Bangladesh.
Heart Signal Analysis Using Multistage Classification Denoising Model
Authors: Choudhary Ravi Raj , Rani Mamta , Kaur Ranjit , Bhadu Mahendra
Published: May 2024

Cardiovascular disease is a major cause of death worldwide, and the COVID-19 pandemic has only made the situation worse. The purpose of this work is to explore various time-frequency analysis methods that can be used to classify heart sound signals and identify multiple abnormalities in the heart, such as aortic stenosis, mitral stenosis, and mitral valve prolapse. The signal has been modified using three techniques—tunable quality wavelet transform (TQWT), discrete wavelet transform (DWT), and empirical mode decomposition—to detect heart signal abnormality. The proposed model detects heart signal abnormality at two stages, the user end and the clinical end. At the user end, binary classification of signals is performed, and if signals are abnormal then further classification is done at the clinic. The approach starts with signal preprocessing and uses the discrete wavelet transform (DWT) coefficients to train the hybrid model, which consists of one long short-term memory (LSTM) network layer and three convolutional neural network (CNN) layers. This method produced comparable results, with a 98.9% classification accuracy for signals, through the utilization of the CNN and LSTM model. Combining the CNN’s skill in feature extraction with the LSTM’s capacity to record time-dependent features improves the efficacy of the model. Identifying issues early and initiating appropriate medication can alleviate the burden associated with heart valve diseases.
Semiquantitative Risk Evaluation Reveals Drivers of African Swine Fever Virus Transmission in Smallholder Pig Farms and Gaps in Biosecurity, Tanzania
Authors: Fasina Folorunso O. , Mtui-Malamsha Niwael , Nonga Hezron E. , Ranga Svetlana , Sambu Rosamystica M. , Majaliwa Jerome , Kamani Enos , Okuthe Sam , Kivaria Fredrick , Bebay Charles , Penrith Mary-Louise
Published: May 2024

African swine fever (ASF) has remained persistent in Tanzania since the early 2000s. Between 2020 and 2021, pig farms in twelve districts in Tanzania were infected with ASF, and ≥4,804 pigs reportedly died directly due to the disease with disruption to livelihoods. We conducted semiquantitative field investigations and rapid risk assessment (RRA) to understand the risk factors and drivers of ASF virus (ASFV) amplification and transmission in smallholder pig farms, and determine the gaps in biosecurity through hazard profiling, focus group discussions and expert opinion. Outbreaks were connected by road and aligned along the pig product value chain and reported in the northern, central, and southern parts of Tanzania. The patterns of outbreaks and impacts differed among districts, but cases of ASF appeared to be self‐limiting following significant mortality of pigs in farms. Movement of infected pigs, movement of contaminated pig products, and fomites associated with service providers, vehicles, and equipment, as well as the inadvertent risks associated with movements of animal health practitioners, visitors, and scavengers were the riskiest pathways to introduce ASFV into smallholder pig farms. Identified drivers and facilitators of risk of ASFV infection in smallholder pig farms were traders in whole pigs, middlemen, pig farmers, transporters, unauthorized animal health service providers, and traders in pork. All identified pig groups were susceptible to ASFV, particularly shared adult boars, pregnant and lactating sows, and other adult females. The risk of ASF for smallholder pig farms in Tanzania remains very high based on a systematic risk classification. The majority of the farms had poor biosecurity and no single farm implemented all identified biosecurity measures. Risky practices and breaches of biosecurity in the pig value chain in Tanzania are profit driven and are extremely difficult to change. Behavioural change communication must target identified drivers of infections, attitudes, and practices.
Molecular Detection and Characterization of Hemotropic Mycoplasma in Assamese Macaques (Macaca assamensis) of Northern Thailand
Authors: Rucksaken Rucksak , Kaewchot Supakarn , Jarudecha Thitichai , Vitithumakhun Netnapa , Niyomdham Jira , Ngamkala Suchanit , Sricharern Wanat
Published: May 2024

Hemotropic mycoplasmas, also known as hemoplasmas, are parasitic bacteria that infect red blood cells, potentially leading to varying degrees of anemia across numerous mammalian species, including nonhuman primates. The present study aims to investigate the prevalence of hemoplasma infection and identify the species involved among free‐ranging Assamese macaques (Macaca assamensis) inhabiting northern Thailand. A total of 133 blood samples were collected from Assamese macaques in Chiang Rai province, Thailand, and subjected to screening for hemoplasma infection utilizing nested PCR amplification targeting the 16S rRNA gene. Positive samples were subsequently analyzed through nucleotide sequencing and phylogenetic analysis for putative species identification. Current study results revealed that 17.3% (23/133; 95% CI 11.29‐24.81) of Assamese macaques tested positive for hemoplasma infection using the nested PCR assay. Partial 16S rRNA sequences derived from hemoplasma isolates in Assamese macaques exhibited 99% homology, forming a cluster within the same phylogenetic clade as “Candidatus Mycoplasma haematomacacae,” previously identified in long‐tailed macaques, rhesus macaques, and Japanese macaques. These findings suggest the presence of “Ca. M. haematomacacae” not only in long‐tailed macaques and rhesus macaques but also in Assamese macaques in Thailand. To our knowledge, this marks the first molecular detection of “Ca. M. haematomacacae” in Assamese macaques in Thailand. These results hold significance as they enhance our understanding of hemoplasma infection distribution among macaque populations in Thailand.
Impact of Socioeconomic Factors and Health Insurance Coverage on Out-of-Pocket Health Expenditure among Ghanaian Women: Implications for Health Financing Policy
Authors: Ekholuenetale Michael , Igwegbe Nzoputam Chimezie , Ehimwenma Joshua Charity , Barrow Amadou
Published: May 2024

Background. The cost of health financing is an age-long social challenge in resource-constrained settings. Out-of-pocket (OOP) health spending adversely affects maternal healthcare provisions and use, making health insurance one of the most effective social interventions. Objective. The purpose of this research was to study the effect of OOP health expenditure on socioeconomic factors and health insurance coverage among Ghanaian women. Materials and Methods. Secondary statistical data pulled out from Ghana Demographic and Health Survey (GDHS)—2014 was investigated. A sample of 9,396 women whose ages ranged from 15 to 49 years was studied. We used marginal predictive model to examine the interaction effect between socioeconomic factors and health insurance coverage on OOP health expenditure. The significance level was determined at 5%. Results. Overall, about 41.9% (95% CI: 39.4%−44.4%) of Ghanaian women reported OOP health expenditure for drugs and services. Amongst those covered by health insurance, this was 37.9% (95% CI: 35.3%−44.4%). The marginal interaction effects of OOP health expenditure were higher for women in the lowest neighborhood socioeconomic disadvantage group (42.6%) than those in the highest neighborhood socioeconomic disadvantage group (26.0%) who were covered by health insurance. In addition, the marginal interaction effects of OOP health expenditure were found to be greater among women who had higher education (43.8%) compared with those who had no formal education (34.0%) who were covered by health insurance. Furthermore, the marginal interaction effects of OOP health expenditure were higher for rural (39.0%), than their urban counterpart (36.6.0%) who were under the covering of health insurance. Conclusion. There is a gap in health insurance coverage, which leads to increased OOP health expenditure. The OOP health expenditure effect was more concentrated among high socioeconomic women with health insurance. The healthcare system’s stakeholders should implement policies aimed at eliminating OOP health expenditure for maternal health services.
IL-15/IL-15Rα-Fc-Fusion Protein XmAb24306 Potentiates Activity of CD3 Bispecific Antibodies through Enhancing T-Cell Expansion
Authors: Li Ji , Clark Robyn , Slaga Dionysos , Avery Kendra , Liu Ke , Schubbert Suzanne , Varma Rajat , Chiang Eugene , Totpal Klara , Bernett Matthew J. , Holder Patrick G. , Junttila Teemu T.
Published: May 2024

An insufficient quantity of functional T cells is a likely factor limiting the clinical activity of T-cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate the activity of T-cell dependent (TDB) antibodies. The activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in the upregulation of the IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to IL-15. XmAb24306 enhanced T-cell bispecific antibody-induced CD8+ and CD4+ T-cell proliferation and expansion. In vitro combination of XmAb24306 with cevostamab or anti-HER2/CD3 TDB resulted in significant enhancement of tumor cell killing, which was reversed when T-cell numbers were normalized, suggesting that T-cell expansion is the main mechanism of the observed benefit. Pretreatment of immunocompetent mice with a mouse-reactive surrogate of XmAb24306 (mIL-15-Fc) resulted in a significant increase of T cells in the blood, spleen, and tumors and converted transient anti-HER2/CD3 TDB responses to complete durable responses. In summary, our results support the hypothesis that the number of tumor-infiltrating T cells is rate limiting for the activity of solid tumor-targeting TDBs. Upregulation of CD122 by TDB treatment and the observed synergy with XmAb24306 and T-cell bispecific antibodies support clinical evaluation of this novel immunotherapy combination.
TABLE 1 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

The effect of acute exercise on lymphocyte subsets
Supplementary Figure S3 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

Supplemental Figure S3: Schematic of the overall study design and conclusions.
Supplementary Figure S2 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

Supplemental Figure S2: The specific lysis of K562 cells by expanded Vγ9Vδ2+ T-cells with respective blocking of TCR-γδ or CMA.
FIGURE 5 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

Systemic β-AR activation through either acute exercise or ISO infusion evoke similar transcriptomic and surface phenotype shifts among ex vivo expanded Vγ9Vδ2+ T-cells. A, The percentage of activating, inhibitory, and chemokine receptors among expanded Vγ9Vδ2+ T-cells before (REST) and during (EX) exercise or ISO infusion. (n = 8). Statistical significance set as *, P < 0.05. GSEA performed using KEGG and GO terms showing enriched pathways on expanded Vγ9Vδ2+ T-cells that were expanded after (B) exercise or (C) ISO infusion. Graphs show enriched upregulated (blue) and downregulated (red) pathways as well as the percentage of DEGs contributing to each mechanism. Statistical significance set as FDR ≤ 0.25. Data are represented as mean.
FIGURE 4 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

ISO infusion enhances the antileukemic activity of ex vivo expanded Vγ9Vδ2+ T-cells in vitro and in vivo. A, Schematic of the experimental design for in vitro and in vivo experiments. B, The total number (1 × 106) of Vγ9Vδ2+ cells isolated before (REST) and during the final 5 minutes of ISO infusion at day 0, and the total number of Vγ9Vδ2+ T-cells generated in the expanded cell products after stimulation with ZOL+IL2 for 14 days. The number of Vγ9Vδ2+ cells generated at day 14 relative to the number of γδ cells in the PBMC fractions at day 0. The cellular composition of the expanded Vγ9Vδ2+ T-cell products at day 14. The proportions of naïve (N), CM, EM, and CD45RA+ EMRA cells among Vγ9Vδ2+ T-cells after 14 days of expansion (n = 7). C, The in vitro anti-tumor activity of ex vivo expanded Vγ9Vδ2+ T-cells against K562, Daudi, and U266 cells via flow cytometry–based assays. Significance indicated by ** (P < 0.01) and *** (P < 0.001). D, To determine the in vivo GvL effect of ISO expanded Vγ9Vδ2+, NSG-IL15 mice were injected with REST or ISO expanded Vγ9Vδ2+ (10 × 106) and challenged with 1 × 106 luciferase tagged human chronic myeloid leukemia cells (K562-luc). A subset of mice in each group were also provided weekly injections of ZOL (REST+ZOL; ISO+ZOL; VEHICLE +ZOL). The BLI (photons/second) scores, TFS, change in BW, and probability of survival after injection of expanded Vγ9Vδ2+ T-cells with or without ZOL sensitization (n = 7–8/group). BLI significant difference from EX+ZOL and EX conditions indicated by * and #, respectively (all conditions were significantly different from vehicle controls). TFS, BW, and OS significant difference from vehicle controls were indicated by * (TFS; EX, EX+ZOL, and REST+ZOL significance indicated by a single marker). E, Representative bioluminescence images of leukemia-bearing mice that received (from left to right) vehicle, vehicle + ZOL, REST expanded Vγ9Vδ2+ T-cells, REST expanded Vγ9Vδ2+ T-cells + ZOL, ISO expanded Vγ9Vδ2+ T-cells, and ISO expanded Vγ9Vδ2+ T-cells + ZOL. BLI intensity on a scale from low (purple) to high (red). Data are represented as mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by Students two-tailed paired t test (B); Repeated measures two-way ANOVA or LMM with Bonferroni post hoc test (C–D); log-rank (Mantel–Cox) test (D).
FIGURE 3 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

Blockade of β2-AR blunts the mobilization and expansion of Vγ9Vδ2+ T-cells. A, The physiologic effects of a placebo, β1-AR antagonist (10 mg bisoprolol), or a nonselective β1+β2 antagonist (80 mg, nadolol) on VO2 (mL/minute), systolic blood pressure (mmHg), HR (bpm), epinephrine (ng/mL), and norepinephrine (ng/mL) during the last minutes of acute exercise (n = 9). The effects of a placebo, β1-AR antagonist, or a nonselective β1+β2 antagonist on the total number of Vγ9Vδ2+ T-cells mobilized with exercise (B) and the ex vivo expansion of Vγ9Vδ2+ T-cells after 14 days with ZOL+IL2 (n = 9; C). Data are represented as mean ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by repeated measures one-way ANOVA with Bonferroni post hoc test.
FIGURE 1 from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

Exercise preferentially mobilizes γδ T-cells with phenotypic and transcriptomic profiles associated with anti-tumor immunity. A, The percentage or MFI of activating, inhibitory, and chemokine receptors among Vδ2+ and Vδ1+ T-cells before (REST) and during (EX) acute exercise (n = 8). Significance is indicated by * (P < 0.05). B, GSEA performed using KEGG and GO terms showing enriched pathways on exercise mobilized γδ T-cells (n = 3). Graphs show enriched upregulated (blue) and downregulated (red) pathways as well as the percentage of DEGs contributing to each mechanism. Statistical significance set as FDR ≤ 0.25. C, Azimuth map for human PBMCs showing the 26 clusters identified by scRNA-seq at rest; γδ T-cells mapping is circled in red. (n = 3). D, Chord diagram displaying the leading-edge genes driving the enrichment of terms associated with cytotoxicity and anti-tumor signaling in γδ T-cells (n = 3). Data are represented as mean; *, P < 0.05, Students two-tailed paired t test (A); * ≤0.25, FDR (B).
Data from Exercise-induced β2-adrenergic Receptor Activation Enhances the Antileukemic Activity of Expanded γδ T-Cells via DNAM-1 Upregulation and PVR/Nectin-2 Recognition
Authors: Baker Forrest L. , Smith Kyle A. , Mylabathula Preetesh L. , Zúñiga Tiffany M. , Diak Douglass M. , Batatinha Helena , Niemiro Grace M. , Seckeler Michael D. , Pedlar Charles R. , O'Connor Daniel P. , Colombo Jamie , Katsanis Emmanuel , Simpson Richard J.
Published: May 2024

Abstract
Exercise mobilizes cytotoxic lymphocytes to blood which may allow superior cell products to be harvested and manufactured for cancer therapy. Gamma-Delta (γδ) T-cells have shown promise for treating solid tumors, but there is a need to increase their potency against hematologic malignancies. Here, we show that human γδ T-cells mobilized to blood in response to just 20 minutes of graded exercise have surface phenotypes and transcriptomic profiles associated with cytotoxicity, adhesion, migration, and cytokine signaling. Following 14 days ex vivo expansion with zoledronic acid and IL2, exercise mobilized γδ T-cells had surface phenotypes and transcriptomic profiles associated with enhanced effector functions and demonstrated superior cytotoxic activity against multiple hematologic tumors in vitro and in vivo in leukemia-bearing xenogeneic mice. Infusing humans with the β1+β2-agonist isoproterenol and administering β1 or β1+β2 antagonists prior to exercise revealed these effects to be β2-adrenergic receptor (AR) dependent. Antibody blocking of DNAM-1 on expanded γδ T-cells, as well as the DNAM-1 ligands PVR and Nectin-2 on leukemic targets, abolished the enhanced antileukemic effects of exercise. These findings provide a mechanistic link between exercise, β2-AR activation, and the manufacture of superior γδ T-cell products for adoptive cell therapy against hematologic malignancies.
Significance:
Exercise mobilizes effector γδ T-cells to blood via β2-adrenergic signaling which allows for generation of a potent expanded γδ T-cell product that is highly cytotoxic against hematologic malignancies.
Evaluating the Economic Burden of Acute Myeloid Leukemia in Canada
Authors: Lachaine Jean , Beauchemin Catherine , Dodat Fatéma , Au Yunghan , Evans William K. , Leber Brian , Paulson Kristjan , Schuh Andre , Storring John
Published: May 2024

Introduction: Acute myeloid leukemia (AML) represents a significant burden for patients and their families, and to the healthcare system. This study estimated the total cost of illness associated with newly diagnosed AML patients in Canada. Methods: The economic burden of AML was estimated using an incidence-based model, analyzing different types of AML cases in Canada. Direct and indirect costs were calculated using scientific literature and Canadian clinical experts’ inputs. Patients were categorized depending on their eligibility for intensive chemotherapy (fit and unfit patients) as well as according to age and cytogenetic markers. Results: The total average cost of AML per patient is estimated to be CAD 178,073 with a cost of CAD 210,983 and CAD 145,163 for fit and unfit patients, respectively. The costs related to treatment represent half of the total average cost (52%), followed by hematopoietic stem cell transplant (23%), best supportive care (16%), productivity loss (6%), and wastage (4%). Conclusion: For patients with AML, the costs associated with fit patients are higher than unfit patients. Hospitalization and best supportive care costs are key cost drivers for the total costs of fit and unfit patients, respectively. This study highlights that AML is associated with a significant economic burden in Canada.
Abstract 105: Smooth Muscle Cell-derived Vascular Progenitor Cells Promote Arterial Remodeling and Fibrosis Through Loss of Hedgehog/Wnt/β-catenin/Klf4 Activity
Authors: Lu Sizhao , Jolly Austin J , Strand Keith A , Moulton Karen S , Mutryn Marie F , Tucker Rebecca M , Nemenoff Raphael A , Weiser-Evans Mary C
Published: May 2024

Resident vascular adventitial progenitor cells express the stem cell marker, Sca1 (AdvSca1 cells). Using smooth muscle cell (SMC) lineage tracing models and YFP reporter knock-in, we identified a subpopulation of AdvSca1 cells (AdvSca1-SM) that originate from mature SMCs that undergo reprogramming
in situ
and exhibit a multipotent phenotype. The adventitial microenvironment and induction of the transcription factor, Klf4 is critical to reprogramming; however, the mechanism of Klf4 induction is unknown. We aimed to define the signaling pathways involved in SMC reprogramming and to define the fate of AdvSca1-SM cells in response to vascular injury. Flow sorting was used to isolate YFP
+
Sca1
-
SMCs, YFP
+
Sca1
+
AdvSca1-SM cells, and YFP
-
Sca1
+
non-SMC-derived AdvSca1 cells from aortae (AO) and carotid arteries (CA) of SMC YFP reporter mice. RNA was subjected to RNA-seq analysis. Unbiased hierarchical clustering revealed that genes related to hedgehog/Wnt/β-catenin signaling are significantly enriched in AdvSca1-SM cells, emphasizing the importance of this signaling axis in SMC reprogramming to AdvSca1-SM cells. CA injury was induced by ligating the left common CA of SMC YFP reporter mice. Using RNA-seq, we found that in response to injury, AdvSca1-SM cells downregulate genes in the hedgehog/Wnt/β-catenin signaling pathway, as well as stemness-related genes, and adopt a myofibroblast-like phenotype. To selectively fate-map AdvSca1-SM cells, we took advantage of the high and selective expression of Gli1 by AdvSca1-SM cells and generated Gli1-CreER
T2
-Rosa26-YFP reporter mice. Flow Cytometry and Immunofluorescent (IF) staining show that YFP was expressed exclusively in adventitial Sca1-positive cells, but not all adventitial Sca1-positive cells expressed YFP. RNA-seq analysis confirmed selective upregulation of hedgehog/Wnt signaling in YFP
+
Sca1
+
cell population compared to the YFP
-
Sca1
+
population, supporting this model to faithfully track AdvSca1-SM cells. CA injury induced adventitial expansion and differentiation of AdvSca1-SM cells, as indicated by increased YFP
+
cells and decreased Sca1 expression. Surprisingly, AdvSca1-SM cells selectively contributed to adventitial remodeling and fibrosis, but not neointima formation.
Abstract 108: LMO7, a Negative Feedback Regulator of TGF-beta Signaling and a New Player in Vascular Diseases
Authors: Xie Yi , Ostriker Allison C , Yu Jun , Hwa John , Martin Kathleen A
Published: May 2024

Vascular smooth muscle cells (SMC) synthesize extracellular matrix (ECM) that contributes to tissue remodeling following revascularization interventions. The cytokine transforming growth factor-β (TGF-β) is induced upon tissue injury and regulates tissue remodeling and wound healing, but dysregulated signaling results in excess ECM deposition and fibrosis. The LIM domain protein LMO7 is a TGF-β target gene in hepatoma cells, but its role in vascular physiology and fibrosis is unknown. We employ carotid ligation and femoral artery denudation models in mice with global or inducible smooth muscle-specific deletion of LMO7, and knockout, knockdown, overexpression, and mutagenesis approaches in mouse and human SMC, and human arteriovenous fistula (AVF) and cardiac allograft vasculopathy (CAV) samples to assess the role of LMO7 in neointima and fibrosis. We demonstrate that LMO7 is induced post-injury and by TGF-β in SMC
in vitro
. Global or SMC-specific LMO7 deletion enhanced neointimal formation, TGF-β signaling, ECM deposition and proliferation in vascular injury models. LMO7 loss of function in human and mouse SMC enhanced ECM protein expression at baseline and following TGF-β treatment. TGF-β neutralization or receptor antagonism prevented the exacerbated neointimal formation and ECM synthesis conferred by loss of LMO7. Notably, loss of LMO7 coordinately amplified TGF-β signaling by inducing expression of
Tgfb1
mRNA, TGF-β protein, αv and β3 integrins that promote activation of latent TGF-β, and downstream effectors pSMAD3 and CTGF. Mechanistically, the LMO7 LIM domain interacts with AP-1 transcription factor subunits c-FOS and c-JUN and promotes their ubiquitination and degradation, disrupting AP-1-dependent TGF-β autoinduction. Importantly, preliminary studies suggest that LMO7 is upregulated in human intimal hyperplastic AVF and CAV samples, and inversely correlates with pSMAD3 in CAV.
Description of Protosticta khasia sp. nov. and Yunnanosticta siangi sp. nov., with new records of P. samtsensis Gurung & Phan, 2023 from Northeast India (Odonata: Zygoptera: Platystictidae)
Authors: JOSHI SHANTANU , SARKAR VIVEK , SAWANT DATTAPRASAD , PAWAR UJWALA , KUNTE KRUSHNAMEGH
Published: May 2024

Protosticta Selys is a genus of damselflies of the family Platystictidae Kennedy found in forests of tropical Southeast Asia. The genus Protosticta has rarely been reported from Northeast India. In this paper, we describe Protosticta khasia sp. nov. (subfamily Protostictinae Dijkstra et al.) based on holotype male and paratype female collected from Maraikaphon, East Khasi Hills district, Meghalaya, India. Protosticta khasia can be identified by the markings of the prothorax and the shape of the male paraproct with two arms. We also describe Yunnanosticta siangi sp. nov. (subfamily Sinostictinae Wilson) from Arunachal Pradesh, India, based on two males and two females. This species is differentiated from its congeners by the thoracic and abdominal markings as well as the shape of male caudal appendages. The key for males of Yunnanosticta is provided. Additionally, we provide new records of Protosticta samtsensis Gurung & Phan, along with an updated key to the Protosticta species of Northeast India.
Two new Dismodix Townes (Hymenoptera, Ichneumonidae, Cryptinae) with an exceptionally broad occipital carina
Authors: SUPELETO FERNANDA A. , AGUIAR ALEXANDRE P.
Published: May 2024

Dismodix colai sp. nov., from a reforested legal reserve of Atlantic Forest in southeastern Brazil, and D. gladiata sp. nov., from central Brazil, are described and illustrated. Each new taxon is compared with similar species from both Dismodix Townes and the related Acerastes Cushman. Both species can be separated from all others within each genus by having the occipital carina distinctly widened.
New data on the genus Supella Shelford, 1911 (Dictyoptera: Pseudophyllodromiidae) with description of female of S. eocenica Anisyutkin et Perkovsky, 2023 from Rovno amber
Authors: ANISYUTKIN LEONID N. , VASILENKO DMITRY V. , PERKOVSKY EVGENY E.
Published: May 2024

The paper provides a detailed morphological description of a previously unknown female of Supella eocenica Anisyutkin et Perkovsky, 2023. The structure of the tegmina and wings of the type species of the genus Supella, S. longipalpa (Fabricius, 1798), is also redescribed. Ecology of Rovno and Danish amber cockroaches is discussed.
Attapulgite Enhanced Polyethylene Oxide-Polyvinylidene Difluoride-Based Composite Solid-State Electrolyte for All Solid State Li-Ion Batteries
Authors: Chang Jie , Kong Yazhou , Zhu Yunpeng , Gao Yikai , Xie Canhuang , Chen Yu , Qian Wei , Hu Shihang , Hu Guang , Wang Jianxiong , Lu Huanjun , Hu Weiwei , Zhang Kailong
Published: May 2024

We report an attapulgite-modified poly(ethylene oxide) (PEO) based solid-state composite electrolyte film by solution casting method. The influence of attapulgite and polyvinylidene difluoride (PVDF) on the electrical properties of PEO-based solid-state electrolytes was investigated
and it is found that an optimal 3% attapulgite and 10% PVDF in the electrolyte film (0.9PEO-0.1PVDF-LiClO4-3% attapulgite) exhibited a high ionic conductivity of 2.55×10−4 S cm−1 at room temperature and electronic conductivity of 2.25×10−11
S cm−1. Furthermore, The LiFePO4/0.85PEO-0.15PVDF-LiClO4-3% attapulgite/Li all-solid battery exhibited a promising initial discharge capacity of 120 mAh g−1, and even after 10 cycles at 0.1 C, the specific capacity values of the all-solid
battery remained above 60 mAh g−1.
Characterization of Composite Materials Using Carbon Nano Tube Carboxy Group Introduction and Aluminum Oxide Synthesis
Authors: Kim Han-Byeol , Cheon Min-Woo
Published: May 2024

The high integration and high density of semiconductor packages are generating increased heat in electronic devices, leading to issues such as reduced lifespan and malfunctions in electronic devices. In response, research on thermal interface materials is being conducted to address
heat generated from heat sources, and various studies, particularly those applying carbon nano tube, are notable in this regard. However, in the case of carbon nano tube, there are challenges in industrial application due to the occurrence of cohesive forces through van der Waals interactions.
Therefore, in this study, the characteristics were analyzed through the formation of carbon nano tube carboxyl groups (–COOH) and the synthesis of aluminum oxide via chloride (–COCl) formation. After the chloride process, a functional group –COCl was confirmed at 430 cm−1.
It was confirmed that the electrical properties were improved as a result of the CNT, CNT carboxyl, and chloride process. It is believed that the electrical properties improved as impurities were removed during the acid treatment process. In addition, it is believed that the electrical properties
were improved due to the increase in intermolecular forces between CNTs. Through this, it is determined that the application of carbon nano tube and aluminum oxide composite materials can be highly beneficial for thermal conductivity heat dissipation filler applications.
The bi-directional relationships between diversified leisure activity participation and cognitive function in older adults in China: separating between-person effects from within-person effects
Authors: Wang Jingjing , Li Shaojie , Hu Yang , Ren Longbing , Jiang Yuling , Yu Mingzhi , Liu Zhouwei , Wu Yifei , Zhao Yejin , Zhang Jie , Li Jing , Yao Yao
Published: May 2024

Objective

To examine the bi-directorial association between diversified leisure activity participation and cognitive function over a 7-year period.

Methods

Data analyzed was from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a large-scale longitudinal national study. The baseline survey was conducted in 2011 with follow-up every three years. We traced a total of 2718 participants over a period of 7 years. We used adjusted random intercept cross-lagged panel models (RI-CLPMs) to examine the bi-directorial associations between diversified leisure activity participation and cognitive function.

Results

We observed bi-directorial associations between diversity of leisure activity and cognitive function across waves at the between-person and within-person levels. The adjusted random intercept cross-lagged panel models fitted the data appropriately, and the 3-year cross-lagged effects of prior diversified leisure activity participation on cognitive function (β = 0.058, p < 0.01) and cognitive function on subsequent diversified leisure activity participation (β = 0.047, p < 0.05) were significant. The results remained after adjusting the model for baseline sex, age, educational level, marital status and current residence, the number of chronic diseases, ADL, depressive symptoms, sleep quality, smoking, and drinking.

Conclusion

This study suggests that a reciprocal causality relationship between diversified leisure activity participation and cognitive function, indicating a “positive circle” that further promotes cognition over time.
Association of prothrombin time, thrombin time and activated partial thromboplastin time levels with preeclampsia: a systematic review and meta-analysis
Authors: Alemayehu Ermiyas , Mohammed Ousman , Belete Melaku Ashagrie , Mulatie Zewudu , Debash Habtu , Gedefie Alemu , Weldehanna Daniel Gebretsadik , Eshetu Bruktawit , Shibabaw Agumas , Tekele Saba Gebremichael , Tilahun Mihret , Ebrahim Hussen
Published: May 2024

Background

Preeclampsia (PE), an obstetric disorder, remains one of the leading causes of maternal and infant mortality worldwide. In individuals with PE, the coagulation-fibrinolytic system is believed to be among the most significantly impacted systems due to maternal inflammatory responses and immune dysfunction. Therefore, this systematic review and meta-analysis aimed to assess the association of prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) levels with preeclampsia.

Methods

This systematic review and meta-analysis was conducted in accordance with the PRISMA guidelines. Articles relevant to the study, published from July 26, 2013, to July 26, 2023, were systematically searched across various databases including PubMed, Scopus, Embase, and Hinari. The methodological quality of the articles was evaluated using the Joanna Briggs Institute critical appraisal checklist. Utilizing Stata version 14.0, a random-effects model was employed to estimate the pooled standardized mean difference (SMD) along with the respective 95% CIs. The I2 statistics and Cochrane Q test were utilized to assess heterogeneity, while subgroup analyses were performed to explore its sources. Furthermore, Egger’s regression test and funnel plot were employed to assess publication bias among the included studies.

Results

A total of 30 articles, involving 5,964 individuals (2,883 with PE and 3,081 as normotensive pregnant mothers), were included in this study. The overall pooled SMD for PT, APTT, and TT between PE and normotensive pregnant mothers were 0.97 (95% CI: 0.65–1.29, p < 0.001), 1.05 (95% CI: 0.74–1.36, p < 0.001), and 0.30 (95% CI: -0.08-0.69, p = 0.11), respectively. The pooled SMD indicates a significant increase in PT and APTT levels among PE patients compared to normotensive pregnant mothers, while the increase in TT levels among PE patients was not statistically significant.

Conclusions

The meta-analysis underscores the association between PE and prolonged PT and APTT. This suggests that evaluating coagulation parameters like PT, APTT, and TT in pregnant women could offer easily accessible and cost-effective clinical indicators for assessing PE. However, multicenter longitudinal studies are needed to evaluate their effectiveness across various gestational weeks of pregnancy.
Third-generation sequencing identified a novel complex variant in a patient with rare alpha-thalassemia
Authors: Zhou Cong , Du Yepei , Zhang Haixia , Wei Xing , Li Rui , Wang Jing
Published: May 2024

Background

Thalassemias represent some of the most common monogenic diseases worldwide and are caused by variations in human hemoglobin genes which disrupt the balance of synthesis between the alpha and beta globin chains. Thalassemia gene detection technology is the gold standard to achieve accurate detection of thalassemia, but in clinical practice, most of the tests are only for common genotypes, which can easily lead to missing or misdiagnosis of rare thalassemia genotypes.

Case presentation

We present the case of an 18-year-old Chinese female with abnormal values of routine hematological indices who was admitted for genetic screening for thalassemia. Genomic DNA was extracted and used for the genetic assays. Gap polymerase chain reaction and agarose gel electrophoresis were performed to detect HBA gene deletions, while PCR-reverse dot blot hybridization was used to detect point mutations in the HBA and HBB genes. Next-generation sequencing and third-generation sequencing (TGS) were used to identify known and potentially novel genotypes of thalassemia. We identified a novel complex variant αHb WestmeadαHb Westmeadαanti3.7/-α3.7 in a patient with rare alpha-thalassemia.

Conclusions

Our study identified a novel complex variant that expands the thalassemia gene variants spectrum. Meanwhile, the study suggests that TGS could effectively improve the specificity of thalassemia gene detection, and has promising potential for the discovery of novel thalassemia genotypes, which could also improve the accuracy of genetic counseling. Couples who are thalassemia carriers have the opportunity to reduce their risk of having a child with thalassemia.
Comparison of clinical characteristics and disease burden of febrile seizures in children with and without COVID-19
Authors: Jiang Zhongli , Fang Cuiyun , Peng Fengyimei , Fan Wei
Published: May 2024

Background

Febrile seizures (FS) are the most common seizure disorder in children and a common neurologic complication in children with coronavirus disease 2019 (COVID-19). This study aimed to identify differences in clinical characteristics and disease burden between FS with and without COVID-19.

Materials and methods

We conducted a retrospective analysis of medical data at our hospital from December 2019 to July 2023, focusing on hospitalized patients under the age of 14 diagnosed with FS who underwent COVID-19 polymerase chain reaction (PCR) testing. Descriptive statistics and analysis of variance were employed to compare the COVID-19 and non-COVID-19 groups in terms of clinical characteristics and disease burden.

Results

A total of 514 patients were included, with 106 testing positive for COVID-19 and 408 testing negative. Patients with COVID-19 were older (34.87 ± 6.16 vs. 28.61 ± 11.35 months, P < 0.001) and had a higher proportion of males (79.2% vs. 62.3%, P = 0.001). The COVID-19 group had longer seizure durations (4.57 ± 4.38 vs. 3.22 ± 2.91 min, P = 0.006) and more complex FS (25.5% vs. 15.9%, P = 0.022). Laboratory tests showed lower lymphocyte counts in the COVID-19 group (1.87 ± 1.48 vs. 2.75 ± 1.51 × 103/µL, P < 0.001) and higher creatine kinase levels (158.49 ± 82.89 vs. 110.89 ± 56.11 U/L, P < 0.001). No significant differences were found in hospital costs, length of hospitalization, and intensive care unit admissions.

Conclusion

Clinicians should be knowledgeable about the distinct clinical characteristics of FS in children with COVID-19. Despite distinct features, the prognosis remains favorable and does not require excessive intervention. Ongoing monitoring and research are needed to fully understand the impact of COVID-19 on FS and optimize management strategies.