bluuebunny/crossref_metadata_2025 huggingface dataset:
Disturbances in the IgG Antibody Profile in HIV‐Exposed Uninfected Infants Associated with Maternal Factors
Authors: Camacho-Pacheco Rodrigo T. , Hernández-Pineda Jessica , Brito-Pérez Yesenia , Plazola-Camacho Noemi , Coronado-Zarco Irma A. , Arreola-Ramírez Gabriela , Bermejo-Haro Mextli Y. , Najera-Hernández M. Angel , González-Pérez Gabriela , Herrera-Salazar Alma , Olmos-Ortiz Andrea , Soriano-Becerril Diana , Sandoval-Montes Claudia , Figueroa-Damian Ricardo , Rodríguez-Martínez Sandra , Mancilla-Herrera Ismael
Published: February 2024

Over the last 20 years, the incidence of vertical HIV transmission has decreased from 25%–42% to less than 1%. Although there are no signs of infection, the health of HIV‐exposed uninfected (HEU) infants is notoriously affected during the first months of life, with opportunistic infections being the most common disease. Some studies have reported effects on the vertical transfer of antibodies, but little is known about the subclass distribution of these antibodies. We proposed to evaluate the total IgG concentration and its subclasses in HIV+ mothers and HEU pairs and to determine which maternal factors condition their levels. In this study, plasma from 69 HEU newborns, their mothers, and 71 control pairs was quantified via immunoassays for each IgG isotype. Furthermore, we followed the antibody profile of HEUs throughout the first year of life. We showed that mothers present an antibody profile characterized by high concentrations of IgG1 and IgG3 but reduced IgG2, and HEU infants are born with an IgG subclass profile similar to that of their maternal pair. Interestingly, this passively transferred profile could remain influenced even during their own antibody production in HEU infants, depending on maternal conditions such as CD4+ T‐cell counts and maternal antiretroviral treatment. Our findings indicate that HEU infants exhibit an altered IgG subclass profile influenced by maternal factors, potentially contributing to their increased susceptibility to infections.
The Missing Piece of the Puzzle: Unveiling the Role of PTPN11 Gene in Multiple Osteochondromas in a Large Cohort Study
Authors: Borovikov Artem , Galeeva Nailya , Marakhonov Andrey , Murtazina Aysylu , Kadnikova Varvara , Davydenko Kseniya , Orlova Anna , Sparber Peter , Markova Tatiana , Orlova Maria , Osipova Darya , Nagornova Tatyana , Semenova Natalia , Levchenko Olga , Filatova Alexandra , Sharova Margarita , Vasiluev Peter , Kanivets Ilya , Pyankov Denis , Sharkov Artem , Udalova Vasilisa , Kenis Vladimir , Nikitina Natalia , Sumina Maria , Zherdev Konstantin , Petel'guzov Aleksandr , Chelpachenko Oleg , Zubkov Pavel , Dan Ivan , Snetkov Andrey , Akinshina Alexandra , Buklemishev Yury , Ryzhkova Oxana , Tabakov Vyacheslav , Zakharova Ekaterina , Korostelev Sergey , Zinchenko Rena , Skoblov Mikhail , Polyakov Alexander , Dadali Elena , Kutsev Sergey , Shchagina Olga
Published: February 2024

This study is aimed at investigating the clinical and genetic characteristics of 244 unrelated probands diagnosed with multiple osteochondromas (MO). The diagnosis of MO typically involves identifying multiple benign bone tumors known as osteochondromas (OCs) through imaging studies and physical examinations. However, cases with both OCs and enchondromas (ECs) may indicate the more rare condition metachondromatosis (MC), which is assumed to be distinct disease. Previous cohort studies of MO found heterozygous loss-of-function (LoF) variants only in the EXT1 or EXT2 genes, with DNA diagnostic yield ranging from 78 to 95%. The PTPN11 gene, which is causative for MC, was not previously investigated as a gene candidate for MO. In this study, we detected a total of 177 unique single nucleotide and copy number variants in three genes across 220 probands, consisting of 80 previously reported and 97 novel variants. Specifically, we identified five cases with OCs and no ECs as well as four cases with MC carrying LoF variants in the PTPN11 gene and two additional cases with ECs harboring variants in the EXT1/2 genes. These findings suggest a potential overlap between the MO and MC both phenotypically and genetically. These findings highlight the importance of expanding genetic testing beyond the EXT1 and EXT2 genes in MO cases, as other genes such as PTPN11 may also be causative. This can improve the accuracy of diagnosis and treatment for individuals with MO and MC. It is essential to determine whether MO and MC represent distinct diseases or if they encompass a broader clinical spectrum.
The Neuroimaging Role of Modified Electroconvulsive Therapy in the Major Depressive Disorder: Effectiveness in First-Episode Antipsychotic-Naive Major Depressive Disorder Patients
Authors: Zhong Yi , Li Jianfeng , Li Haitao , Li Mingzhe , Lyu Yanaohai , Cui Minghu , Gao Yujun
Published: February 2024

Objectives. It is a high risk for adolescents with first-episode major depressive disorder (MDD) to commit suicide. However, few studies reported the effect of modified electroconvulsive therapy (MECT) in first-episode antipsychotic-naive MDD adolescents. Methods. The study explores the alternations of regional homogeneity of modified electroconvulsive therapy to treat the first-episode antipsychotic-naive major depressive disorder. 72 first-episode MDD patients were recruited from Tianyou Hospital Affiliated to Wuhan University of Science and Technology from October 2017 to May 2020, and 65 of 72 completed the trial. Results. Before MECT treatment, ReHo values of the bilateral cerebellum and left cuneus were higher, and ReHo value of left postcentral and supramarginal gyrus was lower in MDD patients compared to healthy subjects (HS). After treatment, the MDD patients have higher ReHo values of the right insula and postcentral gyrus, while left fusiform gyrus were lower than the pretreatment. Compared to the HS, the ReHo values of left lingual gyrus, right calcarine cortex, and right mid occipital thalamus were higher in the posttreatment. In the posttreatment, left calcarine cortex and right cerebrum were lower than in healthy subjects. Conclusions. The study confirmed that MECT improves psychotic symptoms in patients with first-episode antipsychotic-naive MDD. These results further contributed to a more tailored treatment approach to MDD from the pathophysiological and neuroimaging views.
Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts
Authors: Sychev Zoi E. , Day Abderrahman , Bergom Hannah E. , Larson Gabrianne , Ali Atef , Ludwig Megan , Boytim Ella , Coleman Ilsa , Corey Eva , Plymate Stephen R. , Nelson Peter S. , Hwang Justin H. , Drake Justin M.
Published: February 2024

Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, which included six different PDX tumors for each group in biological replicates, and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor-matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa.

Implications:

Overall, our study highlights the importance of protein-based identification when compared with RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.
Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer
Authors: Zhang Han , Lee Sanghoon , Muthakana Renee R. , Lu Binfeng , Boone David N. , Lee Daniel , Wang Xiao-Song
Published: February 2024

Immune checkpoint blockade (ICB) can induce durable cancer remission. However, only a small subset of patients gains benefits. While tumor mutation burden (TMB) differentiates responders from nonresponders in some cases, it is a weak predictor in tumor types with low mutation rates. Thus, there is an unmet need to discover a new class of genetic aberrations that predict ICB responses in these tumor types. Here, we report analyses of pan-cancer whole genomes which revealed that intragenic rearrangement (IGR) burden is significantly associated with immune infiltration in breast, ovarian, esophageal, and endometrial cancers, particularly with increased M1 macrophage and CD8+ T-cell signatures. Multivariate regression against spatially counted tumor-infiltrating lymphocytes in breast, endometrial, and ovarian cancers suggested that IGR burden is a more influential covariate than other genetic aberrations in these cancers. In the MEDI4736 trial evaluating durvalumab in esophageal adenocarcinoma, IGR burden correlated with patient benefits. In the IMVigor210 trial evaluating atezolizumab in urothelial carcinoma, IGR burden increased with platinum exposure and predicted patient benefit among TMB-low, platinum-exposed tumors. Altogether, we have demonstrated that IGR burden correlates with T-cell inflammation and predicts ICB benefit in TMB-low, IGR-dominant tumors, and in platinum-exposed tumors.
High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models
Authors: Degagné Émilie , Donohoue Paul D. , Roy Suparna , Scherer Jessica , Fowler Tristan W. , Davis Ryan T. , Reyes Gustavo A. , Kwong George , Stanaway Morena , Larroca Vicena Vanina , Mutha Devin , Guo Raymond , Edwards Leslie , Schilling Benjamin , Shaw McKay , Smith Stephen C. , Kohrs Bryan , Kufeldt Heinrich J. , Churchward Glen , Ruan Finey , Nyer David B. , McSweeney Kyle , Irby Matthew J. , Fuller Christopher K. , Banh Lynda , Toh Mckenzi S. , Thompson Matthew , Owen Arthur L.G. , An Zili , Gradia Scott , Skoble Justin , Bryan Mara , Garner Elizabeth , Kanner Steven B.
Published: February 2024

Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti–B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor–derived T cells using a Cas12a CRISPR hybrid RNA–DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell–mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M–HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma.

See related Spotlight by Caimi and Melenhorst, p. 385
TABLE 1 from Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies
Authors: Subbiah Vivek , Coleman Niamh , Piha-Paul Sarina A. , Tsimberidou Apostolia M. , Janku Filip , Rodon Jordi , Pant Shubham , Dumbrava Ecaterina E. Ileana , Fu Siqing , Hong David S. , Zhang Shizhen , Sun Ming , Jiang Yunfang , Roszik Jason , Song Juhee , Yuan Ying , Meric-Bernstam Funda , Naing Aung
Published: February 2024

Baseline patient demographics
Supplementary Figure 1, Supplementary Table S1, and Supplementary Table S2. from Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies
Authors: Subbiah Vivek , Coleman Niamh , Piha-Paul Sarina A. , Tsimberidou Apostolia M. , Janku Filip , Rodon Jordi , Pant Shubham , Dumbrava Ecaterina E. Ileana , Fu Siqing , Hong David S. , Zhang Shizhen , Sun Ming , Jiang Yunfang , Roszik Jason , Song Juhee , Yuan Ying , Meric-Bernstam Funda , Naing Aung
Published: February 2024

Supplementary figure and tables
Table S4 from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Roué Gael , Valcárcel David , Molero Antonieta , Zamora Lurdes , Xicoy Blanca , Palomo Laura , Acha Pamela , Manzanares Ana , Tobiasson Magnus , Hellström-Lindberg Eva , Solé Francesc , Esteller Manel
Published: February 2024

Allele dropout (ADO) rate per sample (diagnosis and after AZA treatment)
Table S1 from Single-cell Multiomics Analysis of Myelodysplastic Syndromes and Clinical Response to Hypomethylating Therapy
Authors: Campillo-Marcos Ignacio , Casado-Pelaez Marta , Davalos Veronica , Ferrer Gerardo , Mata Caterina , Mereu Elisabetta , Roué Gael , Valcárcel David , Molero Antonieta , Zamora Lurdes , Xicoy Blanca , Palomo Laura , Acha Pamela , Manzanares Ana , Tobiasson Magnus , Hellström-Lindberg Eva , Solé Francesc , Esteller Manel
Published: February 2024

Clinicopathologic information of the studied MDS patients
Early Brain Activity in Very Preterm Infants of Mothers with Gestational Diabetes Mellitus: A Pilot Study
Authors: Sappler Maria , Neubauer Vera , Posod Anna , Schreiner Christina , Kiechl-Kohlendorfer Ursula , Griesmaier Elke
Published: February 2024

Introduction: Neurological consequences of preterm infants born to mothers with gestational diabetes mellitus (GDM) are unclear. In this pilot study, we investigated the effect of GDM on brain activity in very preterm infants. Methods: Preterm infants <32 gestational weeks of mothers with GDM compared to gestational age- and sex-matched controls born between 2011 and 2018 were included. Amplitude-integrated electroencephalography (aEEG) was assessed for total maturation and individual component scores according to Burdjalov and colleagues, the dominating visual background, and the presence of sleep-wake cycles per hour in the first 72 h of life and weekly at days 7, 14, 21, and 28. Results: We included 47 infants of mothers with GDM and 94 control infants. Both the aEEG total maturation score and its individual component scores, as well as the percentage of continuous background pattern, increased equally during the first 4 weeks after birth in both groups. GDM-exposed infants showed a slightly but significantly higher number of sleep-wake cycles per hour. Conclusion: We found normal maturation of brain activity in the first 4 weeks after birth in very preterm infants born to mothers with GDM, not differing from a very preterm control group. The higher number of sleep-wake cycles per hour in GDM-exposed infants could indicate transiently enhanced maturation. Further studies on brain activity and brain development in very preterm infants of mothers with GDM are needed to validate our results.
Association of Antenatal Evaluations with Postmortem and Genetic Findings in the Series of Fetal Osteogenesis Imperfecta
Authors: Senturk Leyli , Gulec Cagri , Sarac Sivrikoz Tugba , Kayserili Hulya , Kalelioglu Ibrahim Halil , Avci Sahin , Has Recep , Coucke Paul , Kalayci Tugba , Wollnik Bernd , Karaman Birsen , Toksoy Guven , Symoens Sofie , Yigit Gokhan , Yuksel Atil , Basaran Seher , Tuysuz Beyhan , Altunoglu Umut , Uyguner Zehra Oya
Published: February 2024

Introduction: Counseling osteogenesis imperfecta (OI) pregnancies is challenging due to the wide range of onsets and clinical severities, from perinatal lethality to milder forms detected later in life. Methods: Thirty-eight individuals from 36 families were diagnosed with OI through prenatal ultrasonography and/or postmortem clinical and radiographic findings. Genetic analysis was conducted on 26 genes associated with OI in these subjects that emerged over the past 20 years; while some genes were examined progressively, all 26 genes were examined in the group where no pathogenic variations were detected. Results: Prenatal and postnatal observations both consistently showed short limbs in 97%, followed by bowing of the long bones in 89%. Among 32 evaluated cases, all exhibited cranial hypomineralization. Fractures were found in 29 (76%) cases, with multiple bones involved in 18 of them. Genetic associations were disclosed in 27 families with 22 (81%) autosomal dominant and five (19%) autosomal recessive forms, revealing 25 variants in six genes (COL1A1, COL1A2, CREB3L1, P3H1, FKBP10, and IFITM5), including nine novels. Postmortem radiological examination showed variability in intrafamily expression of CREBL3- and P3H1-related OI. Conclusion: Prenatal diagnosis for distinguishing OI and its subtypes relies on factors such as family history, timing, ultrasound, genetics, and postmortem evaluation.
Investigation of Recessive Effects of Coding Variants on Common Clinical Phenotypes in Exome-Sequenced UK Biobank Participants
Authors: Curtis David
Published: February 2024

Introduction: Previous studies have demonstrated effects of rare coding variants on common, clinically relevant phenotypes although the additive burden of these variants makes only a small contribution to overall trait variance. Although recessive effects of individual homozygous variants have been studied, little work has been done to elucidate the impact of rare coding variants occurring together as compound heterozygotes. Methods: In this study, attempts were made to identify pairs of variants likely to be occurring as compound heterozygotes using 200,000 exome-sequenced subjects from the UK Biobank. Pairs of variants, which were seen together in the same subject more often than would be expected by chance, were excluded as it was assumed that these might be present in the same haplotype. Attention was restricted to variants with minor allele frequency ≤0.05 and to those predicted to alter amino acid sequence or prevent normal gene expression. For each gene, compound heterozygotes were assigned scores based on the rarity and predicted functional consequences of the constituent variants and the scores were used in a logistic regression analysis to test for association with hypertension, hyperlipidaemia, and type 2 diabetes. Results: No statistically significant associations were observed and the results conformed to the distribution, which would be expected under the null hypothesis. The average number of apparently compound heterozygous subjects for each gene was only 282.2. Conclusion: It seems difficult to detect an effect of compound heterozygotes on the risk of these phenotypes. Even if recessive effects from compound heterozygotes do occur, they would only affect a small number of people and overall would not make a substantial contribution to phenotypic variance. This research has been conducted using the UK Biobank Resource.
Potencialização pós-ativação melhora o desempenho no remoergômetro
Authors: Santana Darlan de Almeida , Silva Antônio Túlio Ferreira , Tavares José Matheus , Gusmão Michel Felipe Silva , Sirieiro Paolo Veiga , Miranda Humberto
Published: February 2024

O presente estudo teve o objetivo de avaliar o efeito de exercícios para membro superior e inferior de alta intensidade no teste de 500m contra o relógio no remo ergômetro. Foram recrutados 11 militares homens da Marinha do Brasil (idade, 26,16 ± 3,40 anos; peso, 76,10 ± 6,09 quilos, altura, 1,77 ± 0,03 metros, IMC, 22,22 ± 1,85 kg/m²). Na primeira sessão realizaram o protocolo tradicional de 500 metros no remo ergômetro com maior esforço possível contra o relógio e, na segunda sessão, realizaram o mesmo protocolo, com a execução de 3 repetições máximas na remada aberta e no agachamento Smith antes do remo ergômetro (protocolo PPA). Para análise estatística foi realizado um teste t e o nível de significância adotado foi de p < 0,01. Os resultados mostram uma melhora significativa de 1,2% no protocolo PPA. Além disso, quando o grupo foi separado entre os mais fortes e os mais fracos, o tamanho do efeito (TE) mostrou maior magnitude da PPA para o grupo mais forte (TE = - 0,35, pequeno vs TE = - 0,33, trivial). Sendo assim, concluímos que a realização de exercícios tradicionais de alta intensidade antes do teste de 500 metros no remo ergômetro, potencializa o desempenho no tempo total, sendo os indivíduos mais fortes, os mais beneficiados da PPA.
Efeito do treinamento com o Método Pilates sobre a pressão arterial de mulheres idosas hipertensas e normotensas
Authors: Brito Dejair Lopes Santos de , Araújo Danielli Soares , Barreto Marcos Vinicius Casais , Freitas Victor Hugo de , Aniceto Rodrigo Ramalho , Castro Marcela Rodrigues de
Published: February 2024

A Hipertensão Arterial Sistêmica (HAS) é o principal fator de risco para doenças cardiovasculares, podendo ser mantida com a prática regular de exercício físico, a exemplo do Método Pilates (MP), treinamento resistido que utiliza a própria massa corporal e/ou equipamentos. Contudo, pouco se sabe acerca dos efeitos do MP sobre respostas hemodinâmicas, especialmente em idosos. Assim, o objetivo desse estudo foi comparar o efeito de 24 semanas de treinamento com MP sobre a PA de idosas hipertensas (GH, n=10) e normotensas (GN, n=7) classificadas conforme parecer médico e o Questionário de Morbidade Autorreferida. A mensuração da PA foi realizada em três momentos: 1) sessões 1,2,3 (pré intervenção); 2) sessões 20,21, 22 (intra intervenção); 3) sessões 42, 43, 44 (pós-intervenção), sendo considerada a média de cada momento. Não foi observada diferença significativa entre os grupos, mas houve reduções significativas tanto da pressão arterial sistólica, quanto da pressão arterial diastólica. Podemos sugerir que MP proporciona redução da PA em idosas hipertensas e normotensas, com tendência de efeitos clínicos mais importantes para as hipertensas.
Opportunities in the Postpartum Period to Reduce Cardiovascular Disease Risk After Adverse Pregnancy Outcomes: A Scientific Statement From the American Heart Association
Authors: Lewey Jennifer , Beckie Theresa M. , Brown Haywood L. , Brown Susan D. , Garovic Vesna D. , Khan Sadiya S. , Miller Eliza C. , Sharma Garima , Mehta Laxmi S. ,   on behalf of the American Heart Association Cardiovascular Disease and Stroke in Women and Underrepresented Populations Committee of the Council on Clinical Cardiology; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; and Council on Cardiovascular and Stroke Nursing
Published: February 2024

Adverse pregnancy outcomes are common among pregnant individuals and are associated with long-term risk of cardiovascular disease. Individuals with adverse pregnancy outcomes also have an increased incidence of cardiovascular disease risk factors after delivery. Despite this, evidence-based approaches to managing these patients after pregnancy to reduce cardiovascular disease risk are lacking. In this scientific statement, we review the current evidence on interpregnancy and postpartum preventive strategies, blood pressure management, and lifestyle interventions for optimizing cardiovascular disease using the American Heart Association Life’s Essential 8 framework. Clinical, health system, and community-level interventions can be used to engage postpartum individuals and to reach populations who experience the highest burden of adverse pregnancy outcomes and cardiovascular disease. Future trials are needed to improve screening of subclinical cardiovascular disease in individuals with a history of adverse pregnancy outcomes, before the onset of symptomatic disease. Interventions in the fourth trimester, defined as the 12 weeks after delivery, have great potential to improve cardiovascular health across the life course.
Utilizing Human-Induced Pluripotent Stem Cells to Study Cardiac Electroporation Pulsed-Field Ablation
Authors: Maizels Leonid , Heller Eyal , Landesberg Michal , Glatstein Shany , Huber Irit , Arbel Gil , Gepstein Amira , Aronson Doron , Sharabi Shirley , Beinart Roy , Segev Amit , Maor Elad , Gepstein Lior
Published: February 2024

BACKGROUND:

Electroporation is a promising nonthermal ablation method for cardiac arrhythmia treatment. Although initial clinical studies found electroporation pulsed-field ablation (PFA) both safe and efficacious, there are significant knowledge gaps concerning the mechanistic nature and electrophysiological consequences of cardiomyocyte electroporation, contributed by the paucity of suitable human in vitro models. Here, we aimed to establish and characterize a functional in vitro model based on human-induced pluripotent stem cells (hiPSCs)-derived cardiac tissue, and to study the fundamentals of cardiac PFA.

METHODS:

hiPSC-derived cardiomyocytes were seeded as circular cell sheets and subjected to different PFA protocols. Detailed optical mapping, cellular, and molecular characterizations were performed to study PFA mechanisms and electrophysiological outcomes.

RESULTS:

PFA generated electrically silenced lesions within the hiPSC-derived cardiac circular cell sheets, resulting in areas of conduction block. Both reversible and irreversible electroporation components were identified. Significant electroporation reversibility was documented within 5 to 15-minutes post-PFA. Irreversibly electroporated regions persisted at 24-hours post-PFA. Per single pulse, high-frequency PFA was less efficacious than standard (monophasic) PFA, whereas increasing pulse-number augmented lesion size and diminished reversible electroporation. PFA augmentation could also be achieved by increasing extracellular Ca
2+
levels. Flow-cytometry experiments revealed that regulated cell death played an important role following PFA. Assessing for PFA antiarrhythmic properties, sustainable lines of conduction block could be generated using PFA, which could either terminate or isolate arrhythmic activity in the hiPSC-derived cardiac circular cell sheets.

CONCLUSIONS:

Cardiac electroporation may be studied using hiPSC-derived cardiac tissue, providing novel insights into PFA temporal and electrophysiological characteristics, facilitating electroporation protocol optimization, screening for potential PFA-sensitizers, and investigating the mechanistic nature of PFA antiarrhythmic properties.
The Macrophage Landscape Across the Lifespan of a Human Cardiac Allograft
Authors: Li Xiao , Turaga Diwakar , Li Rich G. , Tsai Chang-Ru , Quinn Julianna N. , Zhao Yi , Wilson Ruby , Carlson Katherine , Wang Jun , Spinner Joseph A. , Hickey Edward J. , Adachi Iki , Martin James F.
Published: February 2024

BACKGROUND:

Much of our knowledge of organ rejection after transplantation is derived from rodent models.

METHODS:

We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data.

RESULTS:

Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells.

CONCLUSIONS:

Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure.
A Brief Guide to Establishing Phylogenetically Defined Names under the International Code of Phylogenetic Nomenclature (PhyloCode)
Authors: Cantino Philip D. , De Queiroz Kevin , Cellinese Nico
Published: February 2024

To facilitate preparation of nomenclatural treatments that follow the PhyloCode, we provide here an outline of the requirements in the form of a checklist.  Rules are categorized as pertaining to publication requirements, protologue content, the defined clade name, or the phylogenetic definition.  Two sample protologues are included to illustrate the elements that need to be included to establish a name under the PhyloCode.  In addition, we provide detailed instructions for registering a name in RegNum, as required by the PhyloCode.
A taxonomic review of Odontogryllodes Chopard, 1969 (Gryllidae: Landrevinae)
Authors: TAN MING KAI , MUHAMMAD AMIRA AQILAH , ABDULLAH NURUL ASHIKIN , JAPIR RAZY , CHUNG ARTHUR Y.C.
Published: February 2024

The taxonomy of the crickets from the genus Odontogryllodes Chopard, 1969 is reviewed. Two species new to science are described here, one from Peninsular Malaysia (part of Malay Peninsula) and another from East Malaysia (part of Borneo): Odontogryllodes undatus Tan, Muhammad & Abdullah sp. nov. from Panti Forest Reserve and Odontogryllodes magnus Tan, Japir & Chung sp. nov. from Tenompok Forest Reserve, respectively. We also present an updated key to the species of Odontogryllodes. In total, nine species are currently known.
Health service and medication costs associated with common mental disorders and subthreshold symptoms in women: Findings from the Geelong Osteoporosis Study in Australia
Authors: Chatterton Mary Lou , Faller Jan , Le Long Khanh-Dao , Engel Lidia , Williams Lana J , Pasco Julie A , Mihalopoulos Cathy
Published: February 2024

Objective:

This analysis estimated 2013 annual healthcare costs associated with the common mental disorders of mood and anxiety disorders and psychological symptoms within a representative sample of Australian women.

Methods:

Data from the 15-year follow-up of women in the Geelong Osteoporosis Study were linked to 12-month Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data. A Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Non-patient edition identified common mental disorders and the General Health Questionnaire 12 assessed psychological symptoms. Participants were categorised into mutually exclusive groups: (1) common mental disorder (past 12 months), (2) subthreshold (no common mental disorder and General Health Questionnaire 12 score ⩾4) or (3) no common mental disorder and General Health Questionnaire 12 score <4. Two-part and hurdle models estimated differences in service use, and adjusted generalised linear models estimated mean differences in costs between groups.

Results:

Compared to no common mental disorder, women with common mental disorders utilised more Medicare Benefits Schedule services (mean 26.9 vs 20.0, p < 0.001), had higher total Medicare Benefits Schedule cost ($1889 vs $1305, p < 0.01), received more Pharmaceutical Benefits Scheme prescriptions (35.8 vs 20.6, p < 0.001), had higher total Pharmaceutical Benefits Scheme cost ($1226 vs $740, p < 0.05) and had significantly higher annual out-of-pocket costs for Pharmaceutical Benefits Scheme prescriptions ($249 vs $162, p < 0.001). Compared to no common mental disorder, subthreshold women were less likely to use any Medicare Benefits Schedule service (89.6% vs 97.0%, p < 0.01), but more likely to use mental health services (11.4% vs 2.9%, p < 0.01). The subthreshold group received more Pharmaceutical Benefits Scheme prescriptions (mean 43.3 vs 20.6, p < 0.001) and incurred higher total Pharmaceutical Benefits Scheme cost ($1268 vs $740, p < .05) compared to no common mental disorder.

Conclusions:

Common mental disorders and subthreshold psychological symptoms place a substantial economic burden on Australian healthcare services and consumers.
Fractional order second-order sliding mode MRASO for SPMSM
Authors: Liu Jun-Feng , Feng Yuan , Yu Jian-Yong , Tang Jing-Wei , Zhang Lei
Published: February 2024

To improve the accuracy of the sensorless control system for permanent magnet synchronous motors, this paper proposes the based on fractional order integral sliding mode theory in the model reference adaptive system observer. The purpose of this approach is to enhance the robustness of the system. Furthermore, this paper introduces the second-order sliding mode reaching law to suppress chattering phenomena and improve the control accuracy of the observer. Simulation results show that this strategy achieves excellent dynamic and static performance.
Harvesting precarity: The regimes governing migrant labor in Türkiye’s agricultural sector
Authors: Dedeoğlu Saniye
Published: February 2024

Migrant labor is widely used in agricultural production in many parts of Türkiye especially during the harvesting season. This article explores the precaritization process of seasonal agricultural labor markets in Türkiye by highlighting how three regimes—migration management, labor bonding and recruitment—work simultaneously to regulate migrant labor supply. By attracting vulnerable and cheap labor of Syrian, Azeri and Georgian workers, the Turkish agricultural sector has extended its reach to the most disadvantaged groups and intensified the precaritization of the labor force. Based on empirical findings from previous fieldworks conducted between 2015 and 2019 in various agricultural sites throughout Türkiye, this paper argues that precaritization is not only a result of working conditions and job characteristics in the agricultural sector but also a consequence of these three regimes working harmoniously as they generate competition among different worker groups for existing jobs. While migration regime and restrictions on migrant labor determine migrant and refugee labor’s living and working conditions, intermediaries and ethnic ties also facilitate the integration of precarious labor into seasonal wage work. The paper provides valuable insights into the dynamics of labor exploitation in the agricultural sector in Türkiye and the need for regulatory mechanisms that protect the rights of seasonal agricultural workers.
Iterative learning–based model-free adaptive precise heading following of an autonomous underwater vehicle with unknown disturbances
Authors: Dong Donglei , Xiang Xianbo , Li Jinjiang , Yang Shaolong
Published: February 2024

Due to the nonlinearity, strong coupling, and uncertain parameters of autonomous underwater vehicle (AUV), it is difficult to build an accurate dynamic model, which makes precise control of AUV extremely challenging. To handle the precise heading-following problem of AUV, this paper proposes an iterative learning-based redefine model-free adaptive heading control (IL-RMFAC) method for the underactuated AUV with unknown disturbances based on data driven. The control scheme consists of a learning control algorithm, a parameter iterative update algorithm, and a parameter reset algorithm. It is designed using only the input and output (I/O) data of the controlled system and is a data-driven control method. The pseudo partial derivative (PPD) can be iteratively calculated through the parameter iterative update algorithm and reset algorithm to adjust the learning gain, solving the problem of strictly limited initial position of the traditional fixed learning gain iterative learning control (ILC). A linear combination of angle and angular velocity is introduced in the kinematic layer to avoid overshooting of the expected following target, and an iterative learning method is introduced in the dynamics to improve the accuracy. As the number of iterations increases, the steady-state error is gradually decreased. Finally, by comparing traditional proportional–integral–derivative (PID) simulations, the proposed algorithm’s effectiveness and outstanding performance for the AUV heading tracking are confirmed.
Surgical Training Using Augmented Reality-Based Optical Head-Mounted Displays: A Pilot Study
Authors: Jung Seon Min , Song Chang Myeon , Tae Kyung , Yi Byung Ju , Ji Yong Bae
Published: February 2024

While the educational benefits of the modern techniques such as virtual reality (VR) or augmented reality (AR) have been suggested, there is still a lack of reports on actual surgeons’ experiences. In this study, we evaluated the effectiveness of a holographic AR-based surgical training in tonsillectomy. Two otolaryngologists, 1 trainee and 1 instructor, performed 5 tonsillectomies using an AR headset (HoloLens 2, Microsoft, USA). The trainee wore the AR headset to share the surgical view through front camera while the instructor remotely accessed the device using the Microsoft Teams program and provided real-time guidance. The AR-based surgical training offered several advantages, including direct real-time guidance for the trainee and clear instructions without disturbing the surgical process. However, there were also drawbacks, such as the front camera not always matching the trainee’s view and some difficulty with focusing, depending on the depth of the oral cavity. Our study suggests that AR devices are a feasible and alternative method for surgical training. With the ability to provide clear guidance, even from a distance, this technology has the potential to revolutionize surgical training in the future.
On TCR’s Fostering Creative Collaborations and Future Directions
Authors: Celedón-Pattichis Sylvia
Published: February 2024

This commentary focuses on reflections involving the special issue on Teaching and Learning Mathematics and Computing in Multilingual Contexts and the important role that Teachers College Record has played in fostering creative interdisciplinary collaborations among researchers, graduate students, teachers, K-12 students, and parents. A discussion is included on how participating as a Guest Lead Editor of this special issue afforded opportunities to learn more about projects that integrate mathematics and computing as well as transformations that have impacted the work we do in our respective fields. Multilingual contexts contribute much to our understanding of global perspectives on mathematics education. Taking up a memorable moment that involved such a context, I discuss future directions for the Teachers College Record as we consider reaching to multilingual audiences.
Development and Testing of the School Healthcare Partnership Scale for Parents
Authors: Uhm Ju-Yeon , Kim Suhee
Published: February 2024

Background:

Cooperation between parents and school nurses is essential for the successful completion of school courses and a healthy school life for children with long-term conditions. Therefore, this study aimed to develop and test a scale to measure parental perceptions of partnerships between school nurses and parents in the school health care (SHC) system for children with type 1 diabetes (T1D).

Methods:

The content validity, factorial structure validity, convergent validity, discriminant validity, known-group validity, internal consistency reliability, and test-retest reliability of the School Healthcare Partnership Scale for Parents (SHCPS-P) were evaluated. Data were analyzed by performing exploratory factor analysis (EFA), Pearson’s correlation, Cronbach’s α, and independent t-tests. The total sample included 155 parents for the EFA and 49 parents for the stability test. Seventeen items, grouped into 3 dimensions, were extracted through principal axis factoring.

Results:

The total variance explained by these factors was 53.57%. The scale demonstrated a high correlation with parental satisfaction regarding school nursing and a moderate correlation with diabetes-related safety, thereby showing convergent validity. A low correlation with empathy demonstrated discriminant validity. A significant difference existed in the partnership scores in known-group comparisons. Cronbach’s α was 0.95, and the test-retest correlation coefficient was 0.95, which showed reliability.

Conclusions:

This study suggests that the SHCPS-P is a reliable and valid tool for measuring the perception of SHC partnership among parents of children with T1D and can be used as an indicator to measure parents’ perspectives about SHC.
Reducing barriers for inclusion of students with visual impairments in the universities: Focus on educational and psychological needs
Authors: Kija Lucas Luhende , Mgumba Batista Francis
Published: February 2024

Studies indicate that the university environment has quite different and critical social and academic challenges. This article discusses barriers in the learning of students with visual impairments and the extent to which inclusive education can be promoted in the universities. The purpose of this study was to enhance students with visual impairments’ access to quality education in the universities. The study employed a multiple case study design and the qualitative approach for studying behaviour. Non-probability purposive sampling technique was employed to obtain 22 participants who participated in interviews. Findings indicated that in their interaction with the university environment, students with visual impairments were faced by various barriers, including challenges in interaction with the physical and social environment; inadequate learning support services; and inaccessible information. To enable students with visual impairments study smoothly, efforts in promoting inclusive education in the universities should focus on not only adjustment of physical, social, and learning environment but also improvement in counselling services that will adequately address the social and psychological problems that have been disturbing students with visual impairments throughout their life.
Microstructure evolution and mechanical properties of friction welded IN713LC and AISI 4140
Authors: Gaikwad V.T. , Balasundar I. , Tripathi A. , Singh R.K.P. , Mishra M.K.
Published: February 2024

The microstructure and mechanical behavior of rotary friction-welded IN713LC nickel-base superalloy with AISI 4140 steel have been investigated. The microstructure of IN713LC changed from a columnar dendritic structure to equiaxed grains due to dynamic recrystallization with considerable change in in-grain misorientation, morphology, and volume fraction of gamma prime (γ′) precipitates. The observations indicate a counteracting effect of heat input and degree of deformation which resulted in achieving minimum grain size at an intermediate friction pressure. Phase transformation was observed in the weld interface/thermomechanically affected zone region of AISI 4140 steel. These changes in microstructure contribute to the variation in the microhardness across the weld joint. Furthermore, a maximum weld joint tensile strength of 922 MPa was observed at an intermediate friction pressure of 110 MPa.
The clinical and economic impact of chronic venous insufficiency-associated lymphedema and the prevalence of persistent edema after venous intervention
Authors: Genet Matthew , Labropoulos Nicos , Gasparis Antonios , O’Donnell Thomas , Desai Kush
Published: February 2024

Objectives

To determine the demographics, outcomes, and healthcare utilization of patients with chronic venous insufficiency-associated lymphedema (CVI-LED) and the prevalence of lymphedema-specific therapy use after venous intervention.

Methods

The IBM MarketScan Commercial and Medicare Claims Databases were examined for patients with CVI-LED. Patient demographics and the use of lymphedema-specific therapy before and after venous intervention were collected.

Results

Of 85,601 LED patients identified, 8,406 also had a diagnosis of CVI. In the CVI-LED group, 1051 underwent endovenous ablation or venous stent placement. The use of lymphedema-specific therapy before and after venous intervention was 52% and 39%, respectively ( p < .05). The mean time of initiation of LED-specific therapy following venous intervention was 265 days after ablation and 347 days after stent placement.

Conclusion

Treating venous hypertension improves certain venous-related signs and symptoms of CVI. However, a significant proportion of patients have persistent edema which may reflect underlying, sub-optimally treated LED.
Foundations of spatial perception for robotics: Hierarchical representations and real-time systems
Authors: Hughes Nathan , Chang Yun , Hu Siyi , Talak Rajat , Abdulhai Rumaia , Strader Jared , Carlone Luca
Published: February 2024

3D spatial perception is the problem of building and maintaining an actionable and persistent representation of the environment in real-time using sensor data and prior knowledge. Despite the fast-paced progress in robot perception, most existing methods either build purely geometric maps (as in traditional SLAM) or “flat” metric-semantic maps that do not scale to large environments or large dictionaries of semantic labels. The first part of this paper is concerned with representations: we show that scalable representations for spatial perception need to be hierarchical in nature. Hierarchical representations are efficient to store, and lead to layered graphs with small treewidth, which enable provably efficient inference. We then introduce an example of hierarchical representation for indoor environments, namely a 3D scene graph, and discuss its structure and properties. The second part of the paper focuses on algorithms to incrementally construct a 3D scene graph as the robot explores the environment. Our algorithms combine 3D geometry (e.g., to cluster the free space into a graph of places), topology (to cluster the places into rooms), and geometric deep learning (e.g., to classify the type of rooms the robot is moving across). The third part of the paper focuses on algorithms to maintain and correct 3D scene graphs during long-term operation. We propose hierarchical descriptors for loop closure detection and describe how to correct a scene graph in response to loop closures, by solving a 3D scene graph optimization problem. We conclude the paper by combining the proposed perception algorithms into Hydra, a real-time spatial perception system that builds a 3D scene graph from visual-inertial data in real-time. We showcase Hydra’s performance in photo-realistic simulations and real data collected by a Clearpath Jackal robots and a Unitree A1 robot. We release an open-source implementation of Hydra at https://github.com/MIT-SPARK/Hydra .