bluuebunny/crossref_metadata_2025 huggingface dataset:
Back in Action: High Return to Pre-Injury Level of Sports after Arthroscopic Bone Marrow Stimulation for Osteochondral Lesions of the First Metatarsophalangeal (MTP-1) Joint
Authors: ter Laak Bolk Carlijn S. , Rikken Quinten G.H. , Dahmen Jari , Shimozono Yoshiharu , Takao Masato , Stufkens Sjoerd A.S. , Kerkhoffs Gino M.M.J.
Published: September 2023

Objective

The primary aim was to assess the return to sports outcomes of patients with symptomatic osteochondral lesions (OCLs) to the first metatarsophalangeal (MTP-1) joint treated by arthroscopic bone marrow stimulation (BMS). Secondary aims were to present patient-reported outcome measures (PROMs) on pain scores as well as surgery-related complications or reoperations to the MTP-1 joint.

Design

All patients with MTP-1 OCLs treated by arthroscopic BMS with a minimum follow-up of 12 months were included. Outcomes included return to sports and work outcomes, satisfaction outcomes with the performed treatment, PROMs, as well as postoperative complications and reoperations. Medical records were screened by 2 independent reviewers and patients were contacted by phone to partake in an in-depth interview. Complications, reoperations, and revision surgeries were additionally assessed.

Results

Nine patients (median age: 22 years with interquartile range (IQR) 20-29 years) were included with a median follow-up time of 47 (IQR: 23-92) months. Six (86%) out of 7 patients who participated in sports preoperatively returned to sports at any level at a median of 4 (IQR: 2.6-5.8) months. Five patients (71%) returned to pre-injury level of sport and eventually returned to performance at a median of 4 (IQR 2.8-7.5) and 8 (IQR: 4.0-10.5) months, respectively. The median Numeric Rating Scale for pain during walking was 1 (IQR 0-2.5) and all (100%) patients were able to return to work at a median of 4 (IQR: 2-17) weeks. Eighty-nine percent of the patients were very or fairly satisfied with the result of their treatment. No complications, reoperations, or revision surgeries were reported.

Conclusions

Arthroscopic BMS for patients with symptomatic OCLs to the MTP-1 joint can be considered safe and yields an 86% return to sport at any level and a 71% return to pre-injury and performance level, with good clinical, return to work, as well as satisfaction outcomes.
Fear of cancer, its antecedents, correlates, and disease risk estimates
Authors: Shen Lijiang , Acevedo Callejas Michelle L
Published: September 2023

Individuals and society as a whole seem to be particularly fearful of cancer. A web-based study with data collected from Qualtrics panels in the United States ( N = 810) was conducted to investigate the antecedents, consequences, and correlates of fear of cancer. Comparisons were made across four cancers (lung, thyroid, pancreas, and melanoma) that varied in prevalence and death rate, and three non-cancer diseases (heart attack, diabetes, and HIV/AIDS). Individuals were indeed particularly scared of cancer. Their fear was influenced by threat appraisals related to both disease and treatment side effects. Risk estimates for diseases were influenced jointly by emotion and threat appraisal.
The Congenital Heart Surgeons' Society Presidents and Their Contributions
Authors: Mavroudis Constantine , Backer Carl L. , Brown John W. , Williams William G.
Published: September 2023

The Congenital Heart Surgeons’ Society (CHSS) was founded by 16 congenital heart surgeons in 1973, who endeavored to share their clinical advances in an informal setting that would stimulate honest and forthright discussions. As the Society grew, prospective studies were organized from a centralized data center that was established and based first in Birmingham, Alabama, thence to Toronto, and recently in a collaboration between Toronto and the Cleveland Clinic. These studies formed the basis for a myriad of outcomes reports that favorably impacted surgical results. The Kirklin–Ashburn Fellowship was created and endowed by the membership which has been successful in training many congenital heart surgeons. The CHSS was then incorporated into a 501(c) (3) not-for-profit organization with bylaws, officers, and committees in 2002. Increased membership followed. The CHSS has become the face of congenital heart surgery in North America by affiliating with the World Journal for Pediatric and Congenital Heart Surgery, having one designated member on the American Board of Thoracic Surgery, and hosting joint meetings with the European Congenital Heart Surgeons Association. Since 2002, 11 presidents have been elected for two-year terms and have guided the advances that have been achieved by the CHSS. Their contributions and achievements are highlighted in chronological order.
Historical Accounts of Congenital Heart Surgery
Authors: Mavroudis Constantine , Ong Chin Siang , Vricella Luca A. , Cameron Duke E.
Published: September 2023

We present historical accounts of congenital heart surgery since the early 1900s, as our specialty evolved from individual heroic efforts into an established and sophisticated surgical specialty with consistent and excellent results. We highlight colleagues and intrepid pioneers who have strived to solve seemingly insurmountable problems during this remarkable journey and celebrate continued success into the 21st century with surgical advances that have resulted in innovative operations, database inquiries, quality measures, new techniques of medical illustration, and the establishment of the Congenital Heart Surgeons’ Society, which has become the leading organization dedicated to congenital heart surgery in North America.
Anti-SOX1 Antibodies in a 3-Year-old Girl, Post-Varicella
Authors: Wijnand Aline , Verhelst Helene
Published: September 2023

Anti-SRY-related HMG-box gene 1 (SOX1) antibodies were initially described in adults with paraneoplastic neurological disorders, where they are considered high-risk onconeural autoantibodies. Only two pediatric cases of anti-SOX1 antibodies have been reported: a 17-year-old adolescent presenting with paraneoplastic limbic encephalitis due to Hodgkin lymphoma and a 12-year-old girl presenting with non-paraneoplastic encephalitis. We present a unique case of anti-SOX1 antibodies in a 3-year-old girl, post-varicella infection. Initially, she presented with ataxia and dysmetria, with subsequent reports from parents of urinary incontinence and significant behavior changes. Additionally, reflexes in the lower limbs were absent. Anti-SOX1 antibodies tested positive in both serum and cerebrospinal fluid. Oncological screening at presentation and a seven-month follow-up showed no malignancies. The patient exhibited favorable clinical progress without requiring treatment. At the seven-month follow-up, serum antibodies tested negative. This case report broadens the known clinical spectrum, being the first description of post-varicella anti-SOX1 antibodies.
Vitamin D Deficiency and Its Association With Anemia and Blood Transfusion Requirements in Nigerian Adults With Sickle Cell Anemia
Authors: Ochogwu Olanrewaju Lauretta , Salawu Lateef , Owojuyigbe Temilola Oladunmomi , Adedeji Tewogbade Adeoye
Published: September 2023

Background

Vitamin D supplementation has been shown to improve hemoglobin levels in patients with sickle cell anemia (SCA). However, very little is known about the prevalence of its deficiency, its role in hemolysis, and its effects on transfusion requirements in SCA, hence this study.

Patients and Methods

Serum level of vitamin D was determined in 50 SCA patients in steady state, 50 SCA patients in hemolytic crises, and 50 in normal HbAA individuals. All were 18 years or older and were age- and sex-matched. In addition, PCV and hemoglobin (Hb) concentration, absolute reticulocyte count, uric acid, total and conjugated bilirubin, creatinine, lactate dehydrogenase (LDH), and estimated glomerular filtration rate (eGFR) were also assessed in all subjects and controls. Baseline sociodemographic, clinical, and anthropometric data were also recorded.

Results

The prevalence of vitamin D insufficiency and deficiency was found to be 18% and 79%, respectively. The mean serum levels of vitamin D were 18.84 ± 6.86 ng/mL and 17.58 ± 6.23 ng/mL in the steady-state and the hemolytic crises SCA groups, respectively. Transfusion requirements were found to be higher in SCA patients with lower vitamin D levels. Unlike those in crisis who received one or more units of blood transfusion, 42% of those in the steady state did not receive blood transfusion over the same period of 12 months. Hemoglobin levels were, however, found to predict reduced vitamin D levels.

Conclusion

Vitamin D deficiency (VDD) is highly prevalent among adults with SCA and those with lower vitamin D levels are more anemic and hence may require more blood transfusions.
Derivation of a Pharmacokinetic Model to Include a Plasma-Derived, von Willebrand Factor-Containing Factor VIII (Koate®-DVI) Concentrate and its Low-Dose Use
Authors: Hajducek Dagmar M. , Primacakti Fitri , Chozie Novie , Mir Roser , McEneny-King Alanna , Iorio Alfonso , Edginton Andrea
Published: September 2023

Background

Population pharmacokinetics (popPK) has been reliably leveraged to generate individual PK in hemophilia patients. Specific popPK models are suited to predict individual PK under a variety of scenarios that may not be captured by clinical trials, allowing for individualized prophylactic treatment. The Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo) project generates individually predicted pharmacokinetic profiles relying on concentrate-specific popPK models used for Bayesian forecasting.

Objective

Specification of a popPK model for the plasma-derived factor VIII (FVIII) concentrate Koate-DVI and its suitability for pharmacokinetic estimation in low-dose scenarios.

Methods

A popPK model was developed for Koate-DVI WAPPS-Hemo PK data in combination with the existing WAPPS-Hemo Fanhdi/Alphanate model derivation dataset using nonlinear mixed effects modelling, and was validated via cross-validation and prediction-corrected Visual Predictive Checks (pcVPC). Bootstrap and PK outcomes between the Fanhdi/Alphanate and the Fanhdi/Alphanate/Koate models were compared, and the relative error distributions from a limited sampling analysis (LSA) under the latter model for low and normal doses (10 vs 50 IU/kg) and inclusion/exclusion of pre-dose measurements.

Results

A Fanhdi/Alphanate/Koate model was derived (126 patients, ages 1–71 years) after deeming a Koate-brand covariate not clinically significant, resulting in similar parameter estimates than the Fanhdi/Alphanate model with satisfactory goodness of fit, cross-validation and pcVPC results. Low-dose predictions resulted in a higher accuracy and slightly lower precision of half-life ([Formula: see text]-phase) and time to 2% trough (TAT2%) estimates than normal dose (median absolute bias for half-life: 0.12 vs 0.5%; median interquartile range, IQR: 11.79% vs 9.95%). Precision improved under pre-dose designs by 2 to 3% and remained similar between 5- and 2-sample designs (IQR reduction<1.8%).

Conclusions

The Fanhdi/Alphanate/Koate model is appropriate for Bayesian forecasting in the WAPPS-Hemo platform, providing a comparable prediction capability for low and normal dosing regimens (10 vs 50 IU/Kg).
Plasmapheresis and Plasma Donation: Challenges in the Blood/Plasma Supply Chain
Authors: Rivera José , Lozano Miquel
Published: September 2023

Voluntary non-remunerated blood donation is well-established in many countries; however, this approach is under pressure to provide sufficient plasma for future needs. In this article we consider various aspects of plasma donation, including donor characteristics, health and safety issues, and motivating factors, including the potential role of incentives. The status of plasma donation in various European countries, and challenges associated with the COVID-19 pandemic are also discussed. Common motivators for plasma donors include the benefit that donated plasma provides for other people, the sense that helping others is in their nature, a sense of pride at undertaking a special task, and the desire to achieve donation goals. Motivations may differ between age groups and gender. Donating plasma is safe and adverse events are infrequent, with the most common being hypotensive/vasovagal events and phlebotomy events. The main reasons plasma donors discontinue are socioeconomic, relating to the time required and conflicts with work and other commitments. When persuading donors to convert from whole blood to plasma donation, face-to-face requests are more successful than leaflets or telephone/email requests, and clear information addressing health and safety concerns is needed. However, telephone/email communication can be helpful for encouraging plasma donors to return for future donations or to donate more frequently. There is ongoing debate about non-remunerated versus remunerated plasma donation. Remuneration may be an incentive for some individuals, whereas it may deter people who have a strong altruistic drive. It has been suggested that a combination of paid and unpaid donation systems could cover a wider range of potential donors. Most European countries currently have non-remunerated donor systems, but a few do allow monetary compensation.
Reinforced antimyeloma therapy via dual-lymphoid activation mediated by a panel of antibodies armed with bridging-BiTE
Authors: Konishi Tatsuya , Ochi Toshiki , Maruta Masaki , Tanimoto Kazushi , Miyazaki Yukihiro , Iwamoto Chika , Saitou Takashi , Imamura Takeshi , Yasukawa Masaki , Takenaka Katsuto
Published: September 2023

Immunotherapy using bispecific antibodies including bispecific T-cell engager (BiTE) has the potential to enhance the efficacy of treatment for relapsed/refractory multiple myeloma. However, myeloma may still recur after treatment because of downregulation of a target antigen and/or myeloma cell heterogeneity. To strengthen immunotherapy for myeloma while overcoming its characteristics, we have newly developed a BiTE-based modality, referred to as bridging-BiTE (B-BiTE). B-BiTE was able to bind to both a human immunoglobulin G–Fc domain and the CD3 molecule. Clinically available monoclonal antibodies (mAbs) were bound with B-BiTE before administration, and the mAb/B-BiTE complex induced antitumor T-cell responses successfully while preserving and supporting natural killer cell reactivity, resulting in enhanced antimyeloma effects via dual-lymphoid activation. In contrast, any unwanted off-target immune-cell reactivity mediated by mAb/B-BiTE complexes or B-BiTE itself appeared not to be observed in vitro and in vivo. Importantly, sequential immunotherapy using 2 different mAb/B-BiTE complexes appeared to circumvent myeloma cell antigen escape, and further augmented immune responses to myeloma relative to those induced by mAb/B-BiTE monotherapy or sequential therapy with 2 mAbs in the absence of B-BiTE. Therefore, this modality facilitates easy and prompt generation of a broad panel of bispecific antibodies that can induce deep and durable antitumor responses in the presence of clinically available mAbs, supporting further advancement of reinforced immunotherapy for multiple myeloma and other refractory hematologic malignancies.
HEXIM1 is an essential transcription regulator during human erythropoiesis
Authors: Lv Xiurui , Murphy Kristin , Murphy Zachary , Getman Michael , Rahman Nabil , Nakamura Yukio , Blanc Lionel , Gallagher Patrick G. , Palis James , Mohandas Narla , Steiner Laurie A.
Published: September 2023

Regulation of RNA polymerase II (RNAPII) activity is an essential process that governs gene expression; however, its contribution to the fundamental process of erythropoiesis remains unclear. hexamethylene bis-acetamide inducible 1 (HEXIM1) regulates RNAPII activity by controlling the location and activity of positive transcription factor β. We identified a key role for HEXIM1 in controlling erythroid gene expression and function, with overexpression of HEXIM1 promoting erythroid proliferation and fetal globin expression. HEXIM1 regulated erythroid proliferation by enforcing RNAPII pausing at cell cycle check point genes and increasing RNAPII occupancy at genes that promote cycle progression. Genome-wide profiling of HEXIM1 revealed that it was increased at both repressed and activated genes. Surprisingly, there were also genome-wide changes in the distribution of GATA-binding factor 1 (GATA1) and RNAPII. The most dramatic changes occurred at the β-globin loci, where there was loss of RNAPII and GATA1 at β-globin and gain of these factors at γ-globin. This resulted in increased expression of fetal globin, and BGLT3, a long noncoding RNA in the β-globin locus that regulates fetal globin expression. GATA1 was a key determinant of the ability of HEXIM1 to repress or activate gene expression. Genes that gained both HEXIM1 and GATA1 had increased RNAPII and increased gene expression, whereas genes that gained HEXIM1 but lost GATA1 had an increase in RNAPII pausing and decreased expression. Together, our findings reveal a central role for universal transcription machinery in regulating key aspects of erythropoiesis, including cell cycle progression and fetal gene expression, which could be exploited for therapeutic benefit.
Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML
Authors: Man Cheuk-Him , Lam Wing , Dang Chee-Chean , Zeng Xiao-yuan , Zheng Li-Chuan , Chan Natalie Nok-Man , Ng Ka-Lam , Chan Koon-Chuen , Kwok Tsz-Ho , Ng Timothy Chi-Chun , Leung Wing-Yan , Huen Michael Shing-Yan , Wong Carmen Chak-Lui , So Chi Wai Eric , Dou Zhixun , Goyama Susumu , Bray Mark Robert , Mak Tak Wah , Leung Anskar Yu-Hung
Published: September 2023

Acute myeloid leukemia (AML) with TP53 mutation is one of the most lethal cancers and portends an extremely poor prognosis. Based on in silico analyses of druggable genes and differential gene expression in TP53-mutated AML, we identified pololike kinase 4 (PLK4) as a novel therapeutic target and examined its expression, regulation, pathogenetic mechanisms, and therapeutic potential in TP53-mutated AML. PLK4 expression was suppressed by activated p53 signaling in TP53 wild-type AML and was increased in TP53-mutated AML cell lines and primary samples. Short-term PLK4 inhibition induced DNA damage and apoptosis in TP53 wild-type AML. Prolonged PLK4 inhibition suppressed the growth of TP53-mutated AML and was associated with DNA damage, apoptosis, senescence, polyploidy, and defective cytokinesis. A hitherto undescribed PLK4/PRMT5/EZH2/H3K27me3 axis was demonstrated in both TP53 wild-type and mutated AML, resulting in histone modification through PLK4-induced PRMT5 phosphorylation. In TP53-mutated AML, combined effects of histone modification and polyploidy activated the cGAS-STING pathway, leading to secretion of cytokines and chemokines and activation of macrophages and T cells upon coculture with AML cells. In vivo, PLK4 inhibition also induced cytokine and chemokine expression in mouse recipients, and its combination with anti-CD47 antibody, which inhibited the “don’t-eat-me” signal in macrophages, synergistically reduced leukemic burden and prolonged animal survival. The study shed important light on the pathogenetic role of PLK4 and might lead to novel therapeutic strategies in TP53-mutated AML.
O-linked sialic acid residues on platelet membrane glycoprotein IIb mask the human HPA-9b alloepitope
Authors: Zhang Nanyan , Sullivan Mia J. , Curtis Brian R. , Newman Peter J.
Published: September 2023

Sialic acids occupy the terminal position of glycan chains and have the potential to influence the antigenicity of glycoproteins (GP). The polymorphisms of human platelet alloantigens (HPA)-3 and HPA-9, located near the C-terminus of the extracellular domain of platelet membrane GPIIb, are adjacent to sialyl-core 1 O-glycans emanating from serines 845 and 847. Whether the nearby O-glycans affect the antigenicity of HPA-9b or influence the binding of anti-HPA-9b alloantibodies in clinically significant cases of neonatal alloimmune thrombocytopenia is unknown. To address this issue, we generated a series of O-glycan mutant HPA-9 allele-specific induced pluripotent stem cell lines, differentiated them to megakaryocytes (MKs), and examined their ability to bind HPA-9b-specific alloantibodies. We found that both wild-type MKs treated with neuraminidase and those genetically modified to lack the sialidases ST3GAL1 and ST3GAL2 dramatically increased anti-HPA-9b alloantibody binding, indicating that the HPA-9b epitope is partially masked by terminal sialic acids on nearby O-glycans of GPIIb. Interestingly, mutating the serine residues that carry these glycan chains to alanine actually reduced the binding of anti-HPA-9b alloantibodies, indicating that these 2 O-glycan chains contribute to the presentation of the HPA-9b epitope—perhaps by stabilizing the conformation of the GP in this region. Collectively, our data suggest that detection of anti-HPA-9b alloantibodies may be enhanced through the use of HPA-9b-specific MKs that have been genetically altered to lack nearby terminal sialic acid residues but retain the glycan chains to which they are attached.
Tafasitamab and lenalidomide in large B-cell lymphoma: real-world outcomes in a multicenter retrospective study
Authors: Qualls David A. , Lambert Nicholas , Caimi Paolo F. , Merrill Mwanasha , Pullarkat Priyanka , Godby Richard C. , Bond David A. , Wehmeyer Graham T. , Romancik Jason , Amoozgar Behzad , Leslie Lori , Nastoupil Loretta J. , Crombie Jennifer L. , Abramson Jeremy S. , Khurana Arushi , Nowakowski Grzegorz S. , Maddocks Kami , Rutherford Sarah C. , Kahl Brad , Okwali Michelle , Buege Michael J. , Seshan Venkatraman , Batlevi Connie L. , Salles Gilles
Published: September 2023

In this real-world evaluation of tafasitamab-lenalidomide (TL) in relapsed or refractory LBCL, patients receiving TL had higher rates of comorbidities and high-risk disease characteristics, and substantially lower progression-free survival and overall survival, compared with the L-MIND registration clinical trial for TL.
TCRαβ/CD19 cell–depleted HLA-haploidentical transplantation to treat pediatric acute leukemia: updated final analysis
Authors: Merli Pietro , Algeri Mattia , Galaverna Federica , Bertaina Valentina , Lucarelli Barbarella , Boccieri Emilia , Becilli Marco , Quagliarella Francesco , Rosignoli Chiara , Biagini Simone , Girolami Elia , Meschini Antonella , Del Principe Giovanna , Sborgia Raffaella , Catanoso Maria Luigia , Carta Roberto , Strocchio Luisa , Pinto Rita Maria , Buldini Barbara , Falco Michela , Meazza Raffaella , Pende Daniela , Andreani Marco , Li Pira Giuseppina , Pagliara Daria , Locatelli Franco
Published: September 2023

TCRαβ/CD19 cell depletion is a promising graft manipulation technique frequently used in the context of human leukocyte antigen (HLA)–haploidentical hematopoietic stem cell transplantation (HSCT). We previously reported the results of a phase I-II clinical trial (NCT01810120) to assess the safety and the efficacy of this type of exvivo T-cell depletion in 80 children with acute leukemia, showing promising survival outcomes. We now report an updated analysis on a cohort of 213 children with a longer follow-up (median, 47.6 months for surviving patients). With a 5-year cumulative incidence of nonrelapse mortality of 5.2% (95% confidence interval [CI], 2.8%-8.8%) and a cumulative incidence of relapse of 22.7% (95% CI, 16.9%-29.2%), projected 10-year overall and disease-free survival (DFS) were 75.4% (95% CI, 68.6%-80.9%) and 71.6% (95% CI, 64.4%-77.6%), respectively. Cumulative incidence of both grade II-IV acute and chronic graft-versus-host disease were low (14.7% and 8.1%, respectively). In a multivariable analysis for DFS including type of disease, use of total body irradiation in the conditioning regimen (hazard ratio [HR], 0.5; 95% CI, 0.26-0.98; P = .04), disease status at HSCT (complete remission [CR] ≥3 vs CR 1/2; HR, 2.23; 95% CI, 1.20-4.16; P = .01), and high levels of pre-HSCT minimal residual disease (HR, 2.09; 95% CI, 1.01-4.33; P = .04) were independently associated with outcome. In summary, besides confirming the good outcome results already reported (which are almost superimposable on those of transplant from HLA-matched donors), this clinical update allows the identification of patients at higher risk of treatment failure for whom personalized approaches, aimed at reducing the risk of relapse, are warranted.
Mid-Cretaceous extensional magmatism in the Alborz Mountains, north Iran; geochemistry and geochronology of Gasht-Masuleh gabbros
Authors: Rezaei Leila , Timmerman Martin J. , Moazzen Mohssen , Altenberger Uwe , Sláma Jiří , Sudo Masafumi , Günter Christina , Wilke Franziska D. H. , Schleicher Anja M.
Published: September 2023

In the Gasht-Masuleh area in the Alborz Mountains, gabbroic magma intruded Palaeozoic metasediments and Mesozoic sediments and crystallised as isotropic and cumulate gabbros. LREE enrichment points to relatively low degrees of mantle melting and depletion of Ti, Nb and Ta relative to primitive mantle points to an arc related component in the magma. Clinopyroxene compositions indicate MORB to arc signatures. U–Pb zircon crystallisation ages of 99.5 ± 0.6 Ma and 99.4 ± 0.6 Ma and phlogopite 40Ar/39Ar ages of 97.1 ± 0.4 Ma, 97.5 ± 0.4 Ma, 97.1 ± 0.1 Ma, within 2σ error, indicate that gabbro intrusion occurred in the (Albian-)Cenomanian (mid-Cretaceous). As active subduction did not take place in the Cretaceous in North Iran, the small volume mafic magmatism in the Gasht-Masuleh area must be due to local, extension-related mantle melting. Melting was most likely caused by far field effects triggered by roll-back of the Neo-Tethys subducting slab. As subduction took place at a distance of ~ 400 km (present distance) from the Alborz Mountains, the observed arc geochemical signatures must be inherited from a previous subduction event and concomitant mantle metasomatism, possibly in combination with contamination of the magma by crustal material.
Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes
Authors: Wang Mingzhu , Xie Kangling , Zhao Shengnan , Jia Nan , Zong Yujiao , Gu Wenping , Cai Ying
Published: September 2023

Background

It has been documented that aerobic exercise (AE) has a positive effect on improving cognitive function in type 2 diabetes (T2DM) patients. Here, we tried to explore how AE regulates the expression of long non-coding RNA in serum-exosomes (Exos), thereby affecting cognitive impairment in T2DM mice as well as its potential molecular mechanism.

Methods

T2DM mouse models were constructed, and serum-Exos were isolated for whole transcriptome sequencing to screen differentially expressed lncRNA and mRNA, followed by prediction of downstream target genes. The binding ability of miR-382-3p with a long non-coding RNA MALAT1 and brain-derived neurotrophic factor (BDNF) was explored. Then, primary mouse hippocampal neurons were collected for in vitro mechanism verification, as evidenced by the detection of hippocampal neurons' vitality, proliferation, and apoptosis capabilities, and insulin resistance. Finally, in vivo mechanism verification was performed to assess the effect of AE on insulin resistance and cognitive disorder.

Results

Transcriptome sequencing analysis showed that MALAT1 was lowly expressed and miR-382-3p was highly expressed in serum-Exos samples of T2DM mice. There were targeted binding sites between MALAT1 and miR-382-3p and between miR-382-3p and BDNF. In vitro experiments showed that MALAT1 upregulated BDNF expression by inhibiting miR-382-3p. Silencing MALAT1 or overexpressing miR-382-3p could reduce the expression of INSR, IRS-1, IRS-2, PI3K/AKT, and Ras/MAPK, inhibit neuronal proliferation, and promote apoptosis. In vivo experiments further confirmed that AE could increase the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thereby improving cognitive impairment in T2DM mice.

Conclusion

AE may upregulate the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thus improving cognitive impairment in T2DM mice.
Identification of plant vacuole proteins by using graph neural network and contact maps
Authors: Sui Jianan , Chen Jiazi , Chen Yuehui , Iwamori Naoki , Sun Jin
Published: September 2023

Plant vacuoles are essential organelles in the growth and development of plants, and accurate identification of their proteins is crucial for understanding their biological properties. In this study, we developed a novel model called GraphIdn for the identification of plant vacuole proteins. The model uses SeqVec, a deep representation learning model, to initialize the amino acid sequence. We utilized the AlphaFold2 algorithm to obtain the structural information of corresponding plant vacuole proteins, and then fed the calculated contact maps into a graph convolutional neural network. GraphIdn achieved accuracy values of 88.51% and 89.93% in independent testing and fivefold cross-validation, respectively, outperforming previous state-of-the-art predictors. As far as we know, this is the first model to use predicted protein topology structure graphs to identify plant vacuole proteins. Furthermore, we assessed the effectiveness and generalization capability of our GraphIdn model by applying it to identify and locate peroxisomal proteins, which yielded promising outcomes. The source code and datasets can be accessed at https://github.com/SJNNNN/GraphIdn.
Genic constraint against nonsynonymous variation across the mouse genome
Authors: Powell George , Simon Michelle M. , Pulit Sara , Mallon Ann-Marie , Lindgren Cecilia M.
Published: September 2023

Background

Selective constraint, the depletion of variation due to negative selection, provides insights into the functional impact of variants and disease mechanisms. However, its characterization in mice, the most commonly used mammalian model, remains limited. This study aims to quantify mouse gene constraint using a new metric called the nonsynonymous observed expected ratio (NOER) and investigate its relationship with gene function.

Results

NOER was calculated using whole-genome sequencing data from wild mouse populations (Mus musculus sp and Mus spretus). Positive correlations were observed between mouse gene constraint and the number of associated knockout phenotypes, indicating stronger constraint on pleiotropic genes. Furthermore, mouse gene constraint showed a positive correlation with the number of pathogenic variant sites in their human orthologues, supporting the relevance of mouse models in studying human disease variants.

Conclusions

NOER provides a resource for assessing the fitness consequences of genetic variants in mouse genes and understanding the relationship between gene constraint and function. The study’s findings highlight the importance of pleiotropy in selective constraint and support the utility of mouse models in investigating human disease variants. Further research with larger sample sizes can refine constraint estimates in mice and enable more comprehensive comparisons of constraint between mouse and human orthologues.
Comparative pangenomic analysis of predominant human vaginal lactobacilli strains towards population-specific adaptation: understanding the role in sustaining a balanced and healthy vaginal microenvironment
Authors: Bhattacharya Anupam , Das Sushmita , Bhattacharjee Maloyjo Joyraj , Mukherjee Ashis K. , Khan Mojibur Rohman
Published: September 2023

The vaginal microenvironment of healthy women has a predominance of Lactobacillus crispatus, L. iners, L. gasseri, and L. jensenii. The genomic repertoire of the strains of each of the species associated with the key attributes thereby regulating a healthy vaginal environment needs a substantial understanding.

We studied all available human strains of the four lactobacilli across different countries, isolated from vaginal and urinal sources through phylogenetic and pangenomic approaches. The findings showed that L. iners has the highest retention of core genes, and L. crispatus has more gene gain in the evolutionary stratum. Interestingly, L. gasseri and L. jensenii demonstrated major population-specific gene-cluster gain/loss associated with bacteriocin synthesis, iron chelating, adherence, zinc and ATP binding proteins, and hydrolase activity. Gene ontology enrichment analysis revealed that L. crispatus strains showed greater enrichment of functions related to plasma membrane integrity, biosurfactant, hydrogen peroxide synthesis, and iron sequestration as an ancestral derived core function, while bacteriocin and organic acid biosynthesis are strain-specific accessory enriched functions. L. jensenii showed greater enrichment of functions related to adherence, aggregation, and exopolysaccharide synthesis. Notably, the key functionalities are heterogeneously enriched in some specific strains of L. iners and L. gasseri.

This study shed light on the genomic features and their variability that provides advantageous attributes to predominant vaginal Lactobacillus species maintaining vaginal homeostasis. These findings evoke the need to consider region-specific candidate strains of Lactobacillus to formulate prophylactic measures against vaginal dysbiosis for women’s health.
GhIMP10D, an inositol monophosphates family gene, enhances ascorbic acid and antioxidant enzyme activities to confer alkaline tolerance in Gossypium hirsutum L.
Authors: Fan Yapeng , Peng Fanjia , Cui Ruifeng , Wang Shuai , Cui Yupeng , Lu Xuke , Huang Hui , Ni Kesong , Liu Xiaoyu , Jiang Tiantian , Feng Xixian , Liu Mengyue , Lei Yuqian , Chen Wenhua , Meng Yuan , Han Mingge , Wang Delong , Yin Zujun , Chen Xiugui , Wang Junjuan , Li Yujun , Guo Lixue , Zhao Lanjie , Ye Wuwei
Published: September 2023

Background

Inositol monophosphates (IMP) are key enzymes in the ascorbic acid (AsA) synthesis pathways, which play vital roles in regulating plant growth and development and stresses tolerance. To date, no comprehensive analysis of the expression profile of IMP genes and their functions under abiotic stress in cotton has been reported.

Results

In this study, the genetic characteristics, phylogenetic evolution, cis-acting elements and expression patterns of IMP gene family in cotton were systematically analyzed. A total of 28, 27, 13 and 13 IMP genes were identified in Gossypium hirsutum (G. hirsutum), Gossypium barbadense (G. barbadense), Gossypium arboreum (G. arboreum), and Gossypium raimondii (G. raimondii), respectively. Phylogenetic analysis showed that IMP family genes could cluster into 3 clades. Structure analysis of genes showed that GhIMP genes from the same subgroup had similar genetic structure and exon number. And most GhIMP family members contained hormone-related elements (abscisic acid response element, MeJA response element, gibberellin response element) and stress-related elements (low temperature response element, defense and stress response element, wound response element). After exogenous application of abscisic acid (ABA), some GhIMP genes containing ABA response elements positively responded to alkaline stress, indicating that ABA response elements played an important role in response to alkaline stress. qRT-PCR showed that most of GhIMP genes responded positively to alkaline stress, and GhIMP10D significantly upregulated under alkaline stress, with the highest up-regulated expression level. Virus-induced gene silencing (VIGS) experiment showed that compared with 156 plants, MDA content of pYL156:GhIMP10D plants increased significantly, while POD, SOD, chlorophyII and AsA content decreased significantly.

Conclusions

This study provides a thorough overview of the IMP gene family and presents a new perspective on the evolution of this gene family. In particular, some IMP genes may be involved in alkaline stress tolerance regulation, and GhIMP10D showed high expression levels in leaves, stems and roots under alkaline stress, and preliminary functional verification of GhIMP10D gene suggested that it may regulate tolerance to alkaline stress by regulating the activity of antioxidant enzymes and the content of AsA. This study contributes to the subsequent broader discussion of the structure and alkaline resistance of IMP genes in cotton.
Traumatic life events and risk for dementia: a systematic review and meta-analysis
Authors: Severs Emilia , James Tiffeny , Letrondo Pilar , Løvland Lise , Marchant Natalie L. , Mukadam Naaheed
Published: September 2023

Objectives

To systematically review the association between traumatic life events (TLE) and dementia risk.

Design

Systematic review and meta-analysis.

Data sources

APA, PsychINFO, Embase and MEDLINE from their inception to 29.05.21 and updated on 20.04.22.

Eligibility criteria for selecting studies

Original research articles published in peer reviewed journals examining the association between TLE and all cause dementia in individuals aged 60 and over. Two researchers independently assessed the risk of bias using the Newcastle–Ottawa Scale. We conducted a generic inverse variance random effects meta-analysis to provide an overall estimate of TLE impact on dementia risk.

Main outcome measures

Risk, odds and hazards ratios relating to dementia risk.

Results

Initially, 3,487 studies were retrieved in the search and seven studies were included in the meta-analysis with data being used from 276,570 participants. TLE were associated with increased dementia risk. Trauma in general had a pooled HR of 1.21, (95% CI 1.03, 1.43, P = 0.0001). War/ Holocaust trauma and childhood trauma were also associated with increased dementia risk (HR = 1.28 (95% CI 1.01–1.63, P = 0.02) and HR = 1.76 (95% CI 1.17–2.64, P = 0.007) respectively).

Conclusions

We have found an association between TLE and dementia risk. Future research exploring the dimensions of TLE and individual level factors are needed to better understand the relationship between TLE and dementia.

Trial Registration

PROSPERO CRD42021253090.
Survey of knowledge, self-efficacy, and attitudes toward suicide prevention among nursing staff
Authors: Huang Kuan Chin , Jeang Shiow-Rong , Hsieh Hsing-Ling , Chen Jing-Wen , Yi Ching-Hsien , Chiang Yung-Chih , Wu Han-Ping
Published: September 2023

Objective

This study aimed to explore the knowledge, self-efficacy, and attitudes toward suicide prevention among nurses with different demographic characteristics.

Methods

A cross-sectional descriptive design was adopted, and the study was conducted between August and September 2020. The content of the questionnaire included basic demographics, knowledge, self-efficacy, and attitudes toward suicide prevention. Correlation analysis was performed to determine nurses’ knowledge, self-efficacy, and attitudes toward suicide prevention.

Results

The sample comprised 778 nursing staff from a medical center in southern Taiwan. The results showed that age, years of nursing experience, department type, education on suicide prevention, and care experience of nursing staff were associated with their knowledge, self-efficacy, and attitudes toward suicide prevention in general hospital patients. Younger and less experienced nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Nurses who received suicide-related education and training exhibited better self-efficacy and attitudes than those who did not. Nurses with care experience had better knowledge of suicide prevention than those without experience. Knowledge and self-efficacy in suicide prevention were both significantly and positively correlated with attitudes.

Conclusion

Younger, less experienced, psychiatric nurses demonstrated superior knowledge, self-efficacy, and attitudes toward suicide prevention. Therefore, education on suicide prevention should be strengthened for older, experienced, and non-psychiatric nurses.
Midwives’ perspectives about using individualized care plans in the provision of immediate postpartum care in Uganda; an exploratory qualitative study
Authors: Namutebi Mariam , Nalwadda Gorrette K. , Kasasa Simon , Muwanguzi Patience A. , Kaye Dan K.
Published: September 2023

Introduction

Individualized care planning has been slowly integrated into practice in Uganda with minimal documentation of how the concept is applied in providing care. This study explored the perceptions of midwives about the use of individualized care plans (ICPs) in the provision of immediate postpartum care.

Methods

An exploratory descriptive qualitative approach was used in this study. We interviewed fifty midwives from 37 health facilities in Uganda's greater Mpigi region. The midwives, who were certificate and diploma holders, were purposively enrolled in the selected facilities. Deductive content analysis was done based on the COM-B model.

Results

Four themes emerged from the data namely; compatibility, motivation, opportunities, and the midwives’ suggested strategies and targets for improved individualized care planning. The midwives were aware of individualized care planning and they utilized it in their provision of immediate postpartum care especially when assessing clients for risks, preparing clients for referral, caring for Human Immunodeficiency virus (HIV) exposed babies and their mothers, and educating/ supporting first-time mothers (automatic motivation). Having a good nurse-patient relationship, privacy, and ample time to care for the clients were noted as motivators for individualized care plan use, while poor documentation of care, high patient load, and perceived patients’ lack of understanding of the complexities of illness in the immediate postpartum period were the barriers (social opportunity) identified by midwives to the use of individualized care planning.

Conclusion

There are still capability, motivation, and opportunity hindrances to the use of individualized care planning. Staff recruitment, training, and harmonization of the documentation forms may improve the use of care plans in the postpartum period.
Exploring the practicality and acceptability of a brief exercise communication and clinician referral pathway in cancer care: a feasibility study
Authors: Caperchione Cristina M. , English Madeleine , Sharp Paul , Agar Meera R. , Phillips Jane L. , Liauw Winston , Harris Carole A. , McCullough Susan , Lilian Ruth
Published: September 2023

Background

The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway.

Methods

Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken.

Results

Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care.

Conclusions

Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP.

Trial registration

This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.
Use of evidence-based approaches in procurement and implementation of health and welfare technologies – a survey among Swedish municipalities
Authors: Richardson Matt X. , Andersson Sarah Wamala
Published: September 2023

Background

Health and welfare technologies (HWT) are increasingly procured and implemented by public providers in Swedish municipalities, but it remains unclear if and how evidence for these technologies’ effectiveness is used in both processes. The aim of this study was to investigate the use of evidence in Swedish municipal public sector procurement and implementation of HWT.

Methods

A telephone survey of 197 municipalities was conducted with questions regarding the use of evidence in both processes, as well as eventual support needs regarding its use. Standard definitions of HWT and evidence were provided prior to the survey. Response frequencies and percentage proportions were calculated per question. Lambda (Λ) values with corresponding significance values were calculated for associations between responses to selected questions and the size and type of municipality, with values of 0.01 to 0.19 designated as weak associations, 0.20 to 0.39 as moderate, and 0.40 and above as strong.

Results

Sixty-four municipalities completed the entire survey. Consistent use of evidence for effectiveness of HWT occurred in less than half of respondents’ municipal public procurement processes. Two-thirds of municipalities did not have an established model or process for implementation of HWT that used evidence in any manner. More than three quarters of municipalities lacked a systematic plan for follow-up and evaluation of effectiveness of implemented HWT, and of those that did less than half followed their plan consistently. Most municipalities expressed the need for support in using evidence in HWT-related processes but did not consider evidence and systematic evaluation to be prioritized.

Conclusions

Weaknesses and gaps in using evidence in procurement and implementation processes may create a legacy of sub-optimal implementation of HWT in Swedish municipal health- and social care services, and lost opportunities for real-world evidence generation. There was a clear indication of the need for unified national guidance for using and generating evidence in key HWT-related municipal processes and implementation. Such guidance needs to be developed and effectively communicated.