bluuebunny/crossref_metadata_2025 huggingface dataset:
Tyrosine Kinase Inhibition Activates Intratumoral γδ T Cells in Gastrointestinal Stromal Tumor
Authors: Etherington Mark S. , Hanna Andrew N. , Medina Benjamin D. , Liu Mengyuan , Tieniber Andrew D. , Kwak Hyunjee V. , Tardy Katherine J. , Levin Lillian , Do Kevin J. , Rossi Ferdinando , Zeng Shan , DeMatteo Ronald P.
Published: November 2023

γδ T cells are a rare but potent subset of T cells with pleiotropic functions. They commonly reside within tumors but the response of γδ T cells to tyrosine kinase inhibition is unknown. To address this, we studied a genetically engineered mouse model of gastrointestinal stromal tumor (GIST) driven by oncogenic Kit signaling that responds to the Kit inhibitor imatinib. At baseline, γδ T cells were antitumoral, as blockade of either γδ T-cell receptor or IL17A increased tumor weight and decreased antitumor immunity. However, imatinib therapy further stimulated intratumoral γδ T cells, as determined by flow cytometry and single-cell RNA sequencing (scRNA-seq). Imatinib expanded a highly activated γδ T-cell subset with increased IL17A production and higher expression of immune checkpoints and cytolytic effector molecules. Consistent with the mouse model, γδ T cells produced IL17A in fresh human GIST specimens, and imatinib treatment increased γδ T-cell gene signatures, as measured by bulk tumor RNA-seq. Furthermore, tumor γδ T cells correlated with survival in patients with GIST. Our findings highlight the interplay between tumor cell oncogene signaling and antitumor immune responses and identify γδ T cells as targets for immunotherapy in GIST.
Bexmarilimab Activates Human Tumor-Associated Macrophages to Support Adaptive Immune Responses in Interferon-Poor Immune Microenvironments
Authors: Rannikko Jenna H. , Bono Petri , Hynninen Johanna , Hollmén Maija
Published: November 2023

Immune checkpoint inhibitors (ICI) show substantially greater efficacy in inflamed tumors characterized by preexisting T-cell infiltration and IFN signaling than in noninflamed “cold” tumors, which often remain immunotherapy resistant. The cancer immunotherapy bexmarilimab, which inhibits the scavenger receptor Clever-1 to release macrophage immunosuppression and activate adaptive immunity, has shown treatment benefit in subsets of patients with advanced solid malignancies. However, the mechanisms that determine bexmarilimab therapy outcome in individual patients are unknown. Here we characterized bexmarilimab response in ovarian cancer ascites macrophages ex vivo using single-cell RNA sequencing and demonstrated increased IFN signaling and CXCL10 secretion following bexmarilimab treatment. We further showed that bexmarilimab was most efficacious in macrophages with low baseline IFN signaling, as chronic IFNγ priming abolished bexmarilimab-induced TNFα release. These results highlight an approach to target immunologically cold tumors and to increase the likelihood of their subsequent response to ICIs.
Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model
Authors: Leypoldt John K. , Echeverri Jorge , Harenski Kai , Singh Kuljinder
Published: November 2023

Introduction: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. Methods: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. Results: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. Conclusions: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.
Study of Allergy and Sensitization Relationship in Children and Parents in Southern China
Authors: Gan Hui , Huang Zhifeng , Zhu Huiqing , Li Aoli , Chen Tong , Yin Ziyu , Sun Baoqing
Published: November 2023

Introduction: The incidence of allergic diseases has increased globally, with genetics playing an essential role in these conditions’ development. However, there is still a gap in understanding of how parental allergy status affects children’s allergies. Methods: An electronic questionnaire was used to assess allergy-related symptoms in kindergarten children and their parents, with a clinical diagnosis and concurrent serum allergen-specific immunoglobulin E (IgE), total IgE, and blood cell counts obtained. Results: 88 family groups were enrolled, with allergy prevalence of 85.2% in children, 50% in fathers, and 42% in mothers. Allergic rhinoconjunctivitis was the most common allergic disease. When the mother had an allergy, the children’s allergy diagnosis rate was 91.3%; 86.67% when the father had an allergy; and 85.71% when both parents had allergies. The child sensitization rate was 78.26% when the father had sensitization, 59.09% just as the mother had sensitization, and 84.21% when both parents had sensitization. Paternal allergies affected children’s quality of life due to allergic rhinitis but not their rhinitis symptoms. Maternal allergies or sensitization did not significantly affect children’s symptoms or quality-of-life scores. Conclusion: The study found a positive correlation between childhood and parental allergies, and further studies are needed to confirm the findings.
Assessing the Efficacy of Monthly 308 nm Excimer Lamp Double-Stacked Pulse Adjusted Therapy for Alopecia Areata
Authors: Rodríguez-Acosta Elva Dalia , Fernandez Nieto Diego , Berna-Rico Emilio , Galván-García Hector Ricardo , Meza-Castro Ruth Galit , Rosales-Lerma Ana Karen , Guerrero-Cervantes Andrea Viridiana , Ramírez-Marín Hassiel Aurelio
Published: November 2023

Introduction: Alopecia areata (AA) is an autoimmune disease characterized by T cell‐mediated attack on the hair follicle. Although there are a wide range of therapies, the majority of them are not satisfactory due to side effects, pain due to intralesional injections or limited efficacy. In this study, we sought to evaluate the efficacy, influence factors, and safety of 308 nm excimer lamp used in a monthly basis in a double-stacked pulse manner for the treatment of AA. Methods: This was a prospective study, using 308 nm excimer lamp in a double-stacked pulse therapy for AA. The primary endpoint was the improvement in SALT score. Results: A total of 40 patients with AA were enrolled in this study. Forty (100%) patients achieved clinical response. Hyperpigmentation and erythema occurred on the treated alopecic areas of all patients but they were considered tolerable. Patients of younger age or with a smaller area of affection had a better overall treatment response. Conclusion: 308 nm excimer lamp therapy is an excellent option for single or multiple AA because it achieves a good clinical response with less adverse effects than other therapies. This therapy may be useful for low-income countries where new JAK inhibitors are not available, however, for patients with extensive hair loss, it is not as effective and thus, it may be unfit for patients with alopecia totalis and alopecia universals.
Currarino Syndrome in Two Moroccan Siblings with Inherited 7q36 Deletion due to Maternal t(7;21)(q36;p11)mat: A Case Report
Authors: El Amrani Zhour , Natiq Abdelhafid , Sbiti Aziza , Ratbi Ilham , Liehr Thomas , Sefiani Abdelaziz , Sahli Maryem
Published: November 2023

Introduction: Currarino syndrome is a rare syndrome with multiple congenital anomalies including sacral agenesis, anorectal malformation, and presence of a presacral mass. Currarino syndrome is considered to be an autosomal dominant inherited disorder, with low penetrance and variable expressivity, but sporadic cases have also been reported. Mutations in MNX1 gene, mapped to 7q36, are the main causes of this syndrome. To the best of our knowledge, less than 400 cases of this syndrome have been mentioned in the literature. Currarino syndrome is often seen in children and considered to be rare in adults; it is mostly found as incidental finding and suspected to be underdiagnosed. Case Presentation: Recognizing the rarity of this syndrome, we present here two siblings with incomplete form of Currarino syndrome combined with microcephaly and intellectual disability. Banding and molecular cytogenetics were used to characterize the origin of this disorder. Banding cytogenetics together with molecular cytogenetics revealed an unbalanced translocation t(7;21)(q36.2;p11.3)mat, leading to a deletion of the 7q36 region in both affected children. Conclusion: This report highlights the importance of cytogenetics in diagnosis of rare genetic syndromes, with impact on genetic counseling of patients and their families. To the best of our knowledge, this is the first Moroccan Currarino syndrome case due to an unbalanced translocation leading to a der(7)t(7;21)(q36.2;p11.3). Also, this is the first Currarino syndrome case associated with a deletion in 7q36 to be reported in Morocco.
Pediatric Mesangial Proliferative Glomerulonephritis Has Increased the Platelet Thrombus Formation Potentials under High-Shear Flow Condition
Authors: Omae Takashi , Ishikawa Tomoaki , Ogiwara Kenichi , Nogami Keiji
Published: November 2023

Introduction: Blood coagulation is associated with glomerulonephritis (GN) pathophysiology. Using whole-blood-based rotational thromboelastometry, we recently reported that the degree of hypercoagulability in pediatric patients with immunoglobulin A nephropathy (IgAN), a GN, might be associated with pathological severity. To further clarify the coagulation status of mesangial proliferative GN (MesPGN), we assessed the platelet thrombus formation (PTF) under high-shear flow using a microchip-based flow chamber system (T-TAS®). Methods: Thirty-four pediatric patients definitively diagnosed with MesPGN by renal biopsy at Nara Medical University Hospital between 2015 and 2022 were enrolled, and 29 patients (case group; median age, 8.0 years) were assessed. Microchips coated with collagen (PL-chip) were used to assess PTF at high-shear in whole blood. The times to increase by 10 and 30 kPa (T10 and T30) from baseline were calculated and compared with those of the pediatric controls. Changes in the parameters during the treatment course and the relationship between pathological severity and the parameters were evaluated. Results: T10 and T30 parameters in the PL-chip were significantly shorter, and the area under the curves were greater in the case group than those in the control group (both p < 0.05). Each parameter was enhanced during the 3-week treatment but improved after the end of treatment. No significant relationship was observed between pathological severity and these parameters. Little PTF difference was observed between IgAN and Henoch-Schönlein purpura nephritis. Conclusions: Pediatric MesPGN increased the potential for PTF under high-shear flow conditions.
Is Total Neoadjuvant Treatment Beneficial for Locally Advanced Rectal Cancer? A Meta-Analysis of Randomized Controlled Trials
Authors: Wu Hai-Qiong , Li Jun , Miao Ji-Dong , Li Jia-Wei
Published: November 2023

Background: Total neoadjuvant therapy (TNT) is a new strategy combining neoadjuvant therapy and chemotherapy to enhance tumor shrinkage and systemic control. Its effectiveness remains debated. Objectives: This study conducts a meta-analysis of randomized controlled trials (RCTs) to assess TNTs impact and provide high-quality evidence for rectal cancer treatment decisions. Method: We searched China National Knowledge Infrastructure, VIP Database, Wanfang Database, China biomedical literature database, PubMed database, Embase database, and The Cochrane Library for RCTs comparing TNT with neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. The included trials were screened and assessed for quality based on inclusion and exclusion criteria, and meta-analysis was performed using RevMan 5.3 software. Results: A total of 11 RCTs reported in 14 articles, with 1,624 cases in the TNT group and 1,541 cases in the CRT group. The results of the meta-analysis showed that compared with the CRT group, the TNT group had a higher pathological complete response rate (risk ratio [RR] = 1.65, 95% confidence interval [CI]: [1.40, 1.94], p < 0.00001), higher T0 downstaging rate (RR = 1.51, 95% CI: [1.29, 1.77], p < 0.00001), higher 3-year overall survival (hazard ratio [HR] = 0.81, 95% CI: [0.67, 0.98], p = 0.03), and higher 3-year disease-free survival (HR = 0.82, 95% CI: [0.70, 0.95], p = 0.008). However, there was no statistically significant difference between the two groups in terms of R0 resection rate (RR = 1.02, 95% CI: [0.99, 1.05], p = 0.14), sphincter preservation rate (RR = 0.94, 95% CI: [0.88, 1.01], p = 0.12), anastomotic leakage rate (RR = 1.42, 95% CI: [0.85, 2.38], p = 0.18), and grade 3 or higher adverse events (RR = 1.21, 95% CI: [0.95, 1.54], p = 0.13). Conclusions: In the treatment of locally advanced rectal cancer, TNT offers greater survival benefits compared to neoadjuvant CRT and does not significantly increase the incidence of adverse events. However, further data and studies with long-term outcomes are still required.
Association between Dietary Consumption of Vitamin B1 and Advanced Age-Related Macular Degeneration: A Cross-Sectional Observational Study in NHANES 2005–2008
Authors: Zheng Qingqing , Shen Ting , Xu Mengyue , Tan Lingtong , Shen Zeqi , Hong Chaoyang
Published: November 2023

Introduction: One of the most common conditions that causes permanent blindness globally is age-related macular degeneration (AMD). The purpose of the present study was to determine the association between vitamin B1 consumption and the prevalence of late AMD in a representative US sample. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008 were utilized for this cross-sectional analysis. The logistic regression model was used to evaluate the association between vitamin B1 consumption levels and late AMD. Results: Our study included 5,107 people aged 40 years old and above. Vitamin B1 intake levels were inversely associated with the prevalence of late AMD, with OR being 0.40 (95% CI: 0.26–0.62), 0.53 (95% CI: 0.29–0.94), 0.55 (95% CI: 0.31–0.99) for the crude model 1, adjusted model 2, and fully adjusted model 3, respectively. Conclusion: Our study found that vitamin B1 intake levels were inversely associated with the prevalence of late AMD in the USA. Further randomized clinical trials among multiple centers are still warranted to investigate the longitudinal and causal relationship between vitamin B1 intake and late AMD.
Functional Magnetic Resonance Imaging to Monitor Disease Progression: A Prospective Study in Patients with Primary Membranoproliferative Glomerulonephritis
Authors: Villa Giulia , Daina Erica , Brambilla Paolo , Gamba Sara , Leone Valentina Fanny , Carrara Camillo , Rizzo Paola , Noris Marina , Remuzzi Giuseppe , Remuzzi Andrea , Caroli Anna
Published: November 2023

Introduction: Primary membranoproliferative glomerulonephritis (MPGN) is a rare kidney disease with poor prognosis and no specific therapies. The disease heterogeneity and the difficulty of performing repeated kidney biopsies pose big challenges. This study investigates the correlation between non-contrast enhanced magnetic resonance imaging (MRI) and histologic and clinical findings in patients with primary MPGN. Methods: Patients with primary MPGN underwent baseline and 1-year kidney MRI in addition to biopsy and laboratory testing as part of a prospective MRI subproject of a clinical trial (ClinicalTrials.gov identifier NCT03723512). Diffusion-weighted and phase-contrast MRI were used to investigate kidney diffusivity and perfusion. Peritubular interstitial volume and fibrosis were quantified on kidney biopsies. Results: Seven patients with primary MPGN (18[17–21] years, 43% females) were included. Kidney biopsies showed variable degree of global and segmental glomerular sclerosis ([5–30]% and [10–60]%), mild interstitial fibrosis (<10%), and increased peritubular interstitial volume ([19–40]%). MRI and laboratory parameters changed very differently from patient to patient over 1 year. Peritubular interstitial volume and glomerular sclerosis negatively associated with renal blood flow (RBF) (rho = −0.81 and −0.77), and positively with renal vascular resistance (RVR) (rho = 0.65 and 0.73). Urinary albumin to creatinine ratio (uACR) negatively associated with RBF and filtration fraction (FF) (rho = −0.86 and −0.6), while positively with RVR (rho = 0.88). uACR decrease was associated with kidney diffusivity increase (rho = −0.5). Measured glomerular filtration rate (GFR) positively associated with kidney diffusivity, RBF, and FF (rho = 0.87, 0.85, and 0.59), while negatively with RVR (rho = −0.89); GFR increase was associated with kidney diffusivity, RBF, and FF increase (rho = 0.77, 0.7, and 0.7) and RVR decrease (rho = −0.7). Conclusion: The strong correlation found between MRI and histologic and clinical findings, despite the rather limited number of patients, highlights MRI potential to monitor disease progression in patients with rare kidney disease.
The Asymmetries of Displacement: The Spatial Aspects of the Greek-Turkish Population Exchange
Authors: Cankara Melis
Published: November 2023

The Greek-Turkish population exchange convention of 1923 had major effects on both countries in terms of politics, economy, society, and space. Some of the negative impacts were minimized over time. However, there are some long-term impacts, for instance on space, that are still observable in the cities we live in, even though a full century has passed since the exchange. This article focuses on both the local and broader spatial consequences of the population exchange from a comparative perspective.
On Taxonomy. Reflections on the Usefulness of a ‘Non-Modern’ Science
Authors: Wessel Andreas
Published: November 2023

Taxonomy is a science whose roots go back to the dawn of human curiosity. Its evergrowing body of knowledge, laid down in the biological classification, provides the framework within which every biologist operates. Taxonomists have always used the oldest scientific tools for their research — their natural capabilities of observation, gestalt perception, categorization, and classification — as well as the most advanced technologies of the day. Today, taxonomy is firmly anchored in evolutionary theory, spearheading on topics such as the species problem and biodiversity and its development.
Murdering Mangir
Authors: Meyer Verena Hanna
Published: November 2023

Contemporary Javanese Islam is often imagined as unusually peaceful, the result of an allegedly conflict-free early history populated by Sufis and saints. Yet not all of Java’s Islamic history is peaceful, and neither were violent historic episodes always marginalized by historians and writers. This article discusses two literary accounts of a murder that happened in the early years of Mataram, the dynasty that facilitated widespread Islamization. Their two authors—Raden Ngabehi Suradipura and Pramoedya Ananta Toer—used the story as a familiar allegory to process their own experiences of violence and oppression in the colonial and postcolonial state. Belying normative visions of a teleology of peace, they present theo-political imaginaries in which violence is accepted in the cultivation of virtue and the creation—or aspirational creation—of a just polity. Through their literary work, these writers expressed their complex positionalities as they made sense of oppressive regimes, the political role of Islamic beliefs, and the normative content of history.
Sustainability and the politics of the body in alternative food consumption: An embodied materialist perspective
Authors: Dal Gobbo Alice
Published: November 2023

Health is a key dimension of contemporary food consumption. This preoccupation is beginning to overlap with ecological concerns, as healthy diets are said to largely correspond with sustainable diets. Nevertheless, this link remains rather vague and under-researched in practice. This article adopts an ‘embodied materialist’ perspective to inquire into how the health–sustainability nexus is articulated in the everyday labour of people engaging in alternative food consumption. The interviews, carried out in Milan (Italy), suggest that focusing on health might not always be straightforwardly effective for the promotion of deep and systemic changes. The analysis finds three ways in which the health–sustainability nexus is articulated in daily life. If framed within the dominant articulation of labour and value, health is an individualistic preoccupation with limited potential for socio-ecological transformation. When food labour is guided by the very different logic of care, which emphasises relationality, fragility and the search for a shared wellbeing, more ecological practices emerge, but with some ambivalent implications especially with regards to social justice. Collective engagement in alternative food networks politicises the body more deeply, making it a concrete site of struggle against unsustainable food regimes.
The Relative Impact of Historically Black College and University Economics Departments and Economists: Has the Hierarchy Changed Since the Turn of the Century?
Authors: Mixon Franklin G. , Upadhyaya Kamal P.
Published: November 2023

This study examines citation patterns associated with the research being done by the current generation of economists affiliated with America's historically black colleges and universities (HBCUs). In terms of mean citations, we report that the economics department at Bethune-Cookman University ranks first, followed by South Carolina State University and Tennessee State University. In terms of total citations, we find that Howard University ranks first, followed by North Carolina A&T State University and Tennessee State University. Our study is also the first to examine the relative impact of individual economists across the HBCU landscape. In doing so, we report that Elizabeth Asiedu of Howard University ranks first, followed by Ekanayake Ekanayake of Bethune-Cookman University and Faridul Islam of Morgan State University. Lastly, a separate analysis reveals a strong positive correlation between the relative sizes of the economics departments at HBCUs and the research impact of those economics departments. Thus, it appears as though institutions that commit a greater proportion of their resources (i.e., faculty lines) to economics have more influential economists.
The politics of deautomation: Being disaffected by platform capitalism
Authors: Bissell David
Published: November 2023

Being affected in on-demand platform urbanism is a primary site of politics, not an aftereffect that happens once capitalism has had its way. To make this argument, this article begins by expanding automation from its conventional technical purview to better appreciate its overlooked embodied dimensions. Accordingly, through the examples of on-demand mobility and delivery platforms, I explain how automation can be understood as a specific structure of feeling immanent to on-demand platform urbanism that is transforming city life and creating distinctive subjectivities. This article takes as its empirical focus the unravelling of these embodied dimensions of automation, which has been exacerbated by the gradual rollback of COVID-19 restrictions in Melbourne. My argument is that a felt sense of disaffection by both workers and consumers is effectively deautomating this form of on-demand platform capitalism. The article concludes that disaffection in this context has a potentially recuperative dimension, opening up alternative urban futures that were previously unthinkable.
Corrosion behaviour study of Inconel 617 TIG and A-TIG weldments using potentiodynamic polarisation test and intergranular corrosion test
Authors: Sakthivel Senthil Kumaar , Korra Nanda Naik , Kandasami Devakumaran , Kottaimathan Ganesh Kumar
Published: November 2023

Inconel 617 alloy is known for its impressive resistance to numerous corrosive environments and is widely used in high-temperature applications. This study analyses the microstructure and corrosion behaviour of the Inconel 617 weldments fabricated by activated flux tungsten inert gas (A-TIG) welding and TIG welding. Potentiodynamic polarisation (PDP) test in a 3.5% NaCl solution and intergranular corrosion (IGC) test was conducted to analyse the corrosion behaviour of the base metal (BM) and weldments. In accordance with the PDP test evaluation, the BM, TIG weld and A-TIG weld samples had corrosion rates of 0.0028, 0.0156 and 0.0043 mpy, respectively. PDP test results showed that all three samples had outstanding corrosion resistance. According to IGC test findings, the A-TIG weld sample had a greater corrosion resistance of 15.1 mpy when compared to BM and the TIG weld sample, which had corrosion resistances of 19.78 and 23.2 mpy, respectively. Chromium depletion at the grain boundaries caused by carbide formation was the reason for the TIG weld sample's poor corrosion resistance.
Creep behavior of sandstone under the coupling action of stress and pore water pressure using three-dimensional digital image correlation
Authors: Chen Cancan , Xie Heping , Xu Jiang , Peng Shoujian , Li Cunbao , Li Minghui
Published: November 2023

Understanding the damage evolution and time-dependent property of rock creep is of great significance for predicting geohazards and evaluating the long-term stability of geotechnical structures. In this study, a three-dimensional digital image correlation system was adopted to investigate the creep behavior of sandstone under the coupling action of stress and pore water pressure. The apparent strain fields, deformation characteristics of the localization zone, and micromorphology of the fracture surface were analyzed. The results demonstrated that when the applied deviatoric stress level was above σci (crack initial stress) or σcd (crack damage stress), the increase in pore water pressure promoted creep deformation evidently, improved the creep rate significantly and shortened the time-to-failure of the rock obviously. In the radial strain field, the localized development of substantial microcracks on the rock surface was concentrated in the steady-state creep, while the microcracks interconnected to form macroscopic shear cracks that dominated the accelerating creep, and this damage evolution characteristic can be used as a precursor and early warning of rock creep failure. Besides, increasing the pore water pressure also would cause the divergence point of strain curves inside and outside the localization zone to appear earlier at the secondary creep, and produce a wider localization zone at the tertiary creep. The creep fracture surface of the rock was dominated by intergranular microcracks. Increasing the pore water pressure would result in the deterioration of the cemented structure and breakage of the cemented matrix more seriously, thus stimulating the generation of more microcracks.
Prognostic Accuracy of the Different Scoring Systems for Assessing Coagulopathy in Sepsis: A Retrospective Study
Authors: Chen Yuwei , Chen Weiwei , Ba Fuhua , Zheng Yanjun , Zhou Yi , Shi Wen , Li Jian , Yang Zhitao , Mao Enqiang , Chen Erzhen , Chen Ying
Published: November 2023

There is no gold standard for the diagnosis of coagulation dysfunction in sepsis, and the use of the current scoring systems is still controversial. The purpose of this study was to assess the performance of sepsis-induced coagulopathy (SIC), the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC), and the International Society on Thrombosis and Haemostasis overt DIC (ISTH overt-DIC). The relationship between each scoring system and 28-day all-cause mortality was examined. Among 452 patients (mean age, 65 [48,76] years), 306 [66.7%] were men, the median SOFA score was 6 [4,9], and the median APACHE II score was 15 [11,22]. A total of 132 patients (29.2%) died within 28 days. Both the diagnosis of SIC (AUROC, 0.779 [95% CI, 0.728–0.830], P < 0.001) and ISTH overt-DIC (AUROC, 0.782 [95% CI, 0.732–0.833], P < 0.001) performed equally well in the discrimination of 28-day all-cause mortality (between-group difference: SIC versus ISTH overt-DIC, −0.003 [95% CI, −0.025–0.018], P = 0.766). However, the SIC demonstrated greater calibration for 28-day all-cause mortality than ISTH overt-DIC (the coincidence of the calibration curve of the former is higher than that of the latter). The diagnosis of JAAM DIC was not independently associated with 28-day all-cause mortality in sepsis (RR, 1.115, [95% CI 0.660–1.182], P = 0.684). The SIC scoring system demonstrated superior prognostic prediction ability in comparison with the others and is the most appropriate standard for diagnosing coagulopathy in sepsis.
Factors Explaining Resident Stakeholders’ Perception and Support for Wineries and Wine Tourism in Florida
Authors: Back Robin M. , Tasci Asli D.A. , Woosnam Kyle Maurice
Published: November 2023

Although resident support for tourism is accepted as an important determinant of tourism success, knowledge of resident support for wineries/wine tourism has not been substantiated with academic research. This study investigates resident stakeholders’ support towards wineries/wine tourism in a non-traditional wine tourism destination, more popular for its theme parks, and identifies determinants of support. Online survey data from Florida residents living close to wineries were analyzed using a two-step analysis procedure. T-tests and one-way ANOVA were used to test the categorical variables’ relationship with resident support, followed by OLS multiple regression analysis to identify the relative influence of all relevant variables. Results did not support the influence of personal benefits from tourism based on Social Exchange Theory; instead, they indicated that the wine consumer typology identified as Loyal Florida Wine Consumer Type and Occasional Wine Consumer Type had a positive influence on resident stakeholders’ support for wineries/wine tourism in Florida.
Cross-cultural research on early childhood teacher education curriculum design
Authors: He Yuan , Li Ting , Fanoos Azra , Päivi Tynjälä
Published: November 2023

This study was an attempt to compare the distinctive features in current Early Childhood Teacher Education (ECTE) curricula conducted at two universities, one in China, and one in the US. Document reviews, interviews, and questionnaires shed light on the two different approaches to curriculum design. Two program directors and 25 participants, viewed as “cultural outsiders,” were recruited. Results showed that the US model could be viewed as “deep” learning while the Chinese model was seen as “broad” learning. The US ECTE curriculum focused on a robust connection between general education and professional courses, strong standards, content-centered professional courses, multiple cultures, and more credit for field experience. The ECTE curriculum at the Chinese university provided a wide variety of general education and professional courses, arts-related professional courses, national cultures, and more modalities for field experience. This study also examined the impact of culture and society on the ECTE curriculum design.
Policing the data: Can data analytics help law enforcement?
Authors: Partridge Justin , Zaghloul Fatema
Published: November 2023

This case study looks at data analytics within a police force, examining how a police force recognised the need to make better use of the data and information they held, and how they started to professionalise their data analytical capability. This real-world example of the decisions and issues faced by a police force in the UK when looking at data analytics will explore the impact of data analytics on crime prevention, resource allocation, and community engagement, and the associated issues faced by a law enforcement body around culture, ethics and technology when implementing such an approach.
Complication rates after proximal femoral nailing: does level of training matter?
Authors: Haslhofer D. J. , Stiftinger J. M. , Kraml N. , Dannbauer F. , Schmolmüller C. , Gotterbarm T. , Kwasny O. , Klasan A.
Published: November 2023

Background

Surgical treatment of pertrochanteric fractures is one of the most performed surgeries in orthogeriatrics. Proximal femoral nailing, the most performed procedure, is often used as a training surgery for young residents. The objective of this study was to evaluate the relevance of the resident’s training level to complication rates.

Material and methods

This study was a retrospective cohort study. Surgeons were divided into four groups according to their training level. Complications included infection, cut-out, and revision surgery. The study was performed at a level 1 trauma center. All patients who were treated with proximal femoral nailing surgery with a radiological follow-up of at least 3 months were included.

Results

Of the 955 patients extracted, a total of 564 patients met the inclusion criteria. Second-year residents had significantly higher cut-out rates (p = 0.012). Further analysis indicated a correlation between level of training and surgery duration (p < 0.001) as well as a correlation between surgery duration and infection rate (p < 0.001). The overall complication rate was 11.2%. Analyzing overall complications, no significant difference was found when comparing surgeon groups (p = 0.3). No statistically significant difference was found concerning infection (p = 0.6), cut-out (p = 0.7), and revision surgery (p = 0.3) either.

Conclusion

Complication rates after proximal femoral nailing are not higher in patients who are treated by residents. Therefore, proximal femoral nailing is an excellent procedure for general orthopedic training. However, we must keep in mind that accurate positioning of the femoral neck screw is essential to keep cut-out rates as low as possible.

Level of Evidence III.
Atypical compound melanocytic naevus of the urethral meatus case report
Authors: Menzies-Wilson Richard , Bashall Sophie , Rees Rowland , Deverill Sally
Published: November 2023

Background

Atypical melanocytic naevus (AMN) of the urethral meatus is very rare with only a handful of reported cases. It is important to note that the rarity of AMN in the penis may contribute to a delay in diagnosis and treatment, as well as a lack of awareness among healthcare providers. This is the first case report to describe workup and management of AMN of the urethral meatus of a male, making it a valuable contribution to the literature.

Case presentation

A Caucasian male patient in his fourth decade presented with a several month history of a pigmented lesion on his glans penis. The differential diagnosis was of malignant melanoma but after biopsy and specialist pathological review, atypical melanocytic naevus was diagnosed. A punch biopsy, followed by two wide local excisions, was undertaken for complete excision and evaluation of the lesion.

Conclusion

Since AMN cannot be clinically distinguished from malignant melanoma, timely histological evaluation of the lesion is essential for workup. In this case, site and visibility of the lesion, expedient biopsy, and tissue analysis resulted in identification and excision of the naevus early enough for penis preserving surgery to be performed.
Transcriptome software results show significant variation among different commercial pipelines
Authors: Thawng Cung Nawl , Smith Geoffrey Battle
Published: November 2023

Background

We have been documenting the biological responses to low levels of radiation (natural background) and very low level radiation (below background), and thus these studies are testing mild external stimuli to which we would expect relatively mild biological responses. We recently published a transcriptome software comparison study based on RNA-Seqs from a below background radiation treatment of two model organisms, E. coli and C. elegans (Thawng and Smith, BMC Genomics 23:452, 2022). We reported DNAstar-D (Deseq2 in the DNAstar software pipeline) to be the more conservative, realistic tool for differential gene expression compared to other transcriptome software packages (CLC, Partek and DNAstar-E (using edgeR). Here we report two follow-up studies (one with a new model organism, Aedes aegypti and another software package (Azenta) on transcriptome responses from varying dose rates using three different sources of natural radiation.

Results

When E. coli was exposed to varying levels of K40, we again found that the DNAstar-D pipeline yielded a more conservative number of DEGs and a lower fold-difference than the CLC pipeline and DNAstar-E run in parallel. After a 30 read minimum cutoff criterion was applied to the data, the number of significant DEGs ranged from 0 to 81 with DNAstar-D, while the number of significant DEGs ranged from 4 to 117 and 14 to 139 using DNAstar-E and the CLC pipelines, respectively. In terms of the extent of expression, the highest foldchange DEG was observed in DNAstar-E with 19.7-fold followed by 12.5-fold in CLC and 4.3-fold in DNAstar-D. In a recently completed study with Ae. Aegypti and using another software package (Azenta), we analyzed the RNA-Seq response to similar sources of low-level radiation and again found the DNAstar-D pipeline to give the more conservative number and fold-expression of DEGs compared to other softwares. The number of significant DEGs ranged 31–221 in Azenta and 31 to 237 in CLC, 19–252 in DNAstar-E and 0–67 in DNAStar-D. The highest fold-change of DEGs were found in CLC (1,350.9-fold), with DNAstar-E (5.9 -fold) and Azenta (5.5-fold) intermediate, and the lowest levels of expression (4-fold) found in DNAstar-D.

Conclusions

This study once again highlights the importance of choosing appropriate software for transcriptome analysis. Using three different biological models (bacteria, nematode and mosquito) in four different studies testing very low levels of radiation (Van Voorhies et al., Front Public Health 8:581796, 2020; Thawng and Smith, BMC Genomics 23:452, 2022; current study), the CLC software package resulted in what appears to be an exaggerated gene expression response in terms of numbers of DEGs and extent of expression. Setting a 30-read cutoff diminishes this exaggerated response in most of the software tested. We have further affirmed that DNAstar-Deseq2 gives a more conservative transcriptome expression pattern which appears more suitable for studies expecting subtle gene expression patterns.
Characterization of H3K9me3 and DNA methylation co-marked CpG-rich regions during mouse development
Authors: Yang Hui , Wang Yiman , Zhang Yong
Published: November 2023

Background

H3K9me3 and DNA methylation co-marked CpG-rich regions (CHMs) are functionally important in mouse pre-implantation embryos, but their characteristics in other biological processes are still largely unknown.

Results

In this study, we performed a comprehensive analysis to characterize CHMs during 6 mouse developmental processes, identifying over 2,600 CHMs exhibiting stable co-mark of H3K9me3 and DNA methylation patterns at CpG-rich regions. We revealed the distinctive features of CHMs, including elevated H3K9me3 signals and a significant presence in euchromatin and the potential role in silencing younger long terminal repeats (LTRs), especially in some ERVK subfamilies. The results highlight the distinct nature of universal CHMs compared to CpG-rich nonCHMs in terms of location, LTR enrichment, and DNA sequence features, enhancing our understanding of CpG-rich regions' regulatory roles.

Conclusions

This study characterizes the features of CHMs in multiple developmental processes and broadens our understanding of the regulatory roles of CpG-rich regions.
Enhancing powdery mildew resistance in soybean by targeted mutation of MLO genes using the CRISPR/Cas9 system
Authors: Bui Thao Phuong , Le Huy , Ta Dong Thi , Nguyen Cuong Xuan , Le Ngoc Thu , Tran Truong Thi , Van Nguyen Phuong , Stacey Gary , Stacey Minviluz G. , Pham Ngoc Bich , Chu Ha Hoang , Do Phat Tien
Published: November 2023

Background

Powdery mildew is a major disease that causes great losses in soybean yield and seed quality. Disease-resistant varieties, which are generated by reducing the impact of susceptibility genes through mutation in host plants, would be an effective approach to protect crops from this disease. The Mildew Locus O (MLO) genes are well-known susceptibility genes for powdery mildew in plant. In this study, we utilized the CRISPR/Cas9 system to induce targeted mutations in the soybean GmMLO genes to improve powdery mildew resistance.

Results

A dual-sgRNA CRISPR/Cas9 construct was designed and successfully transferred into the Vietnamese soybean cultivar DT26 through Agrobacterium tumefaciens-mediated transformation. Various mutant forms of the GmMLO genes including biallelic, chimeric and homozygous were found at the T0 generation. The inheritance and segregation of CRISPR/Cas9-induced mutations were confirmed and validated at the T1 and T2 generations. Out of six GmMLO genes in the soybean genome, we obtained the Gmmlo02/Gmmlo19/Gmmlo23 triple and Gmmlo02/Gmmlo19/Gmmlo20/Gmmlo23 quadruple knockout mutants at the T2 generation. When challenged with Erysiphe diffusa, a fungus that causes soybean powdery mildew, all mutant plants showed enhanced resistance to the pathogen, especially the quadruple mutant. The powdery mildew severity in the mutant soybeans was reduced by up to 36.4% compared to wild-type plants. In addition, no pleiotropic effect on soybean growth and development under net-house conditions was observed in the CRISPR/Cas9 mutants.

Conclusions

Our results indicate the involvement of GmMLO02, GmMLO19, GmMLO20 and GmMLO23 genes in powdery mildew susceptibility in soybean. Further research should be conducted to investigate the roles of individual tested genes and the involvement of other GmMLO genes in this disease infection mechanism. Importantly, utilizing the CRISPR/Cas9 system successfully created the Gmmlo transgene-free homozygous mutant lines with enhanced resistance to powdery mildew, which could be potential materials for soybean breeding programs.
Gaps in vaccine management practices during vaccination outreach sessions in rural settings in southwestern Uganda
Authors: Flavia Atwiine , Fred Bagenda , Eleanor Turyakira
Published: November 2023

Background

Outreach efforts were developed to bolster people’s access to and use of immunization services in underserved populations. However, there have been multiple outbreaks of diseases like measles in Uganda, prompting policy makers and stakeholders to ask many unanswered questions. This research study was created to uncover the discrepancies between vaccine management practices at immunization outreach sessions in rural South Western Uganda compared with existing standards.

Methods

The observational qualitative study, was done in 16 public health facilities across four districts of Uganda. Data were collected using in-depth interviews, facility record reviews, and observation. We assessed the vaccine management procedures before immunization session, transportation used, set up at the outreach site, management practices during the outreach session and packing of vaccines - according to World Health Organization immunization practice recommendations. The data were transcribed, coded and categories were formed and triangulated. Themes were generated based on a socio-ecologic framework to gain a better understanding of healthcare provider practices during immunization sessions.

Results

Fifty-one individuals were interviewed; four Assistant District Health Officers, four cold chain technicians, 15 focal persons for the Expanded Program on Immunization, and 28 health care providers. The respondents’ mean age was 35, 43 (84.3%) were females and 24 (47.1%) had a diploma. 11 (69%) outreaches were conducted at a distance of 5-12 km from the health facility and 7 (44%) were conducted in a building. For 8 outreaches (50%) health facility staff did not check the vaccine vial monitor status before the outreach while 12(75%) did not keep the vaccine hard lid cover closed during the sessions. The main areas of concern were insufficient vaccine integrity monitoring, improper handling and storage practices, deficient documentation, and inadequate vaccine transportation. These were similar across immunization outreach sites regardless of vaccine preventable disease outbreaks occurrences. The majority of these gaps were located at the individual level but were enabled by policy/environmental factors.

Conclusions

There are poor vaccine management procedures during outreach sessions contrary to established guidelines. Specific tactics to tackle knowledge deficiencies, health worker attitude, and fewer equipment shortages could improve compliance to guidelines.
Long-term efficacy and stability of miniscrew-assisted rapid palatal expansion in mid to late adolescents and adults: a systematic review and meta-analysis
Authors: Zeng Weiqian , Yan Shuyun , Yi Yating , Chen Hao , Sun Tongke , Zhang Yimeng , Zhang Jun
Published: November 2023

Background

The purpose of this study is to investigate the long-term efficacy and stability of Miniscrew-assisted Rapid Palatal Expansion (MARPE), including its primary outcomes, namely the nasomaxillary complex transverse skeletal and dental expansion, and related secondary outcomes.

Methods

Electronic databases and manual literature searches, up to October 31, 2022, were performed. The eligibility criteria were the following: studies on patients with transverse maxillary deficiency treated with MARPE in adults and adolescents over 13.5 years of age.

Results

Ultimately, twelve articles were included in the analysis, one prospective and eleven retrospective observational studies. Five studies showed a moderate risk of bias, while the remaining seven studies were at a serious risk of bias. The GRADE quality of evidence was very low. MARPE is an effective treatment modality for transverse maxillary deficiency (mean success rate: 93.87%). Patients showed increased mean in the skeletal and dental transverse expansion. The basal bone composition, mean alveolar bone and mean dental expansion accounted for 48.85, 7.52, and 43.63% of the total expansion, respectively. There was a certain degree of skeletal and dental relapse over time. MARPE could also cause dental, alveolar, and periodontal side effects, and have an impact on other craniofacial bones, upper airway, and facial soft tissue.

Conclusions

MARPE is an effective treatment for transverse maxillary deficiency, with a high success rate and a certain degree of skeletal and dental relapse over time.