bluuebunny/crossref_metadata_2025 huggingface dataset:
Pomalidomide Improves Motor Behavioral Deficits and Protects Cerebral Cortex and Striatum Against Neurodegeneration Through a Reduction of Oxidative/Nitrosative Damages and Neuroinflammation After Traumatic Brain Injury
Authors: Huang Ya-Ni , Greig Nigel H. , Huang Pen-Sen , Chiang Yung-Hsiao , Hoffer Alan , Yang Chih-Hao , Tweedie David , Chen Ying , Ou Ju-Chi , Wang Jia-Yi
Published: March 2024

Neuronal damage resulting from traumatic brain injury (TBI) causes disruption of neuronal projections and neurotransmission that contribute to behavioral deficits. Cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following TBI. ROS often damage DNA, lipids, proteins, and carbohydrates while RNS attack proteins. The products of lipid peroxidation 4-hydroxynonenal (4-HNE) and protein nitration 3-nitrotyrosine (3-NT) are often used as indicators of oxidative and nitrosative damages, respectively. Increasing evidence has shown that striatum is vulnerable to damage from TBI with a disturbed dopamine neurotransmission. TBI results in neurodegeneration, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy in the striatum and contribute to motor or behavioral deficits. Pomalidomide (Pom) is a Food and Drug Administration (FDA)-approved immunomodulatory drug clinically used in treating multiple myeloma. We previously showed that Pom reduces neuroinflammation and neuronal death induced by TBI in rat cerebral cortex. Here, we further compared the effects of Pom in cortex and striatum focusing on neurodegeneration, oxidative and nitrosative damages, as well as neuroinflammation following TBI. Sprague–Dawley rats subjected to a controlled cortical impact were used as the animal model of TBI. Systemic administration of Pom (0.5 mg/kg, intravenous [i.v.]) at 5 h post-injury alleviated motor behavioral deficits, contusion volume at 24 h after TBI. Pom alleviated TBI-induced neurodegeneration stained by Fluoro-Jade C in both cortex and striatum. Notably, Pom treatment reduces oxidative and nitrosative damages in cortex and striatum and is more efficacious in striatum (93% reduction in 4-HNE-positive and 84% reduction in 3-NT-positive neurons) than in cerebral cortex (42% reduction in 4-HNE-positive and 55% reduction in 3-NT-positive neurons). In addition, Pom attenuated microgliosis, astrogliosis, and elevations of proinflammatory cytokines in cortical and striatal tissue. We conclude that Pom may contribute to improved motor behavioral outcomes after TBI through targeting oxidative/nitrosative damages and neuroinflammation.
Accounting for colonial domination in Liberal and Fascist Italy, 1912–1941
Authors: Antonelli Valerio , Bigoni Michele , D’Alessio Raffaele , Funnell Warwick
Published: March 2024

This article addresses the role played by accounting in the government of the Italian colonies of Africa during the Liberal and Fascist periods. Drawing upon the work of Foucault, Scott and Said and their understandings of governmentality and colonialism, and using a wide range of primary sources, the article contributes to the accounting history literature by showing how calculative practices in the form of colonial budgets and regular censuses of the population helped the Italian government to control activities in its colonies. The article shows how accounting practices evolved under different political regimes in the achievement of different programmes of government. It also offers evidence of the ways in which accounting can be mobilised to enable penetrating interventions in the lives of indigenous populations.
Preoperative Velopharyngeal Closure Predicts Hypernasality Outcomes of Secondary Furlow Double-Opposing Z-Plasty
Authors: Prezelski Kayla , Kim Carolyn , Perez Jeyna , Vant Slot Cortney , Kane Alex A. , Seaward James R.
Published: March 2024

Objective

To determine if preoperative velopharyngeal closure percentage (VCP) is predictive of successful Furlow double opposing Z-plasty (DOZP) and subsequently determine the optimal velopharyngeal closure cutoff for successful DOZP.

Design

Retrospective study

Setting

Tertiary academic center

Patients

110 patients with repaired cleft lip and palate having hypernasality treated with DOZP

Interventions

Speech videofluoroscopy images were used to obtain the preoperative VCP and other measurements.

Main Outcome Measures

Changes in hypernasality scores using the Cleft Audit Protocol for Speech-Augmented-Americleft Modification (CAPS-A-AM) rating system were used as the primary outcome measure. A successful DOZP was defined as a postoperative hypernasality score of ≤ 1 or an improvement of 2 or more scores from baseline. A receiver operating characteristic (ROC) curve was calculated to determine preoperative VCP cutoff.

Results

There were 110 patients who underwent DOZP for treatment of velopharyngeal insufficiency. Of these patients, 94 (85%) had successful surgery as determined by their postoperative CAPS-A-AM hypernasality score. Preoperative VCP was a statistically significant predictor of successful DOZP ( P < .0001). The ROC curve with Youden index (J) determined a cutoff (c*) of 55% preoperative VCP or greater to optimize surgical success rate. Grouping by preoperative VCP showed that surgical success increases directly with preoperative VCP, and patients with low VCP had above a 50% success rate in reducing hypernasality scores.

Conclusions

Preoperative VCP was significantly associated with improved hypernasality ratings postoperatively. A preoperative VCP of ≥55% may be used to help predict success of Furlow palatoplasty treatment. Patients with lower VCP can still benefit from secondary DOZP.
A Longitudinal Analysis of Pre- and Post-Operative Dysmorphology in Metopic Craniosynostosis
Authors: Beiriger Justin W. , Tao Wenzheng , Irgebay Zhazira , Smetona John , Dvoracek Lucas , Kass Nicolás M. , Dixon Angel , Zhang Casey , Mehta Meeti , Whitaker Ross , Goldstein Jesse A.
Published: March 2024

Objective

The purpose of this study is to objectively quantify the degree of overcorrection in our current practice and to evaluate longitudinal morphological changes using CranioRateTM, a novel machine learning skull morphology assessment tool.  

Design

Retrospective cohort study across multiple time points.

Setting

Tertiary care children's hospital.

Patients

Patients with preoperative and postoperative CT scans who underwent fronto-orbital advancement (FOA) for metopic craniosynostosis.

Main Outcome Measures

We evaluated preoperative, postoperative, and two-year follow-up skull morphology using CranioRateTM to generate a Metopic Severity Score (MSS), a measure of degree of metopic dysmorphology, and Cranial Morphology Deviation (CMD) score, a measure of deviation from normal skull morphology.

Results

Fifty-five patients were included, average age at surgery was 1.3 years. Sixteen patients underwent follow-up CT imaging at an average of 3.1 years. Preoperative MSS was 6.3 ± 2.5 (CMD 199.0 ± 39.1), immediate postoperative MSS was −2.0 ± 1.9 (CMD 208.0 ± 27.1), and longitudinal MSS was 1.3 ± 1.1 (CMD 179.8 ± 28.1). MSS approached normal at two-year follow-up (defined as MSS = 0). There was a significant relationship between preoperative MSS and follow-up MSS (R2 = 0.70).

Conclusions

MSS quantifies overcorrection and normalization of head shape, as patients with negative values were less “metopic” than normal postoperatively and approached 0 at 2-year follow-up. CMD worsened postoperatively due to postoperative bony changes associated with surgical displacements following FOA. All patients had similar postoperative metopic dysmorphology, with no significant association with preoperative severity. More severe patients had worse longitudinal dysmorphology, reinforcing that regression to the metopic shape is a postoperative risk which increases with preoperative severity.
Open Reduction Internal Fixation vs Primary Arthrodesis for Displaced Lisfranc Injuries: A Multicenter Randomized Controlled Trial
Authors: Ponkilainen Ville , Mäenpää Heikki , Laine Heikki-Jussi , Partio Nikke , Väistö Olli , Jousmäki Janne , Mattila Ville M. , Haapasalo Heidi
Published: March 2024

Background:

There is no consensus whether the primary surgical method should be open reduction and internal fixation (ORIF) or primary arthrodesis (PA) for Lisfranc injuries. The aim of our randomized controlled trial was to compare ORIF and PA for displaced Lisfranc injuries.

Methods:

This study was a national multicenter randomized controlled trial. Altogether 43 displaced Lisfranc injuries were enrolled in this trial. The primary outcome measure was Visual Analogue Scale Foot and Ankle (VAS-FA) at a 24-months follow-up. The secondary outcome measures were VAS-FA pain, function, and other complaints subscales and the American Orthopaedic Foot & Ankle Society (AOFAS) Midfoot Scale. All outcomes were measured at 6, 12, and 24 months. We were unable to reach the planned sample size of 60 patients; thus, the study remains underpowered.

Results:

The mean VAS-FA Overall score in the ORIF group was 86.5 (95% CI 77.9, 95.1) and 80.1 (95% CI 72.0, 88.1) in the PA group at the 24-month follow-up. We did not find eligible evidence of a difference in VAS-FA Overall scores (mean between-group difference 6.5 [95% CI −5.3, 18.2], Cohen d = 0.100).

Conclusion:

We did not find evidence of a difference in VAS-FA between ORIF and PA in patients with displaced Lisfranc injuries, and thus both are viable options for the initial surgical method. The trial is underpowered; however, the data may be included in a meta-analysis of similarly designed randomized controlled trials. ClinicalTrials.gov identifier: NCT02953067 24 October 2016.
The Efficacy of Social Media Communication in Engaging Citizen Scientists: Insights From the Jozi Bee Hotel Project
Authors: Shilubane Natasha , Iqani Mehita , Reynolds Chevonne
Published: March 2024

The Jozi Bee Hotel Project recruited Johannesburg residents to help gather data on solitary bee abundance. They were motivated and guided by a strategic communications campaign. This study explores social media’s impact on the citizen scientists’ project involvement, particularly their interaction with visual elements of the communications campaign. Analysis of engagement metrics reveals that social media played a crucial role in sustaining volunteer participation. This demonstrates that a well-executed, ongoing social media campaign has the power to maintain participant engagement throughout the duration of a research project. It suggests that a consistent, long-term social media strategy can drive citizen science participation.
Environmental Frameworks for the Gifted in the Periphery and Center Regions in Israel: Parents’ and Teachers’ Perceptions
Authors: Miedijensky Shirley , Grinshtain Yael
Published: March 2024

This study aimed at mapping the environmental frameworks available for gifted children and their families in both the periphery and central regions in Israel, based on Bronfenbrenner’s ecological systems theory. Twenty-six in-depth interviews were conducted with parents and educators from the two regions. The findings indicate that both groups of participants recognize the advantages of the pull-out programs and invest in family activities. However, in the periphery, parents spend more time with their children at home, have little or no contact with the teachers in the pull-out program, do not receive any guidance and support regarding their gifted child’s education, and perceive the governance and local authorities as less conducive to the education of their gifted children in comparison to parents from the center. The findings indicate the significant role of policymakers in the planning and development of frameworks at the individual and group levels for gifted children.
Revision rate following unipolar versus bipolar hemiarthroplasty
Authors: Kugelman David , Robin Joseph X , Schaffler Benjamin C , Davidovitch Roy , Egol Kenneth , Schwarzkopf Ran
Published: March 2024

Introduction:

There has been much debate on use of bipolar or unipolar femoral heads in hemiarthroplasty for the treatment of femoral neck fractures. The outcome of these implants should be studied in the America Joint Replacement Registry (AJRR).

Methods:

All primary femoral neck fractures treated with hemiarthroplasty between January 2012 and June 2020 were searched in the AJRR. All cause-revision of unipolar and bipolar hemiarthroplasty and reasons for revision were assessed for these patients until June of 2023.

Results:

There were no differences in number and reason for all cause revisions between unipolar and bipolar hemiarthroplasty ( p  = 0.41). Bipolar hemiarthroplasty had more revisons at 6 months postoperatively ( p  = 0.0281), but unipolar hemiarthroplasty had more revisions between 2 and 3 years ( p  = 0.0003), and after 3-years ( p  = 0.0085), as analysed with a Cox model. Patients with older age (HR = 0.999; 95% CI, 0.998–0.999; p  = 0.0006) and higher Charlson Comorbidity Index (HR = 0.996; 95% CI, 0.992– 0.999; p  = 0.0192) had a significant increase in revision risk.

Conclusions:

We suggest that surgeons should consider using bipolar prosthesis when performing hemiarthroplasty for femoral neck fracture in patients expected to live >2 years post injury.
Kynurenine Pathway in Respiratory Diseases
Authors: Pamart Guillaume , Gosset Philippe , Le Rouzic Olivier , Pichavant Muriel , Poulain-Godefroy Odile
Published: March 2024

The kynurenine pathway is the primary route for tryptophan catabolism and has received increasing attention as its association with inflammation and the immune system has become more apparent. This review provides a broad overview of the kynurenine pathway in respiratory diseases, from the initial observations to the characterization of the different cell types involved in the synthesis of kynurenine metabolites and the underlying immunoregulatory mechanisms. With a focus on respiratory infections, the various attempts to characterize the kynurenine/tryptophan (K/T) ratio as an inflammatory marker are reviewed. Its implication in chronic lung inflammation and its exacerbation by respiratory pathogens is also discussed. The emergence of preclinical interventional studies targeting the kynurenine pathway opens the way for the future development of new therapies.
Increasing Employee Physical Activity Using Goal Setting and a Smartphone App
Authors: Fetherman Debra L. , Cebrick-Grossman Joan
Published: March 2024

Physical inactivity is a high-priority public health issue in U.S. worksites. There is evidence that physical activity (PA) goal-setting interventions can be effective. Smartphone apps have also been used to deliver accessible and appealing PA interventions. This article describes the use of goal setting and a no-cost PA smartphone app to pilot an 8-week PA intervention, Project Move 2.0, to increase PA among a nonprofit health and social assistance workforce. The community-based partnership identified intervention strategies that addressed moderators for setting PA goals: feedback, goal commitment, situational factors, and ability. The intervention included the use of a no-cost smartphone app for tracking steps/goal setting, an orientation/health education session, weekly text messages, as well as pre- and post-measures for goal setting for PA behaviors and an intervention evaluation questionnaire. There is limited knowledge on the practical aspects of applying goal setting and the use of a no-cost smartphone app to increase employee PA through a workplace PA intervention. Applying goal setting and the use of a no-cost smartphone app shows promise for workplace health promoters to successfully address employee PA.
Catching ZZZs: A Summary of the Most Common Herbal Medications Taken for Insomnia
Authors: Chabo Anita , Srivastava Sneha B.
Published: March 2024

Insomnia is caused by a myriad of factors and can be very disruptive to a person’s quality of life and health. When people see a health care provider, often a thorough assessment occurs and people are given various treatment options that include lifestyle interventions, medications, and/or cognitive behavior therapy. There are also many people that may choose to take over the counter or herbal medications as a remedy for insomnia. While there are many supplements that claim to have sleep benefits, clinical data supporting such claims are not always present. This article will briefly discuss the three most common herbal supplements taken for insomnia: melatonin, valerian, and lavender.
Lived Experience as the Basis of Collaborative Knowing. Inclusivity and Resistance to Stigma in Co-Research
Authors: Kulmala Meri , Venäläinen Satu , Hietala Outi , Nikula Karoliina , Koskivirta Inka
Published: March 2024

Social scientific research has become increasingly aware of power asymmetries and the elitist and exclusive nature of scientific knowledge production. These debates have resulted in more inclusive and participatory research practices. In this article, we focus on co-research, which is a participatory and multi-perspective research strategy that invites the people whom the research concerns to participate as active and influential agents throughout the research process as experts on ‘the studied world.’ Co-research is increasingly being adopted in research involving people who belong to marginalised groups or who face the threat of stigmatisation. Despite its increasing applications, engaging in co-research requires reflection on several methodological and ethical questions that so far have been underexplored in the methodological literature. In this article, we address challenges in practicing inclusion and overcoming power asymmetries in co-research, particularly when it is conducted with people who inhabit societal positions with institutionalised stigma and whose participation in research is usually highly limited. In this article, building on our own experiences from different co-research projects—with care leavers, experts-by-experience with a history of crime and mental health recoverers—we aim to contribute to this literature by specifically focusing on issues of inclusion of co-researchers who face the need to negotiate with institutionally stigmatised positions. We suggest that reflexivity on positionalities and attending to plurality in identity work could provide a fruitful tool for increasing inclusivity in co- (and peer) research. We claim that such reflexivity is crucial from the very beginning of a co-research process (including ways of inviting and recruiting co-researchers) because this stage is crucial, as it forms the basis for the following stages and for the possibility of practising inclusion—even if imperfect—throughout the process.
Countering violent extremism through internet intermediaries: A typology for cross-country comparison
Authors: Wong Vincent Pak-Hong
Published: March 2024

This paper examines the counter-violent extremism and anti-terrorism measures in Australia, China, France, the United Kingdom and the United States by investigating how governments leveraged internet intermediaries as their surrogate censors. Particular attention is paid to how political rhetoric led to legislation passed or proposed in each of the countries studied, and their respective restrictive measures are compared against the recommendations specified by the United Nations Special Rapporteur on the Promotion and Protection of the Right to Freedom of Opinion and Expression. A typology for international comparison is proposed, which provides further insights into a country’s policy focus.
The 1871 Lease of the Theatre Royal Haymarket
Authors: Rogers Vanessa L. , Risdell Marcus
Published: March 2024

John Baldwin Buckstone took over the management at the Theatre Royal Haymarket in 1853, assuming control from Benjamin Webster who had been manager since 1837. They had both served in the company of David Edward Morris, the proprietor who had overseen the building of the new Haymarket Theatre in 1821. When Morris died, his estate passed into a trust on behalf of his widow, Maria Sarah. A lease dating from 1871 (now in the Library at the Garrick Club) describes the agreement between Buckstone and Maria Sarah. Not only does the lease detail the arrangement between the two parties, it also includes an extensive 214-page room-by-room inventory of the Haymarket Theatre, revealing hundreds of items accumulated throughout half a century of constant use. This article outlines the peculiarities of the lease and pays special attention to the music and dance holdings which feature prominently in the inventory. The lease is remarkable not only for the diversity, breadth, and specificity of its contents, but also because it serves as a rare document of theatre business and tells us more about the day-to-day life of one of London's most important theatres in the mid-nineteenth century.
Digestive bleeding due to jejunal stromal tumor: A train can hide another—A case report
Authors: Neirouz Kammoun , Mehdi Trabelsi Mohamed , Mehdi Khalfallah , Mohamed Guelbi , Annouar Oueslati , Ramzi Nouira
Published: March 2024

Gastrointestinal mesenchymal tumors (GIST) are the most prevalent sarcoma tumors affecting the digestive tract. GIST originates from Cajal cells located within the digestive tract’s wall. These cells play a crucial role in regulating digestive peristaltism as they are considered pacemaker cells. These tumors are especially located in the stomach (60%) but can also be seen in the small bowel (30%), in which jejunal stromal tumors are estimated to reach (40%). In this case report, we describe a jejunal GIST, which was initially discovered due to active bleeding, serving as the primary symptom, along with an underlying small loop intussusception. In our knowledge, GIST causing an intussusception is a rare entity in literature as well as GIST causing active bleeding. For that aim, we present a 36-year-old male patient, presented to our department with melena. An abdominal computed tomography scan was performed, revealing a small bowel intussusception associated with a 2 cm tumor. Despite the imprecise cause of the bleeding, due to the ongoing active hemorrhage, we decided to proceed with an emergency laparotomy, suspecting a tumorous origin of the bleeding. During the surgery, the tumor was located in the jejunum. The affected jejunal segment containing the tumor was resected, and an anastomosis was performed. Pathology examination confirmed a stromal tumor. The postoperative follow-up was uneventful.
Clinical application of calcium dobesilate in acute and sub-acute COVID-19: Two case reports
Authors: Arellano Barcenas Alejandra
Published: March 2024

The pathophysiology of the virus causing coronavirus disease 2019, the cytokine storm and severe vasculitis is well known. Diabetic patients and those with microcirculation issues are at risk of complications when diagnosed with coronavirus disease 2019. Calcium dobesilate has been used extensively for microangiopathy, diabetic retinopathy, chronic venous insufficiency, hemorrhoidal and post-thrombotic syndromes. We administered calcium dobesilate to several patients in our coronavirus disease hospital; documenting disease progression outcomes relating to cessation of disease worsening, reduction in glucocorticoid dose and oxygen. We present two case reports: patient 1 with acute and patient 2 with sub-acute coronavirus disease 2019; both patients received standard of care plus calcium dobesilate. Patient 1 achieved clinical, radiographic and laboratory improvements. Patient 2 derived calcium dobesilate benefits during the acute phase of coronavirus disease 2019 negating the need for supplemental oxygen and dose increases of dexamethasone. Further research is required to support the use of calcium dobesilate in coronavirus disease 2019 patients.
Processing Instruction Versus Traditional Instruction: The Transfer-of-Training Effects on Chinese EFL Learners
Authors: Zeng Tao , Xu Chang , Hu Jia , Fu Xiuzhi
Published: March 2024

This research investigated the impact of processing instruction (PI) on the acquisition of the English third-person singular present tense by Chinese English-as-a-foreign-language (EFL) learners and whether this effect would extend to the acquisition of other language components. This study featured the pretest-immediate-posttest design and participants were required to participate in all tests (pretest, immediate posttest, delayed posttest). Two classes were assigned to receive PI and Traditional Instruction (TI) respectively, while another class served as the control group. A language background check was conducted 2 weeks before the main experiment. And after three consecutive class hours, there is an immediate posttest and a delayed posttest in 2 weeks. By comparing the results of the three tests, the study measured and compared the primary effects, secondary transfer-of-training (TOT) effects, and cumulative TOT effects of PI and TI. The findings showed that both PI and TI had significant effects, although they differed in the extent and duration of improvement in acquisition effectiveness. PI was found to be superior to TI, which could be reflected in primary and two TOT effects except the interpretation tasks related to passive voice. This study suggests that PI can be utilized in grammar teaching due to its efficacy in teaching specific linguistic structures and its transfer-of-training effects on other grammar rules.
Biplanar Anterior Opening Wedge Proximal Tibial Osteotomy to Correct Reverse Tibial Slope
Authors: Olson Conner , Tollefson Luke V. , Shoemaker Evan P. , Kennedy Nicholas I. , LaPrade Robert F.
Published: March 2024

Background:

Anatomically, native posterior tibial slope (PTS) ranges from 6° to 10° and have significant effects on cruciate ligament stability. PTS <6° is correlated with increased posterior tibial translation (PTT) and force on the posterior cruciate ligament (PCL), predisposing individuals to PCL injuries and an increased risk of PCL graft attenuation. In rare cases, a reverse tibial slope can occur (<0°) as a result of trauma, physeal arrest, or abnormal development. This results in increased PTT and can lead to posterior tibial subluxation. Reverse tibial slopes in patients can be treated with an anterior opening wedge proximal tibial osteotomy, which increases the PTS to a more anatomic position.

Indications:

Biplanar anterior opening wedge proximal tibial osteotomies are indicated in patients with a reverse tibial slope both with the absence of PCL insufficiency or in conjunction with PCL reconstruction.

Technique Description:

Under fluoroscopic imaging, 2 guide pins were placed perpendicular to the tibial shaft. An oscillating saw and osteotomes completed the osteotomy in line with the guide pins with the posterior cortex remaining intact. The osteotomy site was slowly opened with a spreader device to 9 mm until the posterior drawer was such that the palpable step-off between the anterior aspect of the medial femoral condyle and the medial tibial plateau was comparable to the contralateral knee. Due to the patient having slight valgus coronal plane alignment, an opening-wedge posteriorly sloped plate was then placed anterolaterally and fixed while wedges held the osteotomy open.

Results:

Biplanar anterior opening wedge osteotomies correct a flattened PTS and reverse tibial slope, and coronal malalignment, and has been shown to decrease PCL laxity, preventing future PCL failure.

Discussion:

Biomechanical studies have shown that decreased tibial slope is correlated with an increased risk of PCL injury and PCL graft failure. In patients with reverse tibial slope, experienced instability can mimic PCL insufficiency despite there being no ligamentous damage. We describe a technique that corrects reverse tibial slope and with a discussion of surgical pearls and pitfalls. This technique restores anatomic position and normal function of the knee while correcting the sagittal malalignment that could lead to future injuries.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System
Authors: Elsallab Magdi , Ellithi Moataz , Lunning Matthew A. , D’Angelo Christopher , Ma Jihyun , Perales Miguel-Angel , Frigault Matthew , Maus Marcela V.
Published: March 2024

Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.
A temporal developmental map separates human NK cells from noncytotoxic ILCs through clonal and single-cell analysis
Authors: Vo Dang Nghiem , Yuan Ouyang , Kanaya Minoru , Telliam-Dushime Gladys , Li Hongzhe , Kotova Olga , Caglar Emel , Honnens de Lichtenberg Kristian , Rahman Shamim Herbert , Soneji Shamit , Scheding Stefan , Bryder David , Malmberg Karl-Johan , Sitnicka Ewa
Published: March 2024

Natural killer (NK) cells represent the cytotoxic member within the innate lymphoid cell (ILC) family that are important against viral infections and cancer. Although the NK cell emergence from hematopoietic stem and progenitor cells through multiple intermediate stages and the underlying regulatory gene network has been extensively studied in mice, this process is not well characterized in humans. Here, using a temporal in vitro model to reconstruct the developmental trajectory of NK lineage, we identified an ILC-restricted oligopotent stage 3a CD34−CD117+CD161+CD45RA+CD56− progenitor population, that exclusively gave rise to CD56-expressing ILCs in vitro. We also further investigated a previously nonappreciated heterogeneity within the CD56+CD94−NKp44+ subset, phenotypically equivalent to stage 3b population containing both group-1 ILC and RORγt+ ILC3 cells, that could be further separated based on their differential expression of DNAM-1 and CD161 receptors. We confirmed that DNAM-1hi S3b and CD161hiCD117hi ILC3 populations distinctively differed in their expression of effector molecules, cytokine secretion, and cytotoxic activity. Furthermore, analysis of lineage output using DNA-barcode tracing across these stages supported a close developmental relationship between S3b-NK and S4-NK (CD56+CD94+) cells, whereas distant to the ILC3 subset. Cross-referencing gene signatures of culture-derived NK cells and other noncytotoxic ILCs with publicly available data sets validated that these in vitro stages highly resemble transcriptional profiles of respective in vivo ILC counterparts. Finally, by integrating RNA velocity and gene network analysis through single-cell regulatory network inference and clustering we unravel a network of coordinated and highly dynamic regulons driving the cytotoxic NK cell program, as a guide map for future studies on NK cell regulation.
Economic evaluation: immunoglobulin vs prophylactic antibiotics in hypogammaglobulinemia and hematological malignancies
Authors: Carrillo de Albornoz Sara , Higgins Alisa M. , Petrie Dennis , Irving Adam , Fanning Laura , Weinkove Robert , Crispin Philip , Dendle Claire , Gilbertson Michael , Johnston Anna , Keegan Anastazia , Pepperell Dominic , Pullon Humphrey , Reynolds John , van Tonder Tina , Trotman Judith , Waters Neil , Wellard Cameron , Weston Helen , Morrissey C. Orla , Wood Erica M. , McQuilten Zoe K.
Published: March 2024

Patients with hematological malignancies are at high risk of developing hypogammaglobulinemia (HGG) and infections. Immunoglobulin (Ig) is one recommended option to prevent these infections, but it is expensive, and its cost-effectiveness compared with other prevention strategies remains unknown. We conducted a trial–based economic evaluation from the Australian health care system perspective to estimate the 12-month cost-effectiveness of prophylactic Ig vs prophylactic antibiotics in 63 adults with HGG and hematological malignancies participating in the RATIONAL feasibility trial. Two analyses were conducted: (1) cost-utility analysis to assess the incremental cost per quality-adjusted life year (QALY) gained; and (2) cost-effectiveness analysis to assess the incremental cost per serious infection prevented (grade ≥3) and per any infection (any grade) prevented. Over 12 months, the total cost per patient was significantly higher in the Ig group than in the antibiotic group (mean difference, AU$29 140; P < .001). Most patients received IVIg, which was the main cost driver; only 2 patients in the intervention arm received subcutaneous Ig. There were nonsignificant differences in health outcomes. Results showed Ig was more costly than antibiotics and associated with fewer QALYs. The incremental cost-effectiveness ratio of Ig vs antibiotics was AU$111 262 per serious infection prevented, but Ig was more costly and associated with more infections when all infections were included. On average and for this patient population, Ig prophylaxis may not be cost-effective compared with prophylactic antibiotics. Further research is needed to confirm these findings in a larger population and considering longer-term outcomes. The trial was registered at the Australian and New Zealand Clinical Trials Registry as #ACTRN12616001723471.
The illness burden of severe asthma contrasted to people with mild-to-moderate asthma: a qualitative study
Authors: Majellano Eleanor C. , Yorke Janelle , Clark Vanessa L. , Gibson Peter G. , Smith Amber J. , Holmes Leanne J. , McDonald Vanessa M.
Published: March 2024

Background

Disabling symptoms of asthma including breathlessness, cough, wheeze and chest tightness largely impact quality of life; however, how these symptoms impact people with asthma of different severity levels remains unknown. This study aimed to compare and characterise patients' symptom experience and the burden caused, their quality of life, and the medication preferences of people with severe asthma against those of people with mild-to-moderate asthma.

Methods

This was a multisite qualitative study involving two focus groups and semistructured interviews of adults with severe asthma undertaken in Australia and UK. Interviews were also undertaken in people with mild-to-moderate asthma. Audio recordings were transcribed and analysed thematically.

Results

Participants in both severe asthma and mild-to-moderate asthma groups had a mean±sdage of 57±12 years. Between the severe asthma and mild-to-moderate asthma groups, 62% of participants were female and 86% lived with family. Themes were identified: 1) what is asthma and most bothersome symptoms: both groups reported breathlessness as the most bothersome symptom; 2) impacts on life: disease-related impact differed as people with severe asthma reported significant burden in their quality of life, which encompassed emotional, physical, social and financial wellbeing; and 3) personalised and responsive care: severe asthma interviewees preferred injectable biological therapy as a mode of treatment administration.

Conclusions

People with asthma are burdened by breathlessness and cough and other disabling symptoms resulting in impaired quality of life. Understanding the experiences of people with asthma of different severities can improve the patient–clinician partnership.
Nontuberculous mycobacterial pulmonary disease added burden to COPD and bronchiectasis in Japan
Authors: Wang Ping , Morimoto Kozo , Hasegawa Naoki , Hassan Mariam , Chatterjee Anjan
Published: March 2024

Background and objective

Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence in Japan is among the highest worldwide. COPD and bronchiectasis are common comorbidities among patients with NTM-PD, and it is challenging to treat NTM-PD in patients with these conditions. There are limited data on the incremental burden that NTM-PD adds to underlying COPD or bronchiectasis in Japan. Therefore, the objective of this study was to assess the incremental burden associated with NTM-PD in patients with pre-existing COPD and/or bronchiectasis.

Methods

This nested case–control study was based on JMDC, Inc. claims data (2015–2020). Patients with COPD and/or bronchiectasis with NTM-PD (cases) were age and sex matched 1:3 to patients with COPD and/or bronchiectasis without NTM-PD (controls), resulting in three mutually exclusive patient groups (COPD, bronchiectasis or both; with or without NTM-PD). Incremental burden of NTM-PD was assessed within each group by comparing hospitalisations during the 1-year period after NTM-PD diagnosis (index) between cases and controls with both univariate analysis and multivariate analysis adjusting for pre-index comorbidities.

Results

Univariate analyses in the three patient groups consistently demonstrated incremental hospitalisation burden in casesversuscontrols (e.g.COPD group: 20% of 492 casesversus13% of 1476 controls had all-cause hospitalisations; 11%versus5% had respiratory-related hospitalisations; and 6%versus2% had COPD-related hospitalisations). Subsequent multivariate analysis further confirmed the findings.

Conclusions

The substantial incremental burden of hospitalisation associated with NTM-PD in patients with COPD and/or bronchiectasis highlights the urgent need for appropriate management of NTM-PD in Japan.
Grindability Evaluation of Ultrasonic Assisted Grinding of Silicon Nitride Ceramic Using Minimum Quantity Lubrication Based SiO2 Nanofluid
Authors: Dambatta Yusuf Suleiman , Li Changhe , Sayuti Mohd , Sarhan Ahmed A D , Yang Min , Li Benkai , Chu Anxue , Liu Mingzheng , Zhang Yanbin , Said Zafar , Zhou Zongming
Published: March 2024

Minimum quantity Lubrication (MQL) is a sustainable lubrication system that is famous in many machining systems. It involve the spray of an infinitesimal amount of mist-like lubricants during machining processes. The MQL system is affirmed to exhibit an excellent machining performance, and it is highly economical. The nanofluids are understood to exhibit excellent lubricity and heat evacuation capability, compared to pure oil-based MQL system. Studies have shown that the surface quality and amount of energy expended in the grinding operations can be reduced considerably due to the positive effect of these nanofluids. This work presents an experimental study on the tribological performance of SiO2 nanofluid during grinding of Si3N4 ceramic. The effect different grinding modes and lubrication systems during the grinding operation was also analyzed. Different concentrations of the SiO2 nanofluid was manufactured using canola, corn and sunflower oils. The quantitative evaluation of the grinding process was done based on the amount of grinding forces, specific grinding energy, frictional coefficient, and surface integrity. It was found that the canola oil exhibits optimal lubrication performance compared to corn oil, sunflower oil, and traditional lubrication systems. Additionally, the introduction of ultrasonic vibrations with the SiO2 nanofluid in MQL system was found to reduce the specific grinding energy, normal grinding forces, tangential grinding forces, and surface roughness by 65%, 57%, 65%, and 18% respectively. Finally, regression analysis was used to obtain an optimum parameter combinations. The observations from this work will aid the smooth transition towards ecofriendly and sustainable machining of engineering ceramics.
Calcitonin receptor, calcitonin gene-related peptide and amylin distribution in C1/2 dorsal root ganglia
Authors: Rees Tayla A. , Tasma Zoe , Garelja Michael L. , O’Carroll Simon J. , Walker Christopher S. , Hay Debbie L.
Published: March 2024

Background

The upper cervical dorsal root ganglia (DRG) are important for the transmission of sensory information associated with the back of the head and neck, contributing to head pain. Calcitonin receptor (CTR)-based receptors, such as the amylin 1 (AMY1) receptor, and ligands, calcitonin gene-related peptide (CGRP) and amylin, have been linked to migraine and pain. However, the contribution of this system to nociception involving the cervical DRG is unclear. Therefore, this study aimed to determine the relative distribution of the CTR, CGRP, and amylin in upper cervical DRG.

Methods

CTR, CGRP, and amylin immunofluorescence was examined relative to neural markers in C1/2 DRG from male and female mice, rats, and human cases. Immunofluorescence was supported by RNA-fluorescence in situ hybridization examining amylin mRNA distribution in rat DRG.

Results

Amylin immunofluorescence was observed in neuronal soma and fibres. Amylin mRNA (Iapp) was also detected. Amylin and CGRP co-expression was observed in 19% (mouse), 17% (rat), and 36% (human) of DRG neurons in distinct vesicle-like neuronal puncta from one another. CTR immunoreactivity was present in DRG neurons, and both peptides produced receptor signalling in primary DRG cell cultures. CTR-positive neurons frequently co-expressed amylin and/or CGRP (66% rat; 84% human), with some sex differences.

Conclusions

Amylin and CGRP could both be local peptide agonists for CTR-based receptors in upper cervical DRG, potentially acting through autocrine and/or paracrine signalling mechanisms to modulate neuron function. Amylin and its receptors could represent novel pain targets.
Fabrication of fluidic submicron-channels by pulsed laser-induced buckling of SiOx films on fused silica
Authors: Bakhtiari Nastaran , Ihlemann Jürgen
Published: March 2024

Recently, considerable attention has been drawn to the field of micro/nanofluidic channels. However, current methods for fabricating micro/nanochannels are complex, costly, and time-intensive. In the present work, we successfully fabricated transparent submicron-channels on fused silica substrates (SiO2) using a straightforward laser process. To achieve this, a single-pulse excimer laser irradiation in a rear side configuration was employed to treat a thin film of UV-absorbing silicon suboxide (SiOx) through the transparent SiO2 substrate. A polydimethylsiloxane (PDMS) superstrate (coating layer) was applied over the SiOx film before laser exposure, serving as a confinement for controlled structure formation induced by the laser. Under optimal laser fluence, the thin SiOx film buckled, leading to the formation of channels with a width ranging from 10 to 20 µm and a height of 800 to 1200 nm, exhibiting a bell-like cross-sections following the so-called Euler buckling mode. Wider channels displayed morphologies resembling varicose or telephone cord modes. Subsequent high-temperature annealing led to the oxidation of SiOx, resulting transparent SiO2 channels on the fused silica substrate. The manufactured nanochannels exhibited promising potential for effectively transporting fluids of diverse viscosities. Various fluids were conveyed through these nanochannels via capillary action and in accordance with the Lucas-Washburn equation.
MetaTron: advancing biomedical annotation empowering relation annotation and collaboration
Authors: Irrera Ornella , Marchesin Stefano , Silvello Gianmaria
Published: March 2024

Background

The constant growth of biomedical data is accompanied by the need for new methodologies to effectively and efficiently extract machine-readable knowledge for training and testing purposes. A crucial aspect in this regard is creating large, often manually or semi-manually, annotated corpora vital for developing effective and efficient methods for tasks like relation extraction, topic recognition, and entity linking. However, manual annotation is expensive and time-consuming especially if not assisted by interactive, intuitive, and collaborative computer-aided tools. To support healthcare experts in the annotation process and foster annotated corpora creation, we present MetaTron. MetaTron is an open-source and free-to-use web-based annotation tool to annotate biomedical data interactively and collaboratively; it supports both mention-level and document-level annotations also integrating automatic built-in predictions. Moreover, MetaTron enables relation annotation with the support of ontologies, functionalities often overlooked by off-the-shelf annotation tools.

Results

We conducted a qualitative analysis to compare MetaTron with a set of manual annotation tools including TeamTat, INCEpTION, LightTag, MedTAG, and brat, on three sets of criteria: technical, data, and functional. A quantitative evaluation allowed us to assess MetaTron performances in terms of time and number of clicks to annotate a set of documents. The results indicated that MetaTron fulfills almost all the selected criteria and achieves the best performances.

Conclusions

MetaTron stands out as one of the few annotation tools targeting the biomedical domain supporting the annotation of relations, and fully customizable with documents in several formats—PDF included, as well as abstracts retrieved from PubMed, Semantic Scholar, and OpenAIRE. To meet any user need, we released MetaTron both as an online instance and as a Docker image locally deployable.
Comparative study of the quality indices, antioxidant substances, and mineral elements in different forms of cabbage
Authors: Yue Zhibin , Zhang Guobin , Wang Jie , Wang Jue , Luo Shilei , Zhang Bo , Li Zhaozhuang , Liu Zeci
Published: March 2024

Background

As the second largest leafy vegetable, cabbage (Brassica oleracea L. var. capitata) is grown globally, and the characteristics of the different varieties, forms, and colors of cabbage may differ. In this study, five analysis methods—variance analysis, correlation analysis, cluster analysis, principal component analysis, and comprehensive ranking—were used to evaluate the quality indices (soluble protein, soluble sugar, and nitrate), antioxidant content (vitamin C, polyphenols, and flavonoids), and mineral (K, Ca, Mg, Cu, Fe, Mn, and Zn) content of 159 varieties of four forms (green spherical, green oblate, purple spherical, and green cow heart) of cabbage.

Results

The results showed that there are significant differences among different forms and varieties of cabbage. Compared to the other three forms, the purple spherical cabbage had the highest flavonoid, K, Mg, Cu, Mn, and Zn content. A scatter plot of the principal component analysis showed that the purple spherical and green cow heart cabbage varieties were distributed to the same quadrant, indicating that their quality indices and mineral contents were highly consistent, while those of the green spherical and oblate varieties were irregularly distributed. Overall, the green spherical cabbage ranked first, followed by the green cow heart, green oblate, and purple spherical varieties.

Conclusions

Our results provide a theoretical basis for the cultivation and high-quality breeding of cabbage.