bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced diffusion imaging reveals microstructural characteristics of primary CNS lymphoma, allowing differentiation from glioblastoma
Authors: Würtemberger Urs , Diebold Martin , Rau Alexander , Akgün Veysel , Becker Lucas , Beck Jürgen , Reinacher Peter C , Taschner Christian A , Reisert Marco , Fehrenbacher Luca , Erny Daniel , Scherer Florian , Hohenhaus Marc , Urbach Horst , Demerath Theo
Published: June 2024

Background

Primary CNS lymphoma (PCNSL) and glioblastoma (GBM) both represent frequent intracranial malignancies with differing clinical management. However, distinguishing PCNSL from GBM with conventional MRI can be challenging when atypical imaging features are present. We employed advanced dMRI for noninvasive characterization of the microstructure of PCNSL and differentiation from GBM as the most frequent primary brain malignancy.

Methods

Multiple dMRI metrics including Diffusion Tensor Imaging, Neurite Orientation Dispersion and Density Imaging, and Diffusion Microstructure Imaging were extracted from the contrast-enhancing tumor component in 10 PCNSL and 10 age-matched GBM on 3T MRI. Imaging findings were correlated with cell density and axonal markers obtained from histopathology.

Results

We found significantly increased intra-axonal volume fractions (V-intra and intracellular volume fraction) and microFA in PCNSL compared to GBM (all P < .001). In contrast, mean diffusivity (MD), axial diffusivity (aD), and microADC (all P < .001), and also free water fractions (V-CSF and V-ISO) were significantly lower in PCNSL (all P < .01). Receiver-operating characteristic analysis revealed high predictive values regarding the presence of a PCNSL for MD, aD, microADC, V-intra, ICVF, microFA, V-CSF, and V-ISO (area under the curve [AUC] in all >0.840, highest for MD and ICVF with an AUC of 0.960). Comparative histopathology between PCNSL and GBM revealed a significantly increased cell density in PCNSL and the presence of axonal remnants in a higher proportion of samples.

Conclusions

Advanced diffusion imaging enables the characterization of the microstructure of PCNSL and reliably distinguishes PCNSL from GBM. Both imaging and histopathology revealed a relatively increased cell density and a preserved axonal microstructure in PCNSL.
Behavioral Activation mHealth Application for Smoking Cessation: A Randomized Controlled Pilot Trial
Authors: Heffner Jaimee L , Serfozo Edit , Baker Kelsey , Gasser Melissa , Watson Noreen , Daughters Stacey B , Becoňa Elisardo , McClure Jennifer B
Published: June 2024

Introduction

Behavioral activation (BA) is an effective intervention for both depression and substance use disorders. Combining BA with a standard smoking cessation intervention may improve quit rates by addressing depressive symptoms, a key barrier to quitting. This study preliminarily evaluated the acceptability and efficacy of the BA-based Actify! mobile health application (mHealth app) for smoking cessation.

Aims and Methods

We conducted a pilot randomized controlled trial (n = 242) comparing Actify! with the National Cancer Institute’s (NCI) app for smoking cessation (QuitGuide) on acceptability (user satisfaction, app openings), smoking abstinence, and mechanisms of change (BA and depressive symptoms) at 8 weeks and 6 months postrandomization. Participants were US adults recruited online who smoked daily.

Results

Treatment satisfaction was uniformly higher in the Actify! arm. Number of app openings was similar across arms (M = 34.3 openings over 8 weeks in both arms). Self-reported 30-day point prevalence abstinence (PPA) at 8 weeks was 12.6% for Actify! versus 7.3% for QuitGuide. Differences in 30-day PPA continued through 6 months (18.5% for Actify! vs. 12.2% for QuitGuide). Changes between baseline and 8 weeks in depressive symptoms and BA favored Actify!. Planned subgroup analyses suggested greater benefit of Actify! among participants with pretreatment mild-to-moderate depression symptom severity compared to those with no depression symptoms.

Conclusions

Actify! showed considerable promise as a novel mHealth treatment, as evidenced by its high usage and higher user satisfaction and quit rates than QuitGuide at both short- and long-term follow-up. The next step is to evaluate Actify! in a fully powered efficacy trial.

Implications

Study findings demonstrate the promise of a BA-based mobile health app (Actify!) for smoking cessation as a population-level intervention that can effectively address depressive symptoms as a risk factor for worse smoking treatment outcomes. The Actify! app is the first standalone BA-based app to demonstrate potential for improved acceptability and efficacy relative to a standard care comparison app, with user satisfaction and smoking quit rates descriptively exceeding those of the NCI’s QuitGuide app.
Tobacco Images Choice and its Association With Craving and Dependence in People Who Smoke Cigarettes
Authors: Solinas Marcello , Chauvet Claudia , Lafay-Chebassier Claire , Vanderkam Paul , Barillot Lila , Moeller Scott J , Goldstein Rita Z , Noël Xavier , Jaafari Nematollah , Chatard Armand
Published: June 2024

Introduction

Increased salience of drug-related cues over nondrug reinforcers can drive drug use and contribute to tobacco use disorder (TUD). An important scientific and clinical goal is to effectively measure this elevated drug-seeking behavior in TUD. However, most TUD assessments rely on self-reported cravings and cigarette consumption, not providing an objective measure of the impact of drug cues on biasing behavior toward drugs. The probabilistic image choice (PIC) task investigates the choice of viewing drug-related pictures as compared to other salient pictures (eg, pleasant and unpleasant). This study aimed to develop and validate the PIC task for TUD and evaluate the associations between behavioral choice and tobacco craving, daily cigarette consumption, quit attempts and motivation to quit, and nicotine dependence (the Fagerström score).

Methods

We recruited 468 smokers and 121 nonsmokers using the Prolific online platform. Participants performed the PIC task twice (at a 1-month interval) and completed other measures relevant to TUD.

Results

Compared to nonsmokers, tobacco smokers selected to view significantly more tobacco images and less pleasant (nondrug reinforcer) images, a profile that remained stable at retest. Individual differences in choice of tobacco as compared to pleasant images on the PIC task were associated with craving but not with the other tobacco dependence measures, suggesting that the task may serve as a behavioral proxy measure of drug “wanting” rather than of cumulative nicotine exposure or physical dependence.

Conclusions

These results suggest that the PIC task can be a valuable tool for objectively assessing craving-associated tobacco seeking in TUD.

Implications

Most of the current measures of TUD rely on self-reports of consumption, dependence, and craving, and do not take into consideration the role of drug-related cues in driving tobacco seeking. This study shows that the PIC task provides an objective, reliable proxy measure of tobacco image-seeking behavior in people who smoke cigarettes that is linked to craving (desire) for smoking but not to other measures of TUD. Therefore, the PIC task may be a useful complementary tool for the classification, diagnosis, and prognosis of TUD.
Healthcare Visits by Smokers: Does Cessation Treatment Differ Based on Clinical Condition?
Authors: Geletko Karen W , Graves Katelyn , Hogans-Mathews Shermeeka , Harman Jeffrey
Published: June 2024

Introduction

Persons with behavioral health conditions are disproportionally burdened by their tobacco use. Research is limited on how often this patient population is offered tobacco cessation interventions at healthcare visits. This study examines if cessation treatment offered at healthcare visits differs based on the clinical condition.

Aims and Methods

Using data from the 2015 to 2018 National Ambulatory Medical Care Survey, we examined tobacco cessation counseling and medications (bupropion, nicotine replacement therapies, and varenicline) from 4590 visits by patients with current tobacco use. Separate multivariate logistic regressions were used to assess whether the odds of receiving tobacco cessation treatment varied by three groups of clinical conditions: (1) substance use disorder and/or alcohol use disorder, (2) depression, and (3) physical conditions.

Results

The odds of being offered smoking cessation counseling are 4.02 times greater for visits by patients with substance use disorder and/or alcohol use disorder compared to visits by patients with depression (p < .001), while the odds of receiving smoking cessation medication are 2.36 times greater for visits by patients with depression compared to visits by patients with substance use disorder and/or alcohol use disorder (p < .01). Visits by patients with substance use disorder and/or alcohol use disorder have 2.36 times the odds of receiving any combination of tobacco cessation treatment compared to visits by patients with depression (p < .001).

Conclusions

Providers are offering cessation treatment at visits by patients with behavioral health conditions at either higher or comparable rates to those without; however, tobacco cessation treatment continues to be underutilized by providers during office visits.

Implications

The results of our study have implications for increasing educational opportunities for healthcare providers to improve their confidence in offering tobacco cessation treatment to patients with behavioral health conditions. These patients are motivated to quit smoking, yet cessation treatment is underutilized in this population despite having a greater health effect than most other clinical interventions. Incorporating tobacco cessation education in medical school curricula and post-graduate training can help eliminate barriers for physicians to routinely provide cessation assistance. Collaboration between clinicians and behavioral health providers can also enhance tobacco treatment support and improve cessation rates.
Sofosbuvir Off-label Treatment of Yellow Fever Patients During an Outbreak in Brazil, 2018: A Cohort Study
Authors: Rezende Izabela M , Mendonça Diogo Correa , Costa Thais Alkifeles , Oliveria Gabriela Fernanda Garcia de , Arruda Matheus Soares , Gonçalves Andreza Parreiras , Alves Pedro Augusto , Calzavara-Silva Carlos Eduardo , Martins-Filho Olindo A , Teixeira-Carvalho Andréa , Bonjardim Claudio Antonio , Monath Thomas P , LaBeaud A Desiree , Drumond Betânia P , Pascoal-Xavier Marcelo Antônio , Pereira Leonardo S , Ramalho Dario Brock
Published: June 2024

We enrolled 21 patients with laboratory-confirmed yellow fever (YF), hospitalized at Eduardo de Menezes Hospital, Brazil, to be treated with sofosbuvir, a drug approved for hepatitis C. Given the absence of specific YF antiviral treatments, the off-label nonrandomized sofosbuvir treatment aimed to address high disease severity and the risk of fatal outcomes. Patients received a daily dose of 400 mg sofosbuvir from 4 to 10 days post–symptom onset. YF viral load (VL) comparisons were made between treated and nontreated patients who either survived or died. The genomic VL for the treated group steadily decreased after day 7 post–symptom onset, suggesting that sofosbuvir might reduce YF VL. This study underscores the urgent need for YF antiviral therapies, advocating for randomized clinical trials to further explore sofosbuvir's role in YF treatment.
Dynamics near the inner dead-zone edges in a proprotoplanetary disk
Authors: Iwasaki Kazunari , Tomida Kengo , Takasao Shinsuke , Okuzumi Satoshi , Suzuki Takeru K
Published: June 2024

We perform three-dimensional global non-ideal magnetohydrodynamic simulations of a protoplanetary disk containing the inner dead-zone edge. We take into account realistic diffusion coefficients of the Ohmic resistivity and ambipolar diffusion based on detailed chemical reactions with single-size dust grains. We found that the conventional dead zone identified by the Elsässer numbers of the Ohmic resistivity and ambipolar diffusion is divided into two regions: “the transition zone” and “the coherent zone.” The coherent zone has the same properties as the conventional dead zone, and extends outside of the transition zone in the radial direction. Between the active and coherent zones, we discover the transition zone, the inner edge of which is identical to that of the conventional dead zone. The transition zone extends out over the regions where thermal ionization determines diffusion coefficients. The transition zone has completely different physical properties than the conventional dead zone, the so-called undead zone, and the zombie zone. The combination of amplification of the radial magnetic field owing to the ambipolar diffusion and a steep radial gradient of the Ohmic diffusivity causes the efficient evacuation of the net vertical magnetic flux from the transition zone within several rotations. Surface gas accretion occurs in the coherent zone but not in the transition zone. The presence of the transition zone prohibits mass and magnetic flux transport from the coherent zone to the active zone. Mass accumulation occurs at both edges of the transition zone as a result of mass supply from the active and coherent zones.
Pediatric critical care capacity in Canada
Authors: Lalgudi Ganesan Saptharishi , Garros Daniel , Foster Jennifer , Di Genova Tanya , Fontela Patricia S , Murthy Srinivas
Published: June 2024

Objectives

Pediatric intensive care unit (PICU) capacity is a current and future health system challenge. Despite experiencing two pandemics in as many decades and surges every winter, we have little to no information on PICU capacity in Canada. Our objective was to characterize the bed capacity of Canadian PICUs and their ability to accommodate surges in demand.

Methods

We conducted a cross-sectional survey to gather information from Canadian PICUs regarding funded/physical beds, unit characteristics, medical staffing, therapies provided, and challenges related to surge management. The survey was completed by a representative from each PICU and validated by PICU Directors. Quantitative survey results were summarized as counts and proportions, while the free-text response was summarized using inductive content analysis.

Results

Representatives from all 19 Canadian PICUs located in 17 hospitals completed the survey and reported having 275 (217 level 3 and 58 level 2) funded beds and 298 physical bed spaces. Of these, 47 beds (35 level 3 and 12 level 2) are in two specialized cardiac PICUs. Roughly 13,385, 13,419, 11,430, and 12,315 children were admitted in the years 2018, 2019, 2020, and 2021, respectively. During a surge, PICUs reported being able to add 5.9 ± 3.4 beds per unit totaling up to 108 temporary surge beds. Several barriers for the successful implementation of surge plans were identified.

Conclusions

Canadian pediatric critical care capacity is comparable to that in many other high-income countries, though our ability to respond to a pandemic/epidemic with significant pediatric critical illness may be limited.
The impact of early death on birth counts in the United States, 1950 to 2019
Authors: Polizzi Antonino , Tilstra Andrea M
Published: June 2024

In a previous issue of PNAS Nexus, Bor et al. quantified the number of “missing Americans”—the deaths that would have been averted if the United States had experienced the mortality conditions of other wealthy nations. In 2019 alone, their estimates indicate that more than 100,000 individuals in reproductive ages (15–49 years) would have survived. The concept of the “missing Americans” is a valuable one, but here we argue that it is incomplete because it does not include children that would have been born to those who died an early death. We examine 3 indicators to assess the strength of the mortality–fertility nexus at the population level, showing that mortality more negatively affects birth counts in the United States than in other wealthy nations. Using the mortality conditions in other wealthy nations as a reference, we estimate that between 2010 and 2019 alone, approximately 200,000 children were not born in the United States due to the premature death of their potential mothers. Our findings highlight that improving morbidity and mortality among people of reproductive age—without compromising their reproductive autonomy—is critical in the United States.
A review on natural bioactive compounds of Taraxacum officinale Weber: a potential anticancer plant
Authors: Tiwari Deepti , Kewlani Pushpa , Singh Laxman , Rawat Sandeep , Bhatt Indra D , Sundriyal Rakesh C , Pande Veena
Published: June 2024

Objectives

This review analyzed available literature on traditional/ethnomedicinal knowledge, phytochemical composition, anticancer activity reported in vitro and in vivo studies, and the toxicological activity of Taraxacum officinale. The aim is to provide an in-depth analysis of existing research on the anticancer potential of T. officinale.

Key findings

The data was extracted using four search engines, Google Scholar, Web of Science, Scopus, and Pubmed, and systematically analyzed to identify effective plant-based substances for cancer treatment. The different parts of the plant are the source of different bioactive compounds that exhibit several pharmacological activities like antidiabetic, hepatoprotective, antimicrobial, anticancer, analgesic, etc. Traditionally, it is used to treat various ailments such as migraines, cardiac complaints, jaundice, fever, liver and kidney disorders, and hepatitis. Different biologically active compounds isolated from T. officinale are widely investigated against various pharmacological activities, including cancer.

The available evidence on the bioactive potential of Taraxacum officinale provides direction for identifying and developing herbal agents to prevent different types of cancers in the future. However, there is a need to examine the clinical validation of pure compounds for drug development.
Obesity hypoventilation syndrome, literature review
Authors: Orozco González Bertha Nachelly , Rodriguez Plascencia Nidia , Palma Zapata Julio Augusto , Llamas Domínguez Alondra Esthefanía , Rodríguez González Jesús Sacramento , Diaz Juan Manuel , Ponce Muñoz Miguel , Ponce-Campos Silvia Denise
Published: June 2024

Obesity is a global health concern that has been increasing over the years, and it is associated with several pathophysiological changes affecting the respiratory system, including alveolar hypoventilation. Obesity hypoventilation syndrome (OHS) is one of the six subtypes of sleep-hypoventilation disorders. It is defined as the presence of obesity, chronic alveolar hypoventilation leading to daytime hypercapnia and hypoxia, and sleep-disordered breathing. The existence of a sleep disorder is one of the characteristics that patients with OHS present. Among them, 90% of patients have obstructive sleep apnea (OSA), and the remaining 10% of patients with OHS have non-obstructive sleep hypoventilation without OSA or with mild OSA. This review aims to provide a comprehensive understanding of the epidemiological and pathophysiological impact of OHS and to highlight its clinical features, prognosis, and severity, as well as the available treatment options.
The Meaning of Success: Ethno-Gendered Reactions to Discrimination at Work
Authors: Marantz Erez Aharon , Kalev Alexandra , Lewin-Epstein Noah , Gerson Kathleen
Published: June 2024

A growing body of research examines discrimination within racialized organizations, but much less attention has been given to workers’ reactions to such experiences. We offer an identity-based theory for understanding varied career reactions to discrimination and apply it to minority professionals within the Israeli pharmaceutical retail industry. We analyze 116 interviews with Arab-Israeli and Jewish pharmacists to explore the experience of exclusion at work and its impact on career plans. Our findings reveal that marginalized professionals can regain their self-efficacy at work by emphasizing a broader identity-based meaning of career success and adapting their career strategies accordingly, within their labor market constraints. While career reactions are highly gendered, our evidence suggests that variations in reactions are primarily explained by the meaning of career success rather than gender. We discuss the implications of our findings for a theory of agency within racialized organizations.
Advising through Adversity: Urban High Schools’ Diverging Approaches to Postsecondary Planning
Authors: Sageman Joseph
Published: June 2024

This article examines the role urban high schools play in influencing students’ postsecondary plans. While postsecondary aspirations and attendance have become more universal experiences over time for low-income students in the United States, the kinds of high schools they attend are increasingly heterogeneous in their missions and orientations to college. We know little about how variation among high schools maps onto differences in how students are supported or advised on their postsecondary plans. Drawing on 73 in-depth interviews with high school seniors, counselors, and principals in Philadelphia, I find that school structures tend to compound differences among students related to how they think about the value of college, consider which postsecondary programs fit them best, and seek out guidance from adults. I contrast the strategies of socioeconomically diverse and socioeconomically disadvantaged schools on four dimensions: curriculum, counseling, staff and peer networks, and orientation to work. Diverse schools foster exploratory adolescence, orienting students towards open-ended and long-term educational goals. Disadvantaged schools promote expedited adulthood, an approach that prioritizes pragmatic over academic training in hopes of accelerating students’ paths to economic stability and self-sufficiency. These results point to the lasting effects of school segregation and sorting mechanisms that shape students’ long-term educational and career trajectories.
Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis
Authors: Bai Yihua , Huang Lilan , Fan Yang , Li Yaling
Published: June 2024

Diabetic nephropathy (DN) is one of the common microvascular complications in diabetic patients. Marrow mesenchymal stem cells (MSCs) have attracted attention in DN therapy but the underlying mechanism remains unclear. Here, we show that MSC administration alleviates high glucose (HG)‐induced human kidney tubular epithelial cell (HK‐2 cell) injury and ameliorates renal injury in DN mice. We identify that Smad2/3 is responsible for MSCs‐regulated DN progression. The activity of Smad2/3 was predominantly upregulated in HG‐induced HK‐2 cell and DN mice and suppressed with MSC administration. Activation of Smad2/3 via transforming growth factor‐β1 (TGF‐β1) administration abrogates the protective effect of MSCs on HG‐induced HK‐2 cell injury and renal injury of DN mice. Smad2/3 has been reported to interact with methyltransferase of N6‐methyladenosine (m6A) complex and we found a methyltransferase, Wilms' tumor 1‐associating protein (WTAP), is involved in MSCs‐Smad2/3‐regulated DN development. Moreover, WTAP overexpression abrogates the improvement of MSCs on HG‐induced HK‐2 cell injury and renal injury of DN mice. Subsequently, α‐enolase (ENO1) is the downstream target of WTAP‐mediated m6A modification and contributes to the MSCs‐mediated regulation. Collectively, these findings reveal a molecular mechanism in DN progression and indicate that Smad2/3/WTAP/ENO1 may present a target for MSCs‐mediated DN therapy.
Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency
Authors: Díaz‐Tocados Juan Miguel , Rodríguez‐Ortiz María Encarnación , Herencia Carmen , López‐Baltanás Rodrigo , Jurado‐Montoya Daniel , García‐Saez Raquel María , Valdés‐Díaz Karen , Martínez‐Moreno Julio Manuel , Santamaría Rafael , Pendón‐Ruiz de Mier María Victoria , Rodelo‐Haad Cristian , Frazão João Miguel , Felsenfeld Arnold J. , Rodríguez Mariano , Almadén Yolanda , Muñoz‐Castañeda Juan Rafael
Published: June 2024

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH‐clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β‐catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level.
Tumor‐derived hypoxic small extracellular vesicles promote endothelial cell migration and tube formation via ALS2/Rab5/β‐catenin signaling
Authors: Silva Patricio , Hernández Nadia , Tapia Héctor , Gaete‐Ramírez Belén , Torres Pedro , Flores Tania , Herrera Daniela , Cáceres‐Verschae Albano , Acuña Rodrigo A. , Varas‐Godoy Manuel , Torres Vicente A.
Published: June 2024

Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release and cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic extracellular vesicles are known to trigger a variety of angiogenic responses via different mechanisms. We recently showed that hypoxia promotes endosomal signaling in tumor cells via HIF‐1α‐dependent induction of the guanine exchange factor ALS2, which activates Rab5, leading to downstream events involved in cell migration and invasion. Since Rab5‐dependent signaling is required for endothelial cell migration and angiogenesis, we explored the possibility that hypoxia promotes the release of small extracellular vesicles containing ALS2, which in turn activate Rab5 in recipient endothelial cells leading to pro‐angiogenic properties. In doing so, we found that hypoxia promoted ALS2 expression and incorporation as cargo within small extracellular vesicles, leading to subsequent transfer to recipient endothelial cells and promoting cell migration, tube formation, and downstream Rab5 activation. Consequently, ALS2‐containing small extracellular vesicles increased early endosome size and number in recipient endothelial cells, which was followed by subsequent sequestration of components of the β‐catenin destruction complex within endosomal compartments, leading to stabilization and nuclear localization of β‐catenin. These events converged in the expression of β‐catenin target genes involved in angiogenesis. Knockdown of ALS2 in donor tumor cells precluded its incorporation into small extracellular vesicles, preventing Rab5‐downstream events and endothelial cell responses, which depended on Rab5 activity and guanine exchange factor activity of ALS2. These findings indicate that vesicular ALS2, secreted in hypoxia, promotes endothelial cell events leading to angiogenesis. Finally, these events might explain how tumor angiogenesis proceeds in hypoxic conditions.
Identification of potential immune-related mechanisms related to the development of multiple myeloma
Authors: Wang Yaomei , Zhang Wenli , Li Tiandong , Liu Mengmeng , Gao Mengya , Li Xinqing , Chen Yufei , Song Yongping , Li Wei , Du Chunyan , Wang Fang , Liu Lina
Published: June 2024

Background:

Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM.

Methods:

This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients.

Results:

A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG+Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)+DCs, IFN-responding DCs, MHCII+DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that “don’t eat me”-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16+monocytes/macrophages and expression level of CD16. Cell–cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients.

Conclusions:

Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.
Reflectance confocal microscopy versus dermoscopy for the diagnosis of cutaneous melanoma: a head-to-head comparative meta-analysis
Authors: Liu Huasheng , Jiang Hong , Shan Qianqian
Published: June 2024

This meta-analysis aimed to evaluate the comparative diagnostic performance of reflectance confocal microscopy (RCM) and dermoscopy in detecting cutaneous melanoma patients. An extensive search was conducted in the PubMed and Embase databases to identify available publications up to December 2023. Studies were included if they evaluated the diagnostic performance of RCM and dermoscopy in patients with cutaneous melanoma. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. A total of 14 articles involving 2013 patients were included in the meta-analysis. The overall sensitivity of RCM was 0.94 [95% confidence interval (CI), 0.87–0.98], while the overall sensitivity of dermoscopy was 0.84 (95% CI, 0.71–0.95). These results suggested that RCM has a similar level of sensitivity compared with dermoscopy (P = 0.15). In contrast, the overall specificity of RCM was 0.76 (95% CI, 0.67–0.85), while the overall specificity of dermoscopy was 0.47 (95% CI, 0.31–0.63). The results indicated that RCM appears to have a higher specificity in comparison to dermoscopy (P < 0.01). Our meta-analysis indicates that RCM demonstrates superior specificity and similar sensitivity to dermoscopy in detecting cutaneous melanoma patients. The high heterogeneity, however, may impact the evidence of the current study, further larger sample prospective research is required to confirm these findings.
Pain-suppressed consumption of highly palatable liquid in rats
Authors: Craft Rebecca M.
Published: June 2024

This study determined whether consumption of a highly palatable liquid is a reliable measure of inflammatory pain and antinociception in male and female rats. After a 10-day acquisition period, the impact of intraplantar oil vs. complete Freund adjuvant (CFA) on consumption of vanilla-flavored Ensure was assessed, with a sipper tube height 12 or 19 cm above the floor. CFA significantly decreased Ensure consumption, which completely recovered within 4–7 days to levels in oil-treated controls; neither sex nor sipper tube height significantly influenced Ensure consumption. CFA also significantly suppressed Ensure consumption in rats not exposed to the 10-day acquisition period, but only in males. To test the predictive validity of Ensure consumption as a measure of pain, separate rats were pretreated with a vehicle, an opioid, a nonsteroidal anti-inflammatory drug, or a cannabinoid the day after CFA treatment. Morphine and ibuprofen significantly attenuated CFA-suppressed drinking in at least one sex, and tetrahydrocannabinol did not. Neither ibuprofen nor tetrahydrocannabinol significantly altered drinking in oil-injected, ‘pain-free’ controls, but morphine increased drinking. These results demonstrate that CFA decreases consumption of a highly palatable liquid regardless of previous exposure (training) to the consumption procedure, but only in males. Although standard analgesics attenuate CFA-suppressed drinking, nonspecific hyperphagic effects can confound the interpretation of results. Thus, consumption of a highly palatable liquid is not an optimal measure for candidate analgesic screening.
Vascular regenerative cell content in South Asians: the key learnings
Authors: Krishnaraj Aishwarya , Dennis Fallon , Teoh Hwee , Verma Subodh , Hess David A.
Published: June 2024

Purpose of review

We aim to provide a comprehensive examination of the literature linking elevated rates of cardiovascular disease (CVD) in individuals of South Asian ethnicity with the severity of circulating vascular regenerative cell exhaustion.

Recent findings

Recent findings have demonstrated reduced bioavailability of pro-vascular progenitor cell subsets in individuals with T2D and obesity. Depletion of vascular regenerative cells in the bone marrow – coupled with decreased mobilization into circulation – can negatively impact the capacity for vascular repair and exacerbate CVD risk. Several recent studies have established that although South Asian individuals possess similar inflammatory cell burden compared with other ethnicities, they exhibit marked decreases in vessel regenerative hematopoietic progenitor cells and monocyte subsets. Validation of these findings and investigation the functional capacity of vascular regenerative cell subsets to mediate vessel repair is highly warranted.

Vascular regenerative cells play a key role coordinating angiogenic and arteriogenic vessel remodelling. Recent studies have demonstrated that South Asian individuals with T2D show severe depletion in circulating vascular regenerative cell subsets. Because the reversal of vascular regenerative cell exhaustion by current glucose-lowering pharmaceutical agents has recently been documented, early intervention to bolster vascular regenerative cell content may prevent CVD co-morbidities in South Asian individuals with cardiometabolic disease.
Maternal Exposure to Heavy Metals From Industrial Sources During Pregnancy and Childhood Cancer Risk in California
Authors: Chen Yixin , Van Deventer Darcy , Nianogo Roch , Vinceti Marco , Kang Wei , Cockburn Myles , Federman Noah , Heck Julia E.
Published: June 2024

Objective

The study investigated maternal exposure to heavy metals from industrial sources during pregnancy as potential risk factors for childhood cancer.

Methods

Cases ages 0–19 were identified from California Cancer Registry. Controls (20:1 ratio) were randomly selected from California Birth Registry, frequency-matched by birth year (1998–2016). We estimated maternal exposure to lead, nickel, and cobalt in ambient air from the Toxics Release Inventory. We examined “ever/never” and “high/low” exposures categorized by median exposure. Models were adjusted for maternal age, race/ethnicity, method of payment for prenatal care, neighborhood socioeconomic status, and urban/rural residence.

Results

Among highly exposed persons, lead was associated with an increased teratoma risk (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 0.97, 2.37), whereas nickel was associated with an increased rhabdomyosarcoma risk (aOR: 1.45; 95% CI: 1.03, 2.04). Cobalt was associated with an increased glioma risk (aOR: 2.25; 95% CI: 1.39, 3.65) among ever-exposed persons. Inverse associations were found between Wilms tumor and nickel among the ever exposed and highly exposed (ever: aOR: 0.75; 95% CI: 0.59, 0.96; high: aOR: 0.64; 95% CI: 0.45, 0.93).

Conclusions

Findings suggest that air pollution from heavy metals released by industrial sources may elevate childhood cancer risk.
Exposure and Illness Among Workers Filing for COVID-19–Related Workers’ Compensation—California, 2020
Authors: Vergara Ximena P. , Frederick Matt , Gibb Kathryn , Wong Jessie , Harrison Robert
Published: June 2024

Objectives

The aim of the study is to characterize the incidence of SARS-CoV-2 exposure and COVID-19 infection among California workers’ compensation claims in 2020 and examine risk factors for exposure.

Methods

Using a case-control approach, we combined machine learning techniques and job exposure matrices to assess associations between exposures and illness claims and clusters of claims within specific worksites over a 3-week period.

Results

Of the 117,125 COVID-19 claims, most were primarily among younger groups, of shorter tenure, and from health care occupations. Illness claims were among older groups with longer tenure. Jobs with very close physical proximity and high physical activity, along with transportation and warehousing industries, were associated with being part of a cluster of claims.

Conclusions

The findings merit further study but indicate respiratory viral transmission and support efforts to systematically incorporate work-related variables into other California data sources.
Influence of intraoperative blood salvage and autotransfusion on tumor recurrence after deceased donor liver transplantation: a large nationwide cohort study
Authors: Yang Mengfan , Wei Xuyong , Shu Wenzhi , Zhai Xiangyu , Zhou Zhisheng , Cai Jinzhen , Yang Jiayin , Jin Bin , Zheng Shusen , Xu Xiao
Published: June 2024

Background and aims:

The practice of intraoperative blood salvage and autotransfusion (IBSA) during deceased donor liver transplantation for hepatocellular carcinoma (HCC) can potentially reduce the need for allogeneic blood transfusion. However, implementing IBSA remains debatable due to concerns about its possible detrimental effects on oncologic recurrence.

Methods:

This study retrospectively enrolled nationwide recipients of deceased donor liver transplantation for HCC between 2015 and 2020. The focus was on comparing the cumulative recurrence rate and the recurrence-free survival rate. Propensity score matching was conducted repeatedly for further subgroup comparison. Recipients were categorized based on the Milan criteria, macrovascular invasion, and pretransplant α-Fetoprotein (AFP) level to identify subgroups at risk of HCC recurrence.

Results:

A total of 6196 and 329 patients were enrolled in the non-IBSA and IBSA groups in this study. Multivariable competing risk regression analysis identified IBSA as independent risk factors for HCC recurrence (P<0.05). Postmatching, the cumulative recurrence rate and recurrence-free survival rate revealed no significant difference in the IBSA group and non-IBSA group (22.4 vs. 16.5%, P=0.12; 60.3 vs. 60.9%, P=0.74). Recipients beyond Milan criteria had higher, albeit not significant, risk of HCC recurrence if receiving IBSA (33.4 vs. 22.5%, P=0.14). For recipients with macrovascular invasion, the risk of HCC recurrence has no significant difference between the two groups (32.2 vs. 21.3%, P=0.231). For recipients with an AFP level <20 ng/ml, the risk of HCC recurrence was comparable in the IBSA group and the non-IBSA group (12.8 vs. 18.7%, P=0.99). Recipients with an AFP level ≥20 ng/ml, the risk of HCC recurrence was significantly higher in the IBSA group. For those with an AFP level ≥400 ng/ml, the impact of IBSA on the cumulative recurrence rate was even more pronounced (49.8 vs. 21.9%, P=0.011).

Conclusions:

IBSA does not appear to be associated with worse outcomes for recipients with HCC exceeding the Milan criteria or with macrovascular invasion. IBSA could be confidently applied for recipients with a pretransplant AFP level <20 ng/ml. For recipients with AFP levels ≥20 ng/ml, undertaking IBSA would increase the risk of HCC recurrence.
Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: a systematic review and meta-analysis
Authors: Hong Jiaze , Fu Yufan , Chen Xiaoqian , Zhang Yurui , Li Xinyi , Li Tianhang , Liu Yilin , Fan Mengke , Lin Rong
Published: June 2024

Background:

The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC.

Methods:

Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes the authors focus on.

Results:

This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=−0.33; P=0.002 and SMD=−0.59; P<0.001, respectively) and a statistically significant β-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that four genera were significantly increased in PDAC patients compared to HC (e.g. Escherichia-Shigella and Veillonella). CP patients had an increase in four genera (e.g. Escherichia-Shigella and Klebsiella) and a decrease in eight genera (e.g. Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients.

Conclusions:

Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.
Potential of BMI as a screening indicator for extracranial–intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial
Authors: Lu Guangdong , Wang Tao , Yang Fan , Sun Xinyi , Yang Renjie , Luo Jichang , Tong Xiaoguang , Gu Yuxiang , Wang Jiyue , Tong Zhiyong , Kuai Dong , Cai Yiling , Ren Jun , Wang Donghai , Duan Lian , Maimaitili Aisha , Hang Chunhua , Yu Jiasheng , Ma Yan , Liu Sheng , Jiao Liqun ,   for the CMOSS Investigators
Published: June 2024

Background:

To investigate the association between BMI and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial–intracranial bypass surgery.

Materials and Methods:

The authors analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, the authors compared the primary endpoint of CMOSS—stroke or death within 30 days, or IIS after 30 days up to 2 years—among patients with varying BMIs who underwent either surgery or medical treatment.

Results:

Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within 2 years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% CI: 1.06–1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4 vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3 vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6 vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2.

Conclusion:

Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.
Risk factors for deep vein thrombosis after traumatic lower extremity fracture: A systematic review and meta-analysis
Authors: Qian Xiaoliang , Ge Yinping , Luo Jian
Published: June 2024

Background:

The study aimed to predict the risk factors of deep vein thrombosis of lower extremity after traumatic fracture of lower extremity, so as to apply effective strategies to prevent deep vein thrombosis of lower extremity, improve survival rate, and reduce medical cost.

Methods:

The English and Chinese literatures published from January 2005 to November 2023 were extracted from PubMed, Embase, Willey Library, Scopus, CNKI, Wanfang, and VIP databases. Statistical analysis was performed using Stata/SE 16.0 software.

Results:

A total of 13 articles were included in this paper, including 2699 venous thromboembolism (VTE) patients and 130,507 normal controls. According to the meta-results, 5 independent risk factors can be identified: history of VTE was the most significant risk factor for deep vein thrombosis after traumatic lower extremity fracture (risk ratio [RR] = 6.45, 95% confidence interval [CI]: 1.64–11.26); age (≥60) was the risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.60, 95% CI: 1.02–2.18); long-term braking was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.52, 95% CI: 1.11–1.93); heart failure was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.92, 95% CI: 1.51–2.33); obesity was a risk factor for deep vein thrombosis after traumatic lower extremity fracture (RR = 1.59, 95% CI: 1.35–1.83).

Conclusion:

The study confirmed that the history of deep vein thrombosis, age (60 + years), previous history of VTE, obesity, prolonged bed rest, and heart failure are all associated with an increased risk of VTE. By identifying these significant risk factors, we can more intensively treat patients at relatively high risk of VTE, thereby reducing the incidence of VTE. However, the limitation of the study is that the sample may not be diversified enough, and it fails to cover all potential risk factors, which may affect the universal applicability of the results. Future research should include a wider population and consider more variables in order to obtain a more comprehensive risk assessment.