bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis
Authors: Zeng Qingyue , Xu Jiao , Mu Xingyu , Shi Yi , Fan Hong , Li Shuangqing 
Published: October 2023

PurposeA systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity.MethodsA systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran’s Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.)ResultsA total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.ConclusionBased on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400.
Oral exposure to Staphylococcus aureus enterotoxin B could promote the Ovalbumin-induced food allergy by enhancing the activation of DCs and T cells
Authors: Yuan Jin , Tong Ping , Meng Xuanyi , Wu Yong , Li Xin , Gao Jinyan , Chen Hongbing 
Published: October 2023

IntroductionRecent work highlighted the importance of environmental contaminants in the development of allergic diseases.MethodsThe intestinal mucosal barrier, Th (helper T) cells, DCs (dendritic cells), and intestinal flora were analyzed with flow cytometry, RNA-seq, and 16s sequencing in the present study to demonstrate whether the exposure of enterotoxins like Staphylococcus aureus enterotoxin B (SEB) in allergens could promote the development of food allergy.Results and discussionWe found that co-exposure to SEB and Ovalbumin (OVA) could impair the intestinal barrier, imbalance the intestinal Th immune, and cause the decline of intestinal flora diversity in OVA-sensitized mice. Moreover, with the co-stimulation of SEB, the transport of OVA was enhanced in the Caco-2 cell monolayer, the uptake and presentation of OVA were promoted in the bone marrow dendritic cells (BMDCs), and Th cell differentiation was also enhanced. In summary, co-exposure to SEB in allergens should be considered a food allergy risk factor.
Enhanced expression of natural cytotoxicity receptors on cytokine-induced memory-like natural killer cells correlates with effector function
Authors: Carreira-Santos Sofía , López-Sejas Nelson , González-Sánchez Marina , Sánchez-Hernández Eva , Pera Alejandra , Hassouneh Fakhri , Durán Esther , Solana Rafael , Casado Javier G. , Tarazona Raquel 
Published: October 2023

IntroductionNatural killer (NK) cells are a key component of the innate immune system, involved in defending the host against virus-infected cells and tumor immunosurveillance. Under in vitro culture conditions, IL-12/15/18 can induce a memory-like phenotype in NK cells. These cytokine-induced memory-like (CIML) NK cells possess desirable characteristics for immunotherapies, including a longer lifespan and increased cytotoxicity.MethodsIn this study, NK cells were isolated from peripheral blood of healthy donors and stimulated with IL-12/15/18 to induce a memory-like phenotype or with IL-15 alone as a control. After seven days of culture, multiparametric flow cytometry analysis was performed to evaluate the phenotypic and functional profiles of CIML and control NK cells.ResultsOur results showed a significantly higher expression of CD25, CD69, NKG2D, NKp30, NKp44, NKp46, TACTILE, and Granzyme B in CIML NK cells compared to control NK cells. In contrast, KIR2D expression was significantly lower in CIML NK cells than in control NK cells. Moreover, functional experiments demonstrated that CIML NK cells displayed enhanced degranulation capacity and increased intracellular IFN-γ production against the target cell line K562. Interestingly, the degranulation capacity of CIML NK cells was positively correlated with the expression of the activating receptors NKp46 and NKp30, as well as with the inhibitory receptor TACTILE.DiscussionIn conclusion, this study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings.
Prolonged mask wearing changed nasal microbial characterization of young adults during the COVID-19 pandemic in Shanghai, China
Authors: Xiang Guoxiu , Xu Kai , Jian Ying , He Lei , Shen Zhen , Li Min , Liu Qian 
Published: October 2023

BackgroundFace masks have become a common sight during the Coronavirus Disease 2019 (COVID-19) pandemic in many countries. However, the impact of prolonged face mask wearing on nasal microbiota of healthy people is not fully understood.MethodsIn this study, we compared the nasal microbiota of 82 young adults who wore face masks for an extended period of time to 172 mask-free peers from the same school recruited before the COVID-19 pandemic via 16S ribosomal RNA gene sequencing. Diversity, composition, and function of nasal microbiota between the two groups were analyzed. Prevalence of commensal bacteria colonized in the nasal cavity was determined by culture-based analysis.ResultsWe observed that prolonged face mask wearers had significantly different nasal microbial characterization and metabolic function compared to mask-free controls from 2018. Specifically, the nasal microbiota of the prolonged mask wearers displayed increased abundance of Staphylococcus, Pseudoalteromonas, Corynebacterium, etc. Meanwhile, the abundance of several genera including Bacteroides, Faecalibacterium, and Agathobacter was decreased. Moreover, we observed that COVID-19 infection history did not affect the composition of nasal microbiota significantly. Additionally, the culture-based analysis revealed that Staphylococcus aureus and Corynebacterium accolens increased, and Staphylococcus epidermidis decreased in the nasal cavity of prolonged mask wearers.ConclusionsOverall, our study suggests that prolonged face mask wearing can significantly alter the nasal microbiota.
Differences in the inflammatory response among hospitalized patients with distinct variants of SARS-CoV-2
Authors: Homen-Fernandez Jose-Reynaldo , Valls Adrián , García Ana , Cabello Noemí , Ortega Isabel , Orviz Eva , Foncubierta Carlos , Martínez Mercedes , Estrada Vicente 
Published: October 2023

The SARS-CoV-2 variants demonstrate diverse transmission patterns, modifications in infectivity, and immune response. Changes in disease manifestation may be attributed to vaccination and the virus’s reduced capacity to induce inflammation.ObjectivesTo investigate the relationship between the inflammatory response and the characteristics of COVID-19 across successive waves.MethodsA retrospective cross-sectional study was conducted to evaluate sociodemographic, clinical, and laboratory data of Alpha (G1), Delta (G2), and Omicron (G3) variants.ResultsA total of 300 patients from a hospital in Madrid, Spain, were included. The groups exhibited similar sociodemographic and baseline characteristics. The Alpha variant predominantly affected younger patients, while the Omicron variant affected patients with a higher prevalence of comorbidities. The Alpha group had the lowest vaccination rate compared to the highest rate in the Omicron group. The Alpha group received a higher proportion of tocilizumab compared to the other groups. Despite these differences, the severity scores were similar among the three variants. Regarding laboratory parameters, differences were observed in haemoglobin, D-dimer, alkaline phosphatase, and potassium levels. The Omicron variant showed higher D-dimer levels (p=0.04). In the multivariate analysis, differences in leukocyte count, haemoglobin, alkaline phosphatase, and potassium levels were consistently observed among patients from different waves. Omicron exhibited a higher absolute leukocyte count than the Alpha variant (p=0.003).ConclusionNo significant differences were found in inflammation biomarkers among the three variants. Furthermore, there were no significant disparities in mortality or disease severity. The level of inflammatory response in patients may be determined by the severity of COVID-19, rather than the specific viral variant.
Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial
Authors: Cossarizza Andrea , Cozzi-Lepri Alessandro , Mattioli Marco , Paolini Annamaria , Neroni Anita , De Biasi Sara , Tartaro Domenico Lo , Borella Rebecca , Fidanza Lucia , Gibellini Lara , Beghetto Barbara , Roncaglia Enrica , Nardini Giulia , Milic Jovana , Menozzi Marianna , Cuomo Gianluca , Digaetano Margherita , Orlando Gabriella , Borghi Vanni , Guaraldi Giovanni , Mussini Cristina 
Published: October 2023

BackgroundThe aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).MethodsAn open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.ResultsBetween the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = −6.7 cells/mm3; 95% CI; −16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.ConclusionNo evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT04054089.
Diversity of filter feeding and variations in cross-flow filtration of five ram-feeding fish species
Authors: Hamann Leandra , Schreiber Kristina , Hagenmeyer Jan , Eduardo Santiago , Spanke Tobias , Blanke Alexander 
Published: October 2023

IntroductionFilter-feeding fish separate food particles from the surrounding water by cross-flow filtration in which a suspension flows parallel to a porous filter medium, thereby transporting particles along the surface.MethodsHere, we investigate cross-flow filtration in five ram-feeding fish species from two groups, Scombridae (Scomber scombrus and Rastrelliger kanagurta) and Clupeidae (Clupea harengus, Sardina pilchardus, and Engraulis encrasicolus). Using a combination of morphometrics, micro-CT scanning, video analysis, and water tunnel experiments, we give a detailed description of the gill arch system, calculate filtration parameters, observe particle movement, and identify morphological traits that induce cross-flow filtration.ResultsOur findings suggest that these ram-feeding fish species use a combination of cross-flow and dead-end filtration as the underlying filtration principle. Specifically, the particles are transported along the surface of gill rakers and denticles towards the esophagus where they accumulate before being periodically swallowed. We infer three distinct morphotypes characterized by variations in geometry, mesh size, and surface structures, which indicate variations of the general mechanism.DiscussionThe description presented in this study contributes to the development of models for investigating the influence of morphological variation on fluid flow and particle retention in filter-feeding fish and on their ecology and biomimetic application.
The correlation between red cell distribution width to albumin ratio and all-cause mortality in critically ill patients with rheumatic diseases: a population-based retrospective study
Authors: Yin Lijuan , Min Jie , Zhong Lei , Shen Qikai 
Published: October 2023

BackgroundPatients with rheumatic diseases have an increased likelihood of being admitted to the intensive care unit (ICU), highlighting the importance of promptly identifying high-risk individuals to enhance prognosis. This study aimed to assess the correlation of red blood cell distribution width to albumin ratio (RAR) with the 90-days and 360-days survival rates among critically ill rheumatic patients.MethodsAdult rheumatic patients admitted to the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were included. The participants were categorized into two groups, survivors (n = 436) and non-survivors (n = 192), based on their 90-days survival outcome. The population was further classified into tertiles using RAR values, with RAR &lt; 4.63 (n = 208), 4.63–6.07 (n = 211), and &gt; 6.07 (n = 209). Kaplan–Meier curves were utilized to evaluate the cumulative survival rates at 90-days and 360-days. The association between RAR and mortality was assessed using restricted cubic splines (RCS) and multivariate Cox regression analysis. Additional subgroup analyses and sensitivity analyses were conducted to further explore the findings. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive performance of RAR.ResultsThis study involved 628 critically ill patients with rheumatic diseases, and they had an all-cause mortality of 30.57% at 90-days and 38.69% at 360-days. Kaplan–Meier analysis showed a gradual decrease in both 90-days and 360-days cumulative survival with increasing RAR (χ2 = 24.400, p &lt; 0.001; χ2 = 35.360, p &lt; 0.001). RCS revealed that RAR was linearly related to 90-days and 360-days all-cause mortality risk for critically ill patients with rheumatic diseases (χ2 = 4.360, p = 0.225; χ2 = 1.900, p = 0.594). Cox regression analysis indicated that elevated RAR (&gt; 6.07) was significantly correlated with mortality. The ROC curves demonstrated that an optimal cut-off value of RAR for predicting 90-days mortality was determined to be 5.453, yielding a sensitivity of 61.5% and specificity of 60.3%.ConclusionElevated RAR (&gt; 6.07) was associated with all-cause mortality at 90-days and 360-days among critically ill patients with rheumatic diseases, serving as an independent risk factor for unfavorable prognosis.
Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection
Authors: Chen Chen , Parthasarathy Sairam , Leung Jacqueline M. , Wu Michelle J. , Drake Katherine A. , Ridaura Vanessa K. , Zisser Howard C. , Conrad William A. , Tapson Victor F. , Moy James N. , deFilippi Christopher R. , Rosas Ivan O. , Prabhakar Bellur S. , Basit Mujeeb , Salvatore Mirella , Krishnan Jerry A. , Kim Charles C. 
Published: October 2023

BackgroundThe understanding of Post-acute sequelae of SARS-CoV-2 infection (PASC) can be improved by longitudinal assessment of symptoms encompassing the acute illness period. To gain insight into the various disease trajectories of PASC, we assessed symptom evolution and clinical factors associated with the development of PASC over 3 months, starting with the acute illness period.MethodsWe conducted a prospective cohort study to identify parameters associated with PASC. We performed cluster and case control analyses of clinical data, including symptomatology collected over 3 months following infection.ResultsWe identified three phenotypic clusters associated with PASC that could be characterized as remittent, persistent, or incident based on the 3-month change in symptom number compared to study entry: remittent (median; min, max: −4; −17, 3), persistent (−2; −14, 7), or incident (4.5; −5, 17) (p = 0.041 remittent vs. persistent, p &lt; 0.001 remittent vs. incident, p &lt; 0.001 persistent vs. incident). Despite younger age and lower hospitalization rates, the incident phenotype had a greater number of symptoms (15; 8, 24) and a higher proportion of participants with PASC (63.2%) than the persistent (6; 2, 9 and 52.2%) or remittent clusters (1; 0, 6 and 18.7%). Systemic corticosteroid administration during acute infection was also associated with PASC at 3 months [OR (95% CI): 2.23 (1.14, 4.36)].ConclusionAn incident disease phenotype characterized by symptoms that were absent during acute illness and the observed association with high dose steroids during acute illness have potential critical implications for preventing PASC.
Case report: Success of allogeneic hematopoietic stem cell transplantation for refractory systemic-onset juvenile idiopathic arthritis
Authors: Beaufils Camille , Proulx Catherine , Blincoe Annaliesse , Teira Pierre , Bittencourt Henrique , Cellot Sonia , Duval Michel , Morin Marie-Paule , De Bruycker Jean Jacques , Couture Julie , Samaan Kathryn , Decaluwe Hélène , Kleiber Niina , El-Jalbout Ramy , Touzot Fabien , Haddad Elie , Barsalou Julie 
Published: October 2023

ObjectivesThis study reports cases of systemic-onset juvenile idiopathic arthritis (sJIA) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center and reviews published outcomes of allo-HSCT in sJIA.MethodsWe present a case report of two patients with sJIA who underwent allo-HSCT at a tertiary pediatric hospital. Each patient’s disease course and allo-HSCT protocol/outcome are described. Outcomes of published cases of allo-HSCT in sJIA were compared to our experience.ResultsTwo patients with sJIA had allo-HSCT. Both failed multiple lines of disease-modifying anti-rheumatic drugs and experienced severe disease/treatment-related complications. Despite post-HSCT complications, both recovered without sequelae. Five years post-HSCT, patient 1 is in complete remission (CR) and is off medications. Patient 2 was in CR until 11 months post-HSCT after which he developed three disease flares. At 4 years post-HSCT he is currently in CR on Adalimumab monotherapy. Engraftment was excellent with a donor chimerism of 100% for patient 1 and 93% for patient 2. In the literature, the outcome of allo-HSCT is reported in 13 sJIA patients. When merging those with our 2 patients, 1/15 patients died and 13/14 achieved CR, of which 12 are off medications (median [range] follow-up: 2.2 [0.2–7.0] years). Extended follow-up data on 11 of the 13 reported sJIA patients showed that an additional 3 patients flared at 3, 4, and 10 years post-HSCT.ConclusionWe report two patients with severe/refractory sJIA who underwent successful allo-HSCT and achieved CR. Allo-HSCT is a potential curative option for severe/refractory sJIA. It should be considered only after failure of conventional sJIA treatments and when an HLA-matched donor is available in order to lower transplant-related mortality. The outcomes of reported sJIA patients who received allo-HSCT are encouraging but long-term follow-up data are needed to better characterized the risk–benefit ratio of this procedure.
Application of intraarterial superselective indocyanine green angiography in bypass surgery for adult moyamoya disease
Authors: Ni Haojin , Wu Yiwen , Zhou Chenhui , Li Xianru , Zhou Shengjun , Lan Wenting , Zhang Zhimeng , Huang Yi , Wang Haifeng , Lin Jinghui 
Published: October 2023

BackgroundExtracranial-intracranial (EC-IC) bypass surgery is the main treatment approach to moyamoya disease, and an accurate assessment of the patency of anastomosis is critical for successful surgery. So far, the most common way to do this is the intraoperative intravenous indocyanine green (ICG) video-angiography. Intra-arterial ICG-VA has been applied to treat peripheral cerebral aneurysms, spinal arteriovenous fistulas, and dural arteriovenous fistulas, but few reports have concerned the use of arterial injection of ICG to evaluate anastomotic patency. This research aims to explore the feasibility and effects of catheter-guided superficial temporal artery injection of ICG in the evaluation of anastomotic patency after bypass surgery.MethodsIn this study, 20 patients with moyamoya disease or syndrome who underwent bypass surgery were divided into two groups, one who received intravenous ICG angiography and the other who received intra-arterial ICG angiography, to compare the two injection methods for vascular anastomosis patency. We conducted conventional intraoperative digital subtraction angiography (DSA) in a hybrid operating room during extracranial-intracranial (EC-IC) bypass surgery, including the additional step of injecting ICG into the main trunk of the superficial temporal artery (STA) through a catheter.ResultsIntra-arterial injection of indocyanine green video-angiography (ICG-VA) indicated good patency of the vascular anastomosis when compared with conventional digital subtraction angiography (DSA) and intravenous ICG-VA, confirming the feasibility of using the arterial injection of ICG for assessing anastomotic patency. And intra-arterial ICG-VA results in faster visualization than intravenous ICG-VA (p &lt; 0.05). Besides, ICG-VA through arterial injection provided valuable information on the vascular blood flow direction after the bypass surgery, and allowed for visual inspection of the range of cortical brain supply from the superficial temporal artery and venous return from the cortex. Moreover, arterial injection of ICG offered a rapid dye washout effect, reducing the repeat imaging time.ConclusionThis study indicates that intra-arterial ICG-VA has good effects in observing the direction of blood flow in blood vessels and the range of cortical brain supply from the STA, which reflects blood flow near the anastomosis and provides additional information that may allow the postoperative prediction of cerebral hyperperfusion syndrome. However, the procedure of intra-arterial ICG-VA is relatively complicated compared to intravenous ICG-VA.