bluuebunny/crossref_metadata_2025 huggingface dataset:
Indications and outcomes of intraocular Lens Exchange among pseudophakic eyes in a Tertiary Referral Center
Authors: Jafarinasab Mohammadreza , Kalantarion Masomeh , Hooshmandi Sadid , Hassanpour Kiana , Najdi Danial , Kheiri Bahareh , Sabbaghi Hamideh
Published: March 2023

Purpose

To determine the indications and surgical outcomes of intraocular lens (IOL) exchange in pseudophakic patients at Labbafinejad Tertiary Referral Center between 2014 and 2019.

Methods

In this retrospective interventional case series, the medical records of 193 patients with a history of IOL exchange were reviewed. Preoperative data, including clinical characteristics, indications of the first and second IOL implantation, intra- and postoperative complications due to IOL exchange, and the pre-and postoperative refractive error and best-corrected visual acuity (BCVA) were considered the outcome measures in this study. All postoperative data were analyzed at least six months after follow-up.

Results

The mean age of our participants was 59.13 ± 20.97 years old at the time of the IOL exchange, with a male percentage of 63.2%. The mean follow-up after the IOL exchange was 15.72 ± 16.28 months. The main indications of IOL exchange were IOL decentration (50.3%), corneal decompensation (30.6%), and residual refractive errors (8.3%). 57.10% of patients with the postoperative spherical equivalent at -2.00 diopter (D) to + 2.00D. The mean best-corrected visual acuity was 0.82 ± 0.76 LogMAR before the IOL exchange and was improved to 0.73 ± 0.79 LogMAR after the surgery. Corneal decompensation (6.2%), glaucoma (4.7%), retinal detachment (4.1%), cystoid macular edema (2.1%), and uveitis (1%) were found as the postoperative complications. There was only one case with suprachoroidal hemorrhage during IOL exchange.

Conclusions

IOL decentration followed by corneal decompensation was the most common indication of IOL exchange. After IOL exchange, the most complications during follow-up were corneal decompensation, glaucoma, retinal detachment, and cystoid macular edema.
The subjective controllability of exotropia and its effect on surgical outcomes in patients with intermittent exotropia
Authors: Kim Mirae , Kim Hong Kyun , Kim Won Jae
Published: March 2023

Background/aims

We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability.

Methods

We reviewed the medical records of patients aged 6–18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient’s subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near.

Results

Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p < 0.001). The mean control scores of patients with controllability (distance: 1.9, near: 1.5) were lower compared with patients without controllability (distance: 3.0, near: 2.2), reflecting a better level of control. Patients with controllability had a better surgical outcome than those without controllability, as analyzed by log-rank test (p < 0.001). Larger preoperative ocular exodeviation at distance (hazard ratio [HR] = 1.083, confidence interval [CI] = 1.018–1.151, p = 0.012) and near (HR = 1.102, CI = 1.037–1.172, p = 0.002) were significantly related to recurrence in patients with controllability.

Conclusions

Patients with controllability showed better surgical outcomes, later exotropia onset, and better level of control than patients without controllability. Preoperative ocular exodeviation was a significant factor influencing favorable outcomes in patients with controllable exotropia.
Factors associated with public awareness of the relationship between alcohol use and breast cancer risk
Authors: Doyle Anne , O’Dwyer Claire , Mongan Deirdre , Millar Seán R. , Galvin Brian
Published: March 2023

Background

Public awareness of the carcinogenic effects of alcohol is low, particularly the association between alcohol use and the risk of developing breast cancer. Breast cancer is the third most common cancer in Ireland and alcohol use remains high. This study examined factors related to awareness of the association between alcohol use and breast cancer risk.

Methods

Using data from Wave 2 of the national Healthy Ireland Survey, a representative sample of 7,498 Irish adults aged 15 + years, descriptive and logistic regression analyses were conducted to investigate relationships between demographic characteristics, type of drinker and awareness of breast cancer risk.

Results

A low level of awareness of the risk of alcohol use (drinking more than the recommended low–risk limit) associated with breast cancer was found, with just 21% of respondents correctly identifying the relationship. Multivariable regression analyses found that factors most strongly associated with awareness were sex (female), middle age (45—54 years) and higher educational levels.

Conclusion

As breast cancer is a prevalent disease among women in Ireland, it is essential that the public, in particular women who drink, are made aware of this association. Public health messages that highlight the health risks associated with alcohol use, and which target individuals with lower educational levels, are warranted.
Implementation fidelity to a behavioral diabetes prevention intervention in two New York City safety net primary care practices
Authors: Gupta Avni , Hu Jiyuan , Huang Shengnan , Diaz Laura , Gore Radhika , Levy Natalie , Bergman Michael , Tanner Michael , Sherman Scott E. , Islam Nadia , Schwartz Mark D.
Published: March 2023

Background

It is critical to assess implementation fidelity of evidence-based interventions and factors moderating fidelity, to understand the reasons for their success or failure. However, fidelity and fidelity moderators are seldom systematically reported. The study objective was to conduct a concurrent implementation fidelity evaluation and examine fidelity moderators of CHORD (Community Health Outreach to Reduce Diabetes), a pragmatic, cluster-randomized, controlled trial to test the impact of a Community Health Workers (CHW)-led health coaching intervention to prevent incident type 2 Diabetes Mellitus in New York (NY).

Methods

We applied the Conceptual Framework for Implementation Fidelity to assess implementation fidelity and factors moderating it across the four core intervention components: patient goal setting, education topic coaching, primary care (PC) visits, and referrals to address social determinants of health (SDH), using descriptive statistics and regression models. PC patients with prediabetes receiving care from safety-net patient-centered medical homes (PCMHs) at either, VA NY Harbor or at Bellevue Hospital (BH) were eligible to be randomized into the CHW-led CHORD intervention or usual care. Among 559 patients randomized and enrolled in the intervention group, 79.4% completed the intake survey and were included in the analytic sample for fidelity assessment. Fidelity was measured as coverage, content adherence and frequency of each core component, and the moderators assessed were implementation site and patient activation measure.

Results

Content adherence was high for three components with nearly 80.0% of patients setting ≥ 1 goal, having ≥ 1 PC visit and receiving ≥ 1 education session. Only 45.0% patients received ≥ 1 SDH referral. After adjusting for patient gender, language, race, ethnicity, and age, the implementation site moderated adherence to goal setting (77.4% BH vs. 87.7% VA), educational coaching (78.9% BH vs. 88.3% VA), number of successful CHW-patient encounters (6 BH vs 4 VA) and percent of patients receiving all four components (41.1% BH vs. 25.7% VA).

Conclusions

The fidelity to the four CHORD intervention components differed between the two implementation sites, demonstrating the challenges in implementing complex evidence-based interventions in different settings. Our findings underscore the importance of measuring implementation fidelity in contextualizing the outcomes of randomized trials of complex multi-site behavioral interventions.

Trial registration

The trial was registered with ClinicalTrials.gov on 30/12/2016 and the registration number is NCT03006666.
Effect of preoperative dynamic cervical sagittal alignment on the loss of cervical lordosis after laminoplasty
Authors: Liu Chengxin , Shi Bin , Wang Wei , Li Xiangyu , Lu Shibao
Published: March 2023

Purpose

Cervical laminoplasty (CLP) is a developed surgical procedure for the treatment of cervical spondylotic myelopathy (CSM), but only a few of those studies focus on preoperative dynamic cervical sagittal alignment and the study of different degrees of loss of cervical lordosis (LCL) is lacking. This study aimed to analyze patients who underwent CLP to investigate the effect of cervical extension and flexion function on different degrees of LCL.

Methods

In this retrospective case–control study, we analyzed 79 patients who underwent CLP for CSM between January 2019 and December 2020. We measured the cervical sagittal alignment parameters on lateral radiographs (neutral, flexion, and extension positions) and used Japanese Orthopedic Association (JOA) score to assess clinical outcomes. We defined the extension ratio (EXR) as 100 × Ext ROM (cervical range of extension)/ROM (cervical range of motion). We observed the relationships between collected variables (demographic and radiological variables) and LCL. Patients were classified into the following three groups according to the LCL: stability group: (LCL ≤ 5°); mild loss group (5° < LCL ≤ 10°); and severe loss group (LCL > 10°). We compared the differences of collected variables (demographic, surgical and radiological variables) among the three groups.

Results

Seventy-nine patients were enrolled (mean age 62.92 years; 51 men, 28 women) in the study. Among the three groups, cervical Ext ROM was the best in the stability group (p < 0.01). Compared with the stability group, range of flexion (Flex ROM) was significantly higher (p < 0.05) and EXR was significantly lower (p < 0.01) in the severe loss group. Compared with the severe loss group, JOA recovery rates were better (p < 0.01) in the stability group. Receiver-operating characteristic curve (ROC) analysis to predict LCL > 10° (area under the curve = 0.808, p < 0.001). The cutoff value for EXR was 16.80%, with sensitivity and specificity of 72.5% and 82.4%, respectively.

Conclusion

CLP should be carefully considered for patients with a preoperative low Ext ROM and high Flex ROM, as a significant kyphotic change is likely to develop after surgery. EXR is a useful and simple index to predict significant kyphotic changes.
Drivers for low-value imaging: a qualitative study of stakeholders’ perspectives in Norway
Authors: Brandsæter Ingrid Øfsti , Andersen Eivind Richter , Hofmann Bjørn Morten , Kjelle Elin
Published: March 2023

Background

One kind of overutilization of diagnostic imaging is low-value imaging, i.e., imaging that does not lead to altered clinical pathways or improved health outcomes. Despite having well-documented extension and consequences, low-value imaging is still widespread. The objective of this study was to identify the drivers for the use of low-value imaging in the Norwegian healthcare services.

Methods

We conducted individual, semi-structured interviews among representatives from the health authorities, general practitioners, specialists working in hospitals, radiologists, radiographers, and managers of imaging departments. Data analysis was carried out in line with framework analysis consisting of five steps: Familiarization, indexing, charting, mapping, and interpretation.

Results

The analysis included 27 participants and resulted in two themes. The stakeholders identified drivers in the healthcare system and in the interaction between radiologists, referrers, and patients. The identified drivers were categorized in sub-themes, such as organization, communication, competence, expectations, defensive medicine, roles and responsibilities, and referral quality and time constraints. The drivers interact with each other and may strengthen the effect of other drivers.

Conclusions

Several drivers for low-value imaging in Norway were identified at all levels of the healthcare system. The drivers work simultaneously and synergistically. To free resources for high-value imaging, drivers should be targeted by appropriate measures at several levels to reduce low-value imaging.
Identifying potential biomarkers for the diagnosis and treatment of IgA nephropathy based on bioinformatics analysis
Authors: Li Xiaohui , Zeng Mengru , Liu Jialu , Zhang Shumin , Liu Yifei , Zhao Yuee , Wei Cong , Yang Kexin , Huang Ying , Zhang Lei , Xiao Li
Published: March 2023

Background

IgA nephropathy (IgAN) has become the leading cause of end-stage renal disease in young adults. Nevertheless, the current diagnosis exclusively relies on invasive renal biopsy, and specific treatment is deficient. Thus, our study aims to identify potential crucial genes, thereby providing novel biomarkers for the diagnosis and therapy of IgAN.

Methods

Three microarray datasets were downloaded from GEO official website. Differentially expressed genes (DEGs) were identified by limma package. GO and KEGG analysis were conducted. Tissue/organ-specific DEGs were distinguished via BioGPS. GSEA was utilized to elucidate the predominant enrichment pathways. The PPI network of DEGs was established, and hub genes were mined through Cytoscape. The CTD database was employed to determine the association between hub genes and IgAN. Infiltrating immune cells and their relationship to hub genes were evaluated based on CIBERSORT. Furthermore, the diagnostic effectiveness of hub markers was subsequently predicted using the ROC curves. The CMap database was applied to investigate potential therapeutic drugs. The expression level and diagnostic accuracy of TYROBP was validated in the cell model of IgAN and different renal pathologies.

Results

A total of 113 DEGs were screened, which were mostly enriched in peptidase regulator activity, regulation of cytokine production, and collagen-containing extracellular matrix. Among these DEGs, 67 genes manifested pronounced tissue and organ specificity. GSEA analysis revealed that the most significant enriched gene sets were involved in proteasome pathway. Ten hub genes (KNG1, FN1, ALB, PLG, IGF1, EGF, HRG, TYROBP, CSF1R, and ITGB2) were recognized. CTD showed a close connection between ALB, IGF, FN1 and IgAN. Immune infiltration analysis elucidated that IGF1, EGF, HRG, FN1, ITGB2, and TYROBP were closely associated with infiltrating immune cells. ROC curves reflected that all hub genes, especially TYROBP, exhibited a good diagnostic value for IgAN. Verteporfin, moxonidine, and procaine were the most significant three therapeutic drugs. Further exploration proved that TYROBP was not only highly expressed in IgAN, but exhibited high specificity for the diagnosis of IgAN.

Conclusions

This study may offer novel insights into the mechanisms involved in IgAN occurrence and progression and the selection of diagnostic markers and therapeutic targets for IgAN.
Modulation of pulmonary immune function by inhaled cannabis products and consequences for lung disease
Authors: Preteroti Matthew , Wilson Emily T. , Eidelman David H. , Baglole Carolyn J.
Published: March 2023

The lungs, in addition to participating in gas exchange, represent the first line of defense against inhaled pathogens and respiratory toxicants. Cells lining the airways and alveoli include epithelial cells and alveolar macrophages, the latter being resident innate immune cells important in surfactant recycling, protection against bacterial invasion and modulation of lung immune homeostasis. Environmental exposure to toxicants found in cigarette smoke, air pollution and cannabis can alter the number and function of immune cells in the lungs. Cannabis (marijuana) is a plant-derived product that is typically inhaled in the form of smoke from a joint. However, alternative delivery methods such as vaping, which heats the plant without combustion, are becoming more common. Cannabis use has increased in recent years, coinciding with more countries legalizing cannabis for both recreational and medicinal purposes. Cannabis may have numerous health benefits owing to the presence of cannabinoids that dampen immune function and therefore tame inflammation that is associated with chronic diseases such as arthritis. The health effects that could come with cannabis use remain poorly understood, particularly inhaled cannabis products that may directly impact the pulmonary immune system. Herein, we first describe the bioactive phytochemicals present in cannabis, with an emphasis on cannabinoids and their ability to interact with the endocannabinoid system. We also review the current state-of-knowledge as to how inhaled cannabis/cannabinoids can shape immune response in the lungs and discuss the potential consequences of altered pulmonary immunity. Overall, more research is needed to understand how cannabis inhalation shapes the pulmonary immune response to balance physiological and beneficial responses with potential deleterious consequences on the lungs.
Use of a pulmosphere model to evaluate drug antifibrotic responses in interstitial lung diseases
Authors: Dsouza Kevin G. , Surolia Ranu , Kulkarni Tejaswini , Li Fu Jun , Singh Pooja , Zeng Huaxiu , Stephens Crystal , Kumar Abhishek , Wang Zheng , Antony Veena B.
Published: March 2023

Background

Interstitial lung diseases (ILD) encompass a heterogenous group of diffuse parenchymal lung disorders characterized by variable degrees of inflammation and fibrosis. Pretherapeutic clinical testing models for such diseases can serve as a platform to test and develop effective therapeutic strategies. In this study, we developed patient derived 3D organoid model to recapitulate the disease process of ILDs. We characterized the inherent property of invasiveness in this model and tested for antifibrotic responses with an aim to develop a potential platform for personalized medicine in ILDs.

Methods

In this prospective study, 23 patients with ILD were recruited and underwent lung biopsy. 3D organoid-based models (pulmospheres) were developed from the lung biopsy tissues. Pulmonary functioning testing and other relevant clinical parameters were collected at the time of enrollment and follow up visits. The patient derived pulmospheres were compared to normal control pulmospheres obtained from 9 explant lung donor samples. These pulmospheres were characterized by their invasive capabilities and responsiveness to the antifibrotic drugs, pirfenidone and nintedanib.

Results

Invasiveness of the pulmospheres was measured by the zone of invasiveness percentage (ZOI%). The ILD pulmospheres (n = 23) had a higher ZOI% as compared to control pulmospheres (n = 9) (516.2 ± 115.6 versus 54.63 ± 19.6 respectively. ILD pulmospheres were responsive to pirfenidone in 12 of the 23 patients (52%) and responsive to nintedanib in all 23 patients (100%). Pirfenidone was noted to be selectively responsive in patients with connective tissue disease related ILD (CTD-ILD) at low doses. There was no correlation between the basal pulmosphere invasiveness, response to antifibrotics, and FVC change (Δ FVC).

Conclusions

The 3D pulmosphere model demonstrates invasiveness which is unique to each individual subject and is greater in ILD pulmospheres as compared to controls. This property can be utilized to test responses to drugs such as antifibrotics. The 3D pulmosphere model could serve as a platform for the development of personalized approaches to therapeutics and drug development in ILDs and potentially other chronic lung diseases.
PET-PCR reveals low parasitaemia and submicroscopic malarial infections in Honduran Moskitia
Authors: Matamoros Gabriela , Escobar Denis , Pinto Alejandra , Serrano Delmy , Ksandrová Eliška , Grimaldi Nicole , Juárez-Fontecha Gabriel , Moncada Marcela , Valdivia Hugo O. , Fontecha Gustavo
Published: March 2023

Background

Malaria remains a main parasitic disease of humans. Although the largest number of cases is reported in the African region, there are still endemic foci in the Americas. Central America reported 36,000 malaria cases in 2020, which represents 5.5% of cases in the Americas and 0.015% of cases globally. Most malaria infections in Central America are reported in La Moskitia, shared by Honduras and Nicaragua. In the Honduran Moskitia, less than 800 cases were registered in 2020, considering it an area of low endemicity. In low endemicity settings, the number of submicroscopic and asymptomatic infections tends to increase, leaving many cases undetected and untreated. These reservoirs challenge national malaria elimination programmes. This study aimed to assess the diagnostic performance of Light Microscopy (LM), a nested PCR test and a photoinduced electron transfer polymerase chain reaction (PET-PCR) in a population of febrile patients from La Moskitia.

Methods

A total of 309 febrile participants were recruited using a passive surveillance approach at the Puerto Lempira hospital. Blood samples were analysed by LM, nested PCR, and PET-PCR. Diagnostic performance including sensitivity, specificity, negative and positive predictive values, kappa index, accuracy, and ROC analysis was evaluated. The parasitaemia of the positive samples was quantified by both LM and PET-PCR.

Results

The overall prevalence of malaria was 19.1% by LM, 27.8% by nPCR, and 31.1% by PET-PCR. The sensitivity of LM was 67.4% compared to nPCR, and the sensitivity of LM and nPCR was 59.6% and 80.8%, respectively, compared to PET-PCR. LM showed a kappa index of 0.67, with a moderate level of agreement. Forty positive cases by PET-PCR were not detected by LM.

Conclusions

This study demonstrated that LM is unable to detect parasitaemia at low levels and that there is a high degree of submicroscopic infections in the Honduran Moskitia.
Extracellular vesicles from Lactobacillus druckerii inhibit hypertrophic scar fibrosis
Authors: Han Fu , Wang Kejia , Shen Kuo , Wang Jing , Han Shichao , Hu Dahai , Wu Gaofeng
Published: March 2023

Background

Hypertrophic scars (HS) affect millions of people each year and require better treatment strategies. Bacterial extracellular vesicles (EVs) are advantaged by low cost and high yield which was commonly used in the treatment of diseases. Here, we investigated the therapeutic efficacy of EVs obtained from Lactobacillus druckerii in hypertrophic scar. In vitro, the effects of Lactobacillus druckerii-derived EVs (LDEVs) on Collagen I/III and α-SMA in fibroblasts obtained from HS. In vivo, a scleroderma mouse model was used to investigate the effects of LDEVs on fibrosis. The impact of LDEVs on excisional wound healing was explored. The different proteins between PBS and LDEVs treated fibroblasts derived from hypertrophic scar were studied by untargeted proteomic analysis.

Results

In vitro, LDEVs treatment significantly inhibited the expression of Collagen I/III and α-SMA and cell proliferation of fibroblasts derived from HS. In vivo, LDEVs withdrawn the hypertrophic scar formation in scleroderma mouse model and decreased the expression of α-SMA. LDEVs promoted the proliferation of skin cells, new blood vessel formation and wound healing in excisional wound healing mice model. Moreover, proteomics has shown that LDEVs inhibit hypertrophic scar fibrosis through multiple pathways.

Conclusions

Our results indicated that Lactobacillus druckerii-derived EVs has the potential application in the treatment of hypertrophic scars and any other fibrosis diseases.

Graphical Abstract
Fibronectin-targeting and metalloproteinase-activatable smart imaging probe for fluorescence imaging and image-guided surgery of breast cancer
Authors: Cheng Zhongquan , Jin Yushen , Li Jiaqian , Shi Guangyuan , Yu Leyi , Shao Bing , Tian Jie , Du Yang , Yuan Zhu
Published: March 2023

Residual lesions in the tumor bed have been a challenge for conventional white-light breast-conserving surgery. Meanwhile, lung micro-metastasis also requires improved detection methods. Intraoperative accurate identification and elimination of microscopic cancer can improve surgery prognosis. In this study, a smart fibronectin-targeting and metalloproteinase-activatable imaging probe CREKA-GK8-QC is developed. CREKA-GK8-QC possesses an average diameter of 21.7 ± 2.5 nm, excellent MMP-9 protein responsiveness and no obvious cytotoxicity. In vivo experiments demonstrate that NIR-I fluorescence imaging of CREKA-GK8-QC precisely detects orthotopic breast cancer and micro-metastatic lesions (nearly 1 mm) of lungs with excellent imaging contrast ratio and spatial resolution. More notably, fluorescence image-guided surgery facilitates complete resection and avoids residual lesions in the tumor bed, improving survival outcomes. We envision that our newly developed imaging probe shows superior capacity for specific and sensitive targeted imaging, as well as providing guidance for accurate surgical resection of breast cancer.

Graphical Abstract
Mesenchymal stem cells can prevent or promote the progression of colon cancer based on their timing of administration
Authors: Hu Weiqian , Wang Weijun , Jiang Xin , Wang Zeyu , Lin Rong
Published: March 2023

Background

Mesenchymal stem cell (MSC) therapy has been shown to have some therapeutic effects in rodent models and patients with IBD; however, its role in colon tumor models is controversial. In this study, the potential role and mechanisms of bone marrow-derived MSCs (BM-MSCs) in colitis-associated colon cancer (CAC) were investigated.

Methods

The CAC mouse model was established with azoxymethane (AOM) and dextran sulfate sodium (DSS). The mice were administered an intraperitoneal injection of MSCs once weekly for different periods. The progression of CAC and the cytokine expression in tissues was assessed. Immunofluorescence staining was used to detect MSCs localization. Levels of immune cells in the spleen and lamina propria of the colon were detected using flow cytometry. A co-culture of MSCs and naïve T cells was performed to determine the effect of MSCs on naïve T cell differentiation.

Results

Early administration of MSCs inhibited the occurrence of CAC, while late administration promoted the progression of CAC. The inhibitory effect of early injection in mice was characterized by the expression of inflammatory cytokines in colon tissue was decreased, and induction of T regulatory cells (Tregs) infiltration via TGF-β. The promotive effect of late injection was characterized by a shift of T helper (Th) 1/Th2 immune balance toward a Th2 phenotype through IL-4 secretion. IL-12 can reverse this shift to Th2 accumulation in mice.

Conclusion

MSCs can curb the progression of colon cancer by inducing Treg accumulation via TGF-β at the early stage of inflammatory transformation but promote the progression of colon cancer by inducing a shift in Th1/Th2 immune balance to Th2 through IL-4 secretion at the late stage. And the immune balance of Th1/Th2 influenced by MSCs could be reversed by IL-12.
M1 polarization enhances the antitumor activity of chimeric antigen receptor macrophages in solid tumors
Authors: Huo Yi , Zhang Han , Sa Longqi , Zheng Wenjing , He Yang , Lyu Haohan , Sun Mengjie , Zhang Lingling , Shan Lequn , Yang Angang , Wang Tao
Published: March 2023

Background

Chimeric antigen receptor macrophage (CAR-M) therapy is a novel cancer immunotherapy approach that integrates CAR structure and macrophage functions. CAR-M therapy has shown unique and impressive antitumor effects in immunotherapy for solid tumors. However, the polarization state of macrophages can affect the antitumor effect of CAR-M. We hypothesized that the antitumor activity of CAR-Ms may be further improved after inducing M1-type polarization.

Methods

In this report, we constructed a novel HER2-targeting CAR-M, which was composed of humanized anti-HER2 scFv, CD28 hinge region and FcγRI transmembrane domain and intracellular domain. Phagocytosis, tumor-killing capacities, and cytokine release of CAR-Ms were detected with or without M1-polarization pretreatment. Several syngeneic tumor models were used to monitor the in vivo antitumor activity of M1-polarized CAR-Ms.

Results

After polarization with LPS combined with interferon-γ in vitro, we found that the phagocytic and tumor-killing capacities of CAR-Ms against target cells were significantly enhanced. The expression of costimulatory molecules and proinflammatory cytokines was also significantly increased after polarization. By establishing several syngeneic tumor models in vivo, we also demonstrated that infusing polarized M1-type CAR-Ms could effectively suppress tumor progression and prolong the survival of tumor-bearing mice with enhanced cytotoxicity.

Conclusions

We demonstrated that our novel CAR-M can effectively eliminate HER2-positive tumor cells both in vitro and in vivo, and M1 polarization significantly enhanced the antitumor ability of CAR-M, resulting in a stronger therapeutic effect in solid cancer immunotherapy.
Retraction Note: Tripartite motif-containing 14 (TRIM14) promotes epithelial-mesenchymal transition via ZEB2 in glioblastoma cells
Authors: Feng Shuang , Cai Xiaomin , Li Yangyang , Jian Xiaoguang , Zhang Linxin , Li Bin
Published: March 2023

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-019-1070-x.
Chemoembolization combined radiofrequency ablation vs. chemoembolization alone for treatment of beyond the Milan criteria viable hepatocellular carcinoma (CERFA): study protocol for a randomized controlled trial
Authors: Lee Soon Kyu , Yang Hyun , Kwon Jung Hyun , Shim Dong Jae , Kim Doyoung , Nam Soon Woo , Yoo Sun Hong , Bae Si Hyun , Lee Ahlim , Lee Young Joon , Jeon Changho , Jang Jeong Won , Sung Pil Soo , Chun Ho Jong , Kim Su Ho , Choi Joon-Il , Oh Jung Suk , Yang Yun-Jung
Published: March 2023

Background

Many previous studies evaluated a combination of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for treating early hepatocellular carcinoma (HCC); however, studies evaluating combination therapy for beyond-the-Milan criteria HCC are scarce.

Methods

A total of 120 patients with beyond-the-Milan criteria HCC who have viable tumour after first TACE will be enrolled in this multi-institutional, parallel, pragmatic, randomized controlled trial. Patients with metastasis, vascular invasion, or a sum of tumour diameter > 8 cm will be excluded. Eligible patients will be randomly assigned to combination TACE and RFA therapy or TACE monotherapy groups. Patients in the combination therapy group will receive a second TACE and subsequent RFA at the viable tumour. Patients in the TACE monotherapy group will receive only second TACE. Patients in both groups will undergo magnetic resonance imaging 4–6 weeks after second TACE. The primary endpoint is 1-month tumour response, and secondary endpoints are progression-free survival, overall response rate, number of treatments until CR, overall survival, and change in liver function.

Discussion

Although TACE can be used to treat intermediate-stage HCC, it is difficult to achieve CR by first TACE in most intermediate-stage patients. Recent studies show a survival advantage of combination therapy over monotherapy. However, most studies evaluating combination therapy included patients with a single tumour sized < 5 cm, and no studies included patients with intermediate-stage but more advanced (i.e., beyond-the-Milan criteria) HCC. This study will evaluate the efficacy of combined TACE and RFA therapy for patients with advanced HCC within the intermediate stage.

Trial registration

Clinical Research Information Service (CRiS) KCT0006483.
Rational and irrational vaccine hesitancy
Authors: Green Manfred S.
Published: March 2023

In the paper published recently in this journal, Kumar et al. explained why the key to improved COVID-19 vaccine uptake is to understand societal reactions leading to vaccine hesitancy. They conclude that communications strategies should be tailored to the different phases of vaccine hesitancy. However, within the theoretical framework provided in their paper, vaccine hesitancy should be recognized as having both rational and irrational components. Rational vaccine hesitancy is a natural result of the inherent uncertainties in the potential impact of vaccines in controlling the pandemic. In general, irrational hesitancy is based on baseless information obtained from hearsay and deliberately false information. Risk communication should address both with transparent, evidence-based information. Rational concerns can be allayed by sharing the process in which dilemmas and uncertainties are dealt with by the health authorities. Messages on irrational concerns need to address head on the sources spreading unscientific and unsound information. In both cases, there is a need to develop risk communication that restores trust in the health authorities.
Multiple founding paternal lineages inferred from the newly-developed 639-plex Y-SNP panel suggested the complex admixture and migration history of Chinese people
Authors: He Guanglin , Wang Mengge , Miao Lei , Chen Jing , Zhao Jie , Sun Qiuxia , Duan Shuhan , Wang Zhiyong , Xu Xiaofei , Sun Yuntao , Liu Yan , Liu Jing , Wang Zheng , Wei Lanhai , Liu Chao , Ye Jian , Wang Le
Published: March 2023

Background

Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity.

Results

Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history.

Conclusions

Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.
The Rapunzel syndrome: a hairy tale
Authors: Schuler Luca , Hodel Martina , Stieger Claudia
Published: March 2023

Background

Trichobezoars are a rare medical condition, often requiring a surgical approach and commonly associated with an underlying psychiatric disorder. The Rapunzel syndrome is a rare variant of trichobezoar in the stomach extending from the stomach into the small intestine causing a bowel obstruction.

Case presentation

In this case report, the clinical presentation, diagnostic approach, and surgical removal of a large-size bezoar (Rapunzel syndrome) in a young and otherwise healthy female is described. Different surgical strategies are discussed. Psychiatric exploration gives an insight on development of trichophagia ultimately leading to the forming of the trichobezoar.

Conclusions

This brief report sheds light on the importance of the collective mind of a multidisciplinary team preventing a potentially fatal outcome.
Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition
Authors: Zhao Pengxiang , Dang Zheng , Liu Mengyu , Guo Dazhi , Luo Ruiliu , Zhang Mingzi , Xie Fei , Zhang Xujuan , Wang Youbin , Pan Shuyi , Ma Xuemei
Published: March 2023

Background

Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H2 functions in wound healing remains unknown, especially for the link between H2 and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation.

Methods

Here, we established a cutaneous aseptic wound model and applied a high concentration of H2 (66% H2) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging.

Results

We revealed that a high concentration of H2 (66% H2) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H2 group. ECM components early (3 days post-wounding) deposition were found in the H2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H2 accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling.

Conclusion

We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H2 and ECM deposition and EpSCs activation. These H2-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.
Antioxidant properties and cytotoxic effects of Oxalis corniculata on human Hepatocarcinoma (Hep-G2) cell line: an in vitro and in silico evaluation
Authors: Gudasi Sachin , Gharge Shankar , Koli Rahul , Patil Kalpana
Published: March 2023

Background

Oxalis corniculata is a well-known medicinal plant used in folk medicine for the management of many diseases. The aim is to determine the physico-chemical properties, microscopic study, phytochemical properties, in-silico, in-vitro antioxidant and anticancer activity on human Hepatocarcinoma (Hep-G2) cell line of O. corniculata plant extract.

Results

Microscopical study reaveals that presence of pericyclic fibres, starch gains, trichomes etc, and phytochemical screening is carried to find out secondary metabolites. The molecular docking study concluded that some of the phytocompounds showed inhibition of epidermal growth factor receptor tyrosine kinase domain (PDB ID: 1M17) inhibitor. Furthermore, ADMET and drug likeness study hints some of phytocompounds may act as lead for anticancer drug discovery and development. Among selected phytocompounds, compound apigenin possesses − 7.90 kcal/mol as compared to standard drug doxorubicin possesses − 7.63 kcal/mol against the epidermal growth factor receptor tyrosine kinase. The plant extract shown antioxidant activities based on the different tests were performed. The hydroalcoholic plant extracts were found to be selectively cytotoxic in vitro to human Hepatocarcinoma (Hep-G2) cell line with IC50values 34.494 ± 0.42 µg/ml and EAF showed at IC50 value 30.245 ± 0.58 µg/ml of the cells were inhibited at the concentration of 50 µg/ml as compared with standard doxorubicin at IC50 value 24.8939 ± 0.25 µg/ml, respectively.

Conclusion

The present study concluded that O. corniculata possesses potential antioxidant and cytotoxic properties based upon the computer aided drug design models and in-vitro activity.
2.5D magnetization vector inversion of vector magnetic data
Authors: Xie Rukuan , Xiong Shengqing , Duan Shuling , Luo Yao , Wang Ping
Published: March 2023

The remanent magnetization vector records the earth’s magnetic field at the time of the formation process of magnetized geologic units. Recovering the magnetization vector from magnetic data can provide extra information regarding the source properties to differentiate geologic units and reveal thermal evolution or tectonic history. To provide this information, the magnetization vector inversion (MVI) method has been used to invert for the magnetization vector. The MVI usually works with the total-field magnetic anomaly magnitude ([Formula: see text]). The magnitude is an approximation of the projection of the magnetic anomaly vector onto the normal geomagnetic field. For highly magnetic sources, the approximation error of [Formula: see text] cannot be ignored. However, this approximation error can be avoided by using measured vector magnetic data. To reduce the severe ambiguity of 3D MVI, specific constraints based on extra prior information are usually used. For 2D or 2.5D cases, MVI only inverts for magnitude and inclination of the magnetization, which encounters less ambiguity than that of the 3D case. We have developed a 2.5D MVI approach using vector magnetic data. To reduce the divergent and smooth trends in magnetization vectors recovered by MVI in the Cartesian framework, we make use of a focusing constraint method to improve the imaging. The inversion results of synthetic data indicate that the method is able to recover magnetization magnitude and inclinations close to the true values and is fairly robust to inappropriate choice of the profile location and heading. Finally, the method is applied to the measured airborne vector magnetic data from the Qixin area of the East Tianshan Mountains in China. The distributions and directions of magnetization of the mafic-ultramafic rocks and linear structures are revealed, which provides the information for distinguishing geologic units and geologic differentiation.
Anomalous elastic properties of mudrocks bounding reservoirs with high concentrations of naturally occurring CO2
Authors: Sams Mark , Jayasangar Thivyaadarshini
Published: March 2023

Very high concentrations of CO2 have been encountered in solution as carbonic acid in hydrocarbon reservoirs in parts of the Greater Sarawak Basin, offshore Borneo, Malaysia. Concentrations can exceed 80%. Anomalous features in 3D seismic data also are found in areas with high CO2 concentrations. These features appear as halos around reservoirs, cutting across stratigraphy and indicating a hardening of the nonreservoir rocks within the envelope of the halo. These halos can extend for hundreds of meters above and below a reservoir. Elastic log data from wells that pass through and adjacent to these seismic anomalies indicate that mudrocks within the anomalies have higher densities and velocities than would be predicted from locally derived compaction trends. Combinable magnetic resonance measurements indicate that the anomalous properties are the result of lower-than-expected capillary-bound microporosities. It is proposed that carbonic acid in the reservoir fluids diffuses into the bounding rocks, causing a loss of porosity. The amount of porosity lost depends on the clay content of the mudrock and the initial level of compaction, with shallower, more clay-rich shales able to lose more porosity. The anomalous seismic signatures result from a sharp transition (over approximately 5 m) at the diagenetic front between normal and altered rocks. The alteration can significantly change the amplitude variation with offset response of the reservoirs and therefore the ability to correctly predict fluid phase and reservoir quality. No anomalies are observed when the concentration of CO2 in the reservoir is less than 10% but always present when CO2 exceeds 20%. Therefore, it is possible to map the general distribution of high CO2 concentration from seismic data. There is no indication that the scale, amplitude, or shape of the anomalies gives an indication of the concentration of CO2.
Lifting the cloche: Jeroen Bakkers interviews Didier Stainier
Authors: Stainier Didier Y. R. , Bakkers Jeroen
Published: March 2023

Didier Stainier is Director of the Department of Developmental Genetics at the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany. He became acquainted with the zebrafish model as a PhD student in Walter Gilbert's lab at Harvard, which motivated him to champion the use of this powerful model organism to study heart development as a postdoctoral fellow with Mark Fishman at Massachusetts General Hospital. Although his scientific focus has expanded significantly since then, zebrafish modelling and heart development and regeneration remain key topics in his research. The developmental biology and zebrafish modelling communities have embraced him as an inspiring mentor and advocate for basic research.

Jeroen Bakkers is a group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research and Professor of Molecular Cardiogenetics at the University Medical Center Utrecht, The Netherlands. Jeroen did hid PhD with Herman Spaink at Leiden University, The Netherlands. A short visit to Massachusetts Institute of Technology during his doctoral training introduced him to the zebrafish model, which he applied to his PhD project. Zebrafish development remained the focus of his career, including during his postdoctoral training in the lab of Matthias Hammerschmidt at the Max Planck Institute of Immunology and Epigenetics in Freiburg and in his own lab at the Hubrecht Institute, where his group uses this powerful model organism to investigate cardiac development, disease and regeneration.

Jeroen and Didier met up at a recent conference to talk about their shared interest in cardiac regeneration, a zebrafish mutant with a curious name and Didier's commitment to mentorship.