bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of antioxidant-rich Lactiplantibacillus plantarum inoculated alfalfa silage on rumen fermentation, antioxidant and immunity status, and mammary gland gene expression in dairy goats
Authors: Zhang Yixin , Usman Samaila , Li Qiang , Li Fuhou , Zhang Xia , Nussio Luiz Gustavo , Guo Xusheng
Published: January 2024

Background

Milk synthesis in lactating animals demands high energy metabolism, which results in an increased production of reactive oxygen metabolites (ROM) causing an imbalance between oxidants and antioxidants thereby inducing oxidative stress (OS) on the animals. To mitigate OS and postpartum disorders in dairy goats and gain insight into the impact of dietary choices on redox status during lactation, a feeding trial was conducted using alfalfa silage inoculated with a high-antioxidant strain of Lactiplantibacillus plantarum.

Methods

Twenty-four Guanzhong dairy goats (38.1 ± 1.20 kg) were randomly assigned to two dietary treatments: one containing silage inoculated with L. plantarum MTD/1 (RSMTD-1), and the other containing silage inoculated with high antioxidant activity L. plantarum 24-7 (ES24-7).

Results

ES24-7-inoculated silage exhibited better fermentation quality and antioxidant activity compared to RSMTD-1. The ES24-7 diet elevated the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in milk, serum, and feces of lactating goats (with the exception of T-AOC in milk). Additionally, the diet containing ES24-7 inoculated silage enhanced casein yield, milk free fatty acid (FFA) content, and vitamin A level in the goats’ milk. Furthermore, an increase of immunoglobulin (Ig)A, IgG, IgM, interleukin (IL)-4, and IL-10 concentrations were observed, coupled with a reduction in IL-1β, IL-2, IL-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α concentrations in the serum of lactating goats fed ES24-7. Higher concentrations of total volatile fatty acid (VFA), acetate, and propionate were observed in the rumen fluid of dairy goats fed ES24-7 inoculated silage. Moreover, the diet containing ES24-7 inoculated silage significantly upregulated the expression of nuclear factor erythroid 2 like 2 (NFE2L2), beta-carotene oxygenase 1 (BCO1), SOD1, SOD2, SOD3, GPX2, CAT, glutathione-disulfide reductase (GSR), and heme oxygenase 1 (HMOX1) genes in the mammary gland, while decreased the levels of NADPH oxidase 4 (NOX4), TNF, and interferon gamma (IFNG).

Conclusions

These findings indicated that feeding L. plantarum 24-7 inoculated alfalfa silage not only improved rumen fermentation and milk quality in lactating dairy goats but also boosted their immunity and antioxidant status by modulating the expression of several genes related to antioxidant and inflammation in the mammary gland.
Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs
Authors: Zhao Qi , Zong Hong , Zhu Pingping , Su Chang , Tang Wenxue , Chen Zhenzhen , Jin Shuiling
Published: January 2024

Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy has attracted increasing attention. Cancer stem cells (CSCs), a small subset of tumor cells with self-renewal and differentiation capacities, are resistant to traditional therapies such as radiotherapy and chemotherapy. Recently, CSCs have been proven to be the cells driving tumor relapse after immunotherapy. However, the mutual interactions between CSCs and cancer niche immune cells are largely uncharacterized. In this review, we focus on colorectal CSCs, CSC-immune cell interactions and CSC-based immunotherapy. Colorectal CSCs are characterized by robust expression of surface markers such as CD44, CD133 and Lgr5; hyperactivation of stemness-related signaling pathways, such as the Wnt/β-catenin, Hippo/Yap1, Jak/Stat and Notch pathways; and disordered epigenetic modifications, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA action. Moreover, colorectal CSCs express abnormal levels of immune-related genes such as MHC and immune checkpoint molecules and mutually interact with cancer niche cells in multiple tumorigenesis-related processes, including tumor initiation, maintenance, metastasis and drug resistance. To date, many therapies targeting CSCs have been evaluated, including monoclonal antibodies, antibody‒drug conjugates, bispecific antibodies, tumor vaccines adoptive cell therapy, and small molecule inhibitors. With the development of CSC-/niche-targeting technology, as well as the integration of multidisciplinary studies, novel therapies that eliminate CSCs and reverse their immunosuppressive microenvironment are expected to be developed for the treatment of solid tumors, including colorectal cancer.
ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway
Authors: Ding Yang , Ning Yumei , Kang Hui , Yuan Yuan , Lin Kun , Wang Chun , Yi Yun , He Jianghua , Li Lurao , He Xingxing , Chang Ying
Published: January 2024

Background

Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated.

Methods

The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2.

Results

ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/β-catenin pathway.

Conclusion

ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/β-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC.
Effects of simulated atmospheric nitrogen deposition on the bacterial community structure and diversity of four distinct biocolonization types on stone monuments: a case study of the Leshan Giant Buddha, a world heritage site
Authors: Chen Xuli , Song Huixing , Sun Bo , Yang Tianyu
Published: January 2024

Atmospheric nitrogen deposition may affect the biodeterioration process of stone monuments through direct and indirect pathways, but relevant studies are lacking. Therefore, taking the biologically colonized rocks around the Leshan Giant Buddha (World Heritage - Mixed Property) as the research objects, we studied the effects of multiple nitrogen addition levels (0, 9, 18, 36, 72 kg N hm-2 a-1; N0, N1; N2 ; N3; N4) on the bacterial community structure and soil nutrients on the surfaces of stones with four biocolonization types, including naked rock (NR), and lichen (LR), bryophyte (BS) and vascular plant (VS) colonization, to investigate the potential effect of atmospheric nitrogen deposition on the rock weathering of the Leshan Giant Buddha. The results demonstrated that nitrogen addition impacted soil carbon, nitrogen and phosphorus nutrients, as well as bacterial community structure and composition, but the responses to nitrogen input varied among different colonization types. Nitrogen fertilization promoted the accumulation of total organic carbon and total nitrogen in NR and LR, and increased the content of total phosphorus in VS. Bacterial α-diversity decreased with nitrogen addition in NR but increased with nitrogen addition in VS. Nitrogen addition significantly (R > 0.9, p < 0.01) changed the bacterial community composition in the four biocolonization types, and the changes were dominated by species replacement (contributed to 60.98%, 76.32%, 67.27% and 72.14% for bacterial diversity in NR, LR, BS and VS, respectively). Total nitrogen, dissolved organic nitrogen, dissolved organic nitrogen and total phosphorus were the most important ecological factors affecting bacterial community structure in NR, LR, BS and VS, respectively. Nitrogen addition enriched different bacterial taxa in the four biocolonization types. The results of this study provide basic data for the protection of stone monuments and the formulation of sustainable development strategies under a changing climate.
The feasibility of an exercise intervention after robotic-assisted radical cystectomy for urinary bladder cancer, prior to the CanMoRe trial
Authors: Porserud Andrea , Karlsson Patrik , Nygren-Bonnier Malin , Aly Markus , Hagströmer Maria
Published: January 2024

Background

Complications after radical cystectomy for urinary bladder cancer are common. Physical activity after surgery is thought to reduce complications. However, patients with urinary bladder cancer have low levels of physical activity, and interventions supporting physical exercise are needed. This study aimed to evaluate the feasibility of a physical exercise intervention in primary health care. One of the aims of the larger clinical trial will be to reduce complications.

Methods

Patients with urinary bladder cancer and who were scheduled for a robotic-assisted radical cystectomy were recruited from Karolinska University Hospital, between February and May 2019. The patients had to be mobile, understand Swedish, and live in Stockholm. The exercise programme was conducted at one primary health care setting over 12 weeks. The exercise programme included supervised aerobic and strengthening exercises, which were performed twice a week, as well as daily walks. Feasibility was measured with process feasibility, including eligibility criteria, adherence, and acceptability, and scientific feasibility, including the ability of outcomes to indicate change, safety, and progression in the exercise programme.

Results

Ten patients with a median age of 70 years (min 53–max 86) were included. Adherence to all parts of the intervention was not feasible because of patients’ postoperative complications, resulting in dropouts. For the patients who took part in the exercise programme, adherence and acceptability for the exercise period were feasible, but the 6-min walk test was not feasible at discharge from the hospital. Physiotherapists in the primary health care setting perceived the process as feasible. Moreover, the ability of outcomes to indicate change and progression in the exercise programme was feasible, meanwhile no adverse events were registered.

Conclusions

The exercise intervention was feasible for the patients that took part in the exercise programme, with respect to safety and progression through the exercise programme. Furthermore, this study suggests that some improvements needed to be implemented in the process, prior to the upcoming randomised controlled trial.
Serous maculopathy with absence of retinal pigment epithelium (SMARPE) associated with large drusen
Authors: Lima Luiz H. , Braga João Pedro Romero , Melo Gustavo B. , Cella Wener P. , Brandão Adam S. L. , Meirelles Rodrigo L. , Zett Claudio , Cyrino Francyne V. R. , Jorge Rodrigo
Published: January 2024

Purpose

To describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related macular degeneration (AMD).

Methods

A retrospective study of ophthalmic examination and multimodal imaging data of individuals with SMARPE and large drusen observed over a period of 12-month was accomplished. SMARPE was defined as subretinal accumulation of fluid within the macular area due to retinal pigment epithelium (RPE) aperture. Large drusen were identified by the presence of sub-RPE deposits using multimodal imaging analysis (color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography).

Results

Twelve eyes of 7 white patients with a mean age of 77 years were observed to have SMARPE associated with large drusen. The median visual acuity was 20/100. Bilateral SMARPE lesions were observed in 71% of study patients. All SMARPE lesions were hypoautofluorescent, located in the subretinal space between the RPE and the ellipsoid zone, and presented as complete or incomplete RPE apertures associated with subretinal fluid. The SMARPE in this study had coincident multimodal imaging features as the SMARPE described in other reports in the literature.

Conclusions

Bilateral SMARPE can occur in association with typical AMD large drusen. Anomalisms resulting in drusen biogenesis or mechanisms that act alongside to these may be related to SMARPE development.
Clinical application of a three-dimensional-printed model in the treatment of intracranial and extracranial communicating tumors: a pilot study
Authors: Zhang Xiang-heng , Li Jiahao , He Zhenqiang , Wang Dikan , Liao Guiqing , Zhang Si-en , Duan Hao , Mou Yonggao , Liang Yujie
Published: January 2024

Background

Surgical management for intracranial and extracranial communicating tumors is difficult due to the complex anatomical structures. Therefore, assisting methods are urgently needed. Accordingly, this study aimed to investigate the utility of a three-dimensional (3D)-printed model in the treatment of intracranial and extracranial communicating tumors as well as its applicability in surgical planning and resident education.

Methods

Individualized 3D-printed models were created for eight patients with intracranial and extracranial communicating tumors. Based on these 3D-printed models, a comprehensive surgical plan was made for each patient, after which the patients underwent surgery. The clinicopathological data of patients were collected and retrospectively analyzed to determine surgical outcomes. To examine the educational capability of the 3D-printed models, specialists and resident doctors were invited to review three of these cases and then rate the clinical utility of the models using a questionnaire.

Results

The 3D-printed models accurately replicated anatomical structures, including the tumor, surrounding structures, and the skull. Based on these models, customized surgical approaches, including the orbitozygomatic approach and transcervical approach, were designed for the patients. Although parameters such as operation time and blood loss varied among the patients, satisfactory surgical outcomes were achieved, with only one patient developing a postoperative complication. Regarding the educational applicability of the 3D-printed model, the mean agreement for all eight questionnaire items was above six (seven being complete agreement). Moreover, no significant difference was noted in the agreement scores between specialists and residents.

Conclusion

The results revealed that 3D-printed models have good structural accuracy and are potentially beneficial in developing surgical approaches and educating residents. Further research is needed to test the true applicability of these models in the treatment of intracranial and extracranial communicating tumors.
Assessing the impact of comorbid type 2 diabetes mellitus on the disease burden of chronic hepatitis B virus infection and its complications in China from 2006 to 2030: a modeling study
Authors: Xie Jinzhao , Wang Xu , Wang Xinran , Li Jinghua , Jie Yusheng , Hao Yuantao , Gu Jing
Published: January 2024

Background

China bears a high burden of both hepatitis B virus (HBV) infection and type 2 diabetes mellitus (T2DM). T2DM accelerates the progression of liver disease among individuals infected with HBV. This study aims to assess the excess disease burden caused by comorbid T2DM among HBV-infected individuals in China.

Methods

We estimated the disease burden of HBV and its complications in China from 2006 to 2030 using individual-based Markov models. The baseline population consisted of 93 million HBV-infected individuals derived from the 2006 National Serological Epidemiological Survey. We developed two models: one incorporated the impact of T2DM on the disease progression of HBV infection, while the other did not consider the impact of T2DM. By comparing the outcomes between these two models, we estimated the excess disease burden attributable to comorbid T2DM among HBV-infected individuals.

Results

The incidence of severe HBV complications, including cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths, exhibited an increasing trend from 2006 to 2030 among the Chinese HBV-infected population. Comorbid T2DM increased the annual incidence and cumulative cases of severe HBV complications. From 2006 to 2022, comorbid T2DM caused 791,000 (11.41%), 244,000 (9.27%), 377,000 (8.78%), and 796,000 (12.19%) excess cases of compensated cirrhosis, decompensated cirrhosis, HCC, and liver-related deaths, respectively. From 2023 to 2030, comorbid T2DM is projected to result in an 8.69% excess in severe HBV complications and an 8.95% increase in liver-related deaths. Among individuals aged 60 and older at baseline, comorbid T2DM led to a 21.68% excess in severe HBV complications and a 28.70% increase in liver-related deaths from 2006 to 2022, with projections indicating a further 20.76% increase in severe HBV complications and an 18.31% rise in liver-related deaths over the next seven years.

Conclusions

Comorbid T2DM imposes a substantial disease burden on individuals with HBV infection in China. Healthcare providers and health policymakers should develop and implement tailored strategies for the effective management and control of T2DM in individuals with HBV infection.
Pulmonary hemorrhage as a presentation of AL amyloidosis secondary to multiple myeloma: a case report
Authors: Birchenall-Jiménez Claudia , Perdomo-Polania Jesús , Serna María , Méndez-Carrillo Isabella , Hernández-Guerrero Felipe , Mantilla-García Santiago , Quintero-Osorio María , Cortés-Jaramillo Ximena
Published: January 2024

Background

The convergence of pulmonary hemorrhage, pulmonary amyloidosis, and multiple myeloma is uncommon. Amyloidosis can affect the pulmonary parenchyma in a diffuse, tracheobronchial, or parenchymal pattern and may rarely be associated with pulmonary hemorrhage. Additionally, pulmonary amyloidosis is not a frequent manifestation of multiple myeloma. We present a case of a male patient with pulmonary hemorrhage as the initial manifestation of AL pulmonary amyloidosis, and ultimately, confirmation of multiple myeloma through bone marrow biopsy.

Case presentation

The clinical case involves a 60-year-old male with no significant medical history, who was admitted presenting a clinical picture evolving over 6 months characterized by hemoptoic cough, accompanied by dyspnea, a decrease in functional capacity, and constitutional symptoms. Thoracic CT images revealed multilobar ground-glass opacities with suspected alveolar hemorrhage. In response to this clinical presentation, bronchoalveolar lavage with cytology was performed, revealing the presence of hemosiderin-laden macrophages. Given the complexity of the case, further investigation included a wedge biopsy of the lung. The pathological report indicated an atypical lymphoplasmacytoid proliferation with deposits of eosinophilic amorphous material, suggestive of amyloidosis. Congo red staining confirmed the presence of amyloid material. Elevated Kappa light chains were detected in both serum and urine, with an increased K/L ratio. Immunoglobulins G and M were found to be decreased. As part of the comprehensive assessment, a bone marrow biopsy was conducted, confirming the diagnosis of multiple myeloma with 10% atypical plasma cells. In light of this diagnosis, appropriate treatment has been initiated to address this intricate medical condition effectively.

Conclusion

The present case report provides an illustrative perspective on an uncommon presentation of pulmonary amyloidosis secondary to multiple myeloma, with the initial manifestation being pulmonary hemorrhage. The findings from both the physical examination and laboratory tests were consistent with pulmonary amyloidosis, and definitive confirmation of the multiple myeloma diagnosis was achieved through bone marrow biopsy. This case highlights the significance of considering pulmonary amyloidosis as a potential cause of hemoptysis, especially in patients with associated risk factors for multiple myeloma. Early recognition of this clinical association is pivotal for precise diagnosis and prompt therapeutic intervention. The complexity of this case underscores the importance of a comprehensive diagnostic approach in unraveling intricate medical conditions.
Laboratory evaluation of toxicity of selected insecticides against egg and larval stages of cotton pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae)
Authors: Busnoor Abhishek V. , Wadaskar R. M. , Fand Babasaheb B. , Tambe V. J. , Pillai T. , Mahule D. J. , Nagrare V. S. , Prasad Y. G.
Published: January 2024

Background

The cryptic nature of pink bollworm Pectinophora gossypiella (Saunders) larvae enables its reduced vulnerability to insecticidal control. Further, the development of resistance against Bacillus thuringiensis (Bt) toxins posed a serious threat to transgenic cotton cultivation. This necessitated determining the critical timing of spray applications on the control effectiveness. This study assessed the influence of egg age (freshly laid vs. three-day-old) and the location of larvae (directly exposed to the insecticide residues on the boll rind vs. burrowed inside the bolls) on insecticide control efficacy.

Results

The results revealed a significant decrease in the ovicidal activity of tested insecticides with an increase in the age of eggs from one day old to three days old (paired t-test, P < 0.05). The larvae directly exposed to the insecticide residues on the boll rind were more susceptible (> 80% mortality) than the larvae exposed after they had burrowed inside the bolls (< 49% mortality). The inhibitory effects of tested insecticides on developmental biology were more pronounced in the experiment on pre-larval release insecticide treatment compared with insecticide treatment given post-larval release and entry inside the bolls.

Conclusion

Egg age influences the insecticide susceptibility, as does the larval location, directly exposed vs burrowed inside the bolls. Older eggs and the larvae that had burrowed inside the green bolls of cotton were relatively less susceptible to the insecticide treatments. The toxic effects of insecticides on egg and larval stages were primarily ephemeral. These findings are significant for devising a comprehensive strategy for pink bollworm management on a sustainable basis.
Using artificial intelligence for hiring talents in a moderated mechanism
Authors: Islam Muhaiminul , Rahman Md. Mahbubur , Taher Md. Abu , Quaosar G. M. Azmal Ali , Uddin Md. Aftab
Published: January 2024

Globally, artificial intelligence (AI) occupies a burgeoning space among recruiters as it replaces many of the recruitment and selection tasks while hiring the talents. Despite the existence and acceptance of AI being unprecedented among savvy recruiters, the study of it in developing countries’ contexts is still at a fancy stage. Particularly, the extant literature documented that very little is known about the intention and actual use (AU) of AI to hire talents with the intervening effects of voluntariness of usage (VU), tenure, and education of the recruiters elsewhere. Hence, using the doctrine of the extended unified theory of acceptance and use of technology (UTAUT), the present study aims to unpack the intention and AU of AI among hiring professionals in the context of Bangladesh, a developing country in the South Asian region. A multi-item questionnaire survey was employed to collect the data of recruiters from talent acquisition departments in both manufacturing and service organizations with a convenience sampling technique. We used partial least square-based structural equation modeling (PLS-SEM) version 4.0.8.9 to analyze the data. Results showed that performance expectancy (PE), facilitating conditions (FC), and hedonic motivation (HM) have a significant influence on the intention to use (IU) AI (p < 0.05), and IU also predicts AU of AI significantly (p < 0.05). The moderating influence of VU has an insignificant effect on the positive influence of IU on AU. Moreover, the multi-group analysis showed that there is no significant difference between young adults and old adults and highly educated and lowly educated on the association between IU and AU. The findings in this study showed important notations that contributed to advancing the knowledge and filling the gap in the extant literature. Additionally, it also provides fresh insights for developing policy interventions to hire professionals for thriving AI adoption in the context of developing countries effectively.
Achieving customer loyalty during post-pandemic: an asymmetric approach
Authors: Latif Khawaja Fawad , Bashir Shahid
Published: January 2024

The study aims to investigate causal recipes to improve restaurant customers’ loyalty (LOY) during COVID-19 post-pandemic. The study utilizes Fuzzy-set Qualitative Comparative Analysis (fsQCA) within the framework of complexity theory to examine the intricate relationship between antecedent conditions, including Socially Responsible COVID-19 practices (CSR), Service Quality (SR), Customer Experience (EXP), Customer Satisfaction (SAT), Trust (TR), and Customer Commitment (COMM). The study used a quantitative survey approach, using a Likert scale to achieve the study aim. The survey has been strategically developed to gather intricate replies, taking influence from well-established scales within the area. The research purposefully recruited customers from the restaurant industry in Pakistan. A total of 450 full and valid replies were obtained via the use of Google Forms and paper questionnaires. The fsQCA approach is used to examine the data and ascertain configurations or combinations of antecedent situations that contribute to enhanced levels of loyalty. The results indicate that LOY is a multifaceted phenomenon in the post-pandemic phase of COVID-19 and is not only influenced by individual antecedent situations. This study identifies many routes that lead to increased levels of loyalty, highlighting the need to adopt a comprehensive and integrated strategy. The research emphasizes the diverse impacts of important factors, including CSR, SR, EXP, SAT, TR, and COMM, on loyalty. The novelty of this study is in its utilization of fsQCA and complexity theory to investigate LOY inside the restaurant sector among the distinctive circumstances of the post-pandemic period of COVID-19. This paper presents a critique of conventional symmetrical methods and proposes a comprehensive viewpoint on LOY, highlighting the need for sophisticated and integrated theoretical frameworks. Through the exploration of several routes to increased levels of LOY and the identification of the intricate influences of numerous preceding factors, this study enhances both theoretical and practical comprehension. The study places significant importance on an innovative research methodology and its potential impact on restaurant management, making it a noteworthy contribution to the current body of literature.
A comparison of electrocardiographic parameters in e-cigarette users, conventional cigarette smokers, and non-smokers
Authors: Ammar Heba , Hashish Rania , Ali Shrouk Mohamed , Salem Ahmed Salah , Hagras Abeer Mohamed
Published: January 2024

Background

Smoking is a major preventable risk factor for cardiovascular morbidity and mortality. Tobacco smoking induces atherosclerosis, ischemic heart diseases, and arrhythmias. The impact of electronic cigarettes on cardiovascular health is still controversial. This study aimed to evaluate the electrocardiographic parameters in chronic electronic cigarette users compared to chronic conventional cigarette smokers and a non-smoker control group of matched age and gender.

Results

The study involved 105 volunteers with no history of chronic or cardiovascular diseases or cardioactive drug use. Participants were assigned into three study groups, chronic e-cigarette users, conventional cigarette smokers, and non-smokers, each consisting of 35 participants. Demographic data, smoking history, vital signs, and 12-lead electrocardiogram (ECG) were evaluated. Demographic data were insignificantly different among all study groups. The mean heart rate was significantly higher in chronic electronic cigarette users and conventional cigarette smokers compared to non-smokers (p < 0.001).QRS complex duration was significantly shorter in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). Prolonged QT and QTc intervals duration were recorded in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). All the ventricular repolarization indices (T wave—peak to T-end (Tpe) interval, TPe/QT ratio, and TPe/QTc ratio were significantly prolonged in chronic e-cigarette users, and conventional smokers compared to non-smokers (p < 0.001). Mean systolic, diastolic blood pressure, P wave amplitude and duration, and PR interval were insignificantly different between all groups (P > 0.05).

Conclusions

Chronic e-cigarette use is associated with higher heart rates, shorter QRS complex, prolonged QT, QTc duration, and prolonged ventricular repolarization indices compared to non-smokers of matched age and gender. Conclusively, e-cigarette use is associated with negative cardiovascular effects like conventional cigarette smoking.
Role of point of care ultrasound in management of deteriorating respiratory intensive care unit patients and its impact on outcome
Authors: Elgabry Maha Mohammed , Shebl Eman , El-Shetry Mohamed Saad , Elsayed Enaam I. , Zayed Niveen ELSayed
Published: January 2024

Background

Point of care ultrasonography (POCUS) is a real time examination that can be used in the emergency room and intensive care unit (ICU). It can provide low-cost modality in short period of time that can help the clinician in better management the ICU patients. The aim of the current work was to evaluate the impact of POCUS (focused heart, lung, IVC and Doppler lower limb) in improving the outcome of deteriorating patients in the respiratory intensive care unit (RICU), via narrowing differential diagnosis and earlier start of target therapy.

Methods

This prospective study included 126 deteriorated patients in the RICU. The POCUS was performed to all included patients, together with the indicated laboratory and radiological investigations (Chest x-ray, computerized tomography, and conventional echocardiography) to detect the agreement between POCUS and the gold standard techniques to assess the POCUS effectiveness. The impact of applying POCUS on the outcome of the studied patients was evaluated regarding ICU and in hospital length of stay and the 30-day mortality.

Results

The included patients were 51 males (40.5%) and 75 females (59.5%) with a mean ±SD of age 45.4 ± 15.7 years. POCUS showed a good agreement with the gold standard techniques. There was significant improvement in outcome of the studied patients as regard ICU and in hospital stay with early using of POCUS examination but no significant difference in 30 days mortality rate of the studied patients.

Conclusion

POCUS is an effective modality in the management of deteriorating patients in the RICU with a good impact on the patient outcome.
A phase I clinical trial of riluzole in combination with mFOLFOX6 and bevacizumab in treating patients with metastatic colorectal cancer.
Authors: Li Chunjie , Noonan Anne M. , Hays John L. , Roychowdhury Sameek , Malalur Pannaga G. , Elkhatib Rifat T. , Manne Ashish , Mittra Arjun , Rahman Shafia , Phelps Mitch A. , Liang Beiyuan , Storts Hadyen , Khan Misbah , Zhang Evan , Zheng Xinru , Miles Wayne , Wang Jing , Jin Ning
Published: January 2024

101

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the US. 5-fluorouracil (5-FU) based chemotherapies in combination with targeted agents remain the standard of care in patients with metastatic or locally advanced disease. It is essential to develop new treatment strategies in metastatic CRC patients with microsatellite stable disease, in whom immune checkpoint blockade is ineffective. Our preclinical studies showed riluzole, an oral medicine for amyotrophic lateral sclerosis, can increase intratumoral CD8+ T cells and suppress tumor growth in a syngeneic colon cancer mouse model. Riluzole-mediated tumor growth inhibition depends on the presence of CD8+ T cells and activation of cGAS/STING/IFNβ signaling. Methods: This was a single-arm phase I trial of riluzole in combination with mFOLFOX6/bevacizumab for patients with metastatic CRC. The dose of riluzole started from 50 mg twice daily with dose escalation to 100 mg twice daily or dose de-escalation to 50 mg once daily. Patients received riluzole for 16 weeks in combination with mFOLOFX6/bevacizumab for 8 cycles. Then patients either continued mFOLFOX/bevacizumab or switched therapy. The primary objective was adverse events (AE). The secondary objectives were objective response rate (ORR), disease control rate (DCR), and duration of response (DoR). Results: Fourteen patients were enrolled, and twelve patients were evaluable. All patients received FOLFOX in the past; two patients received 2 lines of chemotherapies; one patient received 3 lines and eight patients had ≥ 4 lines before the study. Five patients (41.7%) had disease resistance to FOLFOX. During the study, two patients received only 2 cycles of treatment due to poor PS. Two patients received 7 cycles, and nine patients completed 8 cycles of treatment. The common grade 3 & 4 AEs included neutropenia (46.2%), lymphopenia (30.8%), and abdominal pain (15.4%). No complete response was observed; two patients obtained partial response; nine patients had stable disease, and only one patient had progressive disease. The ORR was 16.7%, and DCR was 91.7%. The median DoR was 5.1 (95% CI 3.2-7.0) months. The maximum tolerated dose for riluzole is 100 mg twice daily. Conclusions: Our study showed that riluzole plus mFOLFOX6/bevacizumab is well tolerated in patients with metastatic CRC and may have clinical activity in patients whose disease is resistant to FOLFOX. Further study is necessary to confirm the immunomodulation effect of riluzole. Clinical trial information: NCT04761614 .
Trifluridine/tipiracil (TAS-102) in combination with anti-EGFR re-challenge versus TAS-102 plus anti-VEGF in patients with mCRC who experienced first-line anti-EGFR-based chemotherapy.
Authors: Chen Ching Tso , Liang Yi-Hsin , Yeh Kun-Huei
Published: January 2024

120

Background: TAS-102 is one of the standard treatments for refractory metastatic colorectal cancer (mCRC). Add-on bevacizumab to TAS-102 has been proved to improve progression-free survival (PFS) and overall survival (OS). However, the two strategies of combination with anti-EGFR or anti-VEGF in RAS/RAF wild-type mCRC patients have not been compared. Methods: We retrospectively collected mCRC patients who received TAS-102 treatment from December 2018 to March 2023 at National Taiwan University Hospital. The key inclusion criteria included RAS/RAF wild-type, first-line treatment with anti-EGFR therapy, and TAS-102 in combination with anti-EGFR re-challenge, or with anti-VEGF therapy. Concurrent use of other chemotherapies was allowed. The patients with combination duration less than 4 weeks were excluded. Results: A total of 30 patients were enrolled. There were 20 patients who received TAS-102 plus anti-EGFR re-challenge, and 10 were treated with TAS-102 plus anti-VEGF. The median treatment line of TAS-102 combined with targeted therapies was 5 (Range 3-11). There was no significant difference in baseline characteristics between the two groups (Table). For TAS-102 plus anti-EGFR vs VEGF, the ORR was 30.0% vs 0%, and the DCR was 70.0% vs 30.0%, respectively. The median PFS was 4.0 vs 2.3 (p=0.389) months, respectively. The median OS was 12.67 vs 9.93 (p=0.722) months, respectively. Conclusions: TAS-102 plus anti-EGFR re-challenge showed a higher ORR than TAS-102 plus anti-VEGF. The PFS and OS were comparable in both arm and numerically longer in the TAS-102 plus anti-EGFR re-challenge group.[Table: see text]
Regorafenib plus FOLFIRI with irinotecan dose escalated according to UGT1A1 genotyping in patients with metastatic colorectal cancer.
Authors: Wang Chao-Yuan , Huang Ching-Wen , Tsai Hsiang-Lin
Published: January 2024

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Background: This multicenter, phase II, randomized, open-label, 2-arm parallel trial aims to compare the efficacy and safety profiles of regorafenib plus irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping with regorafenib alone in previously treated patients with metastatic colorectal cancer (mCRC). Methods: A total of 153 patients were planned to randomize at a ratio of 2:1 for receiving regorafenib plus FOLFIRI (arm A, 102 patients) or regorafenib alone (arm B, 52 patients), respectively. For both arms, regorafenib were given for 21 consecutive days (Day 1 to 21) of each 28-day cycle at a maintained dose of 120 mg. However, for arm A, patients received regorafenib plus FOLFIRI with dose-escalated irinotecan according to UGT1A1 genotypes. FOLFIRI were on the first day of each 28-day cycle only. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and disease control rate (DCR), and adverse events (AEs). Results: Finally, a total of 116 patients were enrolled to be analyzed, including 74 in arm A and 42 in arm B. The significantly better PFS was observed in arm A, 4.8 and 3.0 months, respectively ( p = 0.016). Moreover, in patients with RAS wild type, the significantly better PFS was observed in arm A, 6.3 and 2.1 months, respectively ( p = 0.003). The OS was not significantly different between group A and B, 9.8 and 12.6 months, respectively ( p = 0.970). However, in patients with RAS wild type, the trend of better OS was observed in arm A, 14.3 and 6.9 months, respectively ( p = 0.158). The marginally significant better DCR was observed in arm A, 55.4% and 38.1%, respectively ( p = 0.055). The marginally significant better DCR was observed in arm A, 55.4% and 38.1%, respectively ( p = 0.055). Combination treatment of regorafenib plus FOLFIRI was independent favorable prognostic factor for PFS ( P = 0.008; hazard ratio [HR], 1.892; 95% CI, 1.182 – 3.027). Regarding severe AEs, there were no significant differences between the two groups (all P>0.05). Conclusions: Combination treatment of regorafenib plus FOLFIRI with dose-escalated irinotecan according to UGT1A1genotyping results in a significant better PFS and comparable AEs. Moreover, patients with RAS wild type of CRC would be more beneficial for this combination treatment.
A phase II trial of TAS-102 in patients with colorectal cancer with ctDNA-defined minimal residual disease post-adjuvant therapy: Results from the MD Anderson INTERCEPT Program.
Authors: Pellatt Andrew Jared , Bent Alisha Heather , Parseghian Christine Megerdichian , Johnson Benny , Huey Ryan W , Raghav Kanwal Pratap Singh , Morris Van K. , Overman Michael J. , Morelli Maria Pia , Willis Jason , Le Phat , Shen John Paul Y.C. , Lee Michael Sangmin , Alfaro Kristin , Aziz Kathryn , Kell Robert J. , Sun Ryan , Kopetz Scott , Dasari Arvind
Published: January 2024

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Background: Circulating tumor DNA (ctDNA) has emerged as a novel marker with high specificity and positive predictive value for identifying radiographically occult microscopic or minimal residual disease (MRD) in colorectal cancer (CRC) patients (pts). An additional widely acknowledged unmet need is the development of therapeutic strategies to eradicate MRD and increase the cure rate of the disease. Ongoing trials are evaluating MRD as a biomarker for determining the intensity of post-operative adjuvant therapy. However, the feasibility and efficacy of therapy in pts who are MRD+ during surveillance (after all curative intent treatments including adjuvant chemotherapy) is unknown. Methods: In this proof-of-concept phase II study, pts with stages II-IV CRC noted to be MRD+ during surveillance (ctDNA+ but no radiographic evidence of disease on imaging in last 30 days) received 6 months (m) of TAS-102. Pts were identified through the MD Anderson INTERCEPT program that integrates MRD testing with a tissue informed assay (Signatera) into standard of care for CRC pts. The primary endpoint was 6-m ctDNA clearance and secondary objectives included 3-m ctDNA clearance, and disease-free survival (DFS). Assuming H0 = 5% spontaneous, HA = 30% ctDNA clearance with TAS 102 & 1-sided α = 0.05, 15 patients are required for β = 85%. Results: Between 7/22/22 and 9/7/23,15 pts with MRD were enrolled. Baseline characteristics included a median age of 62 years (range: 37-73), Caucasian (77%), male (77%), resected Stage IV (92%) and median ctDNA level of 1.55 MTM/ml (range 0.04-28.72). At data cutoff, 11 pts had 3-m ctDNA levels and 10 had a decrease in their ctDNA level (91%) including 5 with undetectable levels (45%). At 6-m, 60% of patients had ctDNA levels at or below prior levels; three maintained undetectable ctDNA at 6-m: of those, two pts had subsequent radiographic progression following therapy completion. Median DFS was 9.4-m in the full cohort. Conclusions: We demonstrate the feasibility of identifying and enrolling MRD+ pts through screening during surveillance onto therapeutic trials and show the ability of an experimental therapy to convert patients to MRD negative status, a necessary but not sufficient step for disease eradication. Preliminary results suggest that treatment with TAS-102 is effective in inducing ctDNA clearance in the short term in most pts, but with no evidence of persistent clearance. Updated results including 6-m ctDNA levels and survival data will be presented. Clinical trial information: NCT05343013 .
Results of a prospective phase II study of total neoadjuvant therapy for locally advanced rectal cancer.
Authors: Ma Huiying , Tang Yuan , Zhang Wenjue , Zhou Haitao , Liu Zheng , Zhang Haizeng , Cai Yong , Li Yongheng , Wei Lichun , Liu Shixin , Wang Wenling , Song Yongwen , Chen Bo , Lu Ningning , Qi Shunan , Liu Yueping , Wang Shulian , Wang Xishan , Li Yexiong , Jin Jing
Published: January 2024

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Background: Total neoadjuvant therapy is further accepted for the treatment of locally advanced rectal cancer, which is more valuable for patients with high-risk factors. Optimal schedule of radiotherapy and chemotherapy remains unknown and needs further exploration. Methods: We conducted a multicenter, randomized, phase II trial (ClinicalTrials.gov No.: NCT04543695). Patients aged 18-75 years with initial stage II / III rectal adenocarcinoma (At least one of high-risk factors should be included: mesorectal fascia involvement, T4, N2, positive lateral lymph node, or extramural vessel invasion) were assigned into three groups, 1) Chemoradiotherapy (50 Gy of radiation combined with oral capecitabine) followed by consolidation chemotherapy using six cycles of XELOX(CNCT group), 2) Induction chemotherapy before chemoradiotherapy (INCT group), or 3) Chemoradiotherapy alone (Control group). Then enrolled patients were required to undergo radical surgery after neoadjuvant therapy. Patients in Control group need six cycles of XELOX after surgery. The primary end point was proportion of yp0-II, and watch-and-wait strategy after complete clinical response (cCR) was allowed. Results: Of the 257 patients enrolled, 255 patients were evaluable (Control: CNCT: INCT= 84: 86: 85). Neoadjuvant treatment related grade 3 or 4 toxicity was higher in TNT approach (7.1%, 23.3% and 32.9% in Control, CNCT and INCT, respectively), of with myelosuppression being most common. Compliance of chemoradiotherapy was lower in INCT group (98.8%, 100% and 90.6% in Control, CNCT and INCT, respectively). As to CNCT and INCT, 60.0% and 74.1% of patients completed six cycles of chemotherapy, with 76.7% and 83.5% completing four cycles of chemotherapy, respectively. Proportions of downstage (yp0-II + sustained cCR) were achieved 75.6% in CNCT group and 74.1% in INCT group, respectively, compared to 56.0% in Control group. CR rates (pCR + sustained cCR) were achieved 43.0% in CNCT group and 38.8% in INCT group, respectively, compared to 20.2% in Control group. Both TNT approaches did not increase the incidence of surgical complications (6.0%, 8.1% and 10.9% in Control, CNCT and INCT, respectively), with anastomotic fistula and abdominal infection being of most common. Conclusions: Both TNT approaches increased the probability of ≥ G3 acute toxicities, but most patients could tolerate 4 cycles of neoadjuvant chemotherapy. Both TNT approaches could achieve a higher proportion of downstage and CR rate. Clinical trial information: NCT04543695 .
Comprehensive genomic analysis of molecular residual disease based on circulating tumor DNA in patients with postoperative colorectal cancer.
Authors: Hong Qingqi , Zhu Jingtao , Lin Hexin , Chen Yinan , Bai Haoyu , Yan Linghua , Xiao Li , You Jun
Published: January 2024

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Background: Despite receiving curative resection, a considerable percentage of colorectal cancer (CRC) patients still experience disease recurrence. The early detection of molecular residual disease (MRD) has the potential to improve risk assessment. Methods: A total of 104 patients with stage Ⅰ-Ⅳ CRC were enrolled, of which 259 serial plasma samples were collected. Multi-gene targeted sequencing was conducted on tumor and plasma samples to identify somatic variants. Results: Among the 104 patients, 14 cases had positive landmark MRD and 32 cases had positive longitudinal MRD. Patients with positive landmark MRD had significantly higher recurrence risk compared to those with negative landmark MRD (Hazard Ratio [HR]: 7.325; 95% CI, 2.877-18.647; P < 0.001). Similarly, positive longitudinal MRD was associated with increased recurrence risk (HR: 9.385; 95% CI: 3.085-28.556; P < 0.001), with a higher HR value. Positive MRD detection preceded CT confirmed recurrence in 85.7% of patients, with a median lead time of 198.5 days. In multivariate analysis, positive-MRD was the most significant prognostic factor for DFS. The combination of KRAS variant and MRD status improved the efficiency of prognostic prediction, the area under the curve value for the combination of MRD and KRAS was higher than MRD and KRAS. By analyzing the characteristic of cfDNA fragments, we found that mutation sites tended to be enriched in shorter cell free DNA (cfDNA) fragments. Conclusions: Our study demonstrated an excellent prognostic prediction potential of circulating tumor DNA-based MRD detection among postoperative CRC patients, especially the combination of KRAS variant and MRD improved the efficiency of risk stratification through MRD. This study may facilitate the incorporation of MRD and KRAS into prognostic prediction. Our study revealed that mutation sites tended to be enriched in shorter DNA fragments, providing valuable insights for future ctDNA detection method.