bluuebunny/crossref_metadata_2025 huggingface dataset:
Willingness to accept and participate in a Microsporidia MB-based mosquito release strategy: a community-based rapid assessment in western Kenya
Authors: Bukhari Tullu , Gichuhi Joseph , Mbare Oscar , Ochwal Victoria A. , Fillinger Ulrike , Herren Jeremy K.
Published: April 2024

Background

Microsporidia MB, an endosymbiont naturally found in Anopheles mosquitoes inhibits transmission of Plasmodium and is a promising candidate for a transmission-blocking strategy that may involve mosquito release. A rapid assessment was carried out to develop insight into sociodemographic factors, public health concerns, and malaria awareness, management, and prevention practices with the willingness to accept and participate in Microsporidia MB-based transmission-blocking strategy to develop an informed stakeholder engagement process.

Methods

The assessment consisted of a survey conducted in two communities in western Kenya that involved administering a questionnaire consisting of structured, semi-structured, and open questions to 8108 household heads.

Results

There was an overall high level of willingness to accept (81%) and participate in the implementation of the strategy (96%). Although the willingness to accept was similar in both communities, Ombeyi community was more willing to participate (OR 22, 95% CI 13–36). Women were less willing to accept (OR 0.8, 95% CI 0.7–0.9) compared to men due to fear of increased mosquito bites near homes. Household heads with incomplete primary education were more willing to accept (OR 1.6, 95% CI 01.2–2.2) compared to those educated to primary level or higher. Perceiving malaria as a moderate or low public health issue was also associated with a lower willingness to accept and participate. Experience of > 3 malaria cases in the family over the last six months and knowledge that malaria is transmitted by only mosquito bites, increased the willingness to accept but reduced the willingness to participate. Awareness of malaria control methods based on mosquitoes that cannot transmit malaria increases the willingness to participate.

Conclusion

The study showed a high level of willingness to accept and participate in a Microsporidia MB-based strategy in the community, which is influenced by several factors such as community, disease risk perception, gender, education level, knowledge, and experience of malaria. Further research will need to focus on understanding the concerns of women, educated, and employed community members, and factors that contribute to the lower disease risk perception. This improved understanding will lead to the development of an effective communication strategy.
Survival outcomes in HER2-low versus HER2-zero breast cancer after neoadjuvant chemotherapy: a meta-analysis
Authors: Xia Lin-Yu , Cao Xu-Chen , Yu Yue
Published: April 2024

Background

The survival outcomes in HER2-low versus HER2-zero breast cancer (BC) after neoadjuvant chemotherapy (NACT) remain unclear. The meta-analysis was conducted to summarize current evidence about the survival outcomes in HER2-low versus HER2-zero BC.

Methods

We conducted a systematic search in PubMed and EMBASE databases to identify relevant studies.

Results

A total of 14 studies with 53,714 patients were included. Overall, 34,037 patients (63.37%) were HER2-low, and 19,677 patients (36.63%) were HER2-zero. Patients with HER2-low tumors had a significantly lower pathological complete response (pCR) rate than patients with HER2-zero tumors, regardless of the hormone receptor status. Compared with HER2-zero breast cancer, the overall survival (OS) and disease-free survival (DFS) of HER2-low BC were longer in the overall cohort (HR = 0.72; 95% CI = 0.61–0.85; P < 0.0001; HR = 0.83; 95% CI = 0.75–0.92; P = 0.0002); however, no differences were observed in terms of OS and DFS between HER2-low and HER2-zero BC in the HR-negative group. In the HR-positive group, HER2-low status had no significant impact on OS, while significantly associated with increased DFS (HR = 0.85; 95% CI = 0.76–0.96; P = 0.007).

Conclusion

These results suggest that although HER2-low BC has a poor response to NACT, it is correlated with favorable OS and DFS after NACT in the overall cohort as well as longer DFS in the HR-positive group.
Clinical implications of pediatric biliary intraepithelial neoplasia diagnosed from a choledochal cyst specimen
Authors: Gang Sujin , Kwon Hyunhee , Song In Hye , Namgoong Jung-Man
Published: April 2024

Background

Biliary intraepithelial neoplasia (BilIN), a noninvasive precursor of cholangiocarcinoma, can manifest malignant transformation. Since cholangiocarcinoma (CCA) may progress due to chronic inflammation in the bile ducts and gallbladder, choledochal cysts are considered a precursor to CCA. However, BilIN has rarely been reported in children, to date.

Methods

We reviewed medical records of patients (< 18 years of age, n = 329) who underwent choledochal cyst excision at Asan Medical Center from 2008 to 2022. BilIN was diagnosed in 15 patients. Subsequent analyses were performed of the demographics, surgical procedures, clinical course, and outcomes in these patients. Subgroup analysis and multivariate logistic regression test were performed to identify factors influencing BilIN occurrence.

Results

The mean age of the patients included in our study was 40.1 ± 47.6 months. In 15 patients, BilIN of various grades was diagnosed. Todani type I was prevalent in 80% of the patients. The median age at surgery was 17 months. During a mean follow-up of 63.3 ± 94.0 months, no adverse events such as stone formation in the remnant intrapancreatic common bile duct and intrahepatic duct or cholangiocarcinoma were observed, indicating a favorable outcome until now.

Conclusions

The potential progression of choledochal cysts to BilIN in children was demonstrated. These results could underscore the importance of early and comprehensive excision of choledochal cysts, including resection margins for associated lesions and more thorough postoperative surveillance in patients with or at risk of BilIN.
Age and sex-specific disability-free life expectancy in urban and rural settings of Bangladesh
Authors: Ahmed Khandaker Tanveer , Afrin Aziza , Hasan Mehedi , Sogir Sajjad Bin , Rahman Labiba , Karimuzzaman Md. , Rahman Kazi Arifur , Hossain Md. Moyazzem , Khan Hafiz T. A.
Published: April 2024

Background

Disability-free life expectancy (DFLE) has been used to gain a better understanding of the population’s quality of life.

Objectives

The authors aimed to estimate age and sex-specific disability-free life expectancy (DFLE) for urban and rural areas of Bangladesh, as well as to investigate the differences in DFLE between males and females of urban and rural areas.

Methods

Data from the Bangladesh Sample Vital Statistics-2016 and the Bangladesh Household Income and Expenditure Survey (HIES)-2016 were used to calculate the disability-free life expectancy (DFLE) of urban and rural males and females in Bangladesh in 2016. The DFLE was calculated using the Sullivan method.

Results

With only a few exceptions, rural areas have higher mortality and disability rates than urban areas. For both males and females, statistically significant differences in DFLE were reported between urban and rural areas between the ages of birth and 39 years. In comparison to rural males and females, urban males and females had a longer life expectancy (LE), a longer disability-free life expectancy, and a higher share of life without disability.

Conclusion

This study illuminates stark urban–rural disparities in LE and DFLE, especially among individuals aged < 1–39 years. Gender dynamics reveal longer life expectancy but shorter disability-free life expectancy for Bangladeshi women compared to men, emphasizing the need for targeted interventions to address these pronounced health inequalities.
CSF1R antagonism results in increased supraspinal infiltration in EAE
Authors: Wang Marilyn , Caryotakis Sofia E. , Smith Glendalyn G. , Nguyen Alan V. , Pleasure David E. , Soulika Athena M.
Published: April 2024

Background

Colony stimulating factor 1 receptor (CSF1R) signaling is crucial for the maintenance and function of various myeloid subsets. CSF1R antagonism was previously shown to mitigate clinical severity in experimental autoimmune encephalomyelitis (EAE). The associated mechanisms are still not well delineated.

Methods

To assess the effect of CSF1R signaling, we employed the CSF1R antagonist PLX5622 formulated in chow (PLX5622 diet, PD) and its control chow (control diet, CD). We examined the effect of PD in steady state and EAE by analyzing cells isolated from peripheral immune organs and from the CNS via flow cytometry. We determined CNS infiltration sites and assessed the extent of demyelination using immunohistochemistry of cerebella and spinal cords. Transcripts of genes associated with neuroinflammation were also analyzed in these tissues.

Results

In addition to microglial depletion, PD treatment reduced dendritic cells and macrophages in peripheral immune organs, both during steady state and during EAE. Furthermore, CSF1R antagonism modulated numbers and relative frequencies of T effector cells both in the periphery and in the CNS during the early stages of the disease. Classical neurological symptoms were milder in PD compared to CD mice. Interestingly, a subset of PD mice developed atypical EAE symptoms. Unlike previous studies, we observed that the CNS of PD mice was infiltrated by increased numbers of peripheral immune cells compared to that of CD mice. Immunohistochemical analysis showed that CNS infiltrates in PD mice were mainly localized in the cerebellum while in CD mice infiltrates were primarily localized in the spinal cords during the onset of neurological deficits. Accordingly, during the same timepoint, cerebella of PD but not of CD mice had extensive demyelinating lesions, while spinal cords of CD but not of PD mice were heavily demyelinated.

Conclusions

Our findings suggest that CSF1R activity modulates the cellular composition of immune cells both in the periphery and within the CNS, and affects lesion localization during the early EAE stages.
Relationship between sarcopenia and fatty liver in middle-aged and elderly patients with type 2 diabetes mellitus
Authors: Quan Li , Zhang Fang , Xu Jing , Wang Fei , Fan Yong
Published: April 2024

Objective

In this study, we investigated the relationship between sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with type 2 diabetes mellitus (T2DM) to provide a theoretical foundation for the prevention and treatment of sarcopenia.

Methods

A total of 282 patients diagnosed with T2DM aged 50 and older and were admitted to the Endocrinology Department of Xin Medical University First Affiliated Hospital between December 2021 and February 2023, were selected. Body mass index (BMI), and limb and trunk muscle mass of the patients were measured, and data were collected. Patients were grouped based on the sarcopenia diagnostic criteria. All study participants underwent the same physical examinations and laboratory tests. The relationship between the onset of sarcopenia and fatty liver in middle-aged and elderly patients diagnosed with T2DM was then investigated using statistical analysis.

Results

Comparing the sarcopenia group to the non-sarcopenia group revealed statistically significant variations in gender, BMI, fatty liver prevalence rate, uric acid (UA), alanine aminotransferase (ALT), blood glucose, blood lipid associated indicators, and limb skeletal muscle content. There were, however, no statistically significant differences in age, disease duration, hypertension, smoking, or alcohol intake. There was a positive correlation between BMI, UA, fasting c-peptide, and Appendicular Skeletal Muscle Index (ASMI). Higher levels of BMI, ASMI, and UA were identified as protective variables against sarcopenia by multifactorial logistic regression analysis.

Conclusion

Higher levels of BMI, ASMI, and UA can greatly reduce skeletal muscle atrophy in patients with T2DM. Patients with a fatty liver may be less vulnerable to sarcopenia. There is little evidence, however, that a fatty liver works as a preventive factor against sarcopenia.
Risk factors for poor outcomes in patients with acute lower leg compartment syndrome: a retrospective study of 103 cases
Authors: Lin Zhe , Hou Zhiyong , Guo Jialiang , Lin Yongsheng , Zhang Yingze
Published: April 2024

Purpose

The primary aim of this study was to investigate the risk factors associated with poor outcomes following acute compartment syndrome (ACS) of lower leg. The secondary objective was to determine if delayed fasciotomy is linked to poor outcomes.

Methods

In this retrospective case control study approved by the institutional review board, we identified 103 patients with ACS of the lower leg. Poor outcome was defined as a composite variable that included limb amputation, neurological deficit and contracture. Among these, 44 patients exhibited poor outcome while 59 patients demonstrated a good outcome. Patient-related factors, laboratory values, and treatment-related factors were analyzed using electronic medical records. Univariate statistical and logistic regression analyses were conducted to determine significance.

Results

Bivariate analyses showed that the mechanism of injury (P = 0.021), open injury (P = 0.001), arterial injury (P<0.001), hemoglobin levels (HB) (P < 0.001), white blood cell count (WBC) (P = 0.008), albumin levels (ALB) (P<0.001), creatine kinase levels (CK) at presentation (P = 0.015), CK at peak (P<0.001), creatine kinase levels (Ca) (P = 0.004), dehydrating agent (P = 0.036), and debridement (P = 0.005) were found to be associated with the risk of poor outcomes. Logistic regression analyses revealed that arterial injury [ P< 0.001, OR = 66.172, 95% CI (10.536, 415.611)] was an independent risk factor for poor outcomes. However, HB [P = 0.005, OR = 0.934, 95% CI (0.891, 0.979)] was a protective factor against poor outcomes. Receiver operating characteristic (ROC) curve analysis showed that the cut-off values of HB to prevent poor outcome following ACS was 102.45 g/L.

Conclusions

ACS of the lower leg is a serious complication often associated with a poor prognosis. Patients with arterial injury or lower HB have a significantly increased risk of having poor outcomes. Poor outcomes were not found to be associated with the timing of fasciotomy in this study.
Successful repair of recurrent ventricular septal perforation after myocardial infarction using double patch technique via right ventriculotomy: a case report
Authors: Ashsholih Khoirur Rijal , Takasaki Taiichi , Tomota Mayu , Tokumoto Taika , Go Seimei , Emura Shogo , Ozawa Masamichi , Takahashi Shinya
Published: April 2024

Background

Post-myocardial infarction (MI) ventricular septal perforation (VSP) is a rare but life-threatening complication. Surgical repair is challenging and carries significant risks, particularly in the context of recurrent VSPs. This case study presents a patient with recurrent VSP after initial surgical repair following myocardial infarction.

Case presentation

A 65-year-old male were re-administered to our hospital due to recurrent VSP. He was during follow up after undergone emergency VSP closure surgery 2 months earlier, utilizing the bovine double patch technique via left ventriculostomy. The initial VSP was located in the apical part of the interventricular septum, while the recurrent VSP appeared in the upper middle portion of the interventricular septum (Fig. 1). As the previous patch remained intact, the second surgery employed the bovine double patch technique via right ventriculostomy. The patient’s condition remained stable without the development of heart failure symptoms.

Conclusion

Repairing recurrent VSPs remains a challenge, necessitating the mastery of appropriate approaches to achieve optimal outcomes. Further research and guidelines are required to refine management strategies for recurrent VSPs.
Delayed surgery for acute type A aortic dissection: a retrospective review of an alternative surgical strategy in the COVID-19 era
Authors: Itokawa Rin , Kowatari Ryosuke , Imamura Yuki , Sasaki Hanae , Kondo Norihiro , Daitoku Kazuyuki , Minakawa Masahito
Published: April 2024

Background

During the coronavirus disease (COVID-19) pandemic, medical resources have often been limited to emergency surgeries. This study aimed to evaluate our experience with delayed surgery for acute type A aortic dissections (ATAADs).

Methods

A retrospective study was conducted on 33 patients who underwent surgery for ATAADs between January 2020 and December 2021. The patients were divided into two groups: patients treated within 12 h of arrival (E group; N = 21) and those treated > 12 h after arrival (D group; N = 12) with strict antihypertensive therapy until surgery.

Results

The plasma fibrinogen levels on arrival were lower in the D group than in the E group (174.3 ± 109.1 vs 293.4 ± 165.4, p = 0.038). The time to surgery from symptom onset was longer in the D group than in the E group (4 ± 1 h vs. 86 ± 108 h, p < 0.001). There was one case (3%) of mortality and seven cases (21%) of cerebral infarctions in the E group. There was no significant difference in the intraoperative data and quantity of blood transfused between the two groups.

Conclusion

Thus, delayed surgery for ATAAD with appropriate preoperative management may be an alternative surgical strategy in the COVID-19 era.
On the way to the azygos vein: a road of return rather than ruined
Authors: Feng Yiping , Liu Yeqing , Xu Shanxiang , Zhong Huiming , Jiang Shouyin
Published: April 2024

Background

The malposition of central venous catheters (CVCs) may lead to vascular damage, perforation, and even mediastinal injury. The malposition of CVC from the right subclavian vein into the azygos vein is extremely rare. Here, we report a patient with CVC malposition into the azygos vein via the right subclavian vein. We conduct a comprehensive review of the anatomical structure of the azygos vein and the manifestations associated with azygos vein malposition. Additionally, we explore the resolution of repositioning the catheter into the superior vena cava by carefully withdrawing a specific length of the catheter.

Case presentation

A 79-year-old female presented to our department with symptoms of complete intestinal obstruction. A double-lumen CVC was inserted via the right subclavian vein to facilitate total parenteral nutrition. Due to the slow onset of sedative medications during surgery, the anesthetist erroneously believed that the CVC had penetrated the superior vena cava, leading to the premature removal of the CVC. Postoperative contrast-enhanced computed tomography of the chest confirmed that the central venous catheter had not penetrated the superior vena cava but malpositioned into the azygos vein. The patient was discharged 15 days after surgery without any complications.

Conclusions

CVC malposition into the azygos vein is extremely rare. Clinical practitioners should be vigilant regarding this form of catheter misplacement. Ensuring the accurate positioning of the CVC before each infusion is crucial. Utilizing chest X-rays in both frontal and lateral views, as well as chest computed tomography, can aid in confirming the presence of catheter misplacement.
Heparin-free veno-arterial extracorporeal membrane oxygenation in lung transplantation: a retrospective cohort study
Authors: Huang ZhaoMin , Zheng Jiayi , Wang Mingyang , Zeng Shaoting , Huang Miaoting , Peng Shuyi , Li Jiajun , Ji Jiaming , Chen Quan , Xu Xin , Yang Chao , Peng GuiLin , Yang Hanyu
Published: April 2024

Background

In lung transplantation (LTx) surgery, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide mechanical circulatory support to patients with cardiopulmonary failure. However, the use of heparin in the administration of ECMO can increase blood loss during LTx. This study aimed to evaluate the safety of heparin-free V-A ECMO strategies.

Methods

From September 2019 to April 2022, patients who underwent lung transplantation at the First Affiliated Hospital of Guangzhou Medical University were retrospectively reviewed. A total of 229 patients were included, including 117 patients in the ECMO group and 112 in the non-ECMO group.

Result

There was no significant difference in the incidence of thrombus events and bleeding requiring reoperation between the two groups. The in-hospital survival rate after single lung transplantation (SLTx) was 81.08%in the ECMO group and 85.14% in the Non-ECMO group, (P = 0.585). The in-hospital survival rate after double lung transplantation (DLTx) was 80.00% in the ECMO group and 92.11% in the Non-ECMO groups (P = 0.095).

Conclusions

In conclusion, the findings of this study suggest that the heparin-free V-A ECMO strategy in lung transplantation is a safe approach that does not increase the incidence of perioperative thrombotic events or bleeding requiring reoperation.
Outcomes in patients with aortic stenosis and severely reduced ejection fraction following surgical aortic valve replacement and transcatheter aortic valve replacement
Authors: Bain Eric R. , George Bistees , Jafri Syed H. , Rao Roopa A. , Sinha Anjan K. , Guglin Maya E.
Published: April 2024

Background

Patients with severe aortic stenosis (AS) and left ventricular (LV) dysfunction demonstrate improvement in left ventricular injection fraction (LVEF) after aortic valve replacement (AVR). The timing and magnitude of recovery in patients with very low LVEF (≤ 25%) in surgical or transcatheter AVR is not well studied.

Objective

Determine clinical outcomes following transcatheter aortic valve replacement (TAVR) and surgical aortic valve repair (SAVR) in the subset of patients with severely reduced EF ≤ 25%.

Methods

Single-center, retrospective study with primary endpoint of LVEF 1-week following either procedure. Secondary outcomes included 30-day mortality and delayed postprocedural LVEF. T-test was used to compare variables and linear regression was used to adjust differences among baseline variables.

Results

83 patients were enrolled (TAVR = 56 and SAVR = 27). TAVR patients were older at the time of procedure (TAVR 77.29 ± 8.69 vs. SAVR 65.41 ± 10.05, p < 0.001). One week post procedure, all patients had improved LVEF after both procedures (p < 0.001). There was no significant difference in LVEF between either group (TAVR 33.5 ± 11.77 vs. SAVR 35.3 ± 13.57, p = 0.60). Average LVEF continued to rise and increased by 101% at final follow-up (41.26 ± 13.70). 30-day mortality rates in SAVR and TAVR were similar (7.4% vs. 7.1%, p = 0.91).

Conclusion

Patients with severe AS and LVEF ≤ 25% have a significant recovery in post-procedural EF following AVR regardless of method. LVEF doubled at two years post-procedure. There was no significant difference in 30-day mortality or mean EF recovery between TAVR and SAVR.

Trial registration

Indiana University institutional review board granted approval for above study numbered 15,322.
Impact of postoperative cerebral complications in acute infective endocarditis: a retrospective single-center study
Authors: Sugiyama Kayo , Watanuki Hirotaka , Tochii Masato , Kai Takayuki , Koiwa Daisuke , Matsuyama Katsuhiko
Published: April 2024

Background

The treatment of patients with infective endocarditis (IE) who have preoperative cerebral complications remains less understood. Therefore, this study aimed to retrospectively evaluate the clinical outcomes of patients with acute IE based on preoperative intracranial findings.

Methods

Of 32 patients with acute IE treated at our hospital between August 2015 and March 2022, 31 patients of whom preoperative intracranial imaging evaluation was available were included in our analysis and compared with those with and without intracranial findings. We controlled the mean arterial blood pressure and activated clotting time (ACT) to prevent abnormally high perfusion pressures and ACTs during cardiopulmonary bypass (CPB). The preoperative background, and postoperative courses focusing on postoperative brain complications were reviewed.

Results

Among the 31 patients, 20 (65%) had preoperative imaging findings. The group with intracranial findings was significantly older, with more embolisms in other organs, positive intraoperative pathology findings, and longer CPB times. A new cerebral hemorrhage developed postoperatively in one patient without intracranial findings. There were no early deaths; two patients had recurrent infections in each group, and one died because of sepsis in the late phase in the group with intracranial findings.

Conclusions

Positive intracranial findings indicated significantly active infectious conditions preoperatively but did not affect the postoperative course. Patients without preoperative cerebral complications can develop serious cerebral hemorrhage. Although meticulous examination of preoperative cerebral complications in all patients with IE is essential, a strategy should be adopted to prevent cerebral hemorrhage, even in patients without intracranial findings.
N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1
Authors: Li Jing , Xu Xiaohong , Xu Kaihao , Zhou Xueliang , Wu Kunpeng , Yao Yuan , Liu Zaoqu , Chen Chen , Wang Ling , Sun Zhenqiang , Jiao Dechao , Han Xinwei
Published: April 2024

Background

Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC.

Methods

CircRNAs in paired ICC and adjacent tissues were screened by circRNAs sequencing. To explore the impact of circRNAs on ICC development, experiments involving gain and loss of function were conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, RNA pull-down, chromatin immunoprecipitation (ChIP), ubiquitination assays and so on were employed to identify the molecular regulatory role of circRNAs.

Results

Herein, we reported a new circRNA, which originates from exon 9 to exon 15 of the SLCO1B3 gene (named circSLCO1B3), orchestrated ICC progression by promoting tumor proliferation, metastasis and immune evasion. We found that the circSLCO1B3 gene was highly overexpressed in ICC tissues and related to lymphatic metastasis, tumor sizes, and tumor differentiation. Mechanically, circSLCO1B3 not only promoted ICC proliferation and metastasis via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity via suppressing ubiquitin-proteasome-dependent degradation of PD-L1 by E3 ubiquitin ligase SPOP. We further found that methyltransferase like 3 (METTL3) mediated the m6A methylation of circSLCO1B3 and stabilizes its expression. Our findings indicate that circSLCO1B3 is a potential prognostic marker and therapeutic target in ICC patients.

Conclusions

Taken together, m6A-modified circSLCO1B3 was correlated with poor prognosis in ICC and promoted ICC progression not only by enhancing proliferation and metastasis via potentiating HOXC8 expression, but also by inducing immune evasion via antagonizing PD-L1 degradation. These results suggest that circSLCO1B3 is a potential prognostic marker and therapeutic target for ICC.
Phosphoproteomic analysis reveals changes in A-Raf-related protein phosphorylation in response to Toxoplasma gondii infection in porcine macrophages
Authors: Su Dingzeyang , Zhu Shifan , Xu Kangzhi , Hou Zhaofeng , Hao Fuxing , Xu Fan , Lin Yifan , Zhu Yuyang , Liu Dandan , Duan Qiangde , Zhang Xinjun , Yuan Yuguo , Xu Jinjun , Tao Jianping
Published: April 2024

Background

Toxoplasma gondii is an obligate intracellular protozoan parasite that causes severe threats to humans and livestock. Macrophages are the cell type preferentially infected by T. gondii in vivo. Protein phosphorylation is an important posttranslational modification involved in diverse cellular functions. A rapidly accelerated fibrosarcoma kinase (A-Raf) is a member of the Raf family of serine/threonine protein kinases that is necessary for MAPK activation. Our previous research found that knockout of A-Raf could reduce T. gondii-induced apoptosis in porcine alveolar macrophages (3D4/21 cells). However, limited information is available on protein phosphorylation variations and the role of A-Raf in macrophages infected with T. gondii.

Methods

We used immobilized metal affinity chromatography (IMAC) in combination with liquid chromatography tandem mass spectrometry (LC–MS/MS) to profile changes in phosphorylation in T. gondii-infected 3D4/21 and 3D4/21-ΔAraf cells.

Results

A total of 1647 differentially expressed phosphorylated proteins (DEPPs) with 3876 differentially phosphorylated sites (DPSs) were identified in T. gondii-infected 3D4/21 cells (p3T group) when compared with uninfected 3D4/21 cells (pho3 group), and 959 DEPPs with 1540 DPSs were identified in the p3T group compared with infected 3D4/21-ΔAraf cells (p3KT group). Venn analysis revealed 552 DPSs corresponding to 406 DEPPs with the same phosphorylated sites when comparing p3T/pho3 versus p3T/p3KT, which were identified as DPSs and DEPPs that were directly or indirectly related to A-Raf.

Conclusions

Our results revealed distinct responses of macrophages to T. gondii infection and the potential roles of A-Raf in fighting infection via phosphorylation of crucial proteins.

Graphical Abstract
Combined cardiac, lung, and diaphragm ultrasound for predicting weaning failure during spontaneous breathing trial
Authors: Song Jia , Luo Qiancheng , Lai Xinle , Hu Weihang , Yu Yihua , Wang Minjia , Yang Kai , Chen Gongze , Chen Wenwei , Li Qian , Hu Caibao , Gong Shijin
Published: April 2024

Background

Weaning from invasive mechanical ventilation (MV) is a complex and challenging process that involves multiple pathophysiological mechanisms. A combined ultrasound evaluation of the heart, lungs, and diaphragm during the weaning phase can help to identify risk factors and underlying mechanisms for weaning failure. This study aimed to investigate the accuracy of lung ultrasound (LUS), transthoracic echocardiography (TTE), and diaphragm ultrasound for predicting weaning failure in critically ill patients.

Methods

Patients undergoing invasive MV for > 48 h and who were readied for their first spontaneous breathing trial (SBT) were studied. Patients were scheduled for a 2-h SBT using low-level pressure support ventilation. LUS and TTE were performed prospectively before and 30 min after starting the SBT, and diaphragm ultrasound was only performed 30 min after starting the SBT. Weaning failure was defined as failure of SBT, re-intubation, or non-invasive ventilation within 48 h.

Results

Fifty-one patients were included, of whom 15 experienced weaning failure. During the SBT, the global, anterior, and antero-lateral LUS scores were higher in the failed group than in the successful group. Receiver operating characteristic curve analysis showed that the areas under the curves for diaphragm thickening fraction (DTF) and global and antero-lateral LUS scores during the SBT to predict weaning failure were 0.678, 0.719, and 0.721, respectively. There was no correlation between the LUS scores and the average E/e’ ratio during the SBT. Multivariate analysis identified antero-lateral LUS score > 7 and DTF < 31% during the SBT as independent predictors of weaning failure.

Conclusion

LUS and diaphragm ultrasound can help to predict weaning failure in patients undergoing an SBT with low-level pressure support. An antero-lateral LUS score > 7 and DTF < 31% during the SBT were associated with weaning failure.

Graphical Abstract
Analyses of lncRNA and mRNA profiles in recurrent atrial fibrillation after catheter ablation
Authors: Tang Huaiguang , Lu Kongmiao , Wang Yan , Shi Yue , Ma Wansheng , Chen Xiaomeng , Li Bingong , Shao Yibing
Published: April 2024

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Catheter ablation has become a crucial treatment for AF. However, there is a possibility of atrial fibrillation recurrence after catheter ablation. Our study sought to elucidate the role of lncRNA‒mRNA regulatory networks in late AF recurrence after catheter ablation.

Methods

We conducted RNA sequencing to profile the transcriptomes of 5 samples from the presence of recurrence after AF ablation (P-RAF) and 5 samples from the absence of recurrence after AF ablation (A-RAF). Differentially expressed genes (DEGs) and long noncoding RNAs (DE-lncRNAs) were analyzed using the DESeq2 R package. The functional correlations of the DEGs were assessed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A protein‒protein interaction (PPI) network was constructed using STRING and Cytoscape. We also established a lncRNA‒mRNA regulatory network between DE-lncRNAs and DEGs using BEDTools v2.1.2 software and the Pearson correlation coefficient method. To validate the high-throughput sequencing results of the hub genes, we conducted quantitative real-time polymerase chain reaction (qRT‒PCR) experiments.

Results

A total of 28,528 mRNAs and 42,333 lncRNAs were detected. A total of 96 DEGs and 203 DE-lncRNAs were identified between the two groups. GO analysis revealed that the DEGs were enriched in the biological processes (BPs) of “regulation of immune response” and “regulation of immune system process”, the cellular components (CCs) of “extracellular matrix” and “cell‒cell junction”, and the molecular functions (MFs) of “signaling adaptor activity” and “protein–macromolecule adaptor activity”. According to the KEGG analysis, the DEGs were associated with the “PI3K–Akt signaling pathway” and “MAPK signaling pathway.” Nine hub genes (MMP9, IGF2, FGFR1, HSPG2, GZMB, PEG10, GNLY, COL6A1, and KCNE3) were identified through the PPI network. lncRNA-TMEM51-AS1-201 was identified as a core regulator in the lncRNA‒mRNA regulatory network, suggesting its potential impact on the recurrence of AF after catheter ablation through the regulation of COL6A1, FGFR1, HSPG2, and IGF2.

Conclusions

The recurrence of atrial fibrillation after catheter ablation may be associated with immune responses and fibrosis, with the extracellular matrix playing a crucial role. TMEM51-AS1-201 has been identified as a potential key target for AF recurrence after catheter ablation.
Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles
Authors: Li Kun , Cui Yadong , Zheng Xue , Min Chunyan , Zhang Jian , Yan Zhanpeng , Ji Yu , Ge Fei , Ji Hualiang , Zhu Fangshi
Published: April 2024

Background

Immunological liver injury (ILI) is a common liver disease associated with the microbiota-gut-liver axis. Jian Gan powder (JGP) exhibits both protective and therapeutic effects on hepatitis virus-induced ILI in the clinic. However, the underlying mechanisms remain elusive. The aim of this study is to investigate the hepatoprotective effects and associated mechanisms of JGP in the context of gut microbiota, utilizing a mouse model of ILI.

Methods

The mouse model was established employing Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS). Following treatment with JGP (7.5, 15, or 30 g/kg), serum, liver, and fresh fecal samples were analyzed. 16S rRNA gene sequencing and untargeted metabolomics profiling were performed to assess the role of JGP on the gut microbiota and its metabolites.

Results

JGP treatment markedly reduced serum IFN-γ, IL-6, IL-22, and hepatic p-STAT3 (phosphorylated transducer and activator of transcription-3) expression. In contrast, JGP increased the percentage of proliferating cell nuclear antigen-positive liver cells in treated mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the levels of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, metabolomics analysis of fecal samples showed that JGP restored the levels of allylestrenol, eplerenone, phosphatidylethanolamine (PE) (P-20:0/0:0), sphingomyelin (SM) d27:1, soyasapogenol C, chrysin, and soyasaponin I.

Conclusions

JGP intervention improves ILI by restoring gut microbiota and modifying its metabolic profiles. These results provide a novel insight into the mechanism of JGP in treating ILI and the scientific basis to support its clinical application.
Specific mortality in patients with diffuse large B-cell lymphoma: a retrospective analysis based on the surveillance, epidemiology, and end results database
Authors: Xu Hui , Yan Rong , Ye Chunmei , Li Jun , Ji Guo
Published: April 2024

Background

The full potential of competing risk modeling approaches in the context of diffuse large B-cell lymphoma (DLBCL) patients has yet to be fully harnessed. This study aims to address this gap by developing a sophisticated competing risk model specifically designed to predict specific mortality in DLBCL patients.

Methods

We extracted DLBCL patients’ data from the SEER (Surveillance, Epidemiology, and End Results) database. To identify relevant variables, we conducted a two-step screening process using univariate and multivariate Fine and Gray regression analyses. Subsequently, a nomogram was constructed based on the results. The model’s consistency index (C-index) was calculated to assess its performance. Additionally, calibration curves and receiver operator characteristic (ROC) curves were generated to validate the model’s effectiveness.

Results

This study enrolled a total of 24,402 patients. The feature selection analysis identified 13 variables that were statistically significant and therefore included in the model. The model validation results demonstrated that the area under the receiver operating characteristic (ROC) curve (AUC) for predicting 6-month, 1-year, and 3-year DLBCL-specific mortality was 0.748, 0.718, and 0.698, respectively, in the training cohort. In the validation cohort, the AUC values were 0.747, 0.721, and 0.697. The calibration curves indicated good consistency between the training and validation cohorts.

Conclusion

The most significant predictor of DLBCL-specific mortality is the age of the patient, followed by the Ann Arbor stage and the administration of chemotherapy. This predictive model has the potential to facilitate the identification of high-risk DLBCL patients by clinicians, ultimately leading to improved prognosis.
Comparison of self-esteem and quality of life in 8-12-year-old children with ADHD with and without learning disorders
Authors: Massoodi Armon , Moudi Sussan , Malekiamiri Maryam , Ahangar Hemmat Gholinia
Published: April 2024

Background

Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common disorders in school-aged children. Learning disorder (LD) is also one of the most important psychiatric disorders in children, which can often be associated with ADHD. In this study, we sought to compare self-esteem and quality of life in 8 to 12-year-old children with attention deficit/hyperactivity disorder with and without co-occurring learning disorders in order to emphasize the importance of attention and diagnosis in children with ADHD.

Method

Among the 8- to 12-year-old outpatients referred to the child and adolescent psychiatry clinic of Omid Babol Clinic, 120 children aged 8 to 12 years with attention deficit/hyperactivity disorder whose disease was diagnosed by a child and adolescent psychiatry subspecialist. Among the tools used to collect information was the Colorado Learning Difficulties Questionnaire by Wilcott et al. (CLDQ), five-scale self-esteem test of Pepe et al. (1989) for children and quality-of-life questionnaire for 8–12-year-old children (PedsQL).

Results

This study investigated self-esteem and quality of life in children with ADHD (n = 120, 51.7% boys). Children with ADHD and learning disabilities reported significantly lower self-esteem and quality of life compared to those with ADHD alone.

Conclusion

Considering the relatively high probability of co-occurrence of ADHD and learning disorders, if one of them is diagnosed in a child, it is possible to look for other disorders in the child in order to avoid the more severe negative effects that this co-occurrence can have on the child by diagnosing it as soon as possible.
Nutrients, surfactants, and aeration in constructed wetlands affect bacterial persistence and metabolic activity during the remediation of crude oil-contaminated water
Authors: Hashmat Amer Jamal , Afzal Muhammad , Iqbal Samina , Amin Imran , Arias Carlos Alberto , Brix Hans , Zafar Imran , Riaz Sania , Rehman Rizwan ur , Salamatullah Ahmad Mohammad , Wondmie Gezahign Fentahun , Bourhia Mohammed
Published: April 2024

The use of constructed wetlands (CWs) is one of the best options to treat wastewater. In CWs, microorganisms play a major role in the degradation of organic pollutants but the concentration of nutrients, surfactant, and aeration (NSA) in oil-contaminated water is one of the factors that affect the persistence and metabolic functioning of hydrocarbon-degrading microorganisms. In the present investigation, the influence of the addition of NSA on the persistence of the augmented bacteria, copy of (alkane hydroxylase gene) alkB gene, and its expression level in the water, soil, and plants of CWs were evaluated. The CWs mesocosms were developed by the vegetation of Typha latifolia and Cyperus laevigatus and inoculated with the bacterial consortium (Pseudomonas putida TYRI39, Acinetobacter junii TYRH47, Acinetobacter sp. CYRH17, Pseudomonas sp. CYSI27, and Pseudomonas sp. TYRH42). The mesocosms were provided with nutrients (20 mg l− 1 N, 2.6 mg l− 1 P, and 16.4 mg l− 1 K) in liquid form, surfactant Tween-20 (0.2%, v/v) in liquid form, and aeration (≥ 7.0 ± 1 mg l− 1 DO) using aeration pump. The addition of NSA in CWs enhanced the persistence and metabolic functioning of the inoculated bacteria in the water, rhizospheric soil, and plants. The maximum hydrocarbon removal (97%) was observed in the water treated by CWs having C. laevigatus, bacteria, and NSA, and it is correlated with the copy numbers of alkB and its expression level. The application of NSA in CWs not only improved bacterial persistence and catabolic gene expression but also increased plant development and hydrocarbon removal.
Forecasting relative returns for S&P 500 stocks using machine learning
Authors: Htun Htet Htet , Biehl Michael , Petkov Nicolai
Published: April 2024

Forecasting changes in stock prices is extremely challenging given that numerous factors cause these prices to fluctuate. The random walk hypothesis and efficient market hypothesis essentially state that it is not possible to systematically, reliably predict future stock prices or forecast changes in the stock market overall. Nonetheless, machine learning (ML) techniques that use historical data have been applied to make such predictions. Previous studies focused on a small number of stocks and claimed success with limited statistical confidence. In this study, we construct feature vectors composed of multiple previous relative returns and apply the random forest (RF), support vector machine (SVM), and long short-term memory (LSTM) ML methods as classifiers to predict whether a stock can return 2% more than its index in the following 10 days. We apply this approach to all S&P 500 companies for the period 2017–2022. We assess performance using accuracy, precision, and recall and compare our results with a random choice strategy. We observe that the LSTM classifier outperforms RF and SVM, and the data-driven ML methods outperform the random choice classifier (p = 8.46e−17 for accuracy of LSTM). Thus, we demonstrate that the probability that the random walk and efficient market hypotheses hold in the considered context is negligibly small.
Hepatic artery stenosis following adult liver transplantation: evaluation of different endovascular treatment approaches
Authors: Desai Sagar V. , Natarajan Balasubramani , Khanna Vinit , Brady Paul
Published: April 2024

Purpose

To evaluate the efficacy and safety of hepatic artery interventions (HAI) versus extra-hepatic arterial interventions (EHAI) when managing clinically significant hepatic artery stenosis (HAS) after adult orthotopic liver transplantation.

Materials and methods

A single-center retrospective cohort analysis was conducted on liver transplant patients who underwent intervention for clinically significant HAS from September 2012 to September 2021. The HAI treatment arm included hepatic artery angioplasty and/or stent placement while the EHAI treatment arm comprised of non-hepatic visceral artery embolization. Primary outcomes included peri-procedural complications and 1-year liver-related deaths. Secondary outcomes included biliary ischemic events, longitudinal trends in liver enzymes and ultrasound parameters pre-and post-intervention.

Results

The HAI arm included 21 procedures in 18 patients and the EHAI arm included 27 procedures in 22 patients. There were increased 1-year liver-related deaths (10% [2/21] vs 0% [0/27], p = 0.10) and complications (29% [6/21] vs 4% [1/27], p = 0.015) in the HAI group compared to the EHAI group. Both HAI and EHAI groups exhibited similar improvements in transaminitis including changes of ALT (-72 U/L vs -112.5 U/L, p = 0.60) and AST (-58 U/L vs -48 U/L, p = 0.56) at 1-month post-procedure. Both treatment arms demonstrated increases in post-procedural peak systolic velocity of the hepatic artery distal to the stenosis, while the HAI group also showed significant improvement in resistive indices following the intervention.

Conclusion

Direct hepatic artery interventions remain the definitive treatment for clinically significant hepatic artery stenosis; however, non-hepatic visceral artery embolization can be considered a safe alternative intervention in cases of unfavorable hepatic anatomy.

Graphical Abstract
Screening Cutoff Values for the Detection of Aldosterone-Producing Adenoma by LC-MS/MS and a Novel Noncompetitive CLEIA
Authors: Ono Yoshikiyo , Tezuka Yuta , Omata Kei , Morimoto Ryo , Yamazaki Yuto , Oguro Sota , Takase Kei , Ito Akihiro , Yoshimi Tatsunari , Kojima Satoshi , Ito Sadayoshi , Sasano Hironobu , Suzuki Takashi , Tanaka Tetsuhiro , Katagiri Hideki , Satoh Fumitoshi
Published: April 2024

Context

Detecting patients with surgically curable aldosterone-producing adenoma (APA) among hypertensive individuals is clinically pivotal. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is the ideal method of measuring plasma aldosterone concentration (PAC) because of the inaccuracy of conventional chemiluminescent enzyme immunoassay (CLEIA). However, LC-MS/MS is expensive and requires expertise. We have developed a novel noncompetitive CLEIA (NC-CLEIA) for measuring PAC in 30 minutes.

Objective

This work aimed to validate NC-CLEIA PAC measurements by comparing them with LC-MS/MS measurements and determining screening cutoffs for both measurements detecting APA.

Methods

We retrospectively measured PAC using LC-MS/MS and NC-CLEIA in 133 patients with APA, 100 with bilateral hyperaldosteronism, and 111 with essential hypertension to explore the accuracy of NC-CLEIA PAC measurements by comparing with LC-MS/MS measurements and determined the cutoffs for detecting APA.

Results

Passing-Bablok analysis revealed that the values by NC-CLEIA (the regression slope, intercept, and correlation coefficient were 0.962, −0.043, and 0.994, respectively) were significantly correlated and equivalent to those by LC-MS/MS. Bland-Altman plot analysis of NC-CLEIA and LC-MS/MS also demonstrated smaller systemic errors (a bias of −0.348 ng/dL with limits of agreement of −4.390 and 3.694 within a 95% CI) in NC-CLEIA than LC-MS/MS. The receiver operating characteristic analysis demonstrated that cutoff values for aldosterone/renin activity ratio obtained by LC-MS/MS and NC-CLEIA were 31.2 and 31.5 (ng/dL per ng/mL/hour), with a sensitivity of 91.0% and 90.2% and specificity of 75.4% and 76.8%, respectively, to differentiate APA from non-APA.

Conclusion

This newly developed NC-CLEIA for measuring PAC could serve as a clinically reliable alternative to LC-MS/MS.