bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomised phase II study of extended pleurectomy/decortication preceded or followed by chemotherapy in patients with early-stage pleural mesothelioma: EORTC 1205
Authors: Raskin Jo , Surmont Veerle , Maat Alexander P.W.M. , Yahia Maha , Burgers Sjaak A. , Pretzenbacher Yassin , De Ryck Frederic , Cornelissen Robin , Klomp Houke M. , Oliveira Ana , Aerts Joachim , Baas Paul , Marreaud Sandrine , Van Meerbeeck Jan P. , Van Schil Paul E.Y.
Published: June 2024

Background

The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown.

Methods

EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0–1) had treatment-naïve, borderline resectable T1–3 N0–1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3–4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality.

Findings

69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8–81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8–62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5–17.2) months and 27.1 (95% CI 22.6–64.3) months in arm A, and 8.0 (95% CI 7.2–21.9) months and 33.8 (95% CI 23.8–44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high.

Interpretation

EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.
Multivariate investigation of Moringa oleifera morpho-physiological and biochemical traits under various water regimes
Authors: Hajaji Afef N. , Heikal Yasmin M. , Hamouda Ragaa A. E. F. , Abassi Mejda , Ammari Youssef
Published: June 2024

Background

The climatic changes crossing the world menace the green life through limitation of water availability. The goal of this study was to determine whether Moringa oleifera Lam. trees cultivated under Tunisian arid climate, retain their tolerance ability to tolerate accentuated environmental stress factors such as drought and salinity. For this reason, the seeds of M. oleifera tree planted in Bouhedma Park (Tunisian arid area), were collected, germinated, and grown in the research area at the National Institute of Research in Rural Engineering, Waters and Forests (INRGREF) of Tunis (Tunisia). The three years aged trees were exposed to four water-holding capacities (25, 50, 75, and 100%) for 60 days to realise this work.

Results

Growth change was traduced by the reduction of several biometric parameters and fluorescence (Fv/Fm) under severe water restriction (25 and 50%). Whereas roots presented miraculous development in length face to the decrease of water availability (25 and 50%) in their rhizospheres. The sensitivity to drought-induced membrane damage (Malondialdehyde (MDA) content) and reactive oxygen species (ROS) liberation (hydrogen peroxide (H2O2) content) was highly correlated with ROS antiradical scavenging (ferric reducing antioxidant power (FRAP) and (2, 2’-diphenyl-1-picrylhydrazyle (DPPH)), phenolic components and osmolytes accumulation. The drought stress tolerance of M. oleifera trees was associated with a dramatic stimulation of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), ascorbate peroxidase (APX), and glutathione peroxidase (GPX) activities.

Conclusion

Based on the several strategies adopted, integrated M. oleifera can grow under drought stress as accentuated adverse environmental condition imposed by climate change.
Programmed death-ligand 1 expression in carcinoma of unknown primary
Authors: Kim Hye Min , Koo Ja Seung
Published: June 2024

We examined the expression of programmed death-ligand 1 (PD-L1) in carcinoma of unknown primary (CUP) and its potential implications. Tissue microarrays were constructed for 72 CUP cases (histologic subtypes: 22 adenocarcinoma, 15 poorly differentiated carcinoma, 19 squamous cell carcinoma, and 14 undifferentiated carcinoma; clinical subtype: favorable type 17 [23.6%], unfavorable type 55 [76.4%]), with immunohistochemical staining performed for PD-L1 (22C3, SP142, SP263, and 28 − 8), CK7, and CK20 to determine the association between staining results and clinicopathological parameters. In CUP, the PD-L1 positivity rate was 5.6–48.6% (tumor cells [TC] or tumor proportion score [TPS]: 5.6–36.1%, immune cell score [IC]: 8.3–48.6%, combined positive score [CPS]: 16.7%) using different cutoff values for 22C3 (TPS ≥ 1%, CPS ≥ 10), SP142 (TC ≥ 50%, IC ≥ 10%), SP263, and 28 − 8 (TC and IC ≥ 1%). PD-L1 SP142 TC and PD-L1 SP263 IC showed the lowest (5.6%) and highest (48.6%) positivity rates, respectively. The PD-L1 positivity rate did not significantly differ based on the histologic subtype, clinical subtype, or CK7/CK20 across clones. Considering TC κ ≥ 1%, TC κ ≥ 50%, IC κ ≥ 1%, and IC κ ≥ 10%, the PD-L1 positivity rate was TC = 4.2–36.1% and IC = 9.7–48.6%; the overall agreement between antibodies ranged from 69.4 to 93.1%, showing fair or better agreement (κ ≥ 0.21). In CUP, PD-L1 positivity varied depending on antibodies and scoring systems, with no difference observed according to histologic or clinical subtypes.
New evidence: Metformin unsuitable as routine adjuvant for breast cancer: a drug-target mendelian randomization analysis
Authors: Xu Jing-Xuan , Zhu Qi-Long , Bi Yu-Miao , Peng Yu-Chong
Published: June 2024

Purpose

The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk.

Methods

Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability.

Results

The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results.

Conclusion

The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.
Challenges and opportunities for competency-based health professional education in Bangladesh: an interview, observation and mapping study
Authors: Byrne-Davis Lucie , Carr Natalie , Roy Tapash , Chowdhury Salim , Omer Usmaan , Nawaz Saher , Advani Dolce , Byrne Olivia , Hart Jo
Published: June 2024

Background

Bangladesh has a shortfall of health professionals. The World Health Organization states that improving education will increase recruitment and retention of health workers. Traditional learning approaches, in medical education particularly, focus on didactic teaching, teaching of subjects and knowledge testing. These approaches have been superseded in some programmes, with a greater focus on active learning, integrated teaching and learning of knowledge, application, skills and attitudes or values and associated testing of competencies as educational outcomes. In addition, some regions do not have continuous professional development or clinical placements for health worker students, contributing to difficulties in retention of health workers. This study aims to explore the experiences of health professional education in Bangladesh, focusing on what is through observation of health professional education sessions and experiences of educators.

Methods

This mixed method study included 22 observations of teaching sessions in clinical and educational settings, detailed analysis of 8 national curricula documents mapped to Global Competency and Outcomes Framework for Universal Health Coverage and 15 interviews of professionals responsible for health education. An observational checklist was created based on previous literature which assessed training of within dimensions of basic clinical skills; diagnosis and management; professionalism; professional development; and effective communication. Interviews explored current practices within health education in Bangladesh, as well as barriers and facilitators to incorporating different approaches to learning.

Results

Observations revealed a variety of approaches and frameworks followed across institutions. Only one observation included all sub-competencies of the checklist. National curricula documents varied in their coverage of the Global Competency and Outcomes Framework domains. Three key themes were generated from a thematic analysis of interview transcripts: (1) education across the career span; (2) challenges for health professional education; (3) contextual factors and health professional education. Opportunities for progression and development post qualification are limited and certain professions are favoured over others.

Conclusion

Traditional approaches seem to predominate but there is some enthusiasm for a more clinical focus to education and for more competency based approaches to teaching, learning and assessment.
E-learning platforms in ideological and political education at universities: students’ motivation and learning performance
Authors: Yang Huabing
Published: June 2024

Background

The study aimed to examine the impact of using the MOODLE e-learning platform in ideological and political education on Chinese students’ motivation and academic performance.

Methods

The study involved 447 students from China-based universities (the experimental group − 232 students who studied using electronic educational platforms, and the control group − 215 students who used no digital technologies in their learning). The following methods were used: Measuring the need to achieve success among students; T. I. Ilyina’s method for studying motivation to study at university; Method for studying student success motivation; Method for studying the motives of students’ educational activities; Method for determining the main motives for choosing a profession (E. M. Pavlyutenkov); Motivation of learning activities: Levels and types (I. S. Dombrovskaya). Students’ academic performance was assessed by testing in the studied disciplines at the beginning and end of the study.

Results

As a result, the significance of the motivational component in achieving the success of ideological and political education and the impact on students’ motivation to use e-learning platforms is theoretically substantiated.

Conclusions

It has been confirmed that using e-learning platforms in ideological and political education helps increase student motivation and academic performance.
The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC
Authors: Li Huizi , Liu Jin , Lai Jie , Su Xinyao , Wang Xiaofeng , Cao Jiaqing , Mao Shengxun , Zhang Tong , Gu Qiuping
Published: June 2024

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.
First detection of Tetraparvovirus ungulate 1 in diseased cattle (Chinese Simmental) from Hunan province, China
Authors: Shi Yin , Tang Hui , Zhou Zhi-Jian , Liao Jing-Ying , Ge Xing-Yi , Xiao Chao-Ting
Published: June 2024

Tetraparvovirus is an emerging parvovirus infecting a variety of mammals and humans, and associated with human diseases including severe acute respiratory infection and acute encephalitis syndrome. In the present study, a Tetraparvovirus ungulate 1 (formerly known as bovine hokovirus) strain HNU-CBY-2023 was identified and characterized from diseased Chinese Simmental from Hunan province, China. The nearly complete genome of HNU-CBY-2023 is 5346 nt in size and showed genomic identities of 85-95.5% to the known Tetraparvovirus ungulate 1 strains from GenBank, indicating a rather genetic variation. Phylogenetic and genetic divergence analyses indicated that Tetraparvovirus ungulate 1 could be divided into two genotypes (I and II), and HNU-CBY-2023 was clustered into genotype II. This study, for the first time, identified Tetraparvovirus ungulate 1 from domestic cattle from mainland China, which will be helpful to understand the prevalence and genetic diversity of Tetraparvovirus ungulate 1.
Assessing the predictive capability of machine learning models in determining clinical outcomes for patients with cervical spondylotic myelopathy treated with laminectomy and posterior spinal fusion
Authors: Alimohammadi Ehsan , Fatahi Elnaz , Abdi Alireza , Reza Bagheri Seyed
Published: June 2024

Background

Cervical spondylotic myelopathy (CSM) is a prevalent degenerative condition resulting from spinal cord compression and injury. Laminectomy with posterior spinal fusion (LPSF) is a commonly employed treatment approach for CSM patients. This study aimed to assess the effectiveness of machine learning models (MLMs) in predicting clinical outcomes in CSM patients undergoing LPSF.

Methods

A retrospective analysis was conducted on 329 CSM patients who underwent LPSF at our institution from Jul 2017 to Jul 2023. Neurological outcomes were evaluated using the modified Japanese Orthopaedic Association (mJOA) scale preoperatively and at the final follow-up. Patients were categorized into two groups based on clinical outcomes: the favorable group (recovery rates ≥ 52.8%) and the unfavorable group (recovery rates < 52.8%). Potential predictors for poor clinical outcomes were compared between the groups. Four MLMs—random forest (RF), logistic regression (LR), support vector machine (SVM), and k-nearest neighborhood (k-NN)—were utilized to predict clinical outcome. RF model was also employed to identify factors associated with poor clinical outcome.

Results

Out of the 329 patients, 185 were male (56.2%) and 144 were female (43.4%), with an average follow-up period of 17.86 ± 1.74 months. Among them, 267 patients (81.2%) had favorable clinical outcomes, while 62 patients (18.8%) did not achieve favorable results. Analysis using binary logistic regression indicated that age, preoperative mJOA scale, and symptom duration (p < 0.05) were independent predictors of unfavorable clinical outcomes. All models performed satisfactorily, with RF achieving the highest accuracy of 0.922. RF also displayed superior sensitivity and specificity (sensitivity = 0.851, specificity = 0.944). The Area under the Curve (AUC) values for RF, Logistic LR, SVM, and k-NN were 0.905, 0.827, 0.851, and 0.883, respectively. The RF model identified preoperative mJOA scale, age, symptom duration, and MRI signal changes as the most significant variables associated with poor clinical outcomes in descending order.

Conclusions

This study highlighted the effectiveness of machine learning models in predicting the clinical outcomes of CSM patients undergoing LPSF. These models have the potential to forecast clinical outcomes in this patient population, providing valuable prognostic insights for preoperative counseling and postoperative management.
Ferroptosis: principles and significance in health and disease
Authors: Chen Fangquan , Kang Rui , Tang Daolin , Liu Jiao
Published: June 2024

Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed by molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic cell death pathway in 2012, ferroptosis has emerged as a crucial mechanism in numerous physiological and pathological contexts, leading to significant therapeutic advancements across a wide range of diseases. This review summarizes the fundamental molecular mechanisms and regulatory pathways underlying ferroptosis, including both GPX4-dependent and -independent antioxidant mechanisms. Additionally, we examine the involvement of ferroptosis in various pathological conditions, including cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, and metabolic disorders. Specifically, we explore the role of ferroptosis in response to chemotherapy, radiotherapy, immunotherapy, nanotherapy, and targeted therapy. Furthermore, we discuss pharmacological strategies for modulating ferroptosis and potential biomarkers for monitoring this process. Lastly, we elucidate the interplay between ferroptosis and other forms of regulated cell death. Such insights hold promise for advancing our understanding of ferroptosis in the context of human health and disease.
Enhancing patient-clinician collaboration during treatment decision-making: study protocol for a community-engaged, mixed method hybrid type 1 trial of collaborative decision skills training (CDST) for veterans with psychosis
Authors: Treichler Emily B. H. , McBride Lauren E. , Gomez Elissa , Jain Joanna , Seaton Sydney , Yu Kasey E. , Oakes David , Perivoliotis Dimitri , Girard Vanessa , Reznik Samantha , Salyers Michelle P. , Thomas Michael L. , Spaulding William D. , Granholm Eric L. , Rabin Borsika A. , Light Gregory A.
Published: June 2024

Background

Patient participation in treatment decision making is a pillar of recovery-oriented care and is associated with improvements in empowerment and well-being. Although demand for increased involvement in treatment decision-making is high among veterans with serious mental illness, rates of involvement are low. Collaborative decision skills training (CDST) is a recovery-oriented, skills-based intervention designed to support meaningful patient participation in treatment decision making. An open trial among veterans with psychosis supported CDST’s feasibility and demonstrated preliminary indications of effectiveness. A randomized control trial (RCT) is needed to test CDST’s effectiveness in comparison with an active control and further evaluate implementation feasibility.

Methods

The planned RCT is a hybrid type 1 trial, which will use mixed methods to systematically evaluate the effectiveness and implementation feasibility of CDST among veterans participating in a VA Psychosocial Rehabilitation and Recovery Center (PRRC) in Southern California. The first aim is to assess the effectiveness of CDST in comparison with the active control via the primary outcome, collaborative decision-making behavior during usual care appointments between veterans and their VA mental health clinicians, and secondary outcomes (i.e., treatment engagement, satisfaction, and outcome). The second aim is to characterize the implementation feasibility of CDST within the VA PRRC using the Practical Robust Implementation and Sustainability Model framework, including barriers and facilitators within the PRRC context to support future implementation.

Discussion

If CDST is found to be effective and feasible, implementation determinants gathered throughout the study can be used to ensure sustained and successful implementation at this PRRC and other PRRCs and similar settings nationally.

Trial registration

ClinicalTrials.gov NCT04324944. Registered on March 27, 2020. Trial registration data can be found in Appendix 1.
Kikuchi disease complicated with aseptic meningitis following COVID-19 Vaccination: a case report
Authors: Kularathna Manana Dewage Sankani Vishvara , Medagama Arjuna , Bandara Ruwanthi , Yasarathna Duminda , Dilani Madugeta Kumarage Ishara , Anuththara Thushani
Published: June 2024

Background

Kikuchi Fujimoto disease is a rare self-limiting disorder mainly affecting young Asian females. The typical presentation is unexplained fever with associated cervical lymphadenopathy. It can mimic many sinister diseases such as lymphoma, tuberculosis, and systemic lupus erythematosus. Aseptic meningitis due to Kikuchi disease is extremely rare, and majority were reported from Japan. There have been no published cases of aseptic meningitis due to Kikuchi disease in Sri Lanka.

Case presentation

A 29 years old Sri Lankan female presented with a prolonged fever for three weeks with an associated headache for five days duration. She developed painful cervical lymphadenopathy during the hospital stay. She has been previously well and had been vaccinated against COVID-19 six weeks before. Her lumbar puncture showed lymphocytic pleocytosis with marginally elevated protein levels and reduced ratio of serum to CSF sugar. Lymph node biopsy was consistent with necrotizing lymphadenitis. She was subsequently diagnosed with Kikuchi disease complicated with aseptic meningitis. She responded to corticosteroids well and had an uneventful recovery.

Conclusion

Kikuchi disease is a rare self-limiting disorder that can be complicated with aseptic meningitis on infrequent occasions. Other conditions such as tuberculosis, lymphoma, systemic lupus erythematosus, and adult-onset Still’s disease should be considered as differential diagnoses. Knowledge of Kikuchi disease and its complications will prevent unnecessary investigations which delay the early diagnosis and treatment.
Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement
Authors: Sakamuri Anil , Visniauskas Bruna , Kilanowski-Doroh Isabella , McNally Alexandra B. , Imulinde Ariane , Kamau Anne , Sengottaian Divya , McLachlan John , Anguera Montserrat , Mauvais-Jarvis Franck , Lindsey Sarah H. , Ogola Benard O.
Published: June 2024

Background

Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men’s health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes. Testosterone replacement is beneficial or neutral to men’s cardiovascular health. Testosterone deficiency is associated with cardiovascular events. Testosterone supplementation to hypogonadal men improves libido, increases muscle strength, and enhances mood. We hypothesized that sex chromosomes (XX and XY) interaction with testosterone plays a role in arterial stiffening.

Methods

We used four core genotype male mice to understand the inherent contribution of sex hormones and sex chromosome complement in arterial stiffening. Age-matched mice were either gonadal intact or castrated at eight weeks plus an additional eight weeks to clear endogenous sex hormones. This was followed by assessing blood pressure, pulse wave velocity, echocardiography, and ex vivo passive vascular mechanics.

Results

Arterial stiffening but not blood pressure was more significant in castrated than testes-intact mice independent of sex chromosome complement. Castrated mice showed a leftward shift in stress–strain curves and carotid wall thinning. Sex chromosome complement (XX) in the absence of testosterone increased collagen deposition in the aorta and Kdm6a gene expression.

Conclusion

Testosterone deprivation increases arterial stiffening and vascular wall remodeling. Castration increases Col1α1 in male mice with XX sex chromosome complement. Our study shows decreased aortic contractile genes in castrated mice with XX than XY sex chromosomes.

Graphical Abstract
The performance of microbial fuel cell with sodium alginate and super activated carbon composite gel modified anode
Authors: Cheng Liangyue , Jiang Limin , Yang Xiaowen , Gao Yuhao , Gai Ruiyuan , Wang Mingpeng , Chen Lei
Published: June 2024

Microbial fuel cells (MFCs) have the functions of wastewater treatment and power generation. The incorporation of modified anodes enhances the sustainable power generation performance of MFCs. In this study, to evaluate the feasibility of sodium alginate (SA) as a biocompatible binder, hydrogel mixed with super activated carbon (SAC) and SA was modified the carbon cloth anode of MFC. The results showed that the maximum output voltage in the SAC/SA hydrogel modified anode MFC was 0.028 V, which was increased by 115%, compared with the blank carbon cloth anode. The internal resistance of MFC was 9429 Ω, which was 18% lower than that of control (11560 Ω). The maximum power density was 6.14 mW/m2, which was increased by 365% compared to the control. After modification of SAC/SA hydrogel, the chemical oxygen demand (COD) removal efficiency reached to 56.36% and was 12.72% higher than the control. Coulombic efficiency with modified anode MFC reached 17.65%, which was increased by 104%, compared with the control. Our findings demonstrate the feasibility of utilizing SA as a biocompatible binder for anode modification, thereby imparting sustainable and enhanced power generation performance to MFCs. This study presented a new selectivity for harnessing algal bioresources and improving anode binders in future MFC applications.
Trajectory pattern of serially measured acute kidney injury biomarkers in critically ill patients: a prospective observational study
Authors: Horie Ryohei , Hayase Naoki , Asada Toshifumi , Yamamoto Miyuki , Matsubara Takehiro , Doi Kent
Published: June 2024

Background

The clinical value of the trajectory of temporal changes in acute kidney injury (AKI) biomarkers has not been well established among intensive care unit (ICU) patients.

Methods

This is a single-center, prospective observational study, performed at a mixed ICU in a teaching medical institute in Tokyo, Japan. Adult ICU patients with an arterial line and urethral catheter were enrolled from September 2014 to March 2015. Patients who stayed in the ICU for less than 48 h and patients with known end-stage renal disease were excluded from the study. Blood and urine samples were collected for measurement of AKI biomarkers at 0, 12, 24, and 48 h after ICU admission. The primary outcome was major adverse kidney events (MAKE) at discharge, defined as a composite of death, dialysis dependency, and persistent loss of kidney function (≥ 25% decline in eGFR).

Results

The study included 156 patients. Serum creatinine-based estimated glomerular filtration rate (eGFR), plasma neutrophil gelatinase-associated lipocalin (NGAL), and urinary liver-type fatty acid-binding protein (uL-FABP) were serially measured and each variable was classified into three groups based on group-based trajectory modeling analysis. While the trajectory curves moved parallel to each other (i.e., “low,” “middle,” and “high”) for eGFR and plasma NGAL, the uL-FABP curves showed distinct trajectory patterns and moved in different directions (“low and constant,” “high and exponential decrease,” and “high and exponential increase”). These trajectory patterns were significantly associated with MAKE. MAKE occurred in 16 (18%), 16 (40%), and 9 (100%) patients in the “low and constant,” “high and exponential decrease,” and “high and exponential increase” groups, respectively, based on uL-FABP levels (p-value < 0.001). The initial value and the 12-h change in uL-FABP were both significantly associated with MAKE, even after adjusting for eGFR [Odds ratio (95% confidence interval): 1.45 (1.17–1.83) and 1.43 (1.12–1.88) for increase of initial value and 12-h change of log-transformed uL-FABP by 1 point, respectively].

Conclusions

Trajectory pattern of serially measured urinary L-FABP was significantly associated with MAKE in ICU patients.
Impulsive coupled systems with regular and singular ϕ-Laplacians and generalized jump conditions
Authors: Minhós Feliz , Rodrigues Gracino
Published: June 2024

This work contains sufficient conditions for the solvability of a third-order coupled system with two differential equations involving different Laplacians, fully discontinuous nonlinearities, two-point boundary conditions, and two sets of impulsive effects. The first existing result is obtained from Schauder’s fixed point theorem, and the second one provides also the localization of a solution via the lower and upper solutions technique.

We point out that it is the first time that impulsive coupled systems with strongly nonlinear fully differential equations and generalized impulse effects are considered simultaneously. Moreover, the singular case is applied to a special relativity model in classical electrodynamics.
Investigation of multiple nosocomial infections using a semi-Markov multi-state model
Authors: Zhong Xiao , Wang Dong-Li , Xiao Li-Hua , Liu Yan , Yang Shan-Wen , Mo Lan-Fang , Wu Qin-Fei , Lin Mei , He Lan-Fang , Luo Xiao-Feng
Published: June 2024

Background

The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS).

Method

This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI).

Results

The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06–8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03–18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be.

Conclusion

The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures.
Facilitators and barriers to adopting or expanding medications for opioid use disorder provision in rural Colorado jails: a qualitative analysis
Authors: McNeely Heidi L. , Schreiber Terri L. , Swann William L. , Amura Claudia R.
Published: June 2024

Background

Opioid use disorder (OUD) is common among individuals who are incarcerated. However, OUD treatment services are sparse in smaller county jails found in many rural areas, which limits a healthy and supportive jail environment. This study assesses the facilitators of and barriers to medications for opioid use disorder (MOUD) adoption or expansion in rural Colorado jails. A qualitative descriptive design was implemented during the summer of 2022 using semi-structured interviews with jail staff, sheriffs, and contracted personnel. Interview questions focused on facilitators of existing MOUD services and barriers to adopting or expanding services. To identify the facilitators and barriers, data were coded using thematic analysis.

Results

Seven jails were included in the study. Representatives from each jail participated in the seven interviews, which often included multiple participants per interview. Three of the jails had established routine practices for MOUD administration. Two jails occasionally administered MOUD or had plans in place to be able to administer, while the remaining two did not offer any MOUD. While administrative support, collaborative partnerships, and jail nurses facilitated MOUD use, barriers were more prevalent, including physical space limitations, distance to services, lack of providers in the area, staffing and training issues, funding/budget issues, and perceived risk of diversion.

Conclusion

Making MOUD available to people who are incarcerated is an important and timely step in enhancing the jail environment, especially in rural areas that often lack access to MOUD. As states look to require MOUD availability for people who are incarcerated, facilitators to MOUD adoption/expansion can be leveraged while strategies are needed to overcome barriers.
Face repairing based on transfer learning method with fewer training samples: application to a Terracotta Warrior with facial cracks and a Buddha with a broken nose
Authors: Zhu Jian , Fang Bowei , Chen Tianning , Yang Hesong
Published: June 2024

In this paper, a method based on transfer learning is proposed to recover the three-dimensional shape of cultural relics faces from a single old photo. It can simultaneously reconstruct the three-dimensional facial structure and align the texture of the cultural relics with fewer training samples. The UV position map is used to represent the three-dimensional shape in space and act as the output of the network. A convolutional neural network is used to reconstruct the UV position map from a single 2D image. In the training process, the human face data is used for pre-training, and then a small amount of artifact data is used for fine-tuning. A deep learning model with strong generalization ability is trained with fewer artifact data, and a three-dimensional model of the cultural relic face can be reconstructed from a single old photograph. The methods can train more complex deep networks without a large amount of cultural relic data, and no over-fitting phenomenon occurs, which effectively solves the problem of fewer cultural relic samples. The method is verified by restoring a Chinese Terracotta Warrior with facial cracks and a Buddha with a broken nose. Other applications can be used in the fields such as texture recovery, facial feature extraction, and three-dimensional model estimation of the damaged cultural relics or sculptures in the photos.
Byzantine wall paintings from San Marco d’Alunzio, Sicily: non-invasive diagnostics and microanalytical investigation of pigments and plasters
Authors: Alberghina Maria Francesca , Zicarelli Maria Antonietta , Randazzo Luciana , Schiavone Salvatore , La Russa Mauro Francesco , Labriola Maria , Rigaglia Davide , Ricca Michela
Published: June 2024

A diagnostic investigation was carried out on twelfth century Byzantine wall paintings preserved in the Museum of Byzantine and Norman Culture and Figurative Arts of San Marco d’Alunzio (Messina, Italy) on the occasion of recent restoration works. First, the wall paintings were analyzed using portable X-Ray Fluorescence (p-XRF) and Fiber Optics Reflectance Spectroscopy (FORS) to obtain a non-invasive preliminary identification of the original palette. Then, five fragments were sampled for a micro-stratigraphy study using Digital Optical Microscope (DOM), Polarizing Optical Microscope (POM), and Scanning Electron Microscopy (SEM) combined with Energy Dispersive X-ray Spectrometry (EDS) to characterize the mortars and the blue and black pigments non unequivocally identified through non-invasive techniques. The palette included mainly earthen pigments like red and yellow ochres, green earth, and more valuable lapis lazuli blue applied on a bone black layer; while the analysis of mortars found on the different apses showed the same manufacturing technique and constitutive materials: lime-based binder with the addition of quartz, and rare calcareous lithic fragments as aggregate. The obtained results shed light on the pictorial technique used for the wall paintings and allowed us to compare the Sicilian pictorial cycle with the coeval Byzantine wall paintings preserved in Sardinia and Southern Italy.
Survival rate of patient with glioblastoma: a population-based study
Authors: Sabouri Masih , Dogonchi Aref Famili , Shafiei Mehdi , Tehrani Donya Sheibani
Published: June 2024

Introduction

Glioblastoma, as the most common and lethal primary malignant brain tumor, has estimated mean survival of 15 months. GBM is reported more in men. Malignant glioma is the cause of 2.5% of cancer deaths. The standard therapy for patients with newly diagnosed GBM includes tumor resection surgeries, followed by radiotherapy and chemotherapy. The prognosis of glioma is a major challenge, and the outcome of GBM has remained almost unchanged for past years. The present study aimed to determine patient survival.

Methods

Patients with glioblastoma tumors who visited Al-Zahra and Kashani hospitals from 2013 to 2021 were included in this study. All patients were classified with morphological codes according to the International Classification of Diseases for Oncology. The patients’ information was recorded in the checklist, and then, the patients were followed up by phone. The data were measured regarding age, gender, exposure to chemicals, body mass index (BMI), and survival from the patient's surgery to death. Several questions were asked from the families of deceased patients and survivors based on the KPS Status Scale. Finally, the sample was analyzed with SPSS version 26.

Result

The patient's mean age was 51.93 years, and the male–female ratio was 1:1.7. The patients' mean overall survival was 29 months and a total of 9 patients survived. There was a significant difference between the age groups in terms of 1-year survival so that more deaths were observed in the age group of more than 50 years. The mean tumor size was 5.2 ± 2.1 cm. The survival analysis indicated that the temporal lobe was more than the other in 2-year survival. The most common symptom of patients before surgery was headache (31.8%) followed by motor dysfunction. The 1-year, 2-year, 5-year, and overall survival of the patients was 4.5%, 18.38%, 37.13%, and 33.68%, respectively.

Conclusions

The results of the present study indicated that the patients' survival improved over time with the advancement of adjuvant therapies. Therefore, if patients care get better for the first year after surgery, their survival will improve from the second year after the operation.
Dissemination and implementation research coordination and training to improve cardiovascular health in people living with HIV in sub-Saharan Africa: the research coordinating center of the HLB-SIMPLe Alliance
Authors: Tetteh Emmanuel K. , Effah William , Fuentes Lisa de las , Steger-May Karen , Goss Charles W. , Dowdy David W. , Huffman Mark D. , Williams Makeda J. , Tonwe Veronica , Bansal Geetha P. , Geng Elvin H. , Dávila-Román Victor G. , Rice Treva , Schechtman Kenneth B
Published: June 2024

As global adoption of antiretroviral therapy extends the lifespan of People Living with HIV (PLHIV) through viral suppression, the risk of comorbid conditions such as hypertension has risen, creating a need for effective, scalable interventions to manage comorbidities in PLHIV. The Heart, Lung, and Blood Co-morbiditieS Implementation Models in People Living with HIV (HLB-SIMPLe) Alliance has been funded by the National Heart, Lung, and Blood Institute (NHLBI) and the Fogarty International Center (FIC) since September 2020. The Alliance was created to conduct late-stage implementation research to contextualize, implement, and evaluate evidence-based strategies to integrate the diagnosis, treatment, and control of cardiovascular diseases, particularly hypertension, in PLHIV in low- and middle-income countries (LMICs).

The Alliance consists of six individually-funded clinical trial cooperative agreement research projects based in Botswana, Mozambique, Nigeria, South Africa, Uganda, and Zambia; the Research Coordinating Center; and personnel from NIH, NHLBI, and FIC (the Federal Team). The Federal Team works together with the members of the seven cooperative agreements which comprise the alliance. The Federal Team includes program officials, project scientists, grant management officials and clinical trial specialists. This Alliance of research scientists, trainees, and administrators works collaboratively to provide and support venues for ongoing information sharing within and across the clinical trials, training and capacity building in research methods, publications, data harmonization, and community engagement. The goal is to leverage shared learning to achieve collective success, where the resulting science and training are greater with an Alliance structure rather than what would be expected from isolated and unconnected individual research projects.

In this manuscript, we describe how the Research Coordinating Center performs the role of providing organizational efficiencies, scientific technical assistance, research capacity building, operational coordination, and leadership to support research and training activities in this multi-project cooperative research Alliance. We outline challenges and opportunities during the initial phases of coordinating research and training in the HLB-SIMPLe Alliance, including those most relevant to dissemination and implementation researchers.
Targeting small druggable compounds against 3RZE histamine H1 receptor as potential of anti-allergic drug applying molecular modeling approach
Authors: Akram Adeel , Su Chia-Hung , Fu Chun-Chong
Published: June 2024

Background

Allergic disorders, prevalent global health concerns, afflict a substantial portion of the world’s population. These maladies result from an exaggerated immune system response to ordinarily innocuous substances, such as pollen, dust mites, and specific dietary components. Clinical manifestations of this heightened immune response include itching, swelling, and respiratory impairment, often accompanied by releasing mediators like histamine. The pathophysiological mechanisms of allergy disorders are intricate, arising from a complex interplay between genetic and environmental factors. While clinical presentations may vary, all allergy conditions share a common foundation in the dysregulated immune response to allergens.

Result

The current aim of this study was to identify innovative anti-allergic agents capable of inhibiting histamine and effectively mitigating allergic reactions by utilizing the computer-aided drug design approach by discovery studio (DS) 2022 v 23.1.1 package. The overarching aim was identifying potential drug candidates targeting the active site within the histamine H1 receptor complex; therefore, a collection of 4000 small druggable compounds was curated from ZINC, PubChem, and DRUG BANK databases sources. Four compounds appeared as promising candidates after assessing docking scores and binding energies. Notably, Compound ID 34154, recognized as tymazoline, showed the highest affinity for the H1 receptor of 3RZE, suggesting it may be the most promising choice for more research. Further chemoinformatic and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses were conducted to assess the drug-like qualities of this chosen molecule. In addition, bioisosteric substitution techniques were employed to enhance tymazoline’s ADMET characteristics.

Conclusion

Tymazoline shows strong binding affinity with 3RZE and verified all the drug-likeness criteria to inhibit the allergic disorders. Furthermore, molecular dynamics (MD) studies corroborated tymazoline’s potential as an anti-allergic agent, demonstrating contact between the ligand and the receptor that is well defined and stable.
Neuroleptic malignant syndrome with acute renal failure associated with rhabdomyolysis: a case report
Authors: Sharma Sunakshi , Bhat Sanjay , Ahmed Zahoor
Published: June 2024

Neuroleptic malignant syndrome is a rare, life-threatening neurologic emergency characterized by fever, rigidity, autonomic instability, mental status changes, and an elevated creatine kinase level. It often occurs shortly after the initiation of neuroleptic treatment, or after a dose increase. The management of patients with NMS is based upon clinical severity and includes supportive care and withdrawal of antipsychotic agents and agents like bromocriptine and dantrolene. Complications include acute renal failure associated with rhabdomyolysis, respiratory failure, electrolyte imbalance, hepatic failure, seizures from hyperthermia, metabolic derangements, etc.
Safety and efficacy of trastuzumab deruxtecan for metastatic HER2+ and HER2-low breast cancer: An updated systematic review and meta-analysis of clinical trials.
Authors: Qureshi Zaheer , Altaf Faryal , Jamil Abdur , Siddique Rimsha
Published: June 2024

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Background: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) that has shown promise in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis aimed to evaluate the safety and efficacy of T-DXd in this patient population, integrating data from the latest clinical trials. Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd’s efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data. Results: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR 0.37, 95% CI 0.27–0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR 2.10, 95% CI 1.36–3.25), fatigue (OR 1.56, 95% CI 1.21–2.02), nausea (OR 6.42, 95% CI 4.37–9.42), vomiting (OR 6.21, 95% CI 3.14–12.25), constipation (OR 2.26, 95% CI 1.53–3.34), and notably, drug-related interstitial lung disease (ILD) (OR 10.89, 95% CI 3.81–31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis. Conclusions: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring strategies to enhance safety profiles.