bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the efficacy and safety of drug-eluting beads transarterial chemoembolization in pancreatic cancer liver metastasis
Authors: Ning Zhouyu , Zhu Ying , Xie Lin , Yan Xia , Hua Yongqiang , Meng Zhiqiang
Published: March 2024

Objectives

Drug-eluting beads transarterial chemoembolization (DEB-TACE) has shown promise as a treatment modality for primary liver cancer and colorectal cancer liver metastasis. However, its role in pancreatic cancer liver metastasis (PCLM) remains uncertain. This study aimed to investigate the efficacy and safety of DEB-TACE in PCLM patients.

Methods

A retrospective study included 10 PCLM patients who underwent DEB-TACE using CalliSpheres® microspheres as the chemoembolization material. Treatment response, survival outcomes, adverse events, and liver function indexes were comprehensively assessed.

Results

Among the patients, complete response, partial response, stable disease, and progressive disease rates were 0.0%, 40.0%, 30.0%, and 30.0%, respectively. The objective response rate was 40.0%, and the disease-control rate was 70.0%. The median progression-free survival (PFS) was 12.0 months (95% CI: 0.0-26.7), with a 1-year PFS rate of 48.0%. The median overall survival (OS) was 18.0 months (95% CI: 6.0-30.0), with a 1-year OS rate of 80.0%. Additionally, no significant differences were observed in any of the liver function indexes, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, etc., between pre- and posttreatment evaluations. Adverse events included pain, grade 1-2 vomiting, fever, and transient liver dysfunction.

Conclusions

DEB-TACE demonstrates a promising treatment response, favorable survival profile, and satisfactory safety in PCLM patients.

Advances in knowledge

This study adds to the current research by providing novel evidence on the efficacy, safety, and favorable survival outcomes of DEB-TACE in treating PCLM, highlighting its potential as an effective therapeutic option in this specific population.
The role of cultural competency training to address health disparities in surgical settings
Authors: Mora Roberto , Maze Mervyn
Published: March 2024

Background

Disparities in health care delivered to marginalized groups are unjust and result in poor health outcomes that increase the cost of care for everyone. These disparities are largely avoidable and health care providers, have been targeted with education and specialised training to address these disparities.

Sources of Data

In this manuscript we have sought out both peer-reviewed material on Pubmed, as well as policy statements on the potential role of cultural competency training (CCT) for providers in the surgical care setting. The goal of undertaking this work was to determine whether there is evidence that these endeavours are effective at reducing disparities.

Areas of Agreement

The unjustness of health care disparities is universally accepted.

Areas of Controversy

Whether the outcome of CCT justifies the cost has not been effectively answered.

Growing Points

These include the structure/content of the CCT and whether the training should be delivered to teams in the surgical setting.

Areas timely for developing Research

Because health outcomes are affected by many different inputs, should the effectiveness of CCT be improvement in health outcomes or should we use a proxy or a surrogate of health outcomes.
Cerebral tau pathology in cerebral amyloid angiopathy
Authors: Tsai Hsin-Hsi , Liu Chia-Ju , Lee Bo-Ching , Chen Ya-Fang , Yen Ruoh-Fang , Jeng Jiann-Shing , Tsai Li-Kai
Published: March 2024

Tau, a hallmark of Alzheimer’s disease, is poorly characterized in cerebral amyloid angiopathy. We aimed to assess the clinico-radiological correlations between tau positron emission tomography scans and cerebral amyloid angiopathy. We assessed cerebral amyloid and hyperphosphorylated tau in patients with probable cerebral amyloid angiopathy (n = 31) and hypertensive small vessel disease (n = 27) using 11C-Pittsburgh compound B and 18F-T807 positron emission tomography. Multivariable regression models were employed to assess radio-clinical features related to cerebral tau pathology in cerebral amyloid angiopathy. Cerebral amyloid angiopathy exhibited a higher cerebral tau burden in the inferior temporal lobe [1.25 (1.17–1.42) versus 1.08 (1.05–1.22), P < 0.001] and all Braak stage regions of interest (P < 0.05) than hypertensive small vessel disease, although the differences were attenuated after age adjustment. Cerebral tau pathology was significantly associated with cerebral amyloid angiopathy-related vascular markers, including cortical superficial siderosis (β = 0.12, 95% confidence interval 0.04–0.21) and cerebral amyloid angiopathy score (β = 0.12, 95% confidence interval 0.03–0.21) after adjustment for age, ApoE4 status and whole cortex amyloid load. Tau pathology correlated significantly with cognitive score (Spearman’s ρ=−0.56, P = 0.001) and hippocampal volume (−0.49, P = 0.007), even after adjustment. In conclusion, tau pathology is more frequent in sporadic cerebral amyloid angiopathy than in hypertensive small vessel disease. Cerebral amyloid angiopathy-related vascular pathologies, especially cortical superficial siderosis, are potential markers of cerebral tau pathology suggestive of concomitant Alzheimer’s disease.
Temperature-dependent chlorosomal self-aggregation of bacteriochlorophyll-d analogs with a branched alkyl chain in a single 1-chlorooctane solvent
Authors: Hara Nobuyuki , Tamiaki Hitoshi
Published: March 2024

Recently, the supramolecular polymerization of chlorophyll pigments mimicking a natural light-harvesting apparatus (chlorosome) was demonstrated in low-polar organic solvents or aqueous solutions. To obtain the most aggregation models, a concentrated solution of the pigments in a polar organic solvent was diluted with a large amount of a nonpolar organic solvent or water. Here, bacteriochlorophyll-d analogs possessing branched alkyl chains of different lengths at the peripheral 17-propionate residue on the core chlorin π-system were prepared and their highly soluble chlorosomal supramolecules were produced in single 1-chlorooctane as a low-polar solvent. Temperature-dependent electronic absorption and circular dichroism spectroscopies were employed to analyze their self-aggregation and disaggregation mechanisms. The synthetic analogs were monomeric at high temperatures and self-aggregated during cooling of the hot solution through a non-sigmoidal pathway. The obtained chlorosomal self-aggregates were reversibly monomerized by heating the homogeneous solution. The disaggregation pathway was fitted to an isodesmic model whose melting points depended on the alkyl-chain lengths.
Minimally Invasive Surgery for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Robotic Versus Laparoscopic Surgical Techniques
Authors: Zaman Shafquat , Mohamedahmed Ali Yasen Y , Abdelrahman Widad , Abdalla Hashim E , Wuheb Ali Ahmed , Issa Mohamed Talaat , Faiz Nameer , Yassin Nuha A
Published: March 2024

Background

We aimed to evaluate outcomes of robotic versus conventional laparoscopic colorectal resections in patients with inflammatory bowel disease [IBD].

Methods

Comparative studies of robotic versus laparoscopic colorectal resections in patients with IBD were included. The primary outcome was total post-operative complication rate. Secondary outcomes included operative time, conversion to open surgery, anastomotic leaks, intra-abdominal abscess formation, ileus occurrence, surgical site infection, re-operation, re-admission rate, length of hospital stay, and 30-day mortality. Combined overall effect sizes were calculated using a random-effects model and the Newcastle–Ottawa Scale was used to assess risk of bias.

Results

Eleven non-randomized studies [n = 5566 patients] divided between those undergoing robotic [n = 365] and conventional laparoscopic [n = 5201] surgery were included. Robotic platforms were associated with a significantly lower overall post-operative complication rate compared with laparoscopic surgery [p = 0.03]. Laparoscopic surgery was associated with a significantly shorter operative time [p = 0.00001]. No difference was found in conversion rates to open surgery [p = 0.15], anastomotic leaks [p = 0.84], abscess formation [p = 0.21], paralytic ileus [p = 0.06], surgical site infections [p = 0.78], re-operation [p = 0.26], re-admission rate [p = 0.48], and 30-day mortality [p = 1.00] between the groups. Length of hospital stay was shorter following a robotic sub-total colectomy compared with conventional laparoscopy [p = 0.03].

Conclusion

Outcomes in the surgical management of IBD are comparable between traditional laparoscopic techniques and robotic-assisted minimally invasive surgery, demonstrating the safety and feasibility of robotic platforms. Larger studies investigating the use of robotic technology in Crohn’s disease and ulcerative colitis separately may be of benefit with a specific focus on important IBD-related metrics.
Multidisciplinary approach to long-standing left bundle branch block with dyssynchrony and aortic stenosis: case report
Authors: Maigrot Jean-Luc A , Weiss Aaron J , Wazni Oussama , Starling Randall C
Published: March 2024

Background

Cardiac resynchronization therapy (CRT) is recommended for patients with symptomatic heart failure in sinus rhythm with left ventricular ejection fraction (LVEF) ≤ 35%, QRS duration ≥ 150 ms, and left bundle branch block (LBBB) morphology. However, when severe left ventricular dysfunction and cardiogenic shock are present, treatment paradigms are often limited to palliative medical therapy or advanced therapies with durable left ventricular assist device or heart transplant as the functional and survival benefit of CRT in these patients remains uncertain.

Case summary

A 77-year-old white man with long-standing LBBB with dyssynchrony, severely reduced LVEF of 4%, and severe bicuspid aortic stenosis (AS) presented with worsening heart failure symptoms. After multidisciplinary heart team evaluation and pre-operative optimization, the patient underwent a surgical aortic valve replacement with simultaneous intraoperative initiation of CRT with pacemaker (CRT-P) and temporary mechanical circulatory support. Echocardiography at 44 days and 201 days post-discharge showed an LVEF of 29% and 40%, respectively.

Discussion

This case demonstrates that reverse remodelling and native heart recovery were successfully achieved in a patient with advanced structural heart disease, presenting with cardiogenic shock, through an early and aggressive approach involving multidisciplinary heart team evaluation, treatment of severe AS with surgical aortic valve replacement, prophylactic intraoperative initiation of temporary mechanical circulatory support, and early initiation of CRT-P.
Early chest tube removal on the 1st postoperative day protocol of an enhanced recovery after cardiac surgery programme is safe
Authors: Darras Marc , Schneider Clément , Marguerite Sandrine , Oulehri Walid , Collange Olivier , Mertes Paul-Michel , Mazzucotelli Jean-Philippe , Kindo Michel
Published: March 2024

OBJECTIVES

The aim of this study was to assess the safety of early chest tube removal (CTR) protocol on the 1st postoperative day (POD1) of our Enhanced Recovery After Surgery (ERAS) programme by comparing the risk of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality.

METHODS

All consecutive patients undergoing elective coronary revascularization and/or valve surgery between 2015 and 2021 were assessed in terms of their perioperative management pathways: conventional standard of care (control group) versus standardized systematic perioperative ERAS programme including an early CTR on POD1 (ERAS group). A propensity score matching was applied. The primary end-point was a composite of postoperative pneumothorax, pleural and pericardial effusion requiring intervention and hospital mortality.

RESULTS

A total of 3153 patients were included. Propensity score analysis resulted in 2 groups well-matched pairs of 1026 patients. CTR on POD1 was significantly increased from 29.5% in the control group to 70.3% in the ERAS group (P < 0.001). The incidence of the primary end-point was 6.4% in the control group and 6.9% in the ERAS group (P = 0.658). Patients in the ERAS group, as compared with control group, had significant lower incidence of bronchopneumonia (9.0% vs 13.5%; P = 0.001) and higher incidence of mechanical ventilation ≤6 h (84.6% vs 65.2%; P < 0.001), length of intensive care unit ≤1 day (61.2% vs 50.8%; P < 0.001) and hospital ≤6 days (67.3% vs.43.2%; P < 0.001).

CONCLUSIONS

CTR on POD1 protocol can be safely incorporated into a standardized systematic ERAS programme, enabling early mobilization, and contributing to the improvement of postoperative outcomes.

Clinical trial registration number

Ethics committee of the French Society of Thoracic and Cardio-Vascular Surgery (CERC-SFCTCV-2022-09-13_23140)
Chasing Sequencing Perfection: Marching Toward Higher Accuracy and Lower Costs
Authors: Jia Hangxing , Tan Shengjun , Zhang Yong E
Published: March 2024

Next-generation sequencing (NGS), represented by Illumina platforms, has been an essential cornerstone of basic and applied research. However, the sequencing error rate of 1 per 1000 bp (10−3) represents a serious hurdle for research areas focusing on rare mutations, such as somatic mosaicism or microbe heterogeneity. By examining the high-fidelity sequencing methods developed in the past decade, we summarized three major factors underlying errors and the corresponding 12 strategies mitigating these errors. We then proposed a novel framework to classify 11 preexisting representative methods according to the corresponding combinatory strategies and identified three trends that emerged during methodological developments. We further extended this analysis to eight long-read sequencing methods, emphasizing error reduction strategies. Finally, we suggest two promising future directions that could achieve comparable or even higher accuracy with lower costs in both NGS and long-read sequencing.
How are we handling protein drugs in hospitals? A human factors and systems engineering approach to compare two hospitals and suggest a best practice
Authors: Sabaté-Martínez Clàudia , Paulsson Mattias , González-Suárez Silvia , Elofsson Ulla , Fureby Anna Millqvist , Wahlgren Marie , López-Cabezas Carmen
Published: March 2024

Biopharmaceuticals are complex biological molecules that require careful storage and handling to ensure medication integrity. In this study, a work system analysis of real-world protein drug (PD) handling was performed with the following goals: identify main barriers and facilitators for successful adherence to accepted recommendations in PD handling, analyse differences in two organizations, and define a Best Current Practice in the real-life handling of PDs based on the results of the work system analysis. Observational study was held in two university hospitals in Spain and Sweden. Based on the Systems Engineering Initiative for Patient Safety (SEIPS) model, the tools chosen were: the PETT scan, in order to indicate the presence of barriers or facilitators for the PETT components (People, Environment, Tools, Tasks); the Tasks and tools matrices to construct a checklist to record direct observations during the real-life handling of biopharmaceuticals, and the Journey map to depict the work process. Observations were performed between March and November 2022. Each episode of direct observation included a single protein drug in some point of the supply chain and considered all the elements in the work system. Based on the results of the work system analysis and the literature review, the authors propose a list of items which could be assumed as Best Current Practice for PDs handling in hospitals. There were a total of 34 observations involving 19 PDs. Regarding People involved in the work process, there was a diversity of professionals with different previous training and knowledge, leading to an information gap. With respect to Environment, some structural and organizational differences between hospitals lead to risks related to the time exposure of PDs to room temperature and mechanical stress. Some differences also existed in the Tools and Tasks involved in the process, being especially relevant to the lack of compatibility information of PDs with new technologies, such as pneumatic tube system, robotic reconstitution, or closed-system transfer devices. Finally, 15 suggestions for best current practice are proposed. Main barriers found for compliance with accepted recommendations were related to the information gap detected in professionals involved in the handling of protein drugs, unmonitored temperature, and the lack of compatibility information of protein drugs with some new technologies. By applying a Human Factors and Systems Engineering Approach, the comparison of two European hospitals has led to a suggested list of Best Current Practices in the handling of protein drugs in a hospital.
Staphylococcus epidermidis bacteriocin A37 kills natural competitors with a unique mechanism of action
Authors: Puls Jan-Samuel , Winnerling Benjamin , Power Jeffrey J , Krüger Annika M , Brajtenbach Dominik , Johnson Matthew , Bilici Kevser , Camus Laura , Fließwasser Thomas , Schneider Tanja , Sahl Hans-Georg , Ghosal Debnath , Kubitscheck Ulrich , Heilbronner Simon , Grein Fabian
Published: March 2024

Many bacteria produce antimicrobial compounds such as lantibiotics to gain advantage in the competitive natural environments of microbiomes. Epilancins constitute an until now underexplored family of lantibiotics with an unknown ecological role and unresolved mode of action. We discovered production of an epilancin in the nasal isolate Staphylococcus epidermidis A37. Using bioinformatic tools, we found that epilancins are frequently encoded within staphylococcal genomes, highlighting their ecological relevance. We demonstrate that production of epilancin A37 contributes to Staphylococcus epidermidis competition specifically against natural corynebacterial competitors. Combining microbiological approaches with quantitative in vivo and in vitro fluorescence microscopy and cryo-electron tomography, we show that A37 enters the corynebacterial cytoplasm through a partially transmembrane-potential-driven uptake without impairing the cell membrane function. Upon intracellular aggregation, A37 induces the formation of intracellular membrane vesicles, which are heavily loaded with the compound and are essential for the antibacterial activity of the epilancin. Our work sheds light on the ecological role of epilancins for staphylococci mediated by a mode of action previously unknown for lantibiotics.
The Logic for Mathematics without Ex Falso Quodlibet
Authors: Tennant Neil
Published: March 2024

Informally rigorous mathematical reasoning is relevant. So too should be the premises to the conclusions of formal proofs that regiment it. The rule Ex Falso Quodlibet induces spectacular irrelevance. We therefore drop it. The resulting systems of Core Logic $ \mathbb{C}$ and Classical Core Logic $ \mathbb{C}^{+}$ can formalize all the informally rigorous reasoning in constructive and classical mathematics respectively. We effect a revised match-up between deducibility in Classical Core Logic and a new notion of relevant logical consequence. It matches better the deducibility relation of Classical Core Logic than does the Tarskian notion of consequence. It is implosive, not explosive.
Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism
Authors: Yu Xiaojie , Cheng Lihao , Liu Song , Wang Miaomaio , Zhang Hao , Wang Xiaohong , Zhang Haojie , Yang Zhenlin , Wu Shuhua
Published: March 2024

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug‐resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis‐related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy‐sensitive cases, Ferrous ion (Fe2+) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2O2) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR‐resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion‐mediated ferroptosis by TFRC. Upregulation of TFRC in ADR‐resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.
Consensus-Derived Recommended Skills for Transition to Residency Courses
Authors: Rustici Matthew , Mutter M. Kathryn , Atkins K. Meredith , Holmboe Eric , Morgan Helen Kang , Olson Andrew P.J. , Anderson Andrea , Zell JoAnn , Roosevelt Genie , Brainard Jason
Published: March 2024

Purpose

Transition to residency (TTR) courses facilitate the medical student–residency transition and are an integral part of senior medical student training. The authors established a common set of skills for TTR courses, and an expected level of entrustment students should demonstrate in each skill on TTR course completion.

Method

A modified Delphi approach was used with 3 survey iterations between 2020 and 2022 to establish skills to be included in a TTR course. Nine TTR experts suggested general candidate skills and conducted a literature search to ensure no vital skills were missed. A stakeholder panel was solicited from email lists of TTR educators, residency program directors, and residents at the panelists’ institutions. Consensus was defined as more than 75% of participants selecting a positive inclusion response. An entrustment questionnaire asked panelists to assign a level of expected entrustment to each skill, with 1 indicating observation only and 6 indicating perform independently.

Results

The stakeholder panel initially consisted of 118 respondents with representation across educational contexts and clinical specialties. Response rates were 54% in iteration 2, 42% in iteration 3, and 33% on the entrustment questionnaire. After 3 iterations, 54 skills met consensus and were consolidated into 37 final skills categorized into 18 clinical skills (e.g., assessment and management of inpatient concerns), 14 communication skills (e.g., delivering serious news or having difficult conversations), 4 personal and professional skills (e.g., prioritization of clinical tasks), and 1 procedural skill (mask ventilation). Median entrustment levels were reported for all skills, with 19 skills having a level of expected entrustment of 4 (perform independently and have all findings double-checked).

Conclusions

These consensus skills can serve as the foundation of a standardized national TTR curriculum framework. Entrustment guidance may help educational leaders optimize training and allocation of resources for TTR curriculum development and implementation.
A Comparison of Five Algorithmic Methods and Machine Learning Pattern Recognition for Artifact Detection in Electronic Records of Five Different Vital Signs: A Retrospective Analysis
Authors: Maleczek Mathias , Laxar Daniel , Kapral Lorenz , Kuhrn Melanie , Abulesz Yannic-Tomas , Dibiasi Christoph , Kimberger Oliver
Published: March 2024

Background

Research on electronic health record physiologic data is common, invariably including artifacts. Traditionally, these artifacts have been handled using simple filter techniques. The authors hypothesized that different artifact detection algorithms, including machine learning, may be necessary to provide optimal performance for various vital signs and clinical contexts.

Methods

In a retrospective single-center study, intraoperative operating room and intensive care unit (ICU) electronic health record datasets including heart rate, oxygen saturation, blood pressure, temperature, and capnometry were included. All records were screened for artifacts by at least two human experts. Classical artifact detection methods (cutoff, multiples of SD [z-value], interquartile range, and local outlier factor) and a supervised learning model implementing long short-term memory neural networks were tested for each vital sign against the human expert reference dataset. For each artifact detection algorithm, sensitivity and specificity were calculated.

Results

A total of 106 (53 operating room and 53 ICU) patients were randomly selected, resulting in 392,808 data points. Human experts annotated 5,167 (1.3%) data points as artifacts. The artifact detection algorithms demonstrated large variations in performance. The specificity was above 90% for all detection methods and all vital signs. The neural network showed significantly higher sensitivities than the classic methods for heart rate (ICU, 33.6%; 95% CI, 33.1 to 44.6), systolic invasive blood pressure (in both the operating room [62.2%; 95% CI, 57.5 to 71.9] and the ICU [60.7%; 95% CI, 57.3 to 71.8]), and temperature in the operating room (76.1%; 95% CI, 63.6 to 89.7). The CI for specificity overlapped for all methods. Generally, sensitivity was low, with only the z-value for oxygen saturation in the operating room reaching 88.9%. All other sensitivities were less than 80%.

Conclusions

No single artifact detection method consistently performed well across different vital signs and clinical settings. Neural networks may be a promising artifact detection method for specific vital signs.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Using Negative Control Populations to Assess Unmeasured Confounding and Direct Effects
Authors: Piccininni Marco , Stensrud Mats Julius
Published: March 2024

Sometimes treatment effects are absent in a subgroup of the population. For example, penicillin has no effect on severe symptoms in individuals infected by resistantStaphylococcus aureus, and codeine has no effect on pain in individuals with certain polymorphisms in the CYP2D6 enzyme. Subgroups where a treatment is ineffective are often called negative control populations or placebo groups. They are leveraged to detect bias in different disciplines. Here we present formal criteria that justify the use of negative control populations to rule out unmeasured confounding and mechanistic (direct) causal effects. We further argue that negative control populations, satisfying our formal conditions, are available in many settings, spanning from clinical studies of infectious diseases to epidemiologic studies of public health interventions. Negative control populations can also be used to rule out placebo effects in unblinded randomized experiments. As a case study, we evaluate the effect of mobile stroke unit dispatches on functional outcomes at discharge in individuals with suspected stroke, using data from a large trial. Our analysis supports the hypothesis that mobile stroke units improve functional outcomes in these individuals.
Crosstalk of lysyl oxidase-like 1 and lysyl oxidase prolongs their half-lives and regulates liver fibrosis through Notch signal
Authors: Zhang Ning , Yang Aiting , Zhang Wen , Li Hong , Xu Anjian , Yan Xuzhen , Han Qi , Wang Bingqiong , You Hong , Chen Wei
Published: March 2024

Background:

Lysyl oxidase (LOX) family members (LOX and LOXL1 to 4) are crucial copper-dependent enzymes responsible for cross-linking collagen and elastin. Previous studies have revealed that LOX and LOXL1 are the most dramatically dysregulated LOX isoforms during liver fibrosis. However, the crosstalk between them and the underlying mechanisms involved in the profibrotic behaviors of HSCs, as well as the progression of liver fibrosis, remain unclear.

Methods:

pCol9GFP-HS4,5Tg mice, Loxl1
fl/fl
Gfap
Cre mice, human HSC line, and primary HSCs were enrolled to study the dysregulation pattern, profibrotic roles, and the potential mechanisms of LOX and LOXL1 interaction involved in the myofibroblast-like transition of HSCs and liver fibrogenesis.

Results:

LOX and LOXL1 were synergistically upregulated during liver fibrogenesis, irrespective of etiology, together orchestrating the profibrotic behaviors of HSCs. LOX and LOXL1 coregulated in HSCs, whereas LOXL1 dominated in the coregulation loop. Interestingly, the interaction between LOXL1 and LOX prolonged their half-lives, specifically enhancing the Notch signal-mediated myofibroblast-like transition of HSCs. Selective disruption of Loxl1 in Gfap
+ HSCs deactivated the Notch signal, inhibited HSC activation, and relieved carbon tetrachloride-induced liver fibrosis.

Conclusions:

Our current study confirmed the synergistic roles and the underlying mechanisms of LOXL1 and LOX crosstalk in the profibrotic behaviors of HSCs and liver fibrosis progression, providing experimental evidence for further clear mechanism-based anti-LOXL1 strategy development in the therapy of liver fibrosis.
Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC
Authors: Park Jong Geun , Roh Pu Reun , Kang Min Woo , Cho Sung Woo , Hwangbo Suhyun , Jung Hae Deok , Kim Hyun Uk , Kim Ji Hoon , Yoo Jae-Sung , Han Ji Won , Jang Jeong Won , Choi Jong Young , Yoon Seung Kew , You Young Kyoung , Choi Ho Joong , Ryu Jae Yong , Sung Pil Soo
Published: March 2024

Background and Aims:

Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC.

Approach and Results:

CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels (p<0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68+ cells from patients with high serum IgA levels (p<0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs (p<0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8+ T cells. Interestingly, activated CD8+ T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs (p<0.05).

Conclusions:

Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.
Early onset of pathological polyploidization and cellular senescence in hepatocytes lacking RAD51 creates a pro-fibrotic and pro-tumorigenic inflammatory microenvironment
Authors: Bu Wenqing , Sun Xue , Xue Xiaotong , Geng Shengmiao , Yang Tingting , Zhang Jia , Li Yanan , Feng Chao , Liu Qiao , Zhang Xiyu , Li Peishan , Liu Zhaojian , Shi Yufang , Shao Changshun
Published: March 2024

Background and Aims:

RAD51 recombinase (RAD51) is a highly conserved DNA repair protein and is indispensable for embryonic viability. As a result, the role of RAD51 in liver development and function is unknown. Our aim was to characterize the function of RAD51 in postnatal liver development.

Approach and Results:

RAD51 is highly expressed during liver development and during regeneration following hepatectomy and hepatic injury, and is also elevated in chronic liver diseases. We generated a hepatocyte-specific Rad51 deletion mouse model using Alb-Cre (Rad51-conditional knockout (CKO)) and Adeno-associated virus 8-thyroxine-binding globulin-cyclization recombination enzyme to evaluate the function of RAD51 in liver development and regeneration. The phenotype in Rad51-CKO mice is dependent on CRE dosage, with Rad51
fl/fl; Alb-Cre+/+ manifesting a more severe phenotype than the Rad51
fl/fl; Alb-Cre+/− mice. RAD51 deletion in postnatal hepatocytes results in aborted mitosis and early onset of pathological polyploidization that is associated with oxidative stress and cellular senescence. Remarkable liver fibrosis occurs spontaneously as early as in 3-month-old Rad51
fl/fl; Alb-Cre+/+ mice. While liver regeneration is compromised in Rad51-CKO mice, they are more tolerant of carbon tetrachloride–induced hepatic injury and resistant to diethylnitrosamine/carbon tetrachloride–induced HCC. A chronic inflammatory microenvironment created by the senescent hepatocytes appears to activate ductular reaction the transdifferentiation of cholangiocytes to hepatocytes. The newly derived RAD51 functional immature hepatocytes proliferate vigorously, acquire increased malignancy, and eventually give rise to HCC.

Conclusions:

Our results demonstrate a novel function of RAD51 in liver development, homeostasis, and tumorigenesis. The Rad51-CKO mice represent a unique genetic model for premature liver senescence, fibrosis, and hepatocellular carcinogenesis.
Associations Between Social–Emotional Teaching Practices and Reductions in Preschoolers' Challenging Behavior
Authors: Lee Janice K. , Dunlap Glen
Published: March 2024

It is widely assumed that (1) children with challenging behavior may lack the social–emotional skills to be successful in classroom settings and (2) instruction in social–emotional skills can help prevent the occurrence of young children's challenging behavior. However, no data are available to indicate whether specific social–emotional skills might be most effective in reducing existing challenging behavior. In this study, we used an archival database to examine possible relationships between types of social–emotional instruction and changes over a 4-month period in levels of social skills and challenging behavior. The database, from a randomized trial of an intervention for preschoolers' challenging behavior, included measures of types of social–emotional instruction and children's social skills and challenging behaviors. Correlational analyses revealed statistically significant relationships between two types of social–emotional teaching practices and reductions in preschoolers' challenging behavior for children in the intervention group, teaching children behavior expectations and teaching problem-solving. No other statistically significant associations were identified. The results are discussed in relation to possible implications for social–emotional instruction for preschool children already exhibiting challenging behavior and the value of further research focused on preventing challenging behavior in young children.
Validation of the Inclusion Scale
Authors: Kim Sunyoung , Choi Youn-Jeng , Kang Veronica Y. , Wang Jing , Kim Namhee , Kim Kyoung-Mi
Published: March 2024

Despite the importance of inclusion in education, studies that clearly define and operationalize the concept of early childhood inclusive education in South Korea remain scarce. In this study, we aimed to translate and validate a comprehensive measurement scale to assess Korean early childhood teachers' attitudes and perceptions regarding inclusion. We analyzed data from a group of 224 respondents from 82 daycare centers in South Korea and tested the inclusion scale's internal consistency, subscale reliability, and content and construct validity. The exploratory factor analysis identified four factors with varying number of items in each factor. Researchers could use this instrument to better understand Korean teachers' beliefs about themselves with respect to inclusive education. Implications for research include the utility of the survey instrument with Korean early childhood teachers.
Risk factors and Nomogram Prediction for Splanchnic Venous Thrombosis in Moderate and Severe Acute Pancreatitis
Authors: Li Hai-Chao , He Huan , Huang Bo-Han , Yang Lei , Ding Yi-Xuan , Cao Feng , Li Fei
Published: March 2024

BACKGROUND:

Acute pancreatitis is one of the most common gastrointestinal diseases with significant morbidity and mortality, especially in the moderate to severe types. Splanchnic vein thrombosis(SVT) is related to acute pancreatitis but the pathogenesis of SVT in patients with AP is incompletely understood.

AIM

To investigate the risk factors of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) complicated by splanchnic venous thrombosis.

METHODS

The clinical data of 290 patients with MSAP and SAP admitted to Xuanwu Hospital of Capital Medical University between December 2015 and December 2020 were retrospectively analyzed. Patients were divided into two groups: 1) with thrombosis and 2) without thrombosis. Sex, age, etiology, severity of acute pancreatitis, platelet (PLT), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), prothrombin time (PT), activated partial thrombin time (APTT), D-dimer (D-D) levels, type of pancreatic necrosis, proportion and location of pancreatic parenchymal necrosis (PPN), location of local complications, computed tomography severity index (CTSI) and modified CTSI(mCTSI) were recorded. Univariate, logistic multivariate regression analyses and nomogram were used to determine the risk factors for splanchnic venous thrombosis complicated by acute pancreatitis (AP). A receiver operating characteristic (ROC) curve, decision curve and calibration curve were drawn.

RESULTS

Among 290 patients with AP, 71 (24.5%) had SAP, and 219 (75.5%) had MSAP. The median age of all the patients was 49 years; 172 patients (59.3%) had biliary disease, 91 patients (31.4%) had hypertriglyceridemia, 13 patients (4.5%) had alcohol disease, and 14 patients (4.8%) had other diseases. Of the 290 patients, SVT was detected in 35 (12.1%). Univariate analysis showed that the severity of acute pancreatitis, PLT, CRP, PCT, IL-6, PT, D-D, proportion of pancreatic parenchyma necrosis (PPN), necrosis of body-tail, and necrosis involving perihepatic and right subphrenic space, CTSI and mCTSI in the thrombus group were all statistically significant (P < 0.05). The results of multivariate analysis showed that PLT≧422 × 109/L, necrosis of body-tail, and necrosis involving perihepatic and right subphrenic space were independent risk factors for AP complicated with splanchnic venous thrombosis. The nomogram incorporating these factors demonstrated good discrimination, calibration and clinical utility. The area under the curve was as high as 0.845.

CONCLUSION

PLT≧422 × 109/L, necrosis of body-tail, and necrosis involving perihepatic and right subphrenic space are independent risk factors for splanchnic vein thrombosis. A simple nomogram tool helps in the early, accurate prediction of AP. Early and relevant clinical intervention should be provided.
Intraoperative indocyanine green fluorescence imaging to predict early hepatic arterial complications after liver transplantation
Authors: Terasawa Muga , Imamura Hiroshi , Allard Marc Antoine , Pietrasz Daniel , Ciacio Oriana , Pittau Gabriella , Salloum Chady , Sa Cunha Antonio , Cherqui Daniel , Adam René , Azoulay Daniel , Saiura Akio , Vibert Eric , Golse Nicolas
Published: March 2024

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.
Mechanical Analysis of a Novel Sternal Closure System in Static Tensile Loading
Authors: Yost Gardner , Plott Jeffrey , Angandi Amogh , Locke Conor , Marten Thomas , Haft Jonathan W.
Published: March 2024

The most common means of sternal closure after sternotomy is stainless steel wire cerclage. These wires, while inexpensive and simple in design, are known to be associated with low strength and sternal dehiscence. In this biomechanical analysis, we compare single sternal wires, double sternal wires, and a novel sternal closure device we have designed to mitigate sternal dehiscence. The device uses polymer grommets at the sternal interfaces to distribute load over a large surface area of bone. Samples of each closure device were installed in a bone model and distracted at a rate of 10 mm/min while tensile forces were continuously measured and compared. Single wires generated the lowest stiffness and strength values, followed by the double wires. The novel device demonstrated significantly higher stiffness and strength at all displacements compared with the single and double wires. Clinical use of this device may result in meaningful reduction in complications associated with the use of standard sternal wires such as sternal separation and fracture.
Reactive axillary lymph nodes after COVID-19 mRNA vaccination: comparison of mRNA vs. attenuated whole-virus vaccines
Authors: Adin Mehmet Emin , Isufi Edvin , Wu Jennifer , Pang Yulei , Nguyen Daniel , Simsek Has Duygu , Caner Civan , Aboueldaha Noha , Mossa-Basha Mahmud , Pucar Darko
Published: March 2024

Objective

To compare the incidence and natural course of reactive axillary lymph nodes (RAL) between mRNA and attenuated whole-virus vaccines using Deauville criteria.

Methods

In this multi-institutional PET-CT study comprising multiple vaccine types (Pfizer–BioNTech/Comirnaty, Moderna/Spikevax, Sinovac/CoronaVac and Janssen vaccines), we evaluated the incidence and natural course of RAL in a large cohort of oncological patients utilizing a standardized Deauville scaling system (n=522; 293 Female, Deauville 3-5 positive for RAL). Univariate and multivariate analyses were conducted to evaluate the predictive value of clinical parameters (absolute neutrophil count [ANC], platelets, age, sex, tumor type, and vaccine-to-PET interval) for PET positivity.

Results

Pfizer–BioNTech/Comirnaty and Moderna vaccines revealed similar RAL incidences for the first 20 days after the second dose of vaccine administration (44% for the first 10 days for both groups, 26% vs. 20% for 10–20 days, respectively for Moderna and Pfizer). However, Moderna recipients revealed significantly higher incidences of RAL after 20 days compared to Pfizer–BioNTech/Comirnaty, with nodal reactivity spanning up to the 9th week post-vaccination (15% vs. 4%, respectively P < 0.001). No RAL was observed in patients who received either a single dose of J&J vaccine or two doses of CroronaVac. Younger patients showed increased likelihood of RAL, otherwise, clinical/demographic parameters were not predictive of RAL (P = 0.014 for age, P > 0.05 for additional clinical/demographic parameters).

Conclusion

RAL based on strict PET criteria was observed with mRNA but not with attenuated whole-virus vaccines, in line with higher immunogenicity and stronger protection offered by mRNA vaccines.
Respiratory adenovirus infections in children: a focus on Africa
Authors: van der Zalm Marieke M. , Sam-Agudu Nadia A. , Verhagen Lilly M.
Published: March 2024

Purpose of review

Lower respiratory tract infections (LRTIs) are an important cause of child morbidity and mortality globally, especially in children under the age of 5 years in Africa. Respiratory viruses, including human adenoviruses (HAdVs), are common causes of LRTIs in children. This review aims to shed light on the epidemiology, clinical manifestations, sequelae, and treatment options specific to adenovirus respiratory infections in African children.

Recent findings

Recent evidence has challenged the perception that adenovirus is a negligible cause of LRTIs. Studies show HAdV emerging as the third most common viral pathogen in fatal pneumonias among under-5 children in low-income and middle-income African countries, contributing to 5.5% of all pneumonia deaths and ranking second in hospital-associated viral pneumonia deaths. Predominant HAdV serotypes associated with disease differ by country and region, and have changed over time. Risk factors for increased disease severity and long-term respiratory sequelae in previously healthy African children with HAdV LRTIs are not well established.

Although respiratory viruses, including HAdV, are recognized contributors to LRTIs, the prevalence and impact of adenovirus infections have been under-recognized and understated. Available data suggests that African children, particularly those under 5 years old, are at risk of severe sequelae from respiratory HAdV infections. Long-term sequelae, including bronchiectasis and postinfectious bronchiolitis obliterans, further underscore the significant impact of HAdV infections. However, the scarcity of comprehensive data hampers our understanding of the extent of the impact of HAdV infections on child lung health in Africa. We recommend scaled-up HAdV surveillance, ensuring its consistent inclusion in population-level LRTI assessments, and expanded and equitable access to diagnostics for early recognition of African children at risk of developing chronic sequelae and death. Enhanced understanding of adenovirus epidemiology and clinical outcomes and the availability of therapeutic options are essential for informed public health strategies and clinical care.