bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK cells are never alone: crosstalk and communication in tumour microenvironments
Authors: Zhou Yongqiang , Cheng Lu , Liu Lu , Li Xun 
Published: February 2023

AbstractImmune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration and poor efficacy of natural killer (NK) cell-based immunotherapy, which becomes a key factor triggering tumour progression. Understanding the crosstalk between NK cells and the TME provides new insights for optimising NK cell-based immunotherapy. Here, we present new advances in direct or indirect crosstalk between NK cells and 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, and microbial microenvironments, summarise TME-mediated mechanisms of NK cell function inhibition, and highlight potential targeted therapies for NK-TME crosstalk. Importantly, we discuss novel strategies to overcome the inhibitory TME and provide an attractive outlook for the future.
Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis
Authors: Lee Yujin , Ni Jie , Beretov Julia , Wasinger Valerie C. , Graham Peter , Li Yong 
Published: February 2023

AbstractCurrent clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50–1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50–150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.
Transfer RNA-derived small RNAs in tumor microenvironment
Authors: Yang Mei , Mo Yongzhen , Ren Daixi , Liu Shun , Zeng Zhaoyang , Xiong Wei 
Published: February 2023

AbstractTransfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge.
Complement activation in severely ill patients with sepsis: no relationship with inflammation and disease severity
Authors: de Nooijer Aline H. , Kotsaki Antigone , Kranidioti Eleftheria , Kox Matthijs , Pickkers Peter , Toonen Erik J. M. , Giamarellos-Bourboulis Evangelos J. , Netea Mihai G. 
Published: February 2023

Abstract
Background
Sepsis is characterized by a dysregulated immune response to infection. The complement system plays an important role in the host defence to pathogens. However, exaggerated complement activation might contribute to a hyperinflammatory state. The interplay between complement activation and inflammation in relationship with adverse outcomes in sepsis patients is unclear.

Methods
Secondary analysis of complement factors in a prospective study in 209 hospitalized sepsis patients, of whom the majority presented with shock. Concentrations of complement factors C3, C3a, C3c, C5, C5a, and soluble terminal complement complex were assessed in ethylenediaminetetraacetic acid plasma samples collected within 24 h after sepsis diagnosis using enzyme-linked immunosorbent assays.

Results
The concentration of complement factors in plasma of severely ill sepsis patients indicated profound activation of the complement system (all P < 0.01 compared to healthy controls). Spearman rank correlation tests indicated consistent relationships between the different complement factors measured, but no significant correlations were observed between the complement factors and other inflammatory biomarkers such as leukocyte numbers, C-reactive protein and ferritin concentrations, or HLA-DR expression on monocytes. The concentration of complement factors was not associated with Sequential Organ Failure Assessment score, the incidence of septic shock, and mortality rates (all P > 0.05) in this cohort of patients with high disease severity.

Conclusions
Once an infection progresses to severe sepsis or septic shock, the complement pathway is already profoundly activated and is no longer related to a dysregulated inflammatory response, nor to clinical outcome. This implies that in this patient category with severe disease, the complement system is activated to such an extent that it no longer has predictive value for clinical outcome.
Clonorchis sinensis legumain promotes migration and invasion of cholangiocarcinoma cells via regulating tumor-related molecules
Authors: Chu Yanfei , Shi Doufei , Wang Nan , Ren Lebin , Liu Naiguo , Hu Fengai , Meng Wei , Hong Sung-Jong , Bai Xuelian 
Published: February 2023

Abstract
Background
Clonorchis sinensis infection causes serious pathological changes in the bile duct and is highly correlated with cholangiocarcinoma. The excretory–secretory products (ESP) of C. sinensis play a critical role in the oncogenesis and progression of cholangiocarcinoma, while the components and precise mechanism remain unclear. Here, we evaluated the function of C. sinensis legumain (Cslegumain) in promoting the invasion and migration of cholangiocarcinoma cells and the mechanism involved.

Methods
The structural and molecular characteristics of Cslegumain were predicted and analyzed using the online program Phyre2. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to test the transcriptional level of Cslegumain and its localization in the adult. Native Cslegumain was detected by western blotting assay. The effects of Cslegumain on the proliferation, invasion and migration of cholangiocarcinoma cells were checked using CCK-8 assay, Matrigel transwell assay and scratch wound healing assay. Expression levels of tumor-related molecules regulated by Cslegumain were evaluated by qRT-PCR and western blotting assay.

Results
Cslegumain showed high similarity with human legumain in the secondary and tertiary structures and displayed higher transcriptional levels in the adult worm than in the metacercariae. Native Cslegumain was detected in a catalytic form and was localized mainly in the intestine of the C. sinensis adult and epithelial cells of the intrahepatic bile duct. After transfection into RBE cells, Cslegumain showed high ability in promoting the invasion and migration but not the proliferation of cholangiocarcinoma RBE cells. Furthermore, the expression levels of some molecules including E-cadherin and N-cadherin were downregulated, while the levels of α-actinin 4, β-catenin and inducible nitric oxide synthase (iNOS) were upregulated.

Conclusions
Our findings indicated that Cslegumain showed very similar structures as those of human legumain and could promote the invasion and migration of cholangiocarcinoma cells by regulating some tumor-related molecules.

Graphical Abstract
Niclosamide from an anthelmintic drug to a promising adjuvant therapy for diabetic kidney disease: randomized clinical trial
Authors: El-fatatry Basma Mahrous , El-Haggar Sahar Mohamed , Ibrahim Osama Mohamed , Shalaby Khaled Hamed 
Published: February 2023

Abstract
Background
Diabetic kidney disease (DKD) is a serious complication that begins with albuminuria and often leads to a rapid progressive decline in renal function. Niclosamide is a potent inhibitor of the Wnt/β-catenin pathway, which controls the expression of multiple genes of the renin–angiotensin–aldosterone system (RAAS), which in turn is influences the progression of DKD. This study was conducted to evaluate the effect of niclosamide as adjuvant therapy on DKD.

Methods
Out of 127 patients screened for eligibility, 60 patients completed the study. After randomization, 30 patients in the niclosamide arm received ramipril plus niclosamide, and 30 patients in the control arm received ramipril only for 6 months. The primary outcomes were the changes in urinary albumin to creatinine ratio (UACR), serum creatinine, and estimated glomerular filtration rate (eGFR). The secondary outcomes were measurements of urinary matrix metalloproteinase-7 (MMP-7), 8-hydroxy-2ʹ-deoxyguanosine (8-OHdG), and podocalyxin (PCX). Comparisons between the two arms were done using student t-test. Correlation analysis was done using Pearson correlation.

Results
Niclosamide decreased UACR by 24% (95% CI − 30 to − 18.3%) while there was a rise in UACR in the control arm by 11% (95% CI 4 to 18.2%) after 6 months (P < 0.001). Moreover, a significant reduction in MMP-7 and PCX was noticed in the niclosamide arm. Regression analysis revealed a strong association between MMP-7, which is a noninvasive biomarker predicting the activity of the Wnt/β-catenin signaling, and UACR. A 1 mg/dL decline in MMP-7 level was associated with a 25 mg/g lowering in UACR (B = 24.95, P < 0.001).

Conclusion
The addition of niclosamide to patients with diabetic kidney disease receiving an angiotensin-converting enzyme inhibitor significantly reduces albumin excretion. Further larger-scale trials are needed to confirm our results.
Trial registration: The study was prospectively registered on clinicaltrial.gov on March 23, 2020, with identification code NCT04317430.
Psychological readiness is related to return to sport in judo injuries: a cross-sectional study
Authors: Lambert Christophe , Guenther Daniel , Schütz Lisa-Marie , Kern Niklas , Ritzmann Ramona , Reinert Noémie , Walz Martin , Wafaisade Arasch , Nagy Kolos , Reuter Sven 
Published: February 2023

Abstract
Background
The aim of this study is to investigate the influence of a judoka's psychological readiness in relation to his ability to return to sport. At the present time, the relationship between physical and psychological readiness to return to sport has not been adequately elucidated.

Methods
This is a cross-sectional study. An online survey was distributed via social networks and the German Judo Association collecting data from competitive and recreational judo athletes. The survey collected data on participants’ characteristics, history of injury, and psychological readiness to return to sport after injury as determined by either the Anterior Cruciate Ligament-Return to Sport after Injury Scale, the Shoulder Instability-Return to Sport after Injury Scale, or a modified version of the Return to Sport after Injury Scale depending on the respective type of injury.

Results
The study included 383 judo athletes (272 competitive judo athletes and 112 recreational judo athletes). Regardless of injury location, athletes who achieved return to sports (M = 70.67; SD = 16.47) had higher RSI scores than athletes that did not return to sports (M = 53.88; SD = 19.12; p < 0.0001). Male athletes (M = 65.60; SD = 19.34) did show significantly higher RSI scores than female athletes (M = 60.45; SD = 19.46). The RSI score differed for different time loss categories, F(7, 375) = 11.309, p < 0.001, η2 = .174 with decreasing RSI scores for longer time loss and lowest RSI scores in athletes, who never returned to sports. RSI scores of athletes with knee injuries differed from athletes with other injury locations (10.23, 95% CI [4.08, 16.38]). After adjusting for time loss due to injury, competitive athletes had higher RSI scores than competitive athletes (F (1, 382) = 7.250, p < 0.001, partial η2 = .02). Conservatively treated athletes (M = 66.58; SD = 18.54) had higher RSI scores than surgically treated athletes (M = 59.05; SD = 20.01; p < 0.05).

Conclusion
Based on the data of this study, type of injury, sport level, treatment method, and gender appear to influence psychological readiness on judoka and their ability to return to sport. The multiple factors that influence a judoka and their ability to return to sport argue for individualized treatment of judoka and their psychological state after injury in the return to sport process.
The physician shortage in Israel and a policy proposal for improvement
Authors: Treister-Goltzman Yulia , Peleg Roni 
Published: February 2023

Abstract
Background
There is a decrease in the supply of physicians in Israel resulting from the declining flow of immigrant physicians from the former Soviet Union, a large proportion of whom have reached retirement age in recent years. This problem could become worse because the number of medical students in Israel cannot increase quickly, especially because the number of clinical training sites is inadequate. The quick population growth and anticipated ageing will exacerbate the shortage. The aim of our study was to accurately assess the current situation and factors that affect it, and to propose systematic steps to improve the physician shortage.

Main body
The number of physicians per capita is lower in Israel than in the OECD at 3.1 vs. 3.5 per 1000 population, respectively. About 10% of licensed physicians live outside of Israel. There is a sharp increase in the number of Israelis returning from medical school abroad, but some of those schools are of low academic standard. The main step is a gradual increase in the number of medical students in Israel with a transition of clinical practice to the community, and hospital clinical hours in the evening and in the summer. Students with high psychometric scores who were not admitted to an Israeli medical school would get support to study in quality medical schools abroad. Additional steps include encouraging physicians from abroad to come to Israel, especially in specializations in distress, recruitment of retired physicians, transferring functions to other medical professions, economic incentives for departments and teachers, and incentives to prevent physicians from quitting or migrating to other countries. It is also important to close the gap between the number of physicians working in central Israel and the periphery through grants, employment opportunities for physicians’ spouses, and preferential selection of students from the periphery for medical school.

Conclusions
Manpower planning requires a broad, dynamic perspective and collaboration among governmental and non-governmental organizations.
A non-destructive analytical study of cultural heritage object from Late Antiquity: gold framework and gemstone inlays
Authors: Hanus Radek , Sobek Kamil , Souček Kamil , Staš Lubomír , Georgiou Lucie , Selucká Alena 
Published: February 2023

Abstract
Recently found historical jewellery (Czech Republic) was subjected to detailed analyses to determine the gem inlays and the gold framework in which they are embedded. Such find fits into European jewellery archaeological artefacts containing similar stones from around the fifth century CE. The gemstones were analysed with optical microscopy and Raman micro-spectroscopy to determine their mineralogical characteristics and to find out typical structural-chemical differences based on which their provenance can be found. The results of this measurement discovered two main types of minerals from the garnet group, almandine and pyrope, where pyropes have been identified as Bohemian garnets thanks to the typical photoluminescence (PL) of chromium and vanadium impurities. The craftsmanship and processing of the goldsmith work were studied using X-ray computed tomography. Such a technique is an excellent contribution for detecting and visualising the internal parts hidden behind the placement of the stones. For this reason, 3D visualisation was used to describe and better understand all preserved parts. According to this object's very high cultural and historical value, the chosen methods are suitable for non-destructive study while proving to be essential to deepen our knowledge in archaeometric investigations focused on jewellery from Late Antiquity (with possible application to the jewellery from other periods). Based on the findings presented in this study, it is one of the world's oldest documented items using Bohemian garnets in jewellery. These findings underscore the tremendous economic and political importance of Bohemian garnet mineral resources altogether, with a second completely different type of garnet believed to have originated in distant India or Sri Lanka that was used in jewellery across Europe in Late Antiquity.
Detection of solid and subsolid pulmonary nodules with lung MRI: performance of UTE, T1 gradient-echo, and single-shot T2 fast spin echo
Authors: Sanchez Felipe , Tyrrell Pascal N. , Cheung Patrick , Heyn Chinthaka , Graham Simon , Poon Ian , Ung Yee , Louie Alexander , Tsao May , Oikonomou Anastasia 
Published: February 2023

Abstract
Background
Although MRI is a radiation-free imaging modality, it has historically been limited in lung imaging due to inherent technical restrictions. The aim of this study is to explore the performance of lung MRI in detecting solid and subsolid pulmonary nodules using T1 gradient-echo (GRE) (VIBE, Volumetric interpolated breath-hold examination), ultrashort time echo (UTE) and T2 Fast Spin Echo (HASTE, Half fourier Single-shot Turbo spin-Echo).

Methods
Patients underwent a lung MRI in a 3 T scanner as part of a prospective research project. A baseline Chest CT was obtained as part of their standard of care. Nodules were identified and measured on the baseline CT and categorized according to their density (solid and subsolid) and size (> 4 mm/ ≤ 4 mm). Nodules seen on the baseline CT were classified as present or absent on the different MRI sequences by two thoracic radiologists independently. Interobserver agreement was determined using the simple Kappa coefficient. Paired differences were compared using nonparametric Mann-Whitney U tests. The McNemar test was used to evaluate paired differences in nodule detection between MRI sequences.

Results
Thirty-six patients were prospectively enrolled. One hundred forty-nine nodules (100 solid/49 subsolid) with mean size 10.8 mm (SD = 9.4) were included in the analysis. There was substantial interobserver agreement (k = 0.7, p = 0.05).
Detection for all nodules, solid and subsolid nodules was respectively; UTE: 71.8%/71.0%/73.5%; VIBE: 61.6%/65%/55.1%; HASTE 72.4%/72.2%/72.7%. Detection rate was higher for nodules > 4 mm in all groups: UTE 90.2%/93.4%/85.4%, VIBE 78.4%/88.5%/63.4%, HASTE 89.4%/93.8%/83.8%. Detection of lesions ≤4 mm was low for all sequences. UTE and HASTE performed significantly better than VIBE for detection of all nodules and subsolid nodules (diff = 18.4 and 17.6%, p = < 0.01 and p = 0.03, respectively). There was no significant difference between UTE and HASTE. There were no significant differences amongst MRI sequences for solid nodules.

Conclusions
Lung MRI shows adequate performance for the detection of solid and subsolid pulmonary nodules larger than 4 mm and can serve as a promising radiation-free alternative to CT.
Validity of root cause analysis in investigating adverse events in psychiatry
Authors: Deshpande Mayura , Sinclair Julia M. A. , Baldwin David S. 
Published: February 2023

SummaryRoot cause analysis (RCA), imported from high-reliability industries into health two decades ago, is the mandated methodology to investigate adverse events in most health systems. In this analysis, we argue that the validity of RCA in health and in psychiatry must be established, given the impact of these investigations on mental health policy and practice.
The WHO World Mental Health Report: a call for action
Authors: Cuijpers Pim , Javed Afzal , Bhui Kamaldeep 
Published: February 2023

SummaryThe World Health Organization's World Mental Health Report is a call for action and reminds all of the huge personal and societal impact of mental illnesses. Significant effort is required to engage, inform and motivate policymakers to act. We must develop more effective, context-sensitive and structurally competent care models.
Cancer-Related Stigma in Malawi: Narratives of Cancer Survivors
Authors: Watt Melissa H. , Suneja Gita , Zimba Chifundo , Westmoreland Katherine D. , Bula Agatha , Cutler Lux , Khatri Abhilasha , Painschab Matthew S. , Kimani Stephen 
Published: February 2023

PURPOSE Stigma is an impediment across the cancer care continuum, leading to delayed presentation to care, elevated morbidity and mortality, and reduced quality of life. The goal of this study was to qualitatively examine the drivers, manifestations, and impacts of cancer-related stigma among individuals who received cancer treatment in Malawi, and to identify opportunities to address stigma. METHODS Individuals who had completed treatment for lymphoma (n = 20) or breast cancer (n = 9) were recruited from observational cancer cohorts in Lilongwe, Malawi. Interviews explored the individual's cancer journey, from first symptoms through diagnosis, treatment, and recovery. Interviews were audio-recorded and translated from Chichewa to English. Data were coded for content related to stigma, and thematically analyzed to describe the drivers, manifestations, and impacts of stigma along the cancer journey. RESULTS Drivers of cancer stigma included beliefs of cancer origin (cancer as infectious; cancer as a marker of HIV; cancer due to bewitchment), perceived changes in the individual with cancer (loss of social/economic role; physical changes), and expectations about the individual's future (cancer as death sentence). Cancer stigma manifested through gossip, isolation, and courtesy stigma toward family members. The impacts of cancer stigma included mental health distress, impediments to care engagement, lack of cancer disclosure, and self-isolation. Participants suggested the following programmatic needs: community education about cancer; counseling in health facilities; and peer support from cancer survivors. CONCLUSION The results highlight multifactorial drivers, manifestations, and impacts of cancer-related stigma in Malawi, which may affect success of cancer screening and treatment programs. There is a clear need for multilevel interventions to improve community attitudes toward people with cancer, and to support individuals along the continuum of cancer care.