bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring health-related social deprivation in small areas: development of an index and examination of its association with cancer mortality
Authors: Wang Kailu , Law Chi-Kin , Zhao Jiaying , Hui Alvin Yik-Kiu , Yip Benjamin Hon-Kei , Yeoh Eng Kiong , Chung Roger Yat-Nork 
Published: September 2021

Abstract
Background
The small-area deprivation indices are varied across countries due to different social context and data availability. Due to lack of chronic disease-related social deprivation index (SDI) in Hong Kong, China, this study aimed to develop a new SDI and examine its association with cancer mortality.

Methods
A total of 14 socio-economic variables of 154 large Tertiary Planning Unit groups (LTPUGs) in Hong Kong were obtained from 2016 population by-census. LTPUG-specific all-cause and chronic condition-related mortality and chronic condition inpatient episodes were calculated as health outcomes. Association of socio-economic variables with health outcomes was estimated for variable selection. Candidates for SDI were constructed with selected socio-economic variables and tested for criterion validity using health outcomes. Ecological association between the selected SDI and cancer mortality were examined using zero-inflated negative binomial regression.

Results
A chronic disease-related SDI constructed by six area-level socio-economic variables was selected based on its criterion validity with health outcomes in Hong Kong. It was found that social deprivation was associated with higher cancer mortality during 2011–2016 (most deprived areas: incidence relative risk [IRR] = 1.40, 95% confidence interval [CI]: 1.27–1.55; second most deprived areas: IRR = 1.34, 95%CI: 1.21–1.48; least deprived areas as reference), and the cancer mortality gap became larger in more recent years. Excess cancer death related to social deprivation was found to have increased through 2011–2016.

Conclusions
Our newly developed SDI is a valid and routinely available measurement of social deprivation in small areas and is useful in resource allocation and policy-making for public health purpose in communities. There is a potential large improvement in cancer mortality by offering relevant policies and interventions to reduce health-related deprivation. Further studies can be done to design strategies to reduce the expanding health inequalities between more and less deprived areas.
The impact of anionic polymers on gene delivery: how composition and assembly help evading the toxicity-efficiency dilemma
Authors: Richter Friederike , Leer Katharina , Martin Liam , Mapfumo Prosper , Solomun Jana I. , Kuchenbrod Maren T. , Hoeppener Stephanie , Brendel Johannes C. , Traeger Anja 
Published: September 2021

AbstractCationic polymers have been widely studied for non-viral gene delivery due to their ability to bind genetic material and to interact with cellular membranes. However, their charged nature carries the risk of increased cytotoxicity and interaction with serum proteins, limiting their potential in vivo application. Therefore, hydrophilic or anionic shielding polymers are applied to counteract these effects. Herein, a series of micelle-forming and micelle-shielding polymers were synthesized via RAFT polymerization. The copolymer poly[(n-butyl acrylate)-b-(2-(dimethyl amino)ethyl acrylamide)] (P(nBA-b-DMAEAm)) was assembled into cationic micelles and different shielding polymers were applied, i.e., poly(acrylic acid) (PAA), poly(4-acryloyl morpholine) (PNAM) or P(NAM-b-AA) block copolymer. These systems were compared to a triblock terpolymer micelle comprising PAA as the middle block. The assemblies were investigated regarding their morphology, interaction with pDNA, cytotoxicity, transfection efficiency, polyplex uptake and endosomal escape. The naked cationic micelle exhibited superior transfection efficiency, but increased cytotoxicity. The addition of shielding polymers led to reduced toxicity. In particular, the triblock terpolymer micelle convinced with high cell viability and no significant loss in efficiency. The highest shielding effect was achieved by layering micelles with P(NAM-b-AA) supporting the colloidal stability at neutral zeta potential and completely restoring cell viability while maintaining moderate transfection efficiencies. The high potential of this micelle-layer-combination for gene delivery was illustrated for the first time.
Trapa bispinosa Roxb. extract lowers advanced glycation end-products and increases live births in older patients with assisted reproductive technology: a randomized controlled trial
Authors: Jinno Masao , Nagai Ryoji , Takeuchi Masayoshi , Watanabe Aiko , Teruya Koji , Sugawa Hikari , Hatakeyama Naohisa , Jinno Yuichi 
Published: September 2021

Abstract
Background
Advanced glycation end-products (AGE), which accumulate with insulin resistance and aging, impair folliculogenesis and may decrease endometrial receptivity. Hishi (Trapa bispinosa Roxb.) extract, a safe herbal medicine, strongly inhibits AGE formation in vitro. We determined whether Hishi lowers AGE and increases live births in older assisted reproductive technology (ART) patients.

Methods
This prospective randomized open-label controlled trial included 64 patients 38 to 42 years old undergoing ART with or without Hishi extract between June 11, 2015 and July 12, 2019. None had over 2 ART failures, diabetes, uterine anomalies, or exhausted ovarian reserve. After allocation, the Hishi group received Hishi extract (100 mg/day) until late pregnancy or failure. The control group received no extract. Both groups underwent 1 cycle of conventional infertility treatment; 1 long-protocol cycle of ovarian stimulation, oocyte retrieval, in vitro fertilization/intracytoplasmic sperm injection, and fresh embryo transfer (ET); and, if needed, cryopreserved ET until live birth or embryo depletion. Serum AGE were measured before and during ART, as were AGE in follicular fluid (FF).

Results
Cumulative live birth rate among 32 Hishi patients was 47%, significantly higher than 16% among 31 controls (p<0.01; RR, 4.6; 95% CI, 1.4 – 15.0; 1 control dropped out). Live birth rate per ET, including fresh and cryopreserved, was significantly higher with Hishi (28% in 47 ET vs. 10% in 49 ET; p<0.05; RR, 3.4; 95% CI, 1.1-10.4). Among variables including age, day-3 FSH, anti-Müllerian hormone, and Hishi, logistic regression identified only Hishi as significantly associated with increased cumulative live birth (p<0.05; OR, 5.1; 95% CI, 1.4 - 18.3). Hishi significantly enhanced oocyte developmental potential, improved endometrial receptivity in natural cycles, and decreased AGE in serum and FF. Larger serum AGE decreases with Hishi were associated with more oocytes becoming day-2 embryos.

Conclusions
Hishi decreased AGE in serum and FF and improved oocyte developmental potential and endometrial receptivity, increasing live births in older patients. Treatment of infertility by AGE reduction represents a new addition to infertility treatment. Therapeutic trials of Hishi for other AGE-associated diseases might be considered.

Trial registration
UMIN registration in Japan (UMIN000017758) on June 1, 2015. https://www.umin.ac.jp/ctr/index.htm
The efficacy of intramuscular electrical stimulation in the management of patients with myofascial pain syndrome: a systematic review
Authors: Hadizadeh Monavar , Rahimi Abbas , Javaherian Mohammad , Velayati Meysam , Dommerholt Jan 
Published: September 2021

Abstract
Introduction
Myofascial pain syndrome (MPS) is one of the most common disorders causing chronic muscle pain. Almost one-third of patients with musculoskeletal complaints meet the MPS criteria. The aim of this study is to evaluate the effectiveness of intramuscular electrical stimulation (IMES) in patients with MPS through a systematic review method.

Methods
PubMed, Scopus, Embase, ProQuest, PEDro, Web of Science, and CINAHL were systematically searched to find out the eligible articles without language limitations from 1990 to December 30, 2020. All relevant randomized controlled trials that compared the effectiveness of IMES with sham-IMES, dry needling, or exercise therapy in patients with MPS were included. Full texts of the selected studies were critically appraised using Revised Cochrane risk-of-bias tool for randomized trials (RoB2).

Results
Six studies (out of 397) had met our inclusion criteria (involving 158 patients) and were entered to the systematic review. Outcome measures examined in these studies included pain, range of motion, pressure pain threshold, biochemical factors, disability, and amount of analgesic use. In the most studies, it has been shown that IMES is more effective than the control group in improving some outcome measurements such as pain.

Conclusion
There is preliminary evidence from a few small trials suggesting the efficacy of IMES for the care of myofascial pain syndrome. The data support the conduct of larger trials investigating the efficacy of IMES.
Mechanism exploration of Gouqi-wentang formula against type 2 diabetes mellitus by phytochemistry and network pharmacology-based analysis and biological validation
Authors: Han Lin , Yang Hao-yu , Zheng Yu-jiao , Wei Xiu-xiu , Dan Wen-chao , Zhang Li-li , Ding Qi-you , Ma Xu , Wang Xin-miao , Zhao Lin-hua , Tong Xiao-lin 
Published: September 2021

Abstract
Background
The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear.

Methods
The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments.

Results
First, the “herb-channel tropism” network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, “compound-target” network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a “formula-compound-pathway-symptom” network was constructed to represent a global view of GQWTF in the treatment of T2DM.

Conclusions
This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.
Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial
Authors: Yu Yuetian , Zhu Cheng , Hong Yucai , Chen Lin , Huang Zhiping , Zhou Jiancang , Tian Xin , Liu Dadong , Ren Bo , Zhang Cao , Hu Caibao , Wang Xinan , Yin Rui , Gao Yuan , Zhang Zhongheng 
Published: September 2021

AbstractBackgroundSeptic shock is characterized by an uncontrolled inflammatory response and microcirculatory dysfunction. There is currently no specific agent for treating septic shock. Anisodamine is an agent extracted from traditional Chinese medicine with potent anti-inflammatory effects. However, its clinical effectiveness remains largely unknown.MethodsIn a multicentre, open-label trial, we randomly assigned adults with septic shock to receive either usual care or anisodamine (0.1–0.5 mg per kilogram of body weight per hour), with the anisodamine doses adjusted by clinicians in accordance with the patients’ shock status. The primary end point was death on hospital discharge. The secondary end points were ventilator-free days at 28 days, vasopressor-free days at 28 days, serum lactate and sequential organ failure assessment (SOFA) score from days 0 to 6. The differences in the primary and secondary outcomes were compared between the treatment and usual care groups with theχ2test, Student’s t test or rank-sum test, as appropriate. The false discovery rate was controlled for multiple testing.ResultsOf the 469 patients screened, 355 were assigned to receive the trial drug and were included in the analyses—181 patients received anisodamine, and 174 were in the usual care group. We found no difference between the usual care and anisodamine groups in hospital mortality (36% vs. 30%;p = 0.348), or ventilator-free days (median [Q1, Q3], 24.4 [5.9, 28] vs. 26.0 [8.5, 28];p = 0.411). The serum lactate levels were significantly lower in the treated group than in the usual care group after day 3. Patients in the treated group were less likely to receive vasopressors than those in the usual care group (OR [95% CI] 0.84 [0.50, 0.93] for day 5 and 0.66 [0.37, 0.95] for day 6).ConclusionsThere is no evidence that anisodamine can reduce hospital mortality among critically ill adults with septic shock treated in the intensive care unit.Trial registrationClinicalTrials.gov (NCT02442440; Registered on 13 April 2015).
Single-cell landscape of nuclear configuration and gene expression during stem cell differentiation and X inactivation
Authors: Bonora Giancarlo , Ramani Vijay , Singh Ritambhara , Fang He , Jackson Dana L. , Srivatsan Sanjay , Qiu Ruolan , Lee Choli , Trapnell Cole , Shendure Jay , Duan Zhijun , Deng Xinxian , Noble William S. , Disteche Christine M. 
Published: September 2021

Abstract
Background
Mammalian development is associated with extensive changes in gene expression, chromatin accessibility, and nuclear structure. Here, we follow such changes associated with mouse embryonic stem cell differentiation and X inactivation by integrating, for the first time, allele-specific data from these three modalities obtained by high-throughput single-cell RNA-seq, ATAC-seq, and Hi-C.

Results
Allele-specific contact decay profiles obtained by single-cell Hi-C clearly show that the inactive X chromosome has a unique profile in differentiated cells that have undergone X inactivation. Loss of this inactive X-specific structure at mitosis is followed by its reappearance during the cell cycle, suggesting a “bookmark” mechanism. Differentiation of embryonic stem cells to follow the onset of X inactivation is associated with changes in contact decay profiles that occur in parallel on both the X chromosomes and autosomes. Single-cell RNA-seq and ATAC-seq show evidence of a delay in female versus male cells, due to the presence of two active X chromosomes at early stages of differentiation. The onset of the inactive X-specific structure in single cells occurs later than gene silencing, consistent with the idea that chromatin compaction is a late event of X inactivation. Single-cell Hi-C highlights evidence of discrete changes in nuclear structure characterized by the acquisition of very long-range contacts throughout the nucleus. Novel computational approaches allow for the effective alignment of single-cell gene expression, chromatin accessibility, and 3D chromosome structure.

Conclusions
Based on trajectory analyses, three distinct nuclear structure states are detected reflecting discrete and profound simultaneous changes not only to the structure of the X chromosomes, but also to that of autosomes during differentiation. Our study reveals that long-range structural changes to chromosomes appear as discrete events, unlike progressive changes in gene expression and chromatin accessibility.
Biologically relevant transfer learning improves transcription factor binding prediction
Authors: Novakovsky Gherman , Saraswat Manu , Fornes Oriol , Mostafavi Sara , Wasserman Wyeth W. 
Published: September 2021

AbstractBackgroundDeep learning has proven to be a powerful technique for transcription factor (TF) binding prediction but requires large training datasets. Transfer learning can reduce the amount of data required for deep learning, while improving overall model performance, compared to training a separate model for each new task.ResultsWe assess a transfer learning strategy for TF binding prediction consisting of a pre-training step, wherein we train a multi-task model with multiple TFs, and a fine-tuning step, wherein we initialize single-task models for individual TFs with the weights learned by the multi-task model, after which the single-task models are trained at a lower learning rate. We corroborate that transfer learning improves model performance, especially if in the pre-training step the multi-task model is trained with biologically relevant TFs. We show the effectiveness of transfer learning for TFs with ~ 500 ChIP-seq peak regions. Using model interpretation techniques, we demonstrate that the features learned in the pre-training step are refined in the fine-tuning step to resemble the binding motif of the target TF (i.e., the recipient of transfer learning in the fine-tuning step). Moreover, pre-training with biologically relevant TFs allows single-task models in the fine-tuning step to learn useful features other than the motif of the target TF.ConclusionsOur results confirm that transfer learning is a powerful technique for TF binding prediction.
The ultrasound competency assessment tool for four-view cardiac POCUS
Authors: Bell Colin , Wagner Natalie , Hall Andrew , Newbigging Joseph , Rang Louise , McKaigney Conor 
Published: September 2021

Abstract
Background
Point-of-care ultrasound (POCUS) has been recognized as an essential skill across medicine. However, a lack of reliable and streamlined POCUS assessment tools with demonstrated validity remains a significant barrier to widespread clinical integration. The ultrasound competency assessment tool (UCAT) was derived to be a simple, entrustment-based competency assessment tool applicable to multiple POCUS applications. When used to assess a FAST, the UCAT demonstrated high internal consistency and moderate-to-excellent inter-rater reliability. The objective of this study was to validate the UCAT for assessment of a four-view transthoracic cardiac POCUS.

Results
Twenty-two trainees performed a four-view transthoracic cardiac POCUS in a simulated environment while being assessed by two observers. When used to assess a four-view cardiac POCUS the UCAT retained its high internal consistency ($$\alpha =0.90)$$

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0.90
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and moderate-to-excellent inter-rater reliability (ICCs = 0.61–0.91; p’s ≤ 0.01) across all domains. The regression analysis suggestion that level of training, previous number of focused cardiac ultrasound, previous number of total scans, self-rated entrustment, and intent to pursue certification statistically significantly predicted UCAT entrustment scores [F (5,16) = 4.06, p = 0.01; R2 = 0.56].

Conclusion
This study confirms the UCAT is a valid assessment tool for four-view transthoracic cardiac POCUS. The findings from this work and previous studies on the UCAT demonstrate the utility and flexibility of the UCAT tool across multiple POCUS applications and present a promising way forward for POCUS competency assessment.
Identifying social perceptions of people ignoring COVID-19 warnings: a qualitative study in Iran
Authors: Halvaiepour Zohreh , Nosratabadi Mehdi 
Published: September 2021

Abstract
Objective
The COVID-19 pandemic has had various effects on the social life and daily activities of people in most countries in the world, including Iran. Hygienic precautions have been recommended, such as wearing masks and maintaining social distancing, to reduce the spread of the COVID-19. However, some people in society have not considered and ignored these health issues. This study aims to identify the sociological perceptions of people who ignore the COVID-19 warning. A qualitative study was carried out from May to July 2020. The interviewees were purposefully selected from people in Isfahan who avoided paying attention to the COVID-19 warnings. The saturation point was reached in 20 semi-structured interviews. The thematic analysis approach was used to analyze the transcribed documents using MAXQDA software (version 12).

Results
The results show 2 themes and 4 sub-themes related to the sociological perception of people who ignore the COVID-19 warning. The themes and sub-themes include: feelings of social anomie (disruption and social unrest, social distrust), unmet social relationship needs (intention to maintain social participation, Feeling of reduced social support). In order to tackle social perceptions contrary to health observance during the coronavirus pandemic, educational resources such as mass media, cyberspace and social programs on the necessity and importance of health observance need to be used. Policies should also be implemented in the social, cultural and legislative contexts to enhance the degree of individuals' social responsibility.
Challenges and opportunities to delivering cardiac imaging training: a national survey by the Italian college of cardiac radiology
Authors: Gatti Marco , Liguori Carlo , Muscogiuri Giuseppe , Faletti Riccardo , Dell’Aversana Serena , Toia Patrizia , De Rubeis Gianluca , Di Renzi Paolo , Russo Vincenzo , Polizzi Gesualdo , Galea Nicola , Esposito Antonio , Francone Marco 
Published: September 2021

Abstract
Background
Delivering consistent levels of training in cardiac imaging to radiologist is of pivotal importance because of the increasing clinical indications to coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR). Our study sought to capture the heterogeneity of cardiac imaging training programs and to explore residents’ vision on cardiac imaging both in the present and in the future.

Methods
Two web-based surveys were created. The first was administered to all chief residents from the 42 University Hospitals within Italy, aiming to explore the local educational offer in cardiac imaging. The second was administered via social media to all Italian residents, including questions about their overall vision regarding cardiac imaging.

Results
42/42 University Hospitals responded to the first survey and 235 residents to the second. There was at least a 64-slice CT scanner and a 1.5 T MR scanner per center. In the majority of sites, the weekly routine consisted of more than 10 CCTA and more than 5 CMR. Approximately, half of the centers used advanced CCTA and CMR techniques. The majority of the interviewed resident (94%) perceived cardiac imaging training to be moderately to very important, while requirement for external educational resources was advocated in 25% of the cases.

Conclusion
Our survey highlighted a significant awareness of radiology residents regarding the importance of cardiac imaging in their training curriculum. All centers met the technical requirements for cardiac imaging, limiting its use to basic applications in around half of cases. Implementation of an educational network might be the key for supporting the growth of this subspecialty field.