bluuebunny/crossref_metadata_2025_split huggingface dataset:
The 18-month efficacy of an Intensive LifeStyle Modification Program (ILSM) to reduce type 2 diabetes risk among rural women: a cluster randomized controlled trial
Authors: Zhong Qinyi , Chen Yao , Luo Mengchun , Lin Qian , Tan Jianghong , Xiao Shuiyuan , Willey James Allen , Chen Jyu-Lin , Whittemore Robin , Guo Jia 
Published: January 2023

Abstract
Background
Many lifestyle interventions have demonstrated efficacy up to one-year follow-up, yet maintaining improvements at longer-term follow-up is a well-recognized worldwide challenge, especially in underserved areas. The purpose of this study is to compare the 18-month efficacy of an Intensive LifeStyle Modification Program to usual care in reducing the risk for type 2 diabetes (T2D) among women with a history of gestational diabetes mellitus (GDM).

Methods
We conducted a two-arm, cluster randomized controlled trial among women with a history of GDM in China. A total of 16 towns (clusters) in two distinct rural areas in south-central China were randomly selected (8 towns per area) and assigned (1:1) to the intervention (Intensive LifeStyle Modification Program) or control (usual care) group with stratification in the two rural areas. The strategies for maintaining intervention effects were used (including setting recursive goals and providing a supportive environment, etc.) under the guidance of social cognitive theory. The primary outcome was a change in T2D risk; secondary outcomes included glycemic, weight-related, behavioral, and psychological variables. All outcomes were collected at baseline, 6, and 18 months. All participants entered the intention-to-treat analysis. Data were analyzed via generalized estimation equation models (accounting for clusters) at the individual level, with subgroup analysis included in the model.

Results
The sample included 320 women from 16 clusters (20 women per cluster). At 18 months, the intervention group demonstrated a significant improvement in T2D risk score, fasting blood glucose, body mass index (BMI), waist circumference, intention to eat low glycemic index food, perceived stress, quality of life in psychological and environmental domains, and social support over time (p < 0.05) based on the intention-to-treat analysis set. Subgroup analysis showed a significant interaction effect on T2D risk score in subgroups of different BMI, waist circumference, and blood glucose (p < 0.05).

Conclusions
Over 18 months, the Intensive LifeStyle Modification Program reduced T2D risk among rural women with a history of GDM in China. Women who were overweight, had high abdominal adiposity, or had blood glucose intolerance benefited more from this intervention. This program serves as a potential diabetes prevention model for women with a history of GDM in low-resource settings worldwide.

Trial registration
Registered on Chinese Clinical Trial Registry (ChiCTR1800015023) on 1st March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25569
Buccal rotation for wholly impacted maxillary third molar extraction
Authors: Ye Zhou-Xi , Qian Wen-Hao , Wu Yu-Bo , Yang Chi 
Published: January 2023

AbstractBackgroundExtracting wholly impacted maxillary 3rd molars faces difficulty due to the narrow surgical field, adjacent teeth resistances and risk of oroantral communication. This study is designed to introduce and evaluate the applicability of a novel method-buccal rotation to extract maxillary 3rd molars.Materials and methodsIn this cohort study, from October 1st 2020 to September 30th 2021, 72 wholly impacted maxillary 3rd molars were included. Based on the crowns with coronal 1/3, middle 1/3, apical 1/3 of the adjacent teeth roots, teeth were classified into position I, II, III. Based on the angles < 30°, ≥ 30°but < 60°, ≥ 60° to the adjacent teeth, teeth were classified into angulation A, B, C. Traditional method and novel method-buccal rotation were applied based on the surgical simulations. Surgical results were recorded. To analyze the data, Chi-square test was applied.Results82.00% of teeth in position I and 50.00% in position II were designed to use traditional method, 83.33% in position III were using the novel method (p < 0.05). 81.25% of teeth in angulation A and 52.63% in angulation B were designed to use traditional method, 80.00% in angulation C were using the novel method (p < 0.05). Four cases got temporary complications.ConclusionBuccal rotation was applicable to extract the deep impacted maxillary third molars with large angles towards the adjacent teeth.
Evaluating remote facilitation intensity for multi-national translation of nurse-initiated stroke protocols (QASC Australasia): a protocol for a cluster randomised controlled trial
Authors: Fasugba O. , Dale S. , McInnes E. , Cadilhac D. A. , Noetel M. , Coughlan K. , McElduff B. , Kim J. , Langley T. , Cheung N. W. , Hill K. , Pollnow V. , Page K. , Sanjuan Menendez E. , Neal E. , Griffith S. , Christie L. J. , Slark J. , Ranta A. , Levi C. , Grimshaw J. M. , Middleton S. 
Published: January 2023

Abstract
Background
Facilitated implementation of nurse-initiated protocols to manage fever, hyperglycaemia (sugar) and swallowing difficulties (FeSS Protocols) in 19 Australian stroke units resulted in reduced death and dependency for stroke patients. However, a significant gap remains in translating this evidence-based care bundle protocol into standard practice in Australia and New Zealand. Facilitation is a key component for increasing implementation. However, its contribution to evidence translation initiatives requires further investigation. We aim to evaluate two levels of intensity of external remote facilitation as part of a multifaceted intervention to improve FeSS Protocol uptake and quality of care for patients with stroke in Australian and New Zealand acute care hospitals.

Methods
A three-arm cluster randomised controlled trial with a process evaluation and economic evaluation. Australian and New Zealand hospitals with a stroke unit or service will be recruited and randomised in blocks of five to one of the three study arms—high- or low-intensity external remote facilitation or a no facilitation control group—in a 2:2:1 ratio. The multicomponent implementation strategy will incorporate implementation science frameworks (Theoretical Domains Framework, Capability, Opportunity, Motivation – Behaviour Model and the Consolidated Framework for Implementation Research) and include an online education package, audit and feedback reports, local clinical champions, barrier and enabler assessments, action plans, reminders and external remote facilitation. The primary outcome is implementation effectiveness using a composite measure comprising six monitoring and treatment elements of the FeSS Protocols. Secondary outcome measures are as follows: composite outcome of adherence to each of the combined monitoring and treatment elements for (i) fever (n=5); (ii) hyperglycaemia (n=6); and (iii) swallowing protocols (n=7); adherence to the individual elements that make up each of these protocols; comparison for composite outcomes between (i) metropolitan and rural/remote hospitals; and (ii) stroke units and stroke services. A process evaluation will examine contextual factors influencing intervention uptake. An economic evaluation will describe cost differences relative to each intervention and study outcomes.

Discussion
We will generate new evidence on the most effective facilitation intensity to support implementation of nurse-initiated stroke protocols nationwide, reducing geographical barriers for those in rural and remote areas.

Trial registration
ACTRN12622000028707. Registered 14 January, 2022.
Changes in the characteristics of patients treated for brain metastases with repeat stereotactic radiotherapy (SRT): a retrospective study of 184 patients
Authors: Kuntz L. , Le Fèvre C. , Jarnet D. , Keller A. , Meyer P. , Thiery A. , Cebula H. , Noel G. , Antoni D. 
Published: January 2023

Abstract
Purpose
Brain metastases (BMs) are the leading cause of intracranial malignant neoplasms in adults. WHO, Karnofsky performance status (KPS), age, number of BMs, extracerebral progression (ECP), recursive partitioning analysis (RPA), diagnosis-specific graded prognostic assessment (Ds-GPA) are validated prognostic tools to help clinicians decide on treatment. No consensus exists for repeat stereotactic radiotherapy (SRT) for BMs. The aim of this study was to review the changes in patient characteristics treated with repeated SRTs.

Methods and materials
The data of patients treated between 2010 and 2020 with at least two courses of SRT without previous whole brain radiotherapy (WBRT) were reviewed. Age, WHO, KPS, ECP, type of systemic treatment, number of BMs were recorded. RPA, Ds-GPA and brain metastasis velocity (BMV) were calculated.

Results
184 patients were treated for 915 BMs and received two to six SRTs for local or distant brain recurrence. The median number of BMs treated per SRT was 1 (range: 1–6), for a median of 4 BMs treated during all sessions (range: 2–19). WHO, Ds-GPA and RPA were stable between each session of SRT, whereas KPS was significantly better in SRT1 than in the following SRT. The number of BMs was not significantly different between each SRT, but there was a tendency for more BM at SRT1 (p = 0.06). At SRT1, patients had largest BM and undergo more surgery than during the following SRT (p < 0.001). 6.5%, 37.5% and 56% of patients were classified as high, intermediate, and low BMV, respectively, at the last SRT session. There was almost perfect concordance between the BMV-grade calculated at the last SRT session and at SRT2 (r = 0.89; p < 0.001).

Conclusion
Repeated SRT doesn't lead to a marked alteration in the general condition, KPS was maintained at over 70% for more than 95% of patients during all SRTs. Long survival can be expected, especially in low-grade BMV patients. WBRT shouldn't be aborted, especially for patients developing more than twelve BMs annually.
A survey exploring caregiver burden and health-related quality of life in hereditary transthyretin amyloidosis
Authors: Acaster Sarah , Lo Siu Hing , Nestler-Parr Sandra 
Published: January 2023

Abstract
Background
Hereditary transthyretin amyloidosis (ATTRv) is an ultra-rare, life-shortening disease with a high unmet need. This study examined ATTRv caregiver health-related quality of life (HRQoL) and productivity.

Methods
A cross-sectional online survey, including EQ-5D-3L, Hospital anxiety and depression scale (HADS), and caregiver and patient characteristics questions, was developed to assess ATTRv caregiver burden. A companion general population survey collected EQ-5D-3L, HADS and chronic health conditions data. Caregiver-control group differences in HRQoL were assessed using t-tests and chi-square tests. Ordinary Least Squares regression was used to estimate the disutility of being a caregiver compared to controls stratified by patient ambulatory status.

Results
Thirty-six caregivers and matched controls completed the survey (n = 72). The disease severity of patients they cared for was varied: 33% required no assistance walking, 58% required assistance with walking and 9% required a wheelchair/were bedridden. On average, caregivers spent 6 h daily on practical care and 4 h daily on emotional support. Fifty-six percent indicated that they had changed their employment due to providing ATTRv care. Caregivers reported lower HRQoL, as indicated by lower EQ-5D 3L utility scores (M = 0.772, SD = 0.178 vs. M = 0.849, SD = 0.218) and higher HADS anxiety (9.3 vs. 6.1, p < 0.01) and depression (7.6 vs. 4.4, p < 0.01) scores, compared with matched controls. Caregivers were also more likely to report sleep problems (33% vs. 8%, p < 0.01) and stress (42% vs. 0%, p < 0.001) as chronic conditions than controls.

Conclusions
The study results indicate that caring for a person with ATTRv can have a considerable negative impact on caregivers’ HRQoL and productivity. The study findings provide important information for economic evaluations of ATTRv treatments.
Underestimating attacks: comparing two sources of publicly-available data about attacks on health care in 2017
Authors: Parada Vanessa , Fast Larissa , Briody Carolyn , Wille Christina , Coninx Rudi 
Published: January 2023

AbstractBackgroundAttacks on health care represent an area of growing international concern. Publicly available data are important in documenting attacks, and are often the only easily accessible data source. Data collection processes about attacks on health and their implications have received little attention, despite the fact that datasets and their collection processes may result in differing numbers. Comparing two separate datasets compiled using publicly-available data revealed minimal overlap. This article aims to explain the reasons for the lack of overlap, to better understand the gaps and their implications.MethodsWe compared the data collection processes for datasets comprised of publicly-reported attacks on health care from the World Health Organization (WHO) and Insecurity Insight’s Security in Numbers Database (SiND). We compared each individual event to compile a comparable dataset and identify unique and matched events in order to determine the overlap between them. We report descriptive statistics for this comparison.ResultsWe identified a common dataset of 287 events from 2017, of which only 33 appeared in both datasets, resulting in a mere 12.9% (n = 254) overlap. Events affecting personnel and facilities appeared most often in both, and 22 of 31 countries lacked any overlap between datasets.ConclusionsWe conclude that the minimal overlap suggests significant underreporting of attacks on health care, and furthermore, that dataset definitions and parameters affect data collection. Source variation appears to best explain the discrepancies and closer comparison of the collection processes reveal weaknesses of both automated and manual data collection that rely on hidden curation processes. To generate more accurate datasets compiled from public sources requires systematic work to translate definitions into effective online search mechanisms to better capture the full range of events, and to increase the diversity of languages and local sources to better capture events across geographies.
RN-Autoencoder: Reduced Noise Autoencoder for classifying imbalanced cancer genomic data
Authors: Arafa Ahmed , El-Fishawy Nawal , Badawy Mohammed , Radad Marwa 
Published: January 2023

Abstract
Background
In the current genomic era, gene expression datasets have become one of the main tools utilized in cancer classification. Both curse of dimensionality and class imbalance problems are inherent characteristics of these datasets. These characteristics have a negative impact on the performance of most classifiers when used to classify cancer using genomic datasets.

Results
This paper introduces Reduced Noise-Autoencoder (RN-Autoencoder) for pre-processing imbalanced genomic datasets for precise cancer classification. Firstly, RN-Autoencoder solves the curse of dimensionality problem by utilizing the autoencoder for feature reduction and hence generating new extracted data with lower dimensionality. In the next stage, RN-Autoencoder introduces the extracted data to the well-known Reduced Noise-Synthesis Minority Over Sampling Technique (RN- SMOTE) that efficiently solve the problem of class imbalance in the extracted data. RN-Autoencoder has been evaluated using different classifiers and various imbalanced datasets with different imbalance ratios. The results proved that the performance of the classifiers has been improved with RN-Autoencoder and outperformed the performance with original data and extracted data with percentages based on the classifier, dataset and evaluation metric. Also, the performance of RN-Autoencoder has been compared to the performance of the current state of the art and resulted in an increase up to 18.017, 19.183, 18.58 and 8.87% in terms of test accuracy using colon, leukemia, Diffuse Large B-Cell Lymphoma (DLBCL) and Wisconsin Diagnostic Breast Cancer (WDBC) datasets respectively.

Conclusion
RN-Autoencoder is a model for cancer classification using imbalanced gene expression datasets. It utilizes the autoencoder to reduce the high dimensionality of the gene expression datasets and then handles the class imbalance using RN-SMOTE. RN-Autoencoder has been evaluated using many different classifiers and many different imbalanced datasets. The performance of many classifiers has improved and some have succeeded in classifying cancer with 100% performance in terms of all used metrics. In addition, RN-Autoencoder outperformed many recent works using the same datasets.
Presenilins regulate synaptic plasticity in the perforant pathways of the hippocampus
Authors: Lee Sang Hun , Bolshakov Vadim Y. , Shen Jie 
Published: January 2023

AbstractMutations in the Presenilin genes (PSEN1 and PSEN2) are the major cause of familial Alzheimer’s disease (AD), highlighting the importance of Presenilin (PS) in AD pathogenesis. Previous studies of PS function in the hippocampus demonstrated that loss of PS results in the impairment of short- and long-term synaptic plasticity and neurotransmitter release at hippocampal Schaffer collateral (SC) and mossy fiber (MF) synapses. Cortical input to the hippocampus through the lateral perforant pathway (LPP) and the medial perforant pathway (MPP) is critical for normal cognitive functions and is particularly vulnerable during aging and early stages of AD. Whether PS regulates synaptic function in the perforant pathways, however, remained unknown. In the current study, we investigate PS function in the LPP and MPP by performing whole-cell and field-potential electrophysiological recordings using acute hippocampal slices from postnatal forebrain-restricted excitatory neuron-specific PS conditional double knockout (cDKO) mice. We found that paired-pulse ratio (PPR) is reduced in the LPP and MPP of PS cDKO mice. Moreover, synaptic frequency facilitation or depression in the LPP or MPP, respectively, is impaired in PS cDKO mice. Notably, depletion of intracellular Ca2+ stores by inhibition of sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) minics and occludes the effects of PS inactivation, as evidenced by decreases of the evoked excitatory postsynaptic currents (EPSCs) amplitude in the LPP and MPP of control neurons but no effect on the EPSC amplitude in PS cDKO neurons, suggesting that impaired intracellular calcium homeostasis in the absence of PS may contribute to the observed deficits in synaptic transmission. While spontaneous synaptic events, such as both the frequency and the amplitude of spontaneous or miniature EPSCs, are similar between PS cDKO and control neurons, long-term potentiation (LTP) is impaired in the LPP and MPP of PS cDKO mice, accompanied with reduction of evoked NMDA receptor-mediated responses. These findings show the importance of PS in the regulation of synaptic plasticity and intracellular calcium homeostasis in the hippocampal perforant pathways.
Patient-derived cell-based pharmacogenomic assessment to unveil underlying resistance mechanisms and novel therapeutics for advanced lung cancer
Authors: Yu Namhee , Hwang Mihwa , Lee Youngjoo , Song Bo Ram , Kang Eun Hye , Sim Hanna , Ahn Beung-Chul , Hwang Kum Hui , Kim Jihyun , Hong Sehwa , Kim Sunshin , Park Charny , Han Ji-Youn 
Published: January 2023

Abstract
Background
A pharmacogenomic platform using patient-derived cells (PDCs) was established to identify the underlying resistance mechanisms and tailored treatment for patients with advanced or refractory lung cancer.

Methods
Drug sensitivity screening and multi-omics datasets were acquired from lung cancer PDCs (n = 102). Integrative analysis was performed to explore drug candidates according to genetic variants, gene expression, and clinical profiles.

Results
PDCs had genomic characteristics resembled with those of solid lung cancer tissues. PDC molecular subtyping classified patients into four groups: (1) inflammatory, (2) epithelial-to-mesenchymal transition (EMT)-like, (3) stemness, and (4) epithelial growth factor receptor (EGFR)-dominant. EGFR mutations of the EMT-like subtype were associated with a reduced response to EGFR-tyrosine kinase inhibitor therapy. Moreover, although RB1/TP53 mutations were significantly enriched in small-cell lung cancer (SCLC) PDCs, they were also present in non-SCLC PDCs. In contrast to its effect in the cell lines, alpelisib (a PI3K-AKT inhibitor) significantly inhibited both RB1/TP53 expression and SCLC cell growth in our PDC model. Furthermore, cell cycle inhibitors could effectively target SCLC cells. Finally, the upregulation of transforming growth factor-β expression and the YAP/TAZ pathway was observed in osimertinib-resistant PDCs, predisposing them to the EMT-like subtype. Our platform selected XAV939 (a WNT-TNKS-β-catenin inhibitor) for the treatment of osimertinib-resistant PDCs. Using an in vitro model, we further demonstrated that acquisition of osimertinib resistance enhances invasive characteristics and EMT, upregulates the YAP/TAZ-AXL axis, and increases the sensitivity of cancer cells to XAV939.

Conclusions
Our PDC models recapitulated the molecular characteristics of lung cancer, and pharmacogenomics analysis provided plausible therapeutic candidates.
Integrated multi-dimensional analysis highlights DHCR7 mutations involving in cholesterol biosynthesis and contributing therapy of gastric cancer
Authors: Chen Yuqi , Yan Wenying , Yang Kexi , Qian Yiting , Chen Yanjun , Wang Ruoqin , Zhu Jinghan , He Yuxin , Wu Hongya , Zhang Guangbo , Shi Tongguo , Chen Weichang 
Published: January 2023

Abstract
Background
Genetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis.

Methods
A GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets.

Results
At the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis.

Conclusion
In this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.