bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stage IIB-IVA cervix carcinoma in elderly patients treated with radiation therapy: a longitudinal cohort study by propensity score matching analysis
Authors: Shou Huafeng , Wan Qiuyan , Xu Hong’en , Shi Lei , Song Tao 
Published: May 2023

Abstract
Objective
We aimed to evaluate the treatment modality and prognostic impact of the age at diagnosis on stage IIB-IVA cervix carcinoma (CC) patients who received radiotherapy (RT).The evaluation was performed using the Surveillance, Epidemiology, and End Results (SEER) database.

Patients and methods
From the SEER database, we included the patients with a histopathological diagnosis of CC between 2004 and 2016. Subsequently, we compared the treatment outcomes between patients aged ≥ 65 years (OG) and < 65 years (YG) by propensity score matching (PSM) analysis and Cox proportional hazard regression models.

Results
The data of 5,705 CC patients were obtained from the SEER database. We observed that the OG patients were significantly less likely to receive chemotherapy, brachytherapy, or combination treatment compared to the YG (P < 0.001). Further, the advanced age at diagnosis was an independent prognostic factor associated with decreasing overall survival (OS) before and after PSM. Even in the subgroup analysis of patients who received trimodal therapy, an advanced age had a significant negative impact on OS compared to their younger counterparts.

Conclusion
Advanced age is associated with less aggressive treatment regimens and is independently associated with impaired OS for stage IIB-IVA CC patients who received RT. Hence, future studies should incorporate geriatric assessment into clinical decision-making to select appropriate and effective treatment strategies for elderly CC patients.
Reconstructing feedback in graduate medical education: development of the REFLECT scale to measure feedback delivery in medical residency training
Authors: Ilaghi Mehran , Shafian Sara , Soltanizadeh Adel , Karamoozian Ali , Okhovati Maryam , Aflatoonian Sarah 
Published: May 2023

Abstract
Background
Feedback plays a pivotal role in graduate medical education, where medical residents are expected to acquire a wide range of practical and professional competencies. Assessing the feedback delivery status is a preliminary step for educators to enhance the quality of feedback provided. This study aims to develop an instrument to assess the various aspects of feedback delivery in medical residency training.

Methods
The fifteen-item REFLECT (Residency Education Feedback Level Evaluation in Clinical Training) questionnaire was developed. The content validity was evaluated according to a panel member consisting of fourteen clinical professors and medical education instructors. After evaluating the test-retest reliability, the questionnaire was distributed to a sample of 154 medical residents and was further assessed in terms of internal consistency and factor analysis.

Results
Content validity analysis resulted in an appropriate content validity ratio and content validity index for the final 15 items. The test-retest reliability resulted in an ICC of 0.949 (95% C.I. 0.870–0.980), indicating excellent reliability. The Cronbach’s alpha for the 15-item questionnaire was α = 0.85, demonstrating good internal consistency. The factor analysis resulted in a four-factor structure: “attitude towards feedback”, “quality of feedback”, “perceived importance of feedback”, and “reaction to feedback”.

Conclusions
REFLECT proved to a reliable tool that could be utilized as a quick assessment method of feedback delivery, making it a suitable aid for educational managers and faculties to design necessary interventions aiming to enhance the quantity and quality of feedback provided.
Rapid start antiretroviral therapies for improved engagement in HIV care: implementation science evaluation protocol
Authors: Bourdeau Beth , Shade Starley B. , Koester Kimberly A. , Rebchook Greg M. , Steward Wayne T. , Agins Bruce M. , Myers Janet J. , Phan Son H. , Matosky Marlene 
Published: May 2023

Abstract
Background
In 2020, the Health Resources and Services Administration’s HIV/AIDS Bureau funded an initiative to promote implementation of rapid antiretroviral therapy initiation in 14 HIV treatment settings across the U.S. The goal of this initiative is to accelerate uptake of this evidence-based strategy and provide an implementation blueprint for other HIV care settings to reduce the time from HIV diagnosis to entry into care, for re-engagement in care for those out of care, initiation of treatment, and viral suppression. As part of the effort, an evaluation and technical assistance provider (ETAP) was funded to study implementation of the model in the 14 implementation sites.

Method
The ETAP has used implementation science methods framed by the Dynamic Capabilities Model integrated with the Conceptual Model of Implementation Research to develop a Hybrid Type II, multi-site mixed-methods evaluation, described in this paper. The results of the evaluation will describe strategies associated with uptake, implementation outcomes, and HIV-related health outcomes for patients.

Discussion
This approach will allow us to understand in detail the processes that sites to implement and integrate rapid initiation of antiretroviral therapy as standard of care as a means of achieving equity in HIV care.
Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: results from the WILLOW trial
Authors: Cipolla David , Zhang Jimin , Korkmaz Brice , Chalmers James D. , Basso Jessica , Lasala Daniel , Fernandez Carlos , Teper Ariel , Mange Kevin C. , Perkins Walter R. , Sullivan Eugene J. 
Published: May 2023

Abstract
Background
Brensocatib is an oral, selective, reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), responsible for activating neutrophil serine proteases (NSPs) including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG). In chronic inflammatory lung diseases such as non-cystic fibrosis bronchiectasis (NCFBE), neutrophils accumulate in the airways resulting in excess active NSPs that cause damaging inflammation and lung destruction.

Methods
The 24-week WILLOW trial (NCT03218917) was a randomized, double-blind, placebo-controlled, parallel-group trial in patients with NCFBE conducted at 116 sites across 14 countries. In this trial, treatment with brensocatib was associated with improvements in clinical outcomes including time to first exacerbation, reduction in exacerbation frequency and a reduction in NE activity in sputum. An exploratory analysis of NE activity in white blood cell (WBC) extracts and NE, PR3 and CatG activity in sputum was conducted to further characterize brensocatib’s effect and identify potential correlated effects.

Results
NE, PR3 and CatG activities were reduced in sputum and NE activity was reduced in WBC extracts in a dose-dependent manner after four weeks of brensocatib treatment, with a return to baseline four weeks after the end of treatment. Brensocatib produced the greatest reduction in the sputum activity of CatG, followed by NE and then PR3. Positive correlations among the sputum NSPs were observed both at baseline and in response to treatment, with the strongest correlation among the sputum NSPs for NE and CatG.

Conclusions
These results suggest a broad anti-inflammatory effect of brensocatib underlying its clinical efficacy observed in NCFBE patients.
Trial registration: The study was approved by the corresponding ethical review boards of all participating centers. The trial was approved by the Food and Drug Administration and registered at clinicaltrials.gov (NCT03218917) on July 17, 2017 and approved by the European Medicines Agency and registered at the European Union Clinical trials Register (EudraCT No. 2017-002533-32). An independent, external data and safety monitoring committee (comprising physicians with pulmonary expertise, a statistician experienced in the evaluation of clinical safety, and experts in periodontal disease and dermatology) reviewed all adverse events.
Blockage of retinoic acid signaling via RARγ suppressed the proliferation of pancreatic cancer cells by arresting the cell cycle progression of the G1-S phase
Authors: Yamakawa Kohei , Koyanagi-Aoi Michiyo , Machinaga Akihito , Kakiuchi Nobuyuki , Hirano Tomonori , Kodama Yuzo , Aoi Takashi 
Published: May 2023

Abstract
Background
Our study and several studies have reported that in some cancers, including pancreatic ductal adenocarcinoma (PDAC), the expression of squamous lineage markers, such as esophagus-tissue-specific genes, correlated with a poor prognosis. However, the mechanism by which the acquisition of squamous lineage phenotypes leads to a poor prognosis remains unclear. We previously reported that retinoic acid signaling via retinoic acid receptor γ (RARγ signaling) determines the differentiation lineage into the esophageal squamous epithelium. These findings hypothesized that the activation of RARγ signaling contributed to acquiring squamous lineage phenotypes and malignant behavior in PDAC.

Methods
This study utilized public databases and immunostaining of surgical specimens to examine RARγ expression in PDAC. We evaluated the function of RARγ signaling by inhibitors and siRNA knockdown using a PDAC cell line and patient-derived PDAC organoids. The mechanism of the tumor-suppressive effects by blocking RARγ signaling was examined by a cell cycle analysis, apoptosis assays, RNA sequencing and Western blotting.

Results
RARγ expression in pancreatic intraepithelial neoplasia (PanIN) and PDAC was higher than that in the normal pancreatic duct. Its expression correlated with a poor patient prognosis in PDAC. In PDAC cell lines, blockade of RARγ signaling suppressed cell proliferation by inducing cell cycle arrest in the G1 phase without causing apoptosis. We demonstrated that blocking RARγ signaling upregulated p21 and p27 and downregulated many cell cycle genes, including cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6. Furthermore, using patient-derived PDAC organoids, we confirmed the tumor-suppressive effect of RARγ inhibition and indicated the synergistic effects of RARγ inhibition with gemcitabine.

Conclusions
This study clarified the function of RARγ signaling in PDAC progression and demonstrated the tumor-suppressive effect of selective blockade of RARγ signaling against PDAC. These results suggest that RARγ signaling might be a new therapeutic target for PDAC.
Prioritizing rehabilitation in low- and middle-income country national health systems: a qualitative thematic synthesis and development of a policy framework
Authors: Neill Rachel , Shawar Yusra Ribhi , Ashraf Lamisa , Das Priyanka , Champagne Sarah N. , Kautsar Hunied , Zia Nukhba , Michlig Georgia J. , Bachani Abdulgafoor M. 
Published: May 2023

Abstract
Background
There is a large and growing unmet need for rehabilitation – a diverse category of services that aim to improve functioning across the life course – particularly in low- and middle-income countries. Yet despite urgent calls to increase political commitment, many low- and middle-income country governments have dedicated little attention to expanding rehabilitation services. Existing policy scholarship explains how and why health issues reach the policy agenda and offers applicable evidence to advance access to physical, medical, psychosocial, and other types of rehabilitation services. Drawing from this scholarship and empirical data on rehabilitation, this paper proposes a policy framework to understand national-level prioritization of rehabilitation in low- and middle-income countries.

Methods
We conducted key informant interviews with rehabilitation stakeholders in 47 countries, complemented by a purposeful review of peer-reviewed and gray literature to achieve thematic saturation. We analyzed the data abductively using a thematic synthesis methodology. Rehabilitation-specific findings were triangulated with policy theory and empirical case studies on the prioritization of other health issues to develop the framework.

Results
The novel policy framework includes three components which shape the prioritization of rehabilitation on low- and middle-income countries’ national government’s health agendas. First, rehabilitation lacks a consistent problem definition, undermining the development of consensus-driven solutions which could advance the issue on policy agendas. Second, governance arrangements are fragmented within and across government ministries, between the government and its citizens, and across national and transnational actors engaged in rehabilitation service provision. Third, national legacies – particularly from civil conflict – and weaknesses in the existing health system influences both rehabilitation needs and implementation feasibility.

Conclusions
This framework can support stakeholders in identifying the key components impeding prioritization for rehabilitation across different national contexts. This is a crucial step for ultimately better advancing the issue on national policy agendas and improving equity in access to rehabilitation services.
Horizontal healthcare utilization inequity in patients with rare diseases in Korea
Authors: Kang Daewon , Choi Sang-Eun 
Published: May 2023

Abstract
Background
Rare diseases (RDs) are difficult to diagnose and expensive to treat. Thus, the South Korean government has implemented several policies to help RD patients, including the Medical Expense Support Project, supporting low- to middle-income RD patients. However, no study in Korea has yet addressed health inequity in RD patients. This study assessed inequity trends in the medical utilization and expenditures of RD patients.

Methods
This study measured the horizontal inequity index (HI) of RD patients and an age- and sex-matched control group using the National Health Insurance Service data from 2006 to 2018. Sex, age, number of chronic diseases, and disability variables were used to model expected medical needs and adjust the concentration index (CI) for medical utilization and expenditures.

Results
The HI index of healthcare utilization in RD patients and the control group ranged from -0.0129 to 0.0145, increasing until 2012 and fluctuating since then. This increasing trend was more apparent for inpatient utilization in the RD patient group than in the outpatient group. The same index in the control group ranged from -0.0112 to -0.0040 without a significant trend. The healthcare expenditure HI in RD patients rose from -0.0640 to -0.0038, showing pro-poor values but moving toward a pro-rich state. In the control group, the HI for healthcare expenditures remained between 0.0029 and 0.0085.

Conclusions
The HI of inpatient utilization and inpatient expenditures increased in a pro-rich state. The study results showed that implementing a policy that supports inpatient service utilization could help achieve health equity for RD patients.
Horizontal inequity trends of health care utilization in rural China after the medicine and healthcare system reform: based on longitudinal data from 2010 to 2018
Authors: Xu Jinpeng , Tian Guomei , Sun Jiale , Liu Jian , Chen Fangting , Shi Qi , Zhang Ting , Zhang Hongyu , He Jingran , Deng Fangmin , Zhang Bokai , Wang Haixin , Wu Qunhong , Kang Zheng 
Published: May 2023

Abstract
Background
To assess the effectiveness of China's medicine and health care reform in promoting equity in health care utilization among rural residents, it is necessary to analyze temporal trends in equity in health care utilization among rural residents in China. This study is the first to assess horizontal inequity trends in health care utilization among rural Chinese residents from 2010 to 2018 and provides evidence for improving government health policies.

Methods
Longitudinal data obtained from China Family Panel Studies from 2010 to 2018 were used to determine trends in outpatient and inpatient utilization. Concentration index, concentration curve, and horizontal inequity index were calculated to measure inequalities. Decomposition analysis was applied to measure the contribution of need and non-need factors to the unfairness.

Results
From 2010 to 2018, outpatient utilization among rural residents increased by 35.10%, while inpatient utilization increased by 80.68%. Concentration indices for health care utilization were negative in all years. In 2012, there was an increase in the concentration index for outpatient utilization (CI = -0.0219). The concentration index for inpatient utilization decreased from -0.0478 in 2010 to -0.0888 in 2018. Except for outpatient utilization in 2012 (HI = 0.0214), horizontal inequity indices for outpatient utilization were negative in all years. The horizontal inequity index for inpatient utilization was highest in 2010 (HI = -0.0068) and lowest in 2018 (HI = -0.0303). The contribution of need factors to the inequity exceeded 50% in all years.

Conclusions
Between 2010 and 2018, low-income groups in rural China used more health services. This seemingly pro-poor income-related inequality was due in large part to the greater health care need among low-income groups. Government policies aimed at increasing access to health services, particularly primary health care had helped to make health care utilization in rural China more equitable. It is necessary to design better health policies for disadvantaged groups to reduce future inequities in the use of health services by rural populations.
Dissemination of Neisseria gonorrhoeae with decreased susceptibility to extended-spectrum cephalosporins in Southern China, 2021: a genome-wide surveillance from 20 cities
Authors: Liao Yiwen , Xie Qinghui , Li Xiaoxiao , Yin Xiaona , Wu Xingzhong , Liu Mingjing , Pan Yuying , Zeng Lihong , Yang Jianjiang , Feng Zhanqin , Qin Xiaolin , Zheng Heping 
Published: May 2023

Abstract
Background
Antimicrobial resistance (AMR) of untreatable gonococcal infection is an emerging threat, especially in Guangdong, a prosperous province in Southern China.

Methods
N.gonorrhoeae was isolated from 20 cities in Guangdong and determined antimicrobial susceptibility. Through whole-genome sequencing (WGS), multilocus sequence typing (MLST), N.gonorrhoeae multiantigen sequence typing (NG-MAST), and N.gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were obtained based on the PubMLST database (https://pubmlst.org/). Phylogenetic analysis was used for dissemination and tracking analysis.

Results
Antimicrobial susceptibility was performed on 347 isolates, and 50 isolates were identified as decreased susceptibility (DS) to cephalosporins. Of which 16.0% (8/50) were ceftriaxone DS, 38.0% (19/50) were cefixime DS, and 46.0% (23/50) were both ceftriaxone and cefixime DS. In all, the dual-resistant rate of the cephalosporin-DS isolates was 96.0% for penicillin and 98.0% for tetracycline-resistant, and 10.0% (5/50) were resistant to azithromycin. All cephalosporin-DS isolates were resistant to ciprofloxacin but sensitive to spectinomycin. The predominant MLSTs were ST7363 (16%, 8/50), ST1903 (14%, 7/50), ST1901 (12%, 6/50), and ST7365 (10%, 5/50). Besides some isolates that failed genotyping (NA), NG-STAR ST1143 (n = 6) and NG-MAST ST17748 (n = 4) were the most prevalent. Twelve isolates with mosaic penA-60.001 allele retained the most elevated cephalosporin MIC (Minimum Inhibitory Concentration). Phylogenetic analysis revealed that epidemic penA-60.001 clones, either domestic or foreign, had spread to nine cities in Guangdong, and 9/12 clones were from the Pearl River Delta region.

Conclusions
N. gonorrhoeae with cephalosporins-DS was extensively disseminated in Guangdong, Southern China, requiring strict surveillance.
Biased data, biased AI: deep networks predict the acquisition site of TCGA images
Authors: Dehkharghanian Taher , Bidgoli Azam Asilian , Riasatian Abtin , Mazaheri Pooria , Campbell Clinton J. V. , Pantanowitz Liron , Tizhoosh H. R. , Rahnamayan Shahryar 
Published: May 2023

AbstractBackgroundDeep learning models applied to healthcare applications including digital pathology have been increasing their scope and importance in recent years. Many of these models have been trained on The Cancer Genome Atlas (TCGA) atlas of digital images, or use it as a validation source. One crucial factor that seems to have been widely ignored is the internal bias that originates from the institutions that contributed WSIs to the TCGA dataset, and its effects on models trained on this dataset.Methods8,579 paraffin-embedded, hematoxylin and eosin stained, digital slides were selected from the TCGA dataset. More than 140 medical institutions (acquisition sites) contributed to this dataset. Two deep neural networks (DenseNet121 and KimiaNet were used to extract deep features at 20× magnification. DenseNet was pre-trained on non-medical objects. KimiaNet has the same structure but trained for cancer type classification on TCGA images. The extracted deep features were later used to detect each slide’s acquisition site, and also for slide representation in image search.ResultsDenseNet’s deep features could distinguish acquisition sites with 70% accuracy whereas KimiaNet’s deep features could reveal acquisition sites with more than 86% accuracy. These findings suggest that there are acquisition site specific patterns that could be picked up by deep neural networks. It has also been shown that these medically irrelevant patterns can interfere with other applications of deep learning in digital pathology, namely image search.SummaryThis study shows that there are acquisition site specific patterns that can be used to identify tissue acquisition sites without any explicit training. Furthermore, it was observed that a model trained for cancer subtype classification has exploited such medically irrelevant patterns to classify cancer types. Digital scanner configuration and noise, tissue stain variation and artifacts, and source site patient demographics are among factors that likely account for the observed bias. Therefore, researchers should be cautious of such bias when using histopathology datasets for developing and training deep networks.
The use of a new high-speed shielded curved drill is associated with improved intraoperative and clinical outcomes after cervical corpectomy and fusion procedures: a retrospective case series
Authors: Peloza John , Malone Hani , Jacobian Erel , Kolsky Daniel E. , Harel Ran , Guyer Richard D. , Millgram Michael A. , Ashkenazi Ely 
Published: May 2023

Abstract
Background
Anterior cervical corpectomy and fusion (ACCF) is an effective technique to address multi-level degenerative cervical myelopathy. However, as the number of surgical levels increases, the outcomes worsen with respect to complication rates, range of motion and length of surgery. This study aimed to determine the clinical outcome of ACCF procedures performed using a new distally curved and shielded drilling device.

Methods
A retrospective study was conducted on 43 ACCF procedures in which the device was used for osteophyte removal. Patient files were reviewed to assess the early clinical results and complications following ACCF. Clinical outcomes were evaluated using patient neck and arm pain scores and SF-36 questionnaires. Hospitalization characteristics were compared with historical controls.

Results
All procedures were uneventful and without major complications or neurological deterioration. Single-level ACCF procedures required an average of 71 min and followed by an average hospitalization of 3.3 days. Osteophyte removal, verified by intraoperative imaging, was satisfactory. Average neck pain score was improved by 0.9 points (p = 0.24). Average arm pain score was improved by 1.8 points (p = 0.06). SF-36 scores were improved in all domains.

Conclusions
The new curved device enabled safe and efficient removal of osteophytes sparing adjacent vertebral removal in ACCF procedures, thus improving the clinical outcome.