bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolving frontline immunochemotherapy for mantle cell lymphoma and the impact on survival outcomes
Authors: Castellino Alessia , Wang Yucai , Larson Melissa C. , Maurer Matthew J. , Link Brian K. , Farooq Umar , Feldman Andrew L. , Syrbu Sergei I. , Habermann Thomas M. , Paludo Jonas , Inwards David J. , Witzig Thomas E. , Ansell Stephen M. , Allmer Cristine , Slager Susan L. , Cohen Jonathon B. , Martin Peter , Cerhan James R. , Nowakowski Grzegorz S. 
Published: October 2021

AbstractBecause there have been a dvances in frontline treatment for mantle cell lymphoma (MCL) over the last 2 decades, we sought to characterize the changes in frontline treatment patterns and their association with outcomes. Patients with newly diagnosed MCL from September 2002 through June 2015 were enrolled in a prospective cohort study, and clinical characteristics, treatment, and clinical outcomes were compared between patients diagnosed from 2002 to 2009 (Era 1) compared with 2010 to 2015 (Era 2). Patient age, sex, and simplified MCL International Prognostic Index (sMIPI) score were similar between the 2 groups. In patients age 65 years or younger, there was less use of rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-Hyper-CVAD) (16.1% vs 8.8%) but more use of rituximab plus maximum-strength cyclophosphamide, doxorubicin, vincristine, and prednisone (R-maxi-CHOP) alternating with rituximab plus high-dose cytarabine (R-HiDAC), also known as the Nordic regimen, and R-CHOP alternating with rituximab plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) (1.1% vs 26.4%) and less use of R-CHOP or R-CHOP-like regimens (64.5% vs 35.2%) but more use of R-bendamustine (0% vs 12.1%) in Era 2 (P &lt; .001). These changes were associated with improved event-free survival (EFS; 5-year EFS, 34.3% vs 50.0%; P = .010) and overall survival (OS; 5-year OS, 68.8% vs 81.6%; P = .017) in Era 2. In patients older than age 65 years, there was less use of R-CHOP or R-CHOP-like therapy (39.0% vs 14.3%) and nonstandard systemic therapy (36.6% vs 13.0%) but more use of R-bendamustine (0% vs 49.4%). These changes were associated with a trend for improved EFS (5-year EFS, 25.4% vs 37.5%; P = .051) in Era 2. The shift from R-CHOP or R-CHOP-like regimens to R-bendamustine was associated with improved EFS (5-year EFS, 25.0% vs 44.6%; P = .008) in Era 2. Results from this prospective cohort study provide critical real-world evidence for improved outcomes with evolving frontline patterns of care in patients with MCL.
Differential expression analysis using a model-based gene clustering algorithm for RNA-seq data
Authors: Osabe Takayuki , Shimizu Kentaro , Kadota Koji 
Published: October 2021

AbstractBackgroundRNA-seq is a tool for measuring gene expression and is commonly used to identify differentially expressed genes (DEGs). Gene clustering is used to classify DEGs with similar expression patterns for the subsequent analyses of data from experiments such as time-courses or multi-group comparisons. However, gene clustering has rarely been used for analyzing simple two-group data or differential expression (DE). In this study, we report that a model-based clustering algorithm implemented in an R package, MBCluster.Seq, can also be used for DE analysis.ResultsThe input data originally used by MBCluster.Seq is DEGs, and the proposed method (called MBCdeg) uses all genes for the analysis. The method uses posterior probabilities of genes assigned to a cluster displaying non-DEG pattern for overall gene ranking. We compared the performance of MBCdeg with conventional R packages such as edgeR, DESeq2, and TCC that are specialized for DE analysis using simulated and real data. Our results showed that MBCdeg outperformed other methods when the proportion of DEG (PDEG) was less than 50%. However, the DEG identification using MBCdeg was less consistent than with conventional methods. We compared the effects of different normalization algorithms using MBCdeg, and performed an analysis using MBCdeg in combination with a robust normalization algorithm (called DEGES) that was not implemented in MBCluster.Seq. The new analysis method showed greater stability than using the original MBCdeg with the default normalization algorithm.ConclusionsMBCdeg with DEGES normalization can be used in the identification of DEGs when thePDEGis relatively low. As the method is based on gene clustering, the DE result includes information on which expression pattern the gene belongs to. The new method may be useful for the analysis of time-course and multi-group data, where the classification of expression patterns is often required.
Adherence to recommendations for secondary prevention medications after myocardial infarction in Estonia: comparison of real-world data from 2004 to 2005 and 2017 to 2018
Authors: Lõiveke Piret , Marandi Toomas , Ainla Tiia , Fischer Krista , Eha Jaan 
Published: October 2021

Abstract
Background
Relatively high rates of adherence to myocardial infarction (MI) secondary prevention medications have been reported, but register-based, objective real-world data is scarce. We aimed to analyse adherence to guideline-recommended medications for secondary prevention of MI in 2017 to 2018 (period II) and compare the results with data from 2004 to 2005 (period I) in Estonia.

Methods
Study populations were formed based on data from the Estonian Health Insurance Fund’s database and on Estonian Myocardial Infarction Register. By linking to the Estonian Medical Prescription Centre database adherence to guideline-recommended medications for MI secondary prevention was assessed for 1 year follow-up period from the first hospitalization due to MI. Data was analysed using the defined daily dosages methodology.

Results
Total of 6694 and 6060 cases of MI were reported in periods I and II, respectively. At least one prescription during the follow up period was found for beta-blockers in 81.0% and 83.5% (p = 0.001), for angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) in 76.9% and 66.0% (p < 0.001), and for statins in 44.0% and 67.0% (p < 0.001) of patients in period I and II, respectively. P2Y12 inhibitors were used by 76.4% of patients in period II. The logistic regression analysis adjusted to gender and age revealed that some drugs and drug combinations were not allocated similarly in different age and gender groups.

Conclusions
In Estonia, adherence to MI secondary prevention guideline-recommended medications has improved. But as adherence is still not ideal more attention should be drawn to MI secondary prevention through systematic guideline implementation.
Association between regular arrangement of collecting venules and Helicobacter pylori status in routine endoscopy
Authors: Yuan Cong , Lin Xue-Mei , Ou Yan , Cai Lin , Cheng Qian , Zhou Ping , Liao Juan 
Published: October 2021

AbstractBackgroundThe sensitivity of regular arrangement of collecting venules (RAC)-positive pattern for predictingHelicobacter pylori(H. pylori)-negative status greatly altered from 93.8 to 48.0% in recent two decades of various studies, while the reason behind it remained obscure. The aim of this study was to investigate the value of RAC as an endoscopic feature for judgingH. pyloristatus in routine endoscopy and reviewed the underlying mechanism.MethodsA prospective study with high-definition non-magnifying endoscopy was performed. RAC-positive and RAC-negative patients were classified according to the collecting venules morphology of the lesser curvature in gastric corpus. Gastric biopsy specimens were obtained from the lesser and greater curvature of corpus with normal RAC-positive or abnormal RAC-negative mucosal patterns.Helicobacter pyloristatus was established by hematoxylin and eosin staining and immunohistochemistry.Results41 RAC-positive and 124 RAC-negative patients were enrolled from June 2020 to September 2020. The prevalence ofH. pyloriinfection in patients with RAC-positive pattern and RAC-negative pattern was 7.3% (3/41) and 71.0% (88/124), respectively. Among all 124 RAC-negative patients, 36 (29.0%) patients wereH. pylori-negative status. Ten patients (32.3%) demonstrated RAC-positive pattern in 31H. pylori-eradicated cases. The sensitivity, specificity, positive predictive value, and negative predictive value of RAC-positive pattern for predictingH. pylori-negative status were 51.4% (95% CI, 0.395–0.630), 96.7% (95% CI, 0.900–0.991), 92.7% (95% CI, 0.790–0.981), and 71.0% (95% CI, 0.620–0.786), respectively.ConclusionsRAC presence can accurately rule outH. pyloriinfection of gastric corpus, andH. pylori-positive status cannot be predicted only by RAC absence in routine endoscopy.Trial registrationThe present study is a non-interventional trial.
Evaluation of the response to electric pulp testing in multiple sclerosis patients without a history of trigeminal neuralgia: a case-control study
Authors: Owlia Fatemeh , Mahmoudzade Nazanin , Modaresi Jalil , Zarchi Marzieh Abutorabi 
Published: October 2021

Abstract
Background
The importance of evaluating the pulpal threshold to electrical stimulation, as a side effect of probable neuropathy in Multiple Sclerosis (MS) patients is a novel issue. This study aimed to investigate electrical pulp test thresholds in MS patients without a history of trigeminal neuralgia compared to healthy individuals.

Methods
Sixty-nine maxillary central incisors, belonging to 34 relapsing-remitting MS patients, and 35 healthy individuals were included in this survey. The MS patients matched for intended variables, were 22–50 years old, had a more than 1-year history of MS, no history of trigeminal neuralgia and/or other neuropathy. The electric pulp sensibility test was performed on all samples. Electric pulp testing (EPT) results were recorded based on the pulp tester’s grade that evoked a response. Data were analyzed with paired T-test, Mann-Whitney test, and Spearman correlation (P < 0.05).

Results
According to the results of this study, the mean values of response to EPT were 1.2 ± 0.5 and 1.8 ± 0.5 in MS patients and healthy individuals, respectively. The pulpal response to EPT between the two groups was significantly different (P < 0.0001).

Conclusions
MS patients showed a significantly reduced response to the electric pulp test in their maxillary central incisors in comparison to matched healthy persons.
Clinical verification of body mass index and tumor immune response in patients with breast cancer receiving preoperative chemotherapy
Authors: Takada Koji , Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Ishihara Sae , Morisaki Tamami , Shibutani Masatsune , Tanaka Hiroaki , Hirakawa Kosei , Ohira Masaichi 
Published: October 2021

Abstract
Purpose
The body mass index (BMI) is commonly used as a simple indicator of obesity; patients with early-stage breast cancer who are obese (OB) per BMI measurements have been shown to have high postoperative recurrence and low survival rates. On the other hand, it has been shown that lymphocytes present in the vicinity of malignant growths that are involved in the tumors’ immune responses influence the efficacy chemotherapy. Therefore, we hypothesized that OB patients with breast cancer have a lower density of tumor-infiltrating lymphocytes (TILs), which may influence the therapeutic effect of preoperative chemotherapy (POC). In this study, we measured pretreatment BMI and TILs in patients with breast cancer who underwent POC, examined the correlations between these two factors, and retrospectively analyzed their therapeutic outcomes and prognoses.

Methods
The participants in this study were 421 patients with breast cancer who underwent surgical treatment after POC between February 2007 and January 2019. The patient’s height and weight were measured before POC to calculate the BMI (weight [kg] divided by the square of the height [m2]). According to the World Health Organization categorization, patients who weighed under 18.5 kg/m2 were classified as underweight (UW), those ≥18.5 kg/m2 and > 25 kg/m2 were considered normal weight (NW), those ≥25 kg/m2 and < 30 kg/m2 were overweight (OW), and those ≥30 kg/m2 were OB. The TILs were those lymphocytes that infiltrated the tumor stroma according to the definition of the International TILs Working Group 2014.

Results
The median BMI was 21.9 kg/m2 (range, 14.3–38.5 kg/m2); most patients (244; 64.5%) were NW. Among all 378 patients with breast cancer, the TIL density was significantly lower in OB than in NW and OW patients (vs. NW: p = 0.001; vs. OW: p = 0.003). Furthermore, when examining patients with each breast cancer type individually, the OS of those with TNBC who had low BMIs was significantly poorer than that of their high-BMI counterparts (log rank p = 0.031).

Conclusions
Our data did not support the hypothesis that obesity affects the tumor immune microenvironment; however, we showed that being UW does affect the tumor immune microenvironment.
Stigmatization and psychological impact of COVID-19 pandemic on frontline healthcare Workers in Nigeria: a qualitative study
Authors: Kwaghe Ayi Vandi , Kwaghe Vivian Gga , Habib Zaiyad Garba , Kwaghe Gga Vandi , Ilesanmi Olayinka Stephen , Ekele Bissalah Ahmed , Umeokonkwo Chukwuma David , Balogun Muhammad Shakir 
Published: October 2021

AbstractIntroductionThe COVID-19 pandemic has had a great toll on global health. Frontline healthcare workers (FHCW) directly involved in the treatment of COVID-19 patients have faced some physical and psychological challenges. This study explored the stigma and traumatic experiences of the FHCW during the COVID-19 pandemic in Nigeria.MethodsWe recruited twenty FHCW directly involved in the treatment of COVID-19 patients through purposive and snowball sampling techniques. Face-to-face in-depth interviews were conducted for all participants, and qualitative analysis of data was done using Colaizzi’s phenomenological method.ResultsFive themes identified were: Early stage of the pandemic (fear, anxiety, public fright, other countries repatriating their citizens, the socio-economic impact of the pandemic and a call to duty for the FHCW); working with COVID-19 patients (excitement on patients recovery and duty stress); psychological, mental and emotional trauma; stigmatization (stigmatized by colleagues, family, friends or their residential communities, reasons for stigmatization which were fear of infection, limited knowledge of the virus and working at the isolation centre and the effect of stigma); and recommendations (education and awareness creation, government showing more care towards the FHCW and provision of health insurance for FHCW to take care of those that get infected in the line of duty).ConclusionStigmatization has proven to be a major challenge for FHCW in conducting their duties. The psychological impact experienced by FHCW may affect the quality of the services rendered by these workers. The study reveals the need of education and awareness creation in the ongoing pandemic. There is a need for the government and society to acknowledge and appreciate the efforts of FHCW.
Perceptions, behaviours and attitudes towards smoking held by the male partners of Chinese pregnant women: a qualitative study
Authors: Xia Wei , Li Ho Cheung William , Song Peige , Ho Ka Yan , Luo Yuanhui , Liang Tingna , Ho Laurie Long Kwan , Cheung Ankie Tan , Cai Wenzhi 
Published: October 2021

Abstract
Background
Direct associations of tobacco exposure during pregnancy with pregnancy complications and adverse birth outcomes have been proven. Previous studies suggest that expecting a child provides a valuable opportunity to promote behavioural changes, such as smoking cessation, among the male partners of pregnant women. Thorough understandings of Chinese expectant fathers’ smoking behaviour during the transition to fatherhood is a prerequisite to the development of appropriate interventions to facilitate smoking cessation. This study aimed to explore the perceptions, behaviours and attitudes related to smoking among male partners of pregnant women in China.

Methods
A descriptive phenomenological approach was adopted. A purposive sample of expectant fathers aged 18 years or older who had a tobacco use history within the past year were recruited at obstetrics and gynaecology clinics and invited to participate in one-to-one, 20–30-min semi-structured interviews. The data analysis followed Colaizzi’s descriptive phenomenological method.

Results
Twenty-five expectant fathers were interviewed. Four themes were generated: 1) the benefits of smoking and respondents’ misperceptions of the impact of smoking and SHS and neglectful attitude of the impact of smoking, which were given as the major reasons for continuing to smoke; 2) factors contributing to smoking cessation, including concern for the potential health impact of continued smoking on the pregnant partner and baby, the role of being father, and the encouragement to quit from family members; and 3) perceived barriers to smoking cessation, including withdrawal symptoms or cigarette cravings, absence of smoking cessation support, and increasing stress.

Conclusion
This study provides a comprehensive understanding of the perception, behaviours, and attitudes related to smoking among Chinese expectant fathers. The findings of this study can guide healthcare professionals and policymakers in combining the distribution of educational information about the hazards of SHS for maternal and neonatal health with smoking cessation assistance for expectant fathers through policy initiatives and other types of incentives and programmes targeted to enhance smoking cessation among this population.

Trial registration
Prospectively registered at clinicaltrial.org (NCT03401021) on 8 Jan 2018.
Prognosis does not change the landscape: palliative home care clients experience high rates of pain and nausea, regardless of prognosis
Authors: Williams Nicole , Hermans Kirsten , Stevens Tara , Hirdes John P. , Declercq Anja , Cohen Joachim , Guthrie Dawn M. 
Published: October 2021

Abstract
Background
Most individuals who typically receive palliative care (PC) tend to have cancer and a relatively short prognosis (< 6 months). People with other life-limiting illnesses can also benefit from a palliative care approach. However, little is known about those who receive palliative home care in Ontario, Canada’s largest province. To address this gap, the goal of this project was to understand the needs, symptoms and potential differences between those with a shorter (< 6 months) and longer prognosis (6+ months) for individuals receiving PC in the community.

Methods
A cross-sectional analysis was conducted using interRAI Palliative Care (interRAI PC) assessment data collected between 2011 and 2018. Individuals with a shorter prognosis (< 6 months; n = 48,019 or 64.1%) were compared to those with a longer prognosis (6+ months; n = 26,945) across several clinical symptoms. The standardized difference (stdiff), between proportions, was calculated to identify statistically meaningful differences between those with a shorter and longer prognosis. Values of the stdiff of 0.2 or higher (absolute value) indicated a statistically significant difference.

Results
Overall, cancer was the most prevalent diagnosis (83.2%). Those with a shorter prognosis were significantly more likely to experience fatigue (75.3% vs. 59.5%; stdiff = 0.34) and shortness of breath at rest (22.1% vs. 13.4%; stdiff = 0.23). However, the two groups were similar in terms of severe pain (73.5% vs. 66.5%; stdiff = − 0.15), depressive symptoms (13.2% vs. 10.7%; stdiff = 0.08) and nausea (35.7% vs. 29.4%; stdiff = 0.13).

Conclusions
These results highlight the importance of earlier identification of individuals who could benefit from a palliative approach to their care as individuals with a longer prognosis also experience high rates of symptoms such as pain and nausea. Providing PC earlier in the illness trajectory has the potential to improve an individual’s overall quality of life throughout the duration of their illness.
Prediction of synergistic drug combinations using PCA-initialized deep learning
Authors: Ma Jun , Motsinger-Reif Alison 
Published: October 2021

Abstract
Background
Cancer is one of the main causes of death worldwide. Combination drug therapy has been a mainstay of cancer treatment for decades and has been shown to reduce host toxicity and prevent the development of acquired drug resistance. However, the immense number of possible drug combinations and large synergistic space makes it infeasible to screen all effective drug pairs experimentally. Therefore, it is crucial to develop computational approaches to predict drug synergy and guide experimental design for the discovery of rational combinations for therapy.

Results
We present a new deep learning approach to predict synergistic drug combinations by integrating gene expression profiles from cell lines and chemical structure data. Specifically, we use principal component analysis (PCA) to reduce the dimensionality of the chemical descriptor data and gene expression data. We then propagate the low-dimensional data through a neural network to predict drug synergy values. We apply our method to O’Neil’s high-throughput drug combination screening data as well as a dataset from the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge. We compare the neural network approach with and without dimension reduction. Additionally, we demonstrate the effectiveness of our deep learning approach and compare its performance with three state-of-the-art machine learning methods: Random Forests, XGBoost, and elastic net, with and without PCA-based dimensionality reduction.

Conclusions
Our developed approach outperforms other machine learning methods, and the use of dimension reduction dramatically decreases the computation time without sacrificing accuracy.
The roles of sex and gender in women’s eye health disparities in the United States
Authors: Aninye Irene O. , Digre Kathleen , Hartnett M. Elizabeth , Baldonado Kira , Shriver Erin M. , Periman Laura M. , Grutzmacher Julie , Clayton Janine A. ,   Society for Women’s Health Research Women’s Eye Health Working Group
Published: October 2021

Abstract
Background
In the United States, women are at a higher risk of developing vision impairment or a serious eye disease (such as age-related macular degeneration, thyroid eye disease, or chronic dry eye disease) than men. Disparities in eye diseases due to biology widen even further when considering factors such as social determinants of health; gaps in research data, literature, and policy; insufficient provider and patient education; and limitations in screening and treatment options. Sex and gender disparities in eye health are clinically under-addressed and burdensome on both patient quality of life and the health care and economic systems, resulting in a pressing population health issue that negatively impacts women.

Design
The Society for Women’s Health Research convened a working group of expert clinicians, researchers, and patient advocates to review the current state of science regarding sex and gender disparities in women’s eye health, identify knowledge gaps and unmet needs, and explore better means to advance research, improve patient care, and raise awareness of key issues.

Discussion
The SWHR Women’s Eye Health Working Group identified priority areas in research, clinical care, and education to reduce disparities and improve patient care in women’s eye health. The working group recommends using a systems approach that incorporates a comprehensive research framework with a sex and gender lens to guide future work and that increases health care provider and public education, as well as engagement by expanding partnerships among ophthalmologic providers, researchers, and non-vision stakeholders.