bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant Therapy Effects on Invasive Mammary Carcinomas: Comparative Study of Pre- and Post-Therapy Cases and Assessment of Overall Survival Time
Authors: Gomes Virginia , De Castro Carolina , Balabram Debora , Santos Barbara Dos , Nunes Cristiana 
Published: May 2022

PURPOSE To evaluate the pathological effects of neoadjuvant therapy (NT) on prognostic and predictive factors of invasive mammary carcinomas (IMC) and the impact of these changes on overall survival time. METHODS Sixty-eight IMC diagnosed, treated with NT (2008-2016), with surgical excision at Hospital das Clínicas of UFMG showing pathological partial response. All samples were revised by an experienced breast pathologist, classified and graduated according to the WHO criteria. The histological tumor types were divided into three groups (no special type, lobular type and others). Estrogen and Progesterone receptors (ER and PR), HER2 and Ki67 status were evaluated through IHC. Statistical analysis was performed using the SPSS statistical program. RESULTS Nineteen of 55 tumors (34.5%) showed changes in histological type ( P = .024). Although not significant, 26/55 tumors had changes in histological grade, such as higher (27.3%) or lower grade (10.9%). Seven percent showed an increase in the percentage of inflammatory infiltrate ( P = .004) and 35% had a decrease. Twenty-two of 55 (40%) of tumors showed ER changes and 20/55 (36,4%) showed PR changes. 96.4% of cases kept the same HER2 expression. 34.5% of tumors showed changes in the Ki67 expression. Ki67 distribution was different in post-therapy samples (non-normal distribution), diverting from expected ( P = .014). There was an increase in Luminal A-like type (from 18.2% on pre-NT to 25.5% on post-NT samples) and Triple Negative type (from 34.5% on pre-NT to 45.5% on post-NT samples). These pathological changes found in post-neoadjuvant therapy samples did not affect the overall survival time of patients (median time of 44 months). CONCLUSION Prognostic and predictive factors of IMC can change after neoadjuvant therapy. Reclassifying and retesting the residual samples is important to reevaluate treatment. There was no impact on overall survival of patients.
Exploiting Interdata Relationships in Prostate Cancer Proteomes: Clinical Significance of HO-1, HSPB1, DDB1 and 14-3-3ζ/δ Interaction
Authors: Lage-Vickers Sofia , Sanchis Pablo , Bizzotto Juan , Toro Ayelen , Valacco Maria P. , Cotignola Javier , Vazquez Elba , Gueron Geraldine 
Published: May 2022

PURPOSE Prostate cancer (PCa) is the second most common type of cancer in men and the sixth leading cause of cancer-related death in men worldwide. The discovery of new therapeutic avenues in PCa, and the development of effective drugs in the era of personalized medicine, would greatly benefit from the field of proteomics. We have previously shown the anti-tumoral role of Heme oxygenase 1 (HO-1) in PCa. METHODS In this work, we undertook a mass spectrometry-based proteomics study to assess whether in PCa cells and under oxidative stress conditions, HO-1 could interact with proteins previously documented to have nuclear localization. RESULTS Among the HO-1 interactors, we identified 11 proteins with nuclear localization. Significant and positive correlation between HMOX1 and six of those genes was observed, using the GSE70770 dataset. Alternatively, HMOX1 and YWHAZ showed negative correlation. High expression of HNRNPA2B1, HSPB1, NPM1, DDB1, HMGA1, ZC3HAV1, and HMOX1 was associated with an increased relapse-free survival (RFS) in PCa patients through univariable analyses. Further, PCa patients with high HSPB1/HMOX1, DDB1/HMOX1, and YWHAZ/HMOX1 showed a worse RFS compared with patients with lower ratios. Moreover, by using a prognostic risk score model, a decrease in RFS for patients with higher scores of this signature was observed. However, the only factor significantly associated with a higher risk of relapse was high YWHAZ. HSPB1, DDB1 and YWHAZ independence from PCa clinic-pathological parameters was confirmed through multivariable analyses. Moreover, co-immunoprecipitation analysis in PCa cells ascertained HO-1/14-3-3ζ/δ (YWHAZ encoding gene) interaction. CONCLUSION Herein, we report novel interactions between HO-1 and HSPB1, DDB1 and 14-3-3ζ/δ, highlighting their clinical relevance in PCa.
The Cost Implication of Trastuzumab in Patients With HER2-Positive Breast Cancer at Moi Teaching and Referal Hospital, Eldoret, Kenya
Authors: Wabende Lucy Najala , Bhatia Manisha , Kiptoo Stephen , Kisilu Nicholas , Kiboss Caroline , Kibiwot Silvanus , Jepkirui Sally , Awuor Dorice Adhiambo , Busakhala Naftali , Hunter-Squires Joanna 
Published: May 2022

PURPOSE A year course of trastuzumab revolutionized treatment for human epidermal growth factor receptor (HER2)-positive breast cancer by increasing survival rates. However, trastuzumab treatment is cost-prohibitive, and data on abbreviated courses is lacking in advanced disease. At Moi Teaching and Referral Hospital (MTRH), one of two national referral hospitals in Kenya, HER2-positive breast cancer accounts for 20% and 95% of patients present with Stage III/IV disease. The national health insurance fund (NHIF) covers four of the recommended 18 cycles. In this study, we aimed to understand varying trastuzumab treatment plans and patient adherence. METHODS This is a retrospective chart review for breast cancer patients seen at the MTRH oncology clinic from January to December 2020. Immunohistochemistry results were reviewed and those with HER2+ by immunohistochemistry were included. Data was analyzed via NVivo with multivariate analysis. RESULTS Ninety-five patients were included with an average age of 48.7 years. 33.59% (n = 31) completed 18 cycles of trastuzumab. However, 53.3% (n = 16) of those who completed the treatment were inconsistent in treatment schedule. Nearly half, 45.26% (n = 43), received only the four cycles being covered by NHIF. More concerning, 23.15% (n = 22) did not begin trastuzumab. For MTRH patients, the cost of trastuzumab is 111,244 Kenyan Shillings (990 USD), 9 times the average monthly income per family in western Kenya. CONCLUSION Although trastuzumab is lifesaving, < 33% of patients with HER2-positive breast cancer complete treatment in the public sector in western Kenya. Of these patients, half experience treatment delays that may be attributable to secondary costs related to travel and absence from employment. External charity funding has improved patient access but is unsustainable. The Kenyan Ministry of Health can reduce the cost burden for patients by negotiating with pharmaceutical companies to offer subsidies or adjusting NHIF policies to promote drug access. Further studies into shorter course trastuzumab are merited.
Reducing Geographic Barriers for Breast Cancer Diagnosis
Authors: Adaniya Emily , Bhatia Manisha , Kiptoo Stephen , Wabende Lucy Najala , Kisilu Nicholas , Kibiwot Silvanus , Jepkirui Sally , Awuor Dorice Adhiambo , Loehrer Patrick , Hunter-Squires Joanna , Busakhala Naftali 
Published: May 2022

PURPOSE Increasing travel times to the nearest diagnostic facilities and cancer centers are correlated with decreasing prevalence of breast cancer diagnosis and increasing stage of cancer at diagnosis. Moi Teaching and Referral Hospital (MTRH), in Uasin Gishu County, houses the only public cancer center in western Kenya. A MTRH program, the Academic Model Providing Access to Healthcare Breast and Cervical Cancer Control Program (ABCCCP) hosted health fair breast cancer screening events and mentored nurses at local health facilities to complete clinical breast exams (CBEs). The objective is to understand the effect of the ABCCCP in reducing geographic barriers for breast cancer screening/early diagnosis. METHODS This is a retrospective review of the 61,392 patients who underwent breast cancer screening at a ministry of health facility in western Kenya from 2017-2021. ABCCCP hosted health fairs targeted at communities and mentored nurses at health facilities to complete clinical breast exams (CBEs) to target individual patients. Facility distances from MTRH were mapped via Google Maps. Descriptive analyses were performed to a significance of α < 0.05. RESULTS Two-thirds of the screening/early diagnosis CBEs occurred in five of the 22 counties in western Kenya: Busia, Uasin Gishu, Trans-Nzoia, Bungoma, and Kakamega. However, these five counties only had 25% of all ABCCCP screening sites in western Kenya. Only Uasin Gishu and Kakamega provided chemotherapy while Busia and Trans-Nzoia had additional programming promoting preventative healthcare through integration of community health volunteers. In these five counties, no association between the distance of the ministry of health facilities from MTRH and number of CBEs completed existed. CONCLUSION ABCCCP programming reduced some geographic disparities in breast cancer screening/diagnosis in the top five counties. It may be result of the number of mentored nurses and health fair events. Further work should be completed to understand if a relationship between geographic distance from MTRH and the stage and treatment patterns of these patients is also reduced by ABCCCP.
Scaling up Tobacco Control in India: Comparing Smartphone to In-Person Training for Implementing an Evidence-Based Intervention to Reduce Tobacco Use Among Schoolteachers: Study Protocol
Authors: Nagler Eve , Pednekar Mangesh , Gunderson Daniel , Sorensen Glorian , Gupta Prakash 
Published: May 2022

PURPOSE Tobacco-related deaths are rising rapidly in low and middle-income countries (LMICs). In India, approximately 1.2 million people die each year from tobacco-related causes. Reducing tobacco-related deaths in LMICs will require large-scale implementation of evidence-based interventions (EBIs) that promote tobacco control. Currently, implementation of tobacco control EBIs in LMICs relies on in-person training, which has inherent logistical challenges that limit the ability to scale up these programs. New training models are needed to ensure tobacco control EBIs can be implemented broadly and at low cost, especially in rural and under-resourced areas where tobacco use is prevalent. In India, schoolteachers are respected community leaders and role models, representing an important channel for promoting tobacco control. We previously demonstrated the effectiveness of the Tobacco-Free Teachers, Tobacco-Free Society (TFT-TFS) program in increasing tobacco use cessation. To scale this EBI, we will compare two TFT-TFS-training models for headmasters—in-person versus smartphone-based—and examine the effect of each model on TFT-TFS program implementation and effectiveness. METHODS Using a cluster-randomized design, we will randomize school headmasters in the Indian state of Madhya Pradesh to receive in-person or smartphone training. Once trained, headmasters in both groups will implement TFT-TFS within their schools. Accordingly, our aims are to (1) use a participatory, qualitative approach to develop the in-person and smartphone-based training models; (2) compare program implementation fidelity, effectiveness, and cost for both training models using process evaluation and survey data; and (3) identify factors affecting program implementation using mixed methods. RESULTS This study will establish the effects of smartphone vs. in-person training on TFT-TFS implementation, effectiveness, and cost within schools in a low-resource setting. CONCLUSION Our findings will provide insight into scaling up tobacco control EBIs in schools across India and other LMICs and inform the application of smartphone-based training for other public health-related EBIs in resource-constrained areas.
Tissue Proteomics and Custom-Made Transcriptomics Analysis Tool Revel PPP1R12B, FBLN5, CRIP2, and POSTN as Potential Prognostic Biomarkers in Prostate Cancer
Authors: Bizzotto Juan , Lavignolle Rosario , Sabater Agustina , Sanchis Pablo , Lage-Vickers Sofia , Seniuk Rocio , Pascual Gaston , Valacco Pia , Vazquez Elba , Cotignola Javier , Gueron Geraldine 
Published: May 2022

PURPOSE Prostate cancer (PCa) is a progressive disease involving multiple molecular alterations. The Gleason Grade (GG) is used as an aid for physicians to evaluate the prognosis of men with PCa using samples from prostate tissues. However, some PCa that are histo-pathologically grouped in the same GGs can differ significantly in outcome. The aim of this study was to identify molecular biomarkers that could behave independently from GG and other clinical-pathological variables (age, GG and TMPRSS2-ERG fusion status) that can improve risk prediction of PCa. METHODS An in-depth proteomics analysis (LC/ESI-MS/MS) was performed on human prostate adenocarcinoma and benign prostate hyperplasia (BPH) tissues. Protein candidates enriched in PCa vs BPH were further evaluated in-silico using a custom-made pipeline. For this purpose, seven publicly available transcriptomic PCa datasets (ntotal = 875) were selected, and differential expression analyses were performed in R. A Shiny-based tool was then built to execute the search and to allow visualization across multiple datasets. Further multivariable analyses were performed using clinical-pathological parameters as covariates. RESULTS Proteomics analysis yielded a list of 89 proteins enriched in PCa compared with BPH. 58 showed high expression in PCa datasets and nine of those, showed significant association with higher risk of death. Further, when performing a multivariable Cox proportional-hazard model including age, GG and TMPRSS2-ERG fusion status, PPP1R12B, FBLN5, CRIP2, and POSTN displayed associations with poor prognosis, independently from the other co-variates (HR = 1.5, P = .0084; HR = 1.34, P = .035; HR = 1.36, P = .016 and HR = 1.4, P = .0028, respectively). CONCLUSION PPP1R12B, FBLN5, CRIP2, and POSTN proteins were enriched in PCa human tissues. Our custom pipeline revealed increased expression of these genes across multiple PCa datasets and significant association with increased risk of death, independent from known risk factors and predictors of PCa prognosis. Thus, these factors rise as potential prognostic markers.
Identifying Small Molecule Compounds that Have Synergistic Effects With Cisplatin and Other Platinum Drugs Using High Throughput Matrix Screening
Authors: Al-Zubi Layla , Cheff Dorian M. , Itkin Zina , Guo Hui , Shen Min , Hall Matthew D. 
Published: May 2022

PURPOSE High grade serous ovarian cancer (“HGSOC”) is the seventh most common cancer worldwide among women. The disease has no unique symptoms and often women are diagnosed in advance stages. The World Health Organization estimates that 225,500 women are diagnosed and 140,200 will die of this disease per year. In the United States, the 5-year survival rate is 43%, and 85% of all HGSOC patients experience recurrence despite aggressive treatment. More efficacious drug combination treatments are needed. Recently it was found that platinum drugs are inactivated in dimethyl sulfoxide (DMSO). Thus drug discovery platforms that use it as a solvent are not able to study platinum drugs in combination with other drugs easily. Advances in Echo technology at the National Center for Advancing Translational Sciences (NCATS) enabled acoustic transfer of platinum drugs in aqueous solutions. This allows us to find novel small molecule/platinum drug combinations that can be tested in clinical trials. METHODS We ran single-agent dose-response experiments to correctly estimate the dose-ranges needed for the matrix screens utilizing the OVCAR8 human carcinoma cell line. Then, we conducted our pilot matrix screen with compounds that are commonly combined with cisplatin for HGSOC treatment. Lastly, we spotted cisplatin against the Mechanism Interrogation PlatE drug library to identify novel combinations for clinical use against HGSOC. Compounds that show synergistic cell killing will give insight into novel drug combinations to treat HGSOC. RESULTS Several synergistic and antagonistic effects were found. These results were refined with smaller-scale screening and tested in other HGSOC cell lines. CONCLUSION The novel combinations discovered will allow chemotherapy patients to receive lower dosages of platinum drugs while maintaining or improving efficacy of cytotoxicity of cancer cells. This will help alleviate the side-effects of platinum drugs experienced by HGSOC patients.
A Multiclassifier System to Identify and Subtype Congenital Adrenal Hyperplasia Based on Circulating Steroid Hormones
Authors: Ye Lei , Zhao Zhiyun , Ren Huixia , Wang Wencui , Zhou Wenzhong , Zheng Sichang , Han Rulai , Zhang Jie , Li Haorong , Wan Zhihan , Tang Chao , Sun Shouyue , Wang Weiqing , Ning Guang 
Published: May 2022

Abstract

Context
Measurement of plasma steroids is necessary for diagnosis of congenital adrenal hyperplasia (CAH). We sought to establish an efficient strategy for detection and subtyping of CAH with a machine-learning algorithm.

Methods
Clinical phenotype and genetic testing were used to provide CAH diagnosis and subtype. We profiled 13 major steroid hormones by liquid chromatography-tandem mass spectrometry. A multiclassifier system was established to distinguish 11β-hydroxylase deficiency (11βOHD), 17α-hydroxylase/17,20-lyase deficiency (17OHD), and 21α-hydroxylase deficiency (21OHD) in a discovery cohort (n = 226). It was then validated in an independent cohort (n = 111) and finally applied in a perspective cohort of 256 patients. The diagnostic performance on the basis of area under receiver operating characteristic curves (AUCs) was evaluated.

Results
A cascade logistic regression model, we named the “Steroidogenesis Score”, was able to discriminate the 3 most common CAH subtypes: 11βOHD, 17OHD, and 21OHD. In the perspective application cohort, the steroidogenesis score had a high diagnostic accuracy for all 3 subtypes, 11βOHD (AUC, 0.994; 95% CI, 0.983-1.000), 17OHD (AUC, 0.993; 95% CI, 0.985-1.000), and 21OHD (AUC, 0.979; 95% CI, 0.964-0.994). For nonclassic 21OHD patients, the tool presented with significantly higher sensitivity compared with measurement of basal 17α-hydroxyprogesterone (17OHP) (0.973 vs 0.840, P = 0.005) and was not inferior to measurement of basal vs stimulated 17OHP (0.973 vs 0.947, P = 0.681).

Conclusions
The steroidogenesis score was biochemically interpretable and showed high accuracy in identifying CAH patients, especially for nonclassic 21OHD patients, thus offering a standardized approach to diagnose and subtype CAH.
Intrafollicular Concentrations of the Oocyte-secreted Factors GDF9 and BMP15 Vary Inversely in Polycystic Ovaries
Authors: Kristensen Stine Gry , Kumar Ajay , Mamsen Linn Salto , Kalra Bhanu , Pors Susanne Elisabeth , Bøtkjær Jane Alrø , Macklon Kirsten Tryde , Fedder Jens , Ernst Erik , Hardy Kate , Franks Stephen , Andersen Claus Yding 
Published: May 2022

AbstractContextThe oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play essential roles in follicle development and oocyte maturation, and aberrant regulation might contribute to the pathogenesis of polycystic ovary syndrome.ObjectiveAre there measurable differences in concentrations of GDF9, BMP15, and the GDF9/BMP15 heterodimer in small antral follicle fluids from women with and without polycystic ovaries (PCO)?Design and SettingFollicle fluids (n = 356) were collected from 4- to 11-mm follicles in unstimulated ovaries of 87 women undergoing ovarian tissue cryopreservation for fertility preservation.PatientsTwenty-seven women with PCO were identified and 60 women without PCO-like characteristics (non-PCO women) were matched according to age and follicle size.Main outcome measuresIntrafollicular concentrations of GDF9, BMP15, GDF9/BMP15 heterodimer, anti-Mullerian hormone (AMH), inhibin-A and -B, total inhibin, activin-B and -AB, and follistatin were measured using enzyme-linked immunosorbent assays.ResultsThe detectability of GDF9, BMP15, and the GDF9/BMP15 heterodimer were 100%, 94.4%, and 91.5%, respectively, and concentrations were significantly negatively correlated with increasing follicle size (P &lt; 0.0001). GDF9 was significantly higher in women with PCO (PCO: 4230 ± 189 pg/mL [mean ± SEM], n = 188; non-PCO: 3498 ± 199 pg/mL, n = 168; P &lt; 0.03), whereas BMP15 was lower in women with PCO (PCO: 431 ± 40 pg/mL, n = 125; non-PCO: 573 ± 55 pg/mL, n = 109; P = 0.10), leading to a significantly higher GDF9:BMP15 ratio in women with PCO (P &lt; 0.01). Significant positive associations between BMP15 and AMH, activins, and inhibins in non-PCO women switched to negative associations in women with PCO.ConclusionsIntrafollicular concentrations of GDF9 and BMP15 varied inversely in women with PCO reflecting an aberrant endocrine environment. An increased GDF9:BMP15 ratio may be a new biomarker for PCO.
Pituitary MRI Features in Acromegaly Resulting From Ectopic GHRH Secretion From a Neuroendocrine Tumor: Analysis of 30 Cases
Authors: Potorac Iulia , Bonneville Jean-François , Daly Adrian F , de Herder Wouter , Fainstein-Day Patricia , Chanson Philippe , Korbonits Marta , Cordido Fernando , Baranski Lamback Elisa , Abid Mohamed , Raverot Véronique , Raverot Gerald , Anda Apiñániz Emma , Caron Philippe , Du Boullay Helene , Bidlingmaier Martin , Bolanowski Marek , Laloi-Michelin Marie , Borson-Chazot Francoise , Chabre Olivier , Christin-Maitre Sophie , Briet Claire , Diaz-Soto Gonzalo , Bonneville Fabrice , Castinetti Frederic , Gadelha Mônica R , Oliveira Santana Nathalie , Stelmachowska-Banaś Maria , Gudbjartsson Tomas , Villar-Taibo Roció , Zornitzki Taiba , Tshibanda Luaba , Petrossians Patrick , Beckers Albert 
Published: May 2022

Abstract

Context
Ectopic acromegaly is a consequence of rare neuroendocrine tumors (NETs) that secrete GHRH. This abnormal GHRH secretion drives GH and IGF-1 excess, with a clinical presentation similar to classical pituitary acromegaly. Identifying the underlying cause for the GH hypersecretion in the setting of ectopic GHRH excess is, however, essential for proper management both of acromegaly and the NET. Owing to the rarity of NETs, the imaging characteristics of the pituitary in ectopic acromegaly have not been analyzed in depth in a large series.

Objective
Characterize pituitary magnetic resonance imaging (MRI) features at baseline and after NET treatment in patients with ectopic acromegaly.

Design
Multicenter, international, retrospective.

Setting
Tertiary referral pituitary centers.

Patients
Thirty ectopic acromegaly patients having GHRH hypersecretion.

Intervention
None.

Main outcome measure
MRI characteristics of pituitary gland, particularly T2-weighted signal.

Results
In 30 patients with ectopic GHRH-induced acromegaly, we found that most patients had hyperplastic pituitaries. Hyperplasia was usually moderate but was occasionally subtle, with only small volume increases compared with normal ranges for age and sex. T2-weighted signal was hypointense in most patients, especially in those with hyperplastic pituitaries. After treatment of the NET, pituitary size diminished and T2-weighted signal tended to normalize.

Conclusions
This comprehensive study of pituitary MRI characteristics in ectopic acromegaly underlines the utility of performing T2-weighted sequences in the MRI evaluation of patients with acromegaly as an additional tool that can help to establish the correct diagnosis.