bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Gene Polymorphisms on Clinical Outcome for Stage IV Melanoma Patients Treated with Biochemotherapy: An Exploratory Study
Authors: Liu Dongxin , O'Day Steven J. , Yang Dongyun , Boasberg Peter , Milford Robert , Kristedja Tim , Groshen Susan , Weber Jeffrey 
Published: June 2022

AbstractPurpose: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy.Experimental Design: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-α either with or without tamoxifen. Cytokine gene polymorphisms for IFN-γ (+874A→T) and IL-10 (−1082G→A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined.Results: IFN-γ (+874A→T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P &lt; 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-γ (+874A→T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-γ, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P &lt; 0.001), so that patients with more “favorable” polymorphisms had a better outcome.Conclusions: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings.
A Phase I Trial and Pharmacokinetic Study of Tipifarnib, a Farnesyltransferase Inhibitor, and Tamoxifen in Metastatic Breast Cancer
Authors: Lebowitz Peter F. , Eng-Wong Jennifer , Widemann Brigitte C. , Balis Frank M. , Jayaprakash Nalini , Chow Catherine , Clark Geoff , Gantz Susan B. , Venzon David , Zujewski JoAnne 
Published: June 2022

Abstract
Purpose: Farnesyltransferase (FTase) inhibitors, which were designed to inhibit oncogenic Ras, act synergistically with tamoxifen in preclinical breast cancer models. We studied the safety and toxicity of tipifarnib in combination with tamoxifen in metastatic breast cancer. The pharmacokinetics and pharmacodynamics of tipifarnib were also assessed.
Patients and Methods: Patients with metastatic, hormone receptor–positive breast cancer were enrolled. Two cohorts of patients were treated with tipifarnib at either 200 or 300 mg p.o. twice daily for 21 of 28 days. Tamoxifen (20 mg once daily) was started after 1 week of tipifarnib monotherapy to perform pharmacokinetics and FTase inhibition levels in peripheral blood mononuclear cells with tipifarnib alone and with tipifarnib and tamoxifen.
Results: A total of 12 heavily pretreated patients with prior progression on hormonal therapy were enrolled. Minimal toxicity was observed at the 200-mg dose level of tipifarnib. At the 300-mg dose, all six patients required dose reduction of tipifarnib due to toxicities that included grade 2 nausea, rash, and fatigue and grade 3 diarrhea and neutropenia. Tipifarnib pharmacokinetic and pharmacodynamic variables were similar in the presence and absence of tamoxifen. Average FTase inhibition was 42% at 200 mg and 54% at 300 mg in peripheral blood mononuclear cells. Of the 12 patients treated, there were two partial responses and one stable disease for &gt;6 months.
Conclusions: Tipifarnib (200 mg twice daily for 21 of 28 days) and tamoxifen (20 mg once daily) can be given safely with minimal toxicity. Tamoxifen does not have a significant effect on tipifarnib pharmacokinetics.
Accuracy, Feasibility, and Clinical Impact of Prospective Bayesian Pharmacokinetically Guided Dosing of Cyclophosphamide, Thiotepa, and Carboplatin in High-Dose Chemotherapy
Authors: de Jonge Milly E. , Huitema Alwin D.R. , Tukker Annemarie C. , van Dam Selma M. , Rodenhuis Sjoerd , Beijnen Jos H. 
Published: June 2022

Abstract
Purpose: Relationships between toxicity and pharmacokinetics have been shown for cyclophosphamide, thiotepa, and carboplatin (CTC) in high-dose chemotherapy. We prospectively evaluated whether variability in exposure to CTC and their activated metabolites can be decreased with pharmacokinetically guided dose administration and evaluated its clinical effect.
Experimental Design: Patients received multiple 4-day courses of cyclophosphamide (1,000–1,500 mg/m2/d), thiotepa (80–120 mg/m2/d), and carbop latin (area under the plasma concentration-time curve 3.3–5 mg × min/mL/d). Doses were adapted on day 3 based on pharmacokinetic analyses of cyclophosphamide, 4-hydroxycyclophosphamide, thiotepa, tepa, and carboplatin done on day 1 using a Bayesian algorithm. Doses were also adjusted before and during second and third courses. Observed toxicity was compared with that in patients receiving standard dose CTC (n = 43).
Results: A total of 46 patients (108 courses) were included. For cyclophosphamide, thiotepa, and carboplatin, a total of 39, 58, and 65 dose adaptations were done within courses and 17, 40, and 43 before courses. The precision within which the target exposure was reached improved compared with no adaptation, especially after within-course adaptations (precision for cyclophosphamide, thiotepa, and carboplatin is 19%, 16%, and 13%, respectively); &gt;85% led to an exposure within ±25% of the target compared with 60% without dose adjustments. Toxicity was similar to that in a reference population, although the incidence of veno-occlusive disease was reduced.
Conclusions: Bayesian pharmacokinetically guided dosing for CTC was feasible and led to a marked reduction in variability of exposure.
Molecular Mechanisms of Resistance to Therapies Targeting the Epidermal Growth Factor Receptor
Authors: Camp E. Ramsay , Summy Justin , Bauer Todd W. , Liu Wenbiao , Gallick Gary E. , Ellis Lee M. 
Published: June 2022

AbstractTargeted therapies that inhibit the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) have shown activity against solid malignancies when used as single agents or in combination with chemotherapy. Although anti-EGFR therapies are active in some patients, eventually disease in nearly all patients will become refractory to therapy. Therefore, a better understanding of the mechanisms of resistance to anti-EGFR therapies is critical to further improve the efficacy of this class of agents. Mechanisms that mediate resistance to anti-EGFR therapies include the presence of redundant tyrosine kinase receptors, increased angiogenesis, and the constitutive activation of downstream mediators. Two recent landmark publications have also shown that specific mutations in the kinase domain of EGFR in some lung carcinomas are associated with markedly improved response rates to an EGFR tyrosine kinase inhibitor. Mutations in the EGFR receptor seem to play a significant role in determining the sensitivity of tumor cells to EGFR inhibitor therapy by altering the conformation and activity of the receptor. As the field of molecular therapeutics continues to evolve, a comprehensive understanding of resistance mechanisms will ultimately lead to refinements in our regimens to provide better care for patients with cancer.
Identification of Gastric Cancer–Related Genes Using a cDNA Microarray Containing Novel Expressed Sequence Tags Expressed in Gastric Cancer Cells
Authors: Kim Jeong-Min , Sohn Ho-Yong , Yoon Sun Young , Oh Jung-Hwa , Yang Jin Ok , Kim Joo Heon , Song Kyu Sang , Rho Seung-Moo , Yoo Hyan Sook , Kim Yong Sung , Kim Jong-Guk , Kim Nam-Soon 
Published: June 2022

Abstract
Purpose: Gastric cancer is one of the most frequently diagnosed malignancies in the world, especially in Korea and Japan. To understand the molecular mechanism associated with gastric carcinogenesis, we attempted to identify novel gastric cancer–related genes using a novel 2K cDNA microarray.
Experimental Design: A 2K cDNA microarray was fabricated from 1,995 novel expressed sequence tags (ESTs) showing no hits or a low homology with ESTs in public databases from our 143,452 ESTs collected from gastric cancer cell lines and tissues. An analysis of the gene expression for human gastric cancer cell lines to a normal cell line was done using this cDNA microarray. Data for the different expressed genes were verified using semiquantitative reverse transcription-PCR, Western blotting, and immunohistochemical staining in the gastric cell lines and tissues.
Results: Forty genes were identified as either up-regulated or down-regulated genes in human gastric cancer cells. Among these, genes such as SKB1, NT5C3, ZNF9, p30, CDC20, and FEN1, were confirmed to be up-regulated genes in nine gastric cell lines and in 25 pairs of tissue samples from patients by semiquantitative reverse transcription-PCR. On the other hand, genes such as MT2A and CXX1 were identified as down-regulated genes. In particular, the SKB1, CDC20, and FEN1 genes were overexpressed in ≥68% of tissues and the MT2A gene was down-expressed in 72% of the tissues. Western blotting and immunohistochemical analyses for CDC20 and SKB1 showed overexpression and localization changes of the corresponding protein in human gastric cancer tissues.
Conclusions: Novel genes that are related to human gastric cancer were identified using cDNA microarray developed in our laboratory. In particular, CDC20 and MT2A represent a potential biomarker of human gastric cancer. These newly identified genes should provide a valuable resource for understanding the molecular mechanism associated with tumorigenesis of gastric carcinogenesis and for the discovery of potential diagnostic markers of gastric cancer.
Breast Differentiation and Its Implication in Cancer Prevention
Authors: Russo Jose , Mailo Daniel , Hu Yun-Fu , Balogh Gabriela , Sheriff Fathima , Russo Irma H. 
Published: June 2022

Abstract
Sporadic breast cancer is a fatal disease most frequently diagnosed in American women from all ethnic groups, suggesting that primary prevention should be the ultimate goal for breast cancer control. We have developed a novel paradigm for breast cancer prevention arising from the well-established knowledge that an early first full-term pregnancy protects the breast against neoplastic transformation, as well as from our studies of the biological principle underlying this protection. We have shown experimentally that the first pregnancy induces the expression of a specific genomic signature in the breast that results from the completion of a cycle in this organ's differentiation driven by the reproductive process. This signature, in turn, is a biomarker associated with a possible overall lifetime decrease in breast cancer risk. We have shown in an experimental model that a short treatment with human chorionic gonadotropin, a placental hormone secreted during pregnancy, induces the same genomic signature that occurs in pregnancy, inhibiting not only the initiation but also the progression of mammary carcinomas, and stopping the development of early lesions such as intraductal proliferations and carcinoma in situ. These observations indicate that human chorionic gonadotropin given for a very short period, only until this genomic signature is acquired, has significant potential as a chemopreventive agent, protecting the normal cell from becoming malignant. This is a novel concept which challenges the current knowledge that a chemopreventive agent needs to be given for a long period of time to suppress a metabolic pathway or abrogate the function of an organ.
Intersexual differences in the exploratory behaviour of blue tits (Cyanistes caeruleus)
Authors: Velasco Adara C. , Ferrer Esperanza S. , Sanz Juan José 
Published: June 2022

Abstract
Breeding performance and survival are mechanisms through which animal personality affects fitness. Exploration behaviour (EB) is an easily obtainable personality trait that correlates to multiple life-history traits, thus it has been widely used in animal personality studies. Through in situ Novel Environment exploration tests, we assessed the exploration behaviour of blue tits (Cyanistes caeruleus) during two breeding seasons. A principal component analysis revealed two behavioural axes regarding the exploration behaviour: slow-fast and timid-daring. We found that male blue tits are significantly slower explorers than female blue tits, suggesting that evolutionary processes act unequally across sexes in our study area. To investigate these processes, we assessed the relationship between exploration behaviour and two fitness aspects: reproduction and survival. Slower-exploring males bred in nests with significantly shorter incubation periods, and timid males had higher local return ratios. Interactions between male and female EB revealed that disassortative pairs were more successful breeders than assortative ones. Further research should explore potential evolutionary implications of intersexual EB differences.
Characterisation of Ditylenchus paraoncogenus n. sp. (Nematoda: Anguinidae), a new stem nematode parasitising tumble thistle
Authors: Hashemi Kobra , Karegar Akbar , Helder Johannes , Holterman Martijn , Mokaram Hesar Abbas 
Published: June 2022

Summary
During a survey, three populations of a new stem nematode were isolated from galls on the shoots of tumble thistle (Gundelia tournefortii) plants in Fars province, Iran, and identified. Ditylenchus paraoncogenus n. sp. is described based on morphometric and morphological characters. It is characterised by having long-sized females, 1252 (943-1628) μm long, narrow lateral fields with six incisures, rather developed stylet 9.9 (9.0-11.3) μm long with round knobs, usually elongate and offset from intestine basal pharyngeal bulb, oocytes in two rows in distal part of ovary, V = 83.3 (80.3-86.2), post-vulval uterine sac 68.1 (46.9-86.1)% of vulva to anus distance long, bursa covering 63.2 (33.3-74.4)% of tail length, spicules 24.7 (21.0-27.9) μm long with minute processes at the base of its manubrium and anteriorly pointed cuticle parts within the lamina, and thick conical tail, usually with a pointed terminus. In addition, the ITS and 18S rDNA sequences of 17 populations of D. destructor, D. dipsaci, D. medicaginis, D. myceliophagus, D. paraoncogenus n. sp., Ditylenchus sp. and Nothotylenchus geraerti plus one population of Anguinidae sp. were analysed. The results showed a close relationship between D. paraoncogenus n. sp. and the stem nematodes D. oncogenus, D. gigas, D. weischeri and D. dipsaci. Ditylenchus species were divided into two clades, one clade comprising stem nematodes and gall-forming nematodes of the family Anguinidae, and the other clade containing fungivorous species. Observations showed that the second-stage juvenile is the dormant stage of D. paraoncogenus n. sp. and can survive in anhydrobiotic condition for at least 4 years.
The Rock Arts of Metolong: Paintings, Archaeology and Cultural Resource Management in Western Lesotho
Authors: Mallen Lara , Pearce David , Arthur Charles , Mitchell Peter 
Published: June 2022

Abstract
Archaeological mitigation efforts in advance of Lesotho’s Metolong Dam involved comprehensive documentation of rock paintings in the area threatened with inundation, as well as pigment characterisation and direct dating. This paper gives an overview of the rock arts found and their key features. Four traditions are present. Most paintings belong to the fine-line San tradition, but there are also examples of Type 3 images previously only recognised in South Africa’s Eastern Cape Province. Two other traditions are identified as being made by local Basotho communities. Contextual evidence suggests that they relate to male identity and, in the case of ochre smears and handprints, specifically to male initiation rituals. Some of the rock art sites identified are, in fact, used today by male and female initiation schools. The importance of comprehensively documenting rock art in other locations where it is at risk of being lost via development projects is stressed. Metolong sets a standard for rock art recording in cultural resource management work in the wider region.
Laryngopharyngeal Reflux: Effect of Race and Insurance Status on Symptomology
Authors: Varelas Eleni A. , Houser Thomas K. , Husain Inna A. 
Published: June 2022

Objectives: Laryngopharyngeal reflux (LPR) is an extraesophageal variant of gastroesophageal reflux disease associated with intermittent dysphonia, throat-clearing, and chronic cough. This study aims to evaluate the impact of race and insurance status on symptoms often attributable to LPR. Methods: Retrospective review of all patients with suspected LPR from 2017 to 2019 was performed at a tertiary care center. The diagnostic criteria comprised evaluation by a fellowship trained laryngologist and Reflux Symptom Index (RSI) scores. Demographics, patient history, and insurance status were recorded. Descriptive statistics were calculated for each parameter using SPSS version 22. Results: A total of 170 patients (96 White, 44 Black, 26 Latinx, 4 Asian) were included in this study. About 57.1% had private insurance, 30.6% had Medicare, and 11.8% had Medicaid. Black and Latinx patients demonstrated higher RSI scores (26.67 ± 8.61, P = .017) when compared to their White and Asian counterparts. RSI scores between all 3 insurance types also varied significantly ( P = .035). Medicaid patients reported higher RSI scores (28.65 ± 10.09, P = .028), while private insurance patients reported significantly lower scores (23.75 ± 7.88, P = .03). Controlling for insurance type eliminates the statistically significant association between RSI scores and Black and Latinx patients. Particularly, within the Medicaid group, Black, Latinx, and White patients did not have statistically different RSI scores. Conclusions: Black and Latinx patients presented with higher RSI scores than White and Asian patients. Similarly, Medicaid patients reported higher RSI scores than the Non-Medicaid cohort. These findings suggest that access to appropriate healthcare, due to varied insurance coverage and socioeconomic, may potentially influence symptoms attributed to LPR.
Self-Perceived and Self-Tested Endurance: Associations with Objective Measures
Authors: Aandstad Anders 
Published: June 2022

Use of self-report (questionnaires) is often the most realistic means of screening physical fitness in large participant samples because this method is quicker and cheaper than objective testing. Yet, previous studies have reported equivocal validity to reports of self-perceived fitness. A hybrid self-report variant is the use of self-administered/reported objective measurement. I sought to investigate the relative validity of this variant method compared to self-perception reports. In total 26,452 young Norwegian men and women participated in this study. I collected data during obligatory selection for military conscript service. Approximately half of the participants were asked to rate their endurance level on a five-point Likert scale in an online questionnaire. The other half performed a self-administered 3000 m run and reported the result online. Within 18 months, all participants completed an objective maximal treadmill test at a conscript selection center. I used Spearman correlations ( rs) and analyses of variance (ANOVAs) to investigate the relationships between these two self-report methods and the observed objective treadmill performance. Self-perceived and self-tested endurance were both identically correlated with the other-observed treadmill run for men ( r s = 0.59 ; p < .001) and for women ( rs = 0.50, p < .001); and ANOVAs revealed significant effects of self-perceived and self-tested endurance on treadmill run time, with higher self-reported endurance related to higher treadmill run time. In conclusion, self-perceived and self-tested endurance produced the same correlation coefficients with objectively measured treadmill run time. While there was a moderate relationship between self-reported and objectively measured endurance at the group level, there was substantial individual measurement error that should be considered for individual reports.
Anaplastic lymphoma kinase rearrangements in patients with non-small cell lung cancer in Jordan
Authors: Maraqa Bayan , Al-Ashhab Maxim , Sughayer Maher A. 
Published: June 2022

Objective Anaplastic lymphoma kinase ( ALK) rearrangement is an important oncogenic driver in some non-small cell lung cancers (NSCLC). Treatment with ALK tyrosine kinase inhibitors improves survival. The availability of diagnostic immunohistochemistry (IHC) has led to a paradigm shift in ALK testing. This study examined the prevalence of ALK rearrangement in Jordanian patients with NSCLC and compared the results of IHC and fluorescence in situ hybridization (FISH) for detecting ALK rearrangement. Methods This retrospective study on 449 patients with NSCLC treated at the King Hussein Cancer Center in Jordan tested biopsy samples for ALK rearrangement using FISH and/or IHC (D5F3) between 2018 and 2020. Results Eighteen patients (4%) had ALK-positive NSCLC. The calculated sensitivity and specificity of ALK immunostaining compared with FISH were 87.5% and 96%, respectively. ALK-positive patients were significantly younger than their ALK-negative counterparts, and women were three times more likely to carry ALK rearrangement than men. ALK rearrangement was significantly associated with smoking history, with most ALK-positive patients being non-smokers, former smokers, or light smokers. Conclusions IHC is a reasonable alternative to FISH for ALK testing with advantages in terms of robustness, turnaround times, and cost-effectiveness.
The effect of action observation training on gait and balance of patients with neurological and musculoskeletal disorders: A systematic review
Authors: Shamsi Fatemeh , Nami Mohammad , Aligholi Hadi , Borhani-Haghighi Afshin , Kavyani Mahsa , Karimi Mohammad T 
Published: June 2022

Background Various treatment approaches are being applied for recovery of gait after different medical conditions. Action observation is a new motor learning approach, which is considered as a complementary training to the conventional rehabilitation programs such as occupational therapy for this purpose. Objective To find out which patients benefit more from action observation training. Methods Electronic databases, including Scopus, PubMed, Web of Science, Science Direct, and PEDro were searched. Prospective studies published in peer-reviewed journals with full text available in English, which investigated the effect of action observation on gait and balance of patients with neurologic or musculoskeletal disorders, were included. The methodological quality of the studies was assessed by the Downs and Black checklist, and the information was presented based on the PICO style. Results Nineteen studies recruiting post-orthopedic patients (4 studies), patients with stroke (11 studies), and Parkinson’s disease (4 studies) fulfilled the eligibility criteria. Quality scores ranged from 51.85% to 81.48%. Balance and walking ability were the most reported primary outcomes. Conclusion Patients in the chronic phase of stroke might benefit more from action observation training plus occupational therapy in different aspects of gait than orthopedic patients and those with Parkinson’s disease.