bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review of clinical and emerging biomarkers for breast cancers: towards precision medicine for patients
Authors: Osei Ernest 
Published: September 2020

AbstractBackground:Breast cancer is the most commonly diagnosed malignancy among women and accounts for about 25% of all new cancer cases and 13% of all cancer deaths in Canadian women. It is a highly heterogeneous disease, encompassing multiple tumour entities, each characterised by distinct morphology, behaviour and clinical implications. Moreover, different breast tumour subtypes have different risk factors, clinical presentation, histopathological features, outcome and response to systemic therapies. Therefore, any strategies capable of the stratification of breast cancer by clinically relevant subtypes are an important requirement for personalised and targeted treatment. Therefore, in the advancement towards the concept of precision medicine that takes individual patient variability into account, several investigators have focused on the identification of effective clinical breast cancer biomarkers that interrogate key aberrant pathways potentially targetable with molecular targeted or immunological therapies.Methods and materials:This paper reports on a review of 11 current clinical and emerging biomarkers used in screening for early detection and diagnosis, to stratify patients by disease subtype, to identify patients’ risk for metastatic disease and subsequent relapse, to monitor patient response to specific treatment and to provide clinicians the possibility of prospectively identifying groups of patients who will benefit from a particular treatment.Conclusion:The future holds promising for the use of effective clinical breast cancer biomarkers for early detection and personalised patient-specific targeted treatment and increased patient survival. Breast cancer biomarkers can potentially assist in early-staged, non-invasive, sensitive and specific breast cancer detection and screening, provide clinically useful information for identification of patients with a greater likelihood of benefiting from the specific treatment, offer a better understanding of the metastatic process in cancer patients, predict disease and for patients with the established disease can assist define the nature of the disease, monitor the success of treatment and guide the clinical management of the disease.
Detection of organic or inorganic material in Martian meteorite Zagami by vibrational spectroscopy?
Authors: do Nascimento-Dias Bruno Leonardo , Zucolotto Maria Elizabeth , Belgo Hugo Camarano , da Silva Talita Valverde Ferreira , dos Anjos Virgĩlio de Carvalho 
Published: September 2020

AbstractZagami is a basaltic shergottite well characterized among Martian meteorites. For this reason, it is used as a reference sample to verify the feasibility of the vibrational spectroscopy techniques. In general, these techniques seeking extract spectral signatures from individual mineral present in the meteorite samples. Among some FTIR results were detected organic compounds in the Zagami meteorite and recorded in some articles. Based on these results, an analysis of a Zagami meteorite sample was performed using FTIR and Raman spectrometry. Examining the fragment of Zagami meteorite using the FTIR technique, it was possible to identify the same band of 2920 and 2850 cm−1 described by other references, which were interpreted as organic components and were recorded such as aliphatic hydrocarbon. Another unusual result in Martian meteorite was the detection of the 1300 cm−1 band using Raman. The main reason for this peculiarity is that band is characterized in meteorites as a D band. Generally, this band is attributed to structural defects and the disordering of carbon. However, care should be taken when interpreting Raman spectra around 1300 cm−1 and FTIR spectra 2950–2840 cm−1 of the sample from oxidizing environments such as Mars. Misconceptions can occur during the interpretations of the bands, and this can lead to incorrect identification. Thus, an analysis of the mentioned peaks, such as chemical and mineralogical assignments, will be provided and suggested in order to compare the results that mentioned the presence of organic compounds in the Zagami meteorite.
What symptoms tell us: A multiple case study of oncology consultations
Authors: Bourquin Céline , Stiefel Friedrich 
Published: September 2020

AbstractObjectivesWhile patients’ symptom experiences have been widely investigated, there is a lack of contextualized studies investigating how symptoms circulate in the medical consultation, how patients present them, what they convey, how physicians respond, and how patients and physicians negotiate with each other to find ways to address them. The aim of this study is to explore patients and physicians handling of symptoms throughout oncological consultations with a multiple case study approach.MethodsFive consultations, purposively selected from an existing dataset of audiotaped consultations with patients with advanced cancer, were analyzed by means of an inductive analytical approach based on a sensitive framework from the literature.ResultsPatients’ symptoms showed multiple dimensions such as medical, cognitive, emotional, psychological, interactional, symbolic, experiential, and existential.Significance of resultsDifferent symptom dimensions remained unnoticed and unaddressed in the consultations. The physician-centered symptom approach that was observed leads to consumed time and missed opportunities for relationship building with the patient. Physicians showed a lack of sensitivity regarding the multiple dimensions of symptoms. Based on the findings, strategies for a more comprehensive symptom approach can be conceived.
Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK-228) in advanced solid tumours, with an expansion phase in renal, endometrial or bladder cancer
Authors: Voss Martin H. , Gordon Michael S. , Mita Monica , Rini Brian , Makker Vicky , Macarulla Teresa , Smith David C. , Cervantes Andrés , Puzanov Igor , Pili Roberto , Wang Ding , Jalal Shadia , Pant Shubham , Patel Manish R. , Neuwirth Rachel l. , Enke Aaron , Shou Yaping , Sedarati Farhad , Faller Douglas V. , Burris Howard A. 
Published: September 2020

Abstract
Background
This Phase 1 dose-escalation/expansion study assessed safety/tolerability of sapanisertib, an oral, highly selective inhibitor of mTORC1/mTORC2, in advanced solid tumours.

Methods
Eligible patients received increasing sapanisertib doses once daily (QD; 31 patients), once weekly (QW; 30 patients), QD for 3 days on/4 days off QW (QD × 3dQW; 33 patients) or QD for 5 days on/2 days off QW (QD × 5dQW; 22 patients). In expansion cohorts, 82 patients with renal cell carcinoma (RCC), endometrial or bladder cancer received sapanisertib 5 mg QD (39 patients), 40 mg QW (26 patients) or 30 mg QW (17 patients).

Results
Maximum tolerated doses of sapanisertib were 6 mg QD, 40 mg QW, 9 mg QD × 3dQW and 7 mg QD × 5dQW. Frequent dose-limiting toxicities (DLTs) included hyperglycaemia, maculo-papular rash (QD), asthenia and stomatitis (QD × 3dQW/QD × 5dQW); expansion phase doses of 5 mg QD and 30 mg QW were selected based on tolerability beyond the DLT evaluation period. One patient with RCC achieved complete response; nine experienced partial responses (RCC: seven patients; carcinoid tumour/endometrial cancer: one patient each). Sapanisertib pharmacokinetics were time-linear and supported multiple dosing. Pharmacodynamic findings demonstrated treatment-related reductions in TORC1/2 biomarkers.

Conclusions
Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer.

Clinical trial registration
ClinicalTrials.gov, NCT01058707.
Controlled coupling of an ultrapotent auristatin warhead to cetuximab yields a next-generation antibody-drug conjugate for EGFR-targeted therapy of KRAS mutant pancreatic cancer
Authors: Greene Michelle K. , Chen Ting , Robinson Eifion , Straubinger Ninfa L. , Minx Charlene , Chan Darren K. W. , Wang Jun , Burrows James F. , Van Schaeybroeck Sandra , Baker James R. , Caddick Stephen , Longley Daniel B. , Mager Donald E. , Straubinger Robert M. , Chudasama Vijay , Scott Christopher J. 
Published: September 2020

Abstract
Background
Antibody-drug conjugate (ADC) construction poses numerous challenges that limit clinical progress. In particular, common bioconjugation methods afford minimal control over the site of drug coupling to antibodies. Here, such difficulties are overcome through re-bridging of the inter-chain disulfides of cetuximab (CTX) with auristatin-bearing pyridazinediones, to yield a highly refined anti-epidermal growth factor receptor (EGFR) ADC.

Methods
In vitro and in vivo assessment of ADC activity was performed in KRAS mutant pancreatic cancer (PaCa) models with known resistance to CTX therapy. Computational modelling was employed for quantitative prediction of tumour response to various ADC dosing regimens.

Results
Site-selective coupling of an auristatin to CTX yielded an ADC with an average drug:antibody ratio (DAR) of 3.9, which elicited concentration- and EGFR-dependent cytotoxicity at sub-nanomolar potency in vitro. In human xenografts, the ADC inhibited tumour growth and prolonged survival, with no overt signs of toxicity. Key insights into factors governing ADC efficacy were obtained through a robust mathematical framework, including target-mediated dispositional effects relating to antigen density on tumour cells.

Conclusions
Together, our findings offer renewed hope for CTX in PaCa therapy, demonstrating that it may be reformatted as a next-generation ADC and combined with a predictive modelling tool to guide successful translation.
A systematic review of meta-analyses assessing the validity of tumour response endpoints as surrogates for progression-free or overall survival in cancer
Authors: Cooper Katy , Tappenden Paul , Cantrell Anna , Ennis Kate 
Published: September 2020

Abstract
Background
Tumour response endpoints, such as overall response rate (ORR) and complete response (CR), are increasingly used in cancer trials. However, the validity of response-based surrogates is unclear. This systematic review summarises meta-analyses assessing the association between response-based outcomes and overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP).

Methods
Five databases were searched to March 2019. Meta-analyses reporting correlation or regression between response-based outcomes and OS, PFS or TTP were summarised.

Results
The systematic review included 63 studies across 20 cancer types, most commonly non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and breast cancer. The strength of association between ORR or CR and either PFS or OS varied widely between and within studies, with no clear pattern by cancer type. The association between ORR and OS appeared weaker and more variable than that between ORR and PFS, both for associations between absolute endpoints and associations between treatment effects.

Conclusions
This systematic review suggests that response-based endpoints, such as ORR and CR, may not be reliable surrogates for PFS or OS. Where it is necessary to use tumour response to predict treatment effects on survival outcomes, it is important to fully reflect all statistical uncertainty in the surrogate relationship.
Global trends in clinical trials involving pluripotent stem cells: a systematic multi-database analysis
Authors: Deinsberger Julia , Reisinger David , Weber Benedikt 
Published: September 2020

AbstractPluripotent stem cells (PSCs) hold great potential for novel therapeutic approaches to regenerate or replace functionally impaired tissues. Since the introduction of the induced pluripotent stem cell technology in 2006, the number of scientific publications on this topic has constantly been increasing. However, so far no therapy based on PSCs has found its way into routine clinical use. In this study, we examined research trends related to clinical trials involving PSCs based on data obtained from ClinicalTrials.gov, the ICTRP database from the World Health Organization, as well as from a search of all individual databases that are included in the ICTRP using a multistep search algorithm. Following a stringent inclusion/exclusion procedure 131 studies remained that could be classified as clinical trials involving PSCs. The magnitude of these studies (77.1%) was observational, which implies that no cells were transplanted into patients, and only a minority of studies (22.9%) were of an interventional study type. The number of clinical trials involving induced pluripotent stem cells (iPSCs, 74.8%) was substantially higher than the one involving embryonic stem cells (ESCs, 25.2%). However, the picture changes completely when focusing on interventional studies, where in the majority (73.3%) of cases ESCs were used. Interestingly, also the study duration was significantly shorter for interventional versus observational trials (p = 0.002). When focusing on the geographical study regions, it became obvious that the greatest part of all observational trials was performed in the USA (41.6%) and in France (16.8%), while the magnitude of interventional studies was performed in Asian countries (China 36.7%, Japan 13.3%, South Korea 10.0%) and in the field of ophthalmology. In summary, these results indicate that only a limited number of trials were focusing on the actual transplantation of PSCs into patients in a rather narrow field of diagnoses. The future will tell us, if the iPSC technology will ultimately overcome the current challenges and will finally make its way into routine clinical use.
Ehrlichia chaffeensis and E. canis hypothetical protein immunoanalysis reveals small secreted immunodominant proteins and conformation-dependent antibody epitopes
Authors: Luo Tian , Patel Jignesh G. , Zhang Xiaofeng , Walker David H. , McBride Jere W. 
Published: September 2020

AbstractImmunomolecular characterization of Ehrlichia chaffeensis (E. ch.) and E. canis (E. ca.) has defined protein orthologs, including tandem repeat proteins (TRPs) that have immunodominant linear antibody epitopes. In this study, we combined bioinformatic analysis and cell-free protein expression to identify undiscovered immunoreactive E. ch. and E. ca. hypothetical proteins. Antigenicity of the E. ch. and E. ca. ORFeomes (n = 1105 and n = 925, respectively) was analyzed by the sequence-based prediction model ANTIGENpro, and we identified ~250 ORFs in each respective ORFeome as highly antigenic. The hypothetical proteins (E. ch. n = 93 and E. ca. n = 98) present in the top 250 antigenic ORFs were further investigated in this study. By ELISA, 46 E. ch. and 30 E. ca. IVTT-expressed hypothetical proteins reacted with antibodies in sera from naturally E. ch.-infected patients or E. ca.-infected dogs. Moreover, 15 E. ch. and 16 E. ca. proteins consistently reacted with a panel of sera from patients or dogs, including many that revealed the immunoreactivity of “gold standard” TRPs. Antibody epitopes in most (>70%) of these proteins exhibited partial or complete conformation-dependence. The majority (23/31; 74%) of the major immunoreactive proteins identified were small (≤250 aa), and 20/31 (65%) were predicted to be secreted effectors. Unlike the strong linear antibody epitopes previously identified in TRP and OMP orthologs, there were contrasting differences in the E. ch. and E. ca. antigenic repertoires, epitopes and ortholog immunoreactivity. This study reveals numerous previously undefined immunodominant and subdominant antigens, and illustrates the breadth, complexity, and diversity of immunoreactive proteins/epitopes in Ehrlichia.
Factors controlling accumulation of organic carbon in a rift-lake, Oligocene Vietnam
Authors: Rizzi M. , Hovikoski J. , Schovsbo N. H. , Therkelsen J. , Olivarius M. , Nytoft H. P. , Nga L. H. , Thuy N. T. T. , Toan D. M. , Bojesen-Koefoed J. , Petersen H. I. , Nielsen L. H. , Abatzis I. , Korte C. , Fyhn M. B. W. 
Published: September 2020

AbstractUnderstanding of the processes of petroleum source rock (SR) accumulation in lacustrine rift basins and the behavior of lake systems as long-term carbon sinks is fragmentary. Investigation of an 800 m thick (500 m core and ~ 300 m outcrop), deep-lacustrine, Oligocene section in Vietnam, provides a rare insight into the controls and deposition of organic carbon (OC) and SR formation in continental rift basins. A multidisciplinary dataset, combining elemental data, inorganic and organic geochemistry with sedimentology, shows that the richest alginite-prone, sapropelic SR developed during periods of relative tectonic quiescence characterized by moderate primary productivity in a mainly dysoxic lacustrine basin. Increased rift activity and further development of graben morphology intensified water column stratification and anoxia, which hindered nutrient recycling. Sapropelic organic matter (OM) continued to accumulate, but with increasing amorphous OM content and decreasing total OC values. Periods of increased seasonality were characterized by thermocline weakening, enhanced mixing of water columns, increased primary productivity and diatom blooming. The results suggest that a change from dysoxia towards anoxia or extreme primary productivity does not necessarily enhance OC burial and SR quality. External nutrient input from a phosphate-rich hinterland is sufficient for sapropel formation, whereas the main limiting factor is methanogenesis.
An algorithm to quantify intratumor heterogeneity based on alterations of gene expression profiles
Authors: Li Mengyuan , Zhang Zhilan , Li Lin , Wang Xiaosheng 
Published: September 2020

AbstractIntratumor heterogeneity (ITH) is a biomarker of tumor progression, metastasis, and immune evasion. Previous studies evaluated ITH mostly based on DNA alterations. Here, we developed a new algorithm (DEPTH) for quantifying ITH based on mRNA alterations in the tumor. DEPTH scores displayed significant correlations with ITH-associated features (genomic instability, tumor advancement, unfavorable prognosis, immunosuppression, and drug response). Compared to DNA-based ITH scores (EXPANDS, PhyloWGS, MATH, and ABSOLUTE), DEPTH scores had stronger correlations with antitumor immune signatures, cell proliferation, stemness, tumor advancement, survival prognosis, and drug response. Compared to two other mRNA-based ITH scores (tITH and sITH), DEPTH scores showed stronger and more consistent associations with genomic instability, unfavorable tumor phenotypes and clinical features, and drug response. We further validated the reliability and robustness of DEPTH in 50 other datasets. In conclusion, DEPTH may provide new insights into tumor biology and potential clinical implications for cancer prognosis and treatment.
Work function seen with sub-meV precision through laser photoemission
Authors: Ishida Y. , Jung J. K. , Kim M. S. , Kwon J. , Kim Y. S. , Chung D. , Song I. , Kim C. , Otsu T. , Kobayashi Y. 
Published: September 2020

AbstractElectron emission can be utilised to measure the work function of the surface. However, the number of significant digits in the values obtained through thermionic-, field- and photo-emission techniques is typically just two or three. Here, we show that the number can go up to five when angle-resolved photoemission spectroscopy (ARPES) is applied. This owes to the capability of ARPES to detect the slowest photoelectrons that are directed only along the surface normal. By using a laser-based source, we optimised our setup for the slow photoelectrons and resolved the slowest-end cutoff of Au(111) with the sharpness not deteriorated by the bandwidth of light nor by Fermi-Dirac distribution. The work function was leveled within ±0.4 meV at least from 30 to 90 K and the surface aging was discerned as a meV shift of the work function. Our study opens the investigations into the fifth significant digit of the work function.
A pyridinium anionic ring-opening reaction applied to the stereodivergent syntheses of Piperaceae natural products
Authors: Primdahl Karoline G. , Nolsøe Jens M. J. , Aursnes Marius 
Published: September 2020

Expanding the scope of a pyridinium ring-opening reaction, a practical oxidation protocol has been devised to access isomerically pure bromodiene esters. The utility is demonstrated in a divergent strategy to obtain two natural TRPV1 agonist motifs.
The interacting nature of dwarf galaxies hosting superluminous supernovae
Authors: Ørum Simon Vanggaard , Ivens David Lykke , Strandberg Patrick , Leloudas Giorgos , Man Allison W. S. , Schulze Steve 
Published: September 2020

Context. Type I superluminous supernovae (SLSNe I) are rare, powerful explosions whose mechanism and progenitors remain elusive. Several studies have shown a preference for SLSNe I to occur in low-metallicity, actively star-forming dwarf galaxies.
Aims. We investigate whether the host galaxies of SLSNe I show increased evidence for interaction. Galaxy interaction can trigger star formation and provide favourable conditions for these exceptional explosions to take place.
Methods. Based on SLSN host galaxy images obtained with the Hubble Space Telescope (HST), we narrowed down a sample of 42 images obtained in the rest-frame ultraviolet over the redshift range between 0 <  z <  2. The number of host galaxy companions was measured by counting the number of objects detected within a given projected radius from the host. As a comparison, we used two different Monte Carlo-based methods to estimate the expected average number of companion objects in the same HST images, as well as a sample of 32 dwarf galaxies that have hosted long gamma-ray bursts (GRBs).
Results. About 50% of SLSN I host galaxies have at least one major companion (within a flux ratio of 1:4) within 5 kpc. The average number of major companions per SLSN I host galaxy is 0.70−0.14+0.19. Our two Monte Carlo comparison methods yield a lower number of companions for random objects of similar brightness in the same image or for the SLSN host after randomly redistributing the sources in the same image. The Anderson-Darling test shows that this difference is statistically significant (p-value < 10−3) independent of the redshift range. The same is true for the projected distance distribution of the companions. The SLSN I hosts are, thus, found in areas of their images, where the object number density is greater than average. The SLSN I hosts have more companions than GRB hosts (0.44−0.13+0.25 companions per host distributed over 25% of the hosts) but the difference is not statistically significant. The difference between their separations is, however, marginally significant with SLSN companions being closer, on average, than those of GRBs.
Conclusions. The dwarf galaxies hosting SLSNe I are often part of interacting systems. This suggests that SLSNe I progenitors are formed after a recent burst of star formation. Low metallicity alone cannot explain this tendency.
Universalité de la saveur leptonique
Authors: Becirevic Damir , Leroy Olivier , Polci Francesco , Wormser Guy 
Published: September 2020

Des résultats récents semblent suggérer que les trois leptons chargés (l’électron, le muon et le tau) ne se comporteraient pas de la même façon vis-à-vis de l’interaction faible, l’une des quatre forces fondamentales. S’ils sont confirmés, ces soupçons pourraient être une indication de nouveaux phénomènes fondamentaux.
Cet article fait le point sur ce questionnement qui intrigue et excite le monde de la physique des particules aujourd’hui, en testant l’universalité de la saveur des leptons dans la désintégration des mésons B.