bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eradicating Metastatic Cancer and the Eco-Evolutionary Dynamics of Anthropocene Extinctions
Authors: Gatenby Robert A. , Artzy-Randrup Yael , Epstein Tamir , Reed Damon R. , Brown Joel S. 
Published: November 2019

Abstract

Curative therapy for metastatic cancers is equivalent to causing extinction of a large, heterogeneous, and geographically dispersed population. Although eradication of dinosaurs is a dramatic example of extinction dynamics, similar application of massive eco-evolutionary force in cancer treatment is typically limited by host toxicity. Here, we investigate the evolutionary dynamics of Anthropocene species extinctions as an alternative model for curative cancer therapy. Human activities can produce extinctions of large, diverse, and geographically distributed populations. The extinction of a species typically follows a pattern in which initial demographic and ecological insults reduce the size and heterogeneity of the population. The surviving individuals, with decreased genetic diversity and often fragmented ecology, are then vulnerable to small stochastic perturbations that further reduce the population until extinction is inevitable. We hypothesize large, diverse, and disseminated cancer populations can be eradicated using similar evolutionary dynamics. Initial therapy is applied to reduce population size and diversity and followed by new treatments to exploit the eco-evolutionary vulnerability of small and/or declining populations. Mathematical models and computer simulations demonstrate initial reductive treatment followed immediately by demographic and ecological perturbations, similar to the empirically derived treatment of pediatric acute lymphocytic leukemia, can consistently achieve curative outcomes in nonpediatric cancers.

Significance:
Anthropocene extinctions suggest a strategy for eradicating metastatic cancers in which initial therapy, by reducing the size and diversity of the population, renders it vulnerable to extinction by rapidly applied additional perturbations.
Detection of Circulating and Disseminated Neuroblastoma Cells Using the ImageStream Flow Cytometer for Use as Predictive and Pharmacodynamic Biomarkers
Authors: Merugu Swathi , Chen Lindi , Gavens Elizabeth , Gabra Hany , Brougham Mark , Makin Guy , Ng Antony , Murphy Dermot , Gabriel Alem S. , Robinson Michael L. , Wright Jennifer H. , Burchill Susan A. , Humphreys Angharad , Bown Nick , Jamieson David , Tweddle Deborah A. 
Published: November 2019

Abstract

Purpose:
Circulating tumor cells (CTCs) serve as noninvasive tumor biomarkers in many types of cancer. Our aim was to detect CTCs from patients with neuroblastoma for use as predictive and pharmacodynamic biomarkers.

Experimental Design:
We collected matched blood and bone marrow samples from 40 patients with neuroblastoma to detect GD2+/CD45− neuroblastoma CTCs from blood and disseminated tumor cells (DTCs) from bone marrow using the Imagestream Imaging flow cytometer (ISx). In six cases, circulating free DNA (cfDNA) extracted from plasma isolated from the CTC sample was analyzed by high-density single-nucleotide polymorphism (SNP) arrays.

Results:
CTCs were detected in 26 of 42 blood samples (1–264/mL) and DTCs in 25 of 35 bone marrow samples (57—291,544/mL). Higher numbers of CTCs in patients with newly diagnosed, high-risk neuroblastoma correlated with failure to obtain a complete bone marrow (BM) metastatic response after induction chemotherapy (P &lt; 0.01). Ex vivo Nutlin-3 (MDM2 inhibitor) treatment of blood and BM increased p53 and p21 expression in CTCs and DTCs compared with DMSO controls. In five of six cases, cfDNA analyzed by SNP arrays revealed copy number abnormalities associated with neuroblastoma.

Conclusions:
This is the first study to show that CTCs and DTCs are detectable in neuroblastoma using the ISx, with concurrently extracted cfDNA used for copy number profiling, and may be useful as pharmacodynamic biomarkers in early-phase clinical trials. Further investigation is required to determine whether CTC numbers are predictive biomarkers of BM response to first-line induction chemotherapy.
A Virus-Infected, Reprogrammed Somatic Cell–Derived Tumor Cell (VIReST) Vaccination Regime Can Prevent Initiation and Progression of Pancreatic Cancer
Authors: Lu Shuangshuang , Zhang Zhe , Du Pan , Chard Louisa S. , Yan Wenli , El Khouri Margueritte , Wang Zhizhong , Zhang Zhongxian , Chu Yongchao , Gao Dongling , Zhang Qinxian , Zhang Lirong , Nagano Ai , Wang Jun , Chelala Claude , Liu Jing , Chen Jiekai , Liu Pentao , Dong Yunshu , Wang Shengdian , Li Xiaozhu , Dong Jianzeng , Lemoine Nick R. , Pei Duanqing , Wang Yaohe 
Published: November 2019

Abstract

Purpose:
Pancreatic cancer remains one of the most lethal cancers, and late detection renders most tumors refractory to conventional therapies. Development of cancer prophylaxis may be the most realistic option for improving mortality associated with this disease. Here, we develop a novel individualized prophylactic and therapeutic vaccination regimen using induced pluripotent stem cells (iPSC), gene editing, and tumor-targeted replicating oncolytic viruses.

Experimental Design:
We created a Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime. iPSCs from healthy cells were induced to pancreatic tumor cells using in situ gene editing via stable provision of KRasG12D and p53R172H tumor driver mutations. These cells were preinfected with oncolytic Adenovirus (AdV) as prime or Vaccinia virus (VV) as boost, to improve vaccine immunogenicity, prior to delivery of vaccines in a sequential regime to young KPC transgenic mice, genetically programmed to develop pancreatic cancer, to prevent and delay disease development.

Results:
Tumor cells preinfected with oncolytic AdV as prime or VV as boost were the best regime to induce tumor-specific immunity. iPSC-derived tumor cells were highly related in antigen repertoire to pancreatic cancer cells of KPC transgenic mice, suggesting that an individual's stem cells can provide an antigenically matched whole tumor cell vaccine. The VIReST vaccination primed tumor-specific T-cell responses, resulting in delayed disease emergence and progression and significantly prolonged survival of KPC transgenic mice. Importantly, this regime was well-tolerated and nontoxic.

Conclusions:
These results provide both proof of concept and a robust technology platform for the development of personalized prophylactic cancer vaccines to prevent pancreatic malignancies in at-risk individuals.
Myeloid Cells Orchestrate Systemic Immunosuppression, Impairing the Efficacy of Immunotherapy against HPV+ Cancers
Authors: Galliverti Gabriele , Wullschleger Stephan , Tichet Mélanie , Murugan Dhaarini , Zangger Nadine , Horton Wesley , Korman Alan J. , Coussens Lisa M. , Swartz Melody A. , Hanahan Douglas 
Published: November 2019

AbstractCancers induced by human papillomaviruses (HPV) should be responsive to immunotherapy by virtue of expressing the immunogenic oncoproteins E6/E7. However, advanced forms of cervical cancer, driven by HPV, are poorly responsive to immune response–enhancing treatments involving therapeutic vaccination against these viral neoantigens. Leveraging a transgenic mouse model of HPV-derived cancers, K14HPV16/H2b, we demonstrated that a potent nanoparticle-based E7 vaccine, but not a conventional “liquid” vaccine, induced E7 tumor antigen–specific CD8+ T cells in cervical tumor–bearing mice. Vaccination alone or in combination with anti-PD-1/anti-CTLA4 did not elicit tumor regression nor increase CD8+ T cells in the tumor microenvironment (TME), suggesting the presence of immune-suppressive barriers. Patients with cervical cancer have poor dendritic cell functions, have weak cytotoxic lymphocyte responses, and demonstrate an accumulation of myeloid cells in the periphery. Here, we illustrated that myeloid cells in K14HPV16/H2b mice possess potent immunosuppressive activity toward antigen-presenting cells and CD8+ T cells, dampening antitumor immunity. These immune-inhibitory effects inhibited synergistic effects of combining our oncoprotein vaccine with immune checkpoint–blocking antibodies. Our data highlighted a link between HPV-induced cancers, systemic amplification of myeloid cells, and the detrimental effects of myeloid cells on CD8+ T-cell activation and recruitment into the TME. These results established immunosuppressive myeloid cells in lymphoid organs as an HPV+ cancer–induced means of circumventing tumor immunity that will require targeted abrogation to enable the induction of efficacious antitumor immune responses.
Plant and fungi diversity of Devi Pindiyan Valley in Trikuta Hills of northwestern Himalaya, India
Authors: Thakur Sajan , Dutt Harish Chander , Singh Bikarma , Sharma Yash Pal , Tashi Nawang , Charak Rajinder Singh , Sharma Geeta , Vidyarathi Om Prakash , Iqbal Tasir , Singh Bishander , Kumar Kewal 
Published: November 2019

The Devi Pindiyan Valley, an abode of Goddess Vaishno Devi, in Trikuta Hills (western Himalaya) is a unique hill-top land ecosystem with a diverse regional mixed subtropical and temperate flora. Because of its suitable geographic location, specific and unique habitat conditions, this mountainous belt of Shivalik Himalaya has a large number of endemic and threatened plant species. This study presents information on the plant diversity of Devi Pindiyan Valley of Trikuta Hills. Several line-transect (100m N-S and 100 E-W) surveys were conducted in which nested quadrats of 10m × 10m were laid for trees, within which interspersed two 5m × 5m sub-quadrats for shrubs and five 1m × 1m sub-quadrants for herbs at different places for determination of floristic composition. In the diverse habitats of this valley, we recorded 213 vascular plant species belonging to 164 genera under 71 families. This study area also harbors rich diversity of fungi, where the most visible 7 species of macrofungi belongs to 7 genera and 4 families were documented. Out of the documented species, 35 species have been categorized as threatened based on the latest IUCN Red list criteria, while 178 species are included in the catalogue of world life. Engelhardtia spicata Lechen ex Blume var. integra (Kurz) Manning ex Steenis has been categorized as Least Concerned (LC) by IUCN Red List site. The species diversity indicates the high conservation value of this area and documenting such an ecologically rich ecosystem becomes a prerequisite for developing and formulating conservation-cum-management strategies. Therefore, we recommend there is need for ecological research in terms of biodiversity conservation on Devi Pindiyan Valley and similar ecosystems.
On the floral biology and pollination of a rare Twining Liana Sarcolobus carinatus Wall. (Asclepiadoideae: Apocynaceae) in Coringa Mangrove Forest, Andhra Pradesh, India
Authors: Raju A.J. Solomon 
Published: November 2019

Sarcolobus carinatus is a rare twining liana distributed towards landward side at Coringa Mangrove Forest. It exhibits pheno-events, leaf fall, leaf flushing, flowering and fruiting sequentially from May-December. It is a hermaphroditic species with specialized pollination system which is substantiated by corolline and staminal coronas. It is pollinated by carpenter bees. Seed dispersal includes anemochory and hydrochory.
The distribution of blue-green algae (Cyanobacteria) from the paddy fields of Patan and Karad tehsils of Satara District, Maharashtra, India
Authors: Ghadage Sharada Jagannath , Karande Vaneeta Chandrashekhar 
Published: November 2019

The distribution pattern of blue-green algae was studied from paddy fields of Patan and Karad tehsils in relation to physico-chemical properties of soil, viz., pH, electrical conductivity, organic carbon %, available N, P, and K. Paddy field soil samples of 38 localities from Patan and 28 localities from Karad were analysed. One-hundred-and-thirty-seven species belonging to 35 genera of 10 families from three orders were encountered from paddy field soils of both the tehsils. Out of 66 soil samples 93.65% samples showed occurrence of unicellular, heterocystous and non heterocystous forms while 6.34% soil samples showed only non heterocystous forms. Anabaena and Oscillatoria were found to be of common occurrence. Significant variation was not observed in distribution pattern of blue-green algal forms in relation to physico-chemical properties during successive surveys.
Cordia diffusa K.C. Jacob, the Kovai Manjack (Boraginaceae): a highly threatened steno-endemic species from Coimbatore City, Tamil Nadu, India
Authors: Arumugam S. , Kumar K. Sampath , Karthik B. , Ravichandran V. 
Published: November 2019

Cordia diffusa K.C. Jacob, belonging to Boraginaceae, discovered in 1938 and named by K.C. Jacob in 1944, is a little-known and the only narrow endemic but neglected plant of Coimbatore City. The lectotype of the steno-endemic is determined and the current status, distribution, potential threats, bioprospecting potential, and suggestions for conservation of the species are discussed. The collection of steno-endemic plant during intensive exploration in its type locality nearly after 90 years is of phytogeographic and conservation significance. The endemic is proposed the category of Critically Endangered (CR) based on criterion D of IUCN (as per versions 3.1 & 13). C. diffusa can be protected by promoting awareness of the rarity of native species and mass propagation through vegetative means so as to introduce it in gardens, parks, and avenues, etc. at once in the city.
Complementary bat (Mammalia: Chiroptera) survey techniques uncover two new country records for Nigeria
Authors: Tanshi Iroro , Ogbeibu Anthony Ekata , Bates Paul Jeremy James 
Published: November 2019

Knowledge of the bat fauna in Nigeria is limited due to use of outdated collection techniques, and infrequent sampling effort. To advance knowledge of bat diversity in the country, a survey of bats from three localities:—Emu, Okomu National Park (ONP), and Ososo—in southern Nigeria was conducted using mist nets set at canopy and at ground level from February–September 2011. During 28 capture nights involving a total of 202.7 mist net/nights, 239 individuals belonging to 27 bat species in eight families (Emballonuridae, Hipposideridae, Megadermatidae, Molossidae, Nycteridae, Pteropodidae, Rhinolophidae, and Vespertilionidae) were recorded. A total of 130, 64, 45 individuals of 8, 13 and 11 species were recorded from Emu, Okomu, and Ososo, respectively. Two new country records, Casinycteris campomaanensis and Chaerephon aloysiisabaudiae, both collected from Okomu National Park, are reported for Nigeria. Whereas the former species was collected in a canopy high stacked mist net setup, the latter was collected in a ground level mist net, demonstrating the value of employing contemporary and complementary sampling techniques especially in such understudied regions of Africa.
Association Between Nitrate‐Reducing Oral Bacteria and Cardiometabolic Outcomes: Results From ORIGINS
Authors: Goh Charlene E. , Trinh Pauline , Colombo Paolo C. , Genkinger Jeanine M. , Mathema Barun , Uhlemann Anne‐Catrin , LeDuc Charles , Leibel Rudolph , Rosenbaum Michael , Paster Bruce J. , Desvarieux Moise , Papapanou Panos N. , Jacobs David R. , Demmer Ryan T. 
Published: November 2019

Background
The enterosalivary nitrate‐nitrite‐nitric oxide pathway is an alternative pathway of nitric oxide generation, potentially linking the oral microbiome to insulin resistance and blood pressure (BP). We hypothesized that increased abundance of nitrate‐reducing oral bacteria would be associated with lower levels of cardiometabolic risk cross‐sectionally.

Methods and Results

ORIGINS
(Oral Infections, Glucose Intolerance, and Insulin Resistance Study) enrolled 300 diabetes mellitus–free adults aged 20 to 55 years (mean=34±10 years) (78% women). Microbial
DNA
was extracted from subgingival dental plaque (n=281) and V3–V4 regions of the 16S
rRNA
gene were sequenced to measure the relative abundances of 20 a priori
–
selected taxa with nitrate‐reducing capacity. Standardized scores of each taxon's relative abundance were summed, producing a nitrate‐reducing taxa summary score (
NO
3
TSS
) for each participant. Natural log‐transformed homeostatic model assessment of insulin resistance, plasma glucose, systolic BP, and diastolic BP were regressed on
NO
3
TSS
in multivariable linear regressions; prediabetes mellitus and hypertension prevalence were regressed on
NO
3
TSS
using modified Poisson regression models. Nitrate‐reducing bacterial species represented 20±16% of all measured taxa. After multivariable adjustment, a 1‐
SD
increase in
NO
3
TSS
, was associated with a −0.09 (95%
CI
, −0.15 to −0.03) and −1.03 mg/dL (95%
CI
, −1.903 to −0.16) lower natural log‐transformed homeostatic model assessment of insulin resistance and plasma glucose, respectively.
NO
3
TSS
was associated with systolic BP only among patients without hypertension; 1‐
SD
increase in
NO
3
TSS
was associated with −1.53 (95%
CI
, −2.82 to −0.24) mm Hg lower mean systolic BP. No associations were observed with prediabetes mellitus and hypertension.

Conclusions
A higher relative abundance of oral nitrate‐reducing bacteria was associated with lower insulin resistance and plasma glucose in the full cohort and with mean systolic BP in participants with normotension.
Legality of China’s Entitlements of Historic Rights beyond the UNCLOS in the South China Sea
Authors: Li Renyuan 
Published: November 2019

Abstract
In the Award of the South China Sea Arbitration, the Tribunal concluded that the Convention had superseded any historic rights in excess of the limits imposed by the Convention. Consequently, China’s claim of historic rights in the relevant part encompassed by the nine-dashed lines in the South China Sea exceeded the limits of China’s maritime entitlements under the Convention. But an analysis on the context and negotiation history of paragraph 8 of the preamble and issues related to historic rights in the Convention leads to an opposite conclusion. For the issues related to historic rights, the negotiation history of the Convention indicated that the Convention does not supersede any historic rights but left lacunae on related issues. According to the text and negotiation history of paragraph 8 of the Convention, historic rights were not superseded but were regulated by general international law.
Dispersion in the Open Ocean Seasonal Pycnocline at Scales of 1–10 km and 1–6 days
Authors: Sundermeyer Miles A. , Birch Daniel A. , Ledwell James R. , Levine Murray D. , Pierce Stephen D. , Kuebel Cervantes Brandy T. 
Published: November 2019

AbstractResults are presented from two dye release experiments conducted in the seasonal thermocline of the Sargasso Sea, one in a region of low horizontal strain rate (~10−6 s−1), the second in a region of intermediate horizontal strain rate (~10−5 s−1). Both experiments lasted ~6 days, covering spatial scales of 1–10 and 1–50 km for the low and intermediate strain rate regimes, respectively. Diapycnal diffusivities estimated from the two experiments were κz = (2–5) × 10−6 m2 s−1, while isopycnal diffusivities were κH = (0.2–3) m2 s−1, with the range in κH being less a reflection of site-to-site variability, and more due to uncertainties in the background strain rate acting on the patch combined with uncertain time dependence. The Site I (low strain) experiment exhibited minimal stretching, elongating to approximately 10 km over 6 days while maintaining a width of ~5 km, and with a notable vertical tilt in the meridional direction. By contrast, the Site II (intermediate strain) experiment exhibited significant stretching, elongating to more than 50 km in length and advecting more than 150 km while still maintaining a width of order 3–5 km. Early surveys from both experiments showed patchy distributions indicative of small-scale stirring at scales of order a few hundred meters. Later surveys show relatively smooth, coherent distributions with only occasional patchiness, suggestive of a diffusive rather than stirring process at the scales of the now larger patches. Together the two experiments provide important clues as to the rates and underlying processes driving diapycnal and isopycnal mixing at these scales.
Outcome Comparison of Graft Bridging and Superior Capsule Reconstruction for Large to Massive Rotator Cuff Tears: A Systematic Review
Authors: Lin Jinrong , Sun Yaying , Chen Qingyan , Liu Shaohua , Ding Zheci , Chen Jiwu 
Published: November 2019

Background: Graft bridging (GB) and superior capsule reconstruction (SCR) were developed to treat large to massive rotator cuff tears (RCTs); however, the outcome differences between GB and SCR remain unclear. Purpose: To systematically review and compare the outcomes of GB and SCR for large to massive RCT. Study Design: Systematic review. Methods: A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of GB or SCR were included according to the inclusion and exclusion criteria. The primary outcome was Constant-Murley score at the final follow-up. Secondary outcomes included the American Shoulder and Elbow Surgeons score, visual analog scale score for pain, active shoulder range of motion, and graft healing rate. Complication rate was the safety outcome measure. Outcomes were summarized into group SCR and group GB, and the results were compared statistically ( P < .05). Results: A total of 23 studies were included in this review: 238 repairs from the 5 studies in group SCR and 593 repairs from the 18 studies in group GB. For group SCR and group GB, the mean age was 61.6 and 63.3 years, and the mean follow-up was 18.0 and 40.1 months, respectively. Overall, both procedures demonstrated improvement of clinical outcomes. When compared with group SCR, group GB had significantly higher mean differences of the Constant-Murley score (41.9 vs 19.8), American Shoulder and Elbow Surgeons score (39.3 vs 33.8), visual analog scale score for pain (4.4 vs 3.4), and active external rotation at side (15.3 vs 9.3). No statistically significant difference was detected in the mean difference of active forward flexion, internal rotation, abduction, and graft healing rate between the groups. The complication rates were 0.84% (2 of 238) in group SCR and 0.67% (4 of 593) in group GB. Conclusion: In general, GB showed significantly better clinical and functional outcomes postoperatively than SCR, with a similar complication rate. The available fair-quality evidence suggested that GB might be a better choice for large to massive RCT. More high-quality randomized controlled studies are required to further evaluate the relative benefits of the 2 procedures.
Assessment of Pharyngitis Management at a University Student Health Services Clinic
Authors: Knoderer Chad A. , Abi-Mansour Tanya V. , Zahn Stephanie O. , Cornelius Abbey , Richardson Kari , Fletcher Maria V. , Nichols Kristen R. 
Published: November 2019

Objective: The objective of this study was to assess the management of students presenting with pharyngitis to a university health clinic. Methods: This was a retrospective cohort study. Electronic medical records of undergraduate students presenting to a university health clinic from January 1, 2012, through December 31, 2014, with complaints of sore throat and a diagnosis code for pharyngitis, tonsillitis, or sore throat were reviewed. Results: Records of 241 patients were screened and 197 patients were included. A rapid antigen detection test (RADT) was obtained in 145 (73.6%) patients. The incidence of group A streptococci (GAS) and non-GAS were 15.2% (30/197) and 10.1% (21/197), respectively. All patients with a positive RADT were prescribed antibiotics, with 13 (46.4%) receiving amoxicillin. Overall, 129 (65%) patients received an antibiotic prescription. Conclusion: Management of pharyngitis at the clinic appears inconsistent with current guidelines. Approximately 2 of every 3 students were prescribed an antibiotic with no clear indication.