bluuebunny/crossref_metadata_2025_split huggingface dataset:
New type of source extension for a two-dimensional special lattice equation and determinant solutions
Authors: Wang Hong-Yan , Zhu Guo-Qing 
Published: January 2021

AbstractWe present a new type of two-dimensional special lattice equations with self-consistent sources using the source generation procedure. Then we obtain the Grammy-type and Casorati-type determinant solutions of the coupled system. Further, we present the one-soliton and two-soliton solutions.
Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
Authors: Almouhanna Fadi , Blagojevic Biljana , Can Suzan , Ghanem Ali , Wölfl Stefan 
Published: January 2021

Abstract
Background
Aerobic glycolysis, discovered by Otto Warburg, is a hallmark of cancer metabolism even though not yet fully understood. The low activity of the cancerous pyruvate kinase isozyme (M2) is thought to play an important role by facilitating the conversion of glycolytic intermediates to other anabolic pathways to support tumors’ high proliferation rate.

Methods
Five breast cancer cell lines representing different molecular subtypes were used in this study where real time measurements of cellular bioenergetics and immunoblotting analysis of energy- and nutrient-sensing pathways were employed to investigate the potential effects of PKM2 allosteric activator (DASA-58) in glucose rewiring.

Results
In this study, we show that DASA-58 can induce pyruvate kinase activity in breast cancer cells without affecting the overall cell survival. The drug is also able to reduce TXNIP levels (an intracellular glucose sensor) probably through depletion of upstream glycolytic metabolites and independent of AMPK and ER signaling. AMPK shows an induction in phosphorylation (T172) in response to treatment an effect that can be potentiated by combining DASA-58 with other metabolic inhibitors.

Conclusions
Altogether, the multifaceted metabolic reprogramming induced by DASA-58 in breast cancer cells increases their susceptibility to other therapeutics suggesting the suitability of the intracellular glucose sensor TXNIP as a marker of PK activity.
Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: a review of recent articles
Authors: Nweze Justus Amuche , Mbaoji Florence N. , Li Yan-Ming , Yang Li-Yan , Huang Shu-Shi , Chigor Vincent N. , Eze Emmanuel A. , Pan Li-Xia , Zhang Ting , Yang Deng-Feng 
Published: January 2021

Abstract
Background
Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis.

Main text
We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020.
Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries.

Conclusions
It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.
Mechanisms of change and heterogeneous treatment effects in psychodynamic and cognitive behavioural therapy for patients with depressive disorder: a randomized controlled trial
Authors: Røssberg J. I. , Evensen J. , Dammen T. , Wilberg T. , Klungsøyr O. , Jones M. , Bøen E. , Egeland R. , Breivik R. , Løvgren A. , Ulberg R. 
Published: January 2021

Abstract
Background
Major depressive disorder (MDD) is a prevalent psychiatric condition associated with significant disability, mortality and economic burden. Cognitive behavioral therapy (CBT) and psychodynamic psychotherapy (PDT) are found to be equally effective for patients with depression. However, many patients do not respond sufficiently to either treatment. To offer individualized treatment, we need to know if some patients benefit more from one of the two therapies. At present little is known about what patient characteristics (moderators) may be associated with differential outcomes of CBT and PDT, and through what therapeutic processes and mechanisms (mediators) improvements occur in each therapy mode. Presently only theoretical assumptions, sparsely supported by research findings, describe what potentially moderates and mediates the treatment effects of CBT and PDT. The overall aim of this study is to examine theoretically derived putative moderators and mediators in CBT and PDT and strengthen the evidence base about for whom and how these treatments works in a representative sample of patients with MDD.

Methods
One hundred patients with a diagnosis of MDD will be randomized to either CBT or PDT. Patients will be treated over 28 weeks with either CBT (one weekly session over 16 weeks and three monthly booster sessions) or PDT (one weekly session over 28 weeks). The patients will be evaluated at baseline, during the course of therapy, at the end of therapy, and at follow-up investigations 1 and 3 years post treatment. A large range of patient and observer rated questionnaires (specific preselected putative moderators and mediators) are included.

Discussion
The clinical outcome of this study may better guide clinicians when deciding what kind of treatment any individual patient should be offered. Moreover, the study aims to further our knowledge of what mechanisms lead to symptom improvement and increased psychosocial functioning.

Trial registration

ClinicalTrials.gov Identifier: NCT03022071.
Bats seek refuge in cluttered environment when exposed to white and red lights at night
Authors: Barré Kévin , Kerbiriou Christian , Ing Ros-Kiri , Bas Yves , Azam Clémentine , Le Viol Isabelle , Spoelstra Kamiel 
Published: January 2021

AbstractBackgroundArtificial light at night is recognized as an increasing threat to biodiversity. However, information on the way highly mobile taxa such as bats spatially respond to light is limited. Following the hypothesis of a behavioural adaptation to the perceived risks of predation, we hypothesised that bats should avoid lit areas by shifting their flight route to less exposed conditions.MethodsUsing 3D acoustic localization at four experimentally illuminated sites, we studied how the distance to streetlights emitting white and red light affected the Probability of bats Flying Inside the Forest (PFIF) versus along the forest edge.ResultsWe show that open-, edge-, and narrow-space foraging bats strongly change flight patterns by increasing PFIF when getting closer to white and red streetlights placed in the forest edge. These behavioural changes occurred mainly on the streetlight side where light was directed.ConclusionsThe results show that bats cope with light exposure by actively seeking refuge in cluttered environment, potentially due to involved predation risks. This is a clear indication that bats make use of landscape structures when reacting to light, and shows the potential of vegetation and streetlight orientation in mitigating effects of light. The study nevertheless calls for preserving darkness as the most efficient way.
Drug supply shortage in Nigeria during COVID-19: efforts and challenges
Authors: Faiva Edward , Hashim Hashim Talib , Ramadhan Mustafa Ahmed , Musa Shingin Kovona , Bchara John , Tuama Yahya Dheyaa , Adebisi Yusuff Adebayo , Kadhim Mustafa Hayder , Essar Mohammad Yasir , Ahmad Shoaib , Lucero-Prisno Don Eliseo 
Published: January 2021

AbstractThe COVID-19 pandemic has resulted in massive disruptions in global supply chains. Nigeria is particularly vulnerable with respect to pharmaceuticals since there is reduced local production and about 70% of the drug supply is imported creating a huge supply–demand disparity particularly in times like COVID-19. Nigeria is in need of huge quantities of quality-assured health commodities to effectively respond to the pandemic. Significant shortages of other essential medicines and medical products across the country could be imminent. Drug scarcity in Nigeria during the COVID-19 pandemic period is because of several accumulated factors, majorly as a result of global lockdown, decreased manufacturing, unaddressed regulatory affairs, poor access to resources by the population, lack of buffer stocks, security instability, and poor funding of the healthcare system. This situation if left unattended, could cause serious drawbacks to the health of the populace as well as the quality of life of Nigerians amid the COVID-19 Pandemic. Appropriate measures should be directed to ensure ethical processes on drug production, importation, pricing, and distribution to avoid such events during unavoidable scenarios, like the COVID-19 pandemic and other public health emergencies.
Multiproxy sedimentological and geochemical analyses across the Lower–Middle Pleistocene boundary: chemostratigraphy and paleoenvironment of the Chiba composite section, central Japan
Authors: Izumi Kentaro , Haneda Yuki , Suganuma Yusuke , Okada Makoto , Kubota Yoshimi , Nishida Naohisa , Kawamata Moto , Matsuzaki Takuya 
Published: January 2021

AbstractThe Chiba composite section (CbCS) in the Kokumoto Formation, Kazusa Group, central Japan is a thick and continuous marine succession that straddles the Lower–Middle Pleistocene boundary and the well-recognized Matuyama–Brunhes paleomagnetic polarity boundary. Although recent studies extensively investigated the CbCS, its chemostratigraphy, particularly around the Lower–Middle Pleistocene boundary, is poorly understood. Therefore, in this study, we performed multiproxy sedimentological and geochemical analyses of the CbCS, including the Chiba section, which is the Global Boundary Stratotype Section and Point for defining the base of the Middle Pleistocene Subseries. The aim of these analyses is to establish the high-resolution chemostratigraphy and to reconstruct the paleoenvironments of its sedimentary basin in detail. We used the K/Ti ratio as a broad proxy for the clastic material grain size of the sediments. Although the K/Ti ratio generally varies throughout the studied interval, the K/Ti ratio especially during Marine Isotope Stage (MIS) 19a shows a variation pattern like those of the foraminiferal oxygen isotope (δ18O) records. The records of the C/N ratio of bulk samples and carbon isotope ratio of the organic carbon (δ13Corg) suggest that the organic matter in the CbCS sediments during MIS 19c mostly originated from marine plankton, whereas the organic matter during MIS 18 and 19a was characterized by a mixture of marine plankton and terrestrial plants. These records are clearly indicative of changes in mixing ratio of marine vs. terrestrial organic matter in association with glacial–interglacial cycles from the late MIS 20 to the early MIS 18. In addition, we calculated the mass accumulation rates (MARs) of organic carbon, biogenic carbonate, and terrigenous material for quantitative interpretations on the paleoenvironmental changes. MAR calculations revealed that the contribution of marine organic carbon relative to terrestrial organic carbon increased during MIS 19c, and that the contribution of the terrigenous material relative to biogenic carbonate decreased during MIS 19c. Furthermore, we observed relatively large variations in the total organic carbon and total nitrogen contents during MIS 19a. These variations were probably caused by the relative decrease in bottom-water oxygen level, which is also supported by our trace-fossil data, although it is not certain whether the increase in organic-carbon flux at ~ 760 ka was due to the synchronous increase in biogenic productivity in surface water. Such a relative decrease in bottom-water oxygen level was partly due to the increased ocean stratification because of the northward displacement of the Kuroshio Extension Front.
Farmers’ awareness of the potential of vetiver grass for soil erosion control on Ogbomoso Agricultural Zone farmlands, south-western Nigeria
Authors: Ewetola E. A. , Fanifosi G. E. , Ezekiel A. A. , Adetona A. A. , Oyewole F. M. , Onatoye N. M. , Idowu I. T. , Akinniku A. K. 
Published: January 2021

Abstract
Background
Soil degradation remains a serious threat to agricultural production. With increase downpour due to climate change effect, more farmlands are exposed to erosion. Therefore, ecologically sound strategies for erosion control are indispensable to farmers, to boost agricultural productivity.

Results
A multistage sampling technique was used to select the respondents for this study, and descriptive and inferential statistics were adopted to determine the farmers’ perception of the awareness, adoption and use of vetiver grass technology in controlling erosion in the study area. A total of four hundred valid questionnaires were subjected to analysis and the result shows that most of the farmers (29%) were between the ages of 41 and 50 years and the average age of the respondents stood at 45.5 years, implying that the farmers were in their productive and active age. Most of the respondents were male and married with an average household size of 5.2. Large number (76%) of the respondents had formal education, which the level ranged from primary to post-secondary education. Large proportion of the respondents engaged in private business as secondary occupation with an average income of $84.6 per cropping season. The effectiveness of vetiver grass adoption and use was significantly influenced by age (P < 0.1), gender (P < 0.01), marital status (P < 0.05), level of education (P < 0.01) and income of the respondents (P < 0.05). Most of the respondents within the ages of 41–50 years were aware of the erosion control potentials of vetiver grass and adopted the grass because it was cheap and affordable, easy to cultivate and maintain, and readily available and perceived to possess the potential effectiveness to control erosion.

Conclusion
Stakeholders are enjoined to increase the awareness of the vetiver grass for increased adoption and utilization, as many farmers were ignorant of the vetiver grass technology for erosion control in the study area.
Utilization of liquid biopsy for advanced gastrointesinal malignancies in a community oncology practice.
Authors: Gupta Niraj K. , Zhang Crystal Siyu , Singh Kirpal , Glass Timothy , Patel Nikhil , Aburajab Murad , Al-Satie Mazen , Crawford Christopher , Anand Aneesha , Tian Jianmin , Rowe Michael , Cantafio Alex , Alkimawi Khalid , Gorantala Kalyan , Swingley Amanda , Puri Sonia , Yousef Mohamad , Shiyab Ala , Harshberger Carolyn , Saxe Jonathan ,   ASCO Oncology
Published: January 2021

127 Background: Liquid biopsy (LB) offers a non-invasive alternative for obtaining genomic signature of malignancies to develop a tailor-made treatment plan. We evaluated the feasibility and impact on clinical management of liquid biopsies performed on patients with advanced gastrointestinal malignancies in a community setting. Methods: A retrospective chart review of adult patients with stage-IV gastrointestinal malignancies was conducted to gather all the pertinent information, including diagnoses, treatment regimens, results of liquid biopsies and any impact on further management. Results: Data on 42 liquid biopsies performed between Aug 2018 and Mar 2020 was collected. M:F ratio was 1.4: 1. Median age was 57yrs (range 31-86). The diagnoses were; Colo-rectal Ca 22(54.7%), pancreatic 9(21.9%), gastric 2(4.7%), biliary 2(4.7%), HCC 2(4.7%), Appendix 1 (2.3%), CUP 1(2.3%) and others 3(7.1%). One (2.3%) LBs was done before first line treatment and 41(97.7%) were done after the failure of first line treatment. There was insufficient sample in the bx to do tissue-NGS for the pt. who had LB before starting treatments. Majority of LBs, 37(88%) were done after the failure of second line/later treatments compared to 5(12%) done after failing the first line treatment. Patient preference and technical challenge to obtain adequate tissue were the commonest reasons for getting the LBs. Results were available in all (100%) the cases. Median turnaround time was 8 days (range:7-13). The commonest mutations were TP53,APC, KRAS, PIK3CA, BRAF, SMAD4. BRCA-2 was identified in 1 pancreatic ca pt. MSI-H was noted in 3 patients; 2 with Colon ca, and 1 with CUP. An actionable alteration was seen in, 40 (95.2%) of the patients. A FDA approved target-matched drug was available for 27/40(67.5%) pts., if we also consider off-label usage. For those who had an alteration, but no FDA approved target-matched drug was available, 13/40 (32.5%), a clinical trial was available for all 13/13 (100%) of the pts.. 43% of those who had a FDA approved target-matched treatment available, but not approved for their disease, were able to receive the drug off-protocol. Two out of 13(15.3%) of the pts. who had a clinical trial available, were enrolled on a study. Conclusions: Liquid biopsies can be efficiently utilized in a community oncology practice. It offers an attractive option to gather genomic information of malignant cells in patients with advanced GI malignancies to be able to deliver state of the art care to all patients, including those who may not have a convenient access to a tertiary center.
Identification of transcriptomic determinants to predict the efficacy of anti-EGFR treatment of colorectal cancer patients.
Authors: Chowdhury Saikat , Shen John Paul Y.C. 
Published: January 2021

130 Background: It is now well known that in colorectal cancer (CRC) activating mutations in KRAS, NRAS, and BRAF confer resistance to anti-EGFR therapy. However, only ~ 40% of patients with RASWT (KRASWT/NRASWT/BRAFWT) tumors respond to therapy. We have used transcriptomic data in addition to somatic mutations to decipher intrinsic resistance mechanisms and identify novel biomarkers of anti-EGFR response in CRC. Methods: The transcriptomic profiles of metastatic CRC patients treated with the anti-EGFR drug cetuximab plus chemotherapy (n = 193) or as a single agent (n = 80) were retrospectively obtained from two independent clinical cohorts (Okita et al., 2018; & Khambata-Ford et al., 2007). Tumor samples were further divided into RASWT and RASMut groups and subsequently in four consensus molecular subtypes (CMS) based on their transcriptomic profile. The transcriptomic profiles of cetuximab treated CRC cell lines (n = 148, Medico et al., 2015) and PDX models (n = 230, Bertotti et al., 2015) were used for validation. Results: In RASWT population of cetuximab plus chemotherapy cohort, the disease control rates (DCR) observed for cetuximab in the second line were 92% (33/36) for CMS2 and 83% (15/18) for CMS4 tumors relative to 50% (2/4) and 59% (13/22) for CMS1 and CMS3 respectively (Chi-square test p-value = 0.037). Similarly, in cetuximab single agent cohort, the DCR were 0% (0/4), 68% (15/22), and 29% (5/17) for CMS1, CMS2, and CMS4, respectively (Chi-square test p-value = 0.029). In the preclinical study of 148 CRC cell lines, 60% (12/20) of CMS2 cell lines with RASWT genes were sensitive to cetuximab, versus no sensitive cell lines from other CMS (CMS1 = 0/4; CMS3 = 0/5; CMS4 = 0/12). In the PDX study, 84% (11/13) of CMS2 tumor showed clinical benefit, followed by CMS4 with 75% (6/8) in RASWT group (CMS1 = 2/5; CMS3 = 2/4). Gene Set Enrichment Analysis (GSEA) of tumor tissue samples identified that Myc (NES = 1.32, FDR = 0.3), E2F (NES = 2.24, FDR = 0.02), and mTOR (NES = 1.54, FDR = 0.1) pathways were active in the cetuximab refractory RASWT CMS2 patients relative to cetuximab sensitive tumors. Similarly, these pathways were also activated (FDR ≤ 0.05) in cetuximab resistant RASWT cell lines and PDX models, suggesting that preclinical models are appropriate for testing of potential therapeutic combinations to overcome resistance to anti-EGFR therapy. Conclusions: Resistance to anti-EGFR therapy in extended RASWT CRC tumors is mediated in part by transcriptional activation and can be predicted by consensus molecular subtype (CMS) and quantifying transcriptional states of Myc, E2F, and mTOR pathway gene sets.
Zanidatamab (ZW25) in HER2-expressing gastroesophageal adenocarcinoma (GEA): Results from a phase I study.
Authors: Meric-Bernstam Funda , Hamilton Erika P. , Beeram Muralidhar , Hanna Diana L. , El-Khoueiry Anthony B. , Kang Yoon-Koo , Lee Keun Wook , Lee Jeeyun , Rha Sun Young , Chaves Jorge M , Oh Do-Youn , Goodwin Rachel Anne , Ajani Jaffer A. , Gray Todd , Woolery Joseph , Elimova Elena 
Published: January 2021

164 Background: For patients with human epidermal growth factor receptor 2 (HER2)-overexpressing GEA, trastuzumab in combination with chemotherapy is the only approved HER2-targeted therapy, and they have limited treatment options after progression. Zanidatamab, a HER2-targeted bispecific antibody, has shown durable anti-tumor activity with good tolerability in a range of HER2-expressing cancers. Methods: In this 3-part Phase 1 study (NCT02892123), zanidatamab (10 mg/kg QW, 20 mg/kg Q2W, or 30 mg/kg Q3W) is administered as a single agent (Parts 1 & 2; QW or Q2W) or in combination with chemotherapy (Part 3; Q2W or Q3W). Eligibility criteria includes GEA with HER2 expression as assessed by immunohistochemistry (IHC) 3+ or IHC 2+, progression after standard of care therapy, and measurable disease per RECIST 1.1 (Part 2 requirement only). Results: In Parts 1 and 2, 36 GEA patients have been treated with zanidatamab (QW [n = 5]; Q2W [n = 31]). In Part 3, 26 GEA patients have been treated (zanidatamab Q2W + (paclitaxel [n = 11] or capecitabine [n = 6]); zanidatamab Q3W + capecitabine [n = 9]). Conclusions: Zanidatamab, both as a single agent and in combination with chemotherapy, is well tolerated with promising and durable anti-tumor activity in heavily pretreated GEA patients (including prior HER2-targeted therapy). These data support further investigation of zanidatamab as a novel therapeutic for patients with HER2-expressing GEA. Clinical trial information: NCT02892123. [Table: see text]