bluuebunny/crossref_metadata_2025 huggingface dataset:
Status of Entrustable Professional Activities (EPA) Implementation at Colleges of Osteopathic Medicine in the United States and Future Considerations
Authors: Linsenmeyer Machelle , Wimsatt Leslie , Speicher Mark , Basehore Pamela , Sexton Patricia S.
Published: September 2020

Context

Competency-based medical education, developmental milestones for residency training, and the single graduate medical education (GME) accreditation system have emerged over the last decade, necessitating new ways to adequately prepare graduates to meet new standards in proficiency, including the 13 Core Entrustable Professional Activities (EPA) for Entering Residency. The American Association of Colleges of Osteopathic Medicine (AACOM) Entrustable Professional Activities (EPA) steering committee has implemented an information-gathering process to provide suggestions for supporting a variety of EPA-related implementation efforts at colleges of osteopathic medicine (COMs) across the country.

Objective

To review the status of EPA implementation at COMs nationally.

Methods

An explanatory mixed-methods design was used to guide information gathering and synthesis of a 41-question survey and interview feedback; the overarching premise of this design was to use qualitative data to build upon initial quantitative findings. This survey was delivered electronically through a link emailed to liaisons at each main, branch, and satellite campus of the 47 schools within the AACOM institutional database. After survey administration, follow-up structured interviews were conducted according to an 18-question script with a purposive sample of 16 institutions with EPA implementation levels ranging from “moderate implementation with reporting” to “full implementation with reporting.” Post-interview, the interview notes were analyzed and results were aggregated for comparison with the original survey findings.

Results

Of the 47 schools surveyed, 42 responded (89.4%). To maintain uniformity in data coding and analysis, 36 of 47 (76.6%) of COMs with independently submitted survey responses were retained in the review. The majority of those respondents (23 of 36; 64%) indicated that their institution was above “somewhat knowledgeable” toward “expert” regarding knowledge of EPAs, but 23 (64%) also indicated “no confidence” or “somewhat confident” regarding EPA implementation. Postinterview results showed that the majority of schools were equally distributed across the “foundational implementation” (10; 28%), “slight implementation” (11; 31%), and “moderate implementation” (11, 31%) categories, with a few schools indicating “no implementation” (2; 5%) or “progressive implementation” (2; 5%).

Conclusion

The results of this review indicate that most osteopathic medical schools are at the early stages of EPA implementation, with emphasis varying by program year in terms of the specific EPAs addressed. Many schools appear engaged in curricular change efforts that will support the advancement of EPA use within their institutions. Faculty development was identified as a continued critical need for a majority of institutions.
Sampling impacts the assessment of tooth growth and replacement rates in archosaurs: implications for paleontological studies
Authors: Kosch Jens C.D. , Zanno Lindsay E.
Published: September 2020

Dietary habits in extinct species cannot be directly observed; thus, in the absence of extraordinary evidence, they must be reconstructed with a combination of morphological proxies. Such proxies often include information on dental organization and function such as tooth formation time and tooth replacement rate. In extinct organisms, tooth formation times and tooth replacement rate are calculated, in part via extrapolation of the space between incremental lines in dental tissues representing daily growth (von Ebner Line Increment Width; VEIW). However, to date, little work has been conducted testing assumptions about the primary data underpinning these calculations, specifically, the potential impact of differential sampling and data extrapolation protocols. To address this, we tested a variety of intradental, intramandibular, and ontogentic sampling effects on calculations of mean VEIW, tooth formation times, and replacement rates using histological sections and CT reconstructions of a growth series of three specimens of the extant archosaurianAlligator mississippiensis. We find transect position within the tooth and transect orientation with respect to von Ebner lines to have the greatest impact on calculations of mean VEIW—a maximum number of VEIW measurements should be made as near to the central axis (CA) as possible. Measuring in regions away from the central axis can reduce mean VEIW by up to 36%, causing inflated calculations of tooth formation time. We find little demonstrable impact to calculations of mean VEIW from the practice of subsampling along a transect, or from using mean VEIW derived from one portion of the dentition to extrapolate for other regions of the dentition. Subsampling along transects contributes only minor variations in mean VEIW (<12%) that are dwarfed by the standard deviation (SD). Moreover, variation in VEIW with distance from the pulp cavity likely reflects idiosyncratic patterns related to life history, which are difficult to control for; however, we recommend increasing the number of VEIW measured to minimize this effect. Our data reveal only a weak correlation between mean VEIW and body length, suggesting minimal ontogenetic impacts. Finally, we provide a relative SD of mean VEIW for Alligator of 29.94%, which can be used by researchers to create data-driven error bars for tooth formation times and replacement rates in fossil taxa with small sample sizes. We caution that small differences in mean VEIW calculations resulting from non-standardized sampling protocols, especially in a comparative context, will produce inflated error in tooth formation time estimations that intensify with crown height. The same holds true for applications of our relative SD to calculations of tooth formation time in extinct taxa, which produce highly variable maximum and minimum estimates in large-toothed taxa (e.g., 718–1,331 days inTyrannosaurus).
Potential COVID-19 papain-like protease PLpro inhibitors: repurposing FDA-approved drugs
Authors: Kouznetsova Valentina L. , Zhang Aidan , Tatineni Mahidhar , Miller Mark A. , Tsigelny Igor F.
Published: September 2020

Using the crystal structure of SARS-CoV-2 papain-like protease (PLpro) as a template, we developed a pharmacophore model of functional centers of the PLpro inhibitor-binding pocket. With this model, we conducted data mining of the conformational database of FDA-approved drugs. This search identified 147 compounds that can be potential inhibitors of SARS-CoV-2 PLpro. The conformations of these compounds underwent 3D fingerprint similarity clusterization, followed by docking of possible conformers to the binding pocket of PLpro. Docking of random compounds to the binding pocket of protease was also done for comparison. Free energies of the docking interaction for the selected compounds were lower than for random compounds. The drug list obtained includes inhibitors of HIV, hepatitis C, and cytomegalovirus (CMV), as well as a set of drugs that have demonstrated some activity in MERS, SARS-CoV, and SARS-CoV-2 therapy. We recommend testing of the selected compounds for treatment of COVID-19
Analysis of the Bank's Health Level and Its Effects on the Profitability of Sharia General Banks Listed in Indonesia's Financial Services Authority Period 2015-2018
Authors: Chairunesia Wieta
Published: September 2020

Aims: To analyze the level of health of sharia general banks in Indonesia and their effects on profitability.

Study Design: The research method used is quantitative descriptive research.

Place and Duration of Study: The sampling technique used was purposive sampling. The study was conducted a Sharia General Bank registered in the Indonesian Financial Services Authority with a research period of 2015-2018.

Methodology: The analytical method used is the inferential statistical analysis test using SmartPLS Professional 3.0 analysis tools, namely with a descriptive test, and inferential statistical analysis.

Results: Sharia Commercial Banks in the 2015-2018 period based on Non-Performing Finance (NPF) have a healthy predicate and have a negative significant effect on profitability. Based on the Fair to Healthy Ratio (FDR) predicate as Healthy, and no significant positive effect on profitability. Based on Good Corporate Governance (GCG) with a healthy predicate, and no significant positive effect on profitability. Based on Operating Efficiency Ratio (OER) with a healthy predicate, and a significant negative effect on profitability. Based on the Capital Adequacy Ratio (CAR) which is categorized as Very Healthy, and no significant positive effect on profitability.

Conclusion: Generally, Islamic commercial banks are in good health. However, the achievement of this soundness level is carried out by always striving to comply with the provisions given by Bank Indonesia, not optimizing the available resources so that the bank remains in a healthy condition while meeting the criteria of Bank Indonesia.
The Effects of Participating in Recreational Games on Health Markers and Reaction Time in Middle-aged Tribal Women
Authors: Murmu Manoj Kumar , Saha Gopal Chandra
Published: September 2020

Background: Taking part in recreational activities, especially outdoors, can greatly improve physical health. People, who take part in park activities such as walking, hiking, or skiing, schedule fewer office visits, maintain lower body fat percentages, and have lower blood pressure and cholesterol levels. Although recreational games was proven to be a useful physical activity to stimulate some health benefits, we do not know if there are significant benefits of recreational games played on a smaller area with fewer players in the middle-age population. Because exercise is known to increase blood flow and oxygen to the skeletal muscles and the brain, it was inferred that exercise would also affect an individual’s reaction time.

Aims: The present study aimed to investigate whether recreational games could improve health and reaction time of middle-aged tribal women after 16 weeks of training. To determine this, twenty subjects gave baseline blood pressure, heart rate, and simple reaction time measurements.

Methodology: Twenty healthy middle-aged tribal women aged 50–55 were randomized in a group to involve in recreational games training (n = 20; age: 52.4 ± 2.48 years). The participants performed 3 training sessions of 40 min per week.

Results: Results from a repeated measure ANOVA indicated a time interaction (pre training, mid training and post training) for Blood Pressure (Systolic), Blood Pressure (Diastolic), Resting Heart Rate and Reaction Time (Audio) in favor of the participants. The results concluded that Recreational games can be an effective training modality to stimulate a decrease in resting HR and reaction time with small improvements in systolic and diastolic Blood Pressure.

Conclusion: To participate in Recreational games only three times per week shows helpful health-related adaptations and decreased reaction time, means there was significant improvement in health markers and reaction time abilities, which may be an affirmative impact to the reduction of the risk of developing lifestyle diseases and is beneficial to people in their daily live.
Understanding the Correlates of Under-five Mortality in Sudan Using Survey Survival Models
Authors: Ayele Dawit Getnet , Satty Ali , Zewotir Temesgen
Published: September 2020

Under-five mortality is among the major public health problems in developing countries, the rate of which is an important factor for a country’s development. For this reason, under-five mortality status is an important outcome to measure for children’s health. This study uses the Cox proportional-hazards model to identify risk factors associated with under-five mortality in Sudan. This study uses the 2014 Sudan Multiple Indicator Cluster Survey (MICS) conducted by the Central Bureau of Statistics in collaboration with several national institutions. The survival Cox proportional-hazards model was used to identify factors that affect under-five child mortality in Sudan. The results show that the weight of a child at birth is positively associated with the under-five child mortality rate. Under-five children who have both small and large weights at birth are at a higher risk of dying before reaching five years. Based on demographic factors associated with under-five mortality, our analysis showed that mothers who were married at the time of the survey are most likely to have higher under-five child mortality as compared to formerly married mothers. In addition to this, that mother’s age at the time of the birth is significantly associated with under-five mortality. Based on the result, the lack of important policies targeting the reduction of socioeconomic inequalities between rural and urban areas is the major problem of public health interventions to improve child health and survival in Sudan.
Biogas Production from Co-digestion of Cotton Yarn Waste and Human Urine
Authors: Twizerimana Maurice , Marimi Milton , Bura Xumay , Nganyi Eric Oyondi
Published: September 2020

Aim: To investigate the feasibility of producing biogas from anaerobic co-digestion of cotton yarn wastes (CY) and human urine (HU) using fresh cow dung as the inoculum.

Study Design: Anaerobic co-digestion of CY waste and HU and CY waste alone were done using batch reactors.

Place and Duration of Study: CY were collected from Rivatex Eastern Africa Limited, Eldoret, Kenya while fresh cow manure used as inoculum was collected from a farm at Moi University, Eldoret, Kenya. Human urine sample was collected in a clean sterile container at Moi University hostel, Eldoret, Kenya. The experimental set up and analyses were performed at Chemical and Process Engineering Laboratory, Moi University, Kenya between January 2020 and May 2020.

Methodology: CY, HU and fresh cow dung were subjected to physicochemical analysis. Batch anaerobic co-digestion of CY and HU, and CY alone were carried out under ambient temperature (25 ± 3 ) conditions for 95 days and 37 days, respectively.

Results: The CY contained 90.46% total solids, 77.12% volatile solids and 9.54% moisture content while the corresponding values for HU were 2.9%, 58.5% and 97.1%, respectively. CY had a high carbon to nitrogen ratio. The biogas yield from anaerobic co-digestion was 35.6% more than digestion of CY alone. The highest daily biogas production for co-digestion and digestion of CY alone were 330 mL and 386 mL on day 12 and 21, respectively. The total biogas yield when CY co-digested for 95 days was 10,125 mL which decreased to 6,519 mL without co-digestion after 37 days.

Conclusion: Our results showed that co-digestion produced more biogas than digestion of CY alone. Conclusively, the presence of HU during anaerobic digestion of CY enhanced the biogas production by more than 35.6% demonstrating that HU could be an effective waste for co-digestion of solid wastes such as CY. Further research should focus on monitoring parameters like temperature, buffering capacity and fatty acid levels to ensure optimal efficiency and maximum biogas yield.
Comprehensive Analysis of Planning Operation and Protection of Microgrid Systems
Authors: Muzzammel Raheel
Published: September 2020

Microgrid is a decentralized system in which electrical sources and loads are connected in a way that operates normally in connection with and in synchronous with conventional grid. This system has the ability to work autonomously by disconnecting from conventional grid in island mode. Microgrid offers large number of advantages in power system. Among them, integration of renewable energy sources, reliability, two-way power flow and cost effectiveness are the significant merits of microgrids. Besides its advantages, different challenges are associated with the planning, operation and protection of microgrid systems. Safe two-way power flow, reliable switching of renewable energy, optimal power flow, quick isolation of faulty part from healthy system and incorporation of energy mix modeling are the major challenges behind its real time implementation. In this research, comprehensive analysis is carried out on the planning, operation and protection of microgrid model. A test system is developed in Matlab/ Simulink in which solar power source, wind power source and diesel power source are modelled and connected to residential, commercial and industrial loads. Optimal power flow is achieved through Newton’s method. In addition to this, operation of microgrid test system is ensured by the observation of voltage, current and power under steady state and transient conditions of wind based power generation, DC and AC parameters for solar power generation and generation and demand of power in the case of diesel based power generation within acceptable limits. Circuit breakers are installed to ensure protection against faults. Priority is made on the basis of promotion of renewable energy sources. Moreover, realization of microgrid is depicted with its hardware prototype.
Histone H3K9 and H3K14 acetylation at the promoter of the LGALS9 gene is associated with mRNA levels in cervical cancer cells
Authors: Armenta‐Castro Erick , Reyes‐Vallejo Tania , Máximo‐Sánchez Daniel , Herrera‐Camacho Irma , López‐López Gustavo , Reyes‐Carmona Sandra , Conde‐Rodríguez Ileana , Ramírez‐Díaz Ivonne , Aguilar‐Lemarroy Adriana , Jave‐Suárez Luis Felipe , Milflores‐Flores Lorena , Santos‐Lopez Gerardo , Reyes‐Leyva Julio , Vallejo‐Ruiz Verónica
Published: September 2020

Galectin‐9 levels have been reported to be altered in several cancer types, but the mechanism that regulates the expression of Galectin‐9 has not been clarified. Galectin‐9 is encoded by the LGALS9 gene, which gives rise to eight mRNA variants. The aims of this study were: (a) to identify the mRNA variants of LGALS9, (b) to characterize CpG methylation and H3K9 and H3K14 histone acetylation at the promoter of the LGALS9 gene, and (c) to characterize the relationship between these modifications and LGALS9 expression level in cervical cancer cells. All mRNA variants were detected in HaCaT (nontumoural keratinocytes) and SiHa cells, and seven were observed in HeLa cells. The promoter region of LGALS9 contains eight CpG dinucleotides. No hypermethylation pattern related to low LGALS9 expression was identified in tumour cells. Chromatin immunoprecipitation analysis demonstrated higher acetylation of H3K9ac and H3K14ac in HaCaT cells, which was related to higher mRNA levels. The presence of the mRNA variants suggests that alternative splicing may regulate the expression of galectin‐9 isoforms. The results of this study suggest that histone acetylation, but not promoter CpG methylation, may be involved in the transcriptional regulation of the LGALS9 gene.
Stretchable and Transparent Ionogels with High Thermoelectric Properties
Authors: Fang Yuanlai , Cheng Hanlin , He Hao , Wang Shan , Li Jianmin , Yue Shizhong , Zhang Lei , Du Zongliang , Ouyang Jianyong
Published: September 2020

Stretchable electronic materials and devices have important applications in flexible electronic systems including wearable electronics and bioelectronics. Convenient electricity generation such as thermoelectric conversion is required for the flexible electronic systems. Hence, it is development of high‐performance thermoelectric materials with high mechanical stretchability would be highly desirable. Here, stretchable and transparent ionogels with high thermoelectric properties are demonstrated. The ionogels made of elastomeric waterborne polyurethane and 1‐ethyl‐3‐methylimidazolium dicyanamide (EMIM:DCA, an ionic liquid) are prepared by solution processing. Their mechanical and electrical properties depend on the loading of EMIM:DCA. The ionogels with 40 wt% EMIM:DCA can have a high mechanical stretchability of up to 156%, low tensile strength of 0.6 MPa, and low Young's modulus of 0.6 MPa. They also exhibit a high ionic thermovoltage of 34.5 mV K−1, high ionic conductivity of 8.4 mS cm−1 and low thermal conductivity of 0.23 W m−1 K−1 at a relative humidity of 90%. As a result, it can have a high ionic figure of merit (ZTi) of 1.3 ± 0.2. Both the thermovoltage and the ZTi value are the highest for stretchable thermoelectric materials. They can be used in ionic thermoelectric capacitors to convert heat into electricity.
Implantable Bioresponsive Nanoarray Enhances Postsurgical Immunotherapy by Activating Pyroptosis and Remodeling Tumor Microenvironment
Authors: Zhao Hongjuan , Song Qingling , Zheng Cuixia , Zhao Beibei , Wu Lixia , Feng Qianhua , Zhang Zhenzhong , Wang Lei
Published: September 2020

Despite the potential of drug‐loaded scaffolds for tumor recurrence and metastasis (TRM) postoperation, their therapeutic benefits are limited by marked immunosuppressive tumor microenvironment (ITME) and drug‐related untargeted toxicity. Herein, an innovative implantable bioresponsive nanoarray is developed to overcome the above limitations. Chemotherapeutics doxorubicin (DOX) and the epigenetic modulator JQ1 are coloaded into tumor‐targeting nanoparticles (HP‐DOX/JQ1 NPs), which are then linked up through a bio‐responsive linker to construct the nanoarray loading with another part of JQ1 (DOX/JQ1‐IBRN). Under high level of H2O2 in TME, the implanted DOX/JQ1‐IBRN disaggregates and release JQ1 while generating small‐sized HP‐DOX/JQ1 NPs for realizing ITME modulation and tumor‐targeting therapy. JQ1 selectively blocks programmed death‐ligand 1 (PD‐L1) mediated immune evasion and reduces regulatory T cells (Tregs)/‐disruptive effect to facilitate immunopositivity. HP‐DOX/JQ1 NPs destroy residual tumor precisely and trigger gasdermin E (GSDME)‐dependent pyroptosis, further enhancing the number and functions of tumor‐infiltrating T lymphocytes for antitumor immunity. It is demonstrated that DOX/JQ1‐IBRN prevents post‐surgical TRM and prolongs survival in multiple murine tumor models with negligible toxicity. This cooperation in tumor accurate pyroptosis and ITME conversion through the implantable nanoarray (a simple, valid, and safe scaffold) is expected to provide crucial insights for post‐surgical treatment.
Origin of the Distinct Thermoelectric Transport Properties of Chalcopyrite ABTe2 (A = Cu, Ag; B = Ga, In)
Authors: Cao Yu , Su Xianli , Meng Fanchen , Bailey Trevor P. , Zhao Jinggeng , Xie Hongyao , He Jian , Uher Ctirad , Tang Xinfeng
Published: September 2020

Despite the same crystal structure and homologous constituent elements, the chalcopyrite compounds ABTe2 (A = Cu, Ag; B = Ga, In) exhibit distinct electronic and thermal transport properties. The aim of this work is to understand the origin of such discrepancy employing experiments and theoretical calculations. The results of Hall coefficient measurements, absorption spectroscopy, and electronic transport studies suggest the deep‐level in‐gap states induced by the native A‐site vacancies play a key role in the observed intrinsic semiconductor to degenerate semiconductor transition and are the origins of the distinct electrical conductivity among ABTe2 compounds. In addition, the cryogenic heat capacity measurements and calculated phonon dispersion relations show that the acoustic and low‐frequency optical modes of AgGaTe2 and AgInTe2 are governed by the vibrations of AgTe clusters while the counterparts of CuGaTe2 and CuInTe2 compounds are dominated by the vibrations of Te atoms, and the coupling between the acoustic and low‐frequency optical modes is notably different among ABTe2 compounds. Specifically, lower avoided‐crossing frequencies, lower sound velocity together with stronger Umklapp process yield lower thermal conductivities of AgGaTe2 and AgInTe2 than CuGaTe2 and CuInTe2. This work provides new insights into the understanding and improvement of electrical and thermal properties toward higher thermoelectric performance of chalcopyrite compounds.
Transparent Fused Nanowire Electrodes by Condensation Coefficient Modulation
Authors: Lee Jaemin , Varagnolo Silvia , Walker Marc , Hatton Ross A.
Published: September 2020

Silver nanowire networks can offer exceptionally high performance as transparent electrodes for stretchable sensors, flexible optoelectronics, and energy harvesting devices. However, this type of electrode suffers from the triple drawbacks of complexity of fabrication, instability of the nanowire junctions, and high surface roughness, which limit electrode performance and utility. Here, a new concept in the fabrication of silver nanowire electrodes is reported that simultaneously addresses all three of these drawbacks, based on an electrospun nanofiber network and supporting substrate having silver vapor condensation coefficients of one and near‐zero, respectively. Consequently, when the whole substrate is exposed to silver vapor by simple thermal evaporation, metal selectively deposits onto the nanofiber network. The advantage of this approach is the simplicity, since there is no mask, chemical or dry metal etching step, or mesh transfer step. Additionally, the contact resistance between nanowires is zero and the surface roughness is sufficiently low for integration into organic photovoltaic devices. This new concept opens the door to continuous roll‐to‐roll fabrication of high‐performance fused silver nanowire electrodes for myriad potential applications.
Ultraflexible, Degradable Organic Synaptic Transistors Based on Natural Polysaccharides for Neuromorphic Applications
Authors: Yang Yahan , Zhao Xiaoli , Zhang Cong , Tong Yanhong , Hu Junli , Zhang Hui , Yang Mihua , Ye Xiaolin , Wang Shuya , Sun Zijing , Tang Qingxin , Liu Yichun
Published: September 2020

Ultraflexible and degradable organic synaptic transistors (OSTs) enable seamless integration with the human body and are capable of disintegrating after completing their specific functions, opening up remarkable new opportunities for “green” electronics in implantable neuromorphic systems, brain‐computer interfaces and wearable artificial intelligence systems. However, it is still an outstanding challenge to realize such synaptic transistors that simultaneously satisfy both ultra flexibility and degradability. The advancement of such electronics critically hinges on the development of ultraflexible and degradable gate dielectrics, which is the vital component to realize synaptic function of transistors. Here, for the first time, a self‐supporting natural dextran membrane is utilized as the gate dielectric to achieve an ultraflexible and degradable OST. The resultant device is only 309 nm thick, and can maintain stable synaptic behavior on various curved surfaces, even on a superfine capillary with the bending radius down to 0.15 mm. After the devices complete their functions, they can rapidly degrade in ambient water without any toxic byproducts, effectively reducing environmental pollution. More strikingly, proton conduction is confirmed to exist in neutral polysaccharides, and the protons originate from the self‐dissociation of water, which provides a meaningful guideline for future synaptic transistors based on neutral natural biomaterials.
Swarming of Perovskite‐Like Bi2WO6 Microrobots Destroy Textile Fibers under Visible Light
Authors: Villa Katherine , Děkanovský Lukáš , Plutnar Jan , Kosina Jiří , Pumera Martin
Published: September 2020

The increasing demand for disposable textiles for multi‐cleansing purposes has led to an uncontrollable accumulation of macro‐ and microdebris in water bodies, resulting in major environmental disruptions and a threat to ecosystems. Considering the emerging nature of this type of contamination, there is still no current treatment to tackle this environmental problem. Here, self‐propelled bismuth tungstate microrobots that can actively move under light irradiation, swarm, and destroy disposable textiles through oxidative pathways are presented. Upon sun‐like illumination, these micromachines attack and degrade both the intertwined network of natural/synthetic textiles and their organic ingredients that are subsequently released into the water. The high efficiency arises from the enhanced intimate contact between the self‐propelled microrobots and the surface of the textiles. This work provides a unique strategy to treat emerging solid waste contamination in water bodies at mild conditions by combining photoactivated microrobots, collective behavior, and photocatalysis.
Engineering of a Core–Shell Nanoplatform to Overcome Multidrug Resistance via ATP Deprivation
Authors: Liu Genhua , Wang Liucan , Liu Junjie , Lu Lu , Mo Dong , Li Ke , Yang Xin , Zeng Rui , Zhang Jixi , Liu Peng , Cai Kaiyong
Published: September 2020

Inhibiting the function of P‐glycoprotein (P‐gp) transporter, which causes drug efflux through adenosine triphosphate (ATP)‐dependent manner, has become an effective strategy to conquer multidrug resistance (MDR) of cancer cells. However, there remains challenges for effective co‐delivery, sequential release of P‐gp modulator and chemotherapeutic agent. In this work, a novel type of core–shell nanoparticle is reported. It can independently encapsulate a high amount (about 683 µg mg−1) of chemotherapeutic agent doxorubicin (DOX) in the mesoporous polydopamine (MPDA) core and glucose oxidase (GOx) in the zeolite imidazolate frameworks‐8 (ZIF‐8) shell, namely MPDA@ZIF‐8/DOX+GOx. The fast release of GOx triggered by acid‐sensitive degradation of the ZIF‐8 shell consumes glucose to starve cancer cells for ATP deprivation and effective suppress ATP‐dependent drug efflux in advance, and then effectively facilitates the accumulation of DOX in MCF‐7/ADR cancer cells. Experiments in vitro and in vivo demonstrate that the fabricated nanosystem can dramatically improve anticancer effects for MDR through sequential release property and exhibit excellent biocompatibility. Overall, this work reveals new insights in the use of GOx for MDR treatment.
Biodegradable Metal–Organic Framework‐Based Microrobots (MOFBOTs)
Authors: Terzopoulou Anastasia , Wang Xiaopu , Chen Xiang‐Zhong , Palacios‐Corella Mario , Pujante Carlos , Herrero‐Martín Javier , Qin Xiao‐Hua , Sort Jordi , deMello Andrew J. , Nelson Bradley J. , Puigmartí‐Luis Josep , Pané Salvador
Published: September 2020

Microrobots and metal–organic frameworks (MOFs) have been identified as promising carriers for drug delivery applications. While clinical applications of microrobots are limited by their low drug loading efficiencies and the poor degradability of the materials used for their fabrication, MOFs lack motility and targeted drug delivery capabilities. The combination of these two fields marks the beginning of a new era; MOF‐based small‐scale robots (MOFBOTs) for biomedical applications. Yet, biodegradability is a major hurdle in the field of micro‐ and nanoswimmers including small‐scale robots. Here, a highly integrated MOFBOT that is able to realize magnetic locomotion, drug delivery, and selective degradation in cell cultures is reported for the first time. The MOF used in the investigations does not only allow a superior loading of chemotherapeutic drugs and their controlled release via a pH‐responsive degradation but it also enables the controlled locomotion of enzymatically biodegradable gelatin‐based helical microrobots under magnetic fields. The degradation of the integrated MOFBOT is observed after two weeks, when all its components fully degrade. Additionally, drug delivery studies performed in cancer cell cultures show reduced viability upon delivery of Doxorubicin within short time frames. This MOFBOT system opens new avenues for highly integrated fully biodegradable small‐scale robots.
HOMO–HOMO Electron Transfer: An Elegant Strategy for p‐Type Doping of Polymer Semiconductors toward Thermoelectric Applications
Authors: Goel Mahima , Siegert Marie , Krauss Gert , Mohanraj John , Hochgesang Adrian , Heinrich David C. , Fried Martina , Pflaum Jens , Thelakkat Mukundan
Published: September 2020

Unlike the conventional p‐doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole‐based polymer PDPP[T]2‐EDOT (OSC‐1) is presented using an oxidized p‐type semiconductor, Spiro‐OMeTAD(TFSI)2 (OSC‐2), exploiting electron transfer from HOMOOSC‐1 to HOMOOSC‐2. A shift of work function toward the HOMOOSC‐1 upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X‐ray photoelectron spectroscopy (XPS) and UV–vis–NIR absorption studies confirm HOMOOSC‐1 to HOMOOSC‐2 electron transfer. The reduction products of Spiro‐OMeTAD(TFSI)2 to Spiro‐OMeTAD(TFSI) and Spiro‐OMeTAD is also confirmed and their relative amounts in doped samples is determined. Mott–Schottky analysis shows two orders of magnitude increase in free charge carrier density and one order of magnitude increase in the charge carrier mobility. The conductivity increases considerably by four orders of magnitude to a maximum of 10 S m−1 for a very low doping ratio of 8 mol%. The doped polymer films exhibit high thermal and ambient stability resulting in a maximum power factor of 0.07 µW m−1 K−2 at a Seebeck coefficient of 140 µV K−1 for a very low doping ratio of 4 mol%. Also, the concept of HOMOOSC‐1 to HOMOOSC‐2 electron transfer is a highly efficient, stable and generic way to p‐dope other conjugated polymers.
Deoxygenative 1,1‐Bis‐trifluoromethylthiolation of Aromatic Aldehydes to Access Bis(trifluoromethylthio)methylarenes
Authors: Liu Yin‐Li , Xu Xiu‐Hua , Qing Feng‐Ling
Published: September 2020

A deoxygenative 1,1‐bis‐trifluoromethylthiolation of readily available aromatic aldehydes with AgSCF3 in the presence of KI and (NH4)2SO4 was established. This reaction delivered a series of bis(trifluoromethylthio)methylarenes in moderate to high yields. The precise control of the generation and decomposition of SCF3 anion is the key to the successful transformation.

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Defluorinative Ring‐Opening Indolylation of Siloxydifluorocyclopropanes: Controlled Synthesis of α‐Fluoro‐β‐Indolyl‐Propanones for Carbazole Construction
Authors: Liu Xiaowei , Du Dongxu , Li Shuting , Wang Xin , Xu Cong , Wang Mang
Published: September 2020

A catalytic defluorinative ring‐opening indolylation of siloxydifluorocyclopropanes was reported. It was found that AgBF4‐catalyzed reaction of siloxydifluorocyclopropanes with indoles could be controlled to deliver α‐fluoro‐β‐indolyl‐propanones within 1.5 hours at room temperature. Cyclization of these α‐fluoroketone derivatives were then carried out in the presence of trifluoroacetic anhydride in toluene at room temperature. Carbazoles were formed efficiently via an intramolecularly nucleophilic addition of the in situ formed enamine intermediate to the keto carbonyl, followed by a sequential hydrolysis and eliminations of trifluoroacetic acid and hydrogen fluoride.

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Metal‐free Decarboxylative Annulation of 2‐Aryl‐2‐isocyano‐acetates with Aryldiazonium Salts: General Access to 1,3‐Diaryl‐1,2,4‐triazoles
Authors: Tian Yu‐Ting , Zhang Fa‐Guang , Nie Jing , Cheung Chi Wai , Ma Jun‐An
Published: September 2020

Isocyanoacetates are versatile substrates for the synthesis of heterocyclic compounds, but the concomitant decarboxylation remains rare. Herein we report a decarboxylative annulation reaction of 2‐aryl‐2‐isocyanoacetates with aryldiazonium salts. This metal‐free, base‐promoted protocol allows for the access to a broad collection of 1,3‐diaryl‐1,2,4‐triazoles, including chiral triazole‐based binaphthalene ligands, drug mimics, and synthetic intermediates of druglike molecules.

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Irrigated grain sorghum response to 55 years of nitrogen, phosphorus, and potassium fertilization
Authors: Schlegel Alan J. , Havlin John L.
Published: September 2020

Although long‐term field experiments provide a valuable resource to assess crop yield response to climate and fertilizer, few studies have included grain sorghum (Sorghum bicolor L.). The objectives of this study were to quantify the effects of 55 yr of annual nitrogen (N), phosphorus (P), and potassium (K) application on irrigated continuous sorghum grain yield, grain nutrient uptake, and economic optimum N rates. Six N rates (0, 45, 90, 134, 179, and 224 kg N ha−1) and three combinations of P and K (0 P with 0 K, 20 kg P ha−1 with 0 K, and 20 kg P ha−1 with 37 kg K ha−1) were applied annually from 1961 to 2015 to a Ulysses silt loam near Tribune, KS. Average maximum grain yield with N was 53% greater than with no N applied; however, application of 20 kg P ha−1 with N resulted in a 70% increase in average maximum grain yield. Potassium fertilization had no effect on grain yield. The N rate required for maximum profit at 20 kg P ha−1 averaged 137 kg N ha−1. At the economic optimum N rate, apparent fertilizer N recovery in grain was 25% with no P and increased to 42% with P. Apparent fertilizer P recovery at the economic optimum N rate was 51% with 20 kg P ha−1. Fifty‐five yr of irrigated sorghum response to N and P fertilization demonstrated a strong positive interaction between N and P on grain yield, apparent N and P recovery, and profitability.
Weed pressure and turfgrass establishment in response to mulching media
Authors: Henry Gerald , Hoyle Jared
Published: September 2020

Turfgrass establishment on the Texas High Plains is often compromised by wind desiccation, high temperatures, and reduced water inputs. Application of cotton gin trash at seeding may help increase germination through buffering and insulation. Therefore, field experiments were conducted to examine weed pressure and establishment of ‘Sahara’ common bermudagrass [Cynodon dactylon (L.) Pers.] and ‘Bowie’ buffalograss [Bouteloua dactyloides (Nutt.) J.T. Columbus] in response to cotton gin trash and industry standards (hydro‐mulch and wheat [Triticum aestivum L.] straw) used as mulching media. The greatest amount of common bermudagrass cover 12 wk after planting (WAP) was observed in response to hydro‐mulch (89%) and no mulch (85%), while wheat straw and gin trash mulch only resulted in 70 and 60% cover, respectively. The greatest amount of buffalograss cover 12 WAP was observed in response to hydro‐mulch (55%). All other treatments resulted in ≤20% buffalograss cover 12 WAP. Weed cover in bermudagrass 12 WAP was highest in response to gin trash (33%) followed by (fb) wheat straw (24%) fb no mulch (12%) and hydro‐mulch (10%). Weed cover in buffalograss 12 WAP was highest in response to wheat straw (72%) fb gin trash (52%) fb no mulch (36%) fb hydro‐mulch (22%). Utilization of gin trash as mulch only resulted in 60% bermudagrass cover and 20% buffalograss cover, while weed pressure was 33–52% cover. Further refinement of gin trash may improve use as a mulch through the reduction of weed seed and removal of cotton plant fragments that limit light infiltration to the soil surface.
Ophthalmological abnormalities in Down syndrome among Brazilian patients
Authors: Bermudez Beatriz Elizabeth Bagatin Veleda , de Souza do Amaral Maria Eduarda , da Silva Gomes Charles , Novadzki Iolanda Maria , de Oliveira Camila Maciel , Serpe Crislaine Caroline
Published: September 2020

Down syndrome is the most common chromosomal disorder, affecting 1/700 live births. Among the clinical findings, one constant concern is the high prevalence of visual disorders that, if left untreated, can negatively affect child development. The aim of this study was to determine the prevalence of ophthalmological findings among patients who attended an outpatient clinic for patients with Down syndrome in southern Brazil between 2005 and 2016. A cross‐sectional study including 1,207 patients medical records were done, which 492 (40.8%) had some ophthalmological disorder. These data were subjected to descriptive analysis using Statistica software. Among the 492 patients with any ophthalmological disease, the need for glasses was found in 434 (36%) patients, keratoconus in 254 (42.1%), congenital cataract in 27 (15.1%), nasolacrimal duct obstruction in 25 (2.0%), strabismus in 22 (1.9%), nystagmus in four (0.3%), and juvenile cataract in two (0.2%). Two young adults with keratoconus underwent corneal transplantation. Although the prevalence of an ophthalmological disease among the present sample (40.8%) was lower than described in the current literature, it still reinforced the importance of routine and early evaluations in infants. These should begin at 6 months of age and be repeated half‐year until 2 years old, annually until 7 years old, biennial in adolescents, and triennial in adults and elderly. Our findings of a high frequency of keratoconus support a detailed corneal study in such patients for early detection and treatment.
Alzheimer‐Related Cerebrovascular Disease in Down Syndrome
Authors: Lao Patrick J. , Gutierrez José , Keator David , Rizvi Batool , Banerjee Arit , Igwe Kay C. , Laing Krystal K. , Sathishkumar Mithra , Moni Fahmida , Andrews Howard , Krinsky‐McHale Sharon , Head Elizabeth , Lee Joseph H. , Lai Florence , Yassa Michael A. , Rosas H. Diana , Silverman Wayne , Lott Ira T. , Schupf Nicole , Brickman Adam M.
Published: September 2020

Objective

Adults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)‐based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross‐sectional relationship with age, beta‐amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status.

Methods

Participants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI‐based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET‐based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment–DS (MCI‐DS), possible AD dementia, or definite AD dementia based on in‐depth assessments of cognition, function, and health status.

Results

There were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI‐DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct.

Interpretation

The findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity. ANN NEUROL 2020;88:1165–1177
The Formosalides: Structure Determination by Total Synthesis
Authors: Schulthoff Saskia , Hamilton James Y. , Heinrich Marc , Kwon Yonghoon , Wirtz Conny , Fürstner Alois
Published: September 2020

Total synthesis allowed the constitution of the cytotoxic marine macrolides of the formosalide family to be confirmed and their previously unknown stereostructure to be assigned with confidence. The underlying blueprint was inherently modular to ensure that each conceivable isomer could be reached. This flexibility derived from the use of strictly catalyst controlled transformations to set the stereocenters, except for the anomeric position, which is under thermodynamic control; as an extra safety measure, all stereogenic centers were set prior to ring closure to preclude any interference of the conformation adopted by the macrolactone rings of the different diastereomers. Late‐stage macrocyclization by ring‐closing alkyne metathesis was followed by a platinum‐catalyzed transannular 6‐exo‐dig hydroalkoxylation/ketalization to craft the polycyclic frame. The side chain featuring a very labile unsaturation pattern was finally attached to the core by Stille coupling.
Linking vegetation patterns, wetlands conservation, and ecosystem services provision: From publication to application
Authors: Bolpagni Rossano
Published: September 2020

Natural wetlands emerge as the best sites to preserve the diversity of aquatic and riparian vegetation; however, especially in the lowlands, pristine wetlands and aquatic ecosystems have almost completely disappeared through land reclamation and agricultural development. Actions are needed, therefore, to maintain and recreate a wide network of wetlands able to preserve adequate levels of vegetation diversity.

Focusing on a complex wetland system located in an overexploited plain, the article entitled ‘The importance of being natural in a human‐altered riverscape: Role of wetland type in supporting habitat heterogeneity and the functional diversity of vegetation’, published in 2016 in Aquatic Conservation: Marine and Freshwater Ecosystems (AQC) explored the role of wetland origin and hydrology as the main drivers of physical and vegetation functional diversity, following a hierarchical sampling approach.

The main results reinforced the key contribution of natural sites in maintaining vegetation diversity in heavily impaired riverine contexts, suggesting a direct effect of the interannual and seasonal dynamics of water‐level variations in the observed vegetation patterns.

The article offered an important contribution to our knowledge of vegetation patterns in wetlands, partly attributed to the innovative functional, hierarchical approach applied which is able to guarantee reliable data on the distribution patterns of physical heterogeneity and wetland vegetation.

The findings of the article have been applied and adopted in a series of technical handbooks designed, inter alia, to support the monitoring programmes of habitats of community interest or vegetation of relevance for aquatic biodiversity conservation. In addition, this article has helped to raise awareness of the essential roles played by wetlands in agricultural landscapes and has emphasized the need for a better synergy between the European Habitats Directive and the Water Framework Directive. Several ecological recovery projects have been funded in line with the results described in the AQC article.
Residual marine protected areas five years on: Are we still favouring ease of establishment over need for protection?
Authors: Devillers Rodolphe , Pressey Robert L. , Ward Trevor J. , Grech Alana , Kittinger John N. , Edgar Graham J. , Watson Reg A.
Published: September 2020

Marine protected areas (MPAs) are today's cornerstone of many marine conservation strategies. Our 2015 study (Devillers et al., 2015) and others have shown, however, that the placement of MPAs is ‘residual’ to commercial uses and biased towards areas of lower economic value or interest.

In this paper, we explored the impact of our study on marine science, policy and management practice.

We reviewed the papers citing our work and compiled expert opinions on some of the impacts of our study.

Results indicate a strong general uptake in the scientific community but more uneven impacts on policy and management in different contexts, with a likely smaller impact of the research on conservation practice.