bluuebunny/crossref_metadata_2025 huggingface dataset:
Intensity‐modulated radiation therapy and doxorubicin in thyroid cancer: A prospective phase 2 trial
Authors: Romesser Paul B. , Sherman Eric J. , Whiting Karissa , Ho Margaret L. , Shaha Ashok R. , Sabra Mona M. , Riaz Nadeem , Waldenberg Todd E. , Sabol Christopher R. , Ganly Ian , McBride Sean M. , Fagin James A. , Zhang Zhigang , Tuttle R. Michael , Wong Richard J. , Lee Nancy Y.
Published: July 2021

Background

The use of external‐beam radiotherapy for locally advanced nonanaplastic thyroid cancer remains controversial. This prospective study evaluated the efficacy and tolerability of intensity‐modulated radiation therapy (IMRT) with or without concurrent chemotherapy in patients with locally advanced thyroid cancer.

Methods

The authors conducted a nonrandomized phase 2 trial of IMRT with or without concurrent doxorubicin in patients with gross residual or unresectable nonanaplastic thyroid carcinoma (ClinicalTrials.gov identifier NCT01882816). The primary end point was 2‐year locoregional progression‐free survival (PFS). Secondary end points included overall survival (OS), safety, patient‐reported outcomes, and functional outcomes.

Results

Twenty‐seven patients were enrolled: 12 (44.4%) with unresectable disease and 15 (55.6%) with gross residual disease. The median follow‐up was 45.6 months (interquartile range, 42.0‐51.6 months); the 2‐year cumulative incidences of locoregional PFS and OS were 79.7% and 77.3%, respectively. The rate of grade 3 or higher acute and late toxicities was 33.4%. There were no significant functional differences 12 months after treatment (assessed objectively by the modified barium swallow study). Patient‐reported quality of life in the experimental group was initially lower but returned to the baseline after 6 months and improved thereafter. In a post hoc analysis, concurrent chemotherapy with intensity‐modulated radiation therapy (CC‐IMRT) resulted in significantly less locoregional failure at 2 years (no failure vs 50%; P = .001), with higher rates of grade 2 or higher acute dermatitis, mucositis, and dysphagia but no difference in long‐term toxicity, functionality, or patient‐reported quality of life.

Conclusions

In light of the excellent locoregional control rates achieved with CC‐IMRT and its acceptable toxicity profile as confirmed by functional assessments and patient‐reported outcomes, CC‐IMRT may be preferred over IMRT alone.
Lack of knowledge regarding HPV and its relation to oropharyngeal cancer among medical students
Authors: Sallam Malik , Dababseh Deema , Yaseen Alaa , Al‐Haidar Ayat , Ettarras Hajar , Jaafreh Dania , Hasan Hanan , Al‐Salahat Khaled , Al‐Fraihat Esraa , Hassona Yazan , Şahin Gülşen Özkaya , Mahafzah Azmi
Published: July 2021

Background

Oropharyngeal cancer (OPC) is an important cause of cancer‐related mortality. Early detection of OPC results in a favorable prognosis and higher survival rates. Infection by high‐risk types of human papillomavirus (HPV) is a risk factor for OPC with an upward trend globally. Medical students' knowledge and awareness of HPV‐related OPC can be crucial in the preventive efforts.

Aim

To assess HPV knowledge among medical students at the University of Jordan, with particular focus on its relation to different cancers.

Methods

This paper‐based survey study was conducted in November 2019. The survey items were based on previously validated surveys used to evaluate HPV‐related OPC knowledge among dental students and professionals. To assess HPV knowledge and students' confidence in personal history taking and physical examination, we developed a knowledge and confidence scores that showed acceptable reliability.

Results

The total number of participants was 1198 students, with a median age of 21 and female predominance (n = 697, 58.2%). Among the participants, 93.3% heard of HPV prior to this survey (n = 1118). Higher levels of knowledge regarding cervical cancer, OPC and HPV vaccination was seen among clinical students compared to their preclinical counterparts, but their overall HPV knowledge was low. Only 18.4% and 21.0% of the clinical students correctly identified the association of HPV with penile and oropharyngeal cancers, respectively. Additionally, 34.5% of the clinical students were not aware of the availability of HPV vaccines. The majority of students (92.0%) reported that the university courses were their major source of knowledge about HPV.

Conclusion

A profound lack of knowledge regarding HPV role in OPC was found among medical students. This insufficiency included several aspects of the virus and its associated diseases. Such gaps in knowledge could have negative consequences in early detection and prevention of OPC and should be addressed by evaluation of the current curriculum.
Platinum‐Catalyzed Alkene Hydrosilylation: Solvent‐Free Process Development from Batch to a Membrane‐Integrated Continuous Process
Authors: Bayrakdar Tahani A. C. A. , Maliszewski Benon P. , Nahra Fady , Ormerod Dominic , Nolan Steven P.
Published: July 2021

The integration of a membrane separation protocol with the platinum‐catalyzed hydrosilylation of olefins is investigated. The catalytic reaction is first optimized in batch where [Pt(IPr*)(dms)Cl2] (IPr*=1,3‐bis[2,6‐bis(diphenylmethyl)‐4‐methylphenyl]imidazol‐2‐ylidene, dms=dimethyl sulfide) demonstrates superior activity compared to the less sterically encumbered [Pt(SIPr)(dms)Cl2] (SIPr=1,3‐bis(2,6‐diisopropylphenyl)imidazolidine) congener. Filtration conditions are identified in membrane screening experiments. Hydrosilylation of 1‐octene catalyzed by [Pt(IPr*)(dms)Cl2] is conducted in continuous mode and the platinum catalyst is separated efficiently over the commercially available BorsigoNF‐2membrane, all under solvent‐free conditions. An advantage of this process is that both reaction and separation are coupled in a single step. Moreover, at the end of the process the intact catalyst was recovered in 80 % yield as an off‐white solid without any further purification.
Great tits (Parus major) flexibly learn that herbivore‐induced plant volatiles indicate prey location: An experimental evidence with two tree species
Authors: Sam Katerina , Kovarova Eliska , Freiberga Inga , Uthe Henriette , Weinhold Alexander , Jorge Leonardo R. , Sreekar Rachakonda
Published: July 2021

When searching for food, great tits (Parus major) can use herbivore‐induced plant volatiles (HIPVs) as an indicator of arthropod presence. Their ability to detect HIPVs was shown to be learned, and not innate, yet the flexibility and generalization of learning remain unclear.

We studied if, and if so how, naïve and trained great tits (Parus major) discriminate between herbivore‐induced and noninduced saplings of Scotch elm (Ulmus glabra) and cattley guava (Psidium cattleyanum). We chemically analyzed the used plants and showed that their HIPVs differed significantly and overlapped only in a few compounds.

Birds trained to discriminate between herbivore‐induced and noninduced saplings preferred the herbivore‐induced saplings of the plant species they were trained to. Naïve birds did not show any preferences. Our results indicate that the attraction of great tits to herbivore‐induced plants is not innate, rather it is a skill that can be acquired through learning, one tree species at a time.

We demonstrate that the ability to learn to associate HIPVs with food reward is flexible, expressed to both tested plant species, even if the plant species has not coevolved with the bird species (i.e., guava). Our results imply that the birds are not capable of generalizing HIPVs among tree species but suggest that they either learn to detect individual compounds or associate whole bouquets with food rewards.
Eagles enter rotor‐swept zones of wind turbines at rates that vary per turbine
Authors: McClure Christopher J. W. , Rolek Brian W. , Braham Melissa A. , Miller Tricia A. , Duerr Adam E. , McCabe Jennifer D. , Dunn Leah , Katzner Todd E.
Published: July 2021

There is increasing pressure on wind energy facilities to manage or mitigate for wildlife collisions. However, little information exists regarding spatial and temporal variation in collision rates, meaning that mitigation is most often a blanket prescription. To address this knowledge gap, we evaluated variation among turbines and months in an aspect of collision risk—probability of entry by an eagle into a rotor‐swept zone (hereafter, “probability of entry”). We examined 10,222 eagle flight paths identified and recorded by an automated bird monitoring system at a wind energy facility in Wyoming, USA. Probabilities of entry per turbine–month combination were 4.03 times greater in some months than others, ranging 0.15 to 0.62. The overall probability of entry for the riskiest turbine (i.e., the one with the greatest probability of entry) was 2.39 times greater than the least‐risky turbine. Our methodology describes large variation across turbines and months in the probability of entry. If subsequently combined with information on other sources of variation (i.e., weather, topography), this approach can identify risky versus safe situations for eagles under which cost of management, curtailment prescriptions, and collision risk can be simultaneously minimized.
Distribution and pollination services of wild bees and hoverflies along an altitudinal gradient in mountain hay meadows
Authors: Baumann Kevin , Keune Julia , Wolters Volkmar , Jauker Frank
Published: July 2021

Extensively managed and flower‐rich mountain hay meadows, hotspots of Europe's biodiversity, are subject to environmental and climatic gradients linked to altitude. While the shift of pollinators from bee‐ to fly‐dominated communities with increasing elevation across vegetation zones is well established, the effect of highland altitudinal gradients on the community structure of pollinators within a specific habitat is poorly understood. We assessed wild bee and hoverfly communities, and their pollination service to three plant species common in mountain hay meadows, in eighteen extensively managed yellow oat grasslands (Trisetum flavescens) with an altitudinal gradient spanning approx. 300 m. Species richness and abundance of pollinators increased with elevation, but no shift between hoverflies and wild bees (mainly bumblebees) occurred. Seedset of the woodland cranesbill (Geranium sylvaticum) increased with hoverfly abundance, and seedset of the marsh thistle (Cirsium palustre) increased with wild bee abundance. Black rampion (Phyteuma nigrum) showed no significant response. The assignment of specific pollinator communities, and their response to altitude in highlands, to different plant species underlines the importance of wild bees and hoverflies as pollinators in extensive grassland systems.
Stochasticity overrides deterministic processes in structuring macroinvertebrate communities in a plateau aquatic system
Authors: Ge Yihao , Meng Xingliang , Heino Jani , García‐Girón Jorge , Liu Yang , Li Zhengfei , Xie Zhicai
Published: July 2021

Deterministic and stochastic processes are two major factors shaping community dynamics, but their relative importance remains unknown for many aquatic systems, including those in the high‐elevation Qinghai–Tibet Plateau. Here, we explored the causes of multidimensional beta diversity patterns (i.e., taxonomic, functional, and phylogenetic) of a macroinvertebrate metacommunity in this large aquatic system by using multiple approaches (i.e., null models, phylogenetic signal testing, and ordination‐based approaches). To obtain insights into community assembly mechanisms, we also analyzed beta diversity in two deconstructed sub‐metacommunities (e.g., different tributaries and the main lake body). We found that most functional traits showed significant phylogenetic signals, indicating that the functional traits were profoundly influenced by evolutionary history. The null models showed randomness of functional and phylogenetic beta diversities for the whole basin and its tributaries, confirming the importance of stochasticity over deterministic processes in controlling community structure. However, both phylogenetic and functional community structures were clustered in the Qinghai Lake, probably reflecting the importance of environmental filtering. Ordination‐based approaches also revealed that both environmental factors and spatial processes accounted for variation in taxonomic, functional, and phylogenetic beta diversity. More specifically, environmental filtering was more important than spatial processes for the functional dimension, but the opposite was true for the taxonomic and phylogenetic dimensions. The paleogeographic history of the Qinghai Lake basin may have contributed substantially to the prevalence of stochastic processes. Overall, this study provides a better understanding of ecological patterns and assembly mechanisms of macroinvertebrate communities across this poorly known high‐elevation aquatic system that is highly sensitive to climate warming.
A Comprehensive Perspective on the Fabrication of CuGaSe2/Si Tandem Solar Cells
Authors: Prathapani Sateesh , Zhan Yiqiang
Published: July 2021

This review points out the current need for further research on tandem solar cells as the commercial single‐junction solar cell technologies report close to their maximum performance limit. First, the conceptual insight and the desired interconnection schemes for tandem solar cells are briefly presented. Then, a comprehensive discussion on the structural, optical, and electronic properties of CuGaSe2, evaluating its use as a top cell absorber material, is presented. Furthermore, the current status and the critical analysis of CuGaSe2solar cells, which finds that the adapted conventional device architecture possesses severe limitations, are presented. Based on the drawbacks of the existing materials in use, new materials to fabricate CuGaSe2solar cells are proposed. Also, tandem configurations with newly proposed CuGaSe2solar cell architecture by choosing Si photovoltaics as bottom cells are devised. In the end, further challenges in the devised tandem configurations with a focus on their band alignments are elucidated.
Accumulated and transient exergy analyses of pneumatic systems with isochoric and isobaric compressed air storage tanks
Authors: Tong Zhengren , Wang Hu , Xiong Wei , Ting David S‐K. , Carriveau Rupp , Wang Zhiwen
Published: July 2021

Low energy efficiency is one of the most significant shortcomings of industrial pneumatic systems. The isobaric air storage tank is a new concept for improving the energy efficiency of pneumatic systems. In this study, comprehensive accumulated and transient exergy analyses are conducted to provide insight into the energy‐saving mechanism of isobaric air storage tanks. The results show that the system exergy efficiency can be improved by replacing the isochoric tank with an isobaric one. There is negligible exergy destruction in both storage tanks. However, the storage tank can bring about significant influences on other components. The isobaric tank can effectively improve the exergy efficiencies of the compressor, cooler, and regulator. Besides, there is a huge potential to improve system exergy efficiency by taking advantage of the wasted exergy from the pneumatic cylinder.
A numerical study on effects of axially and radially cascaded phase change material on charging/discharging time of paraffin based packed bed thermal energy storage
Authors: Rabbi Jawad , Asif Muhammad , Bibi Wajeeha
Published: July 2021

This study manifests the improvement in the charging and discharging time of the encapsulated PCM arranged in packed bed thermal energy storage. The combined effect of the aspect ratio (ratio of height to diameter of the packed bed) and cascaded configurations of phase change materials (PCMs) integrated with the solar water heating system is analyzed numerically. The mathematical model is validated by the experimental study available in the literature. Initially, an optimal aspect ratio of the packed bed is predicted for charging/discharging. And then, PCMs are arranged in different layers in the packed bed based on the optimal aspect ratio to analyze the combined effect of PCM configurations and optimal aspect ratio. The charging and discharging time were decreased with an increasing aspect ratio to 2.5. Afterward, an increased aspect ratio showed a trivial change in the charging and discharging time of latent heat thermal energy storage (LHTES). Furthermore, at an optimal aspect ratio of 2.5, PCMs were arranged in the packed bed with both axial (parallel) and combined axial‐radial layers (parallel and series) to see the impact of the cascaded configuration. Charging and discharging time of combined axial‐radial layers configuration was respectively found to be 17.21% and 18.5%, less than charging time without layers.
Exploring the triggering process of a cancer care reform in three Scandinavian countries
Authors: Mæhle Per Magnus , Hajdarevic Senada , Håland Erna , Aarhus Rikke , Smeland Sigbjørn , Mørk Bjørn Erik
Published: July 2021

Cancer incidence is increasing, and cancer is a leading cause of death in the Scandinavian countries, and at the same time more efficient but very expensive new treatment options are available. Based on the increasing demand, high expectations and limited resources, crises in public legitimacy of cancer care evolved in the three Scandinavian countries. Similar cancer care reforms were introduced in the period 2007–2015 to address the crisis. In this article we explore processes triggering these reforms in countries with similar and well‐developed health care systems. The common objective was the need to reduce time from referral to start treatment, and the tool introduced to accomplish this was integrated care pathways for cancer diagnosis, that is Cancer Patient Pathways. This study investigates the process by drawing on interviews with key actors and public documents. We identified three main logics in play; the economic‐administrative, the medical and the patient‐related logic and explored how institutional entrepreneurs skillfully aligned these logics. The article contributes by describing the triggering processes on politically initiated similar reforms in the three countries studied and also contributes to a better understanding on the orchestrating of politically initiated health care reforms with the intention to change medical practice in hospitals.
Deep‐learning based projection of change in irrigation water‐use under RCP 8.5
Authors: Sung Jang Hyun , Kim Jinsoo , Chung Eun‐Sung , Ryu Young
Published: July 2021

Stream water‐use is essential for both agricultural and hydrological management and yet not many studies have explored its non‐stationarity and nonlinearity with meteorological variables. This study proposed a deep‐learning based model to estimate agricultural water withdrawal using hydro‐meteorological variables, which projected the changes of agricultural water withdrawal influenced by climate change of future. The relationships between meteorological variables and stream water‐use rate (WUR) were quantified using a deep belief network (DBN). The influences of precipitation, potential evapotranspiration, and monthly averaged WUR on the performance of the developed DBN model were tested. As a result, this DBN with potential evapotranspiration (PET) provided better performances than precipitation to estimate the WUR. The PET of multi‐model scenarios for Representative Concentration Pathways 8.5 would be increased as time goes by, and thus leads to increase WUR estimated by DBN in three basins, located in South Korea during the future period. On the contrary, water availability expected to decrease compared to the current. Therefore, managing water‐uses and improving efficiencies can be prepared for the change in agricultural water‐use by climate change in the future.
Aquifer recharge from flash floods in the arid environment: A mass balance approach at the catchment scale
Authors: Farran Mohammed M. , Al‐Amri Nassir , Elfeki Amro M.
Published: July 2021

Estimation of the infiltration/natural recharge to groundwater from rainfall is an important issue in hydrology, particularly in arid regions. This paper proposes the application of The Natural Resources Conservation Service (NRCS) mass balance model to develop infiltration (F)–rainfall (P) relationship from flash flood events. Moreover, the NRCS method is compared with the rational and the Ф‐index methods to investigate the discrepancies between these methods. The methods have been applied to five gauged basins and their 19 sub‐basins (representative basins with detailed measurements) in the southwestern part of Saudi Arabia with 161 storms recorded in 4 years. The F–P relationships developed in this study based on NRCS method are: F = 39% P with R2 = 0.932 for the initial abstraction factor, λ = 0.2. However, F = 77% P with R2 = 0.986 for λ = 0.01. The model at λ = 0.01 is the best to fit the data, therefore, it is recommended to use the formula at λ = 0.01. The results show that the NRCS model is appropriate for the estimation of the F–P relationships in arid regions when compared with the rational and the Ф index methods. The latter overestimates the infiltration because they do not take λ into account. There is no significant difference between F–P relationships at different time scales. This helps the prediction of infiltration rates for aquifer recharge at ungauged basins from monthly and annual rainfall data with a single formula.
The increasing incidence and prevalence of hypereosinophilic syndrome in the United Kingdom
Authors: Requena Gema , Logie John , Gibbons Daniel C. , Steinfeld Jonathan , Van Dyke Melissa K.
Published: July 2021

Introduction

Data on the burden of hypereosinophilic syndrome (HES) are limited. This study investigated the incidence and prevalence of HES using real‐world data from patients in the United Kingdom.

Methods

Primary care data from the Clinical Practice Research Datalink were analyzed. The patients of interest were identified using medical codes specific for HES. Annual incidence rates and prevalence were estimated for the years 2010–2018 (inclusive) using patients observed for a minimum period of one year.

Results

Between 2010 and 2018, 93 patients were identified with HES. During the study period the incidence of HES ranged from less than 0.04, 95% confidence interval (CI) (0.01–0.07) to 0.17, 95% CI (0.10–0.26) per 100,000 person‐years and the prevalence ranged from 0.15, 95% CI (0.10–0.25) to 0.89, 95% CI (0.74–1.09) cases per 100,000 persons. Sensitivity analyses varying the minimum observation period required to identify HES patients gave similar results.

Conclusion

These results provide estimates of the burden of HES in the United Kingdom and indicate that whilst HES is a very rare disease, there is evidence that is increasingly being recorded in UK primary care.
Physicochemical aspects of design of ultrathin films based on chitosan, pectin, and their silver nanocomposites with antiadhesive and bactericidal potential
Authors: Kulikouskaya Viktoryia , Zhdanko Tsimafei , Hileuskaya Kseniya , Kraskouski Aliaksandr , Zhura Alexandr , Skorohod Hennadiy , Butkevich Vasili , Pal Kunal , Tratsyak Stanislau , Agabekov Vladimir
Published: July 2021

Implant‐related infection is one of the serious problems in regenerative medicine. Promising approach to overcome the problems caused by bacterial growth on the medical implants is their modification by bioactive coatings. A versatile technique for designing multilayer films with tailored characteristics at the nanometer scale is layer‐by‐layer assembly. In this study, multilayer films based on biopolymers (pectin and chitosan) and their nanocomposites with silver nanoparticles have been prepared and evaluated. The buildup of multilayers was monitored using the quartz crystal microbalance with dissipation technique. The morphology of the obtained films was investigated by atomic force microscopy. We have demonstrated that pectin–Ag‐containing films were characterized by the linear growth and smooth defect‐free surface. When pectin–Ag was substituted for the pectin in the multilayer systems, the properties of the formed coatings were significantly changed: the film rigidity and surface roughness increased, as well as the film growth acquired the parabolic character. All prepared multilayer films have shown antibacterial activity against gram‐positive (Staphylococcus aureus) and gram‐negative (Escherichia coli) bacteria. The significant decrease in the number of the adhered E. coli on the multilayer surface has been determined; moreover, many of the cells were misshapen with cytoplasm leaking. The prepared multilayer films showed a mild activity against S. aureus predominantly due to the antiadhesive effect. Our results indicate that antibacterial activity of biopolymer multilayers is determined by the film composition and physicochemical characteristics and can be associated with their antiadhesive and bactericidal behaviors.
The clinical use of bone graft substitutes in orthopedic surgery in Germany—A 10‐years survey from 2008 to 2018 of 1,090,167 surgical interventions
Authors: Rupp Markus , Klute Lisa , Baertl Susanne , Walter Nike , Mannala Gopala‐Krishna , Frank Leona , Pfeifer Christian , Alt Volker , Kerschbaum Maximilian
Published: July 2021

Aim of the study was to evaluate (1) the overall use of bone graft substitutes, autografts and allografts, (2) of different types of bone graft substitutes (calcium sulfate, calcium phosphate, calcium phosphate ceramics or polymethyl methacrylate) and of different bone grafts (cancellous vs. cortical), and (3) the use of antibiotic‐loading of bone graft substitutes in orthopedic surgery in Germany. Gross data were provided from the Federal Statistical Office of Germany and revealed an overall increase in bone defect reconstruction procedures using bone graft substitutes, autografts and allografts from 86,294 in 2008 to 99,863 cases in 2018 (+15.7%). The relative use of bone graft substitutes for these interventions strongly increased from 11.8% in 2008 (10,163 cases) to 23.9% in 2018 (23,838 cases) with an increase of +134.4%. Furthermore, antibiotic‐loaded bone graft substitutes were implanted more frequently with an overall increase of +194% (2008: n = 2,657; 2018: n = 7,811). The work shows an increasing use of bone graft substitutes and antibiotic‐loaded bone graft substitutes over the last 10 years in Germany.
Data inaccessibility at sub‐county scale limits implementation of manuresheds
Authors: Booth Eric G. , Kucharik Christopher J.
Published: July 2021

The manureshed concept aims to rebalance surplus manure nutrients produced at animal feeding operations (sources) and the demands from nutrient‐deficient croplands (sinks) to reduce negative environmental impacts and utilize nutrients more efficiently. Due to water quality implications, studies focused on this rebalancing have typically created domain boundaries that match a particular watershed. However, a majority of agricultural datasets that are used to inform these analyses—specifically, livestock populations—are only available at the county scale, which generally does not match watershed boundaries. The common method used to address this mismatch is to weight the county statistics based on the proportion of watershed area within the county. However, these straightforward assumptions imply that animal density is uniform across a county, which can be highly problematic, especially in an era of increasing concentration of livestock production on a smaller land area. We present a case study of the Lake Mendota watershed in south‐central Wisconsin using both a typical county‐based downscaled dataset as well as a more spatially explicit dataset of livestock counts from the Census of Agriculture that aggregates a set of zip codes that best matches the watershed boundary. This comparison reveals a substantial difference in estimated livestock numbers and their associated manure production that is due to a concentration of dairy operations within the watershed compared with the rest of the county. We argue that sub‐county scale data need to become more available and integrated into nutrient and water quality management efforts so that manuresheds can be more effectively delineated and implemented.
MicroRNA‐145‐5p targeting of TRIM2 mediates the apoptosis of retinal ganglion cells via the PI3K/AKT signaling pathway in glaucoma
Authors: Xu Kai , Li Sizhen , Yang Qingsong , Zhou Zixiu , Fu Min , Yang Xiaodong , Hao Kuanxiao , Liu Yating , Ji Heqing
Published: July 2021

Background

There is accumulating evidence to suggest that microRNAs (miRNAs) are associated with the progressive optic neuropathy including glaucoma. Apoptosis of retinal ganglion cells (RGCs) is a hallmark of glaucoma. The present study focused on the effects of miR‐145‐5p on RGC apoptosis in glaucoma.

Methods

We established a glaucoma rat model by intraocular injection of N‐methyl‐d‐aspartic acid (NMDA). RGCs were isolated from newborn rats and treated with NMDA. Hematoxylin and eosin staining was performed to detect morphological changes in the retinas of rats. The expression of miR‐145‐5p and tripartite motif‐containing 2 (TRIM2) in RGCs was measured by RT‐qPCR. The viability of RGCs was measured by MTT assay. Flow cytometry analysis and TUNEL assays were conducted to assess the apoptosis of RGCs. The interaction between miR‐145‐5p and TRIM2 was investigated using a luciferase reporter assay.

Results

Rats injected with NMDA showed a thinner ganglion cell layer (GCL) and inner plexiform layer (IPL) as well as increased expression of miR‐145‐5p. Silencing of miR‐145‐5p significantly increased the GCL and IPL in the glaucoma rat model. Moreover, miR‐145‐5p expression was upregulated in RGCs ex vivo in response to NMDA. Silencing of miR‐145‐5p promoted cell viability and suppressed apoptosis in NMDA‐treated RGCs. Mechanistically, miR‐145‐5p targeted the TRIM2 3′ untranslated region to suppress its expression. TRIM2 was upregulated in NMDA‐treated RGCs and protected RGCs against NMDA‐induced apoptosis. Furthermore, miR‐145‐5p suppressed the PI3K/AKT pathway by downregulating TRIM2 in NMDA‐treated RGCs.

Conclusions

Suppression of miR‐145‐5p inhibited the apoptosis of RGCs via TRIM2‐mediated activation of the PI3K/AKT signaling pathway in NMDA‐induced glaucoma.
The HIV care cascade in sub‐Saharan Africa: systematic review of published criteria and definitions
Authors: Mugglin Catrina , Kläger Delia , Gueler Aysel , Vanobberghen Fiona , Rice Brian , Egger Matthias ,   International epidemiology Databases to Evaluate AIDS in Southern Africa
Published: July 2021

Introduction

The HIV care cascade examines the attrition of people living with HIV from diagnosis to the use of antiretroviral therapy (ART) and suppression of viral replication. We reviewed the literature from sub‐Saharan Africa to assess the definitions used for the different steps in the HIV care cascade.

Methods

We searched PubMed, Embase and CINAHL for articles published from January 2004 to December 2020. Longitudinal and cross‐sectional studies were included if they reported on at least one step of the UNAIDS 90‐90‐90 cascade or two steps of an extended 7‐step cascade. A step was clearly defined if authors reported definitions for numerator and denominator, including the description of the eligible population and methods of assessment or measurement. The review protocol has been published and registered in Prospero.

Results and discussion

Overall, 3364 articles were screened, and 82 studies from 19 countries met the inclusion criteria. Most studies were from Southern (38 studies, 34 from South Africa) and East Africa (29 studies). Fifty‐eight studies (71.6%) were longitudinal, with a median follow‐up of three years. The medium number of steps covered out of 7 steps was 3 (interquartile range [IQR] 2 to 4); the median year of publication was 2015 (IQR 2013 to 2019). The number of different definitions for the numerators ranged from four definitions (for step “People living with HIV”) to 21 (step “Viral suppression”). For the denominators, it ranged from three definitions (“Diagnosed and aware of HIV status”) to 14 (“Viral suppression”). Only 12 studies assessed all three of the 90‐90‐90 steps. Most studies used longitudinal data, but denominator–denominator or denominator–numerator linkages over several steps were rare. Also, cascade data are lacking for many countries. Our review covers the academic literature but did not consider other data, such as government reports on the HIV care cascade. Also, it did not examine disengagement and reengagement in care.

Conclusions

The proportions of patients retained at each step of the HIV care cascade cannot be compared between studies, countries and time periods, nor meta‐analysed, due to the many different definitions used for numerators and denominators. There is a need for standardization of methods and definitions.
Evolution trace of SARS‐CoV‐2 from January 19 to March 12, 2020, in the United States
Authors: Lin Ziying , Qing Hua , Li Rui , Zheng Lei , Yao Huipeng
Published: July 2021

As a kind of human betacoronavirus, SARS‐CoV‐2 has endangered globally public health. As of January 2021, the virus had resulted in 2,209,195 deaths. By studying the evolution trend and characteristics of 265 SARS‐CoV‐2 strains in the United States from January to March, it is found that the strains can be divided into six clades, USA clade‐1, USA clade‐2, USA clade‐3, USA clade‐4, USA clade‐5, and USA clade‐6, in which US clade‐1 may be the most ancestral clade, USA clade‐2 is an interim clade of USA clade‐1 and USA clade‐3, the other three clades have similar codon usage pattern, while USA clade‐6 is the newest and most adaptable clade. Mismatch analysis and protein alignment showed that the evolution of the clades arises from some special mutations in viral proteins, which may help the strain to invade, replicate, transcribe and so on. Compared with previous research and classifications, we suggest that clade O in GISAID should not be an independent clade and Wuhan‐Hu‐1 (EPI_ISL_402125) should not be an ancestral reference sequence. Our study decoded the evolutionary dynamic of SARS‐CoV‐2 in the early stage from the United States, which give some clues to infer the current evolution trend of SARS‐CoV‐2 and study the function of viral mutational protein.
Visualization of early oligomeric α‐synuclein pathology and its impact on the dopaminergic system in the (Thy‐1)‐h[A30P]α‐syn transgenic mouse model
Authors: Behere Anish , Thörnqvist Per‐Ove , Winberg Svante , Ingelsson Martin , Bergström Joakim , Ekmark‐Lewén Sara
Published: July 2021

Aggregation of alpha‐synuclein (α‐syn) into Lewy bodies and Lewy neurites is a pathological hallmark in the Parkinson´s disease (PD) brain. The formation of α‐syn oligomers is believed to be an early pathogenic event and the A30P mutation in the gene encoding α‐syn, causing familial PD, has been shown to cause an accelerated oligomerization. Due to the problem of preserving antigen conformation on tissue surfaces, α‐syn oligomers are difficult to detect ex vivo using conventional immunohistochemistry with oligomer‐selective antibodies. Herein, we have instead employed the previously reported α‐syn oligomer proximity ligation assay (ASO‐PLA), along with a wide variety of biochemical assays, to discern the pathological progression of α‐syn oligomers and their impact on the dopaminergic system in male and female (Thy‐1)‐h[A30P]α‐syn transgenic (A30P‐tg) mice. Our results reveal a previously undetected abundance of α‐syn oligomers in midbrain of young mice, whereas phosphorylated (pS129) and proteinase k‐resistant α‐syn species were observed to a larger extent in aged mice. Although we did not detect loss of dopaminergic neurons in A30P‐tg mice, a dysregulation in the monoaminergic system was recorded in older mice. Taken together, ASO‐PLA should be a useful method for the detection of early changes in α‐syn aggregation on brain tissue, from experimental mouse models in addition to post mortem PD cases.
Characterization of American teduglutide consumers from 2015 to 2020: A large database study
Authors: Loutfy Adam , Kurin Michael , Shah Raj , Davitkov Perica
Published: July 2021

Introduction

Teduglutide, a glucagon‐like peptide‐2 analog, is a novel therapy for intestinal failure that reduces need for parenteral support, especially in patients without a functional terminal ileum or colon. It can also predispose patients to accelerated progression of gastrointestinal (GI) malignancy and fluid overload. We demographically and clinically characterized American patients prescribed teduglutide.

Methods

The Explorys database is an aggregate of deidentified patient data from dozens of US healthcare systems. We used SNOMED classification to identify patients prescribed teduglutide from 2015 to 2019. Through the browse cohort feature we determined the demographics, postsurgical anatomy, comorbidities, and indication for teduglutide use among these patients.

Results

Of approximately 72 million patients, 170 were prescribed teduglutide. A large majority were female (70.6%). Most common etiologies of short‐bowel syndrome were intestinal obstruction (52.9%) and Crohn's disease (41.2%). Common postsurgical anatomy included total colectomy (41.2%) and ileostomy. Common incident symptoms included abdominal pain (41.2%) and nausea (23.5%). Thirty (17.6%) patients were prescribed teduglutide despite comorbid heart failure, and 5.9% despite prior GI malignancy. A total of 11.8% of patients had a history of benign GI neoplasms before starting teduglutide. A total of 5.9% of patients had posttreatment formation of colon polyps.

Conclusion

In a large American database, the teduglutide prescription is rare. Only a minority have postsurgical anatomy associated with the most robust response to teduglutide. Serious adverse events appear rare, but a substantial number of patients are at risk for adverse effects because of the presence of comorbid heart failure or GI neoplasm.
Genome‐wide DNA (hydroxy) methylation reveals the individual epigenetic landscape importance on osteogenic phenotype acquisition in periodontal ligament cells
Authors: Ferreira Rogério S. , Assis Rahyza I. F. , Feltran Geórgia da S. , do Rosário Palma Iasmin Caroline , Françoso Beatriz G. , Zambuzzi Willian F. , Andia Denise C. , da Silva Rodrigo A.
Published: July 2021

Background

Mesenchymal cells’ biology has been an important investigative tool to maximize bone regeneration through tissue engineering. Here we used mesenchymal cells from periodontal ligament (PDLCs) with high (h‐) and low (l‐) osteogenic potential, isolated from different donors, to investigate the impact of the individual epigenetic and transcriptional profiles on the osteogenic potential.

Methods

Genome‐wide and gene‐specific DNA (hydroxy) methylation, mRNA expression and immunofluorescence analysis were carried out in h‐ and l‐PDLCs at DMEM (non‐induced to osteogenesis) and OM (induced—3rd and 10th days of osteogenic differentiation) groups in vitro.

Results

Genome‐wide results showed distinct epigenetic profile among PDLCs with most of the differences on 10th day of OM; DMEMs showed higher concentrations (xOM) of differentially methylated probes in gene body, intronic and open sea (3rd day), increasing this concentration in TSS200 and island regions, at 10 days. At basal levels, h‐ and l‐PDLCs showed different transcriptional profiles; l‐PDLCs demonstrated higher levels of NANOG/OCT4/SOX2, BAPX1, DNMT3A, TET1/3, and lower levels of RUNX2 transcripts, confirmed by NANOG/OCT4 and RUNX2 immunofluorescence. After osteogenic induction, the distinct transcriptional profile of multipotentiality genes was maintained among PDLCs. In l‐PDLCs, the anti‐correlation between DNA methylation and gene expression in RUNX2 and NANOG indicates methylation could play a role in modulating both transcripts.

Conclusions

Epigenetic and transcriptional distinct profiles detected at basal levels among PDLCs were maintained after osteogenic induction. We cannot discard the existence of a complex that represses osteogenesis, suggesting the individual donors’ characteristics have significant impact on the osteogenic phenotype acquisition.
The Impact of COVID‐19 on Psychotherapy Participation Among Individuals With Posttraumatic Stress Disorder Enrolled in Treatment Research
Authors: McLean Carmen P. , Back Sudie E. , Capone Christy , Morland Leslie , Norman Sonya B. , Rauch Sheila A. M. , Schnurr Paula P. , Teng Ellen , Acierno Ron
Published: July 2021

The onset of the COVID‐19 pandemic disrupted many aspects of daily life and required a rapid and unprecedented shift in psychotherapy delivery from in‐person to telemental health. In the present study, we explored the impact of the pandemic on individuals’ ability to participate in posttraumatic stress disorder (PTSD) psychotherapy and the association between the impact of COVID‐19 impact on health and financial well‐being and psychotherapy participation. Participants (N = 161, 63.2% male, Mage = 42.7 years) were United States military veterans (n = 108), active duty military personnel (n = 12), and civilians (n = 6), who were participating in one of nine PTSD treatment trials. The results indicate a predominately negative COVID‐19 impact on therapy participation, although some participants (26.1%) found attending therapy sessions through telehealth to be easier than in‐person therapy. Most participants (66.7%) reported that completing in vivo exposure homework became harder during the pandemic. Moreover, the impact of the pandemic on PTSD symptom severity and daily stress were each associated with increased difficulty with aspects of therapy participation. The findings highlight the unique challenges to engaging in PTSD treatment during the pandemic as well as a negative impact on daily stress and PTSD severity, both of which were related to treatment engagement difficulties.
Surgical Treatment Strategies for Laryngeal Chondrosarcomas: A Single Institution Investigation
Authors: Zeitels Steven M. , Baird Brandon J.
Published: July 2021

Objectives/Hypothesis

Laryngeal chondrosarcomas are rare malignancies with a spectrum of presentations due to varying size, local extension, and biological behavior. Moreover, these neoplasms have differing effects on respiration, phonation, and deglutition. Consequently, it is valuable to assess endoscopic and transcervical treatment strategies.

Study Design

Retrospective case series.

Methods

A retrospective review was done from 2001 to 2020; 25 patients were identified with laryngeal chondrosarcomas. Their tumor pathology and treatment were analyzed.

Results

All 25 chondrosarcomas were in the posterior cricoid and arose in proximity to at least one cricoarytenoid joint: 23 of 25 grade I–II (low‐mid), one of 25 grade II–III (mid‐high), and one of 25 grade III (high). Some tumor was left in 23 of 25 to preserve cricoarytenoid‐joint function. There were no known disease‐specific deaths (~8‐year median follow‐up). Final surgical treatment in 24 of 25 was: 13 of 25 transcervical partial laryngectomy, 7 of 25 transoral‐endoscopic removal, 4 of 25 total laryngectomy, and 1 of 25 observation.

Conclusions

In this series, unresected intercurrent disease with laryngeal chondrosarcomas was not life‐threatening. Therefore, disease was typically left in the posterior cricoid region to preserve mobility of at least one cricoarytenoid joint. This philosophy employed an ultra‐function‐sparing conservation approach that preserved and/or restored optimal voice, airway patency and swallowing.

Level of Evidence

4 Laryngoscope, 132:169–176, 2022
Evaluating the capability of a UAV‐borne spectrometer for soil organic carbon mapping in bare croplands
Authors: Zhang He , Shi Pu , Crucil Giacomo , van Wesemael Bas , Limbourg Quentin , Van Oost Kristof
Published: July 2021

High‐resolution, field‐scale soil organic carbon (SOC) mapping in croplands is crucial for effective and precise agricultural management. Recent developments in unmanned aerial vehicles (UAVs) combined with miniaturized visible–near infrared spectrometers have enabled the rapid and low‐cost field‐scale SOC mapping. However, a field‐specific spectrotransfer model is often needed for such UAV‐based hyperspectral measurements, implying local sampling and model development are still required, and this hampers the widespread application of UAV‐based methods. In this study, we aim to test to what extent SOC prediction models derived from an existing regional soil spectral library (SSL) can be applied to UAV‐based hyperspectral data, without the need for additional field sampling. To this end, an UAV survey was conducted over a bare cropland within the Belgian Loam Belt for field‐scale SOC mapping. We evaluated two calibration approaches, one based on local sampling and model development, and one where we capitalized on an existing (laboratory‐based) regional SSL. For the local calibration approach, we obtained a good prediction performance with RMSE of 0.57 g kg−1 and RPIQ of 2.35. For the regional model, a spectral alignment procedure was needed to resolve the discrepancy between UAV‐ and laboratory‐based measurements. This resulted in a fair SOC prediction accuracy with RMSE of 0.93 g kg−1 and RPIQ of 1.45. The comparison of SOC maps derived from the two approaches, along with an external validation showed a high consistency, indicating that UAV‐based spectral measurements, in combination with SSLs have the potential to improve the efficiency of high‐resolution SOC mapping.
Postoperative antibiotic use in patients with unilateral purulent chronic rhinosinusitis
Authors: Gordon Alex , Benedict Peter , Marcus Sonya , Kingery Matthew , Lebowitz Richard A. , Lieberman Seth M.
Published: July 2021

Objectives

To describe our experience with the use of postoperative antibiotics in the management of unilateral chronic rhinosinusitis (CRS) patients with active infection at the time of surgery, and to evaluate the need for routine postoperative antibiotic administration in this population.

Methods

This retrospective chart review analyzed the medical records of all patients who underwent endoscopic sinus surgery for unilateral purulent CRS between November 2013 and September 2019 at a tertiary care center and who were not prescribed routine postoperative antibiotics. Duration of time until normalization of sinus cavities and whether antibiotics were ultimately prescribed for persistent infectious signs and symptoms were recorded. Patient characteristics and findings were analyzed to determine if any of the evaluated parameters were associated with the need for postoperative antibiotics.

Results

Sixty‐nine patients were included in the study. Thirty‐three (47.8%) did not require antibiotics during the postoperative period. The average time to sinus normalization was 8.1 weeks (range 1‐24 weeks) for patients who received antibiotics and 5.7 weeks (range 1‐16 weeks) for those who did not receive antibiotics (P = .066). No evaluated variables were associated with antibiotic use on univariate or multivariate analysis.

Conclusion

Postoperative antibiotics were not necessary to normalize infected sinus cavities for nearly half of patients with unilateral purulent CRS in this series. Further studies are needed to better delineate which patients would derive benefit from postoperative antibiotics.

Level of Evidence

Level IV.