bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic value of preoperative fine needle aspiration cytology in parotid gland tumors
Authors: Hanege Fatih Mehmet , Tuysuz Ozan , Sakallioglu Oner , Arslan Solmaz Ozgen
Published: June 2020

Background

Salivary gland masses constitute a broad spectrum of lesions ranging from non‐neoplastic to benign and malignant lesions. Parotid is the largest salivary gland and constitutes 75% to 80% of all salivary gland areas. 80% of parotid lesions are benign and 20% are malignant.

Methods

Two‐hundred and eight‐six patients who underwent aspiration cytology in the pathology laboratory between January 1995 and January 2019, evaluated with a sufficient sample and diagnosed, and subsequently underwent surgical treatment were included in the study.

Results

47.9% (137) of the patients were female and 52.1% (149) were male. The mean age was 58 years (range: 38‐84 years). 13 (4.54%) of the cases were evaluated as non‐diagnostic, 12 (4.1%) as atypia of undetermined significance, 196 (68.5%) as benign neoplasm, 43 (15%) as suspicious for malignancy, and 22 (7.86%) were evaluated as malignant. In the histopathological examination of the samples prepared from surgical specimens of 13 non‐diagnostic cases, seven (53.8%) cases were reported as Warthin tumors, four (30.7%) as pleomorphic adenomas, and two (15.5%) were reported as lymph nodes with intraparotid localization.

Conclusion

The diagnosis of Fine needle aspiration cytology (FNAC) in the parotid gland is difficult due to the rarity of malignant salivary gland neoplasms, the diversity of carcinoma types, and the similarity of cytologic findings of benign tumors and low‐grade carcinomas. The diagnostic accuracy of preoperative FNAC is high for benign tumors and low for malignant tumors.
High TG to HDL ratio plays a significant role on atherosclerosis extension in prediabetes and newly diagnosed type 2 diabetes subjects
Authors: Scicali Roberto , Giral Philippe , D'Erasmo Laura , Cluzel Philippe , Redheuil Alban , Di Pino Antonino , Rabuazzo Agata Maria , Piro Salvatore , Arca Marcello , Béliard Sophie , Purrello Francesco , Bruckert Eric , Gallo Antonio
Published: June 2020

Aims

We investigated the role of TG to HDL ratio (TG/HDL) on atherosclerosis extension, defined as presence of coronary artery calcium (CAC), carotid and femoral plaque, in prediabetes or newly diagnosed type 2 diabetes (T2D).

Methods

We performed a retrospective, cross‐sectional, single centre study involving 440 prediabetes or newly diagnosed controlled T2D subjects. Participants underwent CAC analysis by computed tomography and carotid and femoral plaque evaluation by ultrasonography and were stratified in high TG/HDL (H‐TG/HDL) or low TG/HDL (L‐TG/HDL) group according to TG/HDL median value. We estimated atherosclerosis extension according to the number of involved vascular districts.

Results

CAC was higher in the H‐TG/HDL group than L‐TG/HDL group (29.15 [0.0‐95.68] vs 0.0 [0.0‐53.97] AU, P < .01) and CAC > 0 was more prevalent in the H‐TG/HDL group than L‐TG/HDL group (64.5% vs 45%, P < .001). Femoral atherosclerosis was higher in the H‐TG/HDL group than L‐TG/HDL group (57.3% vs 43.6%, P < .01). H‐TG/HDL group exhibited a lower prevalence of subjects with 0‐TWP compared to L‐TG/HDL group (21.8% vs 38.6%, P < .01) and higher percentages of subjects with 2‐TWP or 3‐TWP than L‐TG/HDL group (for 2‐TWP 29.5% vs 21.5%, P < .05; for 3‐TWP 32.7% vs 20.9%, P < .01). Multiple logistic regression analysis showed that a H‐TG/HDL was inversely associated to 0‐TWP (P < .05) and positively associated with 2‐TWP (P < .05) and 3‐TWP (P < .01).

Conclusions

Our data suggest that TG/HDL is a marker of increased atherosclerotic extension in prediabetes and newly diagnosed T2D and may be useful to identify subjects with a higher cardiovascular risk profile.
Co‐microencapsulation of human umbilical cord‐derived mesenchymal stem and pancreatic islet‐derived insulin producing cells in experimental type 1 diabetes
Authors: Montanucci Pia , Pescara Teresa , Greco Alessia , Leonardi Giulia , Marini Luigi , Basta Giuseppe , Calafiore Riccardo
Published: June 2020

Introduction

Post‐partum umbilical cord Wharton Jelly‐derived adult mesenchymal stem cells (hUCMS) hold anti‐inflammatory and immunosuppressive properties. Human pancreatic islet‐derived progenitor cells (hIDC) may de‐differentiate, and subsequently re‐differentiate into insulin producing cells. The two cell types share common molecules that facilitate their synergistic interaction and possibly crosstalk, likely useful for the cell therapy of type 1 diabetes (T1D).

Materials and methods

Upon microencapsulation in sodium alginate (AG), hUCMS and hIDC were able to form cell co‐aggregates that looked well integrated and viable. We then grafted microencapsulated hUCMS/hIDC co‐aggregates into non‐obese diabetic/severe combined immunodeficient (NOD/SCID) mice, and observed an acquired ability of cells to produce and store hormones. Finally, we transplanted these biohybrid constructs into NOD mice with recent onset, spontaneous overt diabetes, observing a decline of blood glucose levels.

Results

In vitro, we have shown that hUCMS inhibited proliferation of allogeneic polymorphonuclear blood cells from patients with T1D, while promoting expansion of FoxP3+ Tregs.

Reversal of hyperglycemia in diabetic NODs seems to suggest that hUCMS and hIDC, upon co‐microencapsulation, anatomically and functionally synergized to accomplish two goals: maintain tracer insulin output by hIDC, while exploting the immunoregulatory properties of hUCMS.

Conclusion

We have gathered preliminary evidence that the two adult stem cell types within AG microcapsules, may synergistically promote tracer insulin production, while “freezing” the autoimmune disease process, and help reversal of the recent onset hyperglycemia in a spontaneous, autoimmune rodent model of diabetes, the NOD mouse, with no need for pharmacologic immunosuppression.
Wildlife roadkill patterns in a fragmented landscape of the Western Amazon
Authors: Filius Jonathan , van der Hoek Yntze , Jarrín‐V Pablo , van Hooft Pim
Published: June 2020

One of the most evident and direct effects of roads on wildlife is the death of animals by vehicle collision. Understanding the spatial patterns behind roadkill helps to plan mitigation measures to reduce the impacts of roads on animal populations. However, although roadkill patterns have been extensively studied in temperate zones, the potential impacts of roads on wildlife in the Neotropics have received less attention and are particularly poorly understood in the Western Amazon. Here, we present the results of a study on roadkill in the Amazon region of Ecuador; a region that is affected by a rapidly increasing development of road infrastructure. Over the course of 50 days, in the wet season between September and November 2017, we searched for road‐killed vertebrates on 15.9 km of roads near the city of Tena, Napo province, for a total of 1,590 surveyed kilometers. We recorded 593 dead specimens, predominantly reptiles (237 specimens, 40%) and amphibians (190, 32%), with birds (102, 17%) and mammals (64, 11%) being less common. Recorded species were assigned to three functional groups, based on their movement behavior and habitat use (“slow,” “intermediate,” and “fast”). Using Ripley's K statistical analyses and 2D HotSpot Identification Analysis, we found multiple distinct spatial clusters or hotspots, where roadkill was particularly frequent. Factors that potentially determined these clusters, and the prevalence of roadkill along road segments in general, differed between functional groups, but often included land cover variables such as native forest and waterbodies, and road characteristics such as speed limit (i.e., positive effect on roadkill frequency). Our study, which provides a first summary of species that are commonly found as roadkill in this part of the Amazon region, contributes to a better understanding of the negative impacts of roads on wildlife and is an important first step toward conservation efforts to mitigate these impacts.
The Effect of Bio‐inspired Co‐electrolytes for Enhancement of Electrochemical Properties of Supercapacitors
Authors: Wadekar Pravin. H. , Khose Rahul. V. , Pethsangave Dattatray. A. , Some Surajit.
Published: June 2020

In the current work, we are introducing the concept of co‐electrolyte in the aqueous medium. Herein, we have prepared the bio‐inspired co‐electrolyte of choline chloride and potassium hydroxide, which in situ produces choline hydroxide and potassium chloride by the ion‐exchange mechanism. The resultant co‐electrolyte (RCE) solution exhibits decent electrochemical property than its parental salts, that is, potassium hydroxide, choline chloride. The RCE further used to enhance the energy storage ability of reduced graphene oxide (RGO). The material exhibits maximum specific capacitance 394 F g−1 and higher energy density 44.3 Wh kg−1 at the current density of 1 A g−1 in the presence of co‐electrolyte, which is higher as compared to its preceding salts as an electrolyte. Also, the material exhibits lower equivalent series resistance, that is, 0.3 Ω in RCE. This concept can be considered as future development in the field of energy storage materials.
Is optimum always optimal? A revisit of the mean‐variance method under nonlinear measures of dependence and non‐normal liquidity constraints
Authors: Al Janabi Mazin A.M.
Published: June 2020

We develop a model for optimizing multiple‐asset portfolios with semi‐parametric liquidity‐adjusted value‐at‐risk (LVaR), whereby linear correlations are substituted by the multivariate nonlinear Kendall's tau dependence measure, under multiple credible operational and budget constraints. When considering a diversified large portfolio of international stock markets of both developed and emerging economies and commodities, under both regular and stressed market perspectives, the obtained results consistently confirm the dominance of our modeling algorithms relative to other competing portfolio strategies, including the traditional mean‐variance VaR approach and global minimum‐variance portfolios. The obtained results are robust to different trading scenarios and promising for practical optimization techniques in large multiple‐asset portfolios and operation research models in financial institution management.
Forecasting bitcoin volatility: Evidence from the options market
Authors: Hoang Lai T. , Baur Dirk G.
Published: June 2020

This paper studies a large number of bitcoin (BTC) options traded on the options exchange Deribit. We use the trades to calculate implied volatility (IV) and analyze if volatility forecasts can be improved using such information. IV is less accurate than AutoRegressive–Moving‐Average or Heterogeneous Auto‐Regressive model forecasts in predicting short‐term BTC volatility (1 day ahead), but superior in predicting long‐term volatility (7, 10, 15 days ahead). Furthermore, a combination of IV and model‐based forecasts provides the highest accuracy for all forecasting horizons revealing that the BTC options market contains unique information.
Cinnabar provenance of Chalcolithic red pigments in the Iberian Peninsula: A lead isotope study
Authors: Rodríguez Javier , Montero‐Ruiz Ignacio , Hunt‐Ortiz Mark , García‐Pavón Evangelina
Published: June 2020

We report lead isotope data for cinnabar from three Chalcolithic settlements and several ore deposits in the Iberian Peninsula. Lead isotope ratios of cinnabar (vermilion) employed in one Bell Beaker grave at Humanejos (Madrid) plot in the field of the Almaden mining district. Cinnabar from the La Velilla dolmen (Palencia) also plots in the isotopic field of Almaden ores but is also comparable to the closer Miñera de Luna deposit in the Cantabrian Ranges. Cinnabar used in the dolmen of Montelirio (Seville) has an unknown origin, as its new lead isotope ratios obtained do not match with any of the studied ore deposits. We conclude that cinnabar was a well‐known raw material and several ore deposits were mined in the Iberian Peninsula during the Chalcolithic. The societies established at the northern and central parts of the peninsula employed locally sourced cinnabar (<200 km away) in their funerary rituals. The Chalcolithic society settled at the estuary of the Guadalquivir river (south of Spain) employed cinnabar of unknown origin, leaving open the possibility of long‐distance cinnabar trade.
Debris flow events of 4000 a BP and its resulting archaeological site destruction in Qian River gorge, the upper reach of Wei River, central China
Authors: Fan Shuanghu , Zhang Tianyu , Chen Shue , Hu Jianmin , Lu Yudong , Du Hua
Published: June 2020

In the study of global change, the relationship between the Holocene climatic disaster events and the rise and fall of ancient civilization is of considerable significance to a profound understanding of civilization evolution and human‐land harmony. During the geological survey in the western Wei River Basin, a debris‐flow event that would have destroyed an archaeological site was uncovered in the Holocene loesson the south bank of the Qian River. They were studied by field observations and laboratory analysis, including magnetic susceptibility, particle size distribution, carbonate content determination, and AMS14C dating. The debris‐flow event was dated at about 3702 BP to 4084 cal BP by using the AMS14C in combination with archaeological artefacts age determination. Mingling with cultural layer, whole pig bones, and covering ash pit and cellars, the debris flow incident was linked to the site destruction. Combined with the global climate background at about 4000 a BP, the palaeo‐floods records in the Wei River Basin, and the regional palaeo‐earthquakes, we infer that the debris‐flow was triggered by large earthquake and heavy rainfall and was a regional hydrological response to the 4.0 ka global climate event. Moreover, the debris‐flow incident and its resulting archaeological site ruin have essential scientific significance for exploring the climate environment evolution, the ancient civilization evolvement, and the human‐land relationship development in the Wei River Basin and surrounding area.
Simulating precipitation in the Northeast United States using a climate‐informed K‐nearest neighbour algorithm
Authors: Armal Saman , Devineni Naresh , Krakauer Nir Y. , Khanbilvardi Reza
Published: June 2020

Decadal prediction using climate models faces long‐standing challenges. While global climate models may reproduce long‐term shifts in climate due to external forcing, in the near term, they often fail to accurately simulate interannual climate variability, as well as seasonal variability, wet and dry spells, and persistence, which are essential for water resources management. We developed a new climate‐informed K‐nearest neighbour (K‐NN)‐based stochastic modelling approach to capture the long‐term trend and variability while replicating intra‐annual statistics. The climate‐informed K‐NN stochastic model utilizes historical data along with climate state information to provide improved simulations of weather for near‐term regional projections. Daily precipitation and temperature simulations are based on analogue weather days that belong to years similar to the current year's climate state. The climate‐informed K‐NN stochastic model is tested using 53 weather stations in the Northeast United States with an evident monotonic trend in annual precipitation. The model is also compared to the original K‐NN weather generator and ISIMIP‐2b GFDL general circulation model bias‐corrected output in a cross‐validation mode. Results indicate that the climate‐informed K‐NN model provides improved simulations for dry and wet regimes, and better uncertainty bounds for annual average precipitation. The model also replicates the within‐year rainfall statistics. For the 1961–1970 dry regime, the model captures annual average precipitation and the intra‐annual coefficient of variation. For the 2005–2014 wet regime, the model replicates the monotonic trend and daily persistence in precipitation. These improved modelled precipitation time series can be used for accurately simulating near‐term streamflow, which in turn can be used for short‐term water resources planning and management.
An experimental study of dispersion of an interactive tracer in chemically heterogeneous medium at a column scale
Authors: Benmahdi Fatiha , Semra Safia , Kolli Mounira , Bouhelassa Mohammed
Published: June 2020

This paper aims at examining the increase of phenol adsorption breakthrough curves spreading caused by the chemical heterogeneity of granular activated carbon fixed beds. The local and the thermodynamic equilibrium assumption, as well as the nonlinear adsorption obeying to Langmuir isotherm, are considered. This study particularly tempts to link the reduced variance of phenol breakthrough curves to a measurable quantifying parameter of the chemical heterogeneity. The investigated artificial heterogeneous media are prepared by alternating layers of two types of granular activated carbon, active and non‐active ones, that have similar physical properties. On the one hand, the chemical heterogeneity is quantified by the active layer relative thickness of the column length, l1/L. On the other hand, it is quantified by the mean value of the probability distribution γ. The latter also represents the mean active grains mass ratio of the total medium mass, hence the medium mean capacity. The obtained results show an increase in the reduced variance and thus the effective global dispersion with the heterogeneity; the increase is as important as the medium capacity decreases. However, the dispersion increase achieves a limit value, even when the heterogeneity increases. The results are statistically modelled using a regression equation function of the capacity variation in terms of γ and the chemical heterogeneity in terms of l1/L. The relationship combining the medium capacity and the chemical heterogeneity is obtained. The relationship implicitly takes into account the effect of the column length.
Analysis of the expression profile of long non‐coding RNAs MALAT1 and THRIL in children with immune thrombocytopenia
Authors: Ayoub Shymaa E. , Hefzy Enas M. , Abd El‐Hmid Rehab G. , Ahmed Naglaa A. , Khalefa Abeer A. , Ali Doaa Y. , Ali Marwa A.
Published: June 2020

Background/Aims

Pediatric immune thrombocytopenia (ITP) is an autoimmune disease; whose etiology is not exactly understood and seems to be highly multifactorial. Long non‐coding RNAs (lncRNAs) are key regulators of different actions, which contribute to the development of many autoimmune diseases. To gain a further understanding, we estimated the relative expression of lncRNAs Metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) and tumor necrosis factor‐α (TNF‐α) and heterogeneous nuclear ribonucleoprotein L (hnRNPL) immune‐regulatory lncRNA (THRIL) in pediatric ITP.

Methods

In this case‐control study, analysis of the expression profiles of these lncRNAs in blood samples from children with ITP and healthy controls (HCs) using quantitative real‐time PCR was done. The association of MALAT1 and THRIL with ITP clinical features and their potential usage as non‐invasive circulating biomarkers for ITP diagnosis was also evaluated. The receiver operating characteristic curve was constructed, and an area under the curve was analyzed.

Results

Both lncRNAs MALAT1 and THRIL were significantly upregulated in ITP patients in comparison to HCs ( p < .0001 and = .001 respectively). In addition, there was a positive significant correlation between the expression level of both biomarkers among patients (r = 0.745, p < .0001). At cutoff points of 1.17 and 1.27 for lncRNAs MALAT1and THRIL, respectively, both biomarkers had an excellent specificity (100% for both) and fair sensitivity (63.6 and 73.3% for lncRNAs MALAT1and THRIL, respectively). Improvement of biomarkers specificity was obtained by evaluation of the combined expression of both biomarkers. Serum lncRNAs MALAT1 and THRIL could be used as potential biomarkers in differentiating childhood ITP patients and HCs.
Estimation and inference for spatial models with heterogeneous coefficients: An application to US house prices
Authors: Aquaro Michele , Bailey Natalia , Pesaran M. Hashem
Published: June 2020

This paper considers the estimation and inference of spatial panel data models with heterogeneous spatial lag coefficients, with and without weakly exogenous regressors, and subject to heteroskedastic errors. A quasi maximum likelihood (QML) estimation procedure is developed and the conditions for identification of the spatial coefficients are derived. The QML estimators of individual spatial coefficients, as well as their mean group estimators, are shown to be consistent and asymptotically normal. Small‐sample properties of the proposed estimators are investigated by Monte Carlo simulations and results are shown to be in line with the paper's key theoretical findings, even for panels with moderate time dimensions and irrespective of the number of cross‐section units. A detailed empirical application to US house price changes during the 1975–2014 period shows a significant degree of heterogeneity in spatiotemporal dynamics over the 338 Metropolitan Statistical Areas considered.
Transcriptional factor engineering in microbes for industrial biotechnology
Authors: Wang Tianwen , Liang Chen , Xing Wenxiu , Wu Wanyu , Hou Yajing , Zhang Linfang , Xiao Sa , Xu Hongju , An Yafei , Zheng Mengyuan , Liu Lu , Nie Lei
Published: June 2020

Transcription can be regulated by controlling the provision of transcriptional factors (TFs), because TFs determine the transcription process by specifying the binding of RNA polymerase holoenzyme on promoters. Manipulations, such as replacing endogenous TFs with mutants obtained through directed evolution (or rational design), and introducing compatible heterogeneous TFs, are effective ways to regulate transcription. Designing artificial TFs with desired properties by following the principles of protein design and reconstructing ancestral TFs with the information gained from a perspective of evolution by multiple sequence alignments of the related TFs, are feasible alternative options. The engineered TFs can be used to create inducible protein expression systems that respond to a specific stimulus. Moreover, the engineered TFs could lead to a transcriptional profile different from that of the wild‐type strains. Accordingly, these engineered TFs could be utilized to construct strains resistant to adverse conditions, since the emergence of resistance generally requires global transcriptional changes at the transcriptomic scale. Meanwhile, these engineered TFs can also be employed in the construction of sophisticatedly designed genetic circuits for diverse purposes. In this paper, we reviewed the advances in the above‐mentioned aspects. © 2020 Society of Chemical Industry
Intrathoracic shunt displacement with massive pleural effusion after successful shunt placement in a hydropic fetus with multilocular macrocystic congenital pulmonary airway malformation
Authors: Hara Asako , Hidaka Nobuhiro , Nitahara Kenta , Sakai Atsuhiko , Kido Saki , Kato Kiyoko
Published: June 2020

We successfully performed shunting for a fetus with a multilocular macrocystic lung mass with hydrops at 22 weeks' gestation. Complete resolution of hydrops was achieved; however, at 35 weeks' gestation, the fetus developed acute massive pleural effusion. Fetal ultrasound examination revealed that one end of the shunting tube had migrated downward in the thoracic cavity, which led to fluid draining from the lung cyst. The baby was delivered at term and was discharged following neonatal intensive care management. Intrathoracic displacement of the shunt can occur, followed by massive pleural effusion due to drainage of cystic fluid.
Genetic counselors’ perspectives on population‐based screening for BRCA‐related hereditary breast and ovarian cancer and Lynch syndrome
Authors: De Simone Lenika M. , Arjunan Aishwarya , Vogel Postula Kristen J. , Maga Tara , Bucheit Leslie A.
Published: June 2020

Early identification of those with BRCA‐related Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch syndrome has the potential for early cancer detection and/or prevention; as such, these conditions are considered Tier 1 genetic conditions by the U.S. Center for Disease Control and Prevention. Given the decreasing cost of genetic testing, population‐based screening (PBS) for such conditions may be the next step toward cancer prevention. This study aimed to understand genetic counselors’ perspectives toward offering PBS for the Tier 1 conditions BRCA‐related HBOC and Lynch syndrome. An online survey was distributed to 3,609 members of the National Society of Genetic Counselors. A total of 367 individuals participated in the study. Fifty percent of respondents felt that PBS for inherited cancer should not be offered; 93.3% felt that the current healthcare system is unprepared for implementation of PBS. However, most respondents agreed that PBS should be implemented within the next 10 years. Attitudes toward offering PBS were associated with respondents’ work setting, cancer specialization, and perceived preparedness (p's < 0.05). The most commonly reported barriers to the implementation of PBS were shortage of genetic professionals and lack of infrastructure. Data in this study provide evidence that infrastructural barriers and educational gaps of non‐genetic professionals would need to be addressed before successful integration of PBS into the healthcare system.
Modelling integrated antiretroviral treatment and harm reduction services on HIV and overdose among people who inject drugs in Tijuana, Mexico
Authors: Cepeda Javier A , Bórquez Annick , Magana Christopher , Vo Anh , Rafful Claudia , Rangel Gudelia , Medina‐Mora María E , Strathdee Steffanie , Martin Natasha K
Published: June 2020

Introduction

The HIV epidemic in Tijuana, Mexico is concentrated in key populations, including people who inject drugs (PWID). However, HIV interventions among PWID are minimal, and federal funding was provided for compulsory abstinence programmes associated with HIV and overdose. Alternatively, opioid agonist therapy reduces overdose, reincarceration, HIV, while improving antiretroviral therapy (ART) outcomes. We assessed potential impact and synergies of scaled‐up integrated ART and opioid agonist therapy, compared to scale‐up of each separately, and potential harms of compulsory abstinence programmes on HIV and fatal overdose among PWID in Tijuana.

Methods

We developed a dynamic model of HIV transmission and overdose among PWID in Tijuana. We simulated scale‐up of opioid agonist therapy from zero to 40% coverage among PWID. We evaluated synergistic benefits of an integrated harm reduction and ART scale‐up strategy (40% opioid agonist therapy coverage and 10‐fold ART recruitment), compared to scale‐up of each intervention alone or no scale‐up of low coverage ART and no harm reduction). We additionally simulated compulsory abstinence programmes (associated with 14% higher risk of receptive syringe sharing and 76% higher odds of overdose) among PWID.

Results

Without intervention, HIV incidence among PWID could increase from 0.72 per 100 person‐years (PY) in 2020 to 0.92 per 100 PY in 2030. Over ten years, opioid agonist therapy scale‐up could avert 31% (95% uncertainty interval (UI): 18%, 46%) and 22% (95% UI: 10%, 28%) new HIV infections and fatal overdoses, respectively, with the majority of HIV impact from the direct effect on HIV transmission due to low ART coverage. Integrating opioid agonist therapy and ART scale‐up provided synergistic benefits, with opioid agonist therapy effects on ART recruitment/retention averting 9% more new infections compared to ART scale‐up alone. The intervention strategy could avert 48% (95% UI: 26%, 68%) of new HIV infections and one‐fifth of fatal overdoses over ten years. Conversely, compulsory abstinence programmes could increase HIV and overdoses.

Conclusions

Integrating ART with opioid agonist therapy could provide synergistic benefits and prevent HIV and overdoses among PWID in Tijuana, whereas compulsory abstinence programmes could cause harm. Policymakers should consider the benefits of integrating harm reduction and HIV services for PWID.
Integrating HIV pre‐exposure prophylaxis and harm reduction among men who have sex with men and transgender women to address intersecting harms associated with stimulant use: a modelling study
Authors: Bórquez Annick , Rich Katherine , Farrell Michael , Degenhardt Louisa , McKetin Rebecca , Tran Lucy T. , Cepeda Javier , Silva‐Santisteban Alfonso , Konda Kelika , Cáceres Carlos F. , Kelly Sherrie , Altice Frederick L. , Martin Natasha K.
Published: June 2020

Introduction

Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre‐exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants.

Methods

We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 [95%CI: 1.17 to 1.57]) obtained from local data, and increased risk of suicide (SMR = 6.26 [95%CI: 2.84 to 13.80]) and CVD (SMR = 1.83 [95%CI: 0.39 to 8.57]) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01‐2020/01‐2021). We also investigated the 10‐year impact (01‐2020/01‐2030) of: (1) PrEP prioritization for stimulant‐using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant‐associated risk.

Results

MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant‐associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade.

Conclusions

MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.
Integrated screening and treatment services for HIV, hypertension and diabetes in Kenya: assessing the epidemiological impact and cost‐effectiveness from a national and regional perspective
Authors: Kasaie Parastu , Weir Brian , Schnure Melissa , Dun Chen , Pennington Jeff , Teng Yu , Wamai Richard , Mutai Kipkoech , Dowdy David , Beyrer Chris
Published: June 2020

Introduction

As people with HIV age, prevention and management of other communicable and non‐communicable diseases (NCDs) will become increasingly important. Integration of screening and treatment for HIV and NCDs is a promising approach for addressing the dual burden of these diseases. The aim of this study was to assess the epidemiological impact and cost‐effectiveness of a community‐wide integrated programme for screening and treatment of HIV, hypertension and diabetes in Kenya.

Methods

Coupling a microsimulation of cardiovascular diseases (CVDs) with a population‐based model of HIV dynamics (the Spectrum), we created a hybrid HIV/CVD model. Interventions were modelled from year 2019 (baseline) to 2023, and population was followed to 2033. Analyses were carried at a national level and for three selected regions (Nairobi, Coast and Central).

Results

At a national level, the model projected 7.62 million individuals living with untreated hypertension, 692,000 with untreated diabetes and 592,000 individuals in need of ART in year 2018. Improving ART coverage from 68% at baseline to 88% in 2033 reduced HIV incidence by an estimated 64%. Providing NCD treatment to 50% of diagnosed cases from 2019 to 2023 and maintaining them on treatment afterwards could avert 116,000 CVD events and 43,600 CVD deaths in Kenya over the next 15 years. At a regional level, the estimated impact of expanded HIV services was highest in Nairobi region (averting 42,100 HIV infections compared to baseline) while Central region experienced the highest impact of expanded NCD treatment (with a reduction of 22,200 CVD events). The integrated HIV/NCD intervention could avert 7.76 million disability‐adjusted‐life‐years (DALYs) over 15 years at an estimated cost of $6.68 billion ($445.27 million per year), or $860.30 per DALY averted. At a cost‐effectiveness threshold of $2,010 per DALY averted, the probability of cost‐effectiveness was 0.92, ranging from 0.71 in Central to 0.92 in Nairobi region.

Conclusions

Integrated screening and treatment of HIV and NCDs can be a cost‐effective and impactful approach to save lives of people with HIV in Kenya, although important variation exists at the regional level. Containing the substantial costs required for scale‐up will be critical for management of HIV and NCDs on a national scale.
Positron emission tomography imaging of a novel Anxa1‐targeted peptide 18F‐Al‐NODA‐Bn‐p‐SCN‐GGGRDN‐IF7 in A431 cancer mouse models
Authors: Chen Fei , Xiao Yichun , Shao Kejing , Zhu Bao , Jiang Mengjun
Published: June 2020

Annexin 1 (Anxa1) is a highly specific surface marker of tumor vasculature in the lung and prostate solid tumors. The IF7 peptide was modified with a hydrophilic linker, GGGRDN, and coupled with a new bifunctional chelating agent NODA‐Bn‐p‐SCN. The resulting peptides (NODA‐Bn‐p‐SCN‐GGGRDN‐IF7) were successfully labeled with Al18F. The targeting characteristics of the radiolabeled peptides were evaluated in the Anxa1 positive A431 tumor model. Micro‐positron emission tomography (micro‐PET) imaging revealed that the A431 tumors were clearly visualized (5.74 ± 1.13%ID/g, 3.92 ± 0.78%ID/g and 1.30 ± 0.43%ID/g at 0.5, 1, and 2 h post‐injection, respectively). Anxa1 binding specificity was also demonstrated by reduced tumor uptake after co‐injection with excessive unlabeled GGGRDN‐IF7 peptide at 30, 60, and 120 min post‐injection. 18F‐Al‐NODA‐Bn‐p‐SCN‐GGGRDN‐IF7 might be a potential PET imaging agent for detecting Anxa1 levels in cancers due to the favorable characteristics such as convenient synthesis, specific Anxa1 targeting, and good tumor uptakes.
Morphology and immunohistochemistry of the olfactory organ in the bloodfin tetra, Aphyocharax anisitsi (Ostariophysi: Characidae)
Authors: Pintos Santiago , Rincon‐Camacho Laura , Pandolfi Matias , Pozzi Andrea G.
Published: June 2020

Among teleost fishes, differences exist in the shape, number, and arrangement of the olfactory lamellae, the distribution of the sensory and non‐sensory epithelium, as well as, the abundance of various receptor cells. The objective of this work was to describe the morphology, immunohistochemistry, and scanning electron microscopy ultrastructure of the olfactory epithelium of the bloodfin tetra, Aphyocharax anisitsi. This is the first complete description including the anatomy, histology, and immunohistochemistry of the peripheral olfactory organ from a Characiformes. Based on the external morphology of the olfactory organ, A. anisitsi was classified as a ditermous species, with an olfactory cavity containing two openings divided by a skin flap that separates the anterior and posterior nostril. This species belongs to the group of isosmates, since the presence of accessory olfactory sacs was not observed, and non‐sensory ciliated cells were identified. A. anisitsi has an olfactory rosette with an arrow‐shaped arrangement, with differences in length between the anterior and posterior lamellae. In the olfactory epithelium, three types of olfactory receptor neurons were identified using histology and confirmed by immunohistochemistry, that is, ciliated olfactory receptor neurons in the basal region of the epithelium, microvillar olfactory receptor neurons in the middle region; and Crypt cells, in smaller numbers compared to the other neuronal types, present in the apical region. Sensory and non‐sensory areas were scattered and mixed along the lamellar lateral surface but the nasal cavity and the midline raphe lacked olfactory receptor neurons. The presence of abundant kinocilia in the non‐sensory cells could be related in A. anisitsi with ventilation and quality control of water entering the olfactory cavity. The spatial organization of the sensory and non‐sensory areas in A. anisitsi was similar to that observed in other species that also inhabit still and slow‐flowing bodies of water with high‐density vegetation.
In memory of tachycardia: A wide complex tachycardia in a young male
Authors: Siroky Gregory P. , Keller Seth , Suri Ranjit
Published: June 2020

We present a case of a 24‐year‐old male with palpitations and a wide complex tachycardia. Baseline electrocardiogram (ECG) after termination of tachycardia demonstrates a normal rhythm but with inferior/anterolateral T‐wave inversions (TWIs). Electrophysiologic study confirmed the diagnosis of posterior fascicular ventricular tachycardia successfully terminated by anatomic ablation of the left posterior fascicle. TWIs on the patient's baseline ECG were consistent with cardiac memory.
Hypermetabolism and Coronavirus Disease 2019
Authors: Yu Pey‐Jen , Cassiere Hugh , DeRosa Sarah , Bocchieri Karl , Yar Shiraz , Hartman Alan
Published: June 2020

Background

Hypermetabolism has been described in stress states such as trauma, sepsis, acute respiratory distress syndrome, and severe burn injuries. We hypothesize that patients with Coronavirus disease 2019 (COVID‐19) may develop a hypermetabolic state, which may be a major contributing factor to the extraordinary ventilatory and oxygenation demands in patients with COVID‐19.

Method

Resting energy expenditure (REE), carbon dioxide production (VCO2), and oxygen consumption (VO2) were measured by indirect calorimetry on 7 critically ill patients with COVID‐19.

Results

The median measured REE was 4044 kcal/d, which was 235.7% ± 51.7% of predicted. The median VCO2 was 452 mL/min (range, 295–582 mL/min), and the median VO2 was 585 mL/min (range, 416–798 mL/min).

Conclusion

Critically ill patients with COVID‐19 are in an extreme hypermetabolic state. This may explain the high failure rates for mechanical ventilation for these patients and highlights the potential need for increased nutrition requirements for such patients.
Optimally estimating the sample standard deviation from the five‐number summary
Authors: Shi Jiandong , Luo Dehui , Weng Hong , Zeng Xian‐Tao , Lin Lu , Chu Haitao , Tong Tiejun
Published: June 2020

When reporting the results of clinical studies, some researchers may choose the five‐number summary (including the sample median, the first and third quartiles, and the minimum and maximum values) rather than the sample mean and standard deviation (SD), particularly for skewed data. For these studies, when included in a meta‐analysis, it is often desired to convert the five‐number summary back to the sample mean and SD. For this purpose, several methods have been proposed in the recent literature and they are increasingly used nowadays. In this article, we propose to further advance the literature by developing a smoothly weighted estimator for the sample SD that fully utilizes the sample size information. For ease of implementation, we also derive an approximation formula for the optimal weight, as well as a shortcut formula for the sample SD. Numerical results show that our new estimator provides a more accurate estimate for normal data and also performs favorably for non‐normal data. Together with the optimal sample mean estimator in Luo et al., our new methods have dramatically improved the existing methods for data transformation, and they are capable to serve as “rules of thumb” in meta‐analysis for studies reported with the five‐number summary. Finally for practical use, an Excel spreadsheet and an online calculator are also provided for implementing our optimal estimators.
Early Response of Specific IgE can Predict Satisfaction with Sublingual Immunotherapy
Authors: Kim Jin Youp , Rhee Chae‐Seo , Mun Sue Jean , Cho Seong H. , Lockey Richard F. , Han Doo Hee
Published: June 2020

Objective

To investigate predictive parameters at baseline and during the early response to sublingual immunotherapy (SLIT) for house dust mites in allergic rhinitis patients.

Study Design

Retrospective cohort study.

Methods

Patients were treated with SLIT for at least 3 years and serological tests performed at baseline and at 1‐year follow‐up to investigate predictive parameters. Satisfaction with SLIT, 4 nasal symptoms, and quality of life were evaluated before and after 3 years of SLIT. Sixty‐one patients were enrolled and divided into two groups depending on their satisfaction after 3 years of SLIT: 43 were satisfied (70.5%) and 18 were not (29.5%).

Results

Immunological parameters at baseline did not differ significantly between the satisfactory and unsatisfactory groups. However, changes in both Dermatophagoides pteronyssinus (Dp)– and D. farinae (Df)–specific IgEs were significantly higher in the unsatisfactory group than in the satisfactory group during the early response to SLIT (P = .006 and P = .045, respectively).

Conclusion

The changes in both Dp‐ and Df‐specific IgE levels during early response may be indicators for favorable long‐term treatment outcomes with SLIT. These results suggest that clinicians could measure these immunological parameters 1 year after Dp and Df SLIT to indicate potential responders versus nonresponders.

Level of Evidence

2b Laryngoscope, 131:467–472, 2021
Chance‐constrained multi‐objective approach for hazardous materials routing and scheduling under demand and service time uncertainty
Authors: Moghaddam Kamran S. , Azadian Farshid
Published: June 2020

The transportation of hazardous materials (hazmat) is a challenging problem that often requires a trade‐off between conflicting objectives. In practice, the complexity of the problem is exacerbated due to the lack of sufficient and reliable historical data. In this research, a stochastic multi‐objective optimization model for hazardous materials (hazmat) vehicle routing and scheduling problem is developed. The goal is to find optimal links and routes to obtain a trade‐off between the safe and fast distribution of hazmat through a transport network under customers' demand and service time uncertainty. We utilized a hybrid game theory based compromise programming to develop a solution algorithm to determine the Pareto‐optimal solutions, which are based on the total travel distance and total risk imposed on the transportation process. Computational results of a realistic numerical case study demonstrate the effectiveness of the proposed model and the solution algorithm in obtaining Pareto‐optimal solutions.
A Convenient Prognostic Tool and Staging System for Progressive Supranuclear Palsy
Authors: Golbe Lawrence I. , Ohman‐Strickland Pamela , Beisser Emily B. , Elghoul Francesca T.
Published: June 2020

Background

Progressive supranuclear palsy (PSP) causes major disability, shortens life, and as yet has no disease‐modifying and little symptomatic treatment. A convenient prognostic tool is needed to assist patients, families, and clinicians in planning care.

Objectives

We calculated times to acquisition of certain disease milestones and death.

Methods

We followed a cohort of 417 patients with PSP–Richardson syndrome from 1995 to 2016, applying the Progressive Supranuclear Palsy Rating Scale (PSPRS) at each visit. We generated median times to acquisition of 13 milestones using the input variables of sex, onset age, rate of disease progression from motor symptom onset to initial visit, and PSPRS score at the baseline. Of the outcome milestones, 5 were stages of a new, provisional PSP staging system. The other 8 milestones comprised death and disabling levels of cognitive loss, gaze palsy, dysarthria, dysphagia, and gait/balance impairment.

Results

We derived median times to milestones, with 25th and 75th percentiles and 95% confidence intervals of the median for baseline PSPRS scores from 25 to 65 (scale range, 0–100). Sex and initial progression velocity significantly influenced the death milestone, but not most of the others. Median time to death ranged from 4.8 years for a man with PSPRS score of 25 and a slow progression velocity from onset to initial visit of 0.51 PSPRS points/month to 1.8 years for a woman with PSPRS 65 and rapid initial velocity of 2.25 points/month.

Conclusions

We have created a convenient, inexpensive, noninvasive reference for counseling patients with PSP–Richardson syndrome on approximate time to encountering 13 life‐altering disease milestones.
From combinations to multitarget‐directed ligands: A continuum in Alzheimer's disease polypharmacology
Authors: Albertini Claudia , Salerno Alessandra , de Sena Murteira Pinheiro Pedro , Bolognesi Maria L.
Published: June 2020

The continued drug discovery failures in complex neurodegenerative diseases, including Alzheimer's disease (AD), has raised questions about the classical paradigm “one‐drug, one‐target, one‐disease.” In parallel, the ever‐increasing awareness of the multiplicity of the underlying pathways has led to the affirmation of polypharmacological approaches. Polypharmacology, which broadly embodies the use of pharmaceutical agents acting on multiple targets, seems to be the best way to restore the complex diseased network and to provide disease‐modifying effects in AD. In this review, our aim is to provide a roadmap into a world that is still only partly explored and that should be seen as a continuum of pharmacological opportunities, from drug combinations to multitarget‐directed ligands (both codrugs and hybrids). Each modality has unique features that can be effectively exploited by medicinal chemists. We argue that understanding their advantages and drawbacks is very helpful in choosing a proper approach and developing successful AD multitarget drug‐discovery endeavors. We also briefly dwell on (co)target validation, an aspect that is quite often neglected, but critical for an efficient clinical translation. We substantiate our discussion with instructive examples taken from the recent literature. Our wish is that, in spite of the specter of the high attrition rates, best researchers preferring to enter, stay, and progress in the field would help grow the sector and develop AD polypharmacology to full potential.