bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating thermal performance of closely related taxa: Support for hotter is not better, but for unexpected reasons
Authors: Montagnes David J. S. , Wang Qing , Lyu Zhao , Shao Chen
Published: March 2022

Temperature drives performance and therefore adaptation; to interpret and understand these, thermal performance curves (TPC) are used, often through meta‐analyses, revealing trends across divergent taxa. Four discrete hypotheses—thermodynamic‐constraint; biochemical‐adaptation (hotter is not better); specialist‐generalist; thermal‐trade‐off—have arisen to explain cross‐phyletic trends. In contrast, detailed comparisons of closely related taxa are rare, yet trends arising from these should reveal mechanisms of adaptation, as taxa diverge. Here, we combine experimental work with TPC theory to assess if the current hypotheses apply equally to closely related taxa. We established TPC for six species (and two strains of one species) of the animal model Tetrahymena (Ciliophora)—characterized by SSU rDNA/COX1 sequences—by examining specific growth rate (r), size (V), production (P = rV), and metabolic rate (rV−0.25) across 15–20 temperatures. Using parameters derived from the mechanistic “Sharpe and DeMichele” function, we established a framework to test which hypothesis best represented the data. We conclude that superficially the “hotter is not better” hypothesis is best but argue that the mechanistic theory underlying it cannot apply at the genus level: trends are likely to arise from little rather than substantial adaptation. Our further analysis suggests: (1) upward shift in the maximum‐functioning temperature (Tmax) is more constrained than the optimal temperature (Topt), leading to a decreased safety margin (Topt−Tmax) and suggesting that species initially succeed in warmer environments through an increase in Topt, followed by increasing Tmax; and (2) thermal performance traits are correlated with phylogeny for closely related species, suggesting that species gradually adapt to new thermal environments.
Wild trout and hydrologic response to restoration of incised streams with improved water use for ranching and fisheries
Authors: Pierce Ron , Rosgen Dave , Geenen Darcie , Rosgen Brandon
Published: March 2022

In the face of climate change and dwindling water supplies, this long‐term monitoring study examines the effectiveness of restoring two incised and degraded streams (Crystal Creek and Black Slough) to benefit livestock ranching and wild trout populations in a spring creek and wetland complex, central Idaho, USA. By raising the incised streambeds and connecting to historical floodplains, the restoration aimed to raise groundwater levels to create subsurface saturation conditions to sustain grazing forage and hay production without flood irrigation; diverted flows from the Big Wood River previously used for flood irrigation were instead routed through the restored systems. The restoration used natural channel design methods to reconstruct 5.2 km of Black Slough and 8.4 km of Crystal Creek to emulate a downstream reference reach (Willow Creek); within the relic incised channels, off‐channel oxbow ponds and wetlands were created while filling other segments. Additionally, screened gravels were placed in the reconstructed channels. We monitored before–after restoration changes in channel morphology, groundwater levels, wetlands, instream flows, spawning substrates and redds, fish populations, and invertebrates for the restored creeks and reference reach over 10+ years. Following restoration, average groundwater levels increased by 0.35 m, mean annual flows at Willow Creek (receiving stream) increased from 0.64 to 1.11 m3/s, and average days per year that baseflows were below 0.28 m3/s decreased from 44.5 to 5.4 despite a decrease in average annual precipitation (16.97 to 11.53 cm). Moreover, residual pool depths increased (<0.18 to >0.90 m), spawning substrate sizes increased (0.1 to 19.0 mm), and egg‐to‐fry trout survival rates increased from <20% to >90%. Six years after restoration, fish diversity increased from three to seven species, matching reference conditions. We also found dramatic increases in Brown Trout and Rainbow Trout redd counts (7 to 161 and 17 to 143, respectively) and relative abundance (0.013 to 1.166 trout/m and 0.029 to 0.222 trout/m, respectively). Invertebrate indices of restoration effectiveness were positive for both restored streams but negative for the reference reach. Overall, this study exemplifies how restoration reduced consumptive water use, created sustainable streams with hydrological connections and ponds and wetlands, and improved trout populations.
Analyses of three‐dimensional species associations reveal departures from neutrality in a tropical forest
Authors: Zambrano Jenny , Arellano Gabriel , Swenson Nathan G. , Staniczenko Phillip P. A. , Thompson Jill , Fagan William F.
Published: March 2022

The study of community spatial structure is central to understanding diversity patterns over space and species co‐occurrence at local scales. Although most analytical approaches consider horizontal and vertical dimensions separately, in this study we introduce a three‐dimensional spatial analysis that simultaneously includes horizontal and vertical species associations. Using tree census data (2000–2016) and allometries from the Luquillo forest plot in Puerto Rico, we show that spatial organization becomes less random over time as the forest recovered from land‐use legacy effects and hurricane disturbance. Tree species vertical segregation is predominant in the forest with almost all species that co‐occur in the horizontal plane avoiding each other in the vertical dimension. Horizontal segregation is less common than vertical, whereas three‐dimensional aggregation (a proxy for direct tree competition) is the least frequent type of spatial association. Furthermore, dominant species are involved in more non‐random spatial associations, implying that species co‐occurrence is facilitated by species segregation in space. This novel three‐dimensional analysis allowed us to identify and quantify tree species spatial distributions, how interspecific competition was reduced through forest structure, and how it changed over time after disturbance, in ways not detectable from two‐dimensional analyses alone.
Temperature impacts the environmental suitability for malaria transmission by Anopheles gambiae and Anopheles stephensi
Authors: Villena Oswaldo C. , Ryan Sadie J. , Murdock Courtney C. , Johnson Leah R.
Published: March 2022

Extrinsic environmental factors influence the spatiotemporal dynamics of many organisms, including insects that transmit the pathogens responsible for vector‐borne diseases (VBDs). Temperature is an especially important constraint on the fitness of a wide variety of ectothermic insects. A mechanistic understanding of how temperature impacts traits of ectotherms, and thus the distribution of ectotherms and vector‐borne infections, is key to predicting the consequences of climate change on transmission of VBDs like malaria. However, the response of transmission to temperature and other drivers is complex, as thermal traits of ectotherms are typically nonlinear, and they interact to determine transmission constraints. In this study, we assess and compare the effect of temperature on the transmission of two malaria parasites, Plasmodium falciparum and Plasmodium vivax, by two malaria vector species, Anopheles gambiae and Anopheles stephensi. We model the nonlinear responses of temperature dependent mosquito and parasite traits (mosquito development rate, bite rate, fecundity, proportion of eggs surviving to adulthood, vector competence, mortality rate, and parasite development rate) and incorporate these traits into a suitability metric based on a model for the basic reproductive number across temperatures. Our model predicts that the optimum temperature for transmission suitability is similar for the four mosquito–parasite combinations assessed in this study, but may differ at the thermal limits. More specifically, we found significant differences in the upper thermal limit between parasites spread by the same mosquito (A. stephensi) and between mosquitoes carrying P. falciparum. In contrast, at the lower thermal limit the significant differences were primarily between the mosquito species that both carried the same pathogen (e.g., A. stephensi and A. gambiae both with P. falciparum). Using prevalence data, we show that the transmission suitability metric calculated from our mechanistic model is consistent with observed P. falciparum prevalence in Africa and Asia but is equivocal for P. vivax prevalence in Asia, and inconsistent with P. vivax prevalence in Africa. We mapped risk to illustrate the number of months various areas in Africa and Asia predicted to be suitable for malaria transmission based on this suitability metric. This mapping provides spatially explicit predictions for suitability and transmission risk.
Microfluidic device integrating single‐cell extraction and electrical lysis for mass spectrometry detection of intracellular compounds
Authors: Václavek Tomáš , Foret František
Published: March 2022

Analysis of cellular composition and metabolism at a single‐cell resolution allows gaining more information about complex relationships of cells within tissues or whole living organisms by resolving the variance stemming from the cellular heterogeneity. Mass spectrometry (MS) is a perfect analytical tool satisfying the demanding requirements of detecting and identifying compounds present in such ultralow‐volume samples of high chemical complexity. However, the method of sampling and sample ionization is crucial in obtaining relevant information. In this work, we present a microfluidic sampling platform that integrates single‐cell extraction from MS‐incompatible media with electrical cell lysis and nanoESI‐MS analysis of human erythrocytes. Hemoglobin alpha and beta chains (300 amol/cell) were successfully identified in mass spectra of single‐erythrocyte lysates.
Evaluation of memantine's efficacy and safety in the treatment of children with autism spectrum disorder: A systematic review and meta‐analysis
Authors: Elnaiem Walaa , Benmelouka Amira Yasmine , Elgendy Ali Mohamed Naguib , Abdelgalil Mahmoud Shaban , Brimo Alsaman Muhamad Zakaria , Mogheeth Aly , Ali Mahmoud M. , Yousof Shimaa Mohammad
Published: March 2022

Background

The United States Food and Drug Administration has approved drugs that address only autism‐related symptoms rather than the underlying impairments. N‐Methyl‐D‐Aspartate  receptor antagonists have recently emerged as a promising treatment option for a variety of neurologic and developmental problems, including autism.

Aims

To review (systematically), for the first time, the medical literature that explores the safety in and efficacy of memantine in autism.

Methods and procedures

A comprehensive electronic search for relevant randomized controlled trials was conducted in four databases. Using RevMan software, we extracted and pooled data as a risk ratio (RR) or normalized mean differences in an inverse variance strategy.

Results

This systematic review and meta‐analysis includes five trials. There was no difference in enhancing social responsiveness when compared to placebo, though memantine lowered the likelihood of anxiety (RR = 0.25; 95% Confidence interval: [0.07; 0.87], p = 0.03). However, memantine aggravated impulsive behaviors. Additionally, in another trial that compared memantine added to risperidone versus risperidone added to placebo, memantine was found to be effective and safe.

Conclusion

Memantine showed safety in reducing acute symptoms of anxiety and other symptoms encountered in pediatric patients with autism spectrum disorders. However, memantine does not improve the core symptoms of autism. Nevertheless, further long‐term trials are needed to explore its potential efficacy.
Limitations of imaging screening tests in the detection of incomplete uterine septum or arcuate uterine anomaly
Authors: Yousif Abdelrahman , Moustafa Ahmed S. Z. , Abuzeid Omar M. , Corrado Jeannette M. , Abdullah Ahmed , Abuzeid Mostafa I.
Published: March 2022

Objectives

To determine the detection rates of hysterosalpingogram (HSG), transvaginal 2D ultrasound (TV 2D US), transvaginal 3D ultrasound (TV 3D US) in diagnosing of incomplete uterine septum (IUS) and significant arcuate uterine anomaly (AUA).

Methods

This retrospective cohort study included patients with infertility or recurrent pregnancy loss (516) that were found to have IUS (317) or significant AUA (199) on diagnostic hysteroscopy (DHS). We compared the detection rate of the various radiological tests in all patients with documented IUS or AUA on DHS.

Results

The diagnosis of IUS and AUA was made in 49.7% on HSG, 54.2% on TV 2D US and 69.5% on TV 3D US. When both HSG and TV 2D US or HSG and TV3D US were used, the diagnosis was correct in 67.7% and 82.6% of patients, respectively.

Conclusion

Although HSG, TV 2D US, TV 3D US are useful in the screening for IUS/AUA, none of these imaging tests alone or in combination are accurate enough to rule out the diagnosis of such congenital uterine anomalies. In patients with a history of infertility or RPL and negative radiologic tests, DHS is the only reliable method to rule out IUS or significant AUA.
Phosphatidylcholine (18:0/20:4), a potential biomarker to predict ethionamide‐induced hepatic steatosis in rats
Authors: Muta Kyotaka , Saito Kosuke , Kemmochi Yusuke , Masuyama Taku , Kobayashi Akio , Saito Yoshiro , Sugai Shoichiro
Published: March 2022

Ethionamide (ETH), a second‐line drug for multidrug‐resistant tuberculosis, is known to cause hepatic steatosis in rats and humans. To investigate predictive biomarkers for ETH‐induced steatosis, we performed lipidomics analysis using plasma and liver samples collected from rats treated orally with ETH at 30 and 100 mg/kg for 14 days. The ETH‐treated rats developed hepatic steatosis with Oil Red O staining‐positive vacuolation in the centrilobular hepatocytes accompanied by increased hepatic contents of triglycerides (TG) and decreased plasma TG and total cholesterol levels. A multivariate analysis for lipid profiles revealed differences in each of the 35 lipid species in the plasma and liver between the control and the ETH‐treated rats. Of those lipids, phosphatidylcholine (PC) (18:0/20:4) decreased dose‐dependently in both the plasma and liver. Moreover, serum TG‐rich very low‐density lipoprotein (VLDL) levels, especially the large particle fraction of VLDL composed of PC containing arachidonic acid (20:4) involved in hepatic secretion of TG, were decreased dose‐dependently. In conclusion, the decreased PC (18:0/20:4) in the liver, possibly leading to suppression of hepatic TG secretion, was considered to be involved in the pathogenesis of the ETH‐induced hepatic steatosis. Therefore, plasma PC (18:0/20:4) levels are proposed as mechanism‐related biomarkers for ETH‐induced hepatic steatosis.
Formononetin attenuates osteoclast differentiation and calcium loss by mediating transcription factor AP‐1 in type I diabetic mice
Authors: Jing Wensen , Feng Lei , Peng Kan , Zhang Weisong , Wang Bo
Published: March 2022

Formononetin (FMN) has been reported as a prospective antiosteoporotic medication. However, the antiosteoporotic properties of FMN are still unclear in a mouse model with diabetes‐induced osteoporosis. An osteoporotic or osteopenic mouse model with type I diabetes mellitus (T1DM) was established using streptozotocin (40 mg/kg) injection for 5 consecutive days. After 12 weeks with FMN intragastric administration (0.5, 5, 20 mg/kg), the antiosteoporotic activity of FMN was evaluated in T1DM mice. FMN supplementation effectively improves Ca excretion and trabecular bone degeneration and impedes osteoclast differentiation and function to attenuate hyperglycemia‐induced bone deterioration. In addition, FMN inhibited activating protein 1 (AP‐1) and osteoclast‐specific gene expression, Nfatc1, Ctsk, and TRAP. The administration of FMN has a beneficial effect to attenuate hyperglycemia‐induced bone deteriorations, including osteoclastogenesis, trabecular bone, and Ca loss. Our study provided a prospective medication for the treatment of T1DM‐related osteopenia or osteoporosis with FMN.
Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions
Authors: Azouz Amany A. , Hersi Fatema , Ali Fares E. M. , Hussein Elkelawy Asmaa M. M. , Omar Hany A.
Published: March 2022

Ischemia/reperfusion injury (IRI) during kidney transplantation is a serious clinical problem with a high mortality rate and a lack of therapy. Therefore, there is a need to improve the ability of the kidney to tolerate IRI during transplantation. This study aimed to investigate the possible protective effect of vinpocetine; a derivative of vincamine alkaloid; against renal IRI in rats with the elucidation of the involved mechanisms. Vinpocetine (25 mg/kg; i.p.) was administered for 10 successive days before the induction of ischemia by bilateral clamping of both renal pedicles for 45 min followed by 24 h of reperfusion. Blood and renal tissue samples were then collected for biochemical, molecular, and histopathological investigations. Vinpocetine significantly reduced serum creatinine and blood urea nitrogen levels in rats subjected to IRI. It also reduced mRNA expression of NADPH oxidase and renal content of malondialdehyde, while enhanced Nrf2 protein expression and renal content of reduced glutathione. The suppression of the provoked inflammatory response was evident by the downregulation of IKKβ and NF‐κB p65 protein expressions, as well as their downstream inflammatory markers; tumor necrosis factor‐α, interleukin‐6, and myeloperoxidase. In addition, vinpocetine reduced protein expression of the apoptotic executioner cleaved caspase‐3. These nephroprotective effects were confirmed by the improvement in histopathological features. Collectively, the protective effect of vinpocetine against IRI could be attributed to modulation of NADPH oxidase/Nrf2, IKKβ/NF‐κB p65, and cleaved caspase‐3 expressions. Thus, vinpocetine could improve oxidant/antioxidant balance, suppress triggered inflammatory response, and promote renal cell survival after IRI.
Psoralidin, a natural compound from Psoralea corylifolia, induces oxidative damage mediated apoptosis in colon cancer cells
Authors: Sun Chong , Zhao Lin , Wang Xianzhe , Hou Ying , Guo Xiuli , Lu Jin‐Jian , Chen Xiuping
Published: March 2022

Psoralidin (PSO) is a natural coumarin isolated from the seeds of Psoralea corylifolia Linn. Previous studies have reported that PSO exerts numerous pharmacological bioactivities including antitumor. The present study aimed to investigate its anticancer effect using colon cancer cells. Cultured HT‐29 and HCT‐116 colon cancer cells were treated with different concentrations of PSO, and the cell viability, the intracellular reactive oxygen species (ROS), the protein expression, and the apoptosis were determined by MTT assay, DCFH2‐DA fluorescence probe, Western blotting, and Annexin V/7‐AAD staining, respectively. The activities of caspase 3/7 were determined by a commercial kit. Our study found that PSO effectively induces apoptotic cell death mediated by caspase 3/7 in HT‐29 and HCT‐116 colon cancer cells. PSO treatment rapidly boosts the ROS generation, which is responsible for the PSO‐triggered DNA damage, mitochondria membrane potential decrease and caspase 3/7 activation, and c‐Jun N‐terminal kinase 1/2 activation. Collectively, these results showed that PSO triggered oxidative damage mediated apoptosis in colon cancer cells.
Is conformation relevant for QSAR purposes? 2D Chemical representation in a 3D‐QSAR perspective
Authors: Daré Joyce K. , Freitas Matheus P.
Published: March 2022

Conformation has a key role in the mechanism of interaction between small molecules and biological receptors. However, encoding this type of information in molecular descriptors for the construction of robust quantitative structure–activity relationships (QSAR) models is not an easy task and, so far, the dependence of these models on such feature has not been thoroughly investigated. In the present study, the authors explore the effects of conformational information on a 3D‐QSAR technique by comparing models built with descriptors that encode fully described tridimensional aspects (structures docked inside a biological target), with descriptors in which this information is suppressed (flat structures) or not fully described (structures with quantum‐chemically optimized geometries). As a result, the validation parameters indicate that the robustness of the models seems to be more related to the alignment aspect of the structures than to how well their tridimensional features are described.
Myeloperoxidase‐induced fibrinogen unfolding and clotting
Authors: Barinov Nikolay A. , Pavlova Elizaveta R. , Tolstova Anna P. , Matveeva Ainur G. , Moskalets Aleksandr P. , Dubrovin Evgeniy V. , Klinov Dmitry V.
Published: March 2022

Due to its unique properties and high biomedical relevance fibrinogen is a promising protein for the development of various matrixes and scaffolds for biotechnological applications. Fibrinogen molecules may form extensive clots either upon specific cleavage by thrombin or in thrombin‐free environment, for example, in the presence of different salts. Here, we report the novel type of non‐conventional fibrinogen clot formation, which is mediated by myeloperoxidase and takes place even at low fibrinogen concentrations (<0.1 mg/ml). We have revealed fibrillar nature of myeloperoxidase‐mediated fibrinogen clots, which differ morphologically from fibrin clots. We have shown that fibrinogen clotting is mediated by direct interaction of myeloperoxidase molecules with the outer globular regions of fibrinogen molecules followed by fibrinogen unfolding from its natural trinodular to a fibrillar structure. We have demonstrated a major role of the Debye screening effect in regulating of myeloperoxidase‐induced fibrinogen clotting, which is facilitated by small ionic strength. While fibrinogen in an aqueous solution with myeloperoxidase undergoes changes, the enzymatic activity of myeloperoxidase is not inhibited in excess of fibrinogen. The obtained results open new insights into fibrinogen clotting, give new possibilities for the development of fibrinogen‐based functional biomaterials, and provide the novel concepts of protein unfolding.
Novel anchoring device for endoscopic ultrasound‐guided gallbladder drainage: Secondary publication
Authors: Okuzono Toru , Miyamoto Ko‐ichiro
Published: March 2022

Background

Recently, endoscopic ultrasound‐guided gallbladder drainage has attracted much attention. However, the risk management of adverse events and techniques to avoid them are not yet mature. Difficulty dilating the fistula with a dilator or placing a stent for drainage often prolongs the procedure time, which increases the risk of peritonitis or the procedure failure rate. Therefore, the result of the procedure will be unstable, and one cause is the lack of adhesion between the gallbladder and the digestive tract walls.

Methods

We developed an anchor to fix the stomach and gallbladder walls prior to endoscopic ultrasound‐guided gallbladder drainage in four live pigs using the anchor.

Results

The stomach and gallbladder walls were fixed in three pigs, and technical success was achieved in all three pigs. In two pigs that were dissected 17 and 34 days post‐procedure, respectively, fixation occurred in one pig. In the other pig, anchoring of the gallbladder and stomach walls did not occur because the wings of the anchor in the gallbladder were damaged.

Conclusions

Although issues remain regarding efficacy and safety, we plan to make improvements in this novel device and aim for clinical application.
High‐Resolution Vessel Wall MR Imaging in Diagnosis and Length Measurement of Cerebral Arterial Thrombosis: A Feasibility Study
Authors: Zhang Chao , Dou Weiqiang , Jiang Shu , Dong Dong , Wang Xinyi
Published: March 2022

Background

Detecting and measuring intraluminal thrombus has prognostic and therapeutic implications for stroke patients.

Purpose

To investigate the feasibility of 3D isotropic high‐resolution T1w‐CUBE imaging to detect and measure intraluminal thrombus in stroke patients.

Study Type

Retrospective.

Subjects

A total of 93 patients with acute (N = 39) and subacute (N = 54) stroke.

Field Strength/Sequence

A 3.0 T/spin‐echo echo‐planar diffusion‐weighted imaging (DWI), high‐resolution T1w‐CUBE imaging and 3D flow compensated gradient‐echo susceptibility‐weighted imaging (SWI).

Assessment

Data assessment was performed by three neuroradiologists with 11, 13, and 20 years of clinical experience. The accuracy of T1W‐CUBE and SWI in diagnosing thrombosis was compared by using digital subtraction angiography (DSA) as the reference. For thrombus length measurement, the image quality of proximal and distal thrombus of T1w‐CUBE images was first evaluated with a 4‐point rating system. Then, the proximal and distal positions to lesions were determined on T1w‐CUBE images and compared with those from DSA acquired during endovascular reperfusion therapy. If comparable both locations were found between CUBE and DSA, CUBE imaging can thus be considered for accurate measurement of thrombus length.

Statistical Tests

Fleiss' Kappa; the area under the receiver operating characteristic (ROC) curve (AUC); Pearson's chi‐squared test with Yates' continuity correction.

Results

Moderate‐to‐good interobserver agreements were validated with all Kappa coefficients higher than 0.40 in thrombus diagnosis and measurement. CUBE imaging showed higher clinical efficacy than SWI (AUC: 0.966 vs. 0.850) in thrombus diagnosis. Additionally, high quality of CUBE imaging was confirmed with 3 or 4 points rated by all three observers. Compared to intraoperative DSA, T1w CUBE showed consistent proximal and distal positions of thrombi in 16 of the 18 patients, validating the accuracy of T1w‐CUBE in measuring thrombus length.

Data Conclusion

T1w‐CUBE imaging has potential to facilitate diagnosis and measurement of intraluminal thrombus.

Evidence Level

4

Technical Efficacy

Stage 2
Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review
Authors: Masyeni Sri , Iqhrammullah Muhammad , Frediansyah Andri , Nainu Firzan , Tallei Trina , Emran Talha Bin , Ophinni Youdiil , Dhama Kuldeep , Harapan Harapan
Published: March 2022

Broad‐spectrum antiviral agents targeting viral RNA‐dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID‐19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes COVID‐19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS‐CoV‐2, the virus that causes COVID‐19. Clinical trials of molnupiravir as a therapy for patients with mild‐to‐moderate COVID‐19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS‐CoV‐2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID‐19 pandemic.
An analysis of operating efficiency and policy implications in last‐mile transportation following Amazon's integration
Authors: Wang Lina , Rabinovich Elliot , Guda Harish
Published: March 2022

We examine how Amazon's decision to vertically integrate its retail platform and last‐mile delivery operations can lead to anti‐competitive outcomes as a result of a deterioration in the operating efficiency in the routes served by a last‐mile transportation firm. Based on an operational analysis of the last‐mile transportation firm, we find that Amazon's decision to vertically integrate increases significantly the mileage necessary to deliver parcels in the ZIP code areas where this integration occurs. Moreover, this increase is significantly amplified by the remoteness and proportion of fast deliveries in these areas. These effects translate, on average, into $1.36 in additional costs necessary to cover extra vehicular and labor expenditures per parcel delivered. Because at the root of these outcomes are interactions among multiple organizations with significant market power asymmetries, we expand on a variety of potential anti‐competitive service and pricing outcomes stemming from the impact of Amazon's vertical integration on the last‐mile delivery firm's costs. We then put forth different public policy remedies that could be implemented to address these potential sources of anti‐competitiveness in the last‐mile delivery industry.
Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models
Authors: Gautreaux Malley A. , Tucker Luke J. , Person Xavier J. , Zetterholm Haley K. , Priddy Lauren B.
Published: March 2022

Disease or trauma of orthopedic tissues, including osteomyelitis, osteoporosis, arthritis, and fracture, results in a complex immune response, leading to a change in the concentration and milieu of immunological cells and proteins in the blood. While C‐reactive protein levels and white blood cell counts are used to track inflammation and infection clinically, controlled longitudinal studies of disease/injury progression are limited. Thus, the use of clinically‐relevant animal models can enable a more in‐depth understanding of disease/injury progression and treatment efficacy. Though longitudinal tracking of immunological markers has been performed in rat models of various inflammatory and infectious diseases, currently there is no consensus on which markers are sensitive and reliable for tracking levels of inflammation and/or infection. Here, we discuss the blood markers that are most consistent with other outcome measures of the immune response in the rat, by reviewing their utility for longitudinal tracking of infection and/or inflammation in the following types of models: localized inflammation/arthritis, injury, infection, and injury + infection. While cytokines and acute phase proteins such as haptoglobin, fibrinogen, and α2‐macroglobulin demonstrate utility for tracking immunological response in many inflammation and infection models, there is likely not a singular superior marker for all rat models. Instead, longitudinal characterization of these models may benefit from evaluation of a collection of cytokines and/or acute phase proteins. Identification of immunological plasma markers indicative of the progression of a pathology will allow for the refinement of animal models for understanding, diagnosing, and treating inflammatory and infectious diseases of orthopedic tissues.
Common complement factor H polymorphisms are linked with periodontitis in elderly patients
Authors: Salminen Aino , Pietiäinen Milla , Paju Susanna , Sorsa Timo , Mäntylä Päivi , Buhlin Kåre , Sinisalo Juha , Pussinen Pirkko J.
Published: March 2022

Background

In our recent genome‐wide association study, we found that genetic polymorphisms in the complement factor H (CFH) gene and S100A gene region are strongly associated with serum matrix metalloproteinase 8 (MMP‐8) concentration and the release of MMP‐8 from neutrophils. As MMP‐8 is centrally involved in the pathogenesis of periodontitis, we aimed to evaluate the presence of genetic polymorphisms of S100A8/A9/A12, MMP8, and CFH in periodontitis. In addition, we studied whether polymorphisms of these genes affect the concentrations of S100A8, S100A12, MMP‐8, or complement activation marker in saliva.

Methods

We genotyped four single‐nucleotide polymorphisms (SNPs, rs1560833 in S100A8/A9/A12, rs11225395 in MMP8, rs800292 in CFH, and rs1061170 in CFH) and measured salivary concentrations of S100A8, S100A12, MMP‐8, and terminal complement complex (TCC) in the Parogene cohort (n = 508). The cohort was composed of patients with an indication to coronary angiography and all underwent a clinical and radiographic oral examination.

Results

CFH polymorphisms rs800292 and rs1061170 were associated with periodontal parameters. None of the polymorphisms showed association with salivary proteins. However, salivary concentrations of S100A8, S100A12, MMP‐8, and TCC were strongly associated with the number of periodontal pockets and alveolar bone loss.

Conclusion

Interestingly, genetic variants of CFH, MMP8, and S100A8/A9/A12 gene regions did not affect salivary levels of measured proteins. However, saliva levels of S100A8, S100A12, MMP‐8, and TCC, and CFH polymorphisms were associated with clinical and radiographic signs of periodontitis. Our study further supports the observations that any dysregulation of complement may increase the risk of inflammatory disorders, such as periodontitis.
Locust bean milling‐derived dust as a raw material for the development of biodegradable bioplastics with antioxidant activity
Authors: Lopes Joana , Malheiro Catarina , Prodana Marija , Loureiro Susana , Ferreira Paula , Coimbra Manuel A , Gonçalves Idalina
Published: March 2022

BACKGROUND

Non‐value agrifood byproducts are rich in biomolecules such as proteins and polysaccharides, and possess film‐forming ability, motivating their use in the development of biodegradable plastics. This work studied the feasibility of using locust bean milling‐derived dust (LBMD) as a source of biomolecules suitable for developing biodegradable plastics.

RESULTS

LBMD is composed of 56% protein, 28% carbohydrate, 10% moisture, 6% lipid, and 2% ash. In addition, phenolic compounds are also present. The carbohydrates are mainly composed by (1 → 4)‐mannose, (1 → 4,6)‐mannose, and t‐galactose glycosidic linkages. Depending on the LBMD concentration used, when employed in casting biodegradable plastics, LBMD yields transparent yellowish bioplastics with 90% elongation at break and surface water contact angles ranging from 60° to 90°. Additionally, LBMD‐based bioplastics display antioxidant activity, inhibiting cationic 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radicals up to 61% in just 24 h. LBMD‐based bioplastics are disintegrated when incubated on the soil surface for 34 weeks, perhaps acting as a soil nutrient.

CONCLUSION

LBMD represents a potential source of biomolecules for producing transparent, flexible, water tolerant, antioxidant, and biodegradable bioplastics, opening up opportunities to implement a novel circular strategy to valorize this locust bean industry byproduct. © 2022 Society of Chemical Industry.
Differences in receipt of multimodality therapy by race, insurance status, and socioeconomic disadvantage in patients with resected pancreatic cancer
Authors: Hao Scarlett , Mitsakos Anastasios , Irish William , Tuttle‐Newhall Janet Elizabeth , Parikh Alexander A. , Snyder Rebecca A.
Published: March 2022

Background and Methods

Racial and socioeconomic disparities in receipt of adjuvant chemotherapy affect patients with pancreatic cancer. However, differences in receipt of neoadjuvant chemotherapy among patients undergoing resection are not well‐understood. A retrospective cross‐sectional cohort of patients with resected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified from the National Cancer Database (2014–2017). Outcomes included receipt of neoadjuvant versus adjuvant chemotherapy, or receipt of either, defined as multimodality therapy and were assessed by univariate and multivariate analysis.

Results

Of 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624 (49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received no chemotherapy. On multivariable analysis, Black patients had lower odds of neoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI: 0.67–0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95% CI: 0.77–1.03). Patients with Medicaid or no insurance, low educational attainment, or low median income had significantly lower odds of receiving neoadjuvant chemotherapy or multimodality therapy.

Conclusions

Racial and socioeconomic disparities persist in receipt of neoadjuvant and multimodality therapy in patients with resected pancreatic adenocarcinoma.

Discussion

Policy and interventional implementations are needed to bridge the continued socioeconomic and racial disparity gap in pancreatic cancer care.
The effects of parasocial interaction, authenticity, and self‐congruity on the formation of consumer trust in online travel agencies
Authors: Chen Xiaohua , Hyun Sunghyup Sean , Lee Timothy J.
Published: March 2022

This study uses the theories of parasocial interaction, perceived authenticity, and self‐congruity to analyze the antecedents of source credibility and to confirm the positive effects of this on travel influencers when constructing travel platforms. The respondents are Chinese travelers who had used an online travel agency and who read influencer‐generated content to search for tourism‐related information. The results from the 420 valid questionnaires showed that users' perceived parasocial interaction, perceived authenticity, and self‐congruity have positive effects on source credibility for influencers. The study provides theoretical and managerial backup for influencer marketing efforts and the content marketing of online travel platforms.
THBS2 promotes cell migration and invasion in colorectal cancer via modulating Wnt/β‐catenin signaling pathway
Authors: Qu Hong‐Lan , Hasen Gao‐Wa , Hou Yan‐Yan , Zhang Chun‐Xia
Published: March 2022

Colorectal cancer (CRC) is the most common human digestive malignancy with a poor prognosis; the pathophysiology of colon cancer involves multiple linkages of regulatory networks. Recently, thrombospondin 2 (THBS2) has been extensively studied for its role in cancer progression. In this study, we evaluated the expression of THBS2 in CRC tissues and studied the possible mechanism by which THBS2 regulates CRC progression. Our results showed that the upregulation of THBS2 in CRC tissues and CRC cell lines and high expression of THBS2 was correlated with poor overall survival. The in vitro experimental data showed that THBS2 overexpression promoted CRC cell growth, invasion, and migration, while THBS2 inhibition exerted tumor‐suppressive actions on CRC cells. THBS2 knockdown suppressed the activity of Wnt/β‐catenin signaling. Collectively, the results implied that THBS2 exerted promotional effects on CRC cell proliferation, invasion, and migration, partly by modulating the Wnt/β‐catenin signaling pathway.
Pepsinogen/Proton Pump Co‐Expression in Barrett's Esophageal Cells Induces Cancer‐Associated Changes
Authors: Stabenau Kaleigh A. , Samuels Tina L. , Lam Tina K. , Mathison Angela J. , Wells Clive , Altman Kenneth W. , Battle Michele A. , Johnston Nikki
Published: March 2022

Educational Objective

At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.

Objective

Barrett's esophagus (BE) is a well‐known risk factor for esophageal adenocarcinoma (EAC). Gastric H+/K+ ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H+/K+ ATPase proton pumps.

Study Design

In vitro translational.

Methods

BAR‐T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus‐encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing.

Results

Top canonical pathways associated with protein‐coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR‐T cells included those involved in the tumor microenvironment and epithelial–mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300‐CBP, I‐BET‐151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer.

Conclusions

These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE.

Level of Evidence

NA Laryngoscope, 133:59–69, 2023
Marine atmospheric corrosion of carbon steel in the tropical microclimate of Port Louis
Authors: Seechurn Yashwantraj , Surnam Baboo Y. R. , Wharton Julian A.
Published: March 2022

The atmospheric corrosion performance of S235 carbon steel is assessed when exposed to the tropical/marine aerosol pollutants of Port Louis, Mauritius. Port Louis is situated on the northwest coast and has a distinct microclimate, leading to major atmospheric corrosion concerns. In addition, sulphur dioxide emissions from three heavy oil‐fired power stations complicate corrosion prediction within the region. Mass‐loss analysis shows distinctive corrosion progression behaviours linked to the environmental and geographical variables. The formation of porous surface layers leads to a continuous increase in metal dissolution during the electrochemical process. The surface analysis reveals lepidocrocite and goethite () as the predominant rust phases, with low percentages of magnetite (), akageneite  and jarosite . A key insight in the S235 atmospheric corrosion involves two stages: the early rapid corrosion stage followed by a slow stage of linear or power‐law corrosion kinetics due to the formation of stable rust phases.
Stability and bifurcation analysis of a fractional‐order model of cell‐to‐cell spread of HIV‐1 with a discrete time delay
Authors: Abbas Syed , Tyagi Swati , Kumar Pushpendra , Ertürk Vedat Suat , Momani Shaher
Published: March 2022

In this manuscript, fractional order is introduced onto a time‐delay differential equation model of cell‐to‐cell spread of HIV‐1. The fractional derivative of Caputo type is considered. We deal with the local stability of the resulting system and derive some necessary and sufficient conditions ensuring Hopf bifurcation to occur for this system. Explicit expressions for determining stability of critical surfaces are also given. An Adams‐type predictor–corrector technique is applied to illustrate the numerical results. The main target of this study is to describe the structure of HIV‐1 by using a fractional‐order mathematical model, and the motivation of using fractional derivatives is the ability of these operators to capture memory effects in the system.
Training of deep cross‐modality conversion models with a small data set, and their application in megavoltage CT to kilovoltage CT conversion
Authors: Ozaki Sho , Kaji Shizuo , Nawa Kanabu , Imae Toshikazu , Aoki Atsushi , Nakamoto Takahiro , Ohta Takeshi , Nozawa Yuki , Yamashita Hideomi , Haga Akihiro , Nakagawa Keiichi
Published: March 2022

Purpose

In recent years, deep learning–based image processing has emerged as a valuable tool for medical imaging owing to its high performance. However, the quality of deep learning–based methods heavily relies on the amount of training data; the high cost of acquiring a large data set is a limitation to their utilization in medical fields. Herein, based on deep learning, we developed a computed tomography (CT) modality conversion method requiring only a few unsupervised images.

Methods

The proposed method is based on cycle‐consistency generative adversarial network (CycleGAN) with several extensions tailored for CT images, which aims at preserving the structure in the processed images and reducing the amount of training data. This method was applied to realize the conversion of megavoltage computed tomography (MVCT) to kilovoltage computed tomography (kVCT) images. Training was conducted using several data sets acquired from patients with head and neck cancer. The size of the data sets ranged from 16 slices (two patients) to 2745 slices (137 patients) for MVCT and 2824 slices (98 patients) for kVCT.

Results

The required size of the training data was found to be as small as a few hundred slices. By statistical and visual evaluations, the quality improvement and structure preservation of the MVCT images converted by the proposed model were investigated. As a clinical benefit, it was observed by medical doctors that the converted images enhanced the precision of contouring.

Conclusions

We developed an MVCT to kVCT conversion model based on deep learning, which can be trained using only a few hundred unpaired images. The stability of the model against changes in data size was demonstrated. This study promotes the reliable use of deep learning in clinical medicine by partially answering commonly asked questions, such as “Is our data sufficient?” and “How much data should we acquire?”
Efficient dose‐rate correction of silicon diode relative dose measurements
Authors: Duchaine Jasmine , Markel Daniel , Bouchard Hugo
Published: March 2022

Purpose

Silicon diodes are often the detector of choice for relative dose measurements, particularly in the context of radiotherapy involving small photon beams. However, a major drawback lies in their dose‐rate dependency. Although ionization chambers are often too large for small field output factor (OF) measurements, they are valuable instruments to provide reliable percent‐depth dose (PDD) curves in reference beams. The aim of this work is to propose a practical and accurate method for the characterization of silicon diode dose‐rate dependence correction factors using ionization chamber measurements as a reference.

Methods

The robustness of ionization chambers for PDD measurements is used to quantify the dose‐rate dependency of a diode detector. A mathematical formalism, which exploits the error induced in percent‐depth ionization (PDI) curves for diodes by their dose‐rate dependency, is developed to derive a dose‐rate correction factor applicable to diode relative measurements. The method is based on the definition of the recombination correction factor given in the addendum to TG 51 and is applied to experimental measurements performed on a CyberKnife M6 radiotherapy unit using a PTW 60012 diode detector. A measurement‐based validation is provided by comparing corrected PDI curves to measurements performed with a PTW 60019 diamond detector, which does not exhibit dose‐rate dependence.

Results

Results of dose‐rate correction factors for PDI curves, off‐axis ratios (OARs), tissue‐phantom ratios, and small field OFs are coherent with the expected behavior of silicon diode detectors. For all considered setups and field sizes, the maximum correction and the maximum impact of the uncertainties induced by the correction are obtained for OARs for the 60 mm collimator, with a correction of 2.5% and an uncertainty of 0.34%. For OFs, corrections range from 0.33% to 0.82% for all field sizes considered, and increase with the reduction of the field size. Comparison of PDI curves corrected for dose‐rate and for in‐depth beam quality variations illustrates excellent agreement with measurements performed using the diamond detector.

Conclusion

The proposed method allows the efficient and precise correction of the dose‐rate dependence of silicon diode detectors in the context of clinical relative dosimetry.