bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic pain severity, impact, and opioid use among patients with cancer: An analysis of biopsychosocial factors using the CHOIR learning health care system
Authors: Azizoddin Desiree R. , Schreiber Kristin , Beck Meghan R. , Enzinger Andrea C. , Hruschak Valerie , Darnall Beth D. , Edwards Robert R. , Allsop Matthew J. , Tulsky James A. , Boyer Edward , Mackey Sean
Published: June 2021

Background

Despite the biopsychosocial underpinnings of chronic noncancer pain, relatively little is known about the contribution of psychosocial factors to chronic cancer pain. The authors aimed to characterize associations between biopsychosocial factors and pain and opioid use among individuals with chronic pain and cancer.

Methods

The authors conducted a retrospective, cross‐sectional study of 700 patients with chronic pain and cancer seeking treatment at an academic tertiary pain clinic. Patients completed demographic questionnaires and validated psychosocial and pain measures. Multivariable, hierarchical linear and logistic regressions assessed the relative contributions of biopsychosocial factors to the primary dependent variables of pain severity, pain interference, and opioid use.

Results

Participants were 62% female and 66% White with a mean age of 59 ± 15 years, and 55% held a college degree or higher. Older age, African American or “other” race, sleep disturbance, and pain catastrophizing were significantly associated with higher pain severity (F(5,657) = 22.45; P ≤ .001; R2 = 0.22). Depression, sleep disturbance, pain catastrophizing, lower emotional support, and higher pain severity were significantly associated with pain interference (F(5,653) = 9.47; P ≤ .001; R2 = 0.44). Lastly, a poor cancer prognosis (Exp(B) = 1.62) and sleep disturbance (Exp(B) = 1.02) were associated with taking opioids, whereas identifying as Asian (Exp(B) = 0.48) or Hispanic (Exp(B) = 0.47) was associated with lower odds of using opioids.

Conclusions

Modifiable psychological factors—specifically sleep disturbance, depression, and pain catastrophizing—were uniquely associated with pain and opioid use in patients with chronic pain and diverse cancer diagnoses. Future behavioral pain interventions that concurrently target sleep may improve pain among patients with cancer.

Lay Summary

Feeling depressed, worrying about pain, and bad sleep are related to higher pain symptoms in individuals with chronic pain and cancer.

Specifically, those who struggle to sleep have worse pain and use more opioids.

Also, individuals who have a bad prognosis for their cancer are more likely to be using opioid pain medications.

Although race and cancer are related to chronic pain in patients, psychological well‐being is also strongly related to this same pain.
How limited molecular testing can also offer diagnostic and prognostic evaluation of thyroid nodules processed with liquid‐based cytology: Role of TERT promoter and BRAF V600E mutation analysis
Authors: Dell’Aquila Marco , Fiorentino Vincenzo , Martini Maurizio , Capodimonti Sara , Cenci Tonia , Lombardi Celestino Pio , Raffaelli Marco , Pontecorvi Alfredo , Fadda Guido , Pantanowitz Liron , Larocca Luigi Maria , Rossi Esther Diana
Published: June 2021

Background

Mutational analysis contributes to the diagnosis and prognosis of thyroid nodules analyzed with fine‐needle aspiration cytology (FNAC). Although several advanced molecular tests based on multiple molecular markers are available for clinical use and have increased their impact on clinical management of patients, they are not widely available. Among them is BRAF V600E, one of the most studied mutations. Other genetic alterations, such as TERT promoter mutations, may coexist in thyroid carcinomas. Previous studies have demonstrated that this duet might be involved in the aggressiveness of thyroid cancer, although its prognostic value related to mortality remains undefined. The detection of such genetic alterations in thyroid liquid‐based cytology (LBC) thus may assist with patient management.

Methods

From January 2013 to June 2014, 356 thyroid FNAC samples were processed by LBC, including 174 surgical follow‐up samples. BRAF V600E and TERT mutation analyses were performed on both LBC and histopathology.

Results

The study included 119 samples categorized as atypia of undetermined significance, 42 categorized as follicular neoplasms, 61 categorized as suspicious for malignancy, and 34 categorized as positive for malignancy. BRAF V600E mutation was detected in 10.4% of all cases, whereas TERT promoter mutations were identified in 1.1%. TERT‐mutated cases belonged to the positive for malignancy category, with a histologic diagnosis of tall cell variant of papillary thyroid carcinoma. These genetic alterations correlated with lymph node metastases (P = .0349) and higher disease stage.

Conclusions

BRAF V600E and TERT analysis can be performed on LBC. TERT mutations are rarely identified in well differentiated thyroid carcinoma but are associated with higher stage. Although a larger molecular panel may offer more information, analyzing these few point mutations is still likely to be useful for managing potentially more aggressive thyroid carcinomas.
Cytoarchitectural characteristics associated with cognitive flexibility in raccoons
Authors: Jacob Joanna , Kent Molly , Benson‐Amram Sarah , Herculano‐Houzel Suzana , Raghanti Mary Ann , Ploppert Emily , Drake Jack , Hindi Bilal , Natale Nick R. , Daniels Sarah , Fanelli Rachel , Miller Anderson , Landis Tim , Gilbert Amy , Johnson Shylo , Lai Annie , Hyer Molly , Rzucidlo Amanda , Anchor Chris , Gehrt Stan , Lambert Kelly
Published: June 2021

With rates of psychiatric illnesses such as depression continuing to rise, additional preclinical models are needed to facilitate translational neuroscience research. In the current study, the raccoon (Procyon lotor) was investigated due to its similarities with primate brains, including comparable proportional neuronal densities, cortical magnification of the forepaw area, and cortical gyrification. Specifically, we report on the cytoarchitectural characteristics of raccoons profiled as high, intermediate, or low solvers in a multiaccess problem‐solving task. Isotropic fractionation indicated that high‐solvers had significantly more cells in the hippocampus (HC) than the other solving groups; further, a nonsignificant trend suggested that this increase in cell profile density was due to increased nonneuronal (e.g., glial) cells. Group differences were not observed in the cellular density of the somatosensory cortex. Thionin‐based staining confirmed the presence of von Economo neurons (VENs) in the frontoinsular cortex, although no impact of solving ability on VEN cell profile density levels was observed. Elongated fusiform cells were quantified in the HC dentate gyrus where high‐solvers were observed to have higher levels of this cell type than the other solving groups. In sum, the current findings suggest that varying cytoarchitectural phenotypes contribute to cognitive flexibility. Additional research is necessary to determine the translational value of cytoarchitectural distribution patterns on adaptive behavioral outcomes associated with cognitive performance and mental health.
Not all applications have boring communication patterns: Profiling message matching with BMM
Authors: Groves Taylor , Ravichandrasekaran Naveen , Cook Brandon , Keen Noel , Trebotich David , Wright Nicholas J. , Alverson Bob , Roweth Duncan , Underwood Keith
Published: June 2021

Message matching within MPI is an important performance consideration for applications that utilize two‐sided semantics. In this work, we present an instrumentation of the CrayMPI library that allows the collection of detailed message‐matching statistics as well as an implementation of hashed matching in software. We use this functionality to profile key DOE applications with complex communication patterns to determine under what circumstances an application might benefit from hardware offload capabilities within the NIC to accelerate message matching. We find that there are several applications and libraries that exhibit sufficiently long match list lengths to motivate a Binned Message Matching approach.
Sharing non‐cache‐coherent memory with bounded incoherence
Authors: Ren Yuxin , Parmer Gabriel , Milojicic Dejan
Published: June 2021

Cache coherence in modern computer architectures enables easier programming by sharing data across multiple processors. Unfortunately, it can also limit scalability due to cache coherency traffic initiated by competing memory accesses. Rack‐scale systems introduce shared memory across a whole rack, but without inter‐node cache coherence. This poses memory management and concurrency control challenges for applications that must explicitly manage cache‐lines. To fully utilize rack‐scale systems for low‐latency and scalable computation, applications need to maintain cached memory accesses in spite of non‐coherency. This paper introduces Bounded Incoherence, a memory consistency model that enables cached access to shared data‐structures in non‐cache‐coherency memory. It ensures that updates to memory on one node are visible within at most a bounded amount of time on all other nodes. We evaluate this memory model on modified PowerGraph graph processing framework, and boost its performance by 30% with eight sockets by enabling cached‐access to data‐structures.
A Study of Regulatory Challenges of Pediatric Oncology Phase I/II Trial Submissions and Guidance on Protocol Development
Authors: Beck Lydia , Witt Ruth , Nesper‐Brock Martina , Milde Till , Hettmer Simone , Frühwald Michael C. , Rössig Claudia , Fischer Matthias , Reinhardt Dirk , Taylor Lenka A. , Riedel Claudia , Witt Olaf , van Tilburg Cornelis M.
Published: June 2021

The purpose of this study was to identify key deficiencies in pediatric oncology early phase clinical trial protocols in Germany and to provide guidance for efficient trial protocol development. A systematic review of the response letters of German competent authorities (CAs) and Ethics Committees to phase I/II pediatric oncology trial submissions in the period from 2014 to 2019 was performed. Documents were requested from all five Society for Paediatric Oncology and Haematology in Germany (GPOH) phase I/II trial networks plus all nine German Innovative Therapies for Children with Consortium Cancer (ITCC) centers. A blinded dataset containing aggregated data from 33 studies was analyzed for validation. All deficiencies were reviewed, listed, and weighted using a structured matrix according to frequency, category, significance, and feasibility. In total, documents of 17 trials from 6 different sites were collected. Two hundred fifty deficiencies identified by the CAs were identified and categorized into eight categories. “Toxicity and safety” was the most prominent category (27.6%), followed by “Manufacturing and Import” (18%). The majority of deficiencies were categorized as minor and potential measures as easy to address, but an important group of major and difficult to implement deficiencies was also identified. The blinded validation dataset confirmed these findings. The majority of the EC deficiencies could be resolved by changing the wording in the patient‐facing documents. In conclusion, this study was able to detect a pattern of key deficiencies. Most of the shortcomings can be anticipated by minor changes in the protocol and increased awareness can prevent time‐consuming revisions, withdrawals, or even rejections. A corresponding guideline describing key regulatory aspects is provided.
ZmMATE1 improves grain yield and yield stability in maize cultivated on acid soil
Authors: Vasconcellos Renato C. C. , Mendes Flávia F. , de Oliveira Antônio Carlos , Guimarães Lauro J. M. , Albuquerque Paulo E. P. , Pinto Marcos O. , Barros Beatriz A. , Pastina Maria Marta , Magalhaes Jurandir V. , Guimaraes Claudia T.
Published: June 2021

The development of aluminum (Al)‐tolerant cultivars is a complementary strategy to overcome the constraints caused by Al toxicity on acid soils and can contribute positively to the food supply for the growing global population. A major Al tolerance quantitative trait locus in maize is controlled by a citrate transporter encoded by ZmMATE1. Our goal was to evaluate the impact of the superior allele of ZmMATE1 on the yield performance of maize lines and hybrids cultivated on acid soils. Near‐isogenic lines carrying the superior allele of ZmMATE1, and the recurrent Al‐sensitive parent were crossed with elite lines, generating near‐isogenic hybrids contrasting for these alleles. All maize genotypes carrying this superior allele were more Al tolerant in nutrient solution than their isogenic counterparts having the ZmMATE1 allele derived from the Al‐sensitive parent. These genotypes were cultivated in control and Al stress soils for 2 yr. Aluminum toxicity caused a significant yield reduction of 18.7% for lines and 14.7% for hybrids over the 2 yr. The yield performance of maize genotypes declined in the second year compared with the first year, probably due to water deficiency after the grain‐filling stage. The superior allele of ZmMATE1 in maize hybrids conferred yield gains from 21 to 48% compared with the hybrids harboring the alternative allele in the Al stress soil in the first and second years, respectively. As this superior allele is rare in maize and is likely absent in several elite germplasms, molecular breeding based on ZmMATE1 can improve maize yield stability on acid soils.
Costly mating delays drive female ornamentation in a capital breeder
Authors: Hopkins Juhani , Lehtonen Topi K. , Baudry Gautier , Kaitala Arja
Published: June 2021

How fecundity might be traded off with mate attraction and other aspects of reproduction in females remains poorly understood.

We investigated these allocation trade‐offs using the common glowworm (Lampyris noctiluca), a lampyrid beetle, in which flightless, sedentary females only use resources gathered during the larval stage to attract flying males by glowing.

While sexual signaling was not found to have a significant fecundity cost, a delay in successfully attracting a mate greatly increased the risk of reproductive failure, with fecundity losses being more severe in small females.

These findings are among the first to show that failure to quickly attract a mate can decrease female fecundity. The results also show how the length of delay before mating can drive the evolution of female sexual ornamentation.
Fish community shifts along a strong fluvial environmental gradient revealed by eDNA metabarcoding
Authors: García‐Machado Erik , Laporte Martin , Normandeau Eric , Hernández Cecilia , Côté Guillaume , Paradis Yves , Mingelbier Marc , Bernatchez Louis
Published: June 2021

Large rivers and their estuaries are structurally complex and comprise a diversity of habitats supporting a rich biodiversity. As a result, identifying and monitoring fish communities using traditional methods in such systems may often be logistically challenging. Using the mitochondrial DNA 12S MiFish primers, we performed an eDNA metabarcoding analysis to assess the effect of spatial and environmental factors on the variation of the fish community structure along most of the St. Lawrence River/Estuary/Gulf (Québec Canada), a transect spanning 1300 km across a diversity of habitats from a fluviatile non‐tidal section to a marine environment. A total of 129 species were identified including freshwater and marine species. For the freshwater sectors, eDNA identified 80 species compared with the 85 species previously reported based on conventional sampling. eDNA also revealed similar species diversity and communities in the fluviatile section of the St. Lawrence River. Furthermore, our study improved current knowledge about the brackish and marine sections by describing community transition between freshwater and marine fish communities in association with a drastic shift in environmental conditions observed between the end of the fluvial estuary and the beginning of the middle (brackish) estuary. Altogether, this study exemplifies how eDNA metabarcoding is a powerful tool to document fish community shifts in large temperate lotic ecosystems.
Growth differentiation factor‐15, treatment with liraglutide, and clinical outcomes among patients with heart failure
Authors: Sharma Abhinav , Greene Stephen , Vaduganathan Muthiah , Fudim Marat , Ambrosy Andrew P. , Sun Jie‐Lena , McNulty Steven E. , Hernandez Adrian F. , Borlaug Barry A. , Velazquez Eric J. , Mentz Robert J. , DeVore Adam D. , Alhanti Brooke , Margulies Kenneth , Felker G. Michael
Published: June 2021

Aims

Associations between growth differentiation factor‐15 (GDF‐15), cardiovascular outcomes, and exercise capacity among patients with a recent hospitalization for heart failure (HHF) and heart failure with reduced ejection fraction (HFrEF) are unknown. We utilized data from the ‘Functional Impact of GLP‐1 for Heart Failure Treatment’ (FIGHT) study to address these knowledge gaps.

Methods and results

FIGHT was a randomized clinical trial testing the effect of liraglutide (vs. placebo) among 300 participants with HFrEF and a recent HHF. Multivariable regression models evaluated associations between baseline GDF‐15 and change in GDF‐15 (per 1000 pg/mL increase from baseline to 30 days) with clinical outcomes (at 180 days) and declines in exercise capacity (6 min walk distance ≥ 45 m). At baseline (n = 249), median GDF‐15 value was 3221 pg/mL (interquartile range 1938–5511 pg/mL). Participants in the highest tertile of baseline GDF‐15 were more likely to be male and have more co‐morbidities. After adjustment, an increase in GDF‐15 over 30 days was associated with higher risk of death or HHF [hazard ratio 1.35, 95% confidence interval (CI) 1.11–1.64]. In addition, higher baseline GDF‐15 (per 1000 pg/mL until 6000 pg/mL) and an increase in GDF‐15 over 30 days were associated with declining 6 min walk distance (odds ratio 1.26, 95% CI 1.02–1.55 and odds ratio 1.37, 95% CI 1.12–1.69, respectively). GDF‐15 levels remained stable among participants randomized to liraglutide.

Conclusions

An increase in GDF‐15 over 30 days among patients in HFrEF was independently associated with an increased risk of cardiovascular events and declining exercise capacity. These results support the value of longitudinal GDF‐15 trajectory in informing risk of heart failure disease progression.
Heat Dissipation Effects of Cavity Cooling Plate with Directly Opposite Inlet and Outlet on Lithium‐Ion Battery
Authors: Wang Tong , Zhang Xin , Zeng Qingliang , Gao Kuidong , Jiang Shoubo
Published: June 2021

Due to its high thermal sensitivity, a power lithium‐ion battery for vehicles requires an efficient cooling system to ensure safety and good performance. Excellent heat dissipation capacity enables the liquid cold plate cooling system to have better application prospects. However, all existing cold plates improve their cooling capacity by increasing the complexity of their structure. Therefore, directly opposite inlet and outlet cavity cold plate cooling systems with simple structures are established. Two kinds of cavity cold plates (Model I and Model L) with different inlet and outlet positions are analyzed using the numerical simulation method. The effects of inlet and outlet sizes, coolant mass flow rate (qm), and inlet and outlet positions on the temperature field as well as the cold plate pressure drop are studied. According to the results, maximum temperatures of batteries appear at four corners of cavity cold plates, which are lower than 35 °C. The cooling capacity and temperature uniformity of Model I cooling systems are better than those of Model L. However, the heat dissipation capacity of Model L is more sensitive to qm than that of Model I. Pressure drop of Model L is smaller. This method meets the heat dissipation of vehicle pouch lithium‐ion batteries.
Leaching of Metals from Steel Slag and Their Ecological Effects on a Marine Ecosystem: Validating Field Data with Mesocosm Observations
Authors: Foekema Edwin M. , Tamis Jacqueline E. , Blanco Ainhoa , van der Weide Babeth , Sonneveld Cor , Kleissen Frank , van den Heuvel-Greve Martine J.
Published: June 2021

Steel slag is being used worldwide for a variety of applications, among which is underwater dyke reinforcement. In the present study the leaching and bioaccumulation of 18 inorganic compounds from basic oxygen furnace (BOF) steel slag were monitored in marine experimental ecosystems (mesocosms) for 12 wk. Triplicate mesocosms were installed at 2 refreshment rates, one reflecting the situation in the Oosterschelde estuary where BOF steel slag was applied and the other at a 35 times lower rate. Vanadium in both water and biota turned out to be the best tracer for the presence of BOF steel slag in the mesocosms. The mesocosm data helped to interpret the results of a 4-yr field sampling program in the Oosterschelde estuary where no elevated levels of vanadium in water or biota were found near locations where steel slag was applied. Also, no ecological impact could be established in the field, which was in line with the observations in the mesocosms. The present study shows the added value of a tailor-made mesocosm study for realistic risk assessment and provides support for applying this tool as a basis for designing efficient field monitoring programs. Environ Toxicol Chem 2021;40:2499–2509. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
The synergistic effects of zinc oxide nanoparticles and fennel essential oil on physicochemical, mechanical, and antibacterial properties of potato starch films
Authors: Babapour Hamid , Jalali Hossein , Mohammadi Nafchi Abdorreza
Published: June 2021

The purpose of this study was to evaluate the effects of a combination of zinc oxide (ZnO‐N) nanoparticles and fennel essential oil (FEO) on the functional and antimicrobial properties of potato starch films. Films based on potato starch containing a combination of ZnO‐N (1, 3, and 5%(w/w)) and FEO (1, 2, and 3% (w/w)) produced by casting method and water solubility, water absorption capacity (WAC), barrier properties, mechanical properties, color indexes, and antimicrobial activity of the films against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were studied. The combination of ZnO‐N and FEO had a significant decreasing effect on solubility, WAC, water vapor and oxygen permeability, elongation, and L* index. These additives had an increasing impact on tensile strength, Yang's modulus, and a* and b* indexes (p < .05). By increasing the concentration of ZnO‐N and FEO, the antimicrobial activities of bionanocomposite films significantly increased (p < .05). Both ZnO‐N and FEO had a significant effect in this respect, although the effects of ZnO‐N were more significant. In conclusion, an excellent synergistic effect of ZnO‐N and FEO was observed in potato starch films.
Who leads in intraday gold price discovery and volatility connectedness: Spot, futures, or exchange‐traded fund?
Authors: Sehgal Sanjay , Sobti Neharika , Diesting Florent
Published: June 2021

Gold exchange‐traded funds (ETFs) have amassed massive inflows from institutional investors globally. We examine intraday price discovery and volatility connectedness among three gold instruments—spot, futures, and ETF—across mature and emerging gold markets in domestic and international settings from 2010 to 2018. Using the network approach, we find that gold futures are a global leader in price discovery and volatility spillover. However, during 2016–2018, physical‐gold‐backed ETF and spot challenge the futures' leadership in New York and Shanghai. Intraday variation in price discovery leadership is due to liquidity, hedging effectiveness, price jumps, investor attention, and macroeconomic states.
Mechanisms underlying sensitization of P2X7 receptors in astrocytes for induction of ischemic tolerance
Authors: Hirayama Yuri , Anzai Naohiko , Koizumi Schuichi
Published: June 2021

We previously showed that noninvasive mild ischemia (preconditioning; PC) induced ischemic tolerance by upregulation of P2X7 receptors in astrocytes via a hypoxia inducible factor‐1α (HIF‐1α)‐dependent mechanism. The P2X7 receptor is known as a low‐sensitivity P2 receptor that requires a high extracellular ATP (eATP) concentration for activation. PC increased the eATP level but was not sufficient to activate P2X7 receptors. Here, we show that astrocytes possess an elaborate mechanism for activation of P2X7 receptors, thus contributing to ischemic tolerance. Nicotinamide adenine dinucleotide (NAD+) was shown to increase the sensitivity of P2X7 receptors to eATP via ecto‐ADP‐ribosyltransferase 2 (ARTC2)‐catalyzed ADP‐ribosylation in peripheral immune cells. Although ARTC2‐positive signals were mostly absent in the naïve brain, they were selectively increased in astrocytes by PC. The spatiotemporal pattern of PC‐evoked ARTC2 was well associated with that of P2X7 receptors. In the in vitro experiments, NAD+ increased the sensitivity of P2X7 receptors to ATP, and at higher concentrations, NAD+ itself activated P2X7 receptors without eATP in cultured astrocytes. In the in vivo experiments using middle cerebral artery occlusion model mice, the PC‐evoked increase in HIF‐1α in astrocytes was abolished by the ARTC2 inhibitor S + 16a. S + 16a also abolished PC‐evoked ischemic tolerance. Taken together, the results suggested that P2X7 receptors can be sensitized to ATP by NAD+/ARTC2‐catalyzed ADP‐ribosylation, which allows astrocytes to drive P2X7 receptor‐mediated ischemic tolerance even though PC only slightly increases the amount of eATP.
Altered resting‐state functional network connectivity in profound sensorineural hearing loss infants within an early sensitive period: A group ICA study
Authors: Wang Shanshan , Chen Boyu , Yu Yalian , Yang Huaguang , Cui Wenzhuo , Fan Guoguang , Li Jian
Published: June 2021

Data from both animal models and deaf children provide evidence for that the maturation of auditory cortex has a sensitive period during the first 2–4 years of life. During this period, the auditory stimulation can affect the development of cortical function to the greatest extent. Thus far, little is known about the brain development trajectory after early auditory deprivation within this period. In this study, independent component analysis (ICA) technique was used to detect the characteristics of brain network development in children with bilateral profound sensorineural hearing loss (SNHL) before 3 years old. Seven resting‐state networks (RSN) were identified in 50 SNHL and 36 healthy controls using ICA method, and further their intra‐and inter‐network functional connectivity (FC) were compared between two groups. Compared with the control group, SNHL group showed decreased FC within default mode network, while enhanced FC within auditory network (AUN) and salience network. No significant changes in FC were found in the visual network (VN) and sensorimotor network (SMN). Furthermore, the inter‐network FC between SMN and AUN, frontal network and AUN, SMN and VN, frontal network and VN were significantly increased in SNHL group. The results implicate that the loss and the compensatory reorganization of brain network FC coexist in SNHL infants. It provides a network basis for understanding the brain development trajectory after hearing loss within early sensitive period.
Phase II randomized study of preoperative calcitriol to prevent hypocalcemia following thyroidectomy
Authors: Shonka David C. , Maxwell Anne K. , Petroni Gina R. , Jameson Mark J.
Published: June 2021

Background

A prospective, stratified, randomized, double‐blind, placebo‐controlled study was conducted to observe the impact of preoperative calcitriol supplementation on serum calcium levels following total thyroidectomy.

Methods

Subjects were randomized 1:1 to receive 1 μg calcitriol or placebo for 1 week preceding thyroidectomy. The primary outcome measure was change in serum calcium from baseline to 18 h post‐thyroidectomy. Subjects were also assessed for incidence of symptomatic hypocalcemia, length of stay, readmission for hypocalcemia, and intravenous calcium supplementation.

Results

Forty‐seven patients underwent thyroidectomy; 23 received preoperative calcitriol supplementation, and 24 received placebo. Repeated measures regression demonstrated no difference in postoperative serum calcium over time (p = 0.22). There were no occurrences of hypocalcemia, intravenous calcium supplementation, or readmission in either group. No difference was observed in length of stay (p = 0.38). One patient in the calcitriol group developed Grade 3 hypercalcemia.

Conclusions

Preoperative calcitriol supplementation had no impact on postoperative serum calcium levels compared to placebo.
Long‐coronavirus disease among people living with HIV in western India: An observational study
Authors: Pujari Sanjay , Gaikwad Sunil , Chitalikar Abhishek , Dabhade Digamber , Joshi Kedar , Bele Vivek
Published: June 2021

Background

Long‐COVID is emerging as a significant problem among individuals who recovered from COVID‐19. Scant information is available on the prevalence, characteristics, and risk factors for long‐COVID among people living with HIV (PLHIV).

Setting

A tertiary level, private, HIV clinic in western India.

Methods

A prospective, observational study was conducted to assess the prevalence of long‐COVID among PLHIV. Long‐COVID was defined as the presence of at least one symptom after 30 days of illness onset. A questionnaire for assessing general, cardiorespiratory, neuro‐psychiatric, and gastro‐intestinal symptoms was used to screen individuals with history of confirmed COVID‐19. Data on demographics, HIV‐related variables, comorbidities, and severity of COVID‐19 were abstracted from electronic medical records. Univariate and multivariate logistic regression were used to identify risk factors for long‐COVID.

Results

Ninety‐four PLHIV were screened for long‐COVID. Median (interquartile range [IQR]) age was 51 (47–56) years and 73.4% were males. The majority (76.6%) had a history of asymptomatic–mild COVID‐19 illness. The prevalence of long‐COVID was 43.6% (95% confidence interval [CI], 33.4–54.2). Moderate–severe COVID‐19 illness was significantly associated with long‐COVID (adjusted odds ratio, 4.7; 95% CI, 1.4–17.9; p = .016). Among individuals with long‐COVID, cough (22.3%) and fatigue (19.1%) were the commonest symptoms. The median (IQR) duration for resolution of symptoms was 15 (7–30) days. Ten individuals (10.6%) had persistent symptoms at a median of 109 days since the onset of COVID‐19.

Conclusion

Long‐COVID is common among PLHIV with moderate–severe acute COVID‐19 illness. There is a need for integration of long‐COVID diagnosis and care services within antiretroviral therapy clinics for PLHIV with COVID‐19.
Exploring the challenges of women taking antiretroviral treatment during the COVID‐19 pandemic lockdown in peri‐urban Harare, Zimbabwe
Authors: Nyashanu Mathew , Chireshe Rumbidzai , Mushawa Fungisai , Ekpenyong Mandu S.
Published: June 2021

Objective

To explore the challenges of women taking antiretroviral treatment (ART) during the COVID‐19 pandemic lockdown in a peri‐urban area.

Methods

An exploratory qualitative study approach was used. Semi‐structured questions were devised and used to elicit data on the impact of the COVID‐19 lockdown on women accessing treatment for HIV. Twenty women were interviewed through contacts from community and faith organizations in peri‐urban Harare. All interviews were audio‐recorded, transcribed verbatim and entered into NVivo to make analysis easy. The data were thematically analyzed, underpinned by the four phases of data analysis in the Silences Framework.

Results

The study discovered that transport problems, confusing COVID‐19 restrictions, abuse by police and soldiers at roadblocks, a shortage of medication, lack of health check‐up routines, involuntary default of ART, and a shortage of personal protective equipment affected HIV‐positive women accessing ART during the COVID‐19 lockdown.

Conclusion

People living with HIV need a robust supporting environment and a functioning health system. In response to COVID‐19 all services were halted to prevent the spread of COVID‐19. Pandemic preparedness is important in keeping an adequate supply of ART and responding to the needs of individuals on HIV treatment.
1,25(OH)2D3 attenuates sleep disturbance in mouse models of Lewis lung cancer, in silico and in vivo
Authors: Ai Min , Li Shuang‐shuang , Chen Hong , Wang Xi‐ting , Sun Jiang‐nan , Hou Bao , Cai Wei‐wei , Zhou Yue‐tao , Qiu Li‐ying
Published: June 2021

Many clinical studies have reported that patients diagnosed with cancer will suffer from sleep disturbance during their clinical process, especially among lung cancer patients, and this effect will not easily subside. 1,25‐dihydroxy‐vitamin‐D3 [1,25(OH)2D3], the activated form of vitamin D, can participate in neuronal differentiation and prevent damage to the nervous system. However, little is known about the potential therapeutic effects of cancer‐related psychiatric symptoms. In light of this, we hypothesized that a low circulating level of vitamin D was related to sleep quality in the presence of a tumor, 1,25(OH)2D3 may be an effective way to ameliorate sleep disturbance and neurochemical alterations along with the cancer progress. Male C57BL/6 mice were implanted with intracranial transmitters to monitor electroencephalogram and were subcutaneously inoculated with Lewis lung cancer cells. The results demonstrated that on Days 19–20, tumor‐bearing mice displayed fragmented sleep, shortened wake phase, prolonged sleep in the non‐rapid eye movement phase, and the levels of vitamin D‐associated genes in the brain had changed a lot compared to control mice. Importantly, 1,25(OH)2D3 treatment really effectively saved the sleep quality of tumor‐bearing mice. We further explored and confirmed that 1,25(OH)2D3 repressed tumor‐induced neuroinflammation (IL‐1β, TNF‐α, IL‐6, IL‐10, IFN‐γ, and IL‐2), enhanced neurotrophic factors (brain‐derived neurotrophic factor [BDNF], glialcellline‐derived neurotrophic factor) and 5‐HT system in the hippocampus, hypothalamus or cortex. A molecular docking approah manifested the ability of 1,25(OH)2D3 to affect the activity of tryptophan hydroxylase 2 and BDNF. Together, our results suggested that 1,25(OH)2D3 treatment may attenuate sleep disturbance in Lewis lung cancer‐bearing mice, and become a promising strategy for treating cancer symptom clusters to ameliorate the quality of life of patients with cancer.
Patient risk stratification and tailored clinical management of post‐transplant CMV‐, EBV‐, and BKV‐infections by monitoring virus‐specific T‐cell immunity
Authors: Papadopoulou Anastasia , Koukoulias Kiriakos , Alvanou Maria , Papadopoulos Vassilios K. , Bousiou Zoe , Kalaitzidou Vasiliki , Kika Fotini S. , Papalexandri Apostolia , Mallouri Despina , Batsis Ioannis , Sakellari Ioanna , Anagnostopoulos Achilles , Yannaki Evangelia
Published: June 2021

Background

Despite routine post‐transplant viral monitoring and pre‐emptive therapy, viral infections remain a major cause of allogeneic hematopoietic cell transplantation‐related morbidity and mortality.

Objective

We here aimed to prospectively assess the kinetics and the magnitude of cytomegalovirus‐(CMV), Epstein Barr virus‐(EBV), and BK virus‐(BKV)‐specific T cell responses post‐transplant and evaluate their role in guiding therapeutic decisions by patient risk‐stratification.

Study design

The tri‐virus‐specific immune recovery was assessed by Elispot, in 50 consecutively transplanted patients, on days +20, +30, +60, +100, +150, +200 post‐transplant and in case of reactivation, weekly for 1 month.

Results

The great majority of the patients experienced at least one reactivation, while over 40% of them developed multiple reactivations from more than one of the tested viruses, especially those transplanted from matched or mismatched unrelated donors. The early reconstitution of virus‐specific immunity (day +20), favorably correlated with transplant outcomes. Εxpanding levels of CMV‐, EBV‐, and BKV‐specific T cells (VSTs) post‐reactivation coincided with decreasing viral load and control of infection. Certain cut‐offs of absolute VST numbers or net VST cell expansion post‐reactivation were determined, above which, patients with CMV or BKV reactivation had >90% probability of complete response (CR).

Conclusion

Immune monitoring of virus‐specific T‐cell reconstitution post‐transplant may allow risk‐stratification of virus reactivating patients and enable patient‐tailored treatment. The identification of individuals with high probability of CR will minimize unnecessary overtreatment and drug‐associated toxicity while allowing candidates for pre‐emptive intervention with adoptive transfer of VSTs to be appropriately selected.
LncRNA TUG1 ameliorates diabetic nephropathy via inhibition of PU.1/RTN1 signaling pathway
Authors: Meng Dongdong , Wu Lina , Li Zhifu , Ma Xiaojun , Zhao Shuiying , Zhao Di , Qin Guijun
Published: June 2021

Diabetic nephropathy (DN) is a leading cause of end-stage renal failure. The study aimed to investigate whether long noncoding RNA taurine-upregulated gene 1 (TUG1) can ameliorate the endoplasmic reticulum stress (ERS) and apoptosis of renal tubular epithelial cells in DN, and the underlying mechanism. The DN mouse model was established by streptozocin injection, and the human renal tubular epithelial cell line HK-2 was treated with high glucose (HG) to mimic DN in vitro. The molecular mechanism was explored through dual-luciferase activity assay, RNA pull-down assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (CHIP) assay. The expression of TUG1 was significantly decreased in the renal tubules of DN model mice. Overexpression of TUG1 reduced the levels of ERS markers and apoptosis markers by inhibiting reticulon-1 (RTN1) expression in HG-induced HK-2 cells. Furthermore, TUG1 down-regulated RTN1 expression by inhibiting the binding of transcription factor PU.1 to the RTN1 promoter, thereby reducing the levels of ERS markers and apoptosis markers. Meanwhile, TUG1-overexpression adenovirus plasmids injection significantly alleviated tubular lesions, and reduced RTN1 expression, ERS markers and apoptosis markers, whereas these results were reversed by injection of PU.1-overexpression adenovirus plasmids. TUG1 restrains the ERS and apoptosis of renal tubular epithelial cells and ameliorates DN through inhibition of transcription factor PU.1.
Precipitation influence on and response to early and late Arctic sea ice melt onset during melt season
Authors: Marcovecchio Alexa , Behrangi Ali , Dong Xiquan , Xi Baike , Huang Yiyi
Published: June 2021

The region containing portions of the East Siberian Sea and Laptev Sea (73°–84°N, 90°–155°E) is the area of focus (AOF) for this study. The impacts of precipitation, latent heat (LH) and sensible heat (SH) fluxes on sea ice melt onset in the AOF are investigated. Four early melting years (1990, 2012, 2003, and 1991) and four late melting years (1982, 1983, 1984, and 1996) are compared to better identify the different responses to melt onset timing. A consistency check is performed between multiple Arctic precipitation products (including NASA MERRA‐2, ECMWF ERA‐Interim [ERA‐I], and ECMWF ERA5 reanalyses as well as GPCP V2.3 observations) since there is not yet a high‐quality ground‐truth Arctic precipitation data product. MERRA‐2 has the greatest monthly average precipitation, snowfall, evaporation, and net LH flux. ERA‐I suggests that liquid precipitation starts earlier in the year than MERRA‐2 and ERA5, while GPCP shows different seasonal precipitation variations from the reanalyses. MERRA‐2 has the clearest and most amplified seasonal trends for the parameters used in this study, so the daily time series and anomalies of MERRA‐2 variables before and after the first major melt event are investigated. ERA5 is used to check these results because ERA‐I and ERA5 display similar seasonal trends. According to MERRA‐2, during early melt years, surface SH flux loss and precipitation are above average in the days before and after the first major melt event. During late melt years, surface SH flux loss and precipitation are below average in the month leading up to the first major melt event.
Building a multilevel integrated framework of ambidexterity: The role of dynamically changing environment and human capital management in the performance of Greek firms
Authors: Katou Anastasia A.
Published: June 2021

The purpose of this study is to investigate the serially mediating mechanisms of human capital management practices and organizational ambidexterity, expressed by exploration and exploitation, in the relationship between environmental dynamism and organizational performance, expressed by creativity and productivity. The study is based on 1,183 employees working in 83 Greek private sector firms. By applying multi‐level structural equation modeling, the findings show that the dynamically changing environment has a positive impact on human capital management practices, which in turn have a differential positive impact on exploration and exploitation, which then have a positive influence on organizational creativity and productivity. The study contributes to the literature on organizational ambidexterity by examining whether human capital management practices constitute an antecedent of organizational ambidexterity, and whether organizational performance constitutes a consequence.
Box–Behnken design aided optimization and validation of developed reverse phase HPLC analytical method for simultaneous quantification of dolutegravir sodium and lamivudine co‐loaded in nano‐liposomes
Authors: Mutalik Sadhana P , Mullick Prashansha , Pandey Abhijeet , Kulkarni Smita S. , Mutalik Srinivas
Published: June 2021

A stability‐indicating reversed‐phase high‐performance liquid chromatography method for simultaneous estimation of dolutegravir sodium and lamivudine encapsulated in the nanoliposomal formulation was developed. The chromatographic parameters namely, organic phase ratio, flow rate, and sample injection volume were selected as independent factors and were optimized by multivariate Box–Behnken design. Responses analyzed were retention time, peak area, and resolution. The optimized chromatographic method with Hypersil BDS C8 CN column as stationary phase and methanol and acetonitrile mixture and acidified Milli‐Q water (pH 2.8, adjusted with 0.02% v/v orthophosphoric acid) as the mobile phase in an isocratic elution mode was validated according to parameters of International Conference on Harmonization Q1(R2) guidelines. The validated reversed‐phase high‐performance liquid chromatography method exhibited specificity for both dolutegravir sodium and lamivudine in the presence of degradation products as well as the liposomal matrix. This method was effectively utilized to determine the amount of drug entrapped and drug loading efficiency of dolutegravir sodium and lamivudine in a nano‐liposomal formulation.
Anatomical Features Around Eustachian Tube in Eosinophilic Otitis Media With Eosinophilic Sinusitis
Authors: Ohira Shinya , Komori Manabu , Matsui Hidehito , Furuya Hanae , Kajiwara Riko , Matsuura Kentaro , Wada Kota
Published: June 2021

Objectives/Hypothesis

This study investigated the relationships between anatomical findings around the eustachian tube (ET) and eosinophilic otitis media (EOM) accompanied by eosinophilic chronic rhinosinusitis (ECRS).

Study Design

This study employed axial, coronal, sagittal and oblique computed tomography.

Methods

Patients who underwent endoscopic sinus surgery at the Department of Otolaryngology, Toho University Medical Center Omori Hospital and were diagnosed with ECRS (106 patients) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study were included. Subsequently, the presence of EOM accompanied by ECRS in 212 ear sides was assessed, and preoperative sinus computed tomography was used to evaluate various anatomical findings, such as the development of the sphenoid sinus and mastoid cells at the apex of petrous bone, the angle and length of the ET, and the size of the tympanic orifice of the ET. The relationships between these anatomical findings and the presence of EOM were analyzed statistically.

Results

EOM accompanied by ECRS was associated with a high peripheral blood eosinophil count and bronchial asthma. Among anatomical factors, the absence of peri‐ET cells or petrous apex cells, and a low angle and short length of the ET, were risk factors for the onset of EOM.

Conclusion

Anatomical factors such as the absence of peri‐eustachian cells or petrous apex cells, and low angle or short length of the ET, are risk factors for the onset of EOM along with ECRS. Assessment of these factors may help in preventing the future onset or aggravation of EOM.

Level of Evidence

4 Laryngoscope, 131:E2689–E2695, 2021
Growth‐dependent changes in elemental stoichiometry and macromolecular allocation in the coccolithophore Emiliania huxleyi under different environmental conditions
Authors: Zhang Yong , Li Zhengke , Schulz Kai G. , Hu Yingyu , Irwin Andrew J. , Finkel Zoe V.
Published: June 2021

The growth rate hypothesis (GRH) posits an increase in ribosomal ribonucleic acid (RNA) content, and therefore cellular phosphorus (P), with increasing growth rate. There is evidence that the GRH may not apply to phytoplankton under all conditions. Here, we experimentally controlled four conditions (light, temperature, pH, and CO2) to alter the growth rate of Emiliania huxleyi, a biogeochemically important coccolithophorid, and monitored changes in RNA, protein, and carbohydrate content. We show that an increase in growth rate caused by increasing light, pH, and CO2 resulted in increased RNA per unit of organic carbon (RNA : POC), but that increasing temperature, leading to increase of growth rate, resulted in a decrease in RNA : POC. Protein per unit of organic carbon (protein : POC) increased in our increased temperature, pH, and CO2 treatments that increased growth rate, but there was little change in protein : POC in our light treatment despite it inducing the same increase in growth rate. Carbohydrate per unit of organic carbon (Carbohydrate : POC) increased with growth rate under increased light and CO2 but did not vary significantly in the temperature or pH treatments. These results indicate that physiological acclimation to specific environmental conditions can lead to contrasting patterns in RNA, protein, and carbohydrate composition and therefore contrasting changes in carbon : nitrogen : phosphorus ratios with growth rate in E. huxleyi.
Resonant Nonlinear Synthetic Metasurface with Combined Phase and Amplitude Modulations
Authors: Wang Bingxia , Wang Kai , Hong Xuanmiao , Sheng Yan , Qian Shuhang , Lu Peixiang
Published: June 2021

Nonlinear metasurfaces provide a promising platform for integrated nonlinear photonic devices owing to their unprecedented capability of nonlinear wavefront manipulation. However, the previously reported second‐harmonic (SH) metasurfaces are mainly based on the nonlinear Pancharatnam–Berry phase modulation. While this method is quite convenient and robust, it shows limitations of modulation efficiency and the difficulty in extending to multidimensional combined modulations. Here, the resonant nonlinear synthetic metasurface is proposed and experimentally demonstrated for independent phase and amplitude modulations of the SH beam. A high SH modulation efficiency of 75% (with a theoretical limit of 90%) is achieved in the polarization‐dependent SH metalens. Moreover, SH holographic imaging with phase and amplitude (at 2 and 4 levels) combined modulation is realized experimentally. Compared with the pure‐phase modulation, the signal‐to‐noise ratios are increased by 2 and 3 times when 2‐ and 4‐level amplitude controls are introduced. This is not only an important step in the improvement and innovation of holographic display technology, but also paves a distinct avenue toward multifunctional, higher efficiency, and ultracompact nonlinear optical devices.