bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Method for Reporting Prostate Cancer Grade in MRI-targeted Biopsies
Authors: Deng Fang-Ming , Isaila Bogdan , Jones Derek , Ren Qinghu , Kyung Park , Hoskoppal Deepthi , Huang Hongying , Mirsadraei Leili , Xia Yuhe , Melamed Jonathan
Published: June 2021

When multiple cores are biopsied from a single magnetic resonance imaging (MRI)-targeted lesion, Gleason grade may be assigned for each core separately or for all cores of the lesion in aggregate. Because of the potential for disparate grades, an optimal method for pathology reporting MRI lesion grade awaits validation. We examined our institutional experience on the concordance of biopsy grade with subsequent radical prostatectomy (RP) grade of targeted lesions when grade is determined on individual versus aggregate core basis. For 317 patients (with 367 lesions) who underwent MRI-targeted biopsy followed by RP, targeted lesion grade was assigned as (1) global Grade Group (GG), aggregated positive cores; (2) highest GG (highest grade in single biopsy core); and (3) largest volume GG (grade in the core with longest cancer linear length). The 3 biopsy grades were compared (equivalence, upgrade, or downgrade) with the final grade of the lesion in the RP, using κ and weighted κ coefficients. The biopsy global, highest, and largest GGs were the same as the final RP GG in 73%, 68%, 62% cases, respectively (weighted κ: 0.77, 0.79, and 0.71). For cases where the targeted lesion biopsy grade scores differed from each other when assigned by global, highest, and largest GG, the concordance with the targeted lesion RP GG was 69%, 52%, 31% for biopsy global, highest, and largest GGs tumors (weighted κ: 0.65, 0.68, 0.59). Overall, global, highest, and largest GG of the targeted biopsy show substantial agreement with RP-targeted lesion GG, however targeted global GG yields slightly better agreement than either targeted highest or largest GG. This becomes more apparent in nearly one third of cases when each of the 3 targeted lesion level biopsy scores differ. These results support the use of global (aggregate) GG for reporting of MRI lesion-targeted biopsies, while further validations are awaited.
Brief Report: Ritonavir Concentrations in Hair Predict Virologic Outcomes in HIV-Infected Adolescents With Virologic Failure on Atazanavir-Based or Ritonavir-Based Second-Line Treatment
Authors: Chawana Tariro D. , Nhachi Charles F. B. , Nathoo Kusum , Ngara Bernard , Okochi Hideaki , Louie Alexander , Kuncze Karen , Katzenstein David , Metcalfe John , Gandhi Monica ,   Adolescent Treatment Failure (ATF) Study Team
Published: June 2021

Background:

Suboptimal adherence to antiretroviral therapy (ART) is responsible for most virologic failure among adolescents with HIV. Methods for objectively measuring adherence to ART are limited. This study assessed the association between ritonavir concentrations in hair and self-reported adherence and modified directly administered ART on virologic outcomes among HIV-infected adolescents who were virologically failing second-line ART in Harare, Zimbabwe.

Methods:

HIV-infected adolescents on atazanavir-based or ritonavir-based second-line treatment for >6 months with viral load ≥1000 copies/mL were randomized to either modified directly administered ART (mDAART) plus standard of care (intervention) or standard of care alone (control). Questionnaires were administered; viral load and hair samples were collected at baseline and after 90 days. Virological suppression was defned as <1000 copies/mL after follow-up.

Results:

Fifty adolescents (13–19 years) were enrolled in the study, and 42 adolescents had ritonavir concentrations measured in hair at baseline and at 90 days. Twenty-three participants (46%) were randomized to mDAART. Viral load suppression at follow-up [regression coefficient (standard error): −0.3 (0.1); 95% confidence interval (CI): −0.5 to −0.06; P = 0.01], self-reported adherence at follow-up [regression coefficient (standard error): 0.01 (0.005); 95% CI: 0.004 to 0.02; P = 0.006], and being male sex [regression coefficient (standard error): 0.3 (0.1); 95% CI: 0.08 to 0.5; P = 0.008] were associated with ritonavir concentrations in hair. The intervention, mDAART, was not associated with ritonavir concentrations [regression coefficient (standard error) 0.2 (0.1); 95% CI: −0.07 to 0.4; P = 0.2].

Conclusions:

Ritonavir concentrations in hair predicted virological suppression and were associated with self-reported adherence and being male in this cohort of adolescents with treatment failure to atazanavir-based or ritonavir-based second-line ART. Measuring ritonavir concentrations in hair in adolescents on protease inhibitor–based regimens could assess adherence in this vulnerable group to avert subsequent virologic failure.
Comparison of 18F-AlF-NOTA-FAPI and 18F-FDG Imaging in a Patient With Gastric Signet-Ring Cell Carcinoma
Authors: Guo Yue-Hong , Yang Min-Fu
Published: June 2021

Several case reports have shown fibroblast activation protein inhibitor (FAPI) imaging to be superior to 18F-FDG imaging in the delineation of primary gastric signet-ring cell carcinoma lesions. In this case, 18F-AlF-NOTA-FAPI PET/CT showed more metastatic lesions that had more increased activity than 18F-FDG PET/CT. However, neither 18F-AlF-NOTA-FAPI nor 18F-FDG imaging revealed any abnormal uptake in the primary gastric lesion, which was subsequently demonstrated to be the primary lesion by pathology.
Burkitt Lymphoma/Leukemia Presented on 68Ga-Pentixafor and 18F-FDG PET/CT
Authors: Chen Zhenying , Xue Qianqian , Huang Chao , Yao Shaobo , Miao Weibing
Published: June 2021

An 18-year-old man with newly diagnosed Burkitt lymphoma/leukemia was referred for 18F-FDG and 68Ga-Pentixafor PET/CT. 68Ga-Pentixafor PET/CT revealed similar radioactivity uptake pattern to the 18F-FDG PET/CT in superior phrenic lymph node, ascending colon, ileocecum, peritoneal, marrow, and spleen. This case highlighted that it might be interesting to further investigate the role of 68Ga-Pentixafor PET/CT imaging in staging, treatment evaluation, and especially the feasibility of CXCR4-directed radioligand therapy in Burkitt lymphoma with positive expression of CXCR4.
Genomic consequences of colonisation, migration and genetic drift in barn owl insular populations of the eastern Mediterranean
Authors: Machado Ana Paula , Topaloudis Alexandros , Cumer Tristan , Lavanchy Eléonore , Bontzorlos Vasileios , Ceccherelli Renato , Charter Motti , Kassinis Nikos , Lymberakis Petros , Manzia Francesca , Ducrest Anne-Lyse , Dupasquier Mélanie , Guex Nicolas , Roulin Alexandre , Goudet Jérôme
Published: June 2021

The study of insular populations was key in the development of evolutionary theory. The successful colonisation of an island depends on the geographic context, and specific characteristics of the organism and the island, but also on stochastic processes. As a result, apparently identical islands may harbour populations with contrasting histories. Here, we use whole genome sequences of 65 barn owls to investigate the patterns of inbreeding and genetic diversity of insular populations in the eastern Mediterranean Sea. We focus on Crete and Cyprus, islands with similar size, climate and distance to mainland, that provide natural replicates for a comparative analysis of the impacts of microevolutionary processes on isolated populations. We show that barn owl populations from each island have a separate origin, Crete being genetically more similar to other Greek islands and mainland Greece, and Cyprus more similar to the Levant. Further, our data show that their respective demographic histories following colonisation were also distinct. On the one hand, Crete harbours a small population and maintains very low levels of gene flow with neighbouring populations. This has resulted in low genetic diversity, strong genetic drift, increased relatedness in the population and remote inbreeding. Cyprus, on the other hand, appears to maintain enough gene flow with the mainland to avoid such an outcome. Our work provides a comparative population genomic analysis of the effects of neutral processes on a classical island-mainland model system. It provides empirical evidence for the role of stochastic processes in determining the fate of diverging isolated populations.
Growth allometry and dental topography in Upper Triassic conodonts support trophic differentiation and molar-like element function
Authors: Kelz Valentin , Guenser Pauline , Rigo Manuel , Jarochowska Emilia
Published: June 2021

Conodont elements have high rates of morphological evolution, but the drivers of this disparity are debated. Positive allometric relationships between dimensions of food-processing surfaces and entire P1elements have been used in to argue that these elements performed mechanical digestion. If involved in food processing, the surface of the element should grow at a rate proportional to the increase in energy requirements of the animal. This inference of function relies on the assumption that the energy requirements of the animal grew faster (≅ mass0.75) than the tooth area (≅ mass0.67). We re-evaluate this assumption based on metabolic rates across animals, and calculate the allometry in platform-bearing P1elements of Late Triassic co-occurring taxa,Metapolygnathus communistiandEpigondolella rigoi, using 3D models of ontogenetic series. Positive allometry is found in platform and element dimensions in both species, supporting a grasping-tooth hypothesis, based on the assumption that metabolic rate in conodonts scaled with body mass similarly to that in fish and ectoterms. We also calculate the curvature of P1platform surface using the Dirichlet Normal Energy (DNE) as a proxy for diet.DNE values increase with body mass, supporting the assumption that conodont metabolic rates increased faster than mass0.67. We finally find that adults in both taxa differ in their food bases, which supports trophic diversification as an important driver of the remarkable disparity of conodont elements.
Geopolitical implications of China’s rise in Asia
Authors: Jain Romi , Lee Joseph Tse-Hei
Published: June 2021

Purpose

This introductory essay historicizes the evolution of China’s geopolitical strategy from the Maoist era (1949–1976) to the present. It examines the Chinese strategic thinking in four spatial settings: Eurasia, maritime Southeast Asia, the Indian subcontinent and the wider Indo-Pacific region. The Chinese strategic concerns are comparable across these regions, but the ability to pursue security interests is contingent on many circumstantial factors. This study refers to some snapshots of the ongoing regional disputes to discuss the continuities and breakpoints in China’s strategic outreach in a multipolar world.

Design/methodology/approach

This study draws on the scholarly literature and policy papers to examine the interrelated forces that shape China’s rise to regional dominance: how Beijing has co-opted a series of global and regional crises for its rise to domination; how China, the USA and neighbouring countries have adjusted and adapted to a new changing international order; and how major powers in littoral and maritime Asia respond to an increasingly assertive Chinese state.

Findings

This study documents the combination of smart, soft and sharp power that China has deployed, since the global financial crisis of 2008, to enforce its dominance against the USA across the Pacific Rim and Eurasia. It argues that General Secretary of the Chinese Communist PartyXi Jinping initially launched the Belt and Road Initiative to respond to former US President Barak Obama’s policy of rebalancing Asia, and he has expanded these expansionary projects to counter US President Donald Trump’s “America First” doctrine, thereby asserting Chinese influence abroad and tightening control against discontented populations at home.

Research limitations/implications

Many Western policy analysts are wondering whether a rising China will be a “status quo” state or a revisionist state that attempts to challenge the existing world order. The lack of clarification from Beijing has prompted Washington to shift from a longstanding strategy of diplomatic engagement to that of geostrategic containment to balance against China.

Originality/value

The strategic goals of China in the early 21st century pertain to security reassurance, access to energy resources and national image building. Since the global financial crisis of 2008, China has become immensely confident of its own socio-economic accomplishments and scornful of what it perceives as an American conspiracy to undermine its rise to power. Following in the footsteps of the USA in the post-Second World War era, Japan in the 1980s and Taiwan in the 1990s, Beijing has used international commercial activities and business contracts to achieve specific political, strategic and diplomatic objectives.
Strategies for expanding HACCP certification rate using an awareness survey of dairy farmers
Authors: Chon Jung‐Whan , Koo Rakhyun , Song Kwang‐Young , Kang Il‐Byeong , Kim Dong‐Hyeon , Bae Dongryeoul , Kim Hyunsook , Kim Sae‐Hun , Seo Kun‐Ho
Published: June 2021

This study was performed to provide baseline data for developing strategies for expanding the Hazard Analysis Critical Control Point (HACCP) certification rate using an awareness survey of dairy farmers. A 44‐item questionnaire was used to survey randomly selected respondents comprising 84 HACCP‐certified and 75 noncertified dairy farms. The quality of raw milk in terms of bacterial and somatic cell count in HACCP‐certified farms was statistically (P < 0.05) higher compared with the milk in noncertified farms. Similarly, milk fat and milk protein were statistically (P < 0.05) superior in HACCP‐certified farms. The study finds that the practical barriers to implementing HACCP include inadequate financial assistance, incentive programmes, HACCP consulting and education, consumer awareness and knowledge about HACCP‐certified products, streamlined recording systems, and farm‐oriented mobile operations and maintenance systems. These findings can contribute to the development strategies to increase the rate of HACCP certification of dairy farms around the world.
Visceral fat level correction of the left ventricular hypertrophy electrocardiographic criteria
Authors: Salamaga Szymon , Dydowicz Franciszek , Turowska Agnieszka , Juszczyk Iwona , Matyjasek Mateusz , Kostka‐Jeziorny Katarzyna , Szczepaniak‐Chicheł Ludwina , Tykarski Andrzej , Uruski Paweł
Published: June 2021

Background

Left ventricular hypertrophy (LVH) is a well‐known risk factor for cardiovascular events. Even though there are many electrocardiographic (ECG) criteria for LVH, they still provide poor performance, especially among obese patients. The aim of this study was to examine whether adding visceral fat to ECG LVH criteria improves accuracy in the diagnosis.

Methods

One thousand seven hundred twenty two patients were included in the study. All patients underwent a complete physical examination, office blood pressure measurement, analysis of body composition, 12‐lead ECG, and M‐mode two‐dimensional echocardiography. Four standard ECG criteria for LVH were analyzed, including Cornell voltage criteria, Cornell duration criteria, Sokolow–Lyon voltage criteria, and Sokolow–Lyon product criteria. Adjustments of ECG LVH criteria were performed using visceral fat level (VFATL) and BMI. Transthoracic echocardiography was used as a reference method to compare the quality of ECG LVH criteria.

Results

Multivariate logistic regression models were created and revealed a significant increase of area under curve (AUC) after VFATL and BMI addition to ECG LVH criteria. Improvement of sensitivity at 90% specificity was observed in all created models. The odds ratio (OR) of the analyzed ECG criteria increased after adding VFATL and BMI to the models. Furthermore, ROC curves analysis exposed better characteristics in detecting LVH of VFATL‐adjusted criteria than BMI‐adjusted and unadjusted criteria.

Conclusions

Adjusting ECG indexes to BMI or VFATL improves the sensitivity of LVH detection. VFATL‐corrected indexes are more sufficiently than BMI‐corrected. After advancements in indexes, both lean and morbidly obese individuals outcomes show a greater prevalence of correct LVH diagnosis.
Non‐steroidal anti‐inflammatory drugs, polygenic risk score and colorectal cancer risk
Authors: Chen Xuechen , Guo Feng , Hoffmeister Michael , Chang‐Claude Jenny , Brenner Hermann
Published: June 2021

Background

The regular use of non‐steroidal anti‐inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk.

Aim

To explore whether this association varies according to background polygenic risk for CRC.

Methods

Data were collected from a large population‐based case‐control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC‐related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1 year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the ‘genetic risk equivalent’ (GRE), a recently developed metric for effective risk communication.

Results

In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P = 0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE −32, 95% CI −41, −22).

Conclusions

The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.
Current status in endoscopic management of upper gastrointestinal perforations, leaks and fistulas
Authors: Chan Shannon Melissa , Auyeung Kitty Kit Ying , Lam Siu Fung , Chiu Philip Wai Yan , Teoh Anthony Yuen Bun
Published: June 2021

Recent advancement in endoscopic closure techniques have revolutionized the treatment of gastrointestinal perforations, leaks and fistulas. Traditionally, these have been managed surgically. The treatment strategy depends on the size and location of the defect, degree of contamination, presence of healthy surrounding tissues, patients’ condition and the availability of expertise. One of the basic principles of management includes providing a barricade to the flow of luminal contents across the defect. This can be achieved with a wide range of endoscopic techniques. These include endoclips, stenting, suturing, tissue adhesives and glue, and endoscopic vacuum therapy. Each method has their distinct indications and shortcomings. Often, a combination of these techniques is required. Apart from endoscopic closure, drainage procedures by the interventional radiologist and surgical management also play an important role. In this review article, the outcomes of each of these endoscopic closure techniques in the literature is provided in tables, and practical management algorithms are being proposed.
Persistent visual dysfunction following posterior reversible encephalopathy syndrome due to COVID‐19: Case series and literature review
Authors: Hixon Alison M. , Thaker Ashesh A. , Pelak Victoria S.
Published: June 2021

Background and purpose

The full spectrum of neurological sequelae in COVID‐19 is beginning to emerge. SARS‐CoV‐2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long‐term neurological signs and symptoms. We sought to illuminate persistent neuro‐ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID‐19.

Methods

We identified three individuals with PRES due to COVID‐19 in our hospital system. One patient was identified on presentation to our neuro‐ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID‐19 identified through systematic literature search of PubMed/LitCOVID.

Results

All three patients were hospitalized with severe COVID‐19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID‐19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication.

Conclusions

As we learn about enduring neurological complications of COVID‐19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID‐19.
Comparison of equine synovial sepsis rate following intrasynovial injection in ambulatory versus hospital settings
Authors: Krause Danielle M. , Pezzanite Lynn M. , Griffenhagen Gregg M. , Hendrickson Dean A.
Published: June 2021

Background

Frequency of synovial sepsis in horses following intrasynovial injection has been reported, but not compared with respect to the environment in which the injection was performed.

Objectives

To describe occurrence of synovial sepsis following intrasynovial injections performed in ambulatory vs hospital settings.

Study design

Retrospective cohort study.

Methods

Records from the Colorado State University were evaluated (2014‐2018) and horses receiving intrasynovial injections were identified. Patients presenting for septic synovial structures were excluded. Patient signalment, primary supervising service, medications injected, location (field/hospital), whether synovial sepsis resulted, and at what time sepsis was recognised were recorded. Logistic regression was used to estimate the contributions of covariates to the occurrence of synovial sepsis following injection.

Results

During the study period, 3866 intrasynovial injections were performed in 1112 horses during 1623 sessions, with 643/1623 sessions performed in the field. The most frequently used medications were hyaluronate (846/1623, 52.1%), triamcinolone acetonide (780 /1623, 48.1%) and amikacin sulfate (684/1623, 42.1%). Four horses developed synovial sepsis (0.2% sessions, 0.1% synovial structures); 3/4 were injected in the field, 2/4 received antibiotics with the injection. The frequency of septic synovitis was 10.4 cases per 10 000 injections, or 1 in 967 injections. All horses recovered following synovial lavage and antibiotic therapy. Performing injections in the field (P = .2) or without antibiotics (P = .7) did not alter the risk of synovial sepsis.

Main limitations

Limitations include the retrospective nature of data collection and low rate of infection overall, which prohibited evaluation of individual medication regimes as factors associated with resultant infection.

Conclusions

The frequency of synovial sepsis in this population of horses was not higher when injections were performed in the field or without concurrent antibiotic administration. These data may help to inform practitioners and clients regarding the relative potential risk of complications following intrasynovial medication in different environmental settings.
Automated COVID‐19 detection in chest X‐ray images using fine‐tuned deep learning architectures
Authors: Aggarwal Sonam , Gupta Sheifali , Alhudhaif Adi , Koundal Deepika , Gupta Rupesh , Polat Kemal
Published: June 2021

The COVID‐19 pandemic has a significant impact on human health globally. The illness is due to the presence of a virus manifesting itself in a widespread disease resulting in a high mortality rate in the whole world. According to the study, infected patients have distinct radiographic visual characteristics as well as dry cough, breathlessness, fever, and other symptoms. Although, the reverse transcription polymerase‐chain reaction (RT‐PCR) test has been used for COVID‐19 testing its reliability is very low. Therefore, computed tomography and X‐ray images have been widely used. Artificial intelligence coupled with X‐ray technologies has recently shown to be more effective in the diagnosis of this disease. With this motivation, a comparative analysis of fine‐tuned deep learning architectures has been made to speed up the detection and classification of COVID‐19 patients from other pneumonia groups. The models used for this analysis are MobileNetV2, ResNet50, InceptionV3, NASNetMobile, VGG16, Xception, InceptionResNetV2 DenseNet121, which have been fine‐tuned using a new set of layers replaced with the head of the network. This research work has carried out an analysis on two datasets. Dataset‐1 includes the images of three classes: Normal, COVID, and Pneumonia. Dataset‐2, in contrast, contains the same classes with more focus on two prominent pneumonia categories: bacterial pneumonia and viral pneumonia. The research was conducted on 959 X‐ray images (250 of Bacterial Pneumonia, 250 of Viral Pneumonia, 209 of COVID, and 250 of Normal cases). Using the confusion matrix, the required results of different models have been computed. For the first dataset, DenseNet121 has obtained a 97% accuracy, while for the second dataset, MobileNetV2 has performed best with an accuracy of 81%.
Climatic niche shifts in 815 introduced plant species affect their predicted distributions
Authors: Zachariah Atwater Daniel , Barney Jacob N.
Published: June 2021

Aim

Introduced species often occupy different climates in their introduced than their native range, but to what degree do such ‘climatic niche shifts’ interfere with our ability to predict invasions? Answering this question is crucial if we are to understand the threat invasive species pose to human and natural systems, especially given the ever increasing use of species distribution models as tools for invasive species risk assessment and management. Here we investigated the degree to which climatic niche shifts interfered with the transferability of native‐ and introduced‐range species distribution models.

Location

Our dataset consisted of c. 14 million occurrences distributed worldwide.

Time period

Occurrence data were collected from online repositories dating from c. 1600 with the vast majority being from the 20th century. Climatic data represent means between 1970 and 2000.

Major taxa studied

Our database represented 815 terrestrial plant species.

Methods

We used ordination to identify climatic niche shifts as species moved between continents. Next, we trained separate Maxent models using native‐ or introduced‐range occurrences, and projected those models into each species’ introduced range. We compared the ordination and Maxent models to determine whether niche shifts were associated with errors in Maxent predictions.

Results

Models trained on native‐range occurrences poorly predicted introduced‐range occurrences, and transferability was lowest in species with large climatic niche shifts. Directional shifts in species’ predicted geographic distributions mirrored their niche dynamics. This is concerning because native‐range data are often used to predict introduced‐range distributions.

Main conclusions

Our results highlight the importance of considering niche shifts when modelling the potential geographic distributions of introduced species, and cast doubt on the assumption that the climatic niche of a species can be transferred between native and invasive ranges.
Diabetes and susceptibility to infections: Implication for COVID‐19
Authors: van Niekerk Gustav , van der Merwe Michelle , Engelbrecht Anna‐Mart
Published: June 2021

A number of mechanisms have been proposed to explain the well‐established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID‐19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune‐related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID‐19 infections.
Age‐based inter‐subject variability in platelet and white blood cell concentrations of platelet‐rich plasma prepared using a new application to blood separation system
Authors: Trevisson Bibiana , Becerro‐de‐Bengoa‐Vallejo Ricardo , Sevillano David , González Natalia , Losa‐Iglesias Marta , López‐López Daniel , Alou Luis
Published: June 2021

The benefit of autologous platelet‐rich plasma (PRP) treatment is still under discussion. Variations in PRP products, consequence of the lack of a standardised protocol for the multitude of commercially available blood separation systems and the lack of knowledge of the optimal composition of PRP or its suitability for the proposed indication are some of the reasons behind clinical inconsistencies. The impact of inter‐subject variability in PRP has received less attention in comparison. The purpose of this study was to determine the inter‐subject variability, based on age, in the concentrates prepared by a new blood concentration system. Twenty‐six healthy volunteers of both genders (29‐93 years) were enrolled. Whole blood (WB) was collected from each participant to prepare PRP using the Easy PRP kit. Platelets and white blood cells (WBC) from WB and PRP were analysed after split population by age; patients younger than 65 years (n = 13) and patients ≥65 years old (n = 13). Among the demographic characteristics tested, only age was significantly different between the groups. Cell capture efficiency of the system was specific for each type of blood cell and identical for both age groups. Platelets and WBC in PRP were higher than in WB (P < .001). In WB, platelets and WBC concentrations were significantly lower in older group (P ≤ .035). These differences persisted in the prepared PRP (P ≤ .004). The ageing of population has a strong influence on the haematocrit and therefore on the composition of PRP. Because the efficiency of blood separator system seems to be constant across individuals, the inter‐subject haematocrit variability based on age could be used as a predictor of resulting PRP. The clinical application of PRP should be restricted to the specific cell capture capacity of the different commercial devices.
Effects of the oral testosterone undecanoate Kyzatrex™ on ambulatory blood pressure in hypogonadal men
Authors: White William B. , Bernstein James S. , Rittmaster Roger , Dhingra Om
Published: June 2021

Testosterone replacement therapies have been shown to increase blood pressure (BP) in hypogonadal men. We studied the effects of a new formulation of testosterone undecanoate (Kyzatrex™) on ambulatory blood pressure (ABP) and heart rate, in 155 men with hypogonadism (mean age, 50.5 years, 76.8% white, 36.1% on antihypertensive therapy). The ABP, heart rate and clinical assessments were obtained at baseline and following 120 and 180 days of therapy. Mean changes from baseline in 24‐h ambulatory systolic BP of 1.7 mmHg (95% CI, 0.3, 3.1) at day 120 and 1.8 mmHg (95% CI, 0.3, 3.2) at day 180 were observed post‐treatment. For those men on antihypertensive drug therapy, increases in mean 24‐h systolic BP were greater than those not taking antihypertensive drugs (3.4 vs 0.7 mmHg at day 120 and 3.1 vs 1.0 mmHg at day 180, respectively). Changes from baseline in 24‐h diastolic BP and heart rate at day 120 were smaller (<1 mmHg and <1 beat/min, respectively). There were no relationships observed between testosterone concentration or hemoglobin levels with ABP. Multivariable analyses showed that baseline ambulatory BP and antihypertensive therapy were significantly correlated with BP changes. These data demonstrate small increases in ambulatory BP following 120 days on this oral testosterone undecanoate with no further changes at 180 days. Changes in ambulatory BP were minimal in patients not taking antihypertensive therapy.
Evolutionary dynamics of sex‐biased genes expressed in cricket brains and gonads
Authors: Whittle Carrie A. , Kulkarni Arpita , Extavour Cassandra G.
Published: June 2021

Sex‐biased gene expression, particularly sex‐biased expression in the gonad, has been linked to rates of protein sequence evolution (nonsynonymous to synonymous substitutions, dN/dS) in animals. However, in insects, sex‐biased expression studies remain centred on a few holometabolous species. Moreover, other major tissue types such as the brain remain underexplored. Here, we studied sex‐biased gene expression and protein evolution in a hemimetabolous insect, the cricket Gryllus bimaculatus. We generated novel male and female RNA‐seq data for two sexual tissue types, the gonad and somatic reproductive system, and for two core components of the nervous system, the brain and ventral nerve cord. From a genome‐wide analysis, we report several core findings. Firstly, testis‐biased genes had accelerated evolution, as compared to ovary‐biased and unbiased genes, which was associated with positive selection events. Secondly, although sex‐biased brain genes were much less common than for the gonad, they exhibited a striking tendency for rapid protein sequence evolution, an effect that was stronger for the female than male brain. Further, some sex‐biased brain genes were linked to sexual functions and mating behaviours, which we suggest may have accelerated their evolution via sexual selection. Thirdly, a tendency for narrow cross‐tissue expression breadth, suggesting low pleiotropy, was observed for sex‐biased brain genes, suggesting relaxed purifying selection, which we speculate may allow enhanced freedom to evolve adaptive protein functional changes. The findings of rapid evolution of testis‐biased genes and male and female‐biased brain genes are discussed with respect to pleiotropy, positive selection and the mating biology of this cricket.
Rapid Curricular Innovations During COVID‐19 Clinical Suspension: Maintaining Student Engagement with Simulation Experiences
Authors: Bradford Heather M. , Farley Cindy L. , Escobar Melicia , Heitzler Ella T. , Tringali Tanya , Walker Kelly C.
Published: June 2021

Health care education programs were faced with the need to quickly adapt to a new reality during the coronavirus disease 2019 pandemic. Students were temporarily suspended from campus and clinical sites, requiring prompt changes in structure to their didactic and clinical learning. This article describes the rapid adjustments that one midwifery and women's health nurse practitioner education program created using both synchronous and asynchronous simulation experiences to promote student learning and ongoing engagement. Flexibility and reflexivity were needed by faculty and students alike in the face of the multiple changes wrought by the pandemic. Curricular changes were made simultaneously in many courses. Objective structured clinical examinations simulate telehealth experiences that assess knowledge, clinical reasoning, and professional behaviors via a scripted scenario and an actor patient. On‐call simulations mimic telephone triage and provide students the opportunity to build listening, assessment, and management skills for prenatal and intrapartum scenarios. Students are provided equipment and virtual instruction in an intrauterine device insertion session, which promotes skill acquisition and self‐confidence. Trigger films are used to visualize real‐life or scripted clinical encounters, leading to discussion and decision‐making, particularly in the affective domain. Bilateral learning tools, similar to case studies, provide students an opportunity to demonstrate their knowledge and critical thinking with a mechanism for faculty feedback. Web‐based virtual clinical encounter learning tools using patient avatars prompt additional student learning. Suturing skills introduced in live remote group sessions are augmented with video‐guided individual practice. This article describes each of these adapted and innovative simulation methods and shares lessons learned during their development and implementation.
Positive species interactions shape species' range limits
Authors: Stephan Pauline , Bramon Mora Bernat , Alexander Jake M.
Published: June 2021

The relationship between niche and distribution, and especially the role of biotic interactions in shaping species' geographic distributions, has gained increasing interest in the last two decades. Most ecological research has focused on negative species interactions, especially competition, predation and parasitism. Yet the relevance of positive interactions – mutualisms and commensalisms – have been brought to the fore in recent years by an increasing number of empirical studies exploring their impact on range limits. Based on a review of 73 studies from a Web of Science search, we found strong evidence that positive interactions can influence the extent of species' geographic or ecological ranges through a diversity of mechanisms. More specifically, we found that while obligate interactions, and especially obligate mutualisms, tend to constrain the ranges of one or both partners, facultative positive interactions tend to widen ranges. Nonetheless, there was more variation in effects of facultative interactions on range limits, pointing to important context‐dependencies. Therefore, we propose that conceptual development in this field will come from studying ecological interactions in the context of networks of many species across environmental gradients, since pairwise interactions alone might overlook the indirect and environmentally‐contingent effects that species have on each other in communities of many interacting species. Finally, our study also revealed key data gaps that limit our current understanding of the pervasiveness of effects that positive interactions have on species' ranges, highlighting potential avenues for future theoretical and experimental work.
Tuning the Polarity of Fullerene C60 Derivatives for Enhanced Photodynamic Inactivation†
Authors: Palacios Yohana B. , Durantini Javier E. , Heredia Daniel A. , Martínez Sol R. , González de la Torre Laura , Durantini Andrés M.
Published: June 2021

In this article, four novel fulleropyrrolidines derivatives were synthesized to study how the effect of polarity and positive charge distribution can influence the efficacy of photodynamic inactivation treatments to kill bacteria. The design of the photosensitizers was based on DFT calculations that allowed us to estimate the dipolar moment of the molecules. Neutral compounds bearing N‐methyl bis‐acetoxy‐ethyl (1) and bis‐hydroxyethyl (2) amine were the starting material to obtain the dicationic analogs N,N‐dimethyl bis‐methoxyethyl (3), and bis‐acetoxy‐ethyl) (4) methylammonio. As expected from fullerene C60 derivatives, compounds 1‐4 absorb in the UV region, with a peak at 430 nm, a broader range of absorption up to 710 nm, and exhibit weak fluorescence emission in toluene and reverse micelles. In the biomimetic AOT micellar system, the highest singlet oxygen photosensitization was found for compounds 1, followed by 3, 2, and 4. Whereas 4 was the most effective reducing nitro blue tetrazolium in the presence of β‐NADH. The influence of type I and type II mechanism on the photodynamic activity of compounds 3 and 4 was further examined in the presence of L‐tryptophan and two reactive oxygen species scavengers. In vitro experiments indicated that the compounds with the highest dipolar moments, 3 (37.19 D) and 4 (38.46 D), inactivated methicillin‐resistant Staphylococcus aureus and Escherichia coli bacteria using an energy dose <2.4 J cm−2. No inactivation was observed for the neutral analogs with the lowest dipolar moments. These findings help to optimize sensitizer structures to improve photodynamic inactivation.
The neural–vascular basis of age‐related processing speed decline
Authors: Zhao Yuguang , Liu Peiying , Turner Monroe P. , Abdelkarim Dema , Lu Hanzhang , Rypma Bart
Published: June 2021

Most studies examining neurocognitive aging are based on the blood‐oxygen level‐dependent signal obtained during functional magnetic resonance imaging (fMRI). The physiological basis of this signal is neural–vascular coupling, the process by which neurons signal cerebrovasculature to dilate in response to an increase in active neural metabolism due to stimulation. These fMRI studies of aging rely on the hemodynamic equivalence assumption that this process is not disrupted by physiologic deterioration associated with aging. Studies of neural–vascular coupling challenge this assumption and show that neural–vascular coupling is closely related to cognition. In this review, we put forward a theory of processing speed decline in aging and how it is related to age‐related neural–vascular coupling changes based on the results of studies elucidating the relationships between cognition, cerebrovascular dynamics, and aging.
Towards reconfiguration in European agriculture: Analysing dynamics of change through the lens of the Donau Soja organization
Authors: Bentia Dana C.
Published: June 2021

Recent explorations of agri‐environmental governance which draw on the assemblage perspective highlight the relational aspects, the process dimension and the generative elements of certain sustainability endeavours. This article argues that the implications of this approach are little discussed especially what concerns the transformation potential of agri‐environmental programmes. We focus on the notion of reconfiguration as a significant facet of transformation. We align with recent research in transition studies to claim the need for conceptualizing reconfiguration. We draw on empirical research pursued with the Donau Soja organization to refer to a number of unfolding reconfigurations, in respect to the spatial, the technological and the political dimensions. We focus on the political reconfiguration and discuss some of the spillover effects of scientific research projects and proposals, programmatic papers, policy positioning and lobby work which accompany the everyday work and governance of the Donau Soja organization. We argue that greater attention to the unmeasured and unmeasurable effects of the DS assemblage also implies giving greater attention to the long‐term effects of such programmes. Moreover, the numerous changes unleashed by the organization demand research to re‐evaluate what counts as failure and success in agri‐environmental governance.
Decolonizing Folklore? Diversifying the Fairy Tale Curriculum
Authors: Peabody Seth
Published: June 2021

This article describes strategies that the author employed to make a general education course titled “Fairy Tales and Folklore” more diverse and inclusive. Students read primary texts and secondary articles as part of ongoing debates, then form their own arguments within the debate, thus coming to understand how fairy tales are embedded within open and ongoing critical discussions about contemporary culture. Further, students analyze a classic work of Native American literature that, like the Grimm Brothers’Kinder‐ und Hausmärchen, employs folklore within a project of cultural nationalism, but with very different implications due to systems of power and oppression that emerge at the intersection of folklore and colonization. Finally, students create new tales out of their own experiences. Through analysis of diverse texts, debate, and creative writing that emphasize the role of storytelling as resistance, the course described here takes first steps toward turning the fairy‐tale classroom into a space of empowerment.
A comparative study on perinatal outcomes of red blood cell–alloimmunized pregnancies with anti‐RhD in combination and anti‐RhD alone in China
Authors: Yu Muxue , Tang Tonghui , Zheng Rujiang , Situ Miaoqiong , Feng Jiali
Published: June 2021

Background and Objectives

The advent of intrauterine transfusion (IUT) has improved the survival of severe foetal anaemia. The aim of this study was to compare the perinatal outcomes of red blood cell (RBC)–alloimmunized pregnancies with anti‐RhD in combination and anti‐RhD alone in China.

Materials and Methods

A retrospective study was conducted involving RBC–alloimmunized pregnancies with anti‐RhD in combination and anti‐RhD alone admitted to The First Affiliated Hospital, Sun Yat‐sen University, between January 2007 and December 2019. Obstetric data and neonatal outcomes were compared.

Results

A total of 165 alloimmunized pregnancies were identified, with 32 pregnancies in the anti‐RhD‐in‐combination group (25 pregnancies with anti‐RhD + anti‐RhC and 7 pregnancies with anti‐RhD + anti‐RhE) and 133 pregnancies in the anti‐RhD‐alone group. The anti‐RhD‐in‐combination group had significantly higher frequency of IUTs than the anti‐RhD‐alone group (59.4% [19/32] vs. 30.1% [40/133]; p < 0.01). The postnatal frequency of top‐up transfusions was significantly higher in the anti‐RhD in combination group than the anti‐RhD‐alone group (90.6% [29/32] vs. 70.7% [94/133]; p = 0.02). There was no significant difference in the frequency of exchange transfusions (ETs) between the two groups (15.6% [5/32] vs. 17.3% [23/133]; p = 0.82).

Conclusions

Compared to alloimmunized pregnancies with anti‐RhD alone, pregnancies with anti‐RhD in combination with anti‐RhC or anti‐RhE have an increased requirement for antenatal IUTs and postnatal top‐up transfusions but do not have an increased need for ETs.