bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental study of newly described avian malaria parasite Plasmodium (Novyella) collidatum n. sp., genetic lineage pFANTAIL01 obtained from South Asian migrant bird
Authors: Platonova Elena , Aželytė Justė , Iezhova Tatjana , Ilgūnas Mikas , Mukhin Andrey , Palinauskas Vaidas
Published: February 2021

Background

Avian malaria parasites are microorganisms parasitizing erythrocytes and various tissues of the birds; they are common and distributed worldwide. These parasites are known to infect birds of different taxa and be the cause of the deaths of birds in the wild and in captivity. The species of parasites with the ability to colonize new territories and infect local non-migratory birds are of particular interest. This scenario is likely in temperate zones of Europe, because of climate change and its contribution in spreading vectors of southern origin, which can be involved in the transmission of malaria parasites. In the present study, a tropical Plasmodium parasite from a naturally infected long-distance migrant bird was isolated and tested for its ability to develop in common species of mosquitoes and European short-distance migrant birds.

Methods

Plasmodium sp. (pFANTAIL01) was isolated on the Curonian spit of the Baltic sea coast from the naturally infected Common rosefinch, Carpodacus erythrinus in June 2019. The parasite was described based on the morphological features of its blood stages, the partial mitochondrial cytochrome b gene and development after experimental infection of birds and mosquitoes. The parasite was inoculated into Eurasian siskins, Carduelis spinus. Parasitaemia, haematocrit and weight of birds were monitored. At the end of the survey, internal organs were collected to study exoerythrocytic stages of this parasite. Experimental infection of mosquitoes Culex pipiens form molestus and Culex quinquefasciatus was applied to study sporogonic development of the parasite.

Results

Based on morphological features, the parasite was described as a new species, Plasmodium collidatum n. sp., and attributed to subgenus Novyella. It was revealed that the obtained pFANTAIL01 lineage is a generalist parasite infecting a wide range of avian hosts and most likely is transmitted in South and Southeast (SE) Asia and Oceania. In Europe, this strain was recorded only in adult migratory birds wintering in South Asia. This parasite developed high parasitaemia in experimentally infected siskins and caused 25 % mortality. Exoerythrocytic stages of pFANTAIL01 were found in the lungs, liver, spleen and kidney of the deceased birds. Sporogonic development did not occur in Cx. pipiens form molestus and Cx. quinquefasciatus mosquitoes.

Conclusions

Plasmodium collidatum is a highly virulent for Eurasian siskin and completes its development in these birds, which can be considered as a potential vertebrate host if the transmission of the infection starts occurring in Europe and temperate zones.
“An epoch-making and blessed moment in the history of medicine” –thoughts on international health equity and the Nobel prize in medicine
Authors: Linneman Zachary M. , Satin David J.
Published: February 2021

The Nobel Prize in Physiology or Medicine is a prestigious award given every year for ostensibly the most important discovery in the field. Prizes in Medicine have typically gone to honor foundational knowledge rather than measurable impact. Two recent examples from global health (a rotavirus vaccine, child growth standards) offer alternatives for what might be lauded in medicine. These two examples and historical achievements regarding cholera and smallpox are worthy but do not fall within the scope of Nobel awards for Peace or Economics. The COVID-19 pandemic gives a new context for the idea that discovery and implementation are both keys to medicine. New patterns that redefine achievement in medicine could emerge by Nobel Prize precedent to promote greater health equity and international collaboration.
Civil society involvement in harm reduction drug policy: reflections on the past, expectations for the future
Authors: O’Gorman Aileen , Schatz Eberhard
Published: February 2021

Background

A range of civil society organisations (CSOs) such as drug user groups, non-governmental/third sector organisations and networks of existing organisations, seek to shape the development of drugs policy at national and international levels. However, their capacity to do so is shaped by the contexts in which they operate nationally and internationally. The aim of this paper is to explore the lived experience of civil society participation in these contexts, both from the perspective of CSOs engaged in harm reduction advocacy, and the institutions they engage with, in order to inform future policy development.

Methods

This paper is based on the presentations and discussions from a workshop on ‘Civil Society Involvement in Drug Policy hosted by the Correlation - European Harm Reduction Network at the International Society for the Study of Drugs Policy (ISSDP) annual conference in Paris, 2019. In the aftermath of the workshop, the authors analysed the papers and discussions and identified the key themes arising to inform CSI in developing future harm reduction policy and practice.

Results

Civil society involvement (CSI) in policy decision-making and implementation is acknowledged as an important benefit to representative democracy. Yet, the accounts of CSOs demonstrate the challenges they experience in seeking to shape the contested field of drug policy. Negotiating the complex workings of political institutions, often in adversarial and heavily bureaucratic environments, proved difficult. Nonetheless, an increase in structures which formalised and resourced CSI enabled more meaningful participation at different levels and at different stages of policy making.

Conclusions

Civil society spaces are colonised by a broad range of civil society actors lobbying from different ideological standpoints including those advocating for a ‘drug free world’ and those advocating for harm reduction. In these competitive arena, it may be difficult for harm reduction orientated CSOs to influence the policy process. However, the current COVID-19 public health crisis clearly demonstrates the benefits of partnership between CSOs and political institutions to address the harm reduction needs of people who use drugs. The lessons drawn from our workshop serve to inform all partners on this pathway.
Pattern of failure in prostate cancer previously treated with radical prostatectomy and post-operative radiotherapy: a secondary analysis of two prospective studies using novel molecular imaging techniques
Authors: Rowe Lindsay S. , Harmon Stephanie , Horn Adam , Shankavaram Uma , Roy Soumyajit , Ning Holly , Lindenberg Liza , Mena Esther , Citrin Deborah E. , Choyke Peter , Turkbey Baris
Published: February 2021

Background

Prostate Membrane Specific Antigen (PSMA) positron emission tomography (PET) and multiparametric MRI (mpMRI) have shown high accuracy in identifying recurrent lesions after definitive treatment in prostate cancer (PCa). In this study, we aimed to outline patterns of failure in a group of post-prostatectomy patients who received adjuvant or salvage radiation therapy (PORT) and subsequently experienced biochemical recurrence, using 18F-PSMA PET/CT and mpMRI.

Methods

PCa patients with biochemical failure post-prostatectomy, and no evident site of recurrence on conventional imaging, were enrolled on two prospective trials of first and second generation 18F-PSMA PET agents (18F-DCFBC and 18F-DCFPyL) in combination with MRI between October 2014 and December 2018. The primary aim of our study is to characterize these lesions with respect to their location relative to previous PORT field and received dose.

Results

A total of 34 participants underwent 18F-PSMA PET imaging for biochemical recurrence after radical prostatectomy and PORT, with 32/34 found to have 18F-PSMA avid lesions. On 18F-PSMA, 17/32 patients (53.1%) had metastatic disease, 8/32 (25.0%) patients had locoregional recurrences, and 7/32 (21.9%) had local failure in the prostate fossa. On further exploration, we noted 6/7 (86%) of prostate fossa recurrences were in-field and were encompassed by 100% isodose lines, receiving 64.8–72 Gy. One patient had marginal failure encompassed by the 49 Gy isodose.

Conclusions

18F-PSMA PET imaging demonstrates promise in identifying occult PCa recurrence after PORT. Although distant recurrence was the predominant pattern of failure, in-field recurrence was noted in approximately 1/5th of patients. This should be considered in tailoring radiotherapy practice after prostatectomy.

Trial registrationwww.clinicaltrials.gov, NCT02190279 and NCT03181867. Registered July 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02190279 and June 8 2017, https://clinicaltrials.gov/ct2/show/NCT03181867.
Dose atrophy of vastus medialis obliquus and vastus lateralis exist in patients with patellofemoral pain syndrome
Authors: Dong Conglei , Li Ming , Hao Kuo , Zhao Chao , Piao Kang , Lin Wei , Fan Chongyi , Niu Yingzhen , Fei Wang
Published: February 2021

Background

Whether vastus medialis obliquus atrophy exists in patients with patellofemoral pain syndrome and whether the amount of atrophy differs between the vastus medialis obliquus and vastus lateralis muscles remain unknown.

Materials

From June 2016 to March 2019, 61 patients with patellofemoral pain syndrome were retrospectively included in the study group, and an age-, sex-, and body mass index-matched cohort of 61 patients with normal knees was randomly selected as the control group. All enrolled subjects had undergone CT scans in the supine position. The cross-sectional areas of the vastus medialis obliquus and the vastus lateralis muscle in the sections 0, 5, 10, 15, and 20 mm above the upper pole of the patella were measured, and the vastus medialis obliquus/vastus lateralis muscle area ratio was evaluated.

Results

In the study group, the vastus medialis obliquus areas and the vastus lateralis muscle areas in the sections that were 0, 5, 10, 15, and 20 mm above the upper pole of the patella were significantly smaller than the respective areas in the control group (P< 0.05). The vastus medialis obliquus/vastus lateralis muscle area ratio was significantly smaller at the upper pole of the patella (the section 0 mm above the upper pole of the patella) than the corresponding ratio in the control group (P< 0.05). No significant difference was noted between the two groups in the sections 5, 10, 15, and 20 mm above the upper pole of the patella (P> 0.05).

Conclusion

In patients with patellofemoral pain syndrome, vastus medialis obliquus and vastus lateralis muscle atrophy existed in sections 0–20 mm above the upper pole of the patella, compared with normal controls, and atrophy of the vastus medialis obliquus was more evident than that of the vastus lateralis muscle at the upper pole of the patella. These findings support the rationale for the use of general quadriceps exercise combined with vastus medialis obliquus strengthening exercise as part of the rehabilitation programme for the patients with patellofemoral pain syndrome.
LRSAM1 and the RING domain: Charcot–Marie–Tooth disease and beyond
Authors: Palaima Paulius , Berciano José , Peeters Kristien , Jordanova Albena
Published: February 2021

In the past decade, mutations in LRSAM1 were identified as the genetic cause of both dominant and recessive forms of axonal CMT type 2P (CMT2P). Despite demonstrating different inheritance patterns, dominant CMT2P is usually characterized by relatively mild, slowly progressive axonal neuropathy, mainly involving lower limbs, with age of onset between the second and fifth decades of life. Asymptomatic individuals were identified in several pedigrees exemplifying the strong phenotypic variability of these patients requiring serial clinical evaluation to establish correct diagnosis; in this respect, magnetic resonance imaging of lower-limb musculature showing fatty atrophy might be helpful in detecting subclinical gene mutation carriers. LRSAM1 is a universally expressed RING-type E3 ubiquitin protein ligase catalysing the final step in the ubiquitination cascade. Strikingly, TSG101 remains the only known ubiquitination target hampering our mechanistic understanding of the role of LRSAM1 in the cell. The recessive CMT mutations lead to complete loss of LRSAM1, contrary to the heterozygous dominant variants. These tightly cluster in the C-terminal RING domain highlighting its importance in governing the CMT disease. The domain is crucial for the ubiquitination function of LRSAM1 and CMT mutations disrupt its function, however it remains unknown how this leads to the peripheral neuropathy. Additionally, recent studies have linked LRSAM1 with other neurodegenerative diseases of peripheral and central nervous systems. In this review we share our experience with the challenging clinical diagnosis of CMT2P and summarize the mechanistic insights about the LRSAM1 dysfunction that might be helpful for the neurodegenerative field at large.
Metabolic fingerprints of fear memory consolidation during sleep
Authors: Koyanagi Iyo , Sonomura Kazuhiro , Naoi Toshie , Ohnishi Takaaki , Kaneko Naoko , Sawamoto Kazunobu , Sato Taka-Aki , Sakaguchi Masanori
Published: February 2021

Metabolites underlying brain function and pathology are not as well understood as genes. Here, we applied a novel metabolomics approach to further understand the mechanisms of memory processing in sleep. As hippocampal dentate gyrus neurons are known to consolidate contextual fear memory, we analyzed real-time changes in metabolites in the dentate gyrus in different sleep–wake states in mice. Throughout the study, we consistently detected more than > 200 metabolites. Metabolite profiles changed dramactically upon sleep–wake state transitions, leading to a clear separation of phenotypes between wakefulness and sleep. By contrast, contextual fear memory consolidation induced less obvious metabolite phenotypes. However, changes in purine metabolites were observed upon both sleep–wake state transitions and contextual fear memory consolidation. Dietary supplementation of certain purine metabolites impaired correlations between conditioned fear responses before and after memory consolidation. These results point toward the importance of purine metabolism in fear memory processing during sleep.
Which patient-reported outcomes do rheumatology patients find important to track digitally? A real-world longitudinal study in ArthritisPower
Authors: Nowell W. Benjamin , Gavigan Kelly , Kannowski Carol L. , Cai Zhihong , Hunter Theresa , Venkatachalam Shilpa , Birt Julie , Workman Jennifer , Curtis Jeffrey R.
Published: February 2021

Background

Patient-reported outcomes (PROs) are increasingly used to track symptoms and to assess disease activity, quality of life, and treatment effectiveness. It is therefore important to understand which PROs patients with rheumatic and musculoskeletal disease consider most important to track for disease management.

Methods

Adult US patients within the ArthritisPower registry with ankylosing spondylitis, fibromyalgia syndrome, osteoarthritis, osteoporosis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus were invited to select between 3 and 10 PRO symptom measures they felt were important to digitally track for their condition via the ArthritisPower app. Over the next 3 months, participants (pts) were given the option to continue tracking their previously selected measures or to remove/add measures at 3 subsequent monthly time points (month [m] 1, m2, m3). At m3, pts prioritized up to 5 measures. Measures were rank-ordered, summed, and weighted based on pts rating to produce a summary score for each PRO measure.

Results

Among pts who completed initial selection of PRO assessments at baseline (N = 253), 140 pts confirmed or changed PRO selections across m1–3 within the specified monthly time window (28 days ± 7). PROs ranked as most important for tracking were PROMIS Fatigue, Physical Function, Pain Intensity, Pain Interference, Duration of Morning Joint Stiffness, and Sleep Disturbance. Patient’s preferences regarding the importance of these PROs were stable over time.

Conclusion

The symptoms that rheumatology patients prioritized for longitudinal tracking using a smartphone app were fatigue, physical function, pain, and morning joint stiffness.
Not all biases are bad: equitable and inequitable biases in machine learning and radiology
Authors: Pot Mirjam , Kieusseyan Nathalie , Prainsack Barbara
Published: February 2021

The application of machine learning (ML) technologies in medicine generally but also in radiology more specifically is hoped to improve clinical processes and the provision of healthcare. A central motivation in this regard is to advance patient treatment by reducing human error and increasing the accuracy of prognosis, diagnosis and therapy decisions. There is, however, also increasing awareness about bias in ML technologies and its potentially harmful consequences. Biases refer to systematic distortions of datasets, algorithms, or human decision making. These systematic distortions are understood to have negative effects on the quality of an outcome in terms of accuracy, fairness, or transparency. But biases are not only a technical problem that requires a technical solution. Because they often also have a social dimension, the ‘distorted’ outcomes they yield often have implications for equity. This paper assesses different types of biases that can emerge within applications of ML in radiology, and discusses in what cases such biases are problematic. Drawing upon theories of equity in healthcare, we argue that while some biases are harmful and should be acted upon, others might be unproblematic and even desirable—exactly because they can contribute to overcome inequities.
Eco-friendly analytical methods for the determination of compounds with disparate spectral overlapping: application to antiviral formulation of sofosbuvir and velpatasvir
Authors: El-Yazbi Amira F. , Elashkar Nourhan E. , Abdel-Hay Karim M. , Ahmed Hytham M. , Talaat Wael
Published: February 2021

Green analytical chemistry is one of the newest trends in analytical chemistry nowadays targeting the concept of green laboratory practices on chemists and environment. In this text, green practices are proposed in this work for the determination of sofosbuvir (SF) and velpatasvir (VP) in their pharmaceutical formulation. The analysis of SF in a binary mixture with VP represents an analytical challenge due to the complete overlapping of the UV spectrum of SF by that of VP. Therefore, the direct absorbance and derivative measurements cannot resolve such interference and failed to determine SF. In this paper, three direct and simple methods were developed for the analysis of SF without any interference from VP without sample pre-treatment. The proposed methods include measuring the second derivative amplitude of the ratio spectrum of the mixture using VP as a divisor, measuring the absorbance difference of the mixture in NaOH solution against its HCl solution, and using the derivative compensation technique. On the other hand, VP was determined specifically in presence of SF by two methods. Firstly, by its reaction with 4-chloro-7-nitrobenzofurazan (NBD-Cl) where the reaction product was measured spectrophotometrically and spectrofluorometrically and secondly through the reaction of VP with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH). The calibration curves showed good correlation coefficient (r2 > 0.999). The developed methods were highly precise with RSD% values less than 2%. The method greenness profile was compared with other published methods by applying the eco-scale protocol. Assessment results proved that our analytical procedure is greener than other reported methods. Moreover, upon comparison with other methods, the proposed methods showed better or comparable sensitivity in addition to being inexpensive and ecofriendly. Accordingly, these methods could be readily applied for quality control purposes as an eco-friendly, simple and efficient analytical tool.
Gastrointestinal tract imaging findings in confirmed COVID-19 patients: a non-comparative observational study
Authors: Abdelmohsen Mohsen Ahmed , Alkandari Buthaina M. , Gupta Vikash K. , Elsebaie Nermeen
Published: February 2021

Background

Corona virus disease 2019 (COVID-19) pandemic—as declared by the World Health Organization—is a major threatening public health problem. At the time of writing, more than 60,000,000 patients and more than 1,500,000 deaths were recorded worldwide.

Besides the classical chest symptoms, gastrointestinal tract-related symptoms were noted, like diarrhea, abdominal distention, and hematochezia, adding more difficulties in the diagnosis of the disease.

Although there are many publications evaluated, the thoracic imaging signs and complications of COVID-19, there are few articles—to the best of our knowledge—that evaluated the gastrointestinal tract imaging features and complications related to COVID-19.

Results

In this retrospective study, positive COVID-19 patients who underwent diagnostic computed tomography (CT) for abdominal complaints along a 3-month duration in a large isolation hospital were evaluated. Strict infection control measures were taken during the CT examinations. The data were reviewed on picture archiving and communications systems with clinical data and laboratory result correlation. Thirty patients (30%) showed gastrointestinal (GI) findings, and 70 patients showed unremarkable or non-related GI findings. The 30 patients were classified into four groups: the ischemic group including 10 patients (10/30: 33.33%), the bleeding group included six patients (6/30: 20%), the inflammatory group included nine patients (9/30: 30%), and fluid-filled bowel group included five patients (5/30: 16.6%).

Conclusions

COVID-19 should be evaluated as a systemic disease with extra pulmonary highlights. GI imaging should be considered for COVID-19 patients with related suspicious symptoms. Ischemic GI complications were the most common GI findings.
Anticancer activities of phenolic compounds from Moringa oleifera leaves: in vitro and in silico mechanistic study
Authors: Mumtaz Muhammad Zahid , Kausar Fareeda , Hassan Mubashir , Javaid Shaista , Malik Arif
Published: February 2021

Background

Moringa oleifera is a common vegetable in many countries since ancient times, possesses numerous phenolic compounds having a wide array of biological activities. It possesses anticancer activity that can be used to develop new drugs for treatment of various types of cancers. The current study was conducted to evaluate the composition of phenolic compounds and in vitro and in silico anticancer activities of M. oleifera leaves extracts. The leaves of M. oleifera were subjected to extraction for solvent fraction using n-hexane, chloroform, ethyl acetate, butanol, and aqueous solvents. The solvent fractions were tested for anticancer activity in vitro against Hela cancer cell line and screened for phenolic compounds through reversed-phase high-performance liquid chromatography. The molecular docking approach was employed to check binding conformations of phytochemicals against the target protein.

Result

The result revealed that all the solvent fractions possess in vitro anticancer activity against Hela cancer cell line. The n-hexane fraction showed a 50% reduction in Hela cancer cell viability at 416 μg mL−1 as compared to control. The extracts of solvent-fraction contained 10 phenolic compounds viz. quercetin, gallic acid, sinapic acid, vanillic acid, 4-hydroxy-3-methoxy benzoic acid, p-coumaric acid, m-coumaric acid, 4-hydroxy-3-methoxy cinnamic acid, caffeic acid, and syringic acid. Molecular docking studies revealed that the ligands bind within the active site of target protein have good binding energy values.

Conclusion

This study shows that M. oleifera leaves may have the potential to inhibit cancer cell growth and improving human health in addition to food ingredient innovations. Based on in vitro and in silico results, the phytochemicals from M. oleifera leaves can be used as leading drugs to treat cancer.

Graphical abstract
Effective elastic properties of rocks with transversely isotropic background permeated by a set of vertical fracture cluster
Authors: Shuai Da , Stovas Alexey , Wei Jianxin , Di Bangrang , Zhao Yang
Published: February 2021

The linear slip theory is gradually being used to characterize seismic anisotropy. If the transversely isotropic medium embeds vertical fractures (VFTI medium), the effective medium becomes orthorhombic. The vertical fractures, in reality, may exist in any azimuth angle that leads the effective medium to be monoclinic. We apply the linear slip theory to create a monoclinic medium by only introducing three more physical meaning parameters: the fracture preferred azimuth angle, the fracture azimuth angle, and the angular standard deviation. First, we summarize the effective compliance of a rock as the sum of the background matrix compliance and the fracture excess compliance. Then, we apply the Bond transformation to rotate the fractures to be azimuthally dependent, introduce a Gaussian function to describe the fractures’ azimuth distribution assuming that the fractures are statistically distributed around the preferred azimuth angle, and average each fracture excess compliance over the azimuth. We investigate the influence of the fracture azimuth distribution domain and angular standard deviation on the effective stiffness coefficients, elastic wave velocities, and anisotropy parameters. Our results show that the fracture cluster parameters have a significant influence on the elastic wave velocities. The fracture azimuth distribution domain and angular standard deviation have a bigger influence on the orthorhombic anisotropy parameters in the [Formula: see text] plane than in the [Formula: see text] plane. The fracture azimuth distribution domain and angular standard deviation have little influence on the monoclinic anisotropy parameters responsible for the P-wave NMO ellipse and have a significant influence on the monoclinic anisotropy parameters responsible for the S1- and S2-wave NMO ellipse. The effective monoclinic can degenerate into the VFTI medium.
High-Intensity End-of-Life Care Among Patients With GI Cancer in Puerto Rico: A Population-Based Study
Authors: Ortiz-Ortiz Karen J. , Tortolero-Luna Guillermo , Torres-Cintrón Carlos R. , Zavala-Zegarra Diego E. , Gierbolini-Bermúdez Axel , Ramos-Fernández María R.
Published: February 2021

PURPOSE:

High-intensity care with undue suffering among patients with cancer at the end of life (EoL) is associated with poor quality of life. We examined the pattern and predictors of high-intensity care among patients with GI cancer in Puerto Rico.

METHODS:

This population-based study of data from the Puerto Rico Central Cancer Registry-Health Insurance Linkage Database examined patients with GI cancer who died between 2009 and 2017. EoL care intensity indicators include the following services in the last month before death: emergency room (ER) visits, hospitalizations, intensive care unit (ICU) admissions, life-extending procedures, death in an acute care setting, and the use of chemotherapy in the last 14 days. We used logistic regression models to examine factors associated with EoL care.

RESULTS:

Four thousand six hundred twenty-nine patients with GI cancer were included in the analysis. We found that 11.0% of patients received chemotherapy, 17.3% had > 1 hospitalization, 9.3% were in the ICU, 18.0% had > 1 ER visit, 39.3% died in an acute care setting, and 8.6% received life-extending procedures. A compound indicator of the aggressiveness of care showed that 54.5% of patients had at least one of the selected aggressive indicators. The multivariable model showed that female patients, patients ≥ 60 years of age, patients enrolled in Medicaid, patients dually eligible for both Medicare and Medicaid, and patients who survived > 1 year were less likely to receive aggressive EoL care.

CONCLUSION:

Our findings support the urgent need to improve EoL care in Puerto Rico. Further studies are warranted to fully understand EoL care in patients with cancer in Puerto Rico.
Insulin Resistance in Congenital Adrenal Hyperplasia is Compensated for by Reduced Insulin Clearance
Authors: de Oliveira Daniel Minutti , Tura Andrea , Vasques Ana Carolina Junqueira , Camilo Daniella Fernandes , Lima Marcelo Miranda , de Lemos-Marini Sofia Helena Valente , Goncalves Ezequiel Moreira , Guerra-Junior Gil , Geloneze Bruno
Published: February 2021

Context

Congenital adrenal hyperplasia (CAH) patients have potential normal longevity. However, a greater risk for cardiovascular disease has been reported. Insulin resistance and hyperinsulinemia have been described in CAH patients, whereas the prevalence of overt type 2 diabetes is not higher in CAH than in normal population.

Objective

To examine the contributions of insulin secretion and of hepatic insulin clearance to compensatory hyperinsulinemia in young insulin-resistant adults with classic CAH due to 21-hydroxylase deficiency (21-OHD).

Design

Cross-sectional.

Setting

University outpatient clinics.

Methods

Fifty-one participants: 21 controls, and 30 CAH (15 virilizing and 15 salt-wasting phenotypes), female/male (33/18), age (mean [SD]): 24.0 (3.6) years, body mass index: 24.6 (4.9)kg/m2 with normal glucose tolerance, were submitted to a hyperglycemic clamp study.

Main Outcome Measures

Insulin sensitivity, beta cell function, and hepatic insulin clearance using appropriate modeling.

Results

We found an increased insulin resistance in 21-OHD. The systemic hyperinsulinemia (posthepatic insulin delivery) was elevated in CAH patients. No increases were observed in insulin secretory rate (beta cell function) in the first phase or during the hyperglycemic clamp. The increase in insulin concentrations was totally due to a ~33% reduction in insulin clearance.

Conclusion

21-OHD nonobese subjects have reduced insulin sensitivity and beta cell response unable to compensate for the insulin resistance, probably due to overexposure to glucocorticoids. Compensatory hyperinsulinemia is most related with reduced hepatic insulin clearance. The exclusive adaptation of the liver acts as a gating mechanism to regulate the access of insulin to insulin-sensitive tissues to maintain glucose homeostasis.
Statins Decrease the Risk of Orbitopathy in Newly Diagnosed Patients with Graves Disease
Authors: Nilsson Anton , Tsoumani Kleoniki , Planck Tereza
Published: February 2021

Context/objective

The aim of this study was to examine the effect of statins and other lipid-lowering agents on the development of Graves orbitopathy (GO) in patients with newly diagnosed Graves disease (GD).

Methods

Our sample included the full adult population of individuals living in Sweden with newly diagnosed GD between 2005 and 2018 (n = 34 894). We compared the GO incidence in statin users (n = 5574) and nonusers (n = 34 409) by applying Cox regression with a time-varying exposure variable. We adjusted for age, sex, and treatment for hyperthyroidism in the multivariate analyses.

Results

Periods of nonusage lasted for a median of 4.3 years (interquartile range [IQR] 1.2-8.4), whereas periods of usage lasted for a median of 4.7 years (IQR 2.0-8.1). Among statin users, 77.1% had used simvastatin, 28.9% atorvastatin, and 8.2% had used other statins. Statin users were found to be significantly less likely to develop GO. In the main analysis based on the full cohort, the unadjusted hazard ratio (HR) was 0.74 (CI 0.65-0.84, P < .001), whereas full adjustment altered the effect to 0.87 (CI 0.76-1.00, P = .04). The main results were largely driven by men; the fully adjusted HR was 0.78 (CI 0.58-1.04, P = .09) for men and 0.91 (CI 0.79-1.06, P = .24) for women. Lipid-lowering agents other than statins did not exhibit a similar protective effect.

Conclusion

In newly diagnosed patients with GD, treatment with statins may protect against the development of GO. Statins should be investigated in a clinical trial as a preventive treatment for GO in newly diagnosed patients with GD.
microRNA-483 Protects Pancreatic β-Cells by Targeting ALDH1A3
Authors: Wang Zhihong , Mohan Ramkumar , Chen Xinqian , Matson Katy , Waugh Jackson , Mao Yiping , Zhang Shungang , Li Wanzhen , Tang Xiaohu , Satin Leslie S , Tang Xiaoqing
Published: February 2021

Pancreatic β-cell dysfunction is central to the development and progression of type 2 diabetes. Dysregulation of microRNAs (miRNAs) has been associated with pancreatic islet dysfunction in type 2 diabetes. Previous study has shown that miR-483 is expressed relatively higher in β-cells than in α-cells. To explore the physiological function of miR-483, we generated a β-cell-specific knockout mouse model of miR-483. Loss of miR-483 enhances high-fat diet–induced hyperglycemia and glucose intolerance by the attenuation of diet-induced insulin release. Intriguingly, mice with miR-483 deletion exhibited loss of β-cell features, as indicated by elevated expression of aldehyde dehydrogenase family 1, subfamily A3 (Aldh1a3), a marker of β-cell dedifferentiation. Moreover, Aldh1a3 was validated as a direct target of miR-483 and overexpression of miR-483 repressed Aldh1a3 expression. Genetic ablation of miR-483 also induced alterations in blood lipid profile. Collectively, these data suggest that miR-483 is critical in protecting β-cell function by repressing the β-cell disallowed gene Aldh1a3. The dysregulated miR-483 may impair insulin secretion and initiate β-cell dedifferentiation during the development of type 2 diabetes.
Physiological and Pharmacological Roles of PTH and PTHrP in Bone Using Their Shared Receptor, PTH1R
Authors: Martin T John , Sims Natalie A , Seeman Ego
Published: February 2021

Parathyroid hormone (PTH) and the paracrine factor, PTH-related protein (PTHrP), have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein-coupled receptor, PTH1R, that predominantly uses the cyclic adenosine monophosphate-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two. Mouse genetic studies show that PTHrP is essential for endochondral bone lengthening in the fetus and is essential for bone remodeling. In contrast, the main postnatal function of PTH is hormonal control of calcium homeostasis, with no evidence that PTHrP contributes. Pharmacologically, amino-terminal PTH and PTHrP peptides (teriparatide and abaloparatide) promote bone formation when administered by intermittent (daily) injection. This anabolic effect is remodeling-based with a lesser contribution from modeling. The apparent lesser potency of PTHrP than PTH peptides as skeletal anabolic agents could be explained by lesser bioavailability to PTH1R. By contrast, prolongation of PTH1R stimulation by excessive dosing or infusion, converts the response to a predominantly resorptive one by stimulating osteoclast formation. Physiologically, locally generated PTHrP is better equipped than the circulating hormone to regulate bone remodeling, which occurs asynchronously at widely distributed sites throughout the skeleton where it is needed to replace old or damaged bone. While it remains possible that PTH, circulating within a narrow concentration range, could contribute in some way to remodeling and modeling, its main physiological role is in regulating calcium homeostasis.
Pituitary Neoplasm Nomenclature Workshop: Does Adenoma Stand the Test of Time?
Authors: Ho Ken , Fleseriu Maria , Kaiser Ursula , Salvatori Roberto , Brue Thierry , Lopes M Beatriz , Kunz Pamela , Molitch Mark , Camper Sally A , Gadelha Mônica , Syro Luis V , Laws Edward , Reincke Martin , Nishioka Hiroshi , Grossman Ashley , Barkan Ariel , Casanueva Felipe , Wass John , Mamelak Adam , Katznelson Laurence , van der Lely Aart J , Radovick Sally , Bidlingmaier Martin , Boguszewski Margaret , Bollerslev Jens , Hoffman Andrew R , Oyesiku Nelson , Raverot Gerald , Ben-Shlomo Anat , Fowkes Rob , Shimon Ilan , Fukuoka Hidenori , Pereira Alberto M , Greenman Yona , Heaney Anthony P , Gurnell Mark , Johannsson Gudmundur , Osamura Robert Y , Buchfelder Michael , Zatelli Maria Chiara , Korbonits Marta , Chanson Philippe , Biermasz Nienke , Clemmons David R , Karavitaki Niki , Bronstein Marcello D , Trainer Peter , Melmed Shlomo
Published: February 2021

The WHO Classification of Endocrine Tumours designates pituitary neoplasms as adenomas. A proposed nomenclature change to pituitary neuroendocrine tumors (PitNETs) has been met with concern by some stakeholder groups. The Pituitary Society coordinated the Pituitary Neoplasm Nomenclature (PANOMEN) workshop to address the topic. Experts in pituitary developmental biology, pathology, neurosurgery, endocrinology, and oncology, including representatives nominated by the Endocrine Society, European Society of Endocrinology, European Neuroendocrine Association, Growth Hormone Research Society, and International Society of Pituitary Surgeons. Clinical epidemiology, disease phenotype, management, and prognosis of pituitary adenomas differ from that of most NETs. The vast majority of pituitary adenomas are benign and do not adversely impact life expectancy. A nomenclature change to PitNET does not address the main challenge of prognostic prediction, assigns an uncertain malignancy designation to benign pituitary adenomas, and may adversely affect patients. Due to pandemic restrictions, the workshop was conducted virtually, with audiovisual lectures and written précis on each topic provided to all participants. Feedback was collated and summarized by Content Chairs and discussed during a virtual writing meeting moderated by Session Chairs, which yielded an evidence-based draft document sent to all participants for review and approval. There is not yet a case for adopting the PitNET nomenclature. The PANOMEN Workshop recommends that the term adenoma be retained and that the topic be revisited as new evidence on pituitary neoplasm biology emerges.
Analyzing the Effect of Time in Migration Measurement Using Georeferenced Digital Trace Data
Authors: Fiorio Lee , Zagheni Emilio , Abel Guy , Hill Johnathan , Pestre Gabriel , Letouzé Emmanuel , Cai Jixuan
Published: February 2021

Georeferenced digital trace data offer unprecedented flexibility in migration estimation. Because of their high temporal granularity, many migration estimates can be generated from the same data set by changing the definition parameters. Yet despite the growing application of digital trace data to migration research, strategies for taking advantage of their temporal granularity remain largely underdeveloped. In this paper, we provide a general framework for converting digital trace data into estimates of migration transitions and for systematically analyzing their variation along a quasi-continuous time scale, analogous to a survival function. From migration theory, we develop two simple hypotheses regarding how we expect our estimated migration transition functions to behave. We then test our hypotheses on simulated data and empirical data from three platforms in two internal migration contexts: geotagged Tweets and Gowalla check-ins in the United States, and cell-phone call detail records in Senegal. Our results demonstrate the need for evaluating the internal consistency of migration estimates derived from digital trace data before using them in substantive research. At the same time, however, common patterns across our three empirical data sets point to an emergent research agenda using digital trace data to study the specific functional relationship between estimates of migration and time and how this relationship varies by geography and population characteristics.
Trio family proteins as regulators of cell migration and morphogenesis in development and disease – mechanisms and cellular contexts
Authors: Bircher Josie E. , Koleske Anthony J.
Published: February 2021

The well-studied members of the Trio family of proteins are Trio and kalirin in vertebrates, UNC-73 in Caenorhabditis elegans and Trio in Drosophila. Trio proteins are key regulators of cell morphogenesis and migration, tissue organization, and secretion and protein trafficking in many biological contexts. Recent discoveries have linked Trio and kalirin to human disease, including neurological disorders and cancer. The genes for Trio family proteins encode a series of large multidomain proteins with up to three catalytic activities and multiple scaffolding and protein–protein interaction domains. As such, Trio family proteins engage a wide array of cell surface receptors, substrates and interaction partners to coordinate changes in cytoskeletal regulatory and protein trafficking pathways. We provide a comprehensive review of the specific mechanisms by which Trio family proteins carry out their functions in cells, highlight the biological and cellular contexts in which they occur, and relate how alterations in these functions contribute to human disease.
Cardiorespiratory adjustments to chronic environmental warming improve hypoxia tolerance in European perch (Perca fluviatilis)
Authors: Ekström Andreas , Sundell Erika , Morgenroth Daniel , McArley Tristan , Gårdmark Anna , Huss Magnus , Sandblom Erik
Published: February 2021

Aquatic hypoxia will become increasingly prevalent in the future as a result of eutrophication combined with climate warming. While short-term warming typically constrains fish hypoxia tolerance, many fishes cope with warming by adjusting physiological traits through thermal acclimation. Yet, little is known about how such adjustments affect tolerance to hypoxia. We examined European perch (Perca fluviatilis) from the Biotest enclosure (23°C, Biotest population), a unique ∼1 km2 ecosystem artificially warmed by cooling water from a nuclear power plant, and an adjacent reference site (16–18°C, reference population). Specifically, we evaluated how acute and chronic warming affect routine oxygen consumption rate (ṀO2,routine) and cardiovascular performance in acute hypoxia, alongside assessment of the thermal acclimation of the aerobic contribution to hypoxia tolerance (critical O2 tension for ṀO2,routine: Pcrit) and absolute hypoxia tolerance (O2 tension at loss of equilibrium; PLOE). Chronic adjustments (possibly across lifetime or generations) alleviated energetic costs of warming in Biotest perch by depressing ṀO2,routine and cardiac output, and by increasing blood O2 carrying capacity relative to reference perch acutely warmed to 23°C. These adjustments were associated with improved maintenance of cardiovascular function and ṀO2,routine in hypoxia (i.e. reduced Pcrit). However, while Pcrit was only partially thermally compensated in Biotest perch, they had superior absolute hypoxia tolerance (i.e. lowest PLOE) relative to reference perch irrespective of temperature. We show that European perch can thermally adjust physiological traits to safeguard and even improve hypoxia tolerance during chronic environmental warming. This points to cautious optimism that eurythermal fish species may be resilient to the imposition of impaired hypoxia tolerance with climate warming.
Το φαινόμενο του εκφοβισμού στα σχολεία της δευτεροβάθμιας εκπαίδευσης: Η επίδραση φύλου και εθνο-πολιτισμικής προέλευσης
Authors: Ψάλτη Αναστασία , Κωνσταντίνου Κατερίνα
Published: February 2021

The abstract is available in the PDF
Ομαδική ψυχοθεραπεία: Μετανεωτερικές εξελίξεις και το Συνθετικό-Συστηματικό Μοντέλο
Authors: Παπαστυλιανού Αντωνία
Published: February 2021

The abstract is available in the PDF
Social Cognitive Theory: An Agentic Perspective
Authors: Bandura Albert
Published: February 2021

ABSTRACT IS AVAILABLE IN THE PDF
Πλειοψηφική και μειοψηφική πηγή και επεξεργασία του μηνύματος επιρροής
Authors: Γαρδικιώτης Αντώνης
Published: February 2021

The abstract is available in the PDF
Ψυχολογικές δοκιμασίες και νεοπλασματικά νοσήματα
Authors: Τερλίδου Χ. , Καλιακάτσου Κ. , Καραολίδου Μ. , Μαρκρζίνης Ευ. , Τσέγκος Ι. Κ.
Published: February 2021

The abstract is available in the PDF
Η κατάκτηση της χωρο-χρονικής δόμησης από παιδιά προσχολικής ηλικίας
Authors: Ρεκαλίδου Γαλήνη , Μπεζέ Λουκία
Published: February 2021

The abstract is available in the PDF
Supplemental oxygen in Queen Elizabeth Central Hospital Malawi: a prospective cohort study of patients admitted to medical wards
Authors: Thomson Helen , Mlaviwa Maness , Rylance Jamie , Jones Hannah , Reuben Ammoah , Stolbrink Marie
Published: February 2021

Background: Oxygen is designated an essential drug by the World Health Organisation, and reduces mortality in hypoxic patients. In low-resource settings the provision of oxygen seldom meets its demand. This study describes the predictors and observed time-course of hypoxaemia in order to inform needs assessments for oxygen in hospitals in low and middle income countries.

Methods: A prospective cohort study of adults with hypoxaemia admitted to medical wards of a teaching hospital in Malawi between January and March 2020. Vital signs and oxygen therapy were recorded daily. We analysed outcomes (death, discharge from hospital or ongoing inpatient care at 14 days after admission) using Kaplan-Meier and Cox regression time-to-event analysis.

Results: 33 patients were recruited with median age 45 years (IQR 33-61), and 13 (39%) female. Median pre-treatment oxygen saturations were 84% (IQR 76-87%). Oxygen delivery devices were often shared with other patients (n=10, 33%) and the flow rate was often unknown (n=14, 47%), mostly because of broken equipment (n=8, 57%).

Median duration of oxygen therapy was 3 days (IQR 1-7). Death occurred in 16 (49%). Hazard ratios for short oxygen therapy were reduced in patients who had a chest radiograph performed (HR 0.08, 95% CI 0.02–0.30), in ex-smokers (HR 0.01, 95% CI 0.00-0.22) and in never smokers (HR 0.03, 95% CI 0.00 – 0.78).

Conclusions: Delivering oxygen therapy in lower-middle income countries is challenging; broken equipment and shared delivery devices prevented titration of flow rates. Patients were relatively young and at a high risk of death. Patients with a chest radiograph received oxygen for longer than those without. Knowledge of oxygen therapy durations will allow careful assessment of the oxygen supply need at the hospital level.
Deutsche Bahn Schedules Train Rotations Using Hypergraph Optimization
Authors: Borndörfer Ralf , Eßer Thomas , Frankenberger Patrick , Huck Andreas , Jobmann Christoph , Krostitz Boris , Kuchenbecker Karsten , Mohrhagen Kai , Nagl Philipp , Peterson Michael , Reuther Markus , Schang Thilo , Schoch Michael , Schülldorf Hanno , Schütz Peter , Therolf Tobias , Waas Kerstin , Weider Steffen
Published: February 2021

Deutsche Bahn (DB) operates a large fleet of rolling stock (locomotives, wagons, and train sets) that must be combined into trains to perform rolling stock rotations. This train composition is a special characteristic of railway operations that distinguishes rolling stock rotation planning from the vehicle scheduling problems prevalent in other industries. DB models train compositions using hyperarcs. The resulting hypergraph models are addressed using a novel coarse-to-fine method that implements a hierarchical column generation over three levels of detail. This algorithm is the mathematical core of DB’s fleet employment optimization (FEO) system for rolling stock rotation planning. FEO’s impact within DB’s planning departments has been revolutionary. DB has used it to support the company’s procurements of its newest high-speed passenger train fleet and its intermodal cargo locomotive fleet for crossborder operations. FEO is the key to successful tendering in regional transport and to construction site management in daily operations. DB’s planning departments appreciate FEO’s high-quality results, ability to reoptimize (quickly), and ease of use. Both employees and customers benefit from the increased regularity of operations. DB attributes annual savings of 74 million euro, an annual reduction of 34,000 tons of CO2 emissions, and the elimination of 600 coupling operations in crossborder operations to the implementation of FEO.