bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of efflux transporters by poly ADP‐ribose polymerase inhibitors
Authors: Deng Feng , Sistonen Johanna , Neuvonen Mikko , Niemi Mikko 
Published: August 2023

AbstractPoly ADP‐ribose polymerase (PARP) inhibitors have been approved for the treatment of various cancers. They share a similar mechanism of action but have differences in pharmacokinetic characteristics and potential for drug–drug interactions (DDI). This study evaluated the potential ATP‐binding cassette transporter‐mediated interactions between PARP inhibitors (niraparib, olaparib and rucaparib) and statins (atorvastatin and rosuvastatin). We studied the inhibitory activity of PARP inhibitors on breast cancer resistance protein (BCRP), multidrug resistance‐associated protein 3 (MRP3) and P‐glycoprotein (P‐gp) using vesicular transport assays and determined the concentrations required for 50% inhibition (IC50). Then, we predicted the increase of statin exposure followed by the administration of PARP inhibitors using a mechanistic static model. Rucaparib was the strongest inhibitor of BCRP‐mediated rosuvastatin transport (IC50 13.7 μM), followed by niraparib (42.6 μM) and olaparib (216 μM). PARP inhibitors did not affect MRP3. While niraparib appeared to inhibit P‐gp, the inhibition showed large variability. The inhibition of intestinal BCRP by rucaparib, niraparib and olaparib was predicted to elevate rosuvastatin exposure by 52%, 37% and 24%, respectively. The interactions between PARP inhibitors and rosuvastatin are probably of minor clinical significance alone, but combined with other predisposing factors, they may increase the risk of rosuvastatin‐associated adverse effects.
AhR–STAT3–HO‐1/COX‐2 signalling pathway may restrict ferroptosis and improve hMSC accumulation and efficacy in mouse liver
Authors: Han Li , Ma Chenhui , Wu Zhitao , Xu Huiming , Li Hai , Pan Guoyu 
Published: August 2023

AbstractBackground and PurposeThe low efficacy of mesenchymal stem cells (MSCs) has restricted their application in the treatment of liver disease. Emerging evidence suggested that ferroptosis may provoke hepatocyte dysfunction and exacerbate damage to the liver microenvironment. Here, we have investigated the contribution of liver ferroptosis to the elimination and effectiveness of human MSC (hMSC). Furthermore, potential links between liver ferroptosis and aryl hydrocarbon receptors (AhR) were explored.Experimental ApproachTwo mouse models, iron supplement‐induced hepatic ferroptosis and hepatic ischaemia/reperfusion (I/R) injury, were used to identify effects of ferroptosis on hMSC pharmacokinetics (PK)/pharmacodynamics (PD).Key ResultsAhR inhibition attenuated hepatic ferroptosis and improved survival of hMSCs. hMSC viability was decreased by iron supplementation or serum from I/R mice. The AhR antagonist CH223191 reversed iron overload and oxidative stress induced by ferroptosis and increased hMSC concentration and efficacy in mouse models. Effects of CH223191 were greater than those of deferoxamine, a conventional ferroptosis inhibitor. Transcriptomic results suggested that the AhR–signal transducer and activator of transcription 3 (STAT3)–haem oxygenase 1/COX‐2 signalling pathway is critical to this process. These results were confirmed in a mouse model of hepatic I/R injury. In mice pre‐treated with CH223191, hMSC exhibited more potent protective effects, linked to decreased hepatic ferroptosis.Conclusion and ImplicationsOur findings showed that ferroptosis was a critical factor in determining the fate of hMSCs. Inhibition of AhR decreased hepatic ferroptosis, thereby increasing survival and therapeutic effects of hMSCs in mouse models of liver disease.
Trade‐induced sectoral upgrading and upstream financial flows
Authors: Zhang Haiping 
Published: August 2023

AbstractThis paper shows that deepening trade integration may have non‐monotonic impacts on the direction of financial flows in a world with heterogeneous financial development. By inducing the more financially developed country (North) to specialize towards the financially constrained, high‐return sectors, trade integration reduces the return to capital in the unconstrained, low‐return sectors, which reverses the upstream financial flows, as predicted by Antras and Caballero (2009, Journal of Political Economy). However, if the cross‐country difference in financial development and the investment elasticity in North are sufficiently large, North may offshore the low‐return sectors and specialize fully in the high‐return sectors. In this case, upstream financial flows may not be dampened or reversed in the long run. My findings offer an alternative perspective of understanding the persistent current account imbalances between emerging Asia and the United States.
Carbon tax pass‐through in Canadian retail gasoline markets
Authors: Erutku Can , Hildebrand Vincent 
Published: August 2023

AbstractA carbon tax's pass‐through is one factor influencing its effectiveness in internalizing the externality created by greenhouse gas emissions. This paper measures the pass‐through of carbon taxes introduced in retail gasoline markets of four Canadian provinces that did not meet the carbon pollution pricing federal benchmark stringency requirements. Those four provinces are Saskatchewan, Manitoba, Ontario and New Brunswick. Using daily retail gasoline prices for 40 treated cities and nine control cities we find the pass‐through rates are city‐specific and vary from 0% to over 140%. City‐specific pass‐through rates imply that estimations at a higher level of geographical aggregation assume homogeneous effects where heterogeneous effects might be present. Our results also suggest it would be difficult for a government to impose an optimal and nationwide carbon tax on automotive greenhouse gas emissions. Although the degree of competition can explain city‐specific pass‐through rates, it cannot explain over‐shifting. Over‐shifting can be explained, however, by the demand functional form.
Surveying the Indian research ethics committee response to the COVID‐19 pandemic
Authors: Shetty Yashashri C. , Ramalingam Sudha , Koli Paresh , Shanmugam Karthikeyan , Seetharaman Rajmohan 
Published: August 2023

AbstractResearch ethics committees (RECs) have played a crucial role in expediting the review of research protocols amidst the COVID‐19 pandemic. To improve their performance and identify areas of enhancement, a multicentric study was conducted in India by the Forum for Ethical Review Committees in the Asian and Western Pacific Region (FERCAP). The study aimed to evaluate the preparedness of Indian RECs during the COVID‐19 outbreak while conducting protocol reviews and comprehend the challenges they encountered. After obtaining ethics committee approval, a cross‐sectional observational study was conducted using two validated questionnaires, one for REC member secretaries/chairpersons and another for REC members. The questionnaires consisted of 13 multiple‐choice questions, 10 yes or no questions, and 2 open‐ended questions each. The study was distributed to multiple RECs. A total of 109/200 participants, including 13 REC member secretaries, 12 chairpersons and 84 REC members from a total of 34 REC's, consented to participate in the study. During the COVID‐19 pandemic, 23/25 (92%) of the RECs conducted online meetings. The most common challenges faced by RECs included risk‐benefit analysis (12/25 RECs), review of informed consent (12/25 RECs), and protocols involving vulnerable populations (10/25 RECs). 65% of the REC members reported the need for ethics review training, and 66/84 REC members agreed or strongly agreed that RECs require training in COVID‐19 protocol review. Additionally, 62/84 REC members agreed or strongly agreed that central/joint RECs should review multicenter COVID‐19 protocols. RECs in India encountered difficulties while reviewing risk‐benefit analyses, informed consent documents (ICDs), and COVID‐19 protocols and they suggested providing training on these topics.
Numeracy selectivity of Spanish migrants in colonial America (sixteenth–eighteenth centuries)
Authors: Pérez‐Artés María del Carmen 
Published: August 2023

AbstractSince the arrival of Christopher Columbus in the so‐called New World in 1492, hundreds of thousands of Spaniards settled in Central and South America. This paper assesses the skill selectivity of Spanish migrants who went to Hispanic America during the sixteenth to eighteenth centuries for the first time. The age‐heaping method is employed to estimate numeracy levels as a proxy for human capital. With a database of 33 929 individual observations, the findings show that Spaniards who left the country to settle in the Spanish territories were positively self‐selected. Additionally, differences are observed in the human capital of those who chose to settle in Mexico, who had a higher level of numeracy, than those who chose Peru. These differences might be due to the viceroyalty structure and educational institutions that encouraged the emigration of people with greater human capital to Mexico. Finally, when the level of numeracy of Spaniards in Hispanic America is compared with the numeracy of the total population, emigrants still had higher levels of human capital.
Is source‐resolved magnetoencephalographic mismatch negativity a viable biomarker for early psychosis?
Authors: López‐Caballero Fran , Curtis Mark , Coffman Brian A. , Salisbury Dean F. 
Published: August 2023

AbstractMismatch negativity (MMN) is an auditory event‐related response reflecting the pre‐attentive detection of novel stimuli and is a biomarker of cortical dysfunction in schizophrenia (SZ). MMN to pitch (pMMN) and to duration (dMMN) deviant stimuli are impaired in chronic SZ, but it is less clear if MMN is reduced in first‐episode SZ, with inconsistent findings in scalp‐level EEG studies. Here, we investigated the neural generators of pMMN and dMMN with MEG recordings in 26 first‐episode schizophrenia spectrum (FEsz) and 26 matched healthy controls (C). We projected MEG inverse solutions into precise functionally meaningful auditory cortex areas. MEG‐derived MMN sources were in bilateral primary auditory cortex (A1) and belt areas. In A1, pMMN FEsz reduction showed a trend towards statistical significance (F(1,50) = 3.31; p = .07), and dMMN was reduced in FEsz (F(1,50) = 4.11; p = .04). Hypothesis‐driven comparisons at each hemisphere revealed dMMN reduction in FEsz occurred in the left (t(56) = 2.23; p = .03; d = .61) but not right (t(56) = 1.02; p = .31; d = .28) hemisphere, with a moderate effect size. The added precision of MEG source solution with high‐resolution MRI and parcellation of A1 may be requisite to detect the emerging pathophysiology and indicates a critical role for left hemisphere pathology at psychosis onset. However, the moderate effect size in left A1, albeit larger than reported in scalp MMN meta‐analyses, casts doubt on the clinical utility of MMN for differential diagnosis, as a majority of patients will overlap with the healthy individual's distribution.
Augenblickdiagnose in neurology: Revisiting ‘diagnosis in the blink of an eye’
Authors: Caldeiras Catarina , Seabra Sousa Edgar , Carneiro Diogo Reis , Carvalho João , Rego Ricardo , Varela Ricardo , Araújo Rui 
Published: August 2023

AbstractBackground and purposeThe art of diagnosis in clinical neurology requires attentive listening and careful observation. In certain situations, a fragment of the history or a physical sign may be so distinctive that it allows clinicians to evoke a specific diagnosis. This quick mental process was previously referred to as ‘Augenblickdiagnose’ (‘diagnosis in the blink of an eye’) in a seminal paper by Dr. William Campbell in 1998. We aimed to revisit this concept by providing additional clinical vignettes.MethodsThe authors wrote clinical vignettes using examples from their own clinical practice and performed a non‐systematic review of influential neurology textbooks using the words ‘pathognomonic’ and ‘highly suggestive’.ResultsTwenty examples from various fields of neurology are presented in a table, stratified by major fields of neurology. A short educational reflection is provided for each diagnosis considered.Conclusion‘Augenblickdiagnose’ is an engaging teaching resource that also contributes to ‘neurophilia’, that is, a fascination for neurology, perhaps increasingly in today's modern neurology practice. However, multiple cognitive biases underlying mental shortcuts may lead to an incorrect diagnosis. It is important to stress that good clinical practice in neurology requires taking a thorough history and performing a careful neurological examination.
How registry data are used to inform activities for stroke care quality improvement across 55 countries: A cross‐sectional survey of Registry of Stroke Care Quality (RES‐Q) hospitals
Authors: Fasugba Oyebola , Sedani Rupal , Mikulik Robert , Dale Simeon , Vařecha Miroslav , Coughlan Kelly , McElduff Benjamin , McInnes Elizabeth , Hladíková Sabina , Cadilhac Dominique A. , Middleton Sandy 
Published: August 2023

AbstractBackground and purposeThe Registry of Stroke Care Quality (RES‐Q) is a worldwide quality improvement data platform that captures performance and quality measures, enabling standardized comparisons of hospital care. The aim of this study was to determine if, and how, RES‐Q data are used to influence stroke quality improvement and identify the support and educational needs of clinicians using RES‐Q data to improve stroke care.MethodsA cross‐sectional self‐administered online survey was administered (October 2021–February 2022). Participants were RES‐Q hospital local coordinators responsible for stroke data collection. Descriptive statistics are presented.ResultsSurveys were sent to 1463 hospitals in 74 countries; responses were received from 358 hospitals in 55 countries (response rate 25%). RES‐Q data were used “always” or “often” to: develop quality improvement initiatives (n = 213, 60%); track stroke care quality over time (n = 207, 58%); improve local practice (n = 191, 53%); and benchmark against evidence‐based policies, procedures and/or guidelines to identify practice gaps (n = 179, 50%). Formal training in the use of RES‐Q tools and data were the most frequent support needs identified by respondents (n = 165, 46%). Over half “strongly agreed” or “agreed” that to support clinical practice change, education is needed on: (i) using data to identify evidence–practice gaps (n = 259, 72%) and change clinical practice (n = 263, 74%), and (ii) quality improvement science and methods (n = 255, 71%).ConclusionRES‐Q data are used for monitoring stroke care performance. However, to facilitate their optimal use, effective quality improvement methods are needed. Educating staff in quality improvement science may develop competency and improve use of data in practice.
What do we mean by long COVID? A scoping review of the cognitive sequelae of SARS‐CoV‐2 infection
Authors: Nicotra Alessia , Masserini Federico , Calcaterra Francesca , Di Vito Clara , Doneddu Pietro Emiliano , Pomati Simone , Nobile‐Orazio Eduardo , Riva Agostino , Mavilio Domenico , Pantoni Leonardo 
Published: August 2023

AbstractBackground and purposeMany COVID‐19 patients report persistent symptoms, including cognitive disturbances. We performed a scoping review on this topic, focusing primarily on cognitive manifestations.MethodsAbstracts and full texts of studies published on PubMed (until May 2023) addressing cognitive involvement persisting after SARS‐CoV‐2 infection were reviewed, focusing on terms used to name the cognitive syndrome, reported symptoms, their onset time and duration, and testing batteries employed. Reported psychiatric symptoms, their assessment tools, and more general manifestations were also extracted.ResultsAmong the 947 records identified, 180 studies were included. Only one third of them used a label to define the syndrome. A minority of studies included patients according to stringent temporal criteria of syndrome onset (34%), whereas more studies reported a minimum required symptom duration (77%). The most frequently reported cognitive symptoms were memory and attentional–executive disturbances, and among psychiatric complaints, the most frequent were anxiety symptoms, depression, and sleep disturbances. Most studies reported fatigue among general symptoms. Thirty‐six studies employed cognitive measures: screening tests alone (n = 19), full neuropsychological batteries (n = 25), or both (n = 29); 30 studies performed psychiatric testing. Cognitive deficits were demonstrated in 39% of subjects, the most frequently affected domains being attention/executive functions (90%) and memory (67%).ConclusionsCurrently, no agreement exists on a label for post‐COVID‐19 cognitive syndrome. The time of symptom onset after acute infection and symptom duration are still discussed. Memory and attention–executive complaints and deficits, together with fatigue, anxiety, and depression symptoms, are consistently reported, but the objective evaluation of these symptoms is not standardized.
Peripheral polyneuropathy in children and young adults with ataxia–telangiectasia
Authors: Theis Marius , Donath Helena , Woelke Sandra , Bakhtiar Shahrzad , Salzmann‐Manrique Emilia , Zielen Stefan , Kieslich Matthias 
Published: August 2023

AbstractBackground and purposeAtaxia–telangiectasia (A‐T) is a rare, autosomal recessive, multisystem disorder that leads to progressive neurodegeneration with cerebellar ataxia and peripheral polyneuropathy. Cerebellar neurodegeneration is well described in A‐T. However, peripheral nervous system involvement is an underdiagnosed but important additional target for supportive and systemic therapies. The aim of this study was to conduct neurophysiological measurements to assess peripheral neurodegeneration and the development of age‐dependent neuropathy in A‐T.MethodsIn this prospective study, 42 classical A‐T patients were assessed. The motor and sensory nerve conduction of the median and tibial nerves was evaluated. Data were compared to published standard values and a healthy age‐ and gender‐matched control group of 23 participants. Ataxia scores (Klockgether, Scale for the Assessment and Rating of Ataxia) were also assessed.ResultsIn A‐T, neurophysiological assessment revealed neuropathic changes as early as the first year of life. Subjective symptomatology of neuropathy is rarely described. In the upper extremities, motor neuropathy was predominantly that of a demyelinating type and sensory neuropathy was predominantly that of a mixed type. In the lower extremities, motor and sensory neuropathy was predominantly that of a mixed type. We found significant correlations between age and the development of motor and sensory polyneuropathy in A‐T compared with healthy controls (p < 0.001).ConclusionsIn A‐T, polyneuropathy occurs mostly subclinically as early as the first year of life. The current study of a large national A‐T cohort demonstrates that development of neuropathy in A‐T differs in the upper and lower extremities.
Altered structure indicating reduced barrier function of lesional compared to non‐lesional psoriatic skin—A non‐invasive in vivo study of the human stratum corneum with confocal Raman micro‐spectroscopy
Authors: Zolotas Michael , Schleusener Johannes , Lademann Jürgen , Meinke Martina C. , Kokolakis Georgios , Darvin Maxim E. 
Published: August 2023

AbstractPsoriasis, one of the most common skin diseases affecting roughly 2%–3% of the world population, is associated with a reduced skin barrier function (SBF) that might play an important role in its pathophysiology. The SBF is provided primarily by the stratum corneum (SC) of the skin. Previous studies have revealed a higher trans‐epidermal water loss, lower hydration, abnormal concentration and composition of intercellular lipids, as well as alterations in secondary keratin structure in the psoriatic SC. We compared on molecular level lesional psoriatic skin (LPS) with non‐lesional psoriatic skin (nLPS) from 19 patients non‐invasively in vivo, using confocal Raman micro‐spectroscopy. By analysing the corresponding Raman spectra, we determined SBF‐defining parameters of the SC depth‐dependently. Our results revealed a lower total lipid concentration, a shift of lamellar lipid organisation towards more gauche‐conformers and an increase of the less dense hexagonal lateral packing of the intercellular lipids in LPS. Furthermore, we observed lower natural moisturising factor concentration, lower total water as well as a strong tendency towards less strongly bound and more weakly bound water molecules in LPS. Finally, we detected a less stable secondary keratin structure with increased β‐sheets, in contrast to the tertiary structure, showing a higher degree of folded keratin in LPS. These findings clearly suggest structural differences indicating a reduced SBF in LPS, and are discussed in juxtaposition to preceding outcomes for psoriatic and healthy skin. Understanding the alterations of the psoriatic SC provides insights into the exact pathophysiology of psoriasis and paves the way for optimal future treatments.
Sugarcane molasses spray drying by dehumidified air as the method to enhance powder recovery and physical properties of powders
Authors: Jedlińska Aleksandra , Edris Amr , Samborska Katarzyna 
Published: August 2023

AbstractThe aim of the study was to compare sugarcane molasses powders obtained by conventional high temperature spray drying (inlet/outlet air temperature: 180°C/80°C) and low temperature dehumidified air‐assisted spray drying (80°C/50°C) in terms of drying yield and physical properties. The addition of NUTRIOSE as a carrier was from 0% to 40% (w/w, solids). It was possible to obtain 100% high quality powders without the use of a drying carrier with high process efficiency (up to 93%—with using dehumidified air) by using both methods. Low temperature spray drying positively translated into increased drying yield, lower hygroscopicity and improved flowability of powders. Moreover, the powders obtained by low temperature method were brighter with small, less diversified particle sizes of spherical shapes.Practical ApplicationsMolasses is a by‐product of sugar production. Molasses have diverse applications as cheap food‐grade sweeteners as well as an economically feasible intermediate materials for production of some innovative food additives. Transforming sugarcane molasses from viscous, inconvenient liquid into free‐flowing powder, seems to be important by taking in consideration handling, transportation and the final application. Free‐carrier molasses powders fit well with the sustainability and clean label trends. Low‐temperature spray drying with dehumidified air is an innovation which allows to obtain higher quality powders.