bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional landscape of human microglia implicates age, sex, and APOE‐related immunometabolic pathway perturbations
Authors: Patel Tulsi , Carnwath Troy P. , Wang Xue , Allen Mariet , Lincoln Sarah J. , Lewis‐Tuffin Laura J. , Quicksall Zachary S. , Lin Shu , Tutor‐New Frederick Q. , Ho Charlotte C.G. , Min Yuhao , Malphrus Kimberly G. , Nguyen Thuy T. , Martin Elizabeth , Garcia Cesar A. , Alkharboosh Rawan M. , Grewal Sanjeet , Chaichana Kaisorn , Wharen Robert , Guerrero‐Cazares Hugo , Quinones‐Hinojosa Alfredo , Ertekin‐Taner Nilüfer 
Published: April 2022

AbstractMicroglia have fundamental roles in health and disease; however, effects of age, sex, and genetic factors on human microglia have not been fully explored. We applied bulk and single‐cell approaches to comprehensively characterize human microglia transcriptomes and their associations with age, sex, and APOE. We identified a novel microglial signature, characterized its expression in bulk tissue and single‐cell microglia transcriptomes. We discovered microglial co‐expression network modules associated with age, sex, and APOE‐ε4 that are enriched for lipid and carbohydrate metabolism genes. Integrated analyses of modules with single‐cell transcriptomes revealed significant overlap between age‐associated module genes and both pro‐inflammatory and disease‐associated microglial clusters. These modules and clusters harbor known neurodegenerative disease genes including APOE, PLCG2, and BIN1. Meta‐analyses with published bulk and single‐cell microglial datasets further supported our findings. Thus, these data represent a well‐characterized human microglial transcriptome resource and highlight age, sex, and APOE‐related microglial immunometabolism perturbations with potential relevance in neurodegeneration.
Clinical impact of the worldwide shortage of verteporfin (Visudyne®) on ophthalmic care
Authors: Sirks Marc J. , van Dijk Elon H.C. , Rosenberg Noa , Hollak Carla E.M. , Aslanis Stamatios , Cheung Chui Ming Gemmy , Chowers Itay , Eandi Chiara M. , Freund K. Bailey , Holz Frank G. , Kaiser Peter K. , Lotery Andrew J. , Ohno‐Matsui Kyoko , Querques Giuseppe , Subhi Yousif , Tadayoni Ramin , Wykoff Charles C. , Zur Dinah , Diederen Roselie M.H. , Boon Camiel J.F. , Schlingemann Reinier O. 
Published: April 2022

AbstractIntroductionSince July 2021, a worldwide shortage of verteporfin (Visudyne®) occurred: an essential medicine required for photodynamic therapy (PDT). PDT with verteporfin has a broad range of indications in ophthalmology, including chronic central serous chorioretinopathy, polypoidal choroidal vasculopathy and choroidal haemangioma. For these disorders, PDT is either the first‐choice treatment or regarded as a major treatment option.Materials and methodsA questionnaire was sent to key opinion leaders in the field of medical retina throughout the world, to assess the role of PDT in their country and the effects of the shortage of verteporfin. In addition, information on the application of alternative treatments during shortage of verteporfin was obtained, to further assess the impact of the shortage.ResultsOur questionnaire indicated that the shortage of verteporfin had a major impact on ophthalmic care worldwide and was regarded to be a serious problem by most of our respondents. However, even though there is ample evidence to support the use of PDT in several chorioretinal diseases, we found notable differences in its use in normal patient care throughout the world. Various alternative management strategies were noted during the verteporfin shortage, including lowering the dose of verteporfin per patient, the use of alternative treatment strategies and the use of a centralized system for allocating the remaining ampoules of verteporfin in some countries.ConclusionThe shortage of verteporfin has had a large effect on the care of ophthalmic patients across the world and may have resulted in significant and irreversible vision loss. Mitigation strategies should be developed in consultation with all stakeholders to avoid future medication shortages of verteporfin and other unique ophthalmic medications. These strategies may include mandatory stock keeping, compulsory licensing to an alternative manufacturer or incentivizing the development of competition, for example through novel public‐private partnerships.
Acute‐on‐chronic liver failure: A 20‐year retrospective review of a tertiary paediatric liver centre
Authors: Singh Harveen , Kelgeri Chayarani , Passingham Charlotte , Johansen Lauren , van Mourik Indra , Ong Evelyn , Perera M.Thamara P.R. , Mirza Darius , Sharif Khalid , Hartley Jane , Gupte Girish L. 
Published: April 2022

AbstractAimAcute‐on‐chronic liver failure (ACLF) is an acute deterioration of pre‐existing chronic liver disease related to a precipitating event. We characterised paediatric ACLF at Birmingham Children's Hospital (BCH) utilising European Association of Liver Disease CLIF criteria, including prevalence, triggers and outcomes.MethodsAll BCH patients from 2000 to 2020 with CLD who underwent initial liver transplant or died on the transplant waiting list or whilst too unwell to be listed were reviewed.ResultsFrom 2000 to 2020, 24 (4%) children with ACLF were identified. Death occurred in 18 (75%). Transplant occurred in 9 (36%), 3 of which died. ACLF triggers were sepsis organism negative 11 (46%), sepsis organism positive 8 (33%) and GI bleed 5 (17%). Bilirubin at the time of transplant/death in those with ACLF who lived compared with those who died was 529 umol/L (381) versus 665 (210) (p=0.38), creatinine 138 umol/L (147) versus 67 (46) (p=0.41), PT 33 sec (14) versus (32 (15) (p = 0.72), Grade 3, 4 hepatic encephalopathy 1 (17%) versus 10 (56%) (p = 0.17), vasopressor use 1 (17%) versus 17 (94%) (p = 0.001) and ventilation 3 (50%) versus 17 (94%) (p = 0.035).ConclusionAcute‐on‐chronic liver failure whilst infrequent has high rates of mortality. The use of vasopressors and ventilation is more frequent in those who die from ACLF.
Disability‐based arguments against assisted dying laws
Authors: Colburn Ben 
Published: April 2022

AbstractSome of the most common arguments against legalizing assisted dying are based on appealing to the rights of people with disabilities. This article identifies and responds to those arguments, including that people with disabilities univocally oppose assisted dying laws; that those laws harm people with disabilities, or show disrespect; and that those laws undermine other vital aspects of healthcare. Drawing on philosophical argument, as well as on evidence from jurisdictions where assisted dying is legal, the article concludes that considerations of disability do not in fact generate good arguments against assisted dying laws. In fact, the opposite is true. There are nevertheless important lessons that proponents and defenders of such laws can learn in conversation with people with disabilities, including about safeguards on assisted dying to protect their well‐being and autonomy.
The magic of MAGI‐1: A scaffolding protein with multi signalosomes and functional plasticity
Authors: Excoffon Katherine J. D. A. , Avila Christina L. , Alghamri Mahmoud S. , Kolawole Abimbola O. 
Published: April 2022

AbstractMAGI‐1 is a critical cellular scaffolding protein with over 110 different cellular and microbial protein interactors. Since the discovery of MAGI‐1 in 1997, MAGI‐1 has been implicated in diverse cellular functions such as polarity, cell–cell communication, neurological processes, kidney function, and a host of diseases including cancer and microbial infection. Additionally, MAGI‐1 has undergone nomenclature changes in response to the discovery of an additional PDZ domain, leading to lack of continuity in the literature. We address the nomenclature of MAGI‐1 as well as summarize many of the critical functions of the known interactions. Given the importance of many of the interactors, such as human papillomavirus E6, the Coxsackievirus and adenovirus receptor (CAR), and PTEN, the enhancement or disruption of MAGI‐based interactions has the potential to affect cellular functions that can potentially be harnessed as a therapeutic strategy for a variety of diseases.
Do cross‐border patents promote trade?
Authors: Brunel Claire , Zylkin Thomas 
Published: April 2022

AbstractWhile we would expect that cross‐border patents are used to protect a technology that is made available in another country, that technology could either be produced locally or imported. International patent filings could therefore be either complements or substitutes to international trade. This study combines data on patenting and trade for 149 countries and 249 industries between 1974 and 2006 with a “three‐way” panel data model that addresses several biases emphasized in the trade literature in order to provide a systematic analysis of how bilateral trade responds to cross‐border patent filings. We find that cross‐border patents have a positive (complementary) overall effect on the patent‐filing country's exports to the patent‐granting country and no effect overall on imports flowing in the opposite direction. These effects vary substantially across industry groups, with patents promoting significantly more export growth in industries with a high demand elasticity and in industries that are relatively more downstream in supply chains. We also find that patents, once obtained, are associated with increased trade even in jurisdictions with weak intellectual property regimes.
The immediate costs and long‐term benefits of assisted gene flow in large populations
Authors: Grummer Jared A. , Booker Tom R. , Matthey‐Doret Remi , Nietlisbach Pirmin , Thomaz Andréa T. , Whitlock Michael C. 
Published: April 2022

AbstractWith the genetic health of many plant and animal populations deteriorating due to climate change outpacing adaptation, interventions, such as assisted gene flow (AGF), may provide genetic variation necessary for populations to adapt to climate change. We ran genetic simulations to mimic different AGF scenarios in large populations and measured their outcomes on population‐level fitness to determine circumstances in which it is worthwhile to perform AGF. In the absence of inbreeding depression, AGF was beneficial within a few generations only when introduced genotypes had much higher fitness than local individuals and traits affecting fitness were controlled by a few genes of large effect. AGF was harmful over short periods (e.g., first ∼10–20 generations) if there was strong outbreeding depression or introduced deleterious genetic variation. When the adaptive trait was controlled by many loci of small effect, the benefits of AGF took over 10 generations to realize—potentially too long for most climate‐related management scenarios. The genomic integrity of the recipient population typically remained intact following AGF; the amount of genetic material from the donor population usually constituted no more of the recipient population's genome than the fraction of the population introduced. Significant genomic turnover (e.g., >50% replacement) only occurred when the selective advantage of the adaptive trait and translocation fraction were extremely high. Our results will be useful when adaptive management is used to maintain the genetic health and productivity of large populations under climate change.
Tree ring evidence of rapid development of drunken forest induced by permafrost warming
Authors: Fujii Kazumichi , Yasue Koh , Matsuura Yojiro 
Published: April 2022

AbstractBlack spruce trees growing on warming permafrost lean in all directions due to soil movement, forming a “drunken” forest. Two hypothetical drivers of drunken forest development are (i) loosening of the soil foundation induced by permafrost degradation in warm summers and (ii) mound rising induced by freezing soil in winter. However, no evidence has previously clarified whether recent tree leaning is related to climate warming or is part of a natural hummock formation process. Here, we provide evidence that tree leaning and soil hummock formation have accelerated due to climate warming. We find that trees’ leaning events synchronize with the development of soil hummocks as recorded in tree rings with lignin‐rich cells. Tree leaning is caused by mound rising in winter due to refreezing of soil following deep thaws in summer, rather than by loosening of the soil foundation in summer. Hummock formation shifted from periodic events before 1960 to continuous mound rising in the warmer succeeding 50 years. Although soil change is generally a slow process, recent permafrost warming has induced rapid hummock formation, which threatens the stability of drunken forests and organic carbon in soil hummocks based on shallow permafrost table.
Solutions for Groundwater Flow to a Pumping Well with an Exponentially Decreasing Variable‐Rate in a Sloping Aquifer
Authors: Guo Ziwei , Wen Zhang , Jakada Hamza 
Published: April 2022

AbstractDuring aquifer pumping tests in the field, the attenuation process of the pumping rate is generally monitored, and the aquifer may be slanted, especially in riverbank terraces, piedmont plain and other similar terrains. The combination of these two factors (attenuation process and aquifer slope) has not received enough academic attention, therefore, a two‐dimensional groundwater flow model is developed for an exponentially decreasing variable rate pumping well in a sloping aquifer in this study. The new semi‐analytical solution (based on a linearized free‐surface boundary) is obtained using the Laplace transform and finite Fourier cosine transform. Meanwhile, to depict the linearized boundary precisely with the first‐order free surface equation, a numerical model that considers the decline of the water table is also developed. Results show that under the effect of the variable rate, the time‐drawdown curve presents a downward trend at intermediate times. Additionally, the error caused by the linearization of the free‐surface equation on the analytical model is found to be acceptable except when the sloping angle is larger than π/6. Furthermore, since this study extends the work of Huang et al. (2014), who considered a constant pumping rate, the new solution was found better to interpret real pumping test data reported by Antonio and Pacheco (2002), and the laboratory experiment results. Overall, the new solution proves to be useful for parameter inversion accurately as the average pumping rate tended to underestimate hydraulic parameters when fitting short‐term pumping data.
Human health‐promoting interactions between hydrocolloid‐structured foods and the gut microbiome in the digestive tract: Editorial
Authors: Zhang Bin , Junejo Shahid Ahmed , Yang Xinquan , Yuan Yang 
Published: April 2022

SummaryThere is a growing interest to overcome such diet‐related health issues through the interactions with gut microbiome. A complex network of interactions between nutrition, gut microbiota and health has gradually emerged, which has been rarely explored in its whole. Imbalance of the normal gut microbiota has been linked with gastrointestinal conditions. This editorial highlighted the recent developments in the hydrocolloid‐structured foods and the gut microbiome in the digestive tract.
Predictive model for the preparedness level of the family caregiver
Authors: Gutierrez‐Baena Belen , Romero‐Grimaldi Carmen 
Published: April 2022

AbstractBackgroundMany caregivers are insufficiently prepared, and little is known about measures that can be employed to enhance their preparedness.AimThe aim of this study was to explore the factors associated with caregiver preparedness and establish a predictive model including the relationship between preparedness, burden, resilience and anxiety.DesignA cross‐sectional design was used.MethodsThe sample included 172 family caregivers who were selected from one private hospital and daytime nursing centres. Caregivers were recruited from 2018 to 2019; they completed assessments for caregiver preparedness, anxiety, resilience and burden. A multiple linear regression analysis was performed to identify the factors associated with preparedness.ResultsPreparedness was significantly associated with high levels of resilience and a low level of burden, while it was not associated with anxiety. Caregivers' gender, experience and cohabitation status were the main predictors. Resilience is an explanatory factor for caregiver preparedness in the predictive model.ConclusionThe demographic variables related to preparedness can be used to guide efforts to meet the needs of vulnerable caregivers. A caregiver's preparedness depends on their level of burden and resilience. Nursing interventions focused on these aspects could make the caregiver's role easier and improve the quality of care provided.
A comparative study of in-vitro and in-silico anti-candidal activity and GC–MS profiles of snow mountain garlic vs. normal garlic
Authors: Kaur Bhupinder , Kumar Nitish , Chawla Sonam , Sharma Deepika , Korpole Suresh , Sharma Rajni , Patel Manoj K. , Chopra Kanwaljit , Chaurasia Om Prakash , Saxena Shweta 
Published: April 2022

Abstract

Aim
The study aimed to profile the volatile phytocomposition of snow mountain garlic (SMG) compared to normal garlic and investigate the anti-Candida efficacy against clinically relevant multi-drug resistant isolates of Candida species.

Methods and Results
Herein, SMG has shown significantly superior fungicidal power at 2x-MIC dose against C. albicans and C. glabrata in killing kinetic evaluation unlike the fungistatic effect of normal garlic. GC–MS headspace-based profiling of SMG showed 5 unique volatile compounds and a 5-fold higher content of saponins than normal garlic. In an in-silico analysis, cholesta-4,6-dien-3-ol,(3-beta) was uniquely identified in SMG as a potential inhibitor with high binding affinity to the active site of exo-1,3-betaglucan synthase, an established anti-candida drug target crucial for the biofilm matrix formation, thus suggesting a plausible anti-Candida mechanism.

Conclusion
The in-vitro and in-silico studies have demonstrated the Candida-cidal and anti-biofilm activities of SMG, distinguishing it from the Candida-static efficacy of normal garlic.

Significance and Impact of the study
This is the first report that identifies several phytochemical signatures of SMG along with a potential anti-Candida compound, that is cholesta-4,6-dien-3-ol,(3-beta)-, which appears worthy of detailed studies in the future to explore the utility of SMG as a fungal phytotherapy agent, especially against drug-resistant Candida sp.
Ventricular tachycardia targeted in the aortic sinuses of Valsalva in patients with prior myocardial infarction
Authors: Siontis Konstantinos C. , Njeim Mario , Dabbagh Ghaith S. , Yokokawa Miki , Morady Fred , Bogun Frank 
Published: April 2022

AbstractIntroductionVentricular tachycardia (VT) in structurally normal hearts or nonischemic cardiomyopathy can originate from the aortic sinuses of Valsalva (SoV). It is unknown whether VT can originate from the SoVs in patients with prior myocardial infarction (MI).ObjectiveTo evaluate the prevalence, arrhythmogenic substrate, and ablation outcomes of postinfarction VT originating from the SoVs.MethodsAmong 217 consecutive patients with postinfarction VT undergoing ablation, we identified 13 (6%) patients who had ≥1 VT mapped in a SoV. Control groups of 13 patients with idiopathic SoV VT and 13 postinfarction patients without SoV VT were included.ResultsIn the study group, 17 VTs were mapped in a SoV (right n = 5, left‐right commissure n = 6, left n = 6). SoV VT target sites had low bipolar voltage during sinus rhythm [median 0.42 (IQR: 0.16–0.53) mV] which was significantly lower than target sites in patients with idiopathic SoV VTs [median 1.02 (IQR: 0.89–1.52) mV; p < .001]. An area of endocardial low voltage was found below the aortic valve in all patients with postinfarction SoV VTs compared to 9 (69%) of the patients in the postinfarction control group without SoV VT (p = .02). Morphology characteristics of postinfarction SoV VTs differed from idiopathic SoV VTs. None of the postinfarction SoV VTs were inducible after ablation and none recurred after a median follow‐up of 14 months.ConclusionIn patients with prior MI, VT can be targeted in an aortic SoV. The SoVs should be routinely investigated in postinfarction patients with inferior axis VT and an area of low voltage below the aortic valve.
Treatment of diabetic macular edema in real‐world clinical practice: The effect of aging
Authors: Kusuhara Sentaro , Shimura Masahiko , Kitano Shigehiko , Sugimoto Masahiko , Muramatsu Daisuke , Fukushima Harumi , Takamura Yoshihiro , Matsumoto Makiko , Kokado Masahide , Kogo Jiro , Sasaki Mariko , Morizane Yuki , Utsumi Takuya , Kotake Osamu , Koto Takashi , Terasaki Hiroto , Hirano Takao , Ishikawa Hiroto , Mitamura Yoshinori , Okamoto Fumiki , Kinoshita Takamasa , Kimura Kazuhiro , Yamashiro Kenji , Suzuki Yukihiko , Hikichi Taiichi , Washio Noriaki , Sato Tomohito , Ohkoshi Kishiko , Tsujinaka Hiroki , Kondo Mineo , Takagi Hitoshi , Murata Toshinori , Sakamoto Taiji ,   Japan Clinical Retina Study (J‐CREST) group
Published: April 2022

ABSTRACTAims/IntroductionIn older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME.Materials and MethodsThis is a real‐world clinical study including 1,552 patients with treatment‐naïve center‐involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55–64; C3, 65–74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best‐corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years.ResultsFrom baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were −0.01 in C1, −0.06 in C2, −0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were −136.2 μm in C1, −108.8 μm in C2, −100.6 μm in C3, and −89.5 μm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti‐VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001).ConclusionsCompared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real‐world clinical practice.