bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of bidirectional relationships between brain imaging-derived phenotypes and stroke: a Mendelian randomization study
Authors: Yu Ke , Chen Xiao-Feng , Guo Jing , Wang Sen , Huang Xiao-Ting , Guo Yan , Dong Shan-Shan , Yang Tie-Lin 
Published: July 2023

Abstract
Background
Stroke is a major cause of mortality and long-term disability worldwide. Whether the associations between brain imaging-derived phenotypes (IDPs) and stroke are causal is uncertain.

Methods
We performed two-sample bidirectional Mendelian randomization (MR) analyses to explore the causal associations between IDPs and stroke. Summary data of 587 brain IDPs (up to 33,224 individuals) from the UK Biobank and five stroke types (sample size range from 301,663 to 446,696, case number range from 5,386 to 40,585) from the MEGASTROKE consortium were used.

Results
Forward MR indicated 14 IDPs belong to projection fibers or association fibers were associated with stroke. For example, higher genetically determined mean diffusivity (MD) in the right external capsule was causally associated with an increased risk of small vessel stroke (IVW OR = 2.76, 95% CI 2.07 to 3.68, P = 5.87 × 10−12). Reverse MR indicated that genetically determined higher risk of any ischemic stroke was associated with increased isotropic or free water volume fraction (ISOVF) in body of corpus callosum (IVW β = 0.23, 95% CI 0.14 to 0.33, P = 3.22 × 10−7). This IDP is a commissural fiber and it is not included in the IDPs identified by forward MR.

Conclusions
We identified 14 IDPs with statistically significant evidence of causal effects on stroke or stroke subtypes. We also identified potential causal effects of stroke on one IDP of commissural fiber. These findings might guide further work toward identifying preventative strategies at the brain imaging levels.
A female of progressive familial intrahepatic cholestasis type 3 caused by heterozygous mutations of ABCB4 gene and her cirrhosis improved after treatment of ursodeoxycholic acid: a case report
Authors: Qiao Fei , Ren Feng , Lu Weiting , Yang Haoran , Mo Guiling , Wang Shuangshuang , Liu Lina , Xu Xiangtao 
Published: July 2023

Abstract
Background
Progressive familial intrahepatic cholestasis (PFIC) is a group of rapidly progressive autosomal recessive disorders characterized by intrahepatic cholestasis. PFIC-3 is caused by mutations in the ATP-binding cassette subfamily B member 4 gene (ABCB4), which encodes multidrug resistance protein 3 (MDR3/ABCB4). Patients are usually in infancy or childhood, but cirrhosis and portal hypertension may be the first manifestation in older children or young adults.

Case presentation
A 25-year-old young woman with recurrent abnormal hepatic function was mainly characterized by increased gamma glutamyl transpeptidase (GGT) and bile acid with cryptogenic cirrhosis. After 7 months of treatment with ursodeoxycholic acid (UDCA), her hepatic pathology suggested there were also obvious widening and venous fibrosis around the portal vein, and slight bile duct hyperplasia at the edge of the portal area. Infiltration of inflammatory cells around the portal vein and hepatocyte ABCB4/MDR3 protein was basically normal. Sequencing indicated the patient had heterozygous mutations in the ABCB4 gene: c.2696C > G and wes [hg19]7q21.12(87032513–87033422) × 1. Through SWISS-MODEL Predict for protein structures, the missense mutation results in protein side chain missing a methyl group (-CH3), and the deletion mutation results in the serious damage to the structure of MDR3 protein which lead to phosphatidylcholine deficiency of bile in the capillary bile ducts. The toxic effect of bile salts then damages the bile ducts, causing cholestasis and cholangitis, which can then develop into biliary cirrhosis. Through the analysis of pathogenicity prediction software, the mutations led to PFIC3. After treatment of UDCA for 29 months, her cirrhosis was improved, hepatic function was close to normal.

Conclusion
Novel heterozygous mutations are the molecular pathological cause of PFIC3 in this patient. All young adult patients with occult cirrhosis should be tested for ABCB4. Early diagnosis of PFIC3 and continued treatment with UDCA are key to improving prognosis and delaying the onset of end-stage liver disease.
Perioperative opioid-minimization approach as a useful protocol in the management of patients with Ehlers–Danlos syndrome-hypermobility type, craniocervical instability and severe chronic pain who are to undergo occipito-cervical fixation
Authors: Ramírez-Paesano Carlos , Rodiera Clarens Claudia , Sharp Segovia Allan , Coila Bustinza Alan , Rodiera Olive Josep , Juanola Galceran Albert 
Published: July 2023

AbstractPatients suffering from connective tissue disorders like Ehlers–Danlos syndrome hypermobility type/joint hypermobility syndrome (EDS-HT/JHS) may be affected by craniocervical instability (CCI). These patients experience myalgic encephalomyelitis, chronic fatigue, depression, extreme occipital-cervical pain, and severe widespread pain that is difficult to relieve with opioids. This complex and painful condition can be explained by the development of chronic neuroinflammation, opioid-induced hyperalgesia, and central sensitization. Given the challenges in treating such severe physical pain, we evaluated all the analgesic methods previously used in the perioperative setting, and updated information was presented. It covers important physiopathological aspects for the perioperative care of patients with EDS-HT/JHS and CCI undergoing occipital-cervical/thoracic fixation/fusion. Moreover, a change of paradigm from the current opioid-based management of anesthesia/analgesia in these patients to the perioperative opioid minimization strategies used by the authors was analyzed and proposed as follow-up considerations from our previous case series. These strategies are based on total-intravenous opioid-free anesthesia, multimodal analgesia, and a postoperative combination of anti-hyperalgesic coadjuvants (lidocaine, ketamine, and dexmedetomidine) with an opioid-sparing effect.
The UK BiLEVE and Mendelian randomisation: using multivariable instrumental variables to address “damned if you, damned if you don’t” adjustment problems
Authors: Woolf Benjamin , Gill Dipender , Sallis Hannah , Munafò Marcus R. 
Published: July 2023

Abstract
Objective
To explore the use of multivariable instrumental variables to resolve the “damned if you do, damned if you don’t” adjustment problem created for Mendelian randomisation (MR) analysis using the smoking or lung function related phenotypes in the UK Biobank (UKB).

Result
“damned if you do, damned if you don’t” adjustment problems occur when both adjusting and not-adjusting for a variable will induce bias in an analysis. One instance of this occurs because the genotyping chip of UKB participants differed based on lung function/smoking status. In simulations, we show that multivariable instrumental variables analyses can attenuate potential collider bias introduced by adjusting for a proposed covariate, such as the UKB genotyping chip. We then explore the effect of adjusting for genotyping chip in a multivariable MR model exploring the effect of smoking on seven medical outcomes (lung cancer, emphysema, hypertension, stroke, heart diseases, depression, and disabilities). We additionally compare our results to a traditional univariate MR analysis using genome-wide analyses summary statistics which had and had not adjusted for genotyping chip. This analysis implies that the difference in genotyping chip has introduced only a small amount of bias.
Proteomic dataset of Candida albicans (ATCC 10231) Biofilm
Authors: Zore Gajanan , Abdulghani Mazen , Kazi Rubina , Shelar Amruta , Patil Rajendra 
Published: July 2023

Abstract
Objectives
The ability to form biofilm is considered as one of major virulence factors of Candida albicans, as biofilms form growth confers antifungal resistance and facilitate immune evasion. It is intriguing to understand morphophysiological modulations in the C. albicans cells growing under biofilm form growth.

Data description
In present study, we have profiled biofilm-specific proteins using LC-MS/MS analysis. Whole cell proteins of C. albicans cells grown under biofilm form growth (test) and planktonic (control) growth for 24 h were extracted, digested and identified using micro-Liquid Chromatography-Mass Spectrometry (LC-MS/MS). The present data represents proteomic profile (SWATH Spectral Libraries) of C. albicans biofilm intended to be useful to scientific community as it exhibits reuse potential.
Bovine tuberculosis in Spain, is it really the final countdown?
Authors: Bezos Javier , Sáez-Llorente José Luis , Álvarez Julio , Romero Beatriz , Díez-Guerrier Alberto , Domínguez Lucas , de Juan Lucía 
Published: July 2023

AbstractBovine tuberculosis (bTB) is a severe zoonotic disease that has major impacts on both health and the economy, and which has been subjected to specific eradication programmes in many countries for decades. This manuscript highlights the relevance of this disease in the context of the European Union (EU) and summarizes the epidemiological situation and the main tools (e.g. antemortem diagnostic tests, slaughterhouse surveillance, laboratories, comprehensive databases, etc.) used to control and eradicate bTB in the various EU countries with a focus on the situation in Spain. A comprehensive description of the specific bTB epidemiological situation in Spain is provided, together with an assessment of the evolution of different epidemiological indicators throughout the last decades. Moreover, the main features of the Spanish bTB eradication programme and its control tools are described, along with the studies carried out in Spain that have allowed the updating of and improvement to the programme over the years with the aim of eradication, which has been established for 2030.
Microbe-driven elemental cycling enables microbial adaptation to deep-sea ferromanganese nodule sediment fields
Authors: Zhang Dechao , Li Xudong , Wu Yuehong , Xu Xuewei , Liu Yanxia , Shi Benze , Peng Yujie , Dai Dadong , Sha Zhongli , Zheng Jinshui 
Published: July 2023

Abstract
Background
Ferromanganese nodule-bearing deep-sea sediments cover vast areas of the ocean floor, representing a distinctive habitat in the abyss. These sediments harbor unique conditions characterized by high iron concentration and low degradable nutrient levels, which pose challenges to the survival and growth of most microorganisms. While the microbial diversity in ferromanganese nodule-associated sediments has been surveyed several times, little is known about the functional capacities of the communities adapted to these unique habitats.

Results
Seven sediment samples collected adjacent to ferromanganese nodules from the Clarion–Clipperton Fracture Zone (CCFZ) in the eastern Pacific Ocean were subjected to metagenomic analysis. As a result, 179 high-quality metagenome-assembled genomes (MAGs) were reconstructed and assigned to 21 bacterial phyla and 1 archaeal phylum, with 88.8% of the MAGs remaining unclassified at the species level. The main mechanisms of resistance to heavy metals for microorganisms in sediments included oxidation (Mn), reduction (Cr and Hg), efflux (Pb), synergy of reduction and efflux (As), and synergy of oxidation and efflux (Cu). Iron, which had the highest content among all metallic elements, may occur mainly as Fe(III) that potentially functioned as an electron acceptor. We found that microorganisms with a diverse array of CAZymes did not exhibit higher community abundance. Instead, microorganisms mainly obtained energy from oxidation of metal (e.g., Mn(II)) and sulfur compounds using oxygen or nitrate as an electron acceptor. Chemolithoautotrophic organisms (Thaumarchaeota and Nitrospirota phyla) were found to be potential manganese oxidizers. The functional profile analysis of the dominant microorganisms further indicated that utilization of inorganic nutrients by redox reactions (rather than organic nutrient metabolism) is a major adaptive strategy used by microorganisms to support their survival in the ferromanganese nodule sediments.

Conclusions
This study provides a comprehensive metagenomic analysis of microbes inhabiting metal-rich ferromanganese nodule sediments. Our results reveal extensive redundancy across taxa for pathways of metal resistance and transformation, the highly diverse mechanisms used by microbes to obtain nutrition, and their participation in various element cycles in these unique environments.
Storytelling for impact: the creation of a storytelling program for patient partners in research
Authors: Getchell Leah E. , Reich Marian , Allu Selina , Woods Cathy , Atkinson Teresa , Beaucage Mary , Stalker Leanne , Sparkes Dwight , Turner Catherine , L’Esperance Audrey , Burns Kevin , Elliott Meghan J. , Chiu Helen , Rosenblum Norman D. , Sapir-Pichhadze Ruth 
Published: July 2023

AbstractStorytelling is a powerful means to evoke empathy and understanding among people. When patient partners, which include patients, family members, caregivers and organ donors, share their stories with health professionals, this can prompt listeners to reflect on their practice and consider new ways of driving change in the healthcare system. However, a growing number of patient partners are asked to ‘share their story’ within health care and research settings without adequate support to do so. This may ultimately widen, rather than close, the gap between healthcare practitioners and people affected by chronic disease in this new era of patient and public involvement in research. To better support patient partners with storytelling in the context of a patient-oriented research network, Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) Network adapted an existing in-person storytelling workshop for patient educators within a hospital setting. The result is a 6-week virtual program called Storytelling for Impact, which guides patients, family members, caregivers and organ donors in developing impactful stories and sharing them at health care and research events, e.g., conferences. The online series of synchronous workshops is co-facilitated by story coaches, who are program alumni and Can-SOLVE CKD staff with trained storytelling experience. Each story follows a structure that includes a call to action, which aims to positively impact the priority-setting and delivery of care and research in Canada. The program has been a transformational process for many who have completed it, and numerous other health organizations have expressed interest in sharing this tool with their own patient partners. As result, we have also created an asynchronous online program that can be used by other interested parties outside our network. Patient partners who share their stories can be powerful mediators for inspiring changes in the health care and research landscape, with adequate structured support. We describe two novel programs to support patient partners in impactful storytelling, which are applicable across all health research disciplines. Additional resources are required for sustainability and scale up of training, by having alumni train future storytellers.
The role of mitochondrial genes on nuclear gene expression in neovascular age related macular degeneration: analysis of nuclear VEGF gene expression after ranibizumab treatment in cytoplasmic hybrid retinal pigment epithelial cell lines correlated with clinical evolution
Authors: Costa Rodrigo Donato , Thomaz Neto Farid José , Moustafa M. Tarek , Atilano Shari R. , Chwa Marilyn , Cáceres-del-Carpi Javier , Mohamed Mohamed Hamid , Kenney M. Cristina , Kuppermann Baruch D. 
Published: July 2023

Abstract
Purpose
The present study tests the hypothesis that mitochondrial genes have retrograde signaling capacity that influences the expression of nuclear genes related to angiogenesis pathways. Cytoplasmic hybrid (cybrid) in vitro cell lines with patient specific mitochondria inserted into an immortalized retinal pigment epithelial cell line (ARPE-19) were used to test this hypothesis. This type of analysis can provide important information to identify the optimal regimen of anti-VEGF treatment, personalizing age-related macular degeneration (AMD) therapies.

Methods
Mitochondria deficient ARPE-19 cells (Rho0) were fused with AMD donor’s platelets to create individual cybrid cell lines containing mitochondria from patients with phenotypic AMD disease and nuclear DNA from the immortalized RPE cell line. The cybrids were treated with Ranibizumab (Lucentis, Genentech, San Francisco, CA), at 4 different concentrations for 24 h, and subsequently the levels of reactive oxygen species (ROS), gene expression for VEGF-A, hypoxia-inducible factor 1-alpha (HIF1-a) and manganese superoxide dismutase (SOD2) were measured. The clinical evolution of the two AMD-donors were correlated with the molecular findings found in their ‘personalized’ cybrids.

Results
Cybrids from Patient-01 showed down-regulation of gene expression of VEGF-A and HIF-1a at both 1X and 4X Ranibizumab concentrations. Patient-01 AMD cybrid cultures had an increase in the ROS levels at 1X (P = 0.0317), no changes at 2X (P = 0.8350) and a decrease at 4X (P = 0.0015) and 10X (P = 0.0011) of Ranibizumab. Clinically, Patient-01 responded to anti-VEGF therapy but eventually developed geographic atrophy. Patient-02 cybrids demonstrated up-regulation of gene expression of VEGF-A and HIF-1a at Ranibizumab 1X and 4X concentrations. There was decreased ROS levels with Ranibizumab 1X (P = 0.1606), 2X (P = 0.0388), 4X (P = 0.0010) and 10X (P =  < 0.0001). Clinically, Patient-02 presented with a neovascular lesion associated with a prominent production of intraretinal fluid in clinical follow-up requiring regular and repeated intravitreal injections of Ranibizumab with recurrent subretinal fluid.

Conclusions
Our cybrid model has the potential to help personalize the treatment regimen with anti-VEGF drugs in patients with neovascular AMD. Further investigation is needed to better understand the role that the mitochondria play in the cellular response to anti-VEGF drugs. Future studies that focus on this model have the potential to help personalize anti-VEGF treatment.
Cognitive perspectives on maintaining physicians’ medical expertise: II. Acquiring, maintaining, and updating cognitive skills
Authors: Caddick Zachary A. , Fraundorf Scott H. , Rottman Benjamin M. , Nokes-Malach Timothy J. 
Published: July 2023

AbstractOver the course of training, physicians develop significant knowledge and expertise. We review dual-process theory, the dominant theory in explaining medical decision making: physicians use both heuristics from accumulated experience (System 1) and logical deduction (System 2). We then discuss how the accumulation of System 1 clinical experience can have both positive effects (e.g., quick and accurate pattern recognition) and negative ones (e.g., gaps and biases in knowledge from physicians’ idiosyncratic clinical experience). These idiosyncrasies, biases, and knowledge gaps indicate a need for individuals to engage in appropriate training and study to keep these cognitive skills current lest they decline over time. Indeed, we review converging evidence that physicians further out from training tend to perform worse on tests of medical knowledge and provide poorer patient care. This may reflect a variety of factors, such as specialization of a physician’s practice, but is likely to stem at least in part from cognitive factors. Acquired knowledge or skills gained may not always be readily accessible to physicians for a number of reasons, including an absence of study, cognitive changes with age, and the presence of other similar knowledge or skills that compete in what is brought to mind. Lastly, we discuss the cognitive challenges of keeping up with standards of care that continuously evolve over time.
Addressing neglected tropical diseases in Africa: a health equity perspective
Authors: George Nsikakabasi Samuel , David Success Chekwube , Nabiryo Maxencia , Sunday Blessing Abai , Olanrewaju Omotayo Faith , Yangaza Yonah , Shomuyiwa Deborah Oluwaseun 
Published: July 2023

AbstractAfrica accounts for over one-third of the global burden of neglected tropical diseases (NTDs). Although continental efforts have been made to combat these diseases, there still exists a significant gap in the fight, ranging from a lack of data to multisectoral participation and, most critically, health inequity. Here, we assess the effort made to combat challenges caused by health disparities to prevent and control neglected tropical diseases. This article engages a health equity view to addressing the need for inclusion in achieving universal health coverage towards eradicating NTDs and outlines strategies to achieve such. Health disparities exist, and there is substantial and irrefutable evidence for them. Inequitable distribution and limited access to basic and essential life resources such as water, housing, toilets, soap, and literacy continue to facilitate the existence of NTDs such as Schistosomiasis, soil-transmitted helminths, and trachoma, the occurrence of which can be avoided if affected populations have better access to those resources. To eradicate NTDs, health disparities must be addressed to provide excellent health care to all populations and adequate universal health coverage for long-term sustainability. NTD programmes need to be data-driven to ensure better decision-making and ensure the inclusion of diverse population groups including women, children, and youths. This will ensure that no one is left behind, drawing upon the sustainable development goals. Community participation and engagement should also be considered as an essential approach to ensure people are at the centre of health programmes and their implementation.
Transient synchronous stability analysis and enhancement control strategy of a PLL-based VSC system during asymmetric grid faults
Authors: Luo Yi , Yao Jun , Chen Zhaoyang , Huang Sen , Chen Shiyue , Zhang Qi , Qin Zhentao 
Published: July 2023

AbstractThe stability of a voltage source converters (VSC) system based on phase-locked loop (PLL) is very important issue during asymmetric grid faults. This paper establishes a transient synchronous stability model of a dual-sequence PLL-based VSC system during low voltage ride-through by referring to the equivalent rotor swing equation of synchronous generators. Based on the model, the synchronization characteristics of the VSC system under asymmetric grid faults are described, and the interaction mechanisms, as well as the transient instability phenomena of positive and negative sequence PLL during asymmetric faults are explained. Using the equal area criterion, the influences of sequence control switching action, detection delay, and interaction between the positive and negative sequence PLL on the transient synchronous stability of the VSC system are analyzed, respectively. In addition, a transient stability assessment criterion based on the critical fault clearance angle and time and an enhancement control strategy based on the improved positive and negative sequence PLL are proposed. Finally, the analytical results are validated through simulation and experiments.