bluuebunny/crossref_metadata_2025 huggingface dataset:
PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart
Authors: Li Qinfeng , Li Chao , Elnwasany Abdallah , Sharma Gaurav , An Yu A. , Zhang Guangyu , Elhelaly Waleed M. , Lin Jun , Gong Yingchao , Chen Guihao , Wang Meihui , Zhao Shangang , Dai Chongshan , Smart Charles D. , Liu Juan , Luo Xiang , Deng Yingfeng , Tan Lin , Lv Shuang-Jie , Davidson Shawn M. , Locasale Jason W. , Lorenzi Philip L. , Malloy Craig R. , Gillette Thomas G. , Vander Heiden Matthew G. , Scherer Philipp E. , Szweda Luke I. , Fu Guosheng , Wang Zhao V.
Published: June 2021

Background:

Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload.

Methods:

Cardiac-specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac-specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction. Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and nuclear magnetic resonance spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload.

Results:

We found that PKM1 expression is reduced in failing human and mouse hearts. It is important to note that cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against transverse aortic constriction–induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both in vitro and in vivo levels.

Conclusions:

These findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.
Mapping Cerebrovascular Reactivity Impairment in Patients With Symptomatic Unilateral Carotid Artery Disease
Authors: Sebök Martina , van Niftrik Christiaan Hendrik Bas , Winklhofer Sebastian , Wegener Susanne , Esposito Giuseppe , Stippich Christoph , Luft Andreas , Regli Luca , Fierstra Jorn
Published: June 2021

Background

Comprehensive hemodynamic impairment mapping using blood oxygenation‐level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease.

Methods and Results

This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age‐matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO
2
stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion‐weighted imaging. Sixty‐seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole‐brain and ipsilateral hemisphere mean BOLD‐CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04,
P
=0.004 and 0.09±0.09 versus 0.18±0.04,
P
<0.001) and ICA stenosis cohort (0.12±0.08 versus 0.16±0.05,
P
=0.01 and 0.09±0.09 versus 0.15±0.05,
P
=0.01); however, only 40 (58%) patients of the cohort showed significant BOLD‐CVR impairment. Conversely, there was no difference in mean BOLD‐CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD‐CVR impairment. No significant BOLD‐CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06,
P
=0.12).

Conclusions

Comprehensive BOLD‐CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.
The Sense of Supernatural Agency
Authors: Peters Frederic
Published: June 2021

The sense of supernatural agency constitutes a defining characteristic of the religious sphere of life. But what accounts for the continued cross-cultural recurrence of this psychological phenomenon over the course of human history? This paper reviews evidence indicating that the source of panhuman or universal cognitive patterns of thought and behaviour such as this lies in the common characteristics of the evolved human mind. Further, that the sense of the supernatural is constituted by a unique combination of commonly recurring cognitive processes that together give rise to a panhuman conviction in the reality of supernatural agencies able and (when minded) willing to assist each individual in situations deemed beyond the capacities of that individual. These cognitive processes are driven most acutely by existential anxiety in response to extrinsic physical, economic and social pressures indicating that religiosity is best understood as a social-psychological phenomenon.
Rethinking Religious Cognition and Myth: A New Perspective on how Religions Balance Intuitiveness and Interest-Provokingness/Memorability
Authors: Nakissa Aria
Published: June 2021

In his influential work on the cognitive science of religion (CSR), Pascal Boyer argues that the spread of religious ideas involves a tradeoff between their “intuitiveness” and their interest-provokingness/memorability (i.e.,their capacity to provoke interest and be remembered). For Boyer, religious ideas are “intuitive” insofar as they are easy to understand and learn. However, other CSR studies suggest that religious ideas are “intuitive” insofar as they are easy to believe. In analyzing the spread of religious ideas, no study has considered the tradeoff between interest-provokingness/memorability and intuitiveness in the sense of being easy to believe. The present article takes up this task by considering several religious concepts that are intuitively easy to believe (e.g., immortal souls, spirit beings, a Creator God, a just world). It is argued that, in typical religions, such concepts are incorporated into myths. Through incorporation, these concepts lose some of their intuitive believability but gain interest-provokingness/memorability.
Pitched between Scylla and Charybdis: Metz Jews’ Litigation Hurdles in the Metz Beit Din and Ancien Regime French Courts
Authors: Herman Shael
Published: June 2021

During the eighteenth century, French courts expanded their competence over Jewish disputes in order to consolidate the kingdom’s hegemony over Alsatian Jewry. In Metz, the expansion was sanctioned by a royal order for the composition of the Recueil des Loix, Coutumes, et Usages Observes par les Juifs de Metz (1742). A blend of Jewish law and French customary law tailored for ancien regime Alsatian courts, the Recueil enabled a Jewish claimant to sue in either the beit din or a French tribunal. These judicial alternatives posed strategic dilemmas. French rulings were frequently vehicles for persecuting Jewish claimants and debasing their law, while rabbinical enforcement mechanisms typically lacked the aggressive bite of their French judicial counterparts. This article examines how the law, and these options, worked in practice.
Biblical History in the Thought of R. Ḥaim David Halevy
Authors: Breier Idan
Published: June 2021

R. Ḥaim David Halevy was an exceptional voice in the Religious-Zionist camp in Israel. While espousing faithfulness to the halakhah, he recognized the importance of changing circumstances with respect both to halakhic rulings and philosophical issues arising in Hebrew law. He viewed the study of history as a practical imperative, necessary to avoid repeating the mistakes of the past. Frequently adducing biblical texts, he argued that Israel must learn from the patriarchs and maintain a strong military force. In particular, the events leading to the destruction of the Temple and exile prompted him to posit that the State should remain neutral and not take an active part in international affairs. On the basis of the historiographical and prophetic literature, he maintained that fidelity to the divine covenant – i.e., ethical conduct – would safeguard Israel’s existence.
The Way of the Cross in the Ordinary: Ethnographic Attention to the Good as Invitational Ethics
Authors: Williams Sara A.
Published: June 2021

This essay develops the idea of ‘invitational ethics,’ engagement with ethnographic description as normative praxis. I argue that by attending to ways in which people exercise practical wisdom in ordinary moments, the ethnographer and reader alike are invited to engage their own processes of ethical self-making. I draw on ethnographic fieldwork with the Way of the Cross for Justice, an annual Good Friday public liturgy in Cincinnati, Ohio, as a site for invitational ethics in the frame of what anthropologist Joel Robbins has called an ‘anthropology of the good.’ I conclude by reflecting on how this invited me to engage my own ethical self-making.
Environmental and Internal Controls on Lagrangian Transitions from Closed Cell Mesoscale Cellular Convection over Subtropical Oceans
Authors: Eastman Ryan , McCoy Isabel L. , Wood Robert
Published: June 2021

Classifications of mesoscale cellular convection (MCC) for marine boundary layer clouds are produced using a supervised neural network algorithm applied to MODIS daytime liquid water path data. The classifier, used in prior studies, distinguishes closed, open, and cellular but disorganized MCC. This work uses trajectories in four eastern subtropical ocean basins to compare meteorological variables and the structures of boundary layers for trajectories that begin as closed cells but evolve into either open cells or disorganized cells or remain closed cells over one afternoon–afternoon cycle. Results show contrasts between the trajectory sets: Trajectories for MCC that remain closed cells are more frequently observed nearer coasts, whereas trajectories that break into open and disorganized cells begin farther offshore. The frequency at which closed cells transition to open cells is seasonally invariant. The fraction of trajectories that stay as closed MCC varies throughout the year in opposition to those that break into disorganized cells, so that their annual cycles are 180° out of phase. Trajectories remain as closed cell more frequently in austral spring and boreal summer when the trade inversion is stronger. The closed–disorganized MCC breakup is associated with weaker subsidence, a weaker inversion, a drier free troposphere, and enhanced nighttime boundary layer deepening, consistent with a warming–drying mechanism. The closed–open transition occurs in meteorological conditions similar to closed–closed trajectories. However, prior to the transition, the closed–open trajectories exhibit stronger surface winds and lower cloud droplet concentrations and rain more heavily overnight. Results suggest that multiple, independent mechanisms drive changes in cloud amount and morphology.
Validation of a Prototype Global 4D-Var Data Assimilation System for the MPAS-Atmosphere Model
Authors: Tian Xiaoxu , Zou Xiaolei
Published: June 2021

A four-dimensional variational (4D-Var) data assimilation (DA) system is developed for the global nonhydrostatic atmospheric dynamical core of the Model for Prediction Across Scales (MPAS). The nonlinear forward and adjoint models of the MPAS-Atmosphere dynamic core are included in a Python-driven structure to formulate a continuous 4D-Var DA system, shown to effectively minimize the cost function that measures the distances between the nonlinear model simulations and observations. In this study, three idealized experiments with a six-hour assimilation window are conducted to validate and demonstrate the numerical feasibilities of the 4D-Var DA system for both uniform- and variable-resolution meshes. In the first experiment, only a single point observation is assimilated. The resulting solution shows that the analysis increments have highly flow-dependent features. The observations in the second experiment are all model prognostic variables that span the entire global domain, the purpose of which is to check how well the initial conditions six hours prior to the observations can be reversely inferred. The differences between the analysis and the referenced "truth" are significantly smaller than those calculated with the first guess. The third experiment assimilates the mass field only, i.e., potential temperatures in the case of MPAS-Atmosphere, and examines the impacts on the wind field and the mass field under initial conditions. Both the wind vectors and potential temperatures in the analysis agree more with the referenced "truth" than the first guess because the adjustments made to the initial conditions are dynamically consistent in the 4D-Var system.
Public perception of palliative care: a survey of the general population
Authors: Fliedner Monica C. , Zambrano Sofia C. , Eychmueller Steffen
Published: June 2021

Background:

The public’s view of palliative care often involves its potential to improve of quality-of-life as well as its use as a last resource prior to death.

Objective:

To obtain an idea of the image of palliative care held by the public in the German-speaking part of Switzerland, the authors sought to understand (1) the perceptions of palliative care and the (2) elements important when thinking about their own end of life.

Methods and Sample:

A qualitative design with an inductive reasoning approach based on Mayring (2014) was chosen. Visitors at an exhibition about palliative care in six locations provided hand-written answers on provided cards to two statements: (1) if I hear the term ‘Palliative Care’ I think of … and (2) when thinking about my own end of life, the following is important to me …

Results:

Answers of 199 visitors (mean age 52, mostly in a good/very good health status) were analysed. In response to hearing the term palliative care, six areas were categorized: (1) the main focus; (2) ways of providing palliative care; (3) the best timing; (4) places where palliative care is provided; (5) who is seen as provider and (6) outcomes of palliative care. Five categories to the statement about their own end-of-life were identified: (1) the ability to look back on a fulfilled life and being satisfied; (2) maintaining trusting relationships until the end; (3) organizing affairs and having everything settled; (4) having their family being cared for and (5) relief of suffering with the support of knowledgeable people.

Conclusion:

Palliative care was mostly associated with positive terms acknowledging an interprofessional approach. Maintaining one’s dignity as well as dying without suffering pointed at the persisting stigma that palliative care is mainly limited to end-of-life care. The results may help healthcare professionals to better understand how the public view palliative care.
Genome-wide association analysis of adaptation to oxygen stress in Nile tilapia (Oreochromis niloticus)
Authors: Yu Xiaofei , Megens Hendrik-Jan , Mengistu Samuel Bekele , Bastiaansen John W. M. , Mulder Han A. , Benzie John A. H. , Groenen Martien A. M. , Komen Hans
Published: June 2021

Background

Tilapia is one of the most abundant species in aquaculture. Hypoxia is known to depress growth rate, but the genetic mechanism by which this occurs is unknown. In this study, two groups consisting of 3140 fish that were raised in either aerated (normoxia) or non-aerated pond (nocturnal hypoxia). During grow out, fish were sampled five times to determine individual body weight (BW) gains. We applied a genome-wide association study to identify SNPs and genes associated with the hypoxic and normoxic environments in the 16th generation of a Genetically Improved Farmed Tilapia population.

Results

In the hypoxic environment, 36 SNPs associated with at least one of the five body weight measurements (BW1 till BW5), of which six, located between 19.48 Mb and 21.04 Mb on Linkage group (LG) 8, were significant for body weight in the early growth stage (BW1 to BW2). Further significant associations were found for BW in the later growth stage (BW3 to BW5), located on LG1 and LG8. Analysis of genes within the candidate genomic region suggested that MAPK and VEGF signalling were significantly involved in the later growth stage under the hypoxic environment. Well-known hypoxia-regulated genes such asigf1rb,rora,efna3andaurkwere also associated with growth in the later stage in the hypoxic environment. Conversely, 13 linkage groups containing 29 unique significant and suggestive SNPs were found across the whole growth period under the normoxic environment. A meta-analysis showed that 33 SNPs were significantly associated with BW across the two environments, indicating a shared effect independent of hypoxic or normoxic environment. Functional pathways were involved in nervous system development and organ growth in the early stage, and oocyte maturation in the later stage.

Conclusions

There are clear genotype-growth associations in both normoxic and hypoxic environments, although genome architecture involved changed over the growing period, indicating a transition in metabolism along the way. The involvement of pathways important in hypoxia especially at the later growth stage indicates a genotype-by-environment interaction, in which MAPK and VEGF signalling are important components.
DNAscent v2: detecting replication forks in nanopore sequencing data with deep learning
Authors: Boemo Michael A.
Published: June 2021

Background

Measuring DNA replication dynamics with high throughput and single-molecule resolution is critical for understanding both the basic biology behind how cells replicate their DNA and how DNA replication can be used as a therapeutic target for diseases like cancer. In recent years, the detection of base analogues in Oxford Nanopore Technologies (ONT) sequencing reads has become a promising new method to supersede existing single-molecule methods such as DNA fibre analysis: ONT sequencing yields long reads with high throughput, and sequenced molecules can be mapped to the genome using standard sequence alignment software.

Results

This paper introduces DNAscent v2, software that uses a residual neural network to achieve fast, accurate detection of the thymidine analogue BrdU with single-nucleotide resolution. DNAscent v2 also comes equipped with an autoencoder that interprets the pattern of BrdU incorporation on each ONT-sequenced molecule into replication fork direction to call the location of replication origins termination sites. DNAscent v2 surpasses previous versions of DNAscent in BrdU calling accuracy, origin calling accuracy, speed, and versatility across different experimental protocols. Unlike NanoMod, DNAscent v2 positively identifies BrdU without the need for sequencing unmodified DNA. Unlike RepNano, DNAscent v2 calls BrdU with single-nucleotide resolution and detects more origins than RepNano from the same sequencing data. DNAscent v2 is open-source and available at https://github.com/MBoemo/DNAscent.

Conclusions

This paper shows that DNAscent v2 is the new state-of-the-art in the high-throughput, single-molecule detection of replication fork dynamics. These improvements in DNAscent v2 mark an important step towards measuring DNA replication dynamics in large genomes with single-molecule resolution. Looking forward, the increase in accuracy in single-nucleotide resolution BrdU calls will also allow DNAscent v2 to branch out into other areas of genome stability research, particularly the detection of DNA repair.
Genome-wide analysis of long non-coding RNAs (lncRNAs) in two contrasting soybean genotypes subjected to phosphate starvation
Authors: Zhang Jinyu , Xu Huanqing , Yang Yuming , Zhang Xiangqian , Huang Zhongwen , Zhang Dan
Published: June 2021

Background

Phosphorus (P) is essential for plant growth and development, and low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Long noncoding RNAs (lncRNAs) have recently been reported to be key regulators in the responses of plants to stress conditions, but the mechanism through which LP stress mediates the biogenesis of lncRNAs in soybean remains unclear.

Results

In this study, to explore the response mechanisms of lncRNAs to LP stress, we used the roots of two representative soybean genotypes that present opposite responses to P deficiency, namely, a P-sensitive genotype (Bogao) and a P-tolerant genotype (NN94156), for the construction of RNA sequencing (RNA-seq) libraries. In total, 4,166 novel lncRNAs, including 525 differentially expressed (DE) lncRNAs, were identified from the two genotypes at different P levels. GO and KEGG analyses indicated that numerous DE lncRNAs might be involved in diverse biological processes related to phosphate, such as lipid metabolic processes, catalytic activity, cell membrane formation, signal transduction, and nitrogen fixation. Moreover, lncRNA-mRNA-miRNA and lncRNA-mRNA networks were constructed, and the results identified several promising lncRNAs that might be highly valuable for further analysis of the mechanism underlying the response of soybean to LP stress.

Conclusions

These results revealed that LP stress can significantly alter the genome-wide profiles of lncRNAs, particularly those of the P-sensitive genotype Bogao. Our findings increase the understanding of and provide new insights into the function of lncRNAs in the responses of soybean to P stress.
The role of combination therapy in the treatment of severe infections caused by carbapenem resistant gram-negatives: a systematic review of clinical studies
Authors: Savoldi Alessia , Carrara Elena , Piddock Laura J. V. , Franceschi Francois , Ellis Sally , Chiamenti Margherita , Bragantini Damiano , Righi Elda , Tacconelli Evelina
Published: June 2021

Background

Effective treatment of sepsis due to carbapenem-resistant Gram-negative bacteria (CR-GNB) remains a challenge for clinicians worldwide. In recent years, the combination of antibiotics has become the preferred treatment strategy for CR-GNB infection. However, robust evidence to support this approach is lacking. This systematic review aimed at critically evaluating all available antibiotic options for CR-GNB sepsis with particular focus on combination.

Methods

We systematically searched published literature from January 1945 until December 2018 for observational comparative and non-comparative studies and randomized trials examining any antibiotic option for CR-GNB. Studies were included if reporting microbiologically-confirmed infection caused by Acinetobacter baumannii, Enterobacteriaceae/Klebsiella spp., or Pseudomonas aeruginosa, reporting at least one of the study outcomes, and definitive antibiotic treatment. Carbapenem-resistance was defined as phenotypically-detected in vitro resistance to at least one of the following carbapenems: doripenem, ertapenem, imipenem, meropenem. Each antibiotic regimen was classified as “defined” when at least the molecular class(es) composing the regimen was detailed. Primary outcomes were 30-day and attributable mortality. Bayesian network meta-analysis (NMA) approach was selected for quantitative synthesis to explore feasibility of pooling data on antibiotic regimens.

Results

A total of 6306 records were retrieved and 134 studies including 11,546 patients were included: 54 studies were on Acinetobacter, 52 on Enterobacteriaceae/Klebsiella, 21 on mixed Gram-negative, and 7 on Pseudomonas. Nine (7%) were RCTs; 19 prospective cohorts (14%), 89 (66%) retrospective, and 17 (13%) case series. Forty-one studies (31%) were multicentric. Qualitative synthesis showed an heterogeneous and scattered reporting of key-clinical and microbiological variables across studies. Ninety-two distinct antibiotic regimens were identified with 47 of them (51%, 5863 patients) not reporting any details on numbers, type, dosage and in vitro activity of the included antibiotic molecules. The NMAs could not be performed for any of the selected outcome given the presence of too many disconnected components.

Conclusion

The existing evidence is insufficient to allowing for the formulation of any evidence-based therapeutic recommendation for CR-GNB sepsis. Future studies must provide a standardized definition of antibiotic regimen to drive recommendations for using combination of antibiotics that can be reliably applied to clinical practice.
Risk factors for the development of neonatal sepsis in a neonatal intensive care unit of a tertiary care hospital of Nepal
Authors: Manandhar Sulochana , Amatya Puja , Ansari Imran , Joshi Niva , Maharjan Nhukesh , Dongol Sabina , Basnyat Buddha , Dixit Sameer M. , Baker Stephen , Karkey Abhilasha
Published: June 2021

Background

Sepsis is an overwhelming and life-threatening response to bacteria in bloodstream and a major cause of neonatal morbidity and mortality. Understanding the etiology and potential risk factors for neonatal sepsis is urgently required, particularly in low-income countries where burden of infection is high and its epidemiology is poorly understood.

Methods

A prospective observational cohort study was conducted between April 2016 and October 2017 in a level three NICU at a tertiary care hospital in Nepal to determine the bacterial etiology and potential risk factors for neonatal sepsis.

Results

Among 142 NICU admitted neonates, 15% (21/142) and 32% (46/142) developed blood culture-positive and -negative neonatal sepsis respectively. Klebsiella pneumoniae (34%, 15/44) and Enterobacter spp. (25%, 11/44) were the most common isolates. The antimicrobial resistance of isolates to ampicillin (100%, 43/43), cefotaxime (74%, 31/42) and ampicillin-sulbactam (55%, 21/38) were the highest. BlaTEM (53%, 18/34) and blaKPC (46%, 13/28) were the commonest ESBL and carbapenemase genes respectively. In univariate logistic regression, the odds of sepsis increased with each additional day of use of invasive procedures such as mechanical ventilation (OR 1.086, 95% CI 1.008–1.170), umbilical artery catheter (OR 1.375, 95% CI 1.049–1.803), intravenous cannula (OR 1.140, 95% CI 1.062–1.225); blood transfusion events (OR 3.084, 95% CI 1.407–6.760); NICU stay (OR 1.109, 95% CI 1.040–1.182) and failure to breast feed (OR 1.130, 95% CI 1.060–1.205). Sepsis odds also increased with leukopenia (OR 1.790, 95% CI 1.04–3.082), increase in C-reactive protein (OR 1.028, 95% CI 1.016–1.040) and decrease in platelets count (OR 0.992, 95% CI 0.989–0.994). In multivariate analysis, increase in IV cannula insertion days (OR 1.147, 95% CI 1.039–1.267) and CRP level (OR 1.028, 95% CI 1.008–1.049) increased the odds of sepsis.

Conclusions

Our study indicated various nosocomial risk factors and underscored the need to improve local infection control measures so as to reduce the existing burden of sepsis. We have highlighted certain sepsis associated laboratory parameters along with identification of antimicrobial resistance genes, which can guide for early and better therapeutic management of sepsis. These findings could be extrapolated to other low-income settings within the region.
Prevalence and risk factors associated with multi-drug resistant organisms (MDRO) carriage among pediatric patients at the time of admission in a tertiary care hospital of a developing country. A cross-sectional study
Authors: Qureshi Sonia , Maria Noshi , Zeeshan Mohammad , Irfan Seema , Qamar Farah Naz
Published: June 2021

Background

The rise of Multidrug-resistant organisms (MDROs) poses a considerable burden on the healthcare systems, particularly in low-middle income countries like Pakistan. There is a scarcity of data on the carriage of MDRO particularly in the pediatrics population therefore, we aimed to determine MDRO carriage in pediatric patients at the time of admission to a tertiary care hospital in Karachi, Pakistan, and to identify the risk factors associated with it.

Methods

A cross-sectional study conducted at the pediatric department of Aga Khan University Hospital (AKUH) from May to September 2019 on 347 children aged 1–18 years. For identification of MDRO (i.e., Extended Spectrum Beta-Lactamase (ESBL) producers, Carbapenem Resistant Enterobacteriaceae (CRE), Vancomycin Resistant Enterococci (VRE), Methicillin Resistant Staphylococcus aureus (MRSA), Multidrug-resistant (MDR) Acinetobacter species and MDR Pseudomonas aeruginosa), nasal swabs and rectal swabs or stool samples were cultured on specific media within 72 h of hospitalization. Data was collected on a predesigned structured questionnaire on demographics, prior use of antibiotics for > 48 h in the last 6 months, history of vaccination in last 6 months, exposure to health care facility regardless of the time of exposure, ICU stay for > 72 h, and about the prior use of medical devices (urinary catheter, central venous lines etc.) in last 1 year. Statistical analysis was performed by Standard statistical software.

Results

Out of 347 participants, 237 (68.3%) were found to be MDRO carriers. Forty nine nasal swabs from 346 children (14.2%) showed growth of MRSA. The majority of the stool/rectal swabs (n = 222 of 322; 69%) collected were positive for MDRO. The most isolated species were ESBL Escherichia coli 174/222 (78.3%) followed by ESBL Enterobacter species 37/222 (16.7%) and ESBL Klebsiella pneumoniae 35/222 (15.8%). On univariate analysis, none of the risk factors showed statistically significant association with MDRO carriage.

Conclusion

Overall, a high prevalence of MDRO carriage was identified among admitted pediatric patients. Implementation of systematic screening may help to identify true burden of MDROs carriage in the health care settings.
Pregnancy-related acute kidney injury at high altitude: a retrospective observational study in a single center
Authors: Li Xin , Wu Xiaojing , Zhang Muyin , Xu Lili , Li Guohui , Wen Yumei , Wang Weiming
Published: June 2021

Background

Pregnancy-related acute kidney injury (Pr-AKI) is associated with maternal and fetal morbidity and mortality. There are few studies focusing on Pr-AKI at high altitude in the literature.

Objectives

to investigate the incidence, etiology, clinical features and maternal-fetal outcomes of Pr-AKI in women living at high altitude.

Methods

6,512 pregnant women attending the Department of Obstetrics & Gynecology at local hospital from January 2015 to December 2018 were screened for Pr-AKI. Patients with serum creatinine above normal range(> 70umol/L) then underwent assessment to confirm the diagnosis of Pr-AKI. AKI was diagnosed and staged based on Kidney Disease Improving Global Outcomes(KDIGO) guideline. Individuals meeting the Pr-AKI criteria were recruited. Their clinical data were recorded and retrospectively analyzed.

Results

Pr-AKI was identified in 136/6512(2.09 %) patients. Hypertensive disorders of pregnancy(HDP) was the leading cause of Pr-AKI(35.3 %). 4(2.9 %) women died and the majority(86.1 %) had recovered renal function before discharge. Fetal outcomes were confirmed in 109 deliveries with gestational age ≥ 20 weeks. Pre-term delivery occurred in 30(27.3 %) cases and perinatal deaths in 17(15.5 %). The rate of low birth weight infant(LBWI) and intrauterine growth restriction(IUGR) was 22.0 and 10.9 % respectively. 16(14.5 %) infants were admitted to NICU after birth. Patients with HDP had a higher cesarean rate(56.3 %). More IUGR(25.0 %) and LBWI(37.8 %) were observed in their infants with a higher risk of admission to NICU(22.0 %). High altitude might have an adverse impact on HDP-related Pr-AKI patients with earlier terminated pregnancy and more stillbirth/neonatal death. Logistic regression models indicated that uncontrolled blood pressure, high altitude and advanced AKI were associated with adverse fetal outcomes in HDP-related Pr-AKI patients.

Conclusions

Pr-AKI was not rare in high-altitude regions and caused severe fetal morbidities and mortalities. Uncontrolled blood pressure, high altitude and advanced AKI were all risk factors for adverse fetal outcomes in Pr-AKI patients, especially for those with hypertensive disorders of pregnancy.
Membranous nephropathy associated with multicentric Castleman’s disease that was successfully treated with tocilizumab: a case report and review of the literature
Authors: Saiki Ryosuke , Katayama Kan , Hirabayashi Yosuke , Oda Keiko , Fujimoto Mika , Murata Tomohiro , Nakajima Ayako , Dohi Kaoru
Published: June 2021

Background

Multicentric Castleman’s disease is a life-threatening disorder involving a systemic inflammatory response and multiple organ failure caused by the overproduction of interleukin-6. Although renal complications of Castleman’s disease include AA amyloidosis, thrombotic microangiopathy, and membranoproliferative glomerulonephritis, membranous nephropathy is relatively rare. We experienced a case of secondary membranous nephropathy associated with Castleman’s disease.

Case presentation

The patient was a 43-year-old Japanese man who had shown a high zinc sulfate value in turbidity test, polyclonal hypergammaglobulinemia, anemia, and proteinuria. A physical examination revealed diffuse lymphadenopathy, an enlarged spleen and papulae of the body trunk. A skin biopsy of a papule on the patient’s back showed plasma cells in the perivascular area and he was diagnosed with multicentric Castleman’s disease, plasma cell variant. Kidney biopsy showed the appearance of bubbling in the glomerular basement membranes in Periodic acid methenamine silver stain and electron microscopy revealed electron dense deposits within and outside the glomerular basement membranes. Since immunofluorescence study showed predominant granular deposition of IgG1 and IgG2, he was diagnosed with secondary membranous nephropathy associated with Castleman’s disease. He was initially treated with prednisolone alone, however his biochemical abnormalities did not improve. After intravenous tocilizumab (700 mg every 2 weeks) was started, his C-reactive protein elevation, anemia, and polyclonal gammopathy improved. Furthermore, his urinary protein level declined from 1.58 g/gCr to 0.13 g/gCr. The prednisolone dose was gradually tapered, then discontinued. He has been stable without a recurrence of proteinuria for more than 6 months.

Conclusions

Tocilizumab might be a treatment option for secondary membranous nephropathy associated with Castleman’s disease.
Serial magnetic resonance imaging changes of pseudotumor lesions in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a case report
Authors: Yan Yuying , Jiang Shuai , Wang Ruilin , Wang Xiang , Li Peng , Wu Bo
Published: June 2021

Background

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an adult-onset rare monogenic microvasculopathy. Its typical neuroimaging features are punctate white matter lesions or pseudotumor alterations. RVCL-S is often under-recognized and misdiagnosed because of its rarity and similar imaging manifestations to multiple sclerosis or brain malignant mass.

Case presentation

Here we report a case of a 36-year-old Chinese man who developed multiple tumefactive brain lesions spanning over two years leading to motor aphasia, cognitive decline, and limb weakness. He also presented with slight vision loss, and fundus fluorescein angiography indicated retinal vasculopathy. He underwent brain biopsies twice and showed no evidence of malignancy. Given the family history that his father died of a brain mass of unclear etiology, RVCL-S was suspected, and genetic analysis confirmed the diagnosis with a heterozygous insertion mutation in the three-prime repair exonuclease 1 gene. He was given courses of corticosteroids and cyclophosphamide but received little response.

Conclusions

The present case is one of the few published reports of RVCL-S with two-year detailed imaging data. Serial magnetic resonance images showed the progression pattern of the lesions. Our experience emphasizes that a better understanding of RVCL-S and considering it as a differential diagnosis in patients with tumefactive brain lesions may help avoid unnecessary invasive examinations and make an earlier diagnosis.
Abnormal interhemispheric functional connectivity in patients with strabismic amblyopia: a resting-state fMRI study using voxel-mirrored homotopic connectivity
Authors: Zhang Shuang , Gao Gui-Ping , Shi Wen-Qing , Li Biao , Lin Qi , Shu Hui-Ye , Shao Yi
Published: June 2021

Background

Previous studies have demonstrated that strabismus amblyopia can result in markedly brain function alterations. However, the differences in spontaneous brain activities of strabismus amblyopia (SA) patients still remain unclear. Therefore, the current study intended to employthe voxel-mirrored homotopic connectivity (VMHC) method to investigate the intrinsic brain activity changes in SA patients.

Purpose

To investigate the changes in cerebral hemispheric functional connections in patients with SA and their relationship with clinical manifestations using the VMHC method.

Material and methods

In the present study, a total of 17 patients with SA (eight males and nine females) and 17 age- and weight-matched healthy control (HC) groups were enrolled. Based on the VMHC method, all subjects were examined by functional magnetic resonance imaging. The functional interaction between cerebral hemispheres was directly evaluated. The Pearson’s correlation test was used to analyze the clinical features of patients with SA. In addition, their mean VMHC signal values and the receiver operating characteristic curve were used to distinguish patients with SA and HC groups.

Results

Compared with HC group, patients with SA had higher VMHC values in bilateral cingulum ant, caudate, hippocampus, and cerebellum crus 1. Moreover, the VMHC values of some regions were positively correlated with some clinical manifestations. In addition, receiver operating characteristic curves presented higher diagnostic value in these areas.

Conclusion

SA subjects showed abnormal brain interhemispheric functional connectivity in visual pathways, which might give some instructive information for understanding the neurological mechanisms of SA patients.
Willingness to receive future COVID-19 vaccines following the COVID-19 epidemic in Shanghai, China
Authors: Zhou Yehong , Zhang Junjie , Wu Wenwen , Liang Man , Wu Qiang-Song
Published: June 2021

Background

There are no pharmacological interventions currently available to prevent the transmission of SARS-CoV-2 or to treat COVID-19. The development of vaccines against COVID-19 is essential to contain the pandemic. we conducted a cross-sectional survey of Shanghai residents to understand residents’ willingness to be vaccinated with any future COVID-19 vaccines and take measures to further improve vaccination coverage.

Methods

We conducted a cross-sectional survey using self-administered anonymous questionnaires from 1 July to 8 September 2020. The main outcome was willingness of participants, and any children or older individuals living with them, to receive future COVID-19 vaccines. Logistic regression analyses were used to explore potential factors associated with vaccination willingness.

Results

A total of 1071 participants were asked about their willingness to receive future COVID-19 vaccines, for themselves and at least 747 children and 375 older individuals (≥60 years old) living with them. The highest proportion of expected willingness to vaccinate was among participants (88.6%), followed by children (85.3%) and older individuals (84.0%). The main reasons for reluctance to vaccinate among 119 participants were doubts regarding vaccine safety (60.0%) and efficacy (28.8%). Participants with a self-reported history of influenza vaccination were more likely to accept COVID-19 vaccines for themselves [adjusted odds ratio (OR) = 1.83; 95% confidence interval (CI): 1.19–2.82], their children (adjusted OR = 2.08; 95%CI: 1.30–3.33), and older individuals in their household (adjusted OR = 2.12; 95%CI: 1.14–3.99). Participants with older individuals in their families were less willing to vaccinate themselves (adjusted OR = 0.59; 95%CI: 0.40–0.87) and their children (adjusted OR = 0.58; 95%CI: 0.38–0.89).

Conclusions

Participants were more reluctant to accept COVID-19 vaccines for older individuals living with them. The presence of older individuals in the home also affected willingness of participants and their children to be vaccinated.
Effectiveness of XP-Endo Finisher and passive ultrasonic irrigation on intracanal medicament removal from root canals: a systematic review and meta-analysis
Authors: Zhou Jiani , Liu Tingjun , Guo Lihong
Published: June 2021

Background

XP-Endo Finisher (XPF) and passive ultrasonic irrigation (PUI) are commonly used in intracanal medicament removal. The effectiveness of these two techniques needs to be compared, and evidence-based research should be conducted.

Methods

A comprehensive literature search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar up to December 20th, 2020. The outcomes of the included trials were pooled into the Cochrane Collaboration’s Review Manager 5.3 software. Cochrane’s risk-of-bias tool 2.0 was applied to assess the risk of bias.

Results

Nine articles were included in this systematic review and processed for data extraction, and eight studies were identified for meta-analysis. In general, the use of PUI showed better medicament removal effectiveness than XPF (odds ratio [OR]: 3.09; 95% confidence interval [CI], 1.96–4.86; P < 0.001). PUI was also significantly more efficient than XPF in the apical third (OR: 3.42; 95% CI, 1.32–8.84; P = 0.01). For trials using sodium hypochlorite (NaOCl) alone, PUI was also significantly more effective than XPF on intracanal medicaments removal (OR: 5.23; 95% CI, 2.79–9.82; P < 0.001). However, there was no significant difference between PUI and XPF when NaOCl and ethylenediaminetetraacetic acid (EDTA) were used in combination (OR: 1.51; 95% CI, 0.74–3.09; P = 0.26). In addition, for studies whose intracanal medicament periods were two weeks, the effectiveness of PUI was statistically better than the XPF (OR: 7.73; 95% CI, 3.71–16.07; P < 0.001). Nevertheless, for trials whose intracanal medicament time was one week or over two weeks, no differences between the XPF and PUI were found (OR: 1.54; 95% CI, 0.74–3.22; P = 0.25) (OR: 1.42; 95% CI, 0.44–4.61; P = 0.56).

Conclusions

The meta-analysis is the first study to quantitatively compare the effectiveness of XPF and PUI techniques on intracanal medicaments removal. With rigorous eligibility criteria, the study only included high-quality randomised controlled trials. The study indicated that PUI might be superior over XPF techniques for removing intracanal medicaments from artificial standardized grooves and cavities in the root canal system. The anatomical areas, irrigation protocol, and intracanal medicaments time may influence the cleaning efficacy.
Cognitive changes and neural correlates after oral rehabilitation procedures in older adults: a protocol for an interventional study
Authors: Hedberg Linn , Ekman Urban , Nordin Love Engström , Smedberg Jan-Ivan , Skott Pia , Seiger Åke , Sandborgh-Englund Gunilla , Westman Eric , Kumar Abhishek , Trulsson Mats
Published: June 2021

Background

Epidemiological studies show an association between masticatory function and cognitive impairment. This has further strengthened the notion that tooth loss and impaired masticatory function may be risk factors for dementia and cognitive decline. Animal experiments have indicated a causal relationship and several possible mechanisms have been discussed. This evidence is, however, lacking in humans. Therefore, in the current interventional study, we aim to investigate the effect of rehabilitation of masticatory function on cognition in older adults.

Methods

Eighty patients indicated for prosthodontic rehabilitation will be randomly assigned to an experimental or a control group. Participants will conduct neuropsychological assessments, masticatory performance tests, saliva tests, optional magnetic resonance imaging, and answer questionnaires on oral health impact profiles and hospital anxiety and depression scale before, 3 months, and 1 year after oral rehabilitation. The difference between the two groups is that the control group will be tested an additional time, (at an interval of about 3 months) before the onset of the oral rehabilitation procedure. The primary outcome is a change in measures of episodic memory performance.

Discussion

Although tooth loss and masticatory function are widespread in older people, it is still an underexplored modifiable risk factor potentially contributing to the development of cognitive impairment. If rehabilitation of masticatory function shows positive effects on the neurocognitive function, this will have great implications on future health care for patients with impaired masticatory status. The present project may provide a new avenue for the prevention of cognitive decline in older individuals.

Trial registration: The protocol for the study was retrospectively registered in ClinicalTrials.gov Identifier: NCT04458207, dated 02-07-2020.