bluuebunny/crossref_metadata_2025 huggingface dataset:
Clarifying Values: An Updated and Expanded Systematic Review and Meta-Analysis
Authors: Witteman Holly O. , Ndjaboue Ruth , Vaisson Gratianne , Dansokho Selma Chipenda , Arnold Bob , Bridges John F. P. , Comeau Sandrine , Fagerlin Angela , Gavaruzzi Teresa , Marcoux Melina , Pieterse Arwen , Pignone Michael , Provencher Thierry , Racine Charles , Regier Dean , Rochefort-Brihay Charlotte , Thokala Praveen , Weernink Marieke , White Douglas B. , Wills Celia E. , Jansen Jesse
Published: January 2021

Background

Patient decision aids should help people make evidence-informed decisions aligned with their values. There is limited guidance about how to achieve such alignment.

Purpose

To describe the range of values clarification methods available to patient decision aid developers, synthesize evidence regarding their relative merits, and foster collection of evidence by offering researchers a proposed set of outcomes to report when evaluating the effects of values clarification methods.

Data Sources

MEDLINE, EMBASE, PubMed, Web of Science, the Cochrane Library, CINAHL

Study Selection

We included articles that described randomized trials of one or more explicit values clarification methods. From 30,648 records screened, we identified 33 articles describing trials of 43 values clarification methods.

Data Extraction

Two independent reviewers extracted details about each values clarification method and its evaluation.

Data Synthesis

Compared to control conditions or to implicit values clarification methods, explicit values clarification methods decreased the frequency of values-disgruent choices (risk difference -0.04 95% CI [-0.06 to -0.02], p<.001) and decisional regret (standardized mean difference -0.20 95% CI [-0.29 to -0.11], p<0.001). Multicriteria decision analysis led to more values-congruent decisions than other values clarification methods (Chi-squared(2)=9.25, p=.01). There were no differences between different values clarification methods regarding decisional conflict (Chi-squared(2)=6.08, p=.05).

Limitations

Some meta-analyses had high heterogeneity. We grouped values clarification methods into broad categories.

Conclusions

Current evidence suggests patient decision aids should include an explicit values clarification method. Developers may wish to specifically consider multicriteria decision analysis. Future evaluations of values clarification methods should report their effects on decisional conflict, decisions made, values congruence, and decisional regret.
Complementary frailty and mortality prediction models on older patients as a tool for assessing palliative care needs
Authors: Blanes-Selva Vicent , Doñate-Martínez Ascensión , Linklater Gordon , García-Gómez Juan M.
Published: January 2021

Introduction

Palliative care (PC) has demonstrated benefits for life-limiting illnesses. Nowadays, there is a growing consensus about giving access these care services to non-cancer older patients. Bad survival prognosis and patients’ decline are working criterions to guide PC decision making.

Objective

The main aim of this work is to propose complementary models based on machine learning approaches to predict frailty and mortality in older patients in the context of supporting PC decision making.

Methods

The dataset used in this study is composed by 39,310 hospital admissions for 19,753 older patients (age >= 65) from January 1st, 2011 to December 30th, 2018. Predictive models based on Gradient Boosting Machines and Deep Neural Networks were implemented for binary one-year mortality classification, survival estimation and binary one-year frailty classification. Besides, we tested the similarity between mortality and frailty distributions.

Results

The one-year mortality classifier achieved an AUC ROC of 0.87 [0.86, 0.87]; whereas the mortality regression model achieved an MAE of 333.13 [323.10, 342.49] days. Moreover, the one-year frailty classifier obtained an AUC ROC of 0.89 [0.88, 0.90].

Conclusions

The performance of our one-year mortality model is competitive with the current state-of-the-art. Besides, to our knowledge, this is the first study predicting one-year frailty status based on a frailty index. We found mortality and frailty criteria are weakly correlated and have different distributions; therefore, we interpreted them as complementary assessment measurements for palliative care decision making. Predictive models are accessible as an online tool athttp://demoiapc.upv.es. The models presented here may be part of decision support systems for care services in non-cancer older patients after their external validation.
Does the posteromedial cortex play a primary role for the capacity for consciousness in rats?
Authors: Arena A. , Juel B.E. , Comolatti R. , Thon S. , Storm J.F.
Published: January 2021

It remains unclear how specific cortical regions contribute to the brain’s overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brain’s overall capacity for consciousness.

We recorded electroencephalographic (EEG) responses to cortical electrical stimulation in 6 rats, and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power (HF/LF) from spontaneous EEG activity at each electrode. We repeated these measurements during wakefulness, and under the influence of ketamine anaesthesia at two doses: the minimal dose needed to induce behavioural unresponsiveness and twice this dose.

We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly down with deeper anaesthesia. The high-dose effect was selectively associated with reduced HF/LF ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia, was associated with similar spectral changes in frontal, but not posterior cortical regions.

These findings seem to support the claim that the posteromedial cortex may play a primary role for the capacity for consciousness. Such region-specific associations between cortical activation and the overall capacity for consciousness must be accounted for by theories of consciousness.
Single neuron firing cascades underlie global spontaneous brain events
Authors: Liu Xiao , Leopold David A. , Yang Yifan
Published: January 2021

The resting brain consumes enormous energy and shows highly organized spontaneous activity. To investigate how this activity is manifest among single neurons, we analyzed spiking discharges of ∼10,000 isolated cells recorded from multiple cortical and subcortical regions of the mouse brain during immobile rest. We found that firing of a significant proportion (∼70%) of neurons conformed to a ubiquitous, temporally sequenced cascade of spiking that was synchronized with global events and elapsed over timescales of 5-10 seconds. Across the brain, two intermixed populations of neurons supported orthogonal cascades. The relative phases of these cascades determined, at each moment, the response magnitude evoked by an external visual stimulus. Furthermore, the spiking of individual neurons embedded in these cascades was time locked to physiological indicators of arousal, including local field potential (LFP) power, pupil diameter, and hippocampal ripples. These findings demonstrate that the large-scale coordination of low-frequency spontaneous activity, which is commonly observed in brain imaging and linked to arousal, sensory processing, and memory, is underpinned by sequential, large-scale temporal cascades of neuronal spiking across the brain.
Association between clinical characteristics and laboratory findings with outcome of hospitalized COVID-19 patients, a report from northeast of Iran
Authors: Sobhani Sahar , Aryan Reihaneh , Kalantari Elham , Soltani Salman , Malek Nafise , Pirzadeh Parisa , Yarahmadi Amir , Aghaee Atena
Published: January 2021

Coronavirus disease 2019 (COVID-19) was first discovered in December 2019 in China and has rapidly spread worldwide. Clinical characteristics, laboratory findings, and their association with the outcome of patients with COVID-19 can be decisive in management and early diagnosis. Data were obtained retrospectively from medical records of 397 hospitalized COVID-19 patients between February and May 2020 in Imam Reza hospital, northeast of Iran. Clinical and laboratory features were evaluated among survivors and non-survivors. The correlation between variables and duration of hospitalization and admission to the Intensive Care Unit (ICU) was determined. Male sex, age, hospitalization duration, and admission to ICU were significantly related to mortality rate. Headache was a more common feature in patients who survived (p = 0.017). It was also related to a shorter stay in the hospital (p = 0.032) as opposed to patients who experienced chest pain (p = 0.033). Decreased levels of consciousness and dyspnea were statistically more frequent in non-survivors (p = 0.003 and p = 0.011, respectively). Baseline white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were significantly higher in non-survivors (p < 0.001). Patients with higher WBC and CRP levels were more likely to be admitted to ICU (p = 0.009 and p = 0.001, respectively). Evaluating clinical and laboratory features can help clinicians find ways for risk stratifying patients and even make predictive tools. Chest pain, decreased level of consciousness, dyspnea, and increased CRP and WBC levels seem to be the most potent predictors of severe prognosis.
Long-read metagenomics of soil communities reveals phylum-specific secondary metabolite dynamics
Authors: Van Goethem Marc W. , Osborn Andrew R. , Bowen Benjamin P. , Andeer Peter F. , Swenson Tami L. , Clum Alicia , Riley Robert , He Guifen , Koriabine Maxim , Sandor Laura , Yan Mi , Daum Chris G. , Yoshinaga Yuko , Makhalanyane Thulani P. , Garcia-Pichel Ferran , Visel Axel , Pennacchio Len A. , O’Malley Ronan C. , Northen Trent R.
Published: January 2021

Microbial biosynthetic gene clusters (BGCs) encoding secondary metabolites are thought to impact a plethora of biologically mediated environmental processes, yet their discovery and functional characterization in natural microbiomes remains challenging. Here we describe deep long-read sequencing and assembly of metagenomes from biological soil crusts, a group of soil communities that are rich in BGCs. Taking advantage of the unusually long assemblies produced by this approach, we recovered nearly 3,000 BGCs for analysis, including 695 novel, full-length BGCs. Functional exploration through metatranscriptome analysis of a 3-day wetting experiment uncovered phylum-specific BGC expression upon activation from dormancy, elucidating distinct roles and complex phylogenetic and temporal dynamics in wetting processes. For example, a pronounced increase in BGC transcription occurs at night in cyanobacteria but not in other phyla, implicating BGCs in nutrient scavenging roles and niche competition. Taken together, our results demonstrate that long-read metagenomic sequencing combined with metatranscriptomic analysis provides a direct view into the functional dynamics of BGCs in environmental processes and suggests a central role of secondary metabolites in maintaining phylogenetically conserved niches within biocrusts.
NCodR: A multi-class SVM classification to distinguish between non-coding RNAs in Viridiplantae
Authors: Nithin Chandran , Mukherjee Sunandan , Basak Jolly , Bahadur Ranjit Prasad
Published: January 2021

Non-coding RNAs (ncRNAs) are major players in the regulation of gene expression. This study analyses seven classes of ncRNAs in plants using sequence and secondary structure-based RNA folding measures. We observe distinct regions in the distribution of AU content along with overlapping regions for different ncRNA classes. Additionally, we find similar averages for minimum folding energy index across various ncRNAs classes except for pre-miRNAs and lncRNAs. Various RNA folding measures show similar trends among the different ncRNA classes except for pre-miRNAs and lncRNAs. We observe different k-mer repeat signatures of length three among various ncRNA classes. However, in pre-miRs and lncRNAs, a diffuse pattern of k-mers is observed. Using these attributes, we train eight different classifiers to discriminate various ncRNA classes in plants. Support-vector machines employing radial basis function show the highest accuracy (average F1 of ~91%) in discriminating ncRNAs, and the classifier is implemented as a web server, NCodR.
Using an Ecological and Biological Framing for an Anti-racist Covid-19 Approach
Authors: Camargo Araceli , Hossain Elahi , Aliko Sarah , Akinola-Odusola Daniel , Artus Josh , Kelman Ilan
Published: January 2021

In the United States and the United Kingdom COVID-19 has disproportionately affected Black, Indigenous and People of Colour (BIPOC) and Black, Asian and Minority Ethnic (BAME) people respectively. Multiple studies identify environmental factors such as overcrowded housing and poor workplace conditions as contributing factors for the disproportionate COVID-19 rates amongst BAME and BIPOC communities. This paper will show that to fully understand the phenomenon, both an ecological and biological approach is needed. An ecological approach highlights how a person’s habitat and the experiences within it mediate their susceptibility to disease. Moreover, to understand how this mediation works, this paper will use allostatic load as a biological pathway to link a person to their habitat and the poor health outcomes that contributed to COVID-19 susceptibility. In introducing this new approach, the paper will serve as an anti-racist framework for understanding how COVID-19 affected BAME and BIPOC communities. It is anti-racist by centring poor health outcomes on the habitats people are forced to live in due to structural racism rather than the physiology of a person’s race or ethnicity. This is important in order to avoid similar crises in the future and to improve the health of marginalised communities.
Harnessing testing strategies and public health measures to avert COVID-19 outbreaks during ocean cruises
Authors: Chowell Gerardo , Dahal Sushma , Bono Raquel , Mizumoto Kenji
Published: January 2021

To ensure the safe operation of schools, workplaces, nursing homes, and other businesses during COVID-19 pandemic there is an urgent need to develop cost-effective public health strategies. Here we focus on the cruise industry which was hit early by the COVID-19 pandemic, with more than 40 cruise ships reporting COVID-19 infections. We apply mathematical modeling to assess the impact of testing strategies together with social distancing protocols on the spread of the novel coronavirus during ocean cruises using an individual-level stochastic model of the transmission dynamics of COVID-19. We model the contact network, the potential importation of cases arising during shore excursions, the temporal course of infectivity at the individual level, the effects of social distancing strategies, different testing scenarios characterized by the test’s sensitivity profile, and the testing frequency. Our findings indicate that PCR testing at embarkation and daily testing of all individuals aboard, together with increased social distancing and other public health measures, should allow for rapid detection and isolation of COVID-19 infections and dramatically reducing the probability of onboard COVID-19 community spread. In contrast, relying only on PCR testing at embarkation would not be sufficient to avert outbreaks, even when implementing substantial levels of social distancing measures.
Next generation vaccine platform: polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine
Authors: Lam Jian Hang , Khan Amit Kumar , Cornell Thomas Andrew , Dress Regine Josefine , Chia Teck Wan , William Yeow Wen Wang , Mohd-Ismail Nur Khairiah , Venkatraman Shrinivas , Ng Kim Tien , Tan Yee-Joo , Anderson Danielle E. , Ginhoux Florent , Nallani Madhavan
Published: January 2021

Multiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising of polybutadiene-b-polyethylene glycol and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells, which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of memory CD4+and CD8+T cells that produce Th1 cytokines. This study is an important step towards the development of an efficacious vaccine in humans.
mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants
Authors: Wu Kai , Werner Anne P. , Moliva Juan I. , Koch Matthew , Choi Angela , Stewart-Jones Guillaume B. E. , Bennett Hamilton , Boyoglu-Barnum Seyhan , Shi Wei , Graham Barney S. , Carfi Andrea , Corbett Kizzmekia S. , Seder Robert A. , Edwards Darin K.
Published: January 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative infection of a global pandemic that has led to more than 2 million deaths worldwide. The Moderna mRNA-1273 vaccine has demonstrated ~94% efficacy in a Phase 3 study and has been approved under Emergency Use Authorization. The emergence of SARS-CoV-2 variants with mutations in the spike protein, most recently circulating isolates from the United Kingdom (B.1.1.7) and Republic of South Africa (B.1.351), has led to lower neutralization from convalescent serum by pseudovirus neutralization (PsVN) assays and resistance to certain monoclonal antibodies. Here, using two orthogonal VSV and lentivirus PsVN assays expressing spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants, we assessed the neutralizing capacity of sera from human subjects or non-human primates (NHPs) that received mRNA-1273. No significant impact on neutralization against the B.1.1.7 variant was detected in either case, however reduced neutralization was measured against the mutations present in B.1.351. Geometric mean titer (GMT) of human sera from clinical trial participants in VSV PsVN assay using D614G spike was 1/1852. VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize. Similarly, sera from NHPs immunized with 30 or 100μg of mRNA-1273 had VSV PsVN GMTs of ~ 1/323 or 1/404, respectively, against the full B.1.351 spike variant with a ~ 5 to 10-fold reduction compared to D614G. Individual mutations that are characteristic of the B.1.1.7 and B.1.351 variants had a similar impact on neutralization when tested in VSV or in lentivirus PsVN assays. Despite the observed decreases, the GMT of VSV PsVN titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination.
Modeling autism-associated SHANK3 deficiency using human cortico-striatal organoids generated from single neural rosettes
Authors: Wang Yueqi , Chiola Simone , Yang Guang , Russell Chad , Armstrong Celeste J. , Wu Yuanyuan , Spampanato Jay , Tarboton Paisley , Chang Amelia N. , Harmin David A. , Vezzoli Elena , Besusso Dario , Cui Jun , Cattaneo Elena , Kubanek Jan , Shcheglovitov Aleksandr
Published: January 2021

Our understanding of the human brain is limited by the lack of experimental models to mechanistically probe the properties of brain cells at different developmental stages under normal and pathological conditions. We developed a new method for generating human cortico-striatal organoids from stem cell-derived single neural rosettes (SNRs) and used it to investigate cortico-striatal development and deficits caused by the deficiency of an autism- and intellectual disability-associated geneSHANK3. We show that SNR-derived organoids consist of different cortico-striatal cells, including pallial and subpallial progenitors, primary cortical and striatal neurons, interneurons, as well as macroglial and mural cells. We also demonstrate that neurons in SNR-derived organoids are predictably organized, functionally mature, and capable of establishing functional neural networks. Interestingly, we found that the cellular and electrophysiological deficits in SHANK3-deficient SNR-derived organoids are dependent on the level of SHANK3 expression and that organoids with complete hemizygousSHANK3deletion have disrupted expression of several clustered protocadherins and multiple primate-specific zinc-finger genes. Together, this study describes a new method for using SNRs to generate organoids, provides new insights into the cell lineages associated with human cortico-striatal development, and identifies specific molecular pathways disrupted by hemizygousSHANK3deletion, which is the most common genetic abnormality detected in patients with 22q13 deletion syndrome.
Size-dependent strain in fivefold twins of gold
Authors: Wu Hao , Yu Rong , Zhu Jing , Chen Wei , Li Yadong , Wang Tao
Published: January 2021

Multiple twinned structures are common in low-dimensional materials. They are intrinsically strained due to the geometrical constraint imposed by the non-crystallographic fivefold symmetry. In this study, the strain distributions in sub-10 nm fivefold twins of gold have been analyzed by combining aberration-corrected transmission electron microscopy and first-principles calculations. Bending of atomic planes has been measured by both experiments and calculations, and its contribution to the filling of the angular gap was shown to be size-dependent.
The role of hydrogen bonding in the incommensurate modulation of myo-inositol camphor ketal
Authors: Savic Viktor , Eder Felix , Göb Christian , Mihovilovic Marko D. , Stanetty Christian , Stöger Berthold
Published: January 2021

myo-Inositol-2,3-D-camphor ketal crystallizes as an incommensurate structure with the C2(0σ2½) superspace group symmetry [σ2 = 0.1486 (3) at 100 K]. The bornane and myo-inositol moieties aggregate in distinct layers extending parallel to (001). The myo-inositol rings are connected by a complex hydrogen-bonding network extending in two dimensions, which is disordered in the basic structure and (mostly) ordered in the actual modulated structure. The domains of definition of the H atoms in internal space were derived by chemical reasoning and modeled with crenel functions. By tracing the hydrogen bonding, distinct chains, which are periodic in the [100] direction, are identified. These chains possess one of two possible orientations with respect to the hydrogen bonding. The incommensurate modulation is characterized by a non-periodic succession of the two chain orientations in the [010] direction. On heating, the σ2-component of the modulation wave vector decreases from σ2 = 0.1486 (3) at 100 K to σ2 = 0.1405 (6) at 430 K, which means that the periodicity of the modulation wave increases. No order–disorder phase transition was evidenced up to the melting point (with decomposition).
A Coding Scheme for Studying Group Interactions in International Negotiations: A Methodological Advance on the IPA protocol
Authors: Dowie Cheryl , De Bruijn Oscar , De Mattos Claudio
Published: January 2021

Our increasingly complex global business environment inevitably brings counterparts to the negotiation table. However, the lack of user‐friendly coding systems, and other associated complexities over the last 6 decades, may have discouraged scholars to further their research in negotiation, communication, and its related fields. A viable coding scheme in place can help scholars and practitioners unfold the negotiation process by explaining the ‘cause and effect’ relationship within this social context. We propose a 24‐category typology that stems from Bales’ IPA model, with Field Theory as our theoretical framework. Our empirical data comprises of two‐party negotiation simulations. Some distinct features of our proposed scheme when compared to the IPA model are reduced coding time experienced, a straightforward framework that is less complicated to follow, a valid and reliable scheme and lastly, a scheme with a robust theoretical‐methodological underpinning in its development. The reliability of our scheme is determined through Krippendorff's Alpha (α). Through our methodological contribution, we aim to investigate the dynamics in small group interactions; and encourage future scholars to study the multidimensional nature of international negotiations.
Asset Redeployability and Corporate Tax Avoidance
Authors: Hasan Mostafa Monzur , Habib Ahsan , Alam Nurul
Published: January 2021

Using a large sample of US data, we examine the relationship between asset redeployability and corporate tax avoidance. We also examine the extent to which asset redeployability influences tax avoidance directly and indirectly (through financing constraints channel). We find a significant negative relationship between asset redeployability and tax avoidance, implying that firms with more redeployable assets tend to engage in less tax avoidance. We also confirm that asset redeployability reduces tax avoidance both directly and indirectly (through reducing financing constraints). These results are robust to alternative specifications of asset redeployability and corporate tax avoidance, and to the use of a two‐stage least squares (2SLS) analysis to mitigate any endogeneity concerns relating to omitted variables, reverse causality, and model misspecification. Overall, these findings extend our existing understanding of the implication of asset redeployability in an accounting context and demonstrate that redeployability of assets has important implication for corporate tax planning.
Elevated lipids are associated with reduced regional brain structure in youth with bipolar disorder
Authors: Kennedy Kody G. , Islam Alvi H. , Grigorian Anahit , Fiksenbaum Lisa , Mitchell Rachel H.B. , McCrindle Brian W. , MacIntosh Bradley J. , Goldstein Benjamin I.
Published: January 2021

Objective

Abnormal blood lipid levels are common in bipolar disorder (BD) and correlate with mood symptoms and neurocognition. However, studies have not examined the lipid–brain structure association in BD or youth.

Methods

This study examined low‐density lipoprotein (LDL‐C), high‐density lipoprotein (HDL‐C), triglycerides, and total cholesterol (TC) levels in relation to brain structure utilizing T1‐weighted images, among participants ages 13–20 with BD (n = 55) and healthy controls (HC; n = 47). General linear models investigated group differences in the association of lipids with anterior cingulate cortex (ACC), hippocampus, and inferior parietal lobe structure, controlling for age, sex, body mass index, and intracranial volume. For significant associations, post hoc within‐group analyses were undertaken. Exploratory vertex‐wise analyses further investigated group differences in the lipid–brain structure association.

Results

There were significant group differences in the association of LDL‐C (β = −0.29 p = 0.001), and TC (β = −0.21 p = 0.016), with hippocampal volume, and triglycerides with ACC volume (β = −0.25 p = 0.01) and area (β = −0.26 p = 0.004). Elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC. Post hoc analyses revealed that elevated LDL‐C (β = −0.27 p = 0.007) and reduced HDL‐C (β = 0.24 p = 0.01) were associated with smaller hippocampal volume in the BD group. Exclusion of BD second‐generation antipsychotic users did not alter these results. Vertex‐wise analyses further showed that elevated lipids were associated with smaller brain structure to a significantly greater extent in BD vs HC, across the cortex.

Conclusion

Elevated lipids are associated with smaller brain structure in BD. Research evaluating lipid–brain structure associations prospectively and whether lipid optimization has salutary effects on brain structure is necessary.
Cognitive impairment in preeclampsia complicated by eclampsia and pulmonary edema after delivery
Authors: Bergman Lina , Thorgeirsdottir Lilja , Elden Helen , Hesselman Susanne , Schell Sonja , Ahlm Evelina , Aukes Annet , Cluver Catherine
Published: January 2021

Introduction

We aimed to assess cognitive function in women with preeclampsia stratified by severity, before and after onset of disease.

Material and methods

Prospective study performed at a referral hospital in Cape Town, South Africa. Pregnant women between 20 and 42 weeks of gestation with eclampsia, pulmonary edema and preeclampsia without severe features, and a normotensive pregnancy were approached. Women were included at diagnosis of preeclampsia or at admission for delivery (women with normotensive pregnancies). Two cognitive assessments, the Cognitive Failure Questionnaire to assess the cognitive function subjectively before inclusion in the study, and Montreal Cognitive Assessment to assess the current cognitive function objectively before discharge from the hospital after delivery, were performed.

Results

We included 61 women with eclampsia, 28 with preeclampsia complicated by pulmonary edema, 38 with preeclampsia without severe features, and 26 with normotensive pregnancies. There was no difference in cognitive function from early pregnancy between groups. Women with eclampsia and preeclampsia complicated by pulmonary edema scored lower on the Montreal Cognitive Assessment at time of discharge compared with women with normotensive pregnancies. The results were attenuated in pulmonary edema after adjustment for confounders.

Conclusions

Women with preeclampsia complicated by pulmonary edema and in particular eclampsia had impaired cognitive function after onset of disease compared with women with normotensive pregnancies. The impairment did not seem to be present before onset of disease. Women with preeclampsia without severe features did not have impaired cognitive function.
Reduced‐port surgery for right paraduodenal hernia in an adult patient: A case report and review of the literature
Authors: Oshita Ko , Yoshimitsu Masanori , Yunoki Kosuke , Imaoka Kouki , Yano Takuya , Idani Hitoshi , Okajima Masazumi
Published: January 2021

Paraduodenal hernia (PDH) is a congenital internal hernia caused by an abnormal rotation of the midgut during embryotic life; it is characterized as right‐ or left‐sided according to the hernial sac location. Herein, we describe a case of a 30‐year‐old male patient who was preoperatively diagnosed with right PDH and underwent successful laparoscopic repair using reduced‐port surgery (RPS). The patient presented with postprandial nausea, vomiting, and upper abdominal pain. Contrast‐enhanced CT and an upper gastric series led to the preoperative diagnosis of right PDH associated with intestinal malrotation. Thereafter, laparoscopic repair using RPS was performed. After the small bowels were reduced from the hernial sac, the hernial orifice was opened widely and laterally. The postoperative course was uneventful. This is the first report of a successful laparoscopic surgery on right PDH using RPS.
The association of maternal folic acid supplementation and prenatal folate and vitamin B12 concentrations with child dental development
Authors: Dhamo Brunilda , Jaddoe Vincent W. V. , Steegers Eric A. P. , Wolvius Eppo B. , Ongkosuwito Edwin M.
Published: January 2021

Objective

Low folic acid, folate and vitamin B12 might affect tooth formation and mineralization. The conversion of folic acid into folate is catalysed by the methylenetetrahydrofolate (MTHFR) enzyme which is encoded by the MTHFR gene. Among 3728 mothers and their 10‐year‐old children from the Generation R Study, we investigated associations of maternal folic acid supplementation and prenatal folate and vitamin B12 concentrations with child dental development. Secondly, we checked the modifying effect of MTHFR‐C677T polymorphism.

Methods

Information on folic acid supplementation was obtained by questionnaires. Concentrations of folate and vitamin B12 were measured from venous samples taken in early pregnancy. Developmental stages of teeth were defined by the Demirjian method at the age‐10 assessment. In addition, dental age of the children was calculated using the Dutch standard. GLM and multivariate linear regression models were built to study the associations.

Results

Folic acid supplementation started when pregnancy was known (β = −0.09; 95% CI: −0.17, −0.01) and folic acid supplementation started prior to known pregnancy (β = −0.12; 95% CI: −0.20, −0.04) were both associated with decelerated dental development by 1‐2 months lower dental age of 10‐year‐old children. Folate (β = −0.02, 95% CI: −0.05, 0.02) and vitamin B12 (β = 0.03, 95% CI: −0.00, 0.06) were not associated with dental age. MTHFR‐C677T did not modify the associations.

Conclusions

Maternal folic acid supplementation delays dental development of children by 1‐2 months dental age, whereas maternal folate and vitamin B12 concentrations in early pregnancy do not affect the timing of child dental development.
Comprehensive analysis of alcohol policies in the Latin America and the Caribbean
Authors: Medina‐Mora María Elena , Monteiro Maristela , Rafful Claudia , Samano Itzel
Published: January 2021

Introduction

The aim of this paper is to describe the context of alcohol use and problems in Latin America and the Caribbean (LAC), the environmental context for alcohol‐related policy, drinking trends, harm and policy and to systematically review policies implemented to reduce alcohol‐related burden.

Methods

LAC‐based studies relating to the existence and effects of public health‐oriented alcohol policies are described. The review is informed by a literature search of alcohol policies in LAC in English and in Spanish in several platforms, and in publications of international organisations, including grey and scientific literature.

Results

Only 30 documents measuring policy impact were identified for the policy analysis. Most of the policies are focused on brief interventions, and most have little evidence on their effectiveness. Alcohol taxation and drink‐driving policies appear to have the highest impact if enforcement is adequately performed.

Discussion and Conclusions

The studies reviewed indicate a pattern of modelling policy interventions but implementing only a few, and a paucity of sustained or systematic evaluations. Although patterns of use indicate alcohol use should be a major public health priority, only a few countries in LAC have a national policy or plan dedicated to alcohol, representing a low political commitment to considering alcohol as a public health priority.
Klarzellakanthome
Authors: Wagner Gunnar , Back Walter , Sachse Michael Max
Published: January 2021

Das Klarzellakanthom ist ein selten diagnostizierter Tumor, der aufgrund variabler klinischer Morphologie in der Regel erst anhand seiner histopathologischen Merkmale erkannt wird. Die Primäreffloreszenz ist eine wenige Millimeter durchmessende rote Papel, die als einzelne Läsion häufig an den unteren Extremitäten auftritt. In der Dermatoskopie gilt eine Perlenkettenstruktur der Gefäße (strings of pearls) als weitgehend spezifischer Befund der Klarzellakanthome. Im Gegensatz zu dem zunächst uncharakteristischen klinischen Befund ist das histopathologische Bild der Klarzellakanthome durch eine typische kompakte, scharf begrenzte Akanthose gekennzeichnet, bestehend aus hellen, PAS‐reaktiven Keratinozyten. Bei ungeklärter Ätiologie und Pathogenese ist auch die Nosologie der Klarzellakanthome umstritten. Diskutiert wird die Einordnung als kutane Neoplasie oder als reaktive inflammatorische Dermatose.
Aktualisierung„ Systemtherapie bei Neurodermitis“ zur S2k‐Leitlinie Neurodermitis
Authors: Werfel Thomas , Heratizadeh Annice , Aberer Werner , Ahrens Frank , Augustin Matthias , Biedermann Tilo , Diepgen Thomas , Fölster‐Holst Regina , Kahle Julia , Kapp Alexander , Nemat Katja , Peters Eva , Schlaeger Martin , Schmid‐Grendelmeier Peter , Schmitt Jochen , Schwennesen Thomas , Staab Doris , Traidl‐Hoffmann Claudia , Werner Ricardo , Wollenberg Andreas , Worm Margitta , Ott Hagen
Published: January 2021

Die vorliegende Leitlinie ist eine Aktualisierung vom August 2020 zu Systemtherapeutika der 2015 publizierten AWMF‐S2k‐Leitlinie Neurodermitis. Anlass für die Aktualisierung dieses Kapitels der Leitlinie waren die aktuellen Entwicklungen zur Systemtherapie der Neurodermitis. In der vorliegenden Leitlinie sind die wissenschaftliche Datenlage und die konsentierten Empfehlungen zur Systemtherapie bei Neurodermitis aufgeführt. Aufgrund der Neuzulassung von Dupilumab für die Behandlung mittelschwer bis schwer ausgeprägter Neurodermitis, die mit topischen Medikamenten alleine nicht ausreichend behandelbar ist, wurde dieser Teil der Leitlinie jetzt angepasst und neu konsentiert. Die Indikation zur Systemtherapie und das therapeutische Ansprechen auf die topische und systemische Behandlung sollen in Klinik und Praxis in geeigneter Form erfasst und dokumentiert werden. Eine standardisierte Dokumentation der Indikation zur Systemtherapie bei Neurodermitis kann empfohlen werden und ist ebenfalls Bestandteil des hier vorliegenden aktualisierten Kapitels der Leitlinie.
Unraveling antimicrobial resistance in Helicobacter pylori: Global resistome meets global phylogeny
Authors: Domanovich‐Asor Tal , Craddock Hillary A. , Motro Yair , Khalfin Boris , Peretz Avi , Moran‐Gilad Jacob
Published: January 2021

Background

Antimicrobial resistance (AMR) in Helicobacter pylori is increasing globally and can result in treatment failure and inappropriate antibiotic usage. This study used whole genome sequencing (WGS) to conduct an analysis of the H. pylori resistome and phylogeny.

Materials/methods

A total of 1040 H. pylori isolate sequences were retrieved. Analysis was conducted via an in‐house bioinformatics pipeline targeting point mutations in selected genes frequently associated with AMR (pbp1A, 23S rRNA, gyrA, rdxA, frxA, and rpoB) and phylogenomic analyses using core genome multilocus sequence typing (cgMLST).

Results

Phylogenomic analysis revealed a notable geographical clustering of H. pylori genomes across world regions, but large distances of more than 1000 loci between isolates on individual branches were observed. Resistome analysis revealed the prevalence of common mutations which have previously been found to correlate with phenotypic antibiotic resistance; the most common point mutations for each gene were S589G (pbp1A, 48.8% of perfect aligned sequences), A2143G (23S rRNA, 27.4% of perfectly aligned sequences), N87 K\I\Y (gyrA, 14.7% of perfectly aligned sequences), R131K (rdxA, 65.7% of perfectly aligned sequences), and C193S (frxA, 62.6% of perfectly aligned sequences).

Conclusions

This is the largest study to date featuring the global phylogeny of H. pylori in conjunction with a global snapshot of the H. pylori resistome based on >1000 genomes. Further analyses that combine WGS and phenotypic methods will provide further understanding of the association between the mutations and resistance.
Clinical and molecular characteristics of imerslund‐gräsbeck syndrome: First report of a novel Frameshift variant in Exon 11 of AMN gene
Authors: Elshinawy Mohamed , Gao Harry H. , Al‐Nabhani Dana M. , Al‐Thihli Khalid A.
Published: January 2021

Introduction

Imerslund‐Gräsbeck syndrome (IGS) is a rare autosomal‐recessive disorder characterized by selective vitamin B12 malabsorption, megaloblastic anemia, and proteinuria. The precise incidence of this disorder is unknown in the Middle East and Arab countries. The disease is caused by a homozygous variant in either AMN or CUBN genes. In addition, some compound heterozygous variants are reported.

Methods

Clinical and laboratory data of patients diagnosed with IGS in Oman were retrospectively collected. Mutation analysis for all genes involved in vitamin B12/folic acid metabolism and megaloblastic anemia was conducted using next‐generation sequencing (NGS).

Results

Three siblings (2 girls and a boy) have been diagnosed with the condition. They exhibit a phenotypic variability with different age of presentation and different spectrum of disease. All patients harbor a novel biallelic frameshift mutation in exon 11 of AMN gene (p.Pro409Glyfs*), which was not reported previously in the literature. Both parents are heterozygotes for the same variant. All patients responded well to vitamin B12 parenteral therapy, but proteinuria persisted.

Conclusion

In communities with high incidence of consanguinity, cases of early‐onset vitamin B12 deficiency should be thoroughly investigated to explore the possibility of Imerslund‐Gräsbeck syndrome and other vitamin B12–related hereditary disorders. Further local and regional studies are highly recommended.
Far‐red‐emitting YAl3(BO3)4:Cr3+ phosphors with excellent thermal stability and high luminescent yield for plant growth LEDs
Authors: Shi Meiling , Yao Leqi , Xu Junfeng , Liang Chao , Dong Yan , Shao Qiyue
Published: January 2021

Phosphors‐converted LEDs (pc‐LEDs) are excellent artificial light sources for indoor plant cultivation, in which the far‐red‐emitting component (700−780 nm) plays an important role in regulating the photomorphogenesis of plants. Accordingly, highly efficient and thermally stable far‐red‐emitting phosphors are indispensable for developing high‐performance plant cultivation pc‐LEDs. Herein, far‐red‐emitting YAl3(BO3)4:Cr3+ (YAB:Cr3+) phosphors were synthesized by solid‐state reaction, and their photoluminescence characteristics, thermal quenching, quantum yield (QY), and application in pc‐LEDs were systematically investigated. The YAB:Cr3+ phosphor has an intense broadband absorption to the blue light, simultaneously exhibiting the sharp‐line 2E emission and the broadband 4 T2 emission of Cr3+ with a QY of ~86.7%. The far‐red broadband emissions of YAB:Cr3+ centered at ~735 nm show a high resemblance to the active‐state (PFR) absorption of plant phytochrome. Moreover, the YAB:Cr3+ phosphor shows the thermally enhanced luminescence at temperatures of 303−393 K and the near‐zero thermal quenching up to 423 K. The anomalous thermal enhancement is attributed to the temperature‐dependent repopulation between 2E and 4 T2 states. Finally, a pc‐LED device was fabricated with the YAB:Cr3+ phosphor and blue chip, exhibiting the light out power of ~50.6 mW and energy conversion efficiency of ~17.4% at 100 mA drive current, respectively. The exceptional PL features including suitable excitation/emission wavelengths, suppressed thermal quenching and high QY make YAB:Cr3+ phosphors very promising for applications in plant growth pc‐LEDs.
Comparison of procedural efficacy and biophysical parameters between two competing cryoballoon technologies for pulmonary vein isolation: Insights from an initial multicenter experience
Authors: Yap Sing‐Chien , Anic Ante , Breskovic Toni , Haas Annika , Bhagwandien Rohit E. , Jurisic Zrinka , Szili‐Torok Tamas , Luik Armin
Published: January 2021

Introduction

Recently a novel cryoballoon system (POLARx, Boston Scientific) became available for the treatment of atrial fibrillation. This cryoballoon is comparable with Arctic Front Advance Pro (AFA‐Pro, Medtronic), however, it maintains a constant balloon pressure. We compared the procedural efficacy and biophysical characteristics of both systems.

Methods

One hundred and ten consecutive patients who underwent first‐time cryoballoon ablation (POLARx: n = 57; AFA‐Pro: n = 53) were included in this prospective cohort study.

Results

Acute isolation was achieved in 99.8% of all pulmonary veins (POLARx: 99.5% vs. AFA‐Pro: 100%, p = 1.00). Total procedure time (81 vs. 67 min, p < .001) and balloon in body time (51 vs. 35 min, p < .001) were longer with POLARx. After a learning curve, these times were similar. Cryoablation with POLARx was associated with shorter time to balloon temperature −30°C (27 vs. 31 s, p < .001) and −40°C (32 vs. 54 s, p < .001), lower balloon nadir temperature (−55°C vs. −47°C, p < .001), and longer thawing time till 0°C (16 vs. 9 s, p < .001). There were no differences in time‐to‐isolation (TTI; POLARx: 45 s vs. AFA‐Pro 43 s, p = .441), however, POLARx was associated with a lower balloon temperature at TTI (−46°C vs. −37°C, p < .001). Factors associated with acute isolation differed between groups. The incidence of phrenic nerve palsy was comparable (POLARx: 3.5% vs. AFA‐Pro: 3.7%).

Conclusion

The novel cryoballoon is comparable to AFA‐Pro and requires only a short learning curve to get used to the slightly different handling. It was associated with faster cooling rates and lower balloon temperatures but TTI was similar to AFA‐Pro.
Seraprevir and sofosbuvir for treatment of chronic hepatitis C virus infection: A single‐arm, open‐label, phase 3 trial
Authors: Kong Fei , Wen Xiaoyu , Wen Xiaofeng , Wang Xiaozhong , Wu Guicheng , Lin Shide , Wang Li , Xing Huichun , Yan Xuebing , Zheng Sujun , Ning Qin , Wang Zheng , Zhang Liaoyun , Lin Jianmei , Tong Zhaowei , Huang Chengyu , Su Minghua , Tong Lixin , Jia Jidong , Xin Yongning , Zhu Qingjing , Wang Jing , Chen Li , Li Xiaowen , Wu Xuegang , Niu Duan , Liu Quan , Wei Wei , Zhang Yuexin , Li Guangming , Niu Junqi
Published: January 2021

Background and Aim

This single‐arm, open‐label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis.

Methods

Treatment‐naive or interferon‐experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12).

Results

Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post‐treatment course and 3 discontinued follow‐up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention.

Conclusions

The all‐oral, ribavirin‐free regimen of seraprevir and sofosbuvir is an effective and well‐tolerated treatment option for Chinese patients mono‐infected with HCV, including those with a history of interferon treatment.