bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Mediterranean agricultural residues on microbial community and anaerobic digestion performance
Authors: Valenti Francesca , Rojas‐Sossa Juan Pablo , Zhong Yuan , Porto Simona M. C. , Toscano Attilio , Marsh Terence , Dale Bruce E. , Liu Yan , Liao Wei
Published: November 2021

Understanding the effects of regionally available residues, wastes, and purpose‐grown energy crops on anaerobic microbes and corresponding digestion performance is important for designing and implementing suitable anaerobic digestion systems to manage them appropriately and to use them for bioenergy generation. This study analyzed and compared dynamic changes in anaerobic microbes and digestion performance using mixtures of six different materials (citrus pulp, olive pomace, cattle manure, poultry litter, whey, and corn silage) generated from Mediterranean agro‐industry. The results indicate that the feedstock mixture (FM3) with low citrus pulp (26% dry matter) and high olive pomace (18% dry matter) reached stable methane production of 210 mL methane/g volatile solids (VS) loading within 30 days after the start up. In contrast, the feedstock mixture (FM1) with high citrus pulp (44% dry matter) and low olive pomace (0% dry matter) required a longer time of at least 70 days to achieve a good methane production of 209 mL methane/g VS loading. The microbial community analysis and corresponding non‐metric dimensionless scaling (NMDS) analysis revealed dynamic relationships between microbial community, feedstock mixture, and digestion time. The feedstock mixtures with low citrus pulp content (FM2 and FM3) facilitated the accumulation of Archaea (i.e., Methanosarcinaceae), which led their digestion to reach stable methane production quicker than the digestion of FM1. This study provided useful information to valorize agricultural residues and wastes for bioenergy production in the Mediterranean region. © 2021 Society of Chemical Industry and John Wiley & Sons, Ltd
Evolutionary physiology at 30+: Has the promise been fulfilled?
Authors: Galván Ismael , Schwartz Tonia S. , Garland Theodore
Published: November 2021

Three decades ago, interactions between evolutionary biology and physiology gave rise to evolutionary physiology. This caused comparative physiologists to improve their research methods by incorporating evolutionary thinking. Simultaneously, evolutionary biologists began focusing more on physiological mechanisms that may help to explain constraints on and trade‐offs during microevolutionary processes, as well as macroevolutionary patterns in physiological diversity. Here we argue that evolutionary physiology has yet to reach its full potential, and propose new avenues that may lead to unexpected advances. Viewing physiological adaptations in wild animals as potential solutions to human diseases offers enormous possibilities for biomedicine. New evidence of epigenetic modifications as mechanisms of phenotypic plasticity that regulate physiological traits may also arise in coming years, which may also represent an overlooked enhancer of adaptation via natural selection to explain physiological evolution. Synergistic interactions at these intersections and other areas will lead to a novel understanding of organismal biology.
Highway to hell‐thy meiotic divisions: Chromosome passenger complex functions driven by microtubules
Authors: McKim Kim S.
Published: November 2021

The chromosome passenger complex (CPC) localizes to chromosomes and microtubules, sometimes simultaneously. The CPC also has multiple domains for interacting with chromatin and microtubules. Interactions between the CPC and both the chromatin and microtubules is important for spindle assembly and error correction. Such dual chromatin‐microtubule interactions may increase the concentration of the CPC necessary for efficient kinase activity while also making it responsive to specific conditions or structures in the cell. CPC‐microtubule dependent functions are considered in the context of the first meiotic division. Acentrosomal spindle assembly is a process that depends on transfer of the CPC from the chromosomes to the microtubules. Furthermore, transfer to the microtubules is not only to position the CPC for a later role in cytokinesis; metaphase I error correction and subsequent bi‐orientation of bivalents may depend on microtubule associated CPC interacting with the kinetochores.
Estimation in multivariate linear mixed models for longitudinal data with multiple outputs: Application to PBCseq data analysis
Authors: Taavoni Mozhgan , Arashi Mohammad
Published: November 2021

In many biomedical studies or clinical trials, we have data with more than one response variable on the same subject repeatedly measured over time. In analyzing such data, we adopt a multivariate linear mixed‐effects longitudinal model. On the other hand, in longitudinal data, we often find features that do not impact modeling the response variable and are eliminated from the study. In this paper, we consider the problem of simultaneous variable selection and estimation in a multivariate t linear mixed‐effects model (MtLMM) for analyzing longitudinally measured multioutcome data. This work's motivation comes from a cohort study of patients with primary biliary cirrhosis. The interest is eliminating insignificant variables using the smoothly clipped and absolute deviation penalty function in the MtLMM. The proposed penalized model offers robustness and flexibility to accommodate fat tails. An expectation conditional maximization algorithm is employed for the computation of maximum likelihood estimates of parameters. The calculation of standard errors is affected by an information‐based method. The methodology is illustrated by analyzing Mayo Clinic Primary Biliary Cirrhosis sequential (PBCseq) data and a simulation study. We found drugs and sex can be eliminated from the PBCseq analysis, and over time the disease progresses.
Professionalisation in counselling as a narrative identity project: Insights and implications from counsellor education in Germany
Authors: Rohr Dirk , Baum Robert
Published: November 2021

This article discusses the structure and possible future developments of Counsellors' education in Germany and places these findings in an international context. It presents a concept of narrative professional identity as a ‘core idea’ of Counsellors' education and gives suggestions on how to implement this concept in Counsellors' education in Germany and worldwide.
Promote fair and impartial policing practices with Human Rights training
Authors: Sutton Halley
Published: November 2021

Allen Hill started as Chief of Police at the University of Wisconsin, LaCrosse, in September 2019. And because of the COVID‐19 pandemic, his experience at the institution has been an unusual one. “I have not yet experienced a full semester on campus,” Hill said.
Real‐Time Multi‐Photon Tracking and Bioimaging of Glycosylated Theranostic Prodrugs upon Specific Enzyme Triggered Release
Authors: Calatrava‐Pérez Elena , Marchetti Luke A. , McManus Gavin J. , Lynch Dylan M. , Elmes Robert B. P. , Williams D. Clive , Gunnlaugsson Thorfinnur , Scanlan Eoin M.
Published: November 2021

Real‐time tracking of prodrug uptake, delivery and activation in vivo represents a major challenge for prodrug development. Herein, we demonstrate the use of novel glycosylated theranostics of the cancer pharmacophore Amonafide in highly‐selective, enzymatic triggered release. We show that the use of endogenous enzymes for activated release of the therapeutic component can be observed, in real time, and monitored using one and two‐photon bioimaging, offering unique insight into the prodrug pharmacokinetic profile. Furthermore, we demonstrate that the potent cytotoxicity of Amonafide is preserved using this targeted approach.
Functional Proteomics Driven by Chemical and Computational Approaches
Authors: Chen Ying , Qin Wei , Wang Chu
Published: November 2021

Comprehensive Summary

Functional proteomics is a powerful approach to globally investigate protein functions and their biological significance. Activity‐based protein profiling (ABPP) has been widely applied to explore the activity and ligandability of proteins in complex biological systems. Herein, we summarized our efforts in developing chemical probes and chemical proteomic pipelines to identify protein targets of certain post‐translational modifications (PTMs), covalent drugs, natural products and cellular metabolites. Furthermore, computer‐aided proteomic strategies were developed to globally identify functional residues including hyper‐reactive cysteines, active sites of selenoproteins and proximal anchors for protein activation.

How do you get into this specific field? Could you please share some experiences with our readers?

When I finished my Ph.D. in computational structure biology, I was attracted to chemical biology as it is a highly interdisciplinary field. I was fascinated by how chemical probes can capture and reveal important functions of proteins, particularly in complexed biological settings.

How do you supervise your students?

I tend to let my students explore freely on research subjects they are interested in as long as the topics fit in the scope of functional proteomics. I enjoy the experience of working with them instead of supervising them.

What is the most important personality for scientific research?

In my opinion, the most important personality for scientific research is perseverance, passion and logical thinking.

How do you keep balance between research and family?

Research and family should not conflict with each other and they are both inseparable parts of my life. Practically, I just leave enough family time on my schedule so that they are not interfered by my research works.

What are your hobbies?

My hobbies are watching soccer games and sitcoms. I used to play soccer quite a lot but sadly my knees do not allow it any more. My favorite soccer club is AC Milan and my favorite sitcom is Friends.

Could you please give us some advices on improving Chinese Journal of Chemistry?

Stay diversified, in terms of both research subjects published as well as career stages of contributing authors.
Morphological and distributional properties of SMI‐32 immunoreactive ganglion cells in the rat retina
Authors: Tan Huiying , Li Xiaotao , Huang Kang , Luo Moxuan , Wang Liping
Published: November 2021

SMI‐32 is widely used to identify entire populations of alpha retinal ganglion cells (RGCs), and several SMI‐32+ RGC subsets have been studied thoroughly in rodents. However, due to the thick cover of SMI‐32+ neurofilaments, the morphology of SMI‐32+ RGCs in the central retinal region is obscured and rarely described. Moreover, SMI‐32 labels more than one morphological RGC type and the full morphological characteristics and distribution of SMI‐32+ RGCs have yet to be discovered. Here, using intracellular neurobiotin injections combined with SMI‐32 antibody staining, we investigated morphological and distributional properties of the entire SMI‐32+ RGCs population in the rat retina. We found that SMI‐32+ RGCs were evenly distributed throughout the rat retina. We compared the morphological features of SMI‐32+ ON and OFF cells in the central, middle, and peripheral retinal regions. We found that SMI‐32+ RGCs in different regions have distinct characteristics, such as the soma area and the dendritic field area, and Sholl analysis of ON cells and OFF cells revealed significant differences between each region. We classified SMI‐32+ RGCs into five clusters based on morphological features and found that a majority of SMI‐32+ RGCs belong to alpha‐like cells; however, a small proportion of SMI‐32+ RGCs had small soma and small dendritic fields. Together, we present a full description of the morphology and distribution of SMI‐32 immunoreactive RGCs in the rat retina.
The pigment‐dispersing factor neuronal network systematically grows in developing honey bees
Authors: Beer Katharina , Härtel Stephan , Helfrich‐Förster Charlotte
Published: November 2021

The neuropeptide pigment‐dispersing factor (PDF) plays a prominent role in the circadian clock of many insects including honey bees. In the honey bee brain, PDF is expressed in about 15 clock neurons per hemisphere that lie between the central brain and the optic lobes. As in other insects, the bee PDF neurons form wide arborizations in the brain, but certain differences are evident. For example, they arborize only sparsely in the accessory medulla (AME), which serves as important communication center of the circadian clock in cockroaches and flies. Furthermore, all bee PDF neurons cluster together, which makes it impossible to distinguish individual projections. Here, we investigated the developing bee PDF network and found that the first three PDF neurons arise in the third larval instar and form a dense network of varicose fibers at the base of the developing medulla that strongly resembles the AME of hemimetabolous insects. In addition, they send faint fibers toward the lateral superior protocerebrum. In last larval instar, PDF cells with larger somata appear and send fibers toward the distal medulla and the medial protocerebrum. In the dorsal part of the medulla serpentine layer, a small PDF knot evolves from which PDF fibers extend ventrally. This knot disappears during metamorphosis and the varicose arborizations in the putative AME become fainter. Instead, a new strongly stained PDF fiber hub appears in front of the lobula. Simultaneously, the number of PDF neurons increases and the PDF neuronal network in the brain gets continuously more complex.
Consideration of degree of chromatic adaptation for reproducing illuminated scenes
Authors: Li Yiqian , Chen Siyuan , Wei Minchen , Zhang Xiandou
Published: November 2021

Chromatic adaptation is an important mechanism in the human visual system, which affects the perceived color appearance of scenes and objects under the illumination. Recent studies, however, found that the degree of chromatic adaptation was significantly affected by the chromaticities of the adapting condition, which is not characterized in the existing chromatic adaptation transforms and color appearance models. This work was carefully designed to investigate how the degree of chromatic adaptation needs to be considered to reproduce the overall color tone of scenes under the illumination having a wide range of chromaticities. Human observers viewed a scene under 85 light settings, and then adjusted the color appearance of the scene image shown on a smartphone display to match that of the physical scene. The adjustment of the image color appearance was achieved by performing chromatic adaptation transform with different image white points. The results clearly showed how the degree of chromatic adaptation varied with the illuminant chromaticities, and how the image white point should be adjusted to reproduce the color tone of an illuminated scene.
Integration of Real‐World Data and Genetics to Support Target Identification and Validation
Authors: Davitte Jonathan M. , Stott‐Miller Marni , Ehm Margaret G. , Cunnington Marianne C. , Reynolds Robert F.
Published: November 2021

Even modest improvements in the probability of success of selecting drug targets which are ultimately approved can substantially reduce the costs of research and development. Drug targets with human genetic evidence of disease association are twice as likely to lead to approved drugs. A key enabler of identifying and validating these genetically validated targets is access to association results from genome‐wide genotyping, whole‐exome sequencing, and whole‐genome sequencing studies with observable traits (often diseases) across large numbers of individuals. Today, linkage between genotype and real‐world data (RWD) provides significant opportunities to not only increase the statistical power of genome‐wide association studies by ascertaining additional cases for diseases of interest, but also to improve diversity and coverage of association studies across the disease phenome. As RWD‐genetics linked resources continue to grow in diversity of participants, breadth of data captured, length of observation, and number of participants, there is a greater need to leverage the experience of RWD experts, clinicians, and highly experienced geneticists together to understand which lessons and frameworks from general research using RWD sources are relevant to improve genetics‐driven drug discovery and development. This paper describes new challenges and opportunities for phenotypes enabled by diverse RWD sources, considerations in the use of RWD phenotypes for disease gene identification across the disease phenome, and challenges and opportunities in leveraging RWD phenotypes in target validation. The paper concludes with views on the future directions for phenotype development using RWD, and key questions requiring further research and development to advance this nascent field.
Improved Methods for Single‐Molecule Fluorescence In Situ Hybridization and Immunofluorescence in Caenorhabditis elegans Embryos
Authors: Parker Dylan M. , Winkenbach Lindsay P. , Parker Annemarie , Boyson Sam , Nishimura Erin Osborne
Published: November 2021

Visualization of gene products in Caenorhabditis elegans has provided insights into the molecular and biological functions of many novel genes in their native contexts. Single‐molecule fluorescence in situ hybridization (smFISH) and immunofluorescence (IF) enable the visualization of the abundance and localization of mRNAs and proteins, respectively, allowing researchers to ultimately elucidate the localization, dynamics, and functions of the corresponding genes. Whereas both smFISH and immunofluorescence have been foundational techniques in molecular biology, each protocol poses challenges for use in the C. elegans embryo. smFISH protocols suffer from high initial costs and can photobleach rapidly, and immunofluorescence requires technically challenging permeabilization steps and slide preparation. Most importantly, published smFISH and IF protocols have predominantly been mutually exclusive, preventing the exploration of relationships between an mRNA and a relevant protein in the same sample. Here, we describe protocols to perform immunofluorescence and smFISH in C. elegans embryos either in sequence or simultaneously. We also outline the steps to perform smFISH or immunofluorescence alone, including several improvements and optimizations to existing approaches. These protocols feature improved fixation and permeabilization steps to preserve cellular morphology while maintaining probe and antibody accessibility in the embryo, a streamlined, in‐tube approach for antibody staining that negates freeze‐cracking, a validated method to perform the cost‐reducing single molecule inexpensive FISH (smiFISH) adaptation, slide preparation using empirically determined optimal antifade products, and straightforward quantification and data analysis methods. Finally, we discuss tricks and tips to help the reader optimize and troubleshoot individual steps in each protocol. Together, these protocols simplify existing workflows for single‐molecule RNA and protein detection. Moreover, simultaneous, high‐resolution imaging of proteins and RNAs of interest will permit analysis, quantification, and comparison of protein and RNA distributions, furthering our understanding of the relationship between RNAs and their protein products or cellular markers in early development. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Sequential immunofluorescence and single‐molecule fluorescence in situ hybridization

Alternate Protocol: Abbreviated protocol for simultaneous immunofluorescence and single‐molecule fluorescence in situ hybridization

Basic Protocol 2: Simplified immunofluorescence in C. elegans embryos

Basic Protocol 3: Single‐molecule fluorescence in situ hybridization or single‐molecule inexpensive fluorescence in situ hybridization
A Primer for Assessing the Pathology in Mouse Models of Neuroblastoma
Authors: Gifford Andrew J. , Murray Jayne , Fletcher Jamie I. , Marshall Glenn M. , Norris Murray D. , Haber Michelle
Published: November 2021

Neuroblastoma, the most common extracranial solid tumor in young children, arises from the sympathetic nervous system. Our understanding of neuroblastoma has been improved by the development of both genetically engineered and xenograft mouse models of the disease. Anatomical pathology is an essential component of the phenotyping of mouse models of cancer, characterizing the morphologic effects of genetic manipulation and drug treatment. The Th‐MYCN model, the most widely used of several genetically engineered mouse models of neuroblastoma, was established by targeted expression of the human MYCN gene to murine neural crest cells under the control of the rat tyrosine hydroxylase promoter. Neuroblastoma development in Th‐MYCN mice is preceded by neuroblast hyperplasia—the persistence and proliferation of neural crest–derived neuroblasts within the sympathetic autonomic ganglia. The neuroblastomas that subsequently develop morphologically resemble human neuroblastoma and carry chromosomal gains and losses in regions syntenic with those observed in human tumors. In this overview, we describe the essential pathologic features for investigators when assessing mouse models of neuroblastoma. We outline human neuroblastoma as the foundation for understanding the murine disease, followed by details of the murine sympathetic ganglia from which neuroblastoma arises. Sympathetic ganglia, both with and without neuroblast hyperplasia, are described. The macroscopic and microscopic features of murine neuroblastoma are explained, including assessment of xenografts and tumors following drug treatment. An approach to experimental design is also detailed. Increased understanding of the pathology of murine neuroblastoma should improve reproducibility and comparability of research findings and assist investigators working with mouse models of neuroblastoma. © 2021 Wiley Periodicals LLC.
The skill qualification system for portal hypertension in Japan
Authors: Ohta Masayuki , Murashima Naoya , Ohyama Tetsuji , Yoshida Tomoharu , Hirota Shozo , Kawanaka Hirofumi , Hashizume Makoto , Nakamura Shinichi , Chikamori Fumio , Eguchi Susumu , Tajiri Takashi , Obara Katsutoshi , Kokubu Shigehiro
Published: November 2021

Objectives

The diverse treatments available for portal hypertension require specialized knowledge of hemodynamics and include endoscopic treatments, interventional radiology (IVR), and surgery. The Japan Society for Portal Hypertension has developed the skill qualification system (SQS) for portal hypertension and began examination in 2014. Here, the status and validity of the judgment of the SQS examination were evaluated.

Methods

From 2014 to 2020, 79 applicants were evaluated by the SQS for portal hypertension. Each unedited video submitted as a candidate procedure was evaluated by two judges, and a grade of greater than 70% for the scoring items assessed by the judges was required to pass the examination. Inter‐rater agreement of success/failure between the two judges was investigated by the AC1 coefficient.

Results

The results of two judges differed for 11 of the 79 videos (13.9%), and five applicants (6.3%) ultimately failed the examination. The percentages of total points received by the applicants with endoscopic treatments, IVR, and surgery were 87.3%, 79.4%, and 80.8%, respectively. There were significant differences in the percentages between endoscopic treatments and IVR (P = 0.0015). The AC1 coefficients were 0.84 for the applicants overall, 0.93 for endoscopic treatments, 0.66 for IVR, and 0.72 for surgery. Similarly, there were significant differences in the AC1 coefficient between endoscopic treatments and IVR (P = 0.021).

Conclusions

The SQS for portal hypertension of the Japan Society for Portal Hypertension showed high reliability for video assessments by the judges. This system may contribute to the spread and further development of safe and effective treatments for portal hypertension in Japan.
A Comparative Appraisal of Traditional “Ghee” Derived From the Three Genotypes (Arunachali Yak, Yak–Cow Hybrid, and Cow) Reared Under Semi‐Intensive Conditions
Authors: Singh Tarun Pal , Deshwal Gaurav Kr , Bam Joken , Paul Vijay
Published: November 2021

The present study aims to characterize “ghee” derived from Arunachali yak (AY), yak–cow hybrid (YCH), and cow reared under semi‐intensive conditions in Arunanchal Pradesh, India. The milk obtained from Arunachali yak has significantly (p < 0.05) higher fat, solids‐not‐fat, and protein content compared to YCH and cow. The ghee obtained from three different genotypes is characterized and showed significant variation (p < 0.05) in various physicochemical parameters viz., yield, moisture, specific gravity, saponification value, free fatty acid, cholesterol, vitamin A, and instrumental color profile. Further, the ghee obtained from YCH milk has significantly (p < 0.05) higher oleic acids (35.24% ± 0.21), linoleic acid content (1.18% ± 0.03), and unsaturated fatty acid (UFA)/saturated fatty acid (SFA) ratio (0.69 ± 0.01), whereas cow ghee has significantly (p < 0.05) higher α‐Linolenic acid (0.57% ± 0.04) compared to the other samples. AY ghee has higher saturated fatty acids (63.58% ± 0.07); however, no significant difference is observed in the total fatty acids content of the ghee obtained from AY and YCH. In Fourier transform infrared (FT‐IR) analysis, the characteristic intensity of the absorption peaks in the region of 650–4000 cm−1 is taken. They are nearly comparable, and no differences are detected by the naked eye. It can be concluded that the findings of this study will be useful for characterization and also provide scientific support for further in‐depth study.

Practical applications: The experimental results of this study would aid the increase of information about physicochemical characterization of these three genotypes of foot hills of the Himalayas.
Improved Synthesis of D‐Isoglutamine: Rapid Access to Desmuramyl Analogues of Muramyl Dipeptide for the Activation of Intracellular NOD2 Receptor and Vaccine Adjuvant Applications
Authors: Khan Farooq‐Ahmad , Khanam Rahila , Wasim Qasim Muhammad , Wang Yan , Jiang Zi‐Hua
Published: November 2021

Muramyl dipeptide (MDP) – the smallest immunomodulatory unit of bacterial peptidoglycan – has adjuvant activity and triggers the innate immune system against bacterial and viral infections. The inherited drawbacks of MDP, such as pyrogenicity and poor macrophage penetration, can be resolved by structural modifications, thereby improving its pharmacological profile and adjuvant activity. Herein, several desmuramyl analogues of MDP were designed by replacing the carbohydrate fragment (MurNAc) of the parent molecule with an immunomodulatory xanthine scaffold. The L−D configurations of the pharmacophoric dipeptidyl moiety were conserved and alkyl chains of moderate length were introduced at isoglutamine to enhance their cellular uptake. The synthesis of these analogues features a novel synthetic route for D‐isoglutamine fragment with an overall yield of >50 % in ten to eleven steps. This sufficiently flexible approach provides rapid access to desmuramyl analogues of MDP on a gram scale, which can help accelerate the development of novel NOD2 agonists and immunoadjuvants.
Dopant Free Triphenylamine‐Based Hole Transport Materials with Excellent Photovoltaic Properties for High‐Performance Perovskite Solar Cells
Authors: Naeem Naila , Shehzad Rao Aqil , Ans Muhammad , Akhter Mohammed Salim , Iqbal Javed
Published: November 2021

Recently, scientists are more devoted to designing and synthesizing organic perovskite solar cells for attaining high power conversion efficiency (PCE). Herein, a series of small molecules as hole transport materials with A–π–D–π–A framework, namely (DFA1, DFA2, DFA3, and DFA4) having triphenylamine (TPA)‐based central donor core unit (A1–A4) end‐capped acceptor moieties linked via thiophene spacer is designed theoretically to study optoelectronic and photovoltaic properties. MPW1PW91 hybrid functional in conjunction with 6‐31G** basis set is found the best method to investigate the optoelectronic and photovoltaic properties. All hole transport materials (HTMs) possess a high open‐circuit voltage (0.98–1.41 V) with downshifted highest occupied molecular orbital energy values (−4.98 to −5.41 eV) by tailoring of electron‐withdrawing acceptor moieties. Meanwhile, appropriate elongation of π‐conjugated acceptor units is advantageous for enhancing the molar absorption coefficient and intermolecular electronic coupling. The highest hole mobility and charge transfer integral owing to lower hole reorganization energies indicate these molecules are best for HTMs. DFA1‐DFA4 has a power conversion efficiency of up to 24% which authenticates that these HTMs have excellent photovoltaic attributes compared to the reported reference DFH. The present computational investigation validates the efficacy of the designed techniques and opens a new route for designing high‐performance dopant‐free HTMs in perovskite solar cells.
Effect of iron‐fortified infant cereal on nutritional status of infants in Ghana
Authors: Harrison Obed Akwaa , Hays Nicholas P. , Ansong Richard S. , Datoghe Dominic , Vuvor Frederick , Steiner‐Asiedu Matilda
Published: November 2021

Iron deficiency anemia is prevalent among infants in Ghana. This study evaluated the effect of micronutrient‐fortified infant cereal on the nutritional status of infants in the La Nkwantanang Municipality of the Greater Accra Region of Ghana, located in western Africa. In this double‐blind, controlled trial, infants aged 6–18 months were cluster‐randomized to receive either micronutrient‐fortified infant cereal containing 3.75 mg iron as ferrous fumarate/50 g cereal (INT; n = 107) or the same cereal without iron (CTL; n = 101) to complement other foods and breast milk. The intervention phase lasted six months followed by a two‐month post–intervention phase (with no further study product feeding). Hemoglobin and anthropometry were assessed every 2 months for the 8‐month study period. After the 6‐month intervention phase, adjusted mean ± standard error change in hemoglobin from baseline in INT and CTL was 1.97 ± 0.19 and 1.16 ± 0.21 g/dl, respectively (p < .01 for each); the increase in hemoglobin was significantly larger in INT versus CTL (increase 0.68 ± 0.30 g/dl; p = .02). Prevalence of anemia declined to a significantly greater extent in INT (84.1% to 42.8%) compared to CTL (89.1% to 62.8%; p = .006). There was no significant difference between groups in weight gain (p = .41) or height gain (p = .21) over the study period. In infants aged 6–18 months, micronutrient‐fortified infant cereal consumed for 6 months promoted greater reductions in iron‐deficiency anemia, which is a significant public health concern not only in Ghana but also in many developing countries globally.
Incidence of dementia in a population cohort of older people from São Paulo, Brazil
Authors: Lopes Marcos Antonio , Nassar Silvia Modesto , Barcelos‐Ferreira Ricardo , Folquitto Jefferson Cunha , Litvoc Júlio
Published: November 2021

Objectives

To estimate the incidence of dementia in a community‐dwelling older population from São Paulo city, Brazil.

Methods/Design

This two‐phase prospective cohort study evaluated a representative cluster sample of 1370 individuals aged 60 years old and over from three different socioeconomic levels. The community screening phase consisted of a tested combination of cognitive and functional tests administered among the subjects and informants. In the hospital diagnosis phase, the Cambridge Examination was performed; the diagnosis of dementia and dementia subtypes was made according to DSM IV criteria. Incidence rates were expressed in person‐years, multiplied by 1000. The risk of developing dementia was calculated using Cox regression.

Results

Among 1370 eligible subjects, 678 were accessed, and 489 completed the evaluation. Forty‐two subjects were diagnosed with dementia. The incidence rate of dementia and Alzheimer's disease (AD) were 11.2 (95% CI: 8.0–15.1) and 8.9 (95% CI: 6.1–12.5) per 1000 person‐years, respectively; there were high age‐specific rates of dementia among younger individuals. There was a trend of a higher risk of developing AD for women than for men. Multivariate analysis showed that older age, the presence of diabetes and the presence of amnestic MCI increased the risk of developing dementia.

Conclusions

The age‐specific rates in younger individuals were expressively higher than in worldwide studies and supposedly affected by cardiovascular morbidity. The higher risk in women in a younger sample corroborated the interaction between sex and AD. The increased risk of amnestic MCI reinforced its contribution to the progression to dementia and AD.
In search of convergent regional brain abnormality in cognitive emotion regulation: A transdiagnostic neuroimaging meta‐analysis
Authors: Khodadadifar Tina , Soltaninejad Zahra , Ebneabbasi Amir , Eickhoff Claudia R. , Sorg Christian , Van Eimeren Thilo , Vogeley Kai , Zarei Mojtaba , Eickhoff Simon B. , Tahmasian Masoud
Published: November 2021

Ineffective use of adaptive cognitive strategies (e.g., reappraisal) to regulate emotional states is often reported in a wide variety of psychiatric disorders, suggesting a common characteristic across different diagnostic categories. However, the extent of shared neurobiological impairments is incompletely understood. This study, therefore, aimed to identify the transdiagnostic neural signature of disturbed reappraisal using the coordinate‐based meta‐analysis (CBMA) approach. Following the best‐practice guidelines for conducting neuroimaging meta‐analyses, we systematically searched PubMed, ScienceDirect, and Web of Science databases and tracked the references. Out of 1,608 identified publications, 32 whole‐brain neuroimaging studies were retrieved that compared brain activation in patients with psychiatric disorders and healthy controls during a reappraisal task. Then, the reported peak coordinates of group comparisons were extracted and several activation likelihood estimation (ALE) analyses were performed at three hierarchical levels to identify the potential spatial convergence: the global level (i.e., the pooled analysis and the analyses of increased/decreased activations), the experimental‐contrast level (i.e., the analyses of grouped data based on the regulation goal, stimulus valence, and instruction rule) and the disorder‐group level (i.e., the analyses across the experimental‐contrast level focused on increasing homogeneity of disorders). Surprisingly, none of our analyses provided significant convergent findings. This CBMA indicates a lack of transdiagnostic convergent regional abnormality related to reappraisal task, probably due to the complex nature of cognitive emotion regulation, heterogeneity of clinical populations, and/or experimental and statistical flexibility of individual studies.
The roles of the LpSTS and DLPFC in self‐prioritization: A transcranial magnetic stimulation study
Authors: Liang Qiongdan , Zhang Bozhen , Fu Sinan , Sui Jie , Wang Fei
Published: November 2021

The Self‐Attention Network (SAN) has been proposed to describe the underlying neural mechanism of the self‐prioritization effect, yet the roles of the key nodes in the SAN—the left posterior superior temporal sulcus (LpSTS) and the dorsolateral prefrontal cortex (DLPFC)—still need to be clarified. One hundred and nine participants were randomly assigned into the LpSTS group, the DLPFC group, or the sham group. We used the transcranial magnetic stimulation (TMS) technique to selectively disrupt the functions of the corresponding targeted region, and observed its impacts on self‐prioritization effect based on the difference between the performance of the self‐matching task before and after the targeted stimulation. We analyzed both model‐free performance measures and HDDM‐based performance measures for the self‐matching task. The results showed that the inhibition of LpSTS could lead to reduced performance in processing self‐related stimuli, which establishes a causal role for the LpSTS in self‐related processing and provide direct evidence to support the SAN framework. However, the results of the DLPFC group from HDDM analysis were distinct from the results based on response efficiency. Our investigation further the understanding of the differentiated roles of key nodes in the SAN in supporting the self‐salience in information processing.
Natural disasters and missing children
Authors: Ponnusamy Sundar
Published: November 2021

Using an exogenous measure of natural disasters based on physical intensities, I examine their impact on child mortality. I find that children, mostly, in poor countries are affected — a one standard deviation increase in the natural disaster index leads to an additional 6.77 deaths per 1000 live births in the disaster year. The impact is long lasting, extending beyond the disaster year. I provide suggestive evidence of the potential mechanisms driving these effects, namely, lower GDP and vaccination rates among children, along with an increased maternal mortality and disease incidence in low‐income countries due to disasters. Using an endogenous measure of disasters based on damage records from insurance data leads to severe underestimation of the disaster impact. The results are robust to the use of mortality rates from multiple sources, different functional forms, and an extensive dynamic panel specification as well as various other tests.
A Quantitative Magnetic Resonance Cholangiopancreatography Metric of Intrahepatic Biliary Dilatation Severity Detects High‐Risk Primary Sclerosing Cholangitis
Authors: Selvaraj Emmanuel A. , Ba‐Ssalamah Ahmed , Poetter‐Lang Sarah , Ridgway Gerard R. , Brady J. Michael , Collier Jane , Culver Emma L. , Bailey Adam , Pavlides Michael
Published: November 2021

Magnetic resonance imaging with magnetic resonance cholangiopancreatography (MRI‐MRCP) in primary sclerosing cholangitis (PSC) is currently based on qualitative assessment and has high interobserver variability. We investigated the utility and performance of quantitative metrics derived from a three‐dimensional biliary analysis tool in adult patients with PSC. MRI‐MRCP, blood‐based biomarkers, and FibroScan were prospectively performed in 80 participants with large‐duct PSC and 20 healthy participants. Quantitative analysis was performed using MRCP+ (Perspectum Ltd., United Kingdom), and qualitative reads were performed by radiologists. Inter‐reader agreements were compared. Patients were classified into high risk or low risk for disease progression, using Mayo risk score (MRS), Amsterdam‐Oxford model (AOM), upper limit of normal (ULN) alkaline phosphatase (ALP), disease distribution, and presence of dominant stricture. Performance of noninvasive tools was assessed using binomial logistic regressions and receiver operating characteristic curve analyses. Quantitative biliary metrics performed well to distinguish abnormal from normal bile ducts (P < 0.0001). Interobserver agreements for MRCP+ dilatation metrics (intraclass correlation coefficient, 0.90‐0.96) were superior to modified Amsterdam intrahepatic stricture severity score (κ = 0.74) and Anali score (κ = 0.38). MRCP+ intrahepatic dilatation severity showed excellent performance to classify patients into high‐risk and low‐risk groups, using predictors of disease severity as the reference (MRS, P < 0.0001; AOM, P = 0.0017; 2.2 × ULN ALP, P = 0.0007; 1.5 × ULN ALP, P = 0.0225; extrahepatic disease, P = 0.0331; dominant stricture, P = 0.0019). MRCP+ intrahepatic dilatation severity was an independent predictor of MRS >0 (odds ratio, 31.3; P = 0.035) in the multivariate analysis. Conclusion: Intrahepatic biliary dilatation severity calculated using MRCP+ is elevated in patients with high‐risk PSC and may be used as an adjunct for risk stratification in PSC. This exploratory study has provided the groundwork for examining the utility of novel quantitative biliary metrics in multicenter studies.
High‐Resolution Exposomics and Metabolomics Reveals Specific Associations in Cholestatic Liver Diseases
Authors: Walker Douglas I. , Juran Brian D. , Cheung Angela C. , Schlicht Erik M. , Liang Yongliang , Niedzwiecki Megan , LaRusso Nicholas F. , Gores Gregory J. , Jones Dean P. , Miller Gary W. , Lazaridis Konstantinos N.
Published: November 2021

Progress in development of prognostic and therapeutic options for the rare cholestatic liver diseases, primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), is hampered by limited knowledge of their pathogeneses. In particular, the potential role of hepatotoxic and/or metabolism‐altering environmental chemicals in the pathogenesis of these diseases remains relatively unstudied. Moreover, the extent to which metabolic pathways are altered due to ongoing cholestasis and subsequent liver damage or possibly influenced by hepatotoxic chemicals is poorly understood. In this study, we applied a comprehensive exposomics‐metabolomics approach to uncover potential pathogenic contributors to PSC and PBC. We used untargeted high‐resolution mass spectrometry to characterize a wide range of exogenous chemicals and endogenous metabolites in plasma and tested them for association with disease. Exposome‐wide association studies (EWAS) identified environmental chemicals, including pesticides, additives and persistent pollutants, that were associated with PSC and/or PBC, suggesting potential roles for these compounds in disease pathogenesis. Metabolome‐wide association studies (MWAS) found disease‐associated alterations to amino acid, eicosanoid, lipid, co‐factor, nucleotide, mitochondrial and microbial metabolic pathways, many of which were shared between PSC and PBC. Notably, this analysis implicates a potential role of the 5‐lipoxygenase pathway in the pathogenesis of these diseases. Finally, EWAS × MWAS network analysis uncovered linkages between environmental agents and disrupted metabolic pathways that provide insight into potential mechanisms for PSC and PBC. Conclusion: This study establishes combined exposomics‐metabolomics as a generalizable approach to identify potentially pathogenic environmental agents and enumerate metabolic alterations that may impact PSC and PBC, providing a foundation for diagnostic and therapeutic strategies.
Screening for gestational diabetes mellitus and hyperglycemia in pregnancy with the glucose challenge test administered in early pregnancy
Authors: Sfameni Salvatore F. , Wein Peter , Ngu Andrew C. C.
Published: November 2021

Objective

To determine the cut‐off value for the 75‐g glucose challenge test administered in early pregnancy to screen for gestational diabetes mellitus and abnormal carbohydrate metabolism in pregnancy.

Methods

A prospective study involving 1500 antenatal patients attending a community hospital. Patients were screened with the 75‐g 1‐h glucose challenge test in early pregnancy and subsequently tested with the 75‐g 2‐h glucose tolerance test to diagnose gestational diabetes mellitus. Statistical methods were employed to determine the optimal plasma glucose cut‐off value for a positive result in early pregnancy.

Results

A glucose challenge test value of 6.0 mmol/L (108 mg/dl) or more was selected as the preferred cut‐off level for further testing with a sensitivity of 83.5% (95% confidence interval [CI] 77.0%–88.9%) and specificity of 49.2% (95% CI 46.5%–52.0%).

Conclusion

An early pregnancy glucose challenge test reading of 6.0 mmol/L (108 mg/dl) or more is effective in screening for gestational diabetes mellitus; a value of 10.0 mmol/L (180 mg/dl) or more is effective for finding pre‐pregnancy abnormalities of carbohydrate metabolism. The false‐positive glucose challenge test diagnoses gestational hyperglycemia, the treatment of which will improve perinatal outcome. Further testing based on risk factors will exclude a false‐negative glucose challenge test. A combination of universal early pregnancy screening and selective risk‐factor testing is recommended to detect the full range of abnormalities of carbohydrate metabolism encountered in pregnancy.
Evaluating the feasibility of performing pharmacogenetic guided‐medication therapy management in a retirement community: A prospective, single arm study
Authors: Chaitesipaseut Lena , Wilson Norton Jennifer , Trivelli Kristen , Argon Sophie , Petrie Ichiko , Ragueneau‐Majlessi Isabelle , Mikes Tamatha , Nguyen Hao , Devine Beth
Published: November 2021

Introduction

Pharmacogenomic‐guided medication therapy management (PGx‐MTM) can optimize medication therapy for older adults. Pharmacist‐led PGx‐MTM in retirement communities has been infrequently described.

Objectives

We conducted a prospective, single‐arm feasibility study that incorporated PGx‐MTM services into an academic clinical practice at a retirement community. We posited that provision of PGx‐MTM services would be feasible and would enable us to identify one or more drug therapy‐related problems for each participant.

Methods

We screened residents using a predefined list of gene‐drug pairs for which the level of evidence for clinical impact is highest and consented those who were taking one of these medications (qualifying medication). The clinical pharmacist conducted PGx testing using a DNA buccal swab. Tests were analyzed by a commercial laboratory, and a corresponding Personalized Medicine Report generated. The Report included an assessment of gene‐drug pairs not only for qualifying medications, but for all pairs on our predefined list, in the event participants were prescribed these medications in the future (future medications). Results were risk‐categorized as “consider alternatives,” “use with caution,” or “standard precautions” (no change in therapy).The clinical pharmacist reviewed participant‐specific results for all gene‐drug pairs tested, then forwarded results to participants' providers along with recommendations for modifications in drug therapy. We calculated descriptive statistics to characterize participant‐specific demographic and clinical characteristics, medication use, PGx test results, and corresponding recommendations.

Results

Eighteen participants enrolled. We evaluated 23 results of qualifying medications, associated with six genes, 30% (7/23) of which were categorized as “use with caution” (warfarin) or “consider alternatives” (simvastatin, clopidogrel, and paroxetine). One required a change in therapy (simvastatin). When considering future medications (n = 245), the proportion was the same.

Conclusion

Our work demonstrates the feasibility of and suggests the potential for providing PGx‐MTM in retirement communities using preemptive genotyping, offering a new level of care to an often‐overlooked population, and advancing pharmacy practice.