bluuebunny/crossref_metadata_2025 huggingface dataset:
Anterior Segment Optical Coherence Tomography Angiography Following Trabecular Bypass Minimally Invasive Glaucoma Surgery
Authors: Gan Jinyuan , Sng Chelvin C. A. , Ke Mengyuan , Chieh Chew Shi , Tan Bingyao , Schmetterer Leopold , Ang Marcus
Published: March 2022

Objective

To assess anterior segment optical coherence tomography angiography (AS-OCTA) imaging of the episcleral vessels before and after trabecular bypass minimally invasive glaucoma surgery (MIGS).

Design

A prospective, clinical, single-centre, single-arm pilot feasibility study conducted at National University Hospital, Singapore.

Subjects

Patients with primary glaucomatous optic neuropathy undergoing Hydrus Microstent (Ivantis Inc., Irvine, CA, USA) implantation, who require at least one intra-ocular pressure-lowering medication. One or two eyes per patient may be enrolled.

Methods

We performed AS-OCTA (Nidek RS-3000 Advance 2, Gamagori, Japan) pre- and up to 6 months post-MIGS implantation using a standard protocol in all cornealimbal quadrants, to derive episcleral vessel densities (VD) using a previously described technique.

Main Outcome Measures

Episcleral VD pre- and post-surgery, in sectors with and without the implant.

Results

We obtained serial AS-OCTA images in 25 eyes undergoing MIGS implantation (23 subjects, mean age 70.3 ± 1.5, 61% female) with mean preoperative intraocular pressure (IOP) of 15.5 mmHg ± 4.0. We observed reductions in postoperative episcleral VD compared to preoperative VD at month 1 (mean difference −3.2, p = 0.001), month 3 (mean difference −2.94, p = 0.004) and month 6 (mean difference −2.19, p = 0.039) in sectors with implants (overall 6 month follow-up, p = 0.011). No significant changes were detected in episcleral VD in the sectors without implants (p = 0.910).

Conclusion

In our pilot study, AS-OCTA was able to detect changes in the episcleral VD following trabecular bypass MIGS, which may be a useful modality to evaluate surgical outcomes if validated in future studies.
The Value of Neutrophil-To-Lymphocyte Ratio for Evaluating Blood Stream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae: A Retrospective Cohort Study
Authors: Wu Heng , Mao Yihan , Du Xiaoxing , Zhao Feng , Jiang Yan , Yu Yunsong
Published: March 2022

Background

The neutrophil-to-lymphocyte ratio (NLR) is a useful marker of inflammation. However, the prognostic function of the NLR in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) blood stream infection (BSI) remains largely unknown. The aim of this study was to explore the potential relationship between the NLR and mortality in these patients.

Methods

We performed a retrospective cohort study based on data retrieved from the computerized patient record system in a tertiary hospital from 1 January 2017 to 31 October, 2020. A total of 134 inpatients with CRKP BSI were enrolled in this study, including 54 fatal cases and 80 survival cases, 28 days after the onset of CRKP BSI. A logistic analysis was performed to assess the association between the NLR on the 4th day and 28-day mortality. Multivariate analyses were used to control for the confounders.

Results

The overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis of the data of 134 patients and found that the NLR on the 4th day [odds ratio (OR) 1.148, 95% confidence interval (CI) 1.076–1.225, p < 0.001] and antibiotic exposure before BSI onset (OR 3.847, 95% CI 1.322–11.196, p = 0.013) were independent risk factors for 28-day mortality of patients with CRKP BSI, while appropriate initial therapy (AIT, OR 0.073, 95% CI 0.017–0.307, p < 0.001) was an independent protective factor. Among patients treated with AITs, the Cox proportional hazards regression analysis revealed a significant difference in prognosis (p = 0.006) between the ceftazidime/avibactam contained (CAZ) group and non CAZ-AVI groups. After dividing the non CAZ-AVI group into the tigecycline (TGC), colistin (COL), and TGC + COL groups, there were no differences between the CAZ-AVI group and the TGC group (p = 0.093), but CAZ-AVI group showed lower 28-day mortality than COL (p = 0.002) and TGC + COL (p = 0.002) groups. Meanwhile, there was no difference in NLR on the 1st day (p = 0.958) of patients in different groups but significant difference in NLR on the 4th day (p = 0.047).

Conclusions

The NLR on the 4th day is a readily available and independent prognostic biomarker for patients with CRKP BSI. This marker may have the potential for use in evaluating the efficacy of different anti-infection therapy strategies at an early stage.
Escherichia coli and Pseudomonas aeruginosa Isolated From Urine of Healthy Bovine Have Potential as Emerging Human and Bovine Pathogens
Authors: Giannattasio-Ferraz Silvia , Ene Adriana , Gomes Vitor Júnio , Queiroz Cid Oliveira , Maskeri Laura , Oliveira André Penido , Putonti Catherine , Barbosa-Stancioli Edel F.
Published: March 2022

The study of livestock microbiota has immediate benefits for animal health as well as mitigating food contamination and emerging pathogens. While prior research has indicated the gastrointestinal tract of cattle as the source for many zoonoses, including Shiga-toxin producing Escherichia coli and antibiotic resistant bacteria, the bovine urinary tract microbiota has yet to be thoroughly investigated. Here, we describe 5 E. coli and 4 Pseudomonas aeruginosa strains isolated from urine of dairy Gyr cattle. While both species are typically associated with urinary tract infections and mastitis, all of the animals sampled were healthy. The bovine urinary strains were compared to E. coli and P. aeruginosa isolates from other bovine samples as well as human urinary samples. While the bovine urinary E. coli isolates had genomic similarity to isolates from the gastrointestinal tract of cattle and other agricultural animals, the bovine urinary P. aeruginosa strains were most similar to human isolates suggesting niche adaptation rather than host adaptation. Examination of prophages harbored by these bovine isolates revealed similarity with prophages within distantly related E. coli and P. aeruginosa isolates from the human urinary tract. This suggests that related urinary phages may persist and/or be shared between mammals. Future studies of the bovine urinary microbiota are needed to ascertain if E. coli and P. aeruginosa are resident members of this niche and/or possible sources for emerging pathogens in humans.
The Use of Antibody-Antibiotic Conjugates to Fight Bacterial Infections
Authors: Cavaco Marco , Castanho Miguel A. R. B. , Neves Vera
Published: March 2022

The emergence of antimicrobial resistance (AMR) is rapidly increasing and it is one of the significant twenty-first century’s healthcare challenges. Unfortunately, the development of effective antimicrobial agents is a much slower and complex process compared to the spread of AMR. Consequently, the current options in the treatment of AMR are limited. One of the main alternatives to conventional antibiotics is the use of antibody-antibiotic conjugates (AACs). These innovative bioengineered agents take advantage of the selectivity, favorable pharmacokinetic (PK), and safety of antibodies, allowing the administration of more potent antibiotics with less off-target effects. Although AACs’ development is challenging due to the complexity of the three components, namely, the antibody, the antibiotic, and the linker, some successful examples are currently under clinical studies.
Capture Sequencing Enables Sensitive Detection of Tick-Borne Agents in Human Blood
Authors: Sanchez-Vicente Santiago , Jain Komal , Tagliafierro Teresa , Gokden Alper , Kapoor Vishal , Guo Cheng , Horn Elizabeth J. , Lipkin W. Ian , Tokarz Rafal
Published: March 2022

Assay sensitivity can be a limiting factor in the use of PCR as a tool for the detection of tick-borne pathogens in blood. We evaluated the performance of Tick-borne disease Capture Sequencing Assay (TBDCapSeq), a capture sequencing assay targeting tick-borne agents, to test 158 whole blood specimens obtained from the Lyme Disease Biobank. These included samples from 98 individuals with signs and symptoms of acute Lyme disease, 25 healthy individuals residing in Lyme disease endemic areas, and 35 samples collected from patients admitted to the Massachusetts General Hospital or referred to the infectious disease clinic. Compared to PCR, TBDCapSeq had better sensitivity and could identify infections with a wider range of tick-borne agents. TBDCapSeq identified a higher rate of samples positive for Borrelia burgdorferi (8 vs. 1 by PCR) and Babesia microti (26 vs. 15 by PCR). TBDCapSeq also identified previously unknown infections with Borrelia miyamotoi, Ehrlichia, and Rickettsia species. Overall, TBDCapSeq identified a pathogen in 43 samples vs. 23 using PCR, with four co-infections detected versus zero by PCR. We conclude that capture sequencing enables superior detection of tick-borne agents relative to PCR.
The Essential Role of Rac1 Glucosylation in Clostridioides difficile Toxin B-Induced Arrest of G1-S Transition
Authors: Petersen Lara , Stroh Svenja , Schöttelndreier Dennis , Grassl Guntram A. , Rottner Klemens , Brakebusch Cord , Fahrer Jörg , Genth Harald
Published: March 2022

Clostridioides difficile infection (CDI) in humans causes pseudomembranous colitis (PMC), which is a severe pathology characterized by a loss of epithelial barrier function and massive colonic inflammation. PMC has been attributed to the action of two large protein toxins, Toxin A (TcdA) and Toxin B (TcdB). TcdA and TcdB mono-O-glucosylate and thereby inactivate a broad spectrum of Rho GTPases and (in the case of TcdA) also some Ras GTPases. Rho/Ras GTPases promote G1-S transition through the activation of components of the ERK, AKT, and WNT signaling pathways. With regard to CDI pathology, TcdB is regarded of being capable of inhibiting colonic stem cell proliferation and colonic regeneration, which is likely causative for PMC. In particular, it is still unclear, the glucosylation of which substrate Rho-GTPase is critical for TcdB-induced arrest of G1-S transition. Exploiting SV40-immortalized mouse embryonic fibroblasts (MEFs) with deleted Rho subtype GTPases, evidence is provided that Rac1 (not Cdc42) positively regulates Cyclin D1, an essential factor of G1-S transition. TcdB-catalyzed Rac1 glucosylation results in Cyclin D1 suppression and arrested G1-S transition in MEFs and in human colonic epithelial cells (HCEC), Remarkably, Rac1−/− MEFs are insensitive to TcdB-induced arrest of G1-S transition, suggesting that TcdB arrests G1-S transition in a Rac1 glucosylation-dependent manner. Human intestinal organoids (HIOs) specifically expressed Cyclin D1 (neither Cyclin D2 nor Cyclin D3), which expression was suppressed upon TcdB treatment. In sum, Cyclin D1 expression in colonic cells seems to be regulated by Rho GTPases (most likely Rac1) and in turn seems to be susceptible to TcdB-induced suppression. With regard to PMC, toxin-catalyzed Rac1 glucosylation and subsequent G1-S arrest of colonic stem cells seems to be causative for decreased repair capacity of the colonic epithelium and delayed epithelial renewal.
Correlation Analysis Among Genotype Resistance, Phenotype Resistance, and Eradication Effect After Resistance-Guided Quadruple Therapies in Refractory Helicobacter pylori Infections
Authors: Guo Zijun , Tian Shuxin , Wang Weijun , Zhang Yanbin , Li Jing , Lin Rong
Published: March 2022

Objectives

The antimicrobial resistance of Helicobacter pylori (H. pylori) in most countries and regions has increased significantly. It has not been fully confirmed whether the detection of H. pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical personalized treatment. The objective of this study was to assess and compare the efficacy of different antimicrobial resistance-guided quadruple therapies in refractory H. pylori-infected individuals who had undergone unsuccessful prior eradication treatments.

Methods

From January 2019 to February 2020, genotypic and phenotypic resistances were determined by polymerase chain reaction (PCR), whole genome sequencing (WGS) and broth microdilution test, respectively, in 39 H. pylori-infected patients who have failed eradication for at least twice. The patients were retreated with bismuth quadruple therapy for 14 days according to individual antibiotic resistance results. Eradication status was determined by the 13C-urea breath test.

Results

The overall eradication rate was 79.5% (31/39, 95% CI 64.2–89.5%) in the intention-to-treat (ITT) analysis and 88.6% (31/35, 95% CI 73.5–96.1%) in the per- protocol analysis (PP) analysis. The presence of amoxicillin resistance (OR, 15.60; 95% CI, 1.34–182.09; p = 0.028), female sex (OR, 12.50; 95% CI, 1.10–142.31; p = 0.042) and no less than 3 prior eradication treatments (OR, 20.25; 95% CI, 1.67–245.44; p = 0.018), but not the methods for guiding therapy (p > 0.05) were associated with treatment failure. Resistance-guided therapy achieved eradication rates of more than 80% in these patients. The eradication rate of H. pylori in the phenotypic resistance-guided group was correlated well with genotype resistance-guided groups, including PCR and WGS.

Conclusion

Culture or molecular method guiding therapy can enable personalized, promise salvage treatments, and achieve comparably high eradication rates in patients with refractory H. pylori infection. The detection of H. pylori resistance mutations has a good clinical application prospect.

Protocol Study Register

[clinicaltrials.gov], identifier [ChiCTR1800020009].
Single-Molecule FRET: A Tool to Characterize DNA Nanostructures
Authors: Pal Nibedita
Published: March 2022

DNA nanostructures often involve temporally evolving spatial features. Tracking these temporal behaviors in real time requires sophisticated experimental methods with sufficiently high spatial and temporal resolution. Among the several strategies developed for this purpose, single-molecule FRET (smFRET) offers avenues to observe the structural rearrangement or locomotion of DNA nanostructures in real time and quantitatively measure the kinetics as well at the single nanostructure level. In this mini review, we discuss a few applications of smFRET-based techniques to study DNA nanostructures. These examples exemplify how smFRET signals not only have played an important role in the characterization of the nanostructures but also often have helped to improve the design and overall performance of the nanostructures and the devices designed from those structures. Overall, this review consolidates the potential of smFRET in providing crucial quantitative information on structure–function relations in DNA nanostructures.
Regulatory Roles of Antimicrobial Peptides in the Nervous System: Implications for Neuronal Aging
Authors: Stuart Bradey A. R. , Franitza Ariel L. , E Lezi
Published: March 2022

Antimicrobial peptides (AMPs) are classically known as important effector molecules in innate immunity across all multicellular organisms. However, emerging evidence begins to suggest multifunctional properties of AMPs beyond their antimicrobial activity, surprisingly including their roles in regulating neuronal function, such as sleep and memory formation. Aging, which is fundamental to neurodegeneration in both physiological and disease conditions, interestingly affects the expression pattern of many AMPs in an infection-independent manner. While it remains unclear whether these are coincidental events, or a mechanistic relationship exists, previous studies have suggested a close link between AMPs and a few key proteins involved in neurodegenerative diseases. This review discusses recent literature and advances in understanding the crosstalk between AMPs and the nervous system at both molecular and functional levels, with the aim to explore how AMPs may relate to neuronal vulnerability in aging.
Pain and the Triple Network Model
Authors: De Ridder Dirk , Vanneste Sven , Smith Mark , Adhia Divya
Published: March 2022

Acute pain is a physiological response that causes an unpleasant sensory and emotional experience in the presence of actual or potential tissue injury. Anatomically and symptomatically, chronic pathological pain can be divided into three distinct but interconnected pathways, a lateral “painfulness” pathway, a medial “suffering” pathway and a descending pain inhibitory circuit. Pain (fullness) can exist without suffering and suffering can exist without pain (fullness). The triple network model is offering a generic unifying framework that may be used to understand a variety of neuropsychiatric illnesses. It claims that brain disorders are caused by aberrant interactions within and between three cardinal brain networks: the self-representational default mode network, the behavioral relevance encoding salience network and the goal oriented central executive network. A painful stimulus usually leads to a negative cognitive, emotional, and autonomic response, phenomenologically expressed as pain related suffering, processed by the medial pathway. This anatomically overlaps with the salience network, which encodes behavioral relevance of the painful stimuli and the central sympathetic control network. When pain lasts longer than the healing time and becomes chronic, the pain- associated somatosensory cortex activity may become functionally connected to the self-representational default mode network, i.e., it becomes an intrinsic part of the self-percept. This is most likely an evolutionary adaptation to save energy, by separating pain from sympathetic energy-consuming action. By interacting with the frontoparietal central executive network, this can eventually lead to functional impairment. In conclusion, the three well-known pain pathways can be combined into the triple network model explaining the whole range of pain related co-morbidities. This paves the path for the creation of new customized and personalized treatment methods.
Functional Remodeling Associated With Language Recovery After Repetitive Transcranial Magnetic Stimulation in Chronic Aphasic Stroke
Authors: Lin Bing-Fong , Yeh Shih-Ching , Kao Yu-Chieh Jill , Lu Chia-Feng , Tsai Po-Yi
Published: March 2022

Background

Repetitive transcranial magnetic stimulation (rTMS) has shown promising efficacy in improving the language functions in poststroke aphasia. However, randomized controlled trials were lacking to investigate the rTMS-related neuroimaging changes underlying the therapeutic effects on language improvement in chronic aphasia.

Objective

In this study, we aimed to evaluate the effects of low-frequency rTMS (LF-rTMS) on chronic poststroke aphasia. We hypothesized that the deactivation of the right pars triangularis could restore the balance of interhemispheric inhibition and, hence, facilitated the functional remodeling of language networks in both the hemispheres. Furthermore, the rTMS-induced functional reorganization should underpin the language recovery after rTMS.

Methods

A total of 33 patients (22 males; age: 58.70 ± 13.77 years) with chronic stroke in the left hemisphere and nonfluent aphasia were recruited in this randomized double-blinded study. The ratio of randomization between the rTMS and sham groups is 17:16. All the patients received real 1-Hz rTMS or sham stimulation (placebo coil delivered < 5% of magnetic output with similar audible click-on discharge) at the right posterior pars triangularis for 10 consecutive weekdays (stroke onset to the first stimulation: 10.97 ± 10.35 months). Functional connectivity of language networks measured by resting-state fMRI was calculated and correlated to the scores of the Concise Chinese Aphasia Test by using the stepwise regression analysis.

Results

After LF-rTMS intervention, significant improvement in language functions in terms of comprehension and expression abilities was observed compared with the sham group. The rTMS group showed a significant decrease of coupling strength between right pars triangularis and pars opercularis with a strengthened connection between right pars orbitalis and angular gyrus. Furthermore, the LF-rTMS significantly enhanced the coupling strength associated with left Wernicke area. Results of regression analysis showed that the identified functional remodeling involving both the hemispheres could support and predict the language recovery after LF-rTMS treatment.

Conclusion

We reported the therapeutic effects of LF-rTMS and corresponding functional remodeling in chronic poststroke aphasia. Our results provided neuroimage evidence reflecting the rebalance of interhemispheric inhibition induced by LF-rTMS, which could facilitate future research in the refinement of rTMS protocol to optimize the neuromodulation efficacy and benefit the clinical management of patients with stroke.
The Significance of Atrial Fibrillation in Patients With Transient Global Amnesia
Authors: Simaan Naaem , Honig Asaf , Filioglo Andrei , Jeremy Molad , Leker Ronen R.
Published: March 2022

Background and Purpose

The etiology of transient global amnesia (TGA) remains unclear in a large subset of patients. We aimed to determine the clinical and radiological characteristics of TGA-patients with suspected acute micro-embolic stroke on diffusion-weighted imaging (DWI).

Methods

TGA-patients that had new DWI hippocampal lesions (DWI+) were compared to DWI negative TGA-patients (DWI–). Demographics, risk factors, clinical data, radiological data, and mortality were analyzed.

Results

Out of 83 patients diagnosed with TGA, 56 (65%) underwent MRI during the acute hospitalization and 26 (46%) had new hippocampal DWI lesions. DWI+ patients more often had a history of atrial fibrillation (AF, 26 vs. 7%, p = 0.04) but the frequency of other risk factors did not differ. None of the patients died, however, two DWI+ patients had subsequent stroke during a 2-year follow up and both had AF. In contrast, none of the DWI- patients had recurrent events.

Conclusion

AF is common among DWI+ TGA-patients. The presence of AF in patients with TGA could suggest an increased risk of subsequent stroke.
Recurrence of Anti-N-Methyl-D-Aspartate Receptor Encephalitis: A Cohort Study in Central China
Authors: Feng Jilun , Yang Mu , Cui Dingge , Huang Zhi , Ji Tuo , Lian Yajun
Published: March 2022

Objective

To investigate factors that could impact or predict the probability of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis recurrence in central China.

Methods

From November 2014 to October 2020, observational data of anti-NMDAR encephalitis inpatients in our institution were collected and analyzed prospectively. The demographics, clinical characteristics, tumor status, lesion locations on MRI and immunotherapies, etc. had entered into a Cox regression model for the identification of the factors associated with relapse-free survival.

Results

We enrolled 113 patients in a row (median age: 28 years, range: 1–61 years). The gender distribution was not statistically significant (p = 0.158), with 49 people (43.4%) being female. The median follow-up time was 16 (4–77) months. Among them, 16.8% of patients relapsed. The average interval between recurrences was 8 months (range 3–54 mo). The severity of the initial relapse was less severe than it had been at the start. The first relapse had considerably fewer symptoms (median 2, range 1–6) than the first episode (median 4, range 1–8, p = 0.005). The mRS at first relapse (median 3, mean 2.84, range 1–5) had been significantly lower than that at onset (median 4, mean 3.89, range 3–5, p = 0.004). The length of hospitalization at first relapse (median 17 days, range 5–46) was significantly shorter than the first episode (median 35 days, range 14–102, p = 0.002). In the survival analysis, the risk of recurrence was significantly higher for patients with a brainstem lesion (HR: 4.112, 95% CI: 1.205–14.030; p = 0.024) or ≥3 abnormal sites (HR: 2.926, 95% CI: 1.085–7.896; p = 0.034) on brain MRI at the first episode. There was no significant difference in neurological outcomes between the recurrent and monophasic groups at the most recent follow-up (mRS 0–2 in 17/19 vs. 86/94; p = 0.674).

Conclusions

Anti-NMDAR encephalitis can recur in around one out of every six cases, and symptoms are generally milder than when it first appears. Recurrence is not related to the severity in the acute phase or the prognosis at follow-up. Patients with ≥3 abnormal sites on MRI or lesions located in the brainstem at onset must be alert to the possibility of recurrence.
AT-NeuroEAE: A Joint Extraction Model of Events With Attributes for Research Sharing-Oriented Neuroimaging Provenance Construction
Authors: Lin Shaofu , Xu Zhe , Sheng Ying , Chen Lihong , Chen Jianhui
Published: March 2022

Provenances are a research focus of neuroimaging resources sharing. An amount of work has been done to construct high-quality neuroimaging provenances in a standardized and convenient way. However, besides existing processed-based provenance extraction methods, open research sharing in computational neuroscience still needs one way to extract provenance information from rapidly growing published resources. This paper proposes a literature mining-based approach for research sharing-oriented neuroimaging provenance construction. A group of neuroimaging event-containing attributes are defined to model the whole process of neuroimaging researches, and a joint extraction model based on deep adversarial learning, called AT-NeuroEAE, is proposed to realize the event extraction in a few-shot learning scenario. Finally, a group of experiments were performed on the real data set from the journal PLOS ONE. Experimental results show that the proposed method provides a practical approach to quickly collect research information for neuroimaging provenance construction oriented to open research sharing.
RETRACTED: Dietary Patterns in Adults Following the Christian Orthodox Fasting Regime in Greece
Authors: Kokkinopoulou Anna , Pagkalos Ioannis , Hassapidou Maria , Kafatos Anthony
Published: March 2022

Objective

The aim of the study was to identify and describe the dietary patterns seen in a carefully selected sample that follows the Christian Orthodox Church (COC) fasting regime in Greece.

Methods

A number of 361 individuals from Northern Greece participated in this cross-sectional study. A number of 176 subjects have been fasting according to the COC recommendations since childhood and 185 non-fasters acted as the control group. Dietary data from a validated food frequency questionnaire were used to derive dietary patterns by principal component analysis (PCA).

Results

Three distinct dietary patterns were identified in the fasting population, the “COC Fasting,” the “Western,” and the “Traditional” dietary pattern, whereas in the non-fasting population, two dietary patterns were found the “Western” and the “Traditional.” The dietary patterns in the fasting population were associated with healthier lifestyle choices, such as abstaining from alcohol and smoke and reduced red and processed meats consumption.

Conclusion

Findings from the study revealed that people who adhere to the COC fasting recommendations since childhood tend to follow this dietary pattern throughout the year. By gaining insights into the energy and nutrient intake of this unique dietary pattern, public health stakeholders could promote healthier eating behaviors to prevent non-communicable chronic diseases, such as obesity and metabolic syndrome.
Priority Micronutrient Density in Foods
Authors: Beal Ty , Ortenzi Flaminia
Published: March 2022

Background

Despite concerted efforts to improve diet quality and reduce malnutrition, micronutrient deficiencies remain widespread globally, especially in low- and middle-income countries and among population groups with increased needs, where diets are often inadequate in iron, zinc, folate, vitamin A, calcium, and vitamin B12. There is a need to understand the density of these micronutrients and their bioavailability across diverse foods and the suitability of these foods to help meet requirements for populations with high burdens of micronutrient malnutrition.

Objective

We aimed to identify the top food sources of these commonly lacking micronutrients, which are essential for optimal health, to support efforts to reduce micronutrient malnutrition among various populations globally.

Methods

We built an aggregated global food composition database and calculated recommended nutrient intakes for five population groups with varying requirements. An approach was developed to rate foods according to their density in each and all priority micronutrients for various population groups with different nutrient requirements.

Results

We find that the top sources of priority micronutrients are organs, small fish, dark green leafy vegetables, bivalves, crustaceans, goat, beef, eggs, milk, canned fish with bones, mutton, and lamb. Cheese, goat milk, and pork are also good sources, and to a lesser extent, yogurt, fresh fish, pulses, teff, and canned fish without bones.

Conclusion

The results provide insight into which foods to prioritize to fill common micronutrient gaps and reduce undernutrition.
Dietary Customs and Social Deprivation in an Aging Population From Southern Italy: A Machine Learning Approach
Authors: Tatoli Rossella , Lampignano Luisa , Donghia Rossella , Castellana Fabio , Zupo Roberta , Bortone Ilaria , De Nucci Sara , Campanile Giuseppe , Lofù Domenico , Vimercati Luigi , Lozupone Madia , De Pergola Giovanni , Panza Francesco , Giannelli Gianluigi , Di Noia Tommaso , Boeing Heiner , Sardone Rodolfo
Published: March 2022

Background

Diet and social determinants influence the state of human health. In older adults, the presence of social, physical and psychological barriers increases the probability of deprivation. This study investigated the relationship between social deprivation and eating habits in non-institutionalized older adults from Southern Italy, and identified foods and dietary habits associated with social deprivation.

Methods

We recruited 1,002 subjects, mean age 74 years, from the large population based Salus in Apulia Study. In this cross-sectional study, eating habits and the level of deprivation were assessed with FFQ and DiPCare-Q, respectively.

Results

Deprived subjects (n = 441) included slightly more females, who were slightly older and with a lower level of education. They consumed less fish (23 vs. 26 g), fruiting vegetables (87 vs. 102 g), nuts (6 vs. 9 g) and less “ready to eat” dishes (29 vs. 33 g). A Random Forest (RF) model was used to identify a dietary pattern associated with social deprivation. This pattern included an increased consumption of low-fat dairy products and white meat, and a decreased consumption of wine, leafy vegetables, seafood/shellfish, processed meat, red meat, dairy products, and eggs.

Conclusion

The present study showed that social factors also define diet and eating habits. Subjects with higher levels of deprivation consume cheaper and more readily available food.
The Joint Association Between Multiple Dietary Patterns and Depressive Symptoms in Adults Aged 55 and Over in Northern China
Authors: Ma Yuxia , Li Ruiqiang , Zhan Wenqiang , Huang Xin , Zhang Limin , Liu Zhan
Published: March 2022

Background

Depression is a common psychiatric disorder in older adults that affects their health-related quality of life. Two percent of adults over the age of 55 suffer from major depression, and the prevalence of depression increases with age. Even in the absence of major depressive disorder, 10–15% of older adults have clinically significant depressive symptoms.

Objectives

Epidemiological studies on the association between different gender eating patterns and depression show inconsistent associations. Our study examined whether different gender eating patterns are related to depression. We consider eating patterns individually and as a joint exposure to predefined eating patterns.

Methods

Principal component analysis (PCA) was performed on the data of the 24-h diet recall dietary intake, and the dietary pattern was determined. Linear regression models are used to explore the relationship between different diets and depression of men and women; weighted quantile sum (WQS) regression, quantile g calculation (qgcomp) and Bayesian kernel machine regression (BKMR) are performed as Secondary analysis.

Results

In the dietary patterns model, we found that the vegetable and fruit-based diet has a significant inhibitory effect in women, and the egg-milk-based diet has a significant inhibitory effect in men. We found that when all dietary factors are above the 55th percentile, there is a significant positive correlation between multiple dietary patterns and depression risk. We also determined a positive correlation between meat and obesity risk and a negative correlation between egg and milk and vegetables and fruits.

Conclusions

In the study population, after controlling for other baseline indicators and predictors of dietary pattern exposure, a fruit and vegetable-based diet was associated with a slightly healthier and lower risk of depression, while a meat-based dietary pattern associated with a higher risk of depression, and this association effect varies between genders.
Caspase-8: Friend or Foe in Bortezomib/Lenalidomide-Based Therapy for Myeloma
Authors: Zhou Liang
Published: March 2022

Antiproliferation and proapoptosis are two major molecular mechanisms of action of drugs used for the treatment of multiple myeloma. Proteasome inhibitors, such as bortezomib (PS-341), and immunomodulatory drugs (IMiDs), such as lenalidomide, are the two drug types approved for the treatment of myeloma. Bortezomib and lenalidomide activate caspase-8 and promote the apoptosis of myeloma cells. However, caspase-8 inhibition potentiated the antiproliferative effect of lenalidomide and bortezomib in myeloma cells, suggesting that caspase-8 could regulate proliferation and apoptosis in the opposite pathway. In this mini-review, I summarized recent advances in determining the molecular mechanisms of caspase-8 in bortezomib–lenalidomide-based therapy for myeloma and explored the possible functions of caspase-8 in the proliferation and apoptosis of myeloma cells. Furthermore, future directions of caspase-8-based therapy for myeloma have been discussed.
Is There a Role for Large Exome Sequencing in the Management of Metastatic Non-Small Cell Lung Cancer: A Brief Report of Real Life
Authors: Dalens Lorraine , Niogret Julie , Kaderbhai Courèche Guillaume , Boidot Romain
Published: March 2022

Introduction

Non-small-cell lung cancer (NSCLC) is one of the main causes of death by cancer worldwide. With the rise of targeted therapies, the search for molecular abnormalities is becoming a crucial step in the management of lung cancer. Whole exome sequencing (WES) is developing rapidly and is now accessible in routine care. However, its value, compared to smaller gene panels, remains unclear.

Methods

We conducted a retrospective analysis of all 281 patients with lung carcinoma referred to the Molecular Tumor Board of the Georges-François Leclerc Cancer Center (CGFL) between March 2015 and January 2018. We compared the results of standard molecular testing with the results of WES performed on every patient.

Results

WES highlighted many more mutations than smaller panels (mutations were found in 82 genes, while smaller panels found, at the most, mutations in 12 genes). Most of these mutations were class III or IV according to the ESCAT classification. The exome sensitivity also showed limitations, notably a slightly lower efficiency for common mutations, including classical EGFR mutations.

Conclusion

Small, targeted panels could be preferred over WES at the initial diagnosis of metastatic NSCLC. They are more sensitive for the identification of mutations on the most frequently mutated genes, such as ALK, BRAF, EGFR, ERBB2, KRAS or MET. Larger panels or WES could be useful at disease progression, to enlarge treatment possibilities by highlighting uncommon but potentially targetable mutations that are not covered by smaller, targeted panels.
Case Report: Interest of Positron Emission Tomography in Pediatric Small Vessel Primary Angiitis of the Central Nervous System
Authors: Belcour Morgane , Dontaine Pauline , Monier Anne , Lebrun Laetitia , Salmon Isabelle , De Witte Olivier , Goldman Serge , De Tiège Xavier , Aeby Alec
Published: March 2022

Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease affecting central nervous system vessels. The diagnosis, which requires confirmation by brain biopsy, remains challenging due to unspecific clinical presentation and low specificity of imaging and laboratory exams. In these two pediatric biopsy-proven cases of svPACNS we demonstrate that brain positron emission tomography (PET) show a high metabolic activity that extends beyond brain MRI abnormalities. Therefore, combining MRI and PET abnormalities to adequately guide brain biopsy might increase the diagnostic yield of this rare condition.
The Developing Microbiome From Birth to 3 Years: The Gut-Brain Axis and Neurodevelopmental Outcomes
Authors: Laue Hannah E. , Coker Modupe O. , Madan Juliette C.
Published: March 2022

The volume and breadth of research on the role of the microbiome in neurodevelopmental and neuropsychiatric disorders has expanded greatly over the last decade, opening doors to new models of mechanisms of the gut-brain axis and therapeutic interventions to reduce the burden of these outcomes. Studies have highlighted the window of birth to 3 years as an especially sensitive window when interventions may be the most effective. Harnessing the powerful gut-brain axis during this critical developmental window clarifies important investigations into the microbe-human connection and the developing brain, affording opportunities to prevent rather than treat neurodevelopmental disorders and neuropsychiatric illness. In this review, we present an overview of the developing intestinal microbiome in the critical window of birth to age 3; and its prospective relationship with neurodevelopment, with particular emphasis on immunological mechanisms. Next, the role of the microbiome in neurobehavioral outcomes (such as autism, anxiety, and attention-deficit hyperactivity disorder) as well as cognitive development are described. In these sections, we highlight the importance of pairing mechanistic studies in murine models with large scale epidemiological studies that aim to clarify the typical health promoting microbiome in early life across varied populations in comparison to dysbiosis. The microbiome is an important focus in human studies because it is so readily alterable with simple interventions, and we briefly outline what is known about microbiome targeted interventions in neurodevelopmental outcomes. More novel examinations of known environmental chemicals that adversely impact neurodevelopmental outcomes and the potential role of the microbiome as a mediator or modifier are discussed. Finally, we look to the future and emphasize the need for additional research to identify populations that are sensitive to alterations in their gut microbiome and clarify how interventions might correct and optimize neurodevelopmental outcomes.
Evaluation of Growth Hormone Therapy in Seven Chinese Children With Familial Short Stature Caused by Novel ACAN Variants
Authors: Sun Jie , Jiang Lihong , Liu Geli , Ma Chen , Zheng Jiaqi , Niu Lele
Published: March 2022

Objective

ACAN gene variants are an important cause of familial short stature (FSS). Appropriate growth-promoting therapies effectively improve the patient height. Here, we report a therapeutic assessment of cases of seven families of FSS patients with heterozygous ACAN variants. Our findings provide a valuable theoretical basis for the clinical diagnosis and treatment of this disease.

Methods

From December 2020 to June 2021, 32 FSS patients were examined in Tianjin Medical University General Hospital (Tianjin, China) by whole-exome sequencing to determine whether ACAN variants were present. Their clinical data were summarized and scrupulously analyzed.

Results

We found seven novel heterozygous ACAN variants: c.1051 + 2T > A, c.313T > C (p.S105P), c.2660C > G (p.S887X), c.2153C > A (p. T718K), c.7243delG (p.D2415Tfs*4), c.2911G > T (p.G971X), c.758-7T > C. All seven patients had proportionate short stature and mild skeletal dysplasia. Endocrine examination results were normal. Only one of the patients had an advanced bone age (1.1 years older than chronological age), whereas the other patients had normal bone ages. All of them had a family history of short stature, with or without osteoarthritis or intervertebral disc disease. All seven patients accepted treatment with recombinant human growth hormone (rhGH) and were regularly followed up. One patient did not come at the follow-up visit. The height of the remaining six patients before and after the treatment was −2.89 ± 0.68 SDS, −1.91 ± 0.93 SDS, respectively, with a treatment course of 1.85 ± 1.91 years. A good therapeutic response was observed in all of them.

Conclusions

In this study, seven novel heterozygous variants in ACAN were discovered, which expanded the spectrum of the already established ACAN pathogenic variants. In FSS cohort, the proportion of ACAN variants accounted was large. The treatment with rhGH effectively increased the patient height, but further studies with longer follow-up periods and more extensive observations are required to elucidate the long-term effect.
Familial Experience With Hirschsprung's Disease Improves the Patient's Ability to Cope
Authors: Verkuijl Sanne J. , Meinds Rob J. , van der Steeg Alida F. W. , Sloots Cornelius E. J. , van Heurn Ernst , de Blaauw Ivo , van Gemert Wim G. , Witvliet Marieke J. , Vermeulen Karin M. , Trzpis Monika , Broens Paul M. A.
Published: March 2022

Introduction

Familial occurrence of Hirschsprung's disease may have a positive effect on patients' ability to cope with the disease. The aim was to compare long-term bowel function and generic quality of life between patients with familial and non-familial Hirschsprung's disease.

Methods

This was a nationwide, cross-sectional study in which we included all 830 Hirschsprung patients of 8 years and older who had undergone surgery between 1957 and 2015. We excluded patients with a permanent stoma, intellectual disability, or an unknown or foreign address. We requested patients to complete the validated pediatric or adult Defecation and Fecal Continence questionnaire and the Child Health Questionnaire Child Form-87, or the World Health Organization Quality of Life-100 Assessment Instrument.

Results

We analyzed 336 Hirschsprung patients, 15.8% of whom were familial cases and 84.2% were non-familial cases. After adjusting for aganglionic length, sex, and age, patients with familial Hirschsprung's disease were twice more likely to suffer from constipation (OR = 2.47, 95% CI, 1.21–5.05, p = 0.013). The quality of life of the pediatric patients was comparable, but in adult patients the energy/fatigue, thinking/learning/concentration, and work capacity facets showed better scores in the familial patients with Hirschsprung's disease of the rectosigmoid (p = 0.029, p = 0.024, p = 0.036, respectively).

Conclusions

Different facets of generic quality of life are better in adult patients with familial Hirschsprung's disease of the rectosigmoid. It seems that familial experience with the disease influences patients' coping abilities positively.
Anakinra in Paediatric Rheumatology and Periodic Fever Clinics: Is the Higher Dose Safe?
Authors: Fingerhutová Šárka , Jančová Eva , Doležalová Pavla
Published: March 2022

Objective

Anakinra has been increasingly used in off-label indications as well as dosing and mode of administration in a variety of inflammatory conditions. We aimed to review our clinical practice and compare treatment outcomes with published data.

Methods

Clinical data from electronic records were retrospectively reviewed for patients treated with anakinra over the past 6 years for autoinflammatory diseases (AID).

Results

From 47 eligible patients (27 female patients), 32 were children. Macrophage activation syndrome (MAS) was the indication for anakinra therapy in 42.6% of patients. Systemic juvenile idiopathic arthritis (SJIA) was the most common underlying diagnosis (19/47) followed by the spectrum of AID. Off-label use was noted in 38.3% patients. Recommended dose was exceeded in 21 children (mean induction dose 5.1, highest dose 29.4 mg/kg/day) and two adults; five patients were treated intravenously. The mean treatment duration for SJIA was 1.4 years, that for AID was 2.2 years, and that for patients with higher anakinra dose was 9.7 (19.3) months. The mean follow-up duration was 2.7 (1.7) years. Treatment was effective in the majority of SJIA and cryopyrinopathy patients as well as those with MAS. Anakinra was well-tolerated without any major adverse effects even in patients with long-term administration of higher than recommended doses including two infants treated with a dose of over 20 mg/kg/day.

Conclusion

Our results support early use of anakinra in the individually tailored dosing. In patients with hyperinflammation, anakinra may be lifesaving and may even allow for corticosteroid avoidance. Further studies are needed in order to set up generally accepted response parameters and define condition-specific optimal dosing regimen.
To Probiotic or Not to Probiotic: A Metagenomic Comparison of the Discharge Gut Microbiome of Infants Supplemented With Probiotics in NICU and Those Who Are Not
Authors: Westaway Jacob A. F. , Huerlimann Roger , Kandasamy Yoga , Miller Catherine M. , Norton Robert , Watson David , Infante-Vilamil Sandra , Rudd Donna
Published: March 2022

Background

Preterm birth is associated with the development of both acute and chronic disease, and the disruption of normal gut microbiome development. Recent studies have sought to both characterize and understand the links between disease and the microbiome. Probiotic treatment may correct for these microbial imbalances and, in turn, mitigate disease. However, the criteria for probiotic supplementation in NICU's in North Queensland, Australia limits its usage to the most premature (<32 weeks gestation) and small for gestational age infants (<1,500 g). Here we use a combination of amplicon and shotgun metagenomic sequencing to compare the gut microbiome of infants who fulfill the criteria for probiotic-treatment and those who do not. The aims of this study were to determine if probiotic-supplemented preterm infants have significantly different taxonomic and functional profiles when compared to non-supplemented preterm infants at discharge.

Methods

Preterm infants were recruited in North Queensland, Australia, with fecal samples collected just prior to discharge (36 ± 0.5 weeks gestation), to capture potential changes that could be probiotic induced. All samples underwent 16S rRNA gene amplicon sequencing, with a subset also used for shotgun metagenomics. Mixed effects models were used to assess the effect of probiotics on alpha diversity, beta diversity and taxonomic abundance, whilst accounting for other known covariates.

Results

Mixed effects modeling demonstrated that probiotic treatment had a significant effect on overall community composition (beta diversity), characterized by greater alpha diversity and differing abundances of several taxa, including Bifidobacterium and Lactobacillus, in supplemented infants.

Conclusion

Late preterm-infants who go without probiotic-supplementation may be missing out on stabilizing-effects provided through increased alpha diversity and the presence of commensal microbes, via the use of probiotic-treatment. These findings suggest that late-preterm infants may benefit from probiotic supplementation. More research is needed to both understand the consequences of the differences observed and the long-term effects of this probiotic-treatment.