bluuebunny/crossref_metadata_2025 huggingface dataset:
Mapping Microbial Abundance and Prevalence to Changing Oxygen Concentration in Deep-Sea Sediments Using Machine Learning and Differential Abundance
Authors: Møller Tor Einar , Le Moine Bauer Sven , Hannisdal Bjarte , Zhao Rui , Baumberger Tamara , Roerdink Desiree L. , Dupuis Amandine , Thorseth Ingunn H. , Pedersen Rolf Birger , Jørgensen Steffen Leth
Published: May 2022

Oxygen constitutes one of the strongest factors explaining microbial taxonomic variability in deep-sea sediments. However, deep-sea microbiome studies often lack the spatial resolution to study the oxygen gradient and transition zone beyond the oxic-anoxic dichotomy, thus leaving important questions regarding the microbial response to changing conditions unanswered. Here, we use machine learning and differential abundance analysis on 184 samples from 11 sediment cores retrieved along the Arctic Mid-Ocean Ridge to study how changing oxygen concentrations (1) are predicted by the relative abundance of higher taxa and (2) influence the distribution of individual Operational Taxonomic Units. We find that some of the most abundant classes of microorganisms can be used to classify samples according to oxygen concentration. At the level of Operational Taxonomic Units, however, representatives of common classes are not differentially abundant from high-oxic to low-oxic conditions. This weakened response to changing oxygen concentration suggests that the abundance and prevalence of highly abundant OTUs may be better explained by other variables than oxygen. Our results suggest that a relatively homogeneous microbiome is recruited to the benthos, and that the microbiome then becomes more heterogeneous as oxygen drops below 25 μM. Our analytical approach takes into account the oft-ignored compositional nature of relative abundance data, and provides a framework for extracting biologically meaningful associations from datasets spanning multiple sedimentary cores.
Methanotrophy Alleviates Nitrogen Constraint of Carbon Turnover by Rice Root-Associated Microbiomes
Authors: Cao Weiwei , Cai Yuanfeng , Bao Zhihua , Wang Shuwei , Yan Xiaoyuan , Jia Zhongjun
Published: May 2022

The bioavailability of nitrogen constrains primary productivity, and ecosystem stoichiometry implies stimulation of N2 fixation in association with carbon sequestration in hotspots such as paddy soils. In this study, we show that N2 fixation was triggered by methane oxidation and the methanotrophs serve as microbial engines driving the turnover of carbon and nitrogen in rice roots. 15N2-stable isotope probing showed that N2-fixing activity was stimulated 160-fold by CH4 oxidation from 0.27 to 43.3 μmol N g–1 dry weight root biomass, and approximately 42.5% of the fixed N existed in the form of 15N-NH4+ through microbial mineralization. Nitrate amendment almost completely abolished N2 fixation. Ecophysiology flux measurement indicated that methane oxidation-induced N2 fixation contributed only 1.9% of total nitrogen, whereas methanotrophy-primed mineralization accounted for 21.7% of total nitrogen to facilitate root carbon turnover. DNA-based stable isotope probing further indicated that gammaproteobacterial Methylomonas-like methanotrophs dominated N2 fixation in CH4-consuming roots, whereas nitrate addition resulted in the shift of the active population to alphaproteobacterial Methylocystis-like methanotrophs. Co-occurring pattern analysis of active microbial community further suggested that a number of keystone taxa could have played a major role in nitrogen acquisition through root decomposition and N2 fixation to facilitate nutrient cycling while maintaining soil productivity. This study thus highlights the importance of root-associated methanotrophs as both biofilters of greenhouse gas methane and microbial engines of bioavailable nitrogen for rice growth.
Emergence of a Carbapenem-Resistant Klebsiella pneumoniae Isolate Co-harbouring Dual blaNDM– 6-Carrying Plasmids in China
Authors: Gong Yali , Lu Yifei , Xue Dongdong , Wei Yu , Li Qimeng , Li Gang , Lu Shuguang , Wang Jing , Wang Yunying , Peng Yizhi , Zhao Yan
Published: May 2022

The widespread emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) with limited therapeutic options has become a global concern. In this study, a K. pneumoniae strain called KP2e was recovered from a human case of fatal septic shock in a Chinese hospital. Polymerase chain reaction and sequencing, antimicrobial susceptibility testing, conjugation experiments, S1 nuclease-pulsed field gel electrophoresis/southern blot, whole genome sequencing and comparative genomics were performed to investigate the phenotypic and molecular characteristics of this isolate. KP2e possessed the NDM-6-encoding gene and exhibited resistance to almost all β-lactams except for monobactam. This strain belonged to sequence type 4024, the complete genome of which was composed of one chromosome and three plasmids. Furthermore, blaNDM–6 coexisted on two self-transmissible plasmids, which were assigned to types IncFIB and IncN. A structure of IS26-composite transposon capturing an identical Tn125 remnant (ΔISAba125-blaNDM–6-bleMBL-trpF-dsbC-cutA-groES-ΔgroEL) was identified in the two plasmids, and this conserved blaNDM-surrounding genetic context was similar to that of few IncN plasmids found in other regions of China. Our research appears to be the first description of a clinical strain that emerged co-harbouring dual blaNDM-carrying plasmids, and the first report of NDM-6-positive CRKP in China. These findings demonstrated that IncN is a key medium in the evolution and expanding dissemination of blaNDM genes among various species, which indicates that close monitoring and rapid detection of blaNDM-harbouring plasmids is necessary.
α-Synuclein in the Synaptic Vesicle Liquid Phase: Active Player or Passive Bystander?
Authors: Brodin Lennart , Milovanovic Dragomir , Rizzoli Silvio O. , Shupliakov Oleg
Published: May 2022

The protein α-synuclein, which is well-known for its links to Parkinson’s Disease, is associated with synaptic vesicles (SVs) in nerve terminals. Despite intensive studies, its precise physiological function remains elusive. Accumulating evidence indicates that liquid-liquid phase separation takes part in the assembly and/or maintenance of different synaptic compartments. The current review discusses recent data suggesting α-synuclein as a component of the SV liquid phase. We also consider possible implications of these data for disease.
A Resource to Infer Molecular Paths Linking Cancer Mutations to Perturbation of Cell Metabolism
Authors: Iannuccelli Marta , Lo Surdo Prisca , Licata Luana , Castagnoli Luisa , Cesareni Gianni , Perfetto Livia
Published: May 2022

Some inherited or somatically-acquired gene variants are observed significantly more frequently in the genome of cancer cells. Although many of these cannot be confidently classified as driver mutations, they may contribute to shaping a cell environment that favours cancer onset and development. Understanding how these gene variants causally affect cancer phenotypes may help developing strategies for reverting the disease phenotype. Here we focus on variants of genes whose products have the potential to modulate metabolism to support uncontrolled cell growth. Over recent months our team of expert curators has undertaken an effort to annotate in the database SIGNOR 1) metabolic pathways that are deregulated in cancer and 2) interactions connecting oncogenes and tumour suppressors to metabolic enzymes. In addition, we refined a recently developed graph analysis tool that permits users to infer causal paths leading from any human gene to modulation of metabolic pathways. The tool grounds on a human signed and directed network that connects ∼8400 biological entities such as proteins and protein complexes via causal relationships. The network, which is based on more than 30,000 published causal links, can be downloaded from the SIGNOR website. In addition, as SIGNOR stores information on drugs or other chemicals targeting the activity of many of the genes in the network, the identification of likely functional paths offers a rational framework for exploring new therapeutic strategies that revert the disease phenotype.
Adipose-Derived Mesenchymal Stem Cells Combined With Extracellular Vesicles May Improve Amyotrophic Lateral Sclerosis
Authors: Wang Xichen , Zhang Yong , Jin Tian , Botchway Benson O. A. , Fan Ruihua , Wang Lvxia , Liu Xuehong
Published: May 2022

The complexity of central nervous system diseases together with their intricate pathogenesis complicate the establishment of effective treatment strategies. Presently, the superiority of adipose-derived mesenchymal stem cells (ADSCs) on neuronal injuries has attracted significant attention. Similarly, extracellular vesicles (EVs) are potential interventional agents that could identify and treat nerve injuries. Herein, we reviewed the potential effects of ADSCs and EVs on amyotrophic lateral sclerosis (ALS) injured nerves, and expound on their practical application in the clinic setting. This article predominantly focused on the therapeutic role of ADSCs concerning the pathogenesis of ALS, the protective and reparative effects of EVs on nerve injury, as well as the impact following the combined usage of ADSCs and EVs in ALS.
Association of Circulating Apolipoprotein AI Levels in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis
Authors: Tong Jun-hui , Gong Shi-qiang , Zhang Yan-song , Dong Jian-ru , Zhong Xin , Wei Min-jie , Liu Ming-yan
Published: May 2022

With the development of medicine, our research on Alzheimer's disease (AD) has been further deepened, but the mechanism of its occurrence and development has not been fully revealed, and there is currently no effective treatment method. Several studies have shown that apolipoprotein AI (ApoA-I) can affect the occurrence and development of Alzheimer's disease by binding to amyloid β (Aβ). However, the association between circulating levels of ApoA-I and AD remains controversial. We conducted a meta-analysis of 18 studies published between 1992 and 2017 to determine whether the ApoA-I levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, EMBASE and Web of Science databases without language limitations. A pooled subject sample including 1,077 AD patients and 1,271 healthy controls (HCs) was available to assess circulating ApoA-I levels; 747 AD patients and 680 HCs were included for ApoA-I levels in serum; 246 AD patients and 456 HCs were included for ApoA-I levels in plasma; 201 AD patients and 447 HCs were included for ApoA-I levels in CSF. It was found that serum and plasma levels of ApoA-I were significantly reduced in AD patients compared with HCs {[standardized mean difference (SMD) = −1.16; 95% confidence interval (CI) (−1.72, −0.59); P = 0.000] and [SMD = −1.13; 95% CI (−2.05, −0.21); P = 0.016]}. Patients with AD showed a tendency toward higher CSF ApoA-I levels compared with HCs, although this difference was non-significant [SMD = 0.20; 95% CI (−0.16, 0.56); P = 0.273]. In addition, when we analyzed the ApoA-I levels of serum and plasma together, the circulating ApoA-I levels in AD patients was significantly lower [SMD = −1.15; 95% CI (−1.63, −0.66); P = 0.000]. These results indicate that ApoA-I deficiency may be a risk factor of AD, and ApoA-I has the potential to serve as a biomarker for AD and provide experimental evidence for diagnosis of AD.

Systematic Review Registration: PROSPERO, identifier: 325961.
Neural Processing of Naturalistic Echolocation Signals in Bats
Authors: Beetz M. Jerome , Hechavarría Julio C.
Published: May 2022

Echolocation behavior, a navigation strategy based on acoustic signals, allows scientists to explore neural processing of behaviorally relevant stimuli. For the purpose of orientation, bats broadcast echolocation calls and extract spatial information from the echoes. Because bats control call emission and thus the availability of spatial information, the behavioral relevance of these signals is undiscussable. While most neurophysiological studies, conducted in the past, used synthesized acoustic stimuli that mimic portions of the echolocation signals, recent progress has been made to understand how naturalistic echolocation signals are encoded in the bat brain. Here, we review how does stimulus history affect neural processing, how spatial information from multiple objects and how echolocation signals embedded in a naturalistic, noisy environment are processed in the bat brain. We end our review by discussing the huge potential that state-of-the-art recording techniques provide to gain a more complete picture on the neuroethology of echolocation behavior.
Risk Factors of Ischemic Stroke in Young Adults: A Chinese Single-Center Study
Authors: Tang Mingyu , Han Guangsong , Yao Ming , Peng Bin , Zhu Yicheng , Zhou Lixin , Ni Jun
Published: May 2022

Introduction

The etiology and risk factor profile of ischemic stroke in young adults are different from those in older patients. However, current etiological classifications are more applicable for the older adults, posing a challenge to the diagnosis of young patients with ischemic stroke. In this study, we applied a modified risk factor categorization previously used in the International Pediatric Stroke Study (IPSS) to describe the risk factor profiles of Chinese young patients with ischemic stroke and explore the sex and age differences in the distribution of risk factors.

Methods

This is a single-center retrospective study. Patients aged 18–50 years with a first-ever ischemic stroke admitted to the Peking Union Medical College Hospital between 2013 and 2020 were consecutively included. The risk factors of patients were collected and divided into 10 categories according to the modified IPSS criteria and the sex and age differences were explored.

Results

A total of 538 patients were enrolled in this study. The median age was 39 years and 62.6% were men. At least one IPSS risk factor category was identified in the 93.3% of all patients. The most common IPSS subtype was atherosclerosis-related risk factors (61.7%), followed by prothrombotic states (27.3%), chronic systemic conditions (24.7%), arteriopathy (16.2%), and cardiac disorders (10.4%). Chronic systemic conditions were more prevalent in patients aged <35 years (34.0 vs. 19.6%, p < 0.05) and women (43.3 vs. 13.6%, p < 0.0001). Atherosclerosis-related risk factors were more dominant in patients aged ≥35 years (72.6 vs. 41.9%, p < 0.0001) and men (77.2 vs. 35.8%, p < 0.0001).

Conclusions

The IPSS classification might be a potential tool to better identify the risk factors of ischemic stroke in young adults.
High Protein Diets Improve Liver Fat and Insulin Sensitivity by Prandial but Not Fasting Glucagon Secretion in Type 2 Diabetes
Authors: Zhang Jiudan , Pivovarova-Ramich Olga , Kabisch Stefan , Markova Mariya , Hornemann Silke , Sucher Stephanie , Rohn Sascha , Machann Jürgen , Pfeiffer Andreas F. H.
Published: May 2022

Glucagon (GCGN) plays a key role in glucose and amino acid (AA) metabolism by increasing hepatic glucose output. AA strongly stimulate GCGN secretion which regulates hepatic AA degradation by ureagenesis. Although increased fasting GCGN levels cause hyperglycemia GCGN has beneficial actions by stimulating hepatic lipolysis and improving insulin sensitivity through alanine induced activation of AMPK. Indeed, stimulating prandial GCGN secretion by isocaloric high protein diets (HPDs) strongly reduces intrahepatic lipids (IHLs) and improves glucose metabolism in type 2 diabetes mellitus (T2DM). Therefore, the role of GCGN and circulating AAs in metabolic improvements in 31 patients with T2DM consuming HPD was investigated. Six weeks HPD strongly coordinated GCGN and AA levels with IHL and insulin sensitivity as shown by significant correlations compared to baseline. Reduction of IHL during the intervention by 42% significantly improved insulin sensitivity [homeostatic model assessment for insulin resistance (HOMA-IR) or hyperinsulinemic euglycemic clamps] but not fasting GCGN or AA levels. By contrast, GCGN secretion in mixed meal tolerance tests (MMTTs) decreased depending on IHL reduction together with a selective reduction of GCGN-regulated alanine levels indicating greater GCGN sensitivity. HPD aligned glucose metabolism with GCGN actions. Meal stimulated, but not fasting GCGN, was related to reduced liver fat and improved insulin sensitivity. This supports the concept of GCGN-induced hepatic lipolysis and alanine- and ureagenesis-induced activation of AMPK by HPD.
Trans-Fat Labeling in Packaged Foods Sold in Brazil Before and After Changes in Regulatory Criteria for Trans-Fat-Free Claims on Food Labels
Authors: Barros Beatriz Vasconcellos de , Proença Rossana Pacheco da Costa , Kliemann Nathalie , Hilleshein Daniele , Souza Amanda Alves de , Cembranel Francieli , Bernardo Greyce Luci , Uggioni Paula Lazzarin , Fernandes Ana Carolina
Published: May 2022

Consumption of industrially produced trans-fat acids (TFA) is a public health concern. Therefore, it is important that information on TFA in packaged foods be clearly informed to consumers. This study aimed to assess the evolution of TFA information presented in packaged foods sold in Brazil in 2010 and 2013, before and after the introduction of stricter regulatory requirements for TFA-free claims on food labels. A repeated cross-sectional study was performed through food label censuses of all packaged foods available for sale in two stores from the same supermarket chain, totaling 2,327 foods products in 2010 and 3,176 in 2013. TFA-free claims and information indicating TFA in the ingredients list and nutrition facts label were analyzed by descriptive statistics and Pearson’s chi-square test. There was a 14% decrease in the use of ingredients containing or potentially containing industrially produced TFA (i-TFA), according to analysis of the ingredients list. However, when analyzing foods by groups, it was found that this decrease was significant only for group A (bakery goods, bread, cereals, and related products; from 59 to 35%, p < 0.001). By contrast, food group F (gravies, sauces, ready-made seasonings, broths, soups, and ready-to-eat dishes) showed a 5% increase in i-TFA. The use of specific terms for i-TFA decreased between 2010 and 2013, but there was an increase in the use of alternative terms, such as vegetable fat and margarine, which do not allow consumers to reliably identify whether a food product is a possible source of i-TFA. There was an 18% decrease in the use of TFA-free claims in products containing or potentially containing i-TFA. However, almost one-third of foods sold in 2013 were false negatives, that is, foods reported to contain 0 g of TFA in the nutrition facts label or with TFA-free claims but displaying specific or alternative terms for i-TFA in the ingredients list. The results indicate that adoption of stricter requirements for TFA-free claims on food labels in Brazil helped reduce the prevalence of such claims but was not sufficient to decrease i-TFA in industrialized foods sold in supermarkets.
Inhibitory Effects of Macelignan on Tau Phosphorylation and Aβ Aggregation in the Cell Model of Alzheimer's Disease
Authors: Gu Liang , Cai Nan , Li Meiting , Bi Decheng , Yao Lijun , Fang Weishan , Wu Yan , Hu Zhangli , Liu Qiong , Lin Zhijian , Lu Jun , Xu Xu
Published: May 2022

Alzheimer's disease (AD) is a neurodegenerative disorder mainly affecting old population. In this study, two Tau overexpressing cell lines (SH-SY5Y/Tau and HEK293/Tau), N2a/SweAPP cell line, and 3× Transgene (APPswe/PS1M146V/TauP301L) mouse primary nerve cell lines were used as AD models to study the activity and molecular mechanism of macelignan, a natural compound extracted from Myristica fragrans, against AD. Our study showed that macelignan could reduce the phosphorylation of Tau at Thr 231 site, Ser 396 site, and Ser 404 site in two overexpressing Tau cell lines. It also could decrease the phosphorylation of Tau at Ser 404 site in mouse primary neural cells. Further investigation of its mechanism found that macelignan could reduce the phosphorylation of Tau by increasing the level of autophagy and enhancing PP2A activity in Tau overexpressing cells. Additionally, macelignan could activate the PERK/eIF2α signaling pathway to reduce BACE1 translation, which further inhibits the cleavage of APP and ultimately suppresses Aβ deposition in N2a/SweAPP cells. Taken together, our results indicate that macelignan has the potential to be developed as a treatment for AD.
Characteristics of Mulberry Leaf Powder Enriched With γ-Aminobutyric Acid and Its Antioxidant Capacity as a Potential Functional Food Ingredient
Authors: Jin Yingchun , Tu Jie , Han Xinyao , Zhuo Jun , Liu Guanhui , Han Yanhui , Du Hengjun , Wang Jun , Xiao Hang
Published: May 2022

To improve the functional properties of mulberry leaves, γ-aminobutyric acid (GABA) enrichment treatments were applied. The results showed that the combined treatment of sodium glutamate immersion, cold shock, and anoxic significantly increased the GABA content. HPLC analysis displayed that the quantity of some active phenolics was significantly increased after the treatment. The GABA-enriched mulberry leaf powders were subsequently prepared, and it was found that as the particle size decreased, their water and oil holding capacity and their swelling power decreased, while the angle of repose increased. The dissolution rate of GABA and total phenolics increased as the particle size decreased. Optical observations and SEM results revealed that the fiber structures of the particles were gradually destroyed as the particle size decreased. Further, FTIR analysis showed that the active compounds in the powders were not destroyed. M400 and M140 powder showed the maximum DPPH radical scavenging ability and AGEs inhibition capacity, respectively. Additionally, adding the powders effectively alleviated the staling of bread without any significant effect on taste.
Prestorage High CO2 and 1-MCP Treatment Reduce Chilling Injury, Prolong Storability, and Maintain Sensory Qualities and Antioxidant Activities of “Madoka” Peach Fruit
Authors: Tilahun Shimeles , Jeong Min Jae , Choi Han Ryul , Baek Min Woo , Hong Jin Sung , Jeong Cheon Soon
Published: May 2022

Cold storage is widely used to prolong the storability of peach fruit. However, prolonged storage at low temperatures results in chilling injury (CI) in some susceptible peach cultivars during or after cold storage. Prestorage high CO2 and 1-methylcyclopropene (1-MCP) treatments are among the methods reported to alleviate CI and maintain the firmness of peach fruit. Hence, this study investigated CI, ripening-related physicochemical parameters, sensory qualities, total phenolics and flavonoids, and antioxidant activities of “Madoka” peach fruit to observe the effectiveness of prestorage treatment with high CO2 and 1-MCP during the storage at 0 and 5°C. Based on the CI index, control fruits were acceptable for marketing up to 20 and 16 days of storage at 0 and 5°C, respectively, while the treated fruits could be marketable up to 28 days of storage. The results of firmness and firmness-related parameters [pectin content and polygalacturonase (PG) activity] also revealed that both high CO2 and 1-MCP treatments were effective in delaying the ripening process of Madoka peach, and the storage at 0°C showed better results than at 5°C. However, based on the overall sensory evaluation results, the treated and control fruits were acceptable for marketing up to 20 and 12 days of storage, respectively, in both storage conditions. After deciding on fruit marketability based on the combined objective postharvest quality parameters and subjective sensory qualities, we analyzed the changes in total phenolics, flavonoids, and antioxidant activities at harvest, on the 12 and 20th days of cold storage. Storage of Madoka peach at 0°C maintained total phenolics, flavonoids, and antioxidant activities regardless of prestorage treatment with high CO2 and 1-MCP. In summary, storing Madoka peach fruit at 0°C after treating it with 30% CO2 for 6 h or 0.5 μl L–1 1-MCP for 24 h reduces CI, prolongs storability, and maintains sensory quality and antioxidant properties.
Translational Learnings in the Development of Chemo-Immunotherapy Combination to Bypass the Cold Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma
Authors: Kaplon Hélène
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with a 5-year relative survival rate of 5%. The desmoplastic stroma found in the tumor microenvironment of PDAC is suggested to be partly responsible for the resistance to most therapeutic strategies. This review outlines the clinical results obtained with an immune checkpoint inhibitor in PDAC and discusses the rationale to use a combination of chemotherapy and immune checkpoint therapy. Moreover, essential parameters to take into account in designing an efficient combination have been highlighted.
Association of Acupuncture and Auricular Acupressure With the Improvement of Sleep Disturbances in Cancer Survivors: A Systematic Review and Meta-Analysis
Authors: Wan Qingyun , Luo Shuting , Wang Xiaoqiu , Tian Qianmo , Xi Hanqing , Zheng Shiyu , Fang Qinqin , Chen Hao , Wu Wenzhong , Pan Rui
Published: May 2022

Background

Studies on the efficacy of acupuncture and auricular acupressure on sleep disturbances in cancer patients have been growing, but there is no specific and comprehensive systematic review and meta-analysis. This review aims to evaluate the efficacy and safety of acupuncture and auricular acupressure on sleep disturbances in cancer survivors based on existing randomized clinical trials (RCTs).

Methods

Four English-language and four Chinese-language biomedical databases were searched for RCTs published from database inception to July 30, 2021. RCTs comparing acupuncture and auricular acupressure with sham control, drug therapy, behavior therapy, or usual care for managing cancer were included. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias (ROB) tool. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for the effect sizes.

Results

Thirteen RCTs with 961 patients were included. The risk of performance bias or reporting bias for most of the included trials was high or unclear. Evidence was not found for short-term effects on sleep scales compared to sham control (MD, 1.98; 95% CI, 0.33–3.64; p = 0.02; I2 = 36%), wait list control (MD, 0.40; 95% CI, −0.87–1.68; p = 0.54; I2 = 49%), drug therapy (MD, 1.18; 95% CI, −3.09–5.46; p = 0.59; I2 = 98%). For long-term effect, two sham-controlled RCTs showed no significance of acupuncture on insomnia scale scores (MD, 1.71; 95% CI, −2.38–5.81; p = 0.41; I2 = 89%). Subgroup analyses suggested no evidence that auricular acupressure (MD, 3.14; 95% CI=1.52, 4.76; p = 0.0001; I2 = 0%) or acupuncture (MD, 0.54; 95% CI=−1.27, 2.34; p = 0.56; I2 = 0%) was associated with the reduction in insomnia scale scores.

Conclusions

This systematic review and meta-analysis found no evidence about acupuncture or auricular acupressure in the improvement of sleep disturbances in cancer survivors in terms of short- or long-term effect. Adverse events were minor. The finding was inconsistent with previous research and suggested that more well-designed and large-scale randomized controlled trials are needed to identify the efficacy of acupuncture and auricular acupressure for sleep disturbances in cancer survivors.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, CRD42020171612.
Defining a Standard Set of Patient-Reported Outcomes for Patients With Advanced Ovarian Cancer
Authors: Escudero-Vilaplana Vicente , Bernal Elsa , Casado Gema , Collado-Borrell Roberto , Diez-Fernández Raúl , Fernández Román Ana Beatriz , Folguera Carlos , González-Cortijo Lucía , Herrero-Fernández Marta , Marquina Gloria , Martínez Nieto Concepción , Rodríguez Miguel Angel , Rubio Ana Rosa , Sanmartin-Fenollera Patricia , Vazquez Castillo Maria José , Comellas Marta , Guerra Eva Maria
Published: May 2022

Purpose

Advanced ovarian cancer (AOC) and its treatment cause several symptoms and impact on patients’ health-related quality of life (HRQoL). We aim to reach a consensus on the most relevant patient-reported outcome (PROs), the corresponding measures (PROMs), and measurement frequency during AOC patients’ follow-up from patients’ and healthcare professionals’ (HCP) perspective.

Methods

The project comprised five steps: 1) a literature review, 2) a focus group with patients, 3) a nominal group with HCP, 4) two round-Delphi consultations with patients and HCP, and 5) a final meeting with HCP. Delphi questionnaire was elaborated based on literature review, focus group (n=5 patients), and nominal group (n=16 HCP). The relevance of each PRO and the appropriateness (A) and feasibility (F) of the proposed PROM were assessed (Likert scale 1=strongly agree; 9=strongly disagree). The consensus was reached when at least 75% of the panelists rated it as ‘relevant’, ‘appropriate’, or ‘feasible’ (score 7-9).

Results

A total of 56 HCP [51.8% Hospital Pharmacy; 41.1% Oncology; 3.6% Nursing; and 3.6% Psycho-oncology; mean time in specialty 12.5 (8.0) years] and 10 AOC patients [mean time diagnosis 5.4 (3.0) years] participated in the 1st round. All PROs achieved consensus regarding their relevance, except dry skin (58.0%). Agreement was reached for PRO-CTCAE to be used to assess fatigue (A:84.9%; F:75.8%), neuropathy (A:92.4%; F:77.3%), diarrhea (A:87.9%; F:88.7%), constipation (A:86.4%; F:75.8%), nausea (A:89.4%; F:75.8%), insomnia (A:81.8%; F:88.7%), abdominal bloating (A:82.2%; F:82.2%) and sexuality (A:78.8%; F:88.6%); EQ-5D to determine patients’ HRQoL (A:87.9%; F:80.3%), pain (A:87.9%; F:75.8%) and mood (A:77.7%; F:85.5%); to assess treatment adherence the Morisky-Green (A:90.9%; F:84.9%) and the dispensing register (A:80.3%; F:80.3%) were chosen. It was agreed to note in the medical record whether the patient’s treatment preferences had been considered during decision-making (A:78.8%; F:78.8%) and to use a 5-point Likert scale to assess treatment satisfaction (A:86.4%; F:86.4%). Panelists agreed (A:92.4%; F: 77.3%) to collect these PROs (1) at the time of diagnosis/relapse; (2) one month after starting treatment/change therapeutic strategy; (3) every three months during the 1st-year of treatment; and later (4) every six months until treatment completion/change.

Conclusions

The consensus reached represents the first step towards including the patient’s perspective in AOC follow-up. The standardized collection of PROs in clinical practice may contribute to optimizing the follow-up of these patients and thus improving the quality of care.
The Impact of Maternal Obesity on NICU and Newborn Nursery Costs
Authors: Azher Sharmeen , Pinheiro Joaquim M. B. , Philbin Brendan , Gifford Jamie , Khalak Rubia
Published: May 2022

Background

Research on the effects of maternal obesity on neonates has focused on clinical outcomes. Despite growing interest in obesity as a driver of healthcare expenditure, the financial impact of maternal obesity in the neonatal setting is little understood.

Objective

To determine if maternal obesity is associated with higher incurred costs in NICU and full-term nursery.

Methods

Data for all live births (1/1/14–12/31/19) at our academic medical center was obtained from the New York State Perinatal Data System for infants >23 weeks gestational age. Financial data was obtained from the hospital's cost-processing application. Infants with missing clinical and/or financial data were excluded. The NIH definition of obesity was used (BMI ≥ 30 kg/m2) to separate infants born to obese and non-obese mothers. Student's t-tests and chi square tests were used to compare maternal data, delivery, and infant outcomes between both groups. A logistic regression model was used to compare infant outcomes using odds ratios while controlling for maternal risk factors (smoking status, pre-pregnancy and gestational diabetes, pre-pregnancy and gestational hypertension). Multivariate regression analysis adjusting for maternal risk factors was also used to compare length-of-stay, total and direct costs in the NICU and full-term nursery between infant groups.

Results

Of the 11,610 pregnancies in this retrospective study, obese mothers more frequently had other risk factors (smoke, pre-pregnancy and gestational diabetes, and pre-pregnancy and gestational hypertension). Infants born to obese mothers were more often preterm, had Cesarean delivery, lower APGAR scores, required assisted ventilation in the delivery room, and required NICU admission. Adjusting for maternal risk factors, infants born to obese mothers were less frequently preterm (OR 0.82 [0.74–0.91], p < 0.01) and had NICU stays (OR 0.98 [0.81–0.98], p = 0.02), but more frequently had Cesarean births (OR 1.54 [1.42–1.67], p < 0.01). They also had longer adjusted LOS (2.03 ± 1.51 vs. 1.92 ± 1.45 days, p < 0.01) and higher mean costs per infant in the full-term nursery ($3,638.34 ± $6,316.69 vs. $3,375.04 ± $4,994.18, p = 0.03) but not in NICU.

Conclusions

Maternal obesity correlates with other risk factors. Prolonged maternal stay may explain increased LOS and costs in the full-term nursery for infants born to obese mothers, as infants wait to be discharged with mothers.
Cystic Dysplasia of the Rete Testis: Case Report and Systematic Review of the Literature
Authors: Contini Giorgia , Frediani Simone , Pardi Valerio , Diomedi-Camassei Francesca , Inserra Alessandro
Published: May 2022

Cystic dysplasia of the rete testis (CDRT) is a rare cause of testicular masses in children. The pathogenesis of this malformation remains unclear. It is often associated with other genitourinary anomalies, commonly presenting as agenesis or dysplasia of the ipsilateral kidney. A case involving a 9-year-old boy with a testicular lesion and ipsilateral renal agenesis, who was diagnosed with CDRT after histological examination, is reported. In addition, a systematic review of the literature was performed to better understand this pathology to design the most appropriate treatment and follow-up strategy for patients with CDRT.
Tools for Identifying Potentially Inappropriate Prescriptions for Children and Their Applicability in Clinical Practices: A Systematic Review
Authors: Li Siyu , Huang Liang , Chen Zhe , Zeng Linan , Li Hailong , Diao Sha , Jia Zhi-Jun , Cheng Guo , Yu Qin , Zhang Lingli
Published: May 2022

Background: Drug use safety in children is a global public health problem. The potentially inappropriate prescription screening tools are expected to reduce adverse drug reactions and promote rational drug use.

Objectives: To systematically evaluate children’s potentially inappropriate prescription screening tools and validation studies on these tools.

Methods: We systematically searched six databases PubMed, Embase, Cochrane Library, CNKI, VIP and Wanfang Data. Two reviewers independently selected articles by the eligible criteria and extracted data. Then we evaluated the coverage of diseases or drugs in these tools and the consistency of items between tools.

Results: Five children’s potentially inappropriate prescription screening tools were identified, most tools were formed by Delphi expert consensus and focused on respiratory system drugs, anti-infective drugs, and gastrointestinal drugs. The coincidence rates of items between the POPI and the POPI Int, the POPI and the POPI United Kingdom, the POPI United Kingdom and the POPI int, and the POPI United Kingdom and the PIPc were 82.0, 55.1, 51.0 and 2.2% respectively, and the KIDs List did not overlap other four tools. Only the POPI tool developed by French experts was comprehensively validated by studies and most tools have not been validated.

Conclusion: The development of screening tools for potentially inappropriate prescribing in children is a neglected field and most tools lack studies to validate clinical applicability. More researchers need to form their national potentially inappropriate prescription screening tools for children based on the best available clinical evidence and the actual clinical situation in their countries.
Plasma Metabolites and Gut Microbiota Are Associated With T cell Imbalance in BALB/c Model of Eosinophilic Asthma
Authors: Zhou Yumei , Wang Tieshan , Zhao Xiaoshan , Wang Ji , Wang Qi
Published: May 2022

The pathogenesis of allergic asthma is complex, it is usually caused by immune system imbalance. Th1, Th2, regulatory T cells (Treg) and T helper 17 (Th17) cells have an important role in the pathogenesis of eosinophilic asthma. Yet, the exact role of Th1, Th2, Treg and Th17 cells in eosinophilic asthmatic disease is not fully understood. This study used an untargeted plasma metabolomics combine 16S rDNA technology to identify new biomarkers of plasma metabolites and gut microbiota in ovalbumin-induced eosinophilic allergic asthma in BALB/c mice to further explore the biomarkers in regulating the immune balance or the immune response. We discovered that malate, l-dihydroorotate were associated with Th1/Th2 and Treg/Th17 cells balance, imidazoleacetic acid was associated with Th1/Th2 cell balance, 1,5-anhydro-d-sorbitol was associated with Treg/Th17 cell balance. The results also found that genus Candidatus Arthromitus of gut microbiota were associated with Th1/2, Treg/Th17 balance, genus Ruminiclostridium 6, they were all associated with Th1/2 and Treg/Th17 cell balance, while the gut microbiota were not associated with penh value which reflect airway hyperresponsiveness (AHR) in the eosinophilic asthma mice model. Interestingly, the plasma metabolite biomarkers of malate, l-dihydroorotate are associated with genus Ruminiclostridium 6, they were all associated with Th1/2 and Treg/Th17 cell balance, while imidazoleacetic acid is associated with genus Ruminiclostridium 6 which is associated with Th1/2 balance. Among the differential plasma metabolites, 1,5-anhydro-d-sorbitol is associated with genus Ruminiclostridium 6 and genus Candidatus Arthromitus. Among them, malate participate in the T cell activation, T cell differentiation and activation may be a new research direction in eosinophilic allergic asthma. We firstly study the gut microbiota and plasma metabolites markers of immune balance in eosinophilic asthma in mice model, laying a foundation for drug treatment in eosinophilic allergic asthma.
External Evaluation of Population Pharmacokinetic Models to Inform Precision Dosing of Meropenem in Critically Ill Patients
Authors: Yang Nan , Wang Jing , Xie Yueliang , Ding Junjie , Wu Cuifang , Liu Jingjing , Pei Qi
Published: May 2022

Routine clinical meropenem therapeutic drug monitoring data can be applied to model-informed precision dosing. The current study aimed to evaluate the adequacy and predictive capabilities of the published models with routine meropenem data and identify the dosing adaptations using a priori and Bayesian estimation. For this, 14 meropenem models for the external evaluation carried out on an independent cohort of 134 patients with 205 meropenem concentrations were encoded in NONMEM 7.3. The performance was determined using: 1) prediction-based and simulation-based diagnostics; and 2) predicted meropenem concentrations by a priori prediction using patient covariates only; and Bayesian forecasting using previous observations. The clinical implications were assessed according to the required dose adaptations using the meropenem concentrations. All assessments were stratified based on the patients with or without continuous renal replacement therapy. Although none of the models passed all tests, the model by Muro et al. showed the least bias. Bayesian forecasting could improve the predictability over an a priori approach, with a relative bias of −11.63–68.89% and −302.96%–130.37%, and a relative root mean squared error of 34.99–110.11% and 14.78–241.81%, respectively. A dosing change was required in 40.00–68.97% of the meropenem observation results after Bayesian forecasting. In summary, the published models couldn’t adequately describe the meropenem pharmacokinetics of our center. Although the selection of an initial meropenem dose with a priori prediction is challenging, the further model-based analysis combining therapeutic drug monitoring could be utilized in the clinical practice of meropenem therapy.
Neuroprotective Effects of Quercetin on Ischemic Stroke: A Literature Review
Authors: Zhang Leilei , Ma Jingying , Yang Fan , Li Sishi , Ma Wangran , Chang Xiang , Yang Lin
Published: May 2022

Ischemic stroke (IS) is characterized by high recurrence and disability; however, its therapies are very limited. As one of the effective methods of treating acute attacks of IS, intravenous thrombolysis has a clear time window. Quercetin, a flavonoid widely found in vegetables and fruits, inhibits immune cells from secreting inflammatory cytokines, thereby reducing platelet aggregation and limiting inflammatory thrombosis. In pre-clinical studies, it has been shown to exhibit neuroprotective effects in patients with ischemic brain injury. However, its specific mechanism of action remains unknown. Therefore, this review aims to use published data to elucidate the potential value of quercetin in patients with ischemic brain injury. This article also reviews the plant sources, pharmacological effects, and metabolic processes of quercetinin vivo, thus focusing on its mechanism in inhibiting immune cell activation and inflammatory thrombosis as well as promoting neuroprotection against ischemic brain injury.
Yokukansan Inhibits the Development of Morphine Tolerance by Regulating Presynaptic Proteins in DRG Neurons
Authors: Ohashi Yusuke , Sakhri Fatma Zahra , Ikemoto Hideshi , Okumo Takayuki , Adachi Naoki , Sunagawa Masataka
Published: May 2022

Opioids, such as morphine, are used in clinical settings for the management of acute and chronic pain. However, long-term use of morphine leads to antinociceptive tolerance and hypersensitivity. The cellular and molecular mechanisms of morphine tolerance seem to be quite complex, with suggestions including internalization of the μ-opioid receptor (MOR), neuroinflammation with activation of microglia and astrocytes, and changes in synaptic function in the central nervous system. Yokukansan (YKS), a traditional Kampo medicine consisting of seven herbs, has been used to treat emotional instability, neurosis, and insomnia. Interestingly, recent studies have begun to reveal the inhibitory effect of YKS on the development of morphine tolerance. In the present study, we determined the effect of YKS on morphine tolerance formation and its mechanisms in a rat model, focusing on the synapses between primary sensory neurons and spinal dorsal horn secondary neurons. We found that morphine tolerance formation was significantly inhibited by YKS (0.3 or 1.0 g/kg/day) preadministration for 7 days. Repeated administration of morphine (10 mg/kg/day) increased the expression of presynaptic proteins, including synaptotagmin I, in the spinal cord, which was suppressed by YKS. Furthermore, these changes in presynaptic protein expression were more pronounced at isolectin B4 (IB4)-positive excitatory synapses around the lamina II of the dorsal horn. These results suggest that YKS suppresses the development of morphine tolerance by inhibiting the enhancement of presynaptic function of dorsal root ganglia neurons projecting to spinal dorsal horn neurons caused by continuous morphine administration.
A Pili-Driven Bacterial Turbine
Authors: Pönisch Wolfram , Zaburdaev Vasily
Published: May 2022

Work generated by self-propelled bacteria can be harnessed with the help of microdevices. Such nanofabricated microdevices, immersed in a bacterial bath, may exhibit unidirectional rotational or translational motion. Swimming bacteria that propel with the help of actively rotating flagella are a prototypical example of active agents that can power such microdevices. In this work, we propose a computational model of a micron-sized turbine powered by bacteria that rely on active type IV pili appendages for surface-associated motility. We find that the turbine can rotate persistently over a time scale that significantly exceeds the characteristic times of the single cell motility. The persistent rotation is explained by the collective dynamics of multiple pili of groups of cells attaching to and pulling on turbine. Furthermore, we show that the turbine can rotate permanently in the same direction by altering the pili binding to the turbine surface in an asymmetric fashion. We thus can show that by changing the adhesive properties of the turbine while keeping its symmetric geometry, we can still break the symmetry of its rotation. Altogether, this study widely expands the range of bacteria that can be used to power nanofabricated microdevices, and, due to high pili forces generated by pili retraction, promises to push the harnessed work by several orders of magnitude.
The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity
Authors: Nikolovska Katerina , Seidler Ursula E. , Stock Christian
Published: May 2022

The five plasma membrane Na+/H+exchanger (NHE) isoforms in the gastrointestinal tract are characterized by distinct cellular localization, tissue distribution, inhibitor sensitivities, and physiological regulation. NHE1 (Slc9a1) is ubiquitously expressed along the gastrointestinal tract in the basolateral membrane of enterocytes, but so far, an exclusive role for NHE1 in enterocyte physiology has remained elusive. NHE2 (Slc9a2) and NHE8 (Slc9a8) are apically expressed isoforms with ubiquitous distribution along the colonic crypt axis. They are involved in pHiregulation of intestinal epithelial cells. Combined use of a knockout mouse model, intestinal organoid technology, and specific inhibitors revealed previously unrecognized actions of NHE2 and NHE8 in enterocyte proliferation and differentiation. NHE3 (Slc9a3), expressed in the apical membrane of differentiated intestinal epithelial cells, functions as the predominant nutrient-independent Na+absorptive mechanism in the gut. The new selective NHE3 inhibitor (Tenapanor) allowed discovery of novel pathophysiological and drug-targetable NHE3 functions in cystic-fibrosis associated intestinal obstructions. NHE4, expressed in the basolateral membrane of parietal cells, is essential for parietal cell integrity and acid secretory function, through its role in cell volume regulation. This review focuses on the expression, regulation and activity of the five plasma membrane Na+/H+exchangers in the gastrointestinal tract, emphasizing their role in maintaining intestinal homeostasis, or their impact on disease pathogenesis. We point to major open questions in identifying NHE interacting partners in central cellular pathways and processes and the necessity of determining their physiological role in a system where their endogenous expression/activity is maintained, such as organoids derived from different parts of the gastrointestinal tract.