bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of microtubule associated proteins – a reference proteomic perspective
Authors: Gottschalk Amy C. , Hefti Marco M.
Published: April 2022

Microtubule associated proteins (MAPs), defined as proteins that bind microtubules but are not molecular motors or severing enzymes, play a key role in regulating microtubule stability in neurons. Existing studies of the evolutionary relationships between these proteins are limited to genomic data from a small number of species. We therefore used a large collection of publicly available reference-quality eukaryotic proteomes to carry out a phylogenetic analysis of microtubule associated proteins in both vertebrates and invertebrates. Complete or near-complete reference quality proteomes were obtained from Uniprot. Microtubule associated proteins were identified using InterProtScan, aligned using MUSCLE and then phylogenetic trees constructed using the WAG algorithm. We identified 889 proteins with tubulin binding domains, of which 663 were in eukaryotes, including 168 vertebrates and 64 invertebrates. The vertebrate proteins separated into three families, resembling human MAP 2, MAP4 and MAPT, respectively, while invertebrate MAPs clustered separately. We found significant variation in number of microtubule associated proteins and number of microtubule binding domains between taxa, with fish and mollusks having an unexpectedly high number of MAPs and binding domains, respectively. Our findings represent a novel analysis of the evolution of microtubule associated proteins based on publicly available proteomics data sets. We were able to confirm the phylogeny of MAPs identified based on more limited genomic analyses, and in addition, derived several novel insights on the structure and function of MAPs.
Comparative and phylogenetic analyses of six Kenya Polystachya (Orchidaceae) species based on the complete chloroplast genome sequences
Authors: Jiang Hui , Tian Jing , Yang Jiaxin , Dong Xiang , Zhong Zhixiang , Mwachala Geoffrey , Zhang Caifei , Hu Guangwan , Wang Qingfeng
Published: April 2022

Background

Polystachya Hook. is a large pantropical orchid genus (c. 240 species) distributed in Africa, southern Asia and the Americas, with the center of diversity in Africa. Previous studies on species of this genus have not obtained the complete chloroplast genomes, structures and variations. Additionally, the phylogenetic position of the genus in the Orchidaceae is still controversial and uncertain. Therefore, in this study, we sequenced the complete plastomes of six Kenya Polystachya species based on genome skimming, subjected them to comparative genomic analysis, and reconstructed the phylogenetic relationships with other Orchidaceae species.

Results

The results exhibited that the chloroplast genomes had a typical quadripartite structure with conserved genome arrangement and moderate divergence. The plastomes of the six Polystachya species ranged from 145,484 bp to 149,274 bp in length and had an almost similar GC content of 36.9–37.0%. Gene annotation revealed 106–109 single-copy genes. In addition, 19 genes are duplicated in the inverted regions, and 16 genes each possessd one or more introns. Although no large structural variations were observed among the Polystachya plastomes, about 1 kb inversion was found in Polystachya modesta and all 11 ndh genes in the Polystachya plastomes were lost or pseudogenized. Comparative analysis of the overall sequence identity among six complete chloroplast genomes confirmed that for both coding and non-coding regions in Polystachya, SC regions exhibit higher sequence variation than IRs. Furthermore, there were various amplifications in the IR regions among the six Polystachya species. Most of the protein-coding genes of these species had a high degree of codon preference. We screened out SSRs and found seven relatively highly variable loci. Moreover, 13 genes were discovered with significant positive selection. Phylogenetic analysis showed that the six Polystachya species formed a monophyletic clade and were more closely related to the tribe Vandeae. Phylogenetic relationships of the family Orchidaceae inferred from the 85 chloroplast genome sequences were generally consistent with previous studies and robust.

Conclusions

Our study is the initial report of the complete chloroplast genomes of the six Polystachya species, elucidates the structural characteristics of the chloroplast genome of Polystachya, and filters out highly variable sequences that can contribute to the development of DNA markers for use in the study of genetic variability and evolutionary studies in Polystachya. In addition, the phylogenetic results strongly support that the genus of Polystachya is a part of the tribe Vandeae.
Identification and functional analysis of cation-efflux transporter 1 from Brassica juncea L.
Authors: Han Lu , Wu Xiaohua , Zhang Xinyu , Hou Kailin , Zhang Hongshan , Shen Chenjia
Published: April 2022

Background

Brassica juncea behaves as a moderate-level accumulator of various heavy metal ions and is frequently used for remediation. To investigate the roles of metal ion transporters in B. juncea, a cation-efflux family gene, BjCET1, was cloned and functionally characterized.

Results

BjCET1 contains 382 amino acid residues, including a signature motif of the cation diffusion facilitator protein family, six classic trans-membrane-spanning structures and a cation-efflux domain. A phylogenetic analysis showed that BjCET1 has a high similarity level with metal tolerance proteins from other Brassica plants, indicating that this protein family is highly conserved in Brassica. BjCET1 expression significantly increased at very early stages during both cadmium and zinc treatments. Green fluorescence detection in transgenic tobacco leaves revealed that BjCET1 is a plasma membrane-localized protein. The heterologous expression of BjCET1 in a yeast mutant increased the heavy-metal tolerance and decreased the cadmium or zinc accumulations in yeast cells, suggesting that BjCET1 is a metal ion transporter. The constitutive expression of BjCET1 rescued the heavy-metal tolerance capability of transgenic tobacco plants.

Conclusions

The data suggest that BjCET1 is a membrane-localized efflux transporter that plays essential roles in heavy metal ion homeostasis and hyper-accumulation.
Adaptive design for identifying maximum tolerated dose early to accelerate dose-finding trial
Authors: Kojima Masahiro
Published: April 2022

Purpose

The early identification of maximum tolerated dose (MTD) in phase I trial leads to faster progression to a phase II trial or an expansion cohort to confirm efficacy.

Methods

We propose a novel adaptive design for identifying MTD early to accelerate dose-finding trials. The early identification of MTD is determined adaptively by dose-retainment probability using a trial data via Bayesian analysis. We applied the early identification design to an actual trial. A simulation study evaluates the performance of the early identification design.

Results

In the actual study, we confirmed the MTD could be early identified and the study period was shortened. In the simulation study, the percentage of the correct MTD selection in the early identification Keyboard and early identification Bayesian optimal interval (BOIN) designs was almost same from the non-early identification version. The early identification Keyboard and BOIN designs reduced the study duration by about 50% from the model-assisted designs. In addition, the early identification Keyboard and BOIN designs reduced the study duration by about 20% from time-to-event model-assisted designs.

Conclusion

We proposed the early identification of MTD maintaining the accuracy to be able to short the study period.
Perioperative changes in cell-free DNA for patients undergoing surgery for colon cancer
Authors: Rosen Andreas W. , Gögenur Mikail , Paulsen Isabella W. , Olsen Jesper , Eiholm Susanne , Kirkeby Lene T. , Pedersen Ole B. , Pallisgaard Niels , Gögenur Ismail
Published: April 2022

Background

Various conditions with cellular decay are associated with elevated cell-free DNA (cfDNA). This study aimed to investigate if perioperatively measured cfDNA levels were associated with the surgical approach, complications, or recurrence.

Methods

Plasma was obtained from patients who underwent surgery for colon cancer at admission and at the time of discharge. Quantitative measurement of cfDNA was performed by amplifying two amplicons of 102 base pairs (bp) and 132 bp ofBeta-2-Microglobulin(B2M) andPeptidyl-Prolyl cis–trans Isomerase A(PPIA), respectively.

Results

cfDNA was measured in 48 patients who underwent surgery for colonic cancer. Sixteen patients had recurrence during the follow-up period, fifteen developed a postoperative complication, and seventeen patients developed neither, acting as the control group. Postoperative cfDNA levels were significantly elevated from baseline samples, across all groups, with a median preoperativelyB2Mlevel of 48.3 alleles per mL and postoperatively of 220 alleles per mL and a median preoperatively levelPPIAof 26.9 alleles per mL and postoperatively of 111.6 alleles per mL (p < 0.001 forB2Mandp < 0.001 forPPIA). Postoperative levels of PPIA, but not B2M, were significantly higher in patients experiencing complications than in the control group (p = 0.036). However, a tendency towards an association between the surgical approach and the changes in cfDNA levels was found for PPIA (p = 0.058), and B2M (p = 0.087).

Conclusions

Plasma cfDNA was increased after surgery in all patients with colon cancer. Postoperative PPIA levels were significantly higher in patients experiencing surgical complications but not in B2M levels.
Infectious diseases prevention and control using an integrated health big data system in China
Authors: Zhou Xudong , Lee Edmund Wei Jian , Wang Xiaomin , Lin Leesa , Xuan Ziming , Wu Dan , Lin Hongbo , Shen Peng
Published: April 2022

Background

The Yinzhou Center for Disease Prevention and Control (CDC) in China implemented an integrated health big data platform (IHBDP) that pooled health data from healthcare providers to combat the spread of infectious diseases, such as dengue fever and pulmonary tuberculosis (TB), and to identify gaps in vaccination uptake among migrant children.

Methods

IHBDP is composed of medical data from clinics, electronic health records, residents’ annual medical checkup and immunization records, as well as administrative data, such as student registries. We programmed IHBDP to automatically scan for and detect dengue and TB carriers, as well as identify migrant children with incomplete immunization according to a comprehensive set of screening criteria developed by public health and medical experts. We compared the effectiveness of the big data screening with existing traditional screening methods.

Results

IHBDP successfully identified six cases of dengue out of a pool of 3972 suspected cases, whereas the traditional method only identified four cases (which were also detected by IHBDP). For TB, IHBDP identified 288 suspected cases from a total of 43,521 university students, in which three cases were eventually confirmed to be TB carriers through subsequent follow up CT or T-SPOT.TB tests. As for immunization screenings, IHBDP identified 240 migrant children with incomplete immunization, but the traditional door-to-door screening method only identified 20 ones.

Conclusions

Our study has demonstrated the effectiveness of using IHBDP to detect both acute and chronic infectious disease patients and identify children with incomplete immunization as compared to traditional screening methods.
Influences of gestational diabetes mellitus on the oral microbiota in offspring from birth to 1 month old
Authors: Song Qiying , Xiao Bin , Huang Hongli , Ma Liya , Zhang Jian V. , Zhu Yuanfang
Published: April 2022

Background

Maternal gestational diabetes mellitus (GDM) had long-term influences on the health of their children. However, the influences of GDM on the oral microbiota, which was closely related to oral and systemic health in offspring, were less documented. The present study aimed to explore the oral microbiota of neonates born to mothers with GDM is differentially colonized compared with those born to mothers without GDM, and whether any such differences persist to 1 month of age.

Methods

Oral samples were collected from children of mothers with (n = 20) and without GDM (n = 34) at birth and again at an average age of 1 month. The oral microbiota was characterized by 16S rRNA sequencing (V3-V4). Differences in diversity and composition according to maternal GDM status were assessed, and different metabolic functional pathways and microbial ecological networks were also analyzed.

Results

Although no significant differences were observed in diversity metrics between GDM and non-GDM groups (P > 0.05), we found significant differences in the taxonomic composition of oral microbiota from phylum to genus level between the two groups, with the GDM group exhibiting less abundance of Veillonella in both “Day 1” (P < 0.001) and “Day 30” (P < 0.05) phases. Metabolic pathways analysis showed that 5-aminoimidazole ribonucleotide biosynthesis and inosine-5'-phosphate biosynthesis were enriched in GDM subjects in the “Day 30” phase. Moreover, ecological network analysis revealed apparent differences between GDM and control groups, with the non-GDM group containing more high-degree nodes and microbial interactions compared with the GDM group.

Conclusion

Maternal GDM was associated with an altered oral microbial composition in neonates, although the distinct difference between GDM and non-GDM groups diminished in infancy. The oral microbiota functions and ecological networks differed dramatically between the two groups, highlighting the importance of maternal GDM status on initial oral microbiota in offspring.
HOXA-AS2 enhances GBM cell malignancy by suppressing miR-2116-3p thereby upregulating SERPINA3
Authors: Sun Jianrui , Wang Lin
Published: April 2022

Background

Glioblastoma (GBM) is malignant, demanding more attention to the improvement of the diagnosis and therapy. LncRNAs have been implicated in the malignancy of GBM cells.

Methods

HOXA-AS2, miR-2116-3p and SERPINA3 expression levels in GBM tissues and cell lines were detected by qRT-PCR. Western blotting was performed to detect the protein levels of Bax and Bcl-2. Dual-luciferase reporter assay was for detection of relationship among these factors, together with RIP and RNA pull-down. CCK-8, EdU, wound healing and transwell assays were for detection of the role of HOXA-AS2, miR-2116-3p and SERPINA3 in cell viability, proliferation, migration and invasion in GBM, respectively.

Results

HOXA-AS2 and SERPINA3 showed higher level in GBM tissues and cell lines. Low level of HOXA-AS2 attenuated GBM cell growth in vitro. Moreover, the anti-tumor impact of silenced HOXA-AS2 was restored by miR-2116-3p inhibitor, but its tumor-promotional effect could be reversed by silenced SERPINA3.

Conclusion

HOXA-AS2 enhanced GBM cell malignancy through sponging miR-2116-3p and releasing SERPINA3, which might shed light on the diagnosis and therapy for GBM in the future.
Addressing the COVID-19 pandemic challenges for operational adaptations of a cluster randomized controlled trial on dengue vector control in Malaysia
Authors: Saadatian-Elahi Mitra , Alexander Neal , Möhlmann Tim , Ariffin Farah Diana , Schmitt Frederic , Richardson Jason H. , Rabilloud Muriel , Hamid Nurulhusna Ab
Published: April 2022

Introduction

The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co‐occurrence of COVID‐19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia).

Methods

This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia.

Results

The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible.

Conclusions

Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research.

Trial registration

Trial registration number: ISRCTN-81915073. Date of registration: 17/04/2020, 'Retrospectively registered'.
Prediction of metabolic and pre-metabolic syndromes using machine learning models with anthropometric, lifestyle, and biochemical factors from a middle-aged population in Korea
Authors: Kim Junho , Mun Sujeong , Lee Siwoo , Jeong Kyoungsik , Baek Younghwa
Published: April 2022

Background

Metabolic syndrome (MetS) is a complex condition that appears as a cluster of metabolic abnormalities, and is closely associated with the prevalence of various diseases. Early prediction of the risk of MetS in the middle-aged population provides greater benefits for cardiovascular disease-related health outcomes. This study aimed to apply the latest machine learning techniques to find the optimal MetS prediction model for the middle-aged Korean population.

Methods

We retrieved 20 data types from the Korean Medicine Daejeon Citizen Cohort, a cohort study on a community-based population of adults aged 30–55 years. The data included sex, age, anthropometric data, lifestyle-related data, and blood indicators of 1991 individuals. Participants satisfying two (pre-MetS) or ≥ 3 (MetS) of the five NECP-ATP III criteria were included in the MetS group. MetS prediction used nine machine learning models based on the following algorithms: Decision tree, Gaussian Naïve Bayes, K-nearest neighbor, eXtreme gradient boosting (XGBoost), random forest, logistic regression, support vector machine, multi-layer perceptron, and 1D convolutional neural network. All analyses were performed by sequentially inputting the features in three steps according to their characteristics. The models’ performances were compared after applying the synthetic minority oversampling technique (SMOTE) to resolve data imbalance.

Results

MetS was detected in 33.85% of the subjects. Among the MetS prediction models, the tree-based random forest and XGBoost models showed the best performance, which improved with the number of features used. As a measure of the models’ performance, the area under the receiver operating characteristic curve (AUC) increased by up to 0.091 when the SMOTE was applied, with XGBoost showing the highest AUC of 0.851. Body mass index and waist-to-hip ratio were identified as the most important features in the MetS prediction models for this population.

Conclusions

Tree-based machine learning models were useful in identifying MetS with high accuracy in middle-aged Koreans. Early diagnosis of MetS is important and requires a multidimensional approach that includes self-administered questionnaire, anthropometric, and biochemical measurements.
Malignant epithelioid neoplasm of the ileum with ACTB-GLI1 fusion mimicking an adnexal mass
Authors: Ambrosio Marco , Virgilio Agnese , Raffone Antonio , Arena Alessandro , Raimondo Diego , Alletto Andrea , Seracchioli Renato , Casadio Paolo
Published: April 2022

Background

Malignant epithelioid neoplasm with ACTB-GLI1 fusion are considered different from the more common pericytic lesions, such myopericytoma, because they have a spectrum of different genetic abnormalities. They appear to pursue a benign clinical course in young adults, although in sporadic cases lymph node metastasis were described.
The categorization of this new type of tumor may also lead to new therapeutic strategies, because they might be sensitive to SHH pathway inhibitors.

Case presentation

The case involves a 72-years-old multiparous woman who accessed our department after an incidental finding of a right adnexal mass of 43 mm with contrast-enhancement on a control computed tomography scan made for suspected diverticulitis. Our intervention was a detailed ultrasound description of the suspected neoplasm;
a diagnostic laparoscopy and the contextual laparotomic removal of abdominal mass; its histological and immunohistochemical analysis. Our main outcome measure is the definition and future recognition of new pathologic entity called malignant epithelioid neoplasm with ACTB-GLI1 fusion.

Conclusions

We described for the first time the ultrasound characteristic of this type of lesion using standardized terminology and we believe that it may be the first step to improve the acknowledgement of this novel pathologic entity defined as malignant epithelioid neoplasm with GLI-1 fusions.
Hinokiflavone induces apoptosis, cell cycle arrest and autophagy in chronic myeloid leukemia cells through MAPK/NF-κB signaling pathway
Authors: Qin Xiang , Chen Xi , Guo Ling , Liu Jing , Yang You , Zeng Yan , Li Cheng , Liu Wenjun , Ma Wenzhe
Published: April 2022

Background

Chronic myeloid leukemia (CML) is a myeloproliferative tumor originating from hematopoietic stem cells, and resistance to tyrosine kinase inhibitors (TKI) has become a major cause of treatment failure. Alternative drug therapy is one of the important ways to overcome TKI resistance. Hinokiflavone (HF) is a C-O-C type biflavonoid with low toxicity and antitumor activity. This study investigated the antitumor effect and possible mechanisms of HF in CML cells.

Methods

Cell viability was measured by CCK-8 assay. Cell apoptosis and cell cycle distribution were analyzed by flow cytometry. Western blotting was used to assess protein expression levels.

Results

Our results showed that HF significantly inhibited the viability of K562 cells in a concentration- and time-dependent manner and induced G2/M phase arrest by up-regulating p21 and down-regulating Cdc2 protein. Furthermore, HF induced caspase-dependent apoptosis by activating JNK/p38 MAPK signaling pathway and inhibiting NF-κB activity. In addition, HF induced autophagy by increasing LC3-II expression and p62 degradation. Pretreatment with CQ, a late autophagy inhibitor, significantly increased the levels of LC3-II and p62 proteins and promoted cell survival.

Conclusion

HF shows a good anti-leukemia effect and is expected to become a potential therapeutic drug for CML.
Developing a random forest algorithm to identify patent foramen ovale and atrial septal defects in Ontario administrative databases
Authors: Oliva Laura , Horlick Eric , Wang Bo , Huszti Ella , Hall Ruth , Abrahamyan Lusine
Published: April 2022

Purpose

Routinely collected administrative data is widely used for population-based research. However, although clinically very different, atrial septal defects (ASD) and patent foramen ovale (PFO) share a single diagnostic code (ICD-9: 745.5, ICD-10: Q21.1). Using machine-learning based approaches, we developed and validated an algorithm to differentiate between PFO and ASD patient populations within healthcare administrative data.

Methods

Using data housed at ICES, we identified patients who underwent transcatheter closure in Ontario between October 2002 and December 2017 using a Canadian Classification of Interventions code (1HN80GPFL, N = 4680). A novel random forest model was developed using demographic and clinical information to differentiate those who underwent transcatheter closure for PFO or ASD. Those patients who had undergone transcatheter closure and had records in the CorHealth Ontario cardiac procedure registry (N = 1482) were used as the reference standard. Several algorithms were tested and evaluated for accuracy, sensitivity, and specificity. Variable importance was examined via mean decrease in Gini index.

Results

We tested 7 models in total. The final model included 24 variables, including demographic, comorbidity, and procedural information. After hyperparameter tuning, the final model achieved 0.76 accuracy, 0.76 sensitivity, and 0.75 specificity. Patient age group had the greatest influence on node impurity, and thus ranked highest in variable importance.

Conclusions

Our random forest classification method achieved reasonable accuracy in identifying PFO and ASD closure in administrative data. The algorithm can now be applied to evaluate long term PFO and ASD closure outcomes in Ontario, pending future external validation studies to further test the algorithm.
Intersectoral collaboration at a decentralized level: information flows in child welfare and healthcare networks
Authors: Blanken Mariëlle , Mathijssen Jolanda , van Nieuwenhuizen Chijs , Raab Jörg , van Oers Hans
Published: April 2022

Background

As needs of families with social and behavioral health problems often exceed the expertise and possibilities of a single professional, service or organization, cross-service collaboration is indispensable to adequately meeting those needs. Despite the progressive focus on organizing integrated care, service fragmentation and service duplication remain persistent problems in child welfare and healthcare service delivery systems. A crucial factor to overcome these problems is information exchange between organizations. This study explores and compares the development over time of structures of information exchange in networks, concerning both material and knowledge-based information.

Methods

A comparative case study and social network analysis of three inter-organizational networks of child welfare and healthcare services in different-sized municipalities in the Netherlands. The research population consisted of organizations from various sectors participating in the networks. Data were collected at two moments in time with a mixed method: semi-structured interviews with network managers and an online questionnaire for all network members. Density and degree centralization were used to examine the information exchange structures. Ucinet was used to analyze the data, with use of the statistical tests: Compare Density Procedure and Quadratic Assignment Procedure.

Results

This study shows that different structures of information exchange can be distinguished, concerning both material and knowledge-based information. The overall connectedness of the studied structures of the networks are quite similar, but the way in which the involvement is structured turns out to be different between the networks. Over time, the overall connectedness of those structures appears to be stable, but the internal dynamics reveals a major change in relationships between organizations in the networks.

Conclusions

Our study yields empirical evidence for the existence of and the differences between structures and dynamics of both material and knowledge-based information exchange relationships. With a loss of more than a half of the relations in a year, the relationships between the organizations in the network are not very stable over time. The contrast between major internal dynamics and the stable overall connectedness is an important point of concern for network managers and public officials, since this impermanence of relations means that long-term integrated care cannot be guaranteed.
Extracellular vesicles derived from mesenchymal stem cells alleviate neuroinflammation and mechanical allodynia in interstitial cystitis rats by inhibiting NLRP3 inflammasome activation
Authors: Zhang Chi , Huang Yong , Ouyang Fubing , Su Minzhi , Li Wenbiao , Chen Jialiang , Xiao Hengjun , Zhou Xiangfu , Liu Bolong
Published: April 2022

Background

Neuroinflammation in spinal dorsal horn (SDH) plays an important role in the pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exert potent anti-inflammatory activities in the treatment of various diseases. This study aimed to determine the therapeutic effects of MSC-EVs on IC and furtherly investigate the potential mechanism to attenuate neuroinflammation.

Methods

Female IC rat model was established by intraperitoneal injection of cyclophosphamide (50 mg/kg, every 3 days for 3 doses). Inhibition of NLRP3 inflammasome was performed by intraperitoneal injection of MCC950 (10 mg/kg). MSC-EVs were isolated from the culture supernatants of human umbilical cord derived MSCs using ultracentrifugation, and then injected intrathecally into IC rats (20 μg in 10 μl PBS, every other day for 3 doses). Suprapubic mechanical allodynia was assessed using up-down method with von Frey filaments, and micturition frequency was examined by urodynamics. The expression of NLRP3 inflammasome components (NLRP3 and Caspase-1), glial cell markers (IBA-1 and GFAP), proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-18) and TLR4/NF-κB signal pathway (TLR4, p65 NK-κB and phospho-p65 NK-κB) in L6–S1 SDH was measured by Western blot analysis. The cellular localization of NLRP3 in SDH was detected using immunofluorescence co-staining.

Results

NLRP3 inflammasome was activated in neurons in SDH of IC rats. NLRP3 inflammasome activation contributed to activation of glial cells and process of spinal neuroinflammation in IC rats, and was related to suprapubic mechanical allodynia and frequent micturition. Intrathecal injection of MSC-EVs alleviated suprapubic mechanical allodynia and frequent micturition in IC rats, restrained activation of glial cells and attenuated neuroinflammation in SDH. In addition, MSC-EV treatment significantly inhibited activation of both NLRP3 inflammasomes and TLR4/NF-κB signal pathway.

Conclusions

NLRP3 inflammasome activation is involved in the neuroinflammation of IC. Intrathecal injection of MSC-EVs alleviates neuroinflammation and mechanical allodynia in IC by inhibiting the activation of NLRP3 inflammasome, and TLR4/NF-κB signal pathway may be the potential regulatory target.
Fast tracking in cardiac surgery: is it safe?
Authors: MacLeod Jeffrey B. , D’Souza Kenneth , Aguiar Christie , Brown Craig D. , Pozeg Zlatko , White Christopher , Arora Rakesh C. , Légaré Jean-François , Hassan Ansar
Published: April 2022

Background

While fast track clinical pathways have been demonstrated to reduce resource utilization in patients undergoing cardiac surgery, it remains unclear as to whether they adversely affect post-operative outcomes. The purpose of this study was to determine the impact of fast tracking on post-operative outcomes following cardiac surgery.

Methods

In a retrospective study, all patients undergoing first-time, on-pump, non-emergent coronary artery bypass grafting, valve, or coronary artery bypass grafting + valve at a single centre between 2010 and 2017 were included. Patients were considered to have been fast tracked if they were extubated and transferred from intensive care to a step-down unit on the same day as their procedure. The risk-adjusted effect of fast tracking on a 30-day composite of all-cause mortality, stroke, renal failure, infection, atrial fibrillation, and readmission to hospital was determined. Furthermore, propensity score matching was used to match fasting track patients in a 1-to-1 manner with their nearest “neighbor” in the control group and subsequently compared in terms of 30-day post-operative outcomes.

Results

3252 patients formed the final study population (fast track: n = 245; control: n = 3007). Patients who were fast tracked experienced reduced time to initial extubation (4.3 vs. 5.6 h, p < 0.0001) and lower median initial intensive care unit length of stay (7.8 vs. 20.4 h, p < 0.0001). Fast tracked patients experienced lower 30-day rates of the composite outcome (42.4% vs. 51.5%, p = 0.008). However, following propensity score matching, fast tracked patients experienced similar 30-day rates of the composite outcome as the control group (42.4% vs. 44.5%, p = 0.72). After risk adjustment using multivariable regression modeling, fast tracking was predictive of an improved 30-day composite outcome (OR 0.75, 95% CI 0.57–0.98, p = 0.03).

Conclusion

Fast track clinical pathways was associated with reduced intensive care unit, overall length of stay and similar 30-day post-operative outcomes. These results suggest that fast tracking appropriate patients may reduce resource utilization, while maintaining patient safety.

Graphical abstract
Infection fatality rate and infection attack rate of COVID-19 in South American countries
Authors: Musa Salihu Sabiu , Tariq Amna , Yuan Liu , Haozhen Wei , He Daihai
Published: April 2022

Background

The ongoing COVID-19 pandemic hit South America badly with multiple waves. Different COVID-19 variants have been storming across the region, leading to more severe infections and deaths even in places with high vaccination coverage. This study aims to assess the spatiotemporal variability of the COVID-19 pandemic and estimate the infection fatality rate (IFR), infection attack rate (IAR) and reproduction number ($${R}_{0}$$

R
0

) for twelve most affected South American countries.

Methods

We fit a susceptible-exposed-infectious-recovered (SEIR)-based model with a time-varying transmission rate to the reported COVID-19 deaths for the twelve South American countries with the highest mortalities. Most of the epidemiological datasets analysed in this work are retrieved from the disease surveillance systems by the World Health Organization, Johns Hopkins Coronavirus Resource Center and Our World in Data. We investigate the COVID-19 mortalities in these countries, which could represent the situation  for the overall South American region. We employ COVID-19 dynamic model with-and-without vaccination considering time-varying flexible transmission rate to estimate IFR, IAR and $${R}_{0}$$

R
0

of COVID-19 for the South American countries.

Results

We simulate the model in each scenario under suitable parameter settings and yield biologically reasonable estimates for IFR (varies between 0.303% and 0.723%), IAR (varies between 0.03 and 0.784) and $${R}_{0}$$

R
0

(varies between 0.7 and 2.5) for the 12 South American countries. We observe that the severity, dynamical patterns of deaths and time-varying transmission rates among the countries are highly heterogeneous. Further analysis of the model with the effect of vaccination highlights that increasing the vaccination rate could help suppress the pandemic in South America.

Conclusions

This study reveals possible reasons for the two waves of COVID-19 outbreaks in South America. We observed reductions in the transmission rate corresponding to each wave plausibly due to improvement in nonpharmaceutical interventions measures and human protective behavioral reaction to recent deaths. Thus, strategies coupling social distancing and vaccination could substantially suppress the mortality rate of COVID-19 in South America.

Graphical Abstract
A mediating model of mindfulness, sense of purpose in life and mental health among Chinese graduate students
Authors: Wang Yibin , Tian Tian , Wang Junjie
Published: April 2022

The purpose of the present study is to examine the relationship between mindfulness and mental health of graduate students and the mediating effects of sense of purpose in life on mindfulness and mental health. The participants include 419 graduate students from 6 universities in China, and there are 190 males and 229 females. The Hayes Process is adopted to analyze the effects of the sense of purpose in life on mindfulness and mental health of graduate students. The results reveal that mindfulness can effect the mental health of graduate students positively and significantly. The sense of purpose in life is found to mediate the relationship between mindfulness and mental health. In further moderated mediation analyses, the effect of mindfulness on mental health can be adjusted by family economic condition. The type of degree can adjust the effect of mindfulness on sense of purpose, and academic Interest can adjust the mediating effect of sense of purpose. Finally, this study discusses several empirical and methodological implications of the findings.
Clinical investigation of patients with jaw deformity with comorbidities
Authors: Kasahara Kiyohiro , Hoshino Teruhide , Sugiura Kei , Tanimoto Yuki , Koyachi Masahide , Yamamoto Masae , Sugahara Keisuke , Takano Masayuki , Katakura Akira
Published: April 2022

Background

With improvements in the safety and stability of surgeries, the number of orthognathic surgeries is increasing. Most patients who undergo orthognathic surgeries are younger, and the number of orthognathic surgeries for patients with comorbidities is also increasing. We report a survey and clinical investigation of patients with comorbidities who underwent orthognathic surgeries at our department to improve the safety of orthognathic surgery.

Results

The participants included 296 men and 712 women, with a mean age of 28 years (13–19 years, n=144; 20–29 years, n=483; 30–39 years, n=236; 40–49 years, n=102; 50–59 years, n=39; ≥60 years, n=4). In total, 347 patients underwent one-stage Le Fort type I osteotomy and sagittal split ramus osteotomy (SSRO), 243 underwent SSRO, 287 underwent plate removal, 126 underwent genioplasty and plate removal, and five underwent other surgeries. In total, 529 patients had comorbidities (52%), including allergic diseases (n=220, 33%), respiratory diseases (n=107, 16%), neurologic and psychiatric diseases (n=69, 10%), gynecologic diseases (n=28, 4%), hematologic diseases (n=27, 4%), cardiovascular diseases (n=24, 4%), digestive diseases (n=22, 3%), metabolic and endocrine diseases (n=18, 3%), spinal diseases (n=11, 2%), ophthalmologic diseases (n=11, 2%), renal and urological diseases (n=9, 1%), and other diseases (n=117, 18%). Among the patients with comorbidities, 11 with hemorrhagic diatheses (hemophilia and von Willebrand disease), arrhythmia (atrioventricular block), psychiatric disease (adjustment disorder), and metabolic disease (diabetes) required cautious perioperative management. The patient with hemophilia was managed with regular low-dose recombinant factor VIII replacement therapy, and the patient with type I diabetes mellitus was administered continuous insulin infusion and sliding-scale insulin therapy; both patients had an uneventful course.

Conclusions

The study findings suggest that with the increase in orthognathic surgeries, oral and maxillofacial surgeons should adequately manage cases requiring cautious perioperative control and highlight the importance of preoperative screening. Despite the well-established safety and postoperative stability of orthognathic surgeries, oral surgeons should adopt appropriate additional preventive measures for patients with comorbidities.
Validity and reliability of balance Y-MED application in chronic mechanical low back pain patients
Authors: Amin Noha , El Nahass Bassem , Ibrahim Mona
Published: April 2022

Background

Low back pain patients suffer from balance disturbance. Balance allows a person to interact with the surrounding environment and to do his daily activities. As recent technology has facilitated patient monitoring and enhanced our ability to monitor patients remotely, smartphone apps have been developed to achieve this goal. There are various balance assessment instruments used nowadays. It may be subjective or objective assessments. This study was applied to verify if the measurements of balance Y-MED smartphone applications are valid and reliable compared to the HUMAC balance board in order to offer easy, fast, cost-effective, and time-effective valid and reliable balance assessment that can be used in a clinical setting.

Methods

Fifty-four patients (12 males and 42 females) with chronic mechanical low back pain for more than 3 months was volunteered to participate in the current study with an age range of 25–60 years and BMI range of 18–34 kg/m2. Compared with the HUMAC balance board, the validity of the balance Y-MED smartphone application is evaluated, and the test-retest reliability of the balance Y-MED smartphone application is obtained by the same examiner 3 times.

Results

For concurrent validity, the correlations between balance measurements by Y-MED smartphone application and HUMAC balance board were not significant in both eyes open (r = − 0.12, p = 0.38) and eyes closed (r = 0.26, p = 0.054). The smartphone application showed poor test-retest reliability measurement of balance with eyes open; (ICC was 0.279, with 95% CI − 0.117–0.554) and with eyes closed (ICC was − 0.159, with 95% CI − 0.814–0.287).

Conclusions

According to the evaluation scheme selected in this study, the researchers were unable to confirm the validity of the balance Y-MED smartphone application in the balance assessment of patients with mechanical chronic low back pain. More than that, the balance Y-MED smartphone application has been shown poor score reliability. This makes it inaccurate for use in assessment balance.
Identification of specific genes involved in schizophrenia aetiology – what difference does it make?
Authors: Curtis David
Published: April 2022

Genes in which rare, damaging variants substantially increase risk of developing schizophrenia have now been identified. These findings can influence how we think about mental illness in general as well as yielding specific insights into schizophrenia aetiology. Better understanding of underlying biology might eventually lead to improved treatments.
Topological nature of the transition between the gap and the gapless superconducting states
Authors: Yerin Yuriy , Varlamov A. A. , Petrillo Caterina
Published: April 2022

Recently it was demonstrated that the long-known transition between the gap and gapless superconducting states in the Abrikosov-Gor'kov theory of superconducting alloy with paramagnetic impurities is of the Lifshitz's type, i.e., at zero temperature this is the

order phase transition. Since transitions of this kind in a normal metal are always associated to certain topological changes, then below we clarify the topological nature of the transition under consideration. Namely, we demonstrate that the topological invariant which in process of the transition undergoes the change is nothing but the Euler characteristic. Alternatively, in terms of the theory of catastrophes one can relate this transition to appearance of the cuspidal edge at the corresponding surface of the density of states as the function of energy and superconducting order parameter. The concept of experiments for the confirmation of

order topological phase transition is proposed. The obtained theoretical results can be applied for the explanation of recent experiments with lightwave-induced gapless superconductivity, for the interpretation of the disorder-induced transition

states via gapless phase in two-band superconductors, and the emergence of gapless color superconductivity in quantum chromodynamics.
Seasonal Variation in Thyroid Function in Over 7,000 Healthy Subjects in an Iodine-sufficient Area and Literature Review
Authors: Yamada Sayaka , Horiguchi Kazuhiko , Akuzawa Masako , Sakamaki Koji , Shimomura Yohnosuke , Kobayashi Isao , Andou Yoshitaka , Yamada Masanobu
Published: April 2022

Context

Seasonal variation in thyroid function, especially serum free triiodothyronine (FT3) and free thyroxine (FT4) levels, in healthy subjects remains unclear.

Methods

We examined thyroid function, including serum FT3 and FT4 levels, in healthy Japanese subjects using data of more than 7,000 health check-up participants and applied the analysis of means with transformed ranks (ANOMTR) to compare each month. In addition, we reviewed reports published in the last 2 decades.

Results

The median serum thyrotropin (TSH) level was the highest in January (1.61 mIU/L), and the lowest in May (1.16 mIU/L). ANOMTR revealed that serum TSH levels are high in winter and low in summer. Conversely, the median serum FT3 level was higher in July than in other months, and the ANOMTR plot demonstrated serum FT3 levels to be significantly higher in summer and lower in winter. In contrast, serum FT4 levels were more consistent throughout the year, but statistically, those in February and March, October, and November were higher than those in other months. ANOMTR revealed variations in serum FT4 levels to be small through the year but biphasic.

Conclusions

Taken together with previous reports, our study demonstrated seasonal changes in the serum TSH levels to be high in winter in the northern hemisphere; however, the serum FT3 differed among countries, and those of Japanese, an iodine-sufficient country, were high in summer. In contrast, FT4 levels were more consistent. These changes should be taken into account to precisely evaluate thyroid function.
Ambulatory blood pressure monitoring using telemedicine: proof-of-concept cohort and failure modes and effects analyses
Authors: Armitage Laura C. , Lawson Beth K. , Roman Cristian , Thompson Beth , Biggs Christopher , Rutter Heather , Lewis-Jones Martin , Ede Jody , Tarassenko Lionel , Farmer Andrew , Watkinson Peter
Published: April 2022

Background: The COVID-19 pandemic has accelerated adoption of remote consulting in healthcare. Despite opportunities posed by telemedicine, most hypertension services in Europe have suspended ambulatory blood pressure monitoring (ABPM).

Methods: We examined the process and performance of remotely delivered ABPM using two methodologies: firstly, a Failure Modes and Effects Analysis (FMEA) and secondly, a quantitative analysis comparing ABPM data from a subgroup of 65 participants of the Screening for Hypertension in the INpatient Environment (SHINE) diagnostic accuracy study. The FMEA was performed over seven sessions from February to March 2021, with a multidisciplinary team comprising a patient representative, a research coordinator with technical expertise and four research clinicians.

Results: The FMEA identified a single high-risk step in the remote ABPM process. This was cleaning of monitoring equipment in the context of the COVID-19 pandemic, unrelated to the remote setting.

A total of 14 participants were scheduled for face-to-face ABPM appointments, before the UK March 2020 COVID-19 lockdown; 62 were scheduled for remote ABPM appointments since emergence of the COVID-19 pandemic between November 2020 and August 2021. A total of 65 (88%) participants completed ABPMs; all obtained sufficient successful measurements for interpretation. For the 10 participants who completed face-to-face ABPM, there were 402 attempted ABPM measurements and 361 (89%) were successful. For the 55 participants who completed remote ABPM, there were 2516 attempted measurements and 2214 (88%) were successful. There was no significant difference in the mean per-participant error rate between face-to-face (0.100, SD 0.009) and remote (0.143, SD 0.132) cohorts (95% CI for the difference -0.125 to 0.045 and two-tailed P-value 0.353).

Conclusions: We have demonstrated that ABPM can be safely and appropriately provided in the community remotely and without face-to-face contact, using video technology for remote fitting appointments, alongside courier services for delivery of equipment to participants.