bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating diagnostic and management agreement between physiotherapists and ear, nose and throat specialist in a primary contact physiotherapy-led vestibular clinic: A prospective blinded inter-rater agreement study
Authors: Stewart Vicky , Eakin Jennifer , Weir Kelly , Noonan Fritha , Payten Christopher , Smith Tamsin
Published: March 2023

Background: Dizziness and vertigo are common referrals to Ear Nose Throat (ENT) outpatient services however these services have long waitlists for assessment. While a primary contact physiotherapy-led vestibular clinics is recognized at improving access to care, no published literature has reported on the safety and diagnostic accuracy of such a service. This study investigates diagnostic and management agreement between physiotherapists and ENT specialist for patients attending a primary contact physiotherapy-led vestibular clinic.
Methods: Prospective blinded inter-rater agreement study undertaken in an ENT primary contact physiotherapy-led vestibular clinic. Participants included adults referred to ENT from general practitioners, triaged (Category 2 or 3) to the primary contact physiotherapy-led vestibular clinic with clinical symptoms consistent with vestibular disorder. Primary outcome measures included diagnoses and management decisions (imaging, ENT/ neurology/ physiotherapy management). Adverse events were reviewed 11 months post data collection. Percentage agreement and Gwet’s first order agreement co-efficient (AC1) calculated inter-rater reliability between physiotherapy and ENT.
Results: Fifty-one participants were recruited consecutively from the primary contact physiotherapy-led vestibular clinic. Physiotherapy and ENT had a 78% agreement on categorised diagnosis. Agreements between physiotherapy and ENT for recommending Magnetic resonance imaging was 86%, and 94% for computorised tomography. There was moderate to near-perfect agreement regarding management recommendations between physiotherapy and ENT. An 82% agreement was found for recommendations to ENT, 94% for neurology and 73% for physiotherapy. There were no adverse events from physiotherapist’s management decision, based on final recommendations undertaken 11-months post data collection.
Conclusions: Physiotherapists and ENT made comparable diagnostic and management decisions, based on physiotherapy assessment, for adults with signs of vestibular dysfunction, within an ENT primary contact physiotherapy-led vestibular clinic. This provides reassurance about the competency and safety of vestibular physiotherapists in the management of patients with dizziness.
Prepulse Inhibition Deficit as a Transdiagnostic Process in Neuropsychiatric Disorders: A Systematic Review
Authors: Santos-Carrasco Daniel , Casa Luis Gonzalo De la
Published: March 2023

Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple pathologies. A phenomenon disrupted in several disorders is prepulse inhibition (PPI) of the startle response, in which startle to an intense sensory stimulus, or pulse, is reduced if a weak stimulus, or prepulse, is previously presented. The present systematic review analyzed the role of PPI deficit as a possible transdiagnostic process for three main groups of neuropsychiatric disorders: 1) trauma-, stress-, and anxiety-related disorders 2) mood-related disorders, and 3) neurocognitive disorders. We used Web of Science, Pubmed and PsycInfo databases to search for experimental case-control articles that were analyzed both bibliometrically and based on their potential risk of bias. A total of 41 studies were included in this systematic review. The results showed a general PPI deficit in the three diagnostic groups mentioned, with associated deficits in the dopaminergic neurotransmission system, several areas implied such as the medial prefrontal cortex or the amygdala, and related variables such as cognitive deficits and anxiety symptoms. It can be concluded that the PPI deficit is a transdiagnostic process across most of the neuropsychiatric disorders examined, and it is a relevant measure in translational research for the early detection and intervention of such disorders. Protocol submitted prospectively to PROSPERO 04/30/2022 (CRD42022322031).
Impact of initial dialysis modality on the survival of patients with ESRD: A propensity-score-matched study
Authors: Liu Li , Pang Jie , Xu Juan , Liu Lin-na , Liao Man-yu , Huang Qing-xiu , Li Yan-lin
Published: March 2023

Background
Studies comparing survival of hemodialysis (HD) and peritoneal dialysis (PD) patients are controversial. This study evaluated the impact of initial dialysis modality on the survival of patients with end-stage renal disease (ESRD) in a matched-pair cohort.
Methods
A retrospective cohort study was performed on ESRD patients who initiated renal replacement treatment between January 1, 2010, and December 31, 2018. Propensity score matching was applied to balance the baseline conditions, and multivariate Cox regression analysis was applied to compare mortality between HD and PD patients and evaluate correlations between mortality and various baseline characteristics. Subgroup analysis was performed with respect to diabetes status.
Results
There were 739 patients in our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2018. Of these, 125 PD patients were matched with 125 HD patients. The 1-, 2-, and 3-year survival rates were 96.5%, 90.7%, and 82.5%, respectively, in the HD group and 99.5%, 97.8%, and 92.5%, respectively, in the PD group (log-rank P < 0.001). Among the propensity score-matched cohorts, no significant differences in Kaplan–Meier curves were observed between the two groups (log-rank P = 0.514). Age at dialysis initiation, CCI, congestive heart failure and cerebrovascular disease were risk factors in the multivariable-adjusted model. In subgroups defined by diabetes status, the Kaplan‒Meier survival curve showed that PD survival was significantly higher than that of HD (log-rank P = 0.022).
Conclusions
HD and PD were not significantly different with regard to survival of patients with ESRD. PD was associated with better survival in diabetic ESRD patients.
Clinical value of simultaneous boost intensity modulated radiotherapy in high-risk clinical target volume of stage IIb-IVa cervical carcinoma
Authors: jiang yuqi , Zhang Lei , Wang Jing , Jiang Peng , Wang Xiang , Zhang Yongchun
Published: March 2023

Background
To compare the clinical efficacy of simultaneous modulated accelerated radiotherapy therapy to high-risk clinical volume (CTV-hr) with conventional intensity modulated radiotherapy therapy for stage IIB-IVA cervical cancer, and investigate the value of defining high-risk clinical target areas for parallel radiation dose simultaneous nudging in patients with locally advanced cervical cancer.
Methods
Retrospectively analyzed patients with stage IIB-IVA cervical cancer who received radical radiotherapy at the Affiliated Hospital of Qingdao University from November 2014 to September 2019, divided into hr-SMART group and n- SMART group according to whether to set a high-risk clinical target volume(CTV-hr) and push the volume to 54–56 Gy simultaneously. Both groups were given brachytherapy and chemotherapy and compared the efficacy and adverse effects.
Results
A total of 217 patients were assessed, with 119 and 98 in the hr-SMART and n-SMART groups. Hr-SMART and n-SMART groups had significantly different mortality rate(19.3% vs 41.8%), overall recurrence rates (26.1% vs 50%) with statistically significant differences (p < 0.05). According to the KM survival curve, hr-SMART has a better OS (3-year OS rate, 87.4% vs. 71.4% ; P = 0.001) and PFS (3-year OS rate, 72.3% vs. 51.0% ; P = 0.000)than n-SMART.The objective remission rates (ORR) in the hr-SMART and n-mart groups were 91.6% and 90.8%, respectively, with no statistically significant differences (p༞0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (p > 0.05).
Conclusions
Setting up high-risk clinical target volume and undergoing simultaneous modulated accelerated radiotherapy for patients with stage IIB-IVA cervical cancer can reduce recurrence and improve clinical efficacy with comparable adverse effects.
Genetic diversity and population structure of selected species of Eplingiella (Lamiaceae) using ISSR molecular markers
Authors: Silva Anderson de Carvalho , de Oliveira Lenaldo Muniz , Pastore José Floriano Barêa , Berg Cassio van den , Soares Taliane Leila , de Souza Everton Hilo
Published: March 2023

The present study evaluated the population structure and genetic diversity using ISSR molecular markers in 18 natural populations belonging to three species ofEplingiella(E. cuniloides, E. fruticosaandE. brightoniae), found growing naturally in the semiarid region of Northeast Brazil. Samples of 265 plants were analyzed using nine primer combinations, which generated 131 informative bands.Eplingiellaspp. populations showed moderate genetic diversity (percentage of polymorphic bands, PPB = 75.6–96.9%, Nei's genetic diversityHe = 0.31–0.39, Shannon's information indexI = 0.33–0.48). Molecular variance analysis (AMOVA) revealed that within populations, variations contributed more (74%) to the genetic diversity than between population variations (26%), with percentage of the genetic differentiation coefficient (GST= 0.29). The mean value ofFSTwas 0.175, demonstrating good differentiation between populations. The analysis of the structure by the Bayesian method revealed the formation of two groups (K = 2), with many migrant individuals and a high level of miscegenation. The hierarchical cluster dendrogram grouped the 18 populations into two major clusters, with good support for the main clades (100%). According to principal component analysis (PCA), the two main principal components explained 21.06% of the total variation. The ISSR molecular markers used were effective in identifying the variability of natural populations ofEplingiellaspp., and population structure demonstrated recent diversification of species. The results shed more light on the genetic variation and evolutionary dynamics ofEplingiella, helping to formulate effective breeding strategies.
Salidroside regulates tumor microenvironment of non-small cell lung cancer via Hsp70/Stub1/Foxp3 pathway in Tregs
Authors: Wen Zexin , Liu tong , Zhang Yanli , Yue Qiujuan , Meng Hang , He Yijie , Yang Yi , Li Minghao , Zheng Jianwen , Lin Wei
Published: March 2023

Background:The treatment of non-small cell lung cancer (NSCLC) is challenging due to immune tolerance and evasion. Salidroside (SAL) is an extract in traditional Chinese medicine and has a potential antitumor effect. However, the mechanism of SAL in regulating the immunological microenvironment of NSCLC is yet to be clarified.Methods:The mouse model with Lewis lung cancer cell line (3LL) in C57BL/6 mice was established. And then, the percentage of tumor-infiltrating T cell subsets including Treg was detected in tumor-bearing mice with or without SAL treatment.In vitro, the effect of SAL on the expression of IL-10, Foxp3 and Stub1 and the function of Treg were detected by flow cytometry. Network pharmacology prediction and molecular docking software were used to predict the target of SAL and intermolecular interaction. Furthermore, the effect of SAL on the expression of Hsp70 and the co-localization of Stub1-Foxp3 in Treg was confirmed by flow cytometry and confocal laser microscopy. Finally, Hsp70 inhibitor was used to verify the above molecular expression.Results:We discovered that SAL treatment inhibits the growth of tumor cells by decreasing the percentage of tumor-infiltrated CD4+Foxp3+T cells. SAL treatment downregulates the expression of Foxp3 in Tregs, but increases the expression of Stub1, an E3 ubiquitination ligase upstream of Foxp3, and the expression of Hsp70. Inhibiting the expression of Hsp70 reverses the inhibition of SAL on Foxp3 and disrupts the colocalization of Stub1 and Foxp3 in the nucleus of Tregs.Conclusions:SAL inhibits tumor growth by regulating the Hsp70/stub1/Foxp3 pathway in Treg to suppress the function of Treg. It is a new mechanism of SAL for antitumor therapy.
WITHDRAWN: The Impact of Training and Technological Innovation on Early Childhood Development under a National Home-Visiting Programme in Ecuador: study protocol for a cluster-randomised trial
Authors: Conti Gabriella , Gupta Sweta , Hill Zelee , Jervis Pamela , Paredes Tatiana
Published: March 2023

Background
This study aims to document the effect of teacher training, technology-enabled monitoring, information and motivational nudges in a national home-visiting programme on early childhood development in Ecuador.
Methods
The study is a 2-arm, cluster randomized controlled trial with parallel assignment and an active control group. The clusters are 48 catchment areas (districts) in the Sierra (Highlands) region of Ecuador, and all home-visiting teachers, district analysts, and children in the selected districts are included in the study. In addition, a random sample of 34 children and their biological mothers or caregivers per district will be selected for evaluation of outcomes. The primary outcome measures are: (1) pre-literacy and pre-numeracy skills as measured by the IDELA (2) executive functioning as measured by the IDELA and the Delay Choice Task (3) language development as measured by the TVIP and (4) Child Development (caregiver report) as measured by ECDI.
Discussion
Several small-scale home-visiting trials, targeting undernourished children in developing countries, have shown impacts on early childhood development in the short run. But the important question remains as to whether such results can be achieved at scale. If the intervention under this study is found to be effective at improving child development, it would have important implications for low and middle-income countries where 250 million children under the age of five are at risk of not reaching their full development potential. The intervention is integrated into an existing nation-wide home-visiting programme in Ecuador and involves training existing staff alongside upgrading the digital infrastructure, thus representing a feasible strategy for large-scale implementation.
Trial Registration Number:
ISRCTN16602033. Registered on 14 January 2023, https://www.isrctn.com/ISRCTN16602033.
Positional cloning and functional verification of the epidermal protein gene KWMTBOMO04384 in silkworm, Bombyx mori
Authors: Sun Juan , Liu Min , Zheng Xin , Ouyang Gui , Qian Heying , Chen Anli
Published: March 2023

A body shape mutant n08M with sunken intersegmental membrane was found during the feeding process of silkworm WT-n08. Genetic analysis showed that the mutant trait of n08M is controlled by a recessive gene located at the autosome and follows Mendelian inheritance. Results of positional cloning showed that the epidermal protein gene KWMTBOMO04384 on chromosome 26 was mutated. After KWMTBOMO04384 was knocked out by CRISPR/Cas9, the intersegmental membrane of silkworm was sunken. KWMTBOMO04384 was the target gene that caused the sunken intersegmental membrane in WT-n08 and had an important influence on the body shape of Bombyx mori.
The Clinical Utility of salivary oxytocin as a putatively surrogate early Risk Identification biomarker of nascent Metabolic Syndrome with and without prediabetes
Authors: Bulatova Nailya R. , Kasabri Violet N. , Albsoul Abla M. , Halaseh Lana , Suyagh Maysa
Published: March 2023

Aims and methods This study aimed to compare and correlate pharmacotherapy biomarkers’ plasma and salivary levels (appraised using colorimetric assays of Lipocalin, Nesfatin, Omentin, Oxytocin, RBP-4 (retinol-binding protein-4), Resistin, SIRT 1 (sirtuin 1), Visfatin and ZBED3 (zinc finger, BED-type (ZBED) protein 3), adiposity, and atherogenicity indices in 61 normoglycemic and newly diagnosed drug naive pre-diabetic (PreDM) MetS (metabolic syndrome) patients vs. 29 lean, and normoglycemic controls. Intergroup Comparisons was conducted by ANOVA. Spearman rank correlation was also examined.
Results About three quarters of the participants were females, with gender distribution similar between the two study groups (P = 0.585). Among MetS patients, almost half were normoglycemic, about 43% were prediabetic and about 8% were diabetic. The average age of study participants was 48.6 years, with MetS group being significantly older than the control group (P < 0.001). In accordance to the study selection criteria, glycemic (FPG and A1c) and lipid parameters (TG, HDL-C and non-HDL-C), adiposity indices (BMI, WHR, WtHR, C-index, BAI, LAP, VAI) and atherogenicity indices (AIP, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C and TG/HDL-C) were all significantly higher in the MetS group compared to the control group (P < 0.05). Among the plasma cardiometabolic risk biomarkers of pharmacotherapy, plasma (but not salivary) lipocalin levels and Salivary nesfatin (unlike plasma nesfatin) were significantly higher P < 0.05) in the MetS group compared to the normoglycemic lean controls. Notably, plasma SIRT1 levels were pronouncedly greater (P < 0.05) in MetS recruits in comparison to control’s levels. Conversely; salivary SIRT1 concentrations in MetS pool markedly exceeded those of controls’ salivary levels. Oddly and collectively salivary and blood levels of omentin, oxytocin, RBP-4, resistin, visfatin and ZBED3 lacked comparably pronounced discrepancies in MetS cases vs. those of study controls. Exceptionally oxytocin, amongst 9 cardiometabolic risk biomarkers of pharmacotherapy studied, had proportional significant correlations between plasma and saliva levels, in both total sample and MetS patients (P < 0.05). Plasma OXT in the total sample correlated significantly though inversely with both SBP and FBG (unlike salivary OXT). Interestingly of MetS pool; markedly Proportional correlations of plasma (but not salivary) OXT with TG, and adiposity indices of LAP and VAI, and all atherogenecity indices were delineated. Collectively both blood and saliva OXT in the total study pool, as well as the remaining biomarkers; lacked comparably substantial associations with both adiposity and atherogenecity indices and clinical parameters of fasting lipid profile.
Expression of secretory calcium-binding phosphoprotein (scpp) genes in medaka during the formation and replacement of pharyngeal teeth
Authors: Morita Tsuyoshi , Matsumoto Shin , Baba Otto
Published: March 2023

Background
Analyses of tooth families and tooth-forming units in medaka with regard to tooth replacement cycles and the localization of odontogenic stem cell niches in the pharyngeal dentition clearly indicate that continuous tooth replacement is maintained. The secretory calcium-binding phosphoprotein (SCPP) cluster is involved in the formation of mineralized tissues, such as dental and bone tissues, and the genes encoding multiple SCPPs are conserved in fish, amphibians, reptiles, and mammals. In the present study, we examined the expression patterns of several scpp genes in the pharyngeal teeth of medaka to elucidate their roles during tooth formation and replacement.
Methods
Himedaka (Japanese medaka, Oryzias latipes) of both sexes (body length: 28 to 33 mm) were used in this study. Real-time reverse transcription–polymerase chain reaction (PCR) (qPCR) data were evaluated using one-way analysis of variance for multi-group comparisons, and the significance of differences was determined by Tukey’s comparison test. The expression of scppgenes was examined using in situhybridization (ISH) with a digoxigenin-labeled, single-stranded antisense probe.
Results
qPCR results showed that several scpp genes were strongly expressed in pharyngeal tissues. ISH analysis revealed specific expression of scpp1, scpp5, and sparc in tooth germ, and scpp5 was continually expressed in the odontoblasts of functional teeth but not in osteoblast of pedicles. In addition, many scpp genes were expressed in enameloid cells but not in odontoblasts, and scpp2 consistently showed epithelial-specific expression in the functional teeth. Taken together, these data indicate that specific expression of scpp2 and scpp5 may play a critical role in pharyngeal tooth formation in medaka.
Conclusion
We characterized changes in the expression patterns of scpp genes in medaka during the formation and replacement of pharyngeal teeth.
Translation and Psychometric Evaluation of the Persian Version of “Good Death Inventory- Short Form” from the perspective of family- members of cancer patients
Authors: Roshan Hosein Mohammadi , Ebadi Abbas , Karimi Leila , Barasteh Salman
Published: March 2023

Introduction: Achieving good death and enhancement of end-of-life care are among the objectives of palliative care in patients with cancer. There should be an instrument for evaluating the quality of palliative care provided by family members to provide comprehensive care at the end of life. This study was done for translation and assessment the psychometric properties of good death inventory- short form according to the perspective of family of patients with cancer in Tehran.
Method: This methodological study was done in 2022 at two hospitals in Tehran. The translation was done after receiving permission from the instrument’s developer via forward-backward method. Face validity was examined through cognitive interviewing with 10 family members of patients with cancer. To perform the quantitative and qualitative content validation, the opinions of 10 palliative care specialists were used. The construct validity was explored through exploratory factor analysis and examination of convergent validation with care evaluation scale 2.0 (CES), as well as inspection of correlation by answering two general questions of satisfaction with treatment and end-stage quality of life. The scale’s reliability, internal consistency was calculated using Cronbach’s alpha coefficient and stability via test-retest.
Results:Overall, 204 family members of patients with cancer were included. In the exploratory factor analysis, three factors of peace, hope, and value as well as quality of care were extracted with cumulative variance of 41.8%. We found a significant and suitable correlation between the total scores of the participants Good death inventory-short form and care evaluation scale2.0 (r = 0.459, P < 0.001). Also, there was a positive and significant correlation between the GDI short form total score and general satisfaction with end-of-life care (r=0.423, p<0.001) as well as the patient’s general quality of life at terminal stages (r=0.539, p<0.001). The Cronbach’s alpha coefficient for the questionnaire was found 0.842, and the stability was confirmed with ICC=0.851.
Conclusion: the Persian version of GDI-short form is a valid and reliable questionnaire which can investigate the factors associated with good death according to patients’ family members’ perspective. Thus, this instrument can be used in clinical evaluation as well as research purposes and for family members in Iranian population.
Experimental comparative study on Near-dry wire-cut electrical discharge machining process using moistened wire
Authors: Xie Wenling , Guo Cuixia , Wang Xing , Zhang Jianping
Published: March 2023

The disturbance of flushing to the electrode wire exists in conventional top and bottom flushing process and the machined surface easily being burned in the dry process, a novel dielectric fluid feeding method (moistened wire method) with near-dry high-speed reciprocating wire electrical discharge machine (HS-WEDM) was proposed. A dielectric fluid was poured onto a drum to achieve a moistened wire and packed into the discharge gap by a high-speed running molybdenum wire, and form a gas-liquid double-layer dielectric for discharge machining, cooling and cleaning for the working material. The effect of four processing (conventional top and bottom flushing with emulsion, the dry with atmospheric, the moistened wire with emulsion and moistened wire with emulsion-SiC nanofluids) during the finishing process on the kerf width, average cutting speed, surface roughness, surface morphology, and corner accuracy of the Cr12MoV die steel was studied. Compared to the conventional top and bottom flushingprocess, the moistened wires with emulsion and emulsion-SiC nanofluid processes maintained the high cutting speeds and obtained smooth machined surfaces. The Ra values decreased by 39.8% and 45.8%, the inner circle radius decreased by 4.1% and 4.9%, and outer circle radius decreased by 3.4% and 10.3%, respectively. The results showed that the moistened wire process improved the machined surface quality and corner accuracy of 90° profile without sacrificing the average cutting speed due to their moderate discharge gaps. Compared with the moistened wires with emulsion process, the moistened wires with emulsion-SiC nanofluid process further improved machined quality with lower surface roughness and corner error.
lncRNA TRHDE-AS1 correlated with genomic landscape and clinical outcome in glioma
Authors: Xie Jinxuan , Lin Yi , Li Yajie , Fang Aizhong , Li Xin , Li Wenbin
Published: March 2023

Background
The role of lncRNA in cancer development has received more and more attention in researches. A variety of lncRNAs are associated with the occurrence and development of glioma. However, the role of TRHDE-AS1 in glioma is still unknown.
Result
In this study, we explored the role of TRHDE-AS1 in glioma through bioinformatics methods. We first identified an association between TRHDE-AS1 and tumor prognosis in a pan-cancer analysis. Subsequently, the expression levels of TRHDE-AS1 in various clinical types of glioma were compared, and significant differences were found in pathological classification, WHO classification, molecular classification, IDH mutation and age stratification. We analyzed the genes co-expressed with TRHDE-AS1 in glioma. In the functional analysis of TRHDE-AS1, we found that TRHDE-AS1 may be involved in the regulation of synapse-related functions. In glioma cancer driver gene correlation analysis, it was also found that TRHDE-AS1 was significantly correlated with the expression levels of multiple driver genes such as TP53, BRAF, and IDH1. By comparing the mutant profiles of the high and low TRHDE-AS1 groups, we also found that there may be differences in TP53 and CIC gene mutations in low-grade gliomas. Subsequent correlation analysis between TRHDE-AS1 and glioma immune microenvironment showed that the expression level of TRHDE-AS1 was correlated with a variety of immune cells.
Conclusion
Therefore, we believe that TRHDE-AS1 is involved in the occurrence and development of glioma and has the ability to predict the prognosis of glioma as a biomarker of glioma.
Development of a Genetically Encoded Magnetic Platform in Magnetospirillum gryphiswaldense MSR-1 for Downstream Processing of Protein Expression System
Authors: Wu Sha , Tian Jiesheng , Xue Xianle , Tang Zongwen , Huang Zekai , Hammock Bruce D. , Morisseau Christophe , Li Qing X. , Xu Ting
Published: March 2023

Background: Protein downstream processing remains a challenge in protein production, especially in low yields of products, in spite of ensuring effective disruption of cell and separation of target proteins. It is complicated, expensive and time-consuming. Here, we report a novel nano-bio-purification system for producing recombinant proteins of interest with automatic purification from engineered bacteria.
Results: This system employed a complete genetic engineering downstream processing platform for proteins at low expression levels, referred to as a genetically encoded magnetic platform (GEMP). GEMP consists of four elements as follows. (1) A truncated phage lambda lysis cassette (RRz/Rz1) is controllable for lysis of Magnetospirillum gryphiswaldense MSR-1 (host cell). (2) A surface-expressed nuclease (NucA) is to reduce viscosity of homogenate by hydrolyzing long chain nucleic acids. (3) A bacteriogenic magnetic nanoparticle, known as magnetosome, allows an easy separation system in a magnetic field. (4) An intein realizes abscission of products (nanobodies against tetrabromobisphenol A) from magnetosome.
Conclusions: In this work, removal of most impurities greatly simplified the subsequent purification procedure. The system also facilitated the bioproduction of nanomaterials. The developed platform can substantially simplify industrial protein production and reduce its cost.
Energetics of the non-covalent interactions in the acetonechloroform system by MP2/CBS quantum chemical calculations
Authors: Rosas-Garcia Victor M. , Alanís-Cuevas Cristofer Adrián
Published: March 2023

We studied the energetics of the non-covalent interactions present in the acetone-chloroform system at the MP2/Complete Basis Set level of theory to shed light on the interactions responsible for azeotrope formation. To this end, we did a configurational search for the diverse geometries of homodimers of (acetone)2 and (chloroform)2 , and acetone-chloroform heterodimers. All the structures were subjected to full geometry optimization and their vibrational frequencies calculated. Energies were extrapolated to the Complete Basis Set limit and BSSE correction applied. We found that MP2/Complete Basis Set level of theory predicts the trend (acetone)2 > acetone-chloroform > (chloroform)2 , while MP2/cc-pVDZ severely underestimates the interaction energies as well as predicts a wrong trend in the energies. The resulting wavefunctions were analyzed by Reduced Density Gradient and Non-Covalent Interaction methods yielding a variety of critical points. This revealed that the reported hydrogen bond for the acetone-chloroform dimer likely has a van der Waals component involving interaction between a chlorine in chloroform and a hydrogen in acetone.
A time-motion study of community health workers delivering community-based primary health care in Neno District, Malawi
Authors: Aron Moses Banda , Ndambo Myness Kasanda , Munyaneza Fabien , Mulwafu Manuel , Makungwa Henry , Nhlema Basimenye , Connolly Emilia
Published: March 2023

Introduction: Community Health Workers (CHWs) are vital resources in delivering community-based primary health care, especially in low-and-middle-income countries (LMIC). However, few studies have investigated detailed time and task assessments of CHW's work. We conducted a time-motion study to evaluate CHWs' time on health conditions and specific tasks in Neno District, Malawi.
Methods: We conducted a descriptive quantitative study utilizing a time observation tracker to capture time spent by CHWs on focused health conditions and tasks performed during household visits. We observed 64 CHWs between 29 June and 20 August 2020. We computed counts and median to describe CHW distribution, visit type, and time spent per health condition and task. We utilized Mood’s Median Test to compare the median time spent at a household during monthly visits with the program design standard time. We used Pairwise Median Test to test differences in median time duration for health conditions and assigned tasks.
Results: We observed 660 CHW visits from 64 CHWs, with 95.2% (n= 628) of the visits as monthly household visits. The median time for a monthly household visit was 34 minutes, statistically less than the program design time of 60 minutes (p<0.001). While the CHW program focused on eight disease areas, pretesting with the observation tool showed that CHWs were engaged in additional health areas like COVID-19. Of the 3043 health area touches by CHWs observed, COVID-19, tuberculosis, and non-communicable diseases (NCDs) had the highest touches (19.3%, 17.6%, and 16.6%, respectively). The median time spent on sexually transmitted infections (STIs) and NCDs was statistically higher than in other health areas (p<0.05). Of 3813 tasks completed by CHWs, 1640 (43%) were on health education and promotion. A significant difference was observed in the median time spent on health education, promotion, and screening compared to other tasks (p<0.05).
Conclusion: This study demonstrates that CHWs spend the most time on health education, promotion, and screening per programmatic objectives but, overall, less time than program design. CHWs deliver care for a broader range of health conditions than the programmatic design indicates. Future studies should examine associations between time spent and quality of care delivery.
Quantifying the invasion risk of West Nile virus: insights from a multi-vector/multi host SEIR model
Authors: Ferraguti Martina , Martins Afonso Dimas , Artzy-Randrup Yael
Published: March 2023

The invasion of vector-borne diseases depends on the type of specific features of the vector and hosts at play. Within the Culex pipiens complex, differences in ecology, biology, and vector competence can influence the risk of West Nile virus (WNV) outbreaks. To determine which life-history traits are most important, we constructed an epidemiological Susceptible-Exposed-Infectious-Recovered model with three vector eco-types, Culex pipiens pipiens, Cx. pip. molestus, and their hybrids, and two vertebrate hosts, birds (as amplifying hosts) and humans (as dead-end hosts). We investigated how differences in feeding preferences and transmission rates influenced WNV transmission across different habitats and two simulated scenarios, i.e., global change and increasing urbanisation settings, to investigate the impact of increasing mosquito and human abundance on the WNV transmission risk. Our results showed that vector feeding preferences and the transmission rate between mosquitoes and birds were the parameters that most impacted WNV invasion risk. Natural habitats were overall more susceptible to WNV invasion, although rural habitats were also susceptible in a climate change scenario. Pipiens-type-related factors dominated virus amplification in natural and rural habitats, while molestus-type-related factors drove the spread of WNV in urban environments. Contrary to common opinion, our findings suggest that hybrids may play only a minor role in WNV transmission. Our study will improve current vector surveillance and control programs by targeting specific vector types in specific environments, especially in rural settings, which are most responsive to environmental shifts. This approach can help reduce wasted time and economic costs while maximizing the efficiency of local public health authorities.
Investigating the Atlantic-monsoon teleconnection pathways in PMIP3 Last Millennium Simulations
Authors: Dutta Arijeet , Sivankutty Rahul , Neena J.M.
Published: March 2023

The Atlantic multidecadal oscillation (AMO) is considered as one of the major drivers of Indian Summer monsoon (ISM) multidecadal variability, but the exact mechanism of teleconnection remains elusive. AMO can impact the ISM dominantly by two pathways – by generating upperlevel circulation and heating responses across Eurasia and via the Pacific through the atmospheric bridge mechanism and associated modulations of Hadley-Walker circulations in the Indo-Pacific. Using the PMIP3 Last millennium (LM) simulations, the current study investigates the AMO-ISM teleconnection in the context of these pathways of interaction. A significant positive correlation is observed between AMO and ISM in five of the eight models. While the models display only limited skill in simulating the upper-level circulation and tropospheric temperature responses involved in the Eurasian pathway, they exhibit better skill in capturing the Pacific SST responses induced by the AMO. Four of the five models capture the AMO modulation of summer North Atlantic Oscillation (SNAO), but major discrepancies are observed in the SNAO downstream responses. CCSM4 and MPI exhibit better skill in simulating the AMO forced upper-level circulation responses across Eurasia, while CSIRO, GISS and MRI-CGCM3 exhibit better skill in simulating the AMO modulation of extra tropical-tropical SST gradient over the Pacific. Reliability of decadal climate predictions of ISM largely depends on the fidelity of current generation global models in simulating the teleconnection mechanisms which modulate the ISM multidecadal variability, and results from the current study helps in highlighting some of the main deficiencies in model simulated teleconnection processes.
Phylogenotyping of the Vietnamese infectious bursal disease viruses according to the newly unified genotypic classification scheme
Authors: LE THANH HOA , Le Xuyen Thi Kim , Do Roan Thi , Doan Huong Thi Thanh , Nguyen Khue Thi , Pham Linh Thi Khanh
Published: March 2023

The unified genotypic classification scheme (genotypes A0, A1–A8, and B1–B5) was proposed and applied for the classification of the infectious bursal disease virus (IBDV). Since 1987, IBDVs have circulated and evolved in Vietnam, but little is known about the genotypes present. The IBDV samples were collected in 1987, 2001–2006, 2008, 2011, 2015–2019, and 2021 in 18 provinces. We conducted phylogenotyping analysis based on the alignment of 143 VP2-HVR (439 bp, nt 628–1066; aa 210–355 in VP2), including 64 Vietnamese isolates and two vaccines, and 82 VP1 B-marker (725 bp, nt 13–737; aa 4–245 in VP1) sequences, including four Vietnamese isolates and one vaccine. The analysis revealed three A-genotypes, A1, A3, and A7, and two B-genotypes, B1 and B3, among the Vietnamese IBDVs. The IBDV strains showed the lowest average evolutionary distance at 8.6% between A1 and A3 and the highest (21.7%) between A5 and A7, while 14% was between B1 and B3 and 17% between B3 and B2. The signature residues 222T - 253Q - 256V - 294L - 299(S/N) appeared to be unique for the genotype A2; the 222A - 253Q - 256I - 294I - 299S for the A3, the 222T - 253Q - 256V - 294L - 299N for the A5, the 222Q - 253E - 256K - 294L - 299S for the A6, and the 222A - 253Q - 256A - 294L - 299S for the A8, and each of these could be the genotypical motif for genotypic discrimination. The timeline statistical summary revealed that the A3-genotype predominated (79.8% presence) in Vietnam from 1987 to 2021 and that it has remained dominant in circulating IBDVs over the last five years (2016–2021).
Engineering siRNA-loaded and RGDfC-targeted selenium nanoparticles for highly efficient silencing of DCBLD2 gene for colorectal cancer treatment
Authors: Huang Hongli , Chen Hanqing , Shou Diwen , Quan Ying , Cheng Jiemin , Chen Huiting , Ning Gang , Li Yongqiang , Xia Yu , Zhou Yongjian
Published: March 2023

Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.
Carbonation and sweet taste dysgeusia with Topiramate therapy for migraine prevention treatment: a case report
Authors: Galassi Luca , Facchinetti Federica
Published: March 2023

Introduction
Migraine is a common pathology with a reported incidence up to 12% in the European general population. It can determine a significant impact on patients’ quality of life considering symptoms that can range from headaches, nausea, vomiting or external stimuli hypersensibility.
Migraine treatment includes numerous classes of drugs that can be used both for treatment and prophylaxis including anti-epilepsy drugs such as Topiramate.
Although topiramate has been reported to be associated with a significant number of adverse side effects including dysgeusia. We report the first case of carbonated drink dysgeusia associated with sweet taste perversion.
Case presentation
We present the case of a 30 year-old man with aura migraine that developed carbonation and sweet taste dysgeusia associated with topiramate use.
After the beginning of therapy and reaching the titration of topiramate 100 mg/daily with the complete absence of migraine recurrence, the patient developed dysgeusia for carbonated beverages that started to feel flat and assume a sweet aftertaste, while other sweetened carbonated beverages tasted flat and unsweetened, determining a major impact on his social quality of life and low therapy adherence.
In order to better tolerate therapy, considering the satisfactory results obtained in terms of migraine relapse, the patient was sent for a psychological evaluation and counseling, eventually accepting his condition and to continue therapy.
Conclusions
Although taste misperceptions are often underestimated and causes are still not well defined, it’s mandatory to correctly inform patients on the possible side effects that could influence patients’ quality of life and therapy adherence.
A Meta-analysis Reveals Gastric Microbes Associated with Atrophic Gastritis
Authors: Gao Xiaoxiang , Yin Pingping , Ren Yilin , Yu Leilei , Tian Fengwei , Zhao Jianxin , Chen Wei , Xue Yuzheng , Zhai Qixiao
Published: March 2023

Previous studies have associated microbial alterations with gastritis; however, problems regarding the reproducibility of biomarkers in cohorts remain poorly resolved. Patients from different regions provided excellent information, that was conducive to the exploration of the gastric microbes associated with gastric inflammation. We performed a meta-analysis of seven reliable datasets, consisting of a total of 367 fecal 16s rRNA including atrophic gastritis (AG) (174 patients) and superficial gastritis (SG) (170 patients) after quality control and discarding samples of gastric fluid, since the microbial diversity between gastric fluid and antrum was different. We also investigated the similarity in microbial composition between healthy controls and SG without Helicobacter pylori infection, but not in those with H. pylori infection. According to the linear discriminant analysis effect size and random forest analyses, Bacteroides, Weissella, Actinomyces, Atopobium, Oribacterium, Peptostreptococcus, and Rothia were biomarkers between SG and AG (AG_N) without H. pylori infection, whereas Actinomyces, Cutibacterium, Helicobacter, Novosphingobium, Pseudomonas, and Streptococcus were signatures between SG and AG (AG_P) with H. pylori infection. We also found that the development of AG_N was associated with lower vitamin B12 levels, whereas significant changes in the gastric microbiota functions of AG_P included gallate, amino acid degradation, and heme biosynthesis. In addition, non-dialysis classifiers were developed for AG_N with an area under the curve (AUC) of 0.7417 and for AG_P with an AUC of 0.8862. This study thoroughly profiled the gastric microbiota of AG and SG and provided evidence of the potential of microbial markers as noninvasive classifiers for global AG.
Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating Wnt/β-catenin signal pathway in lung cancer
Authors: Li Ruijie , Li Mengguo , Lv Juan , Sun Qian
Published: March 2023

Objective: To investigate the effect of tumor necrosis factor receptor-associated protein 1 (TRAP1) on aerobic glycolysis in cisplatin-resistant lung cancer and its possible mechanism.
Methods: The expression of TRAP1 in cisplatin resistant lung cancer tissues and A549/CDDP cells were detected. The expression of TRAP1 in A549/CDDP cells were silenced by transfection siRNA. The changes of lactate content, glucose consumption and the expression of lactate dehydrogenase A (LDHA), hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) and sensitivity to cisplatin were detected. The change of Wnt/β-catenin signaling pathway was detected, and the Wnt/β-catenin activator BML-284 was used to conduct reverse expression.
Results TRAP1 expression was increased in cisplatin-resistant tissues and A549/CDDP cells compared with cisplatin-sensitive tissues and A549, respectively (P<0.05); After silencing TRAP1, the lactic content, glucose consumption, LDHA, HK2, PKM2 expression, IC50 concentration of cisplatin were significantly increased (P<0.05). Compared with A549, Wnt/β-catenin pathway was activated in A549/CDDP, and inhibited after TRAP1 silencing. BML-284 can reverse the effects of silencing TRAP1 on aerobic glycolysis and cisplatin sensitivity of A549/CDDP.
Conclusion TRAP1 is involved in the cisplatin resistance in lung cancer, and its mechanism is related to the regulation of aerobic glycolysis by regulating Wnt/β-catenin pathway.
Therapeutic angiogenesis with intramuscular SeV-hFGF2/dF for the treatment of peripheral arterial disease: a phase I clinical trial
Authors: Lian Wenzhuo , Li Fengshi , Rong Zhihua , Wang Peng , Di Xiao , Song Xitao , Ni Leng , Liu Changwei
Published: March 2023

This paper reports a phase I dose-escalation clinical trial for the treatment of peripheral arterial disease (PAD) with BF30, a recombinant Sendai virus vector carrying the human native fibroblast growth factor 2 (hFGF2) gene. Our goal was to evaluate the safety and tolerability of BF30 at varying doses while assessing its preliminary therapeutic effect. Twelve male patients with PAD unsuitable for revascularization procedures that met the enrollment criteria were recruited. Each patient received a BF30 injection on one side of the ischemic lower limb. No deaths occurred prior to the 6-month follow-up. No severe adverse events or Grade 3/4 adverse events related to the BF30 injections were noted. Furthermore, the viral genome level was below the quantization limit after 6 months, and hemagglutination activity was undetectable in seven of the 12 cases. Abnormal changes in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and proinflammatory factor serum levels were not observed. None of the cases exhibited a positive anti-drug antibody signal. In addition, a positive therapeutic effect was demonstrated by the reduction in rest pain and Rutherford classification and improvement of the ankle-brachial index. While a higher dose triggered a stronger immune response, it was more effective in improving the Rutherford classification and quality of life.
Model of non-stationary heat transfer in a supercritical fluid
Authors: Melkikh A. V. , Rutin S. B. , Skripov P. V.
Published: March 2023

This paper continues the process of reconciling results obtained when investigating heat transfer in the supercritical liquid-vapour region inherent in stationary and fast processes. A relatively simple model of non-stationary heat transfer at the microscopic level in a non-idealised system is constructed. The model provides a possible explanation for the increase in the thermal resistance of a supercritical fluid (drop in heat conduction) at a not too great distance from the critical isobar on a scale of small characteristic times and sizes. The model is based on an explicit account of a significant decrease in thermal diffusivity when approaching the critical temperature of the substance. The simulation results are compared with experimental data on the rapid (lasting in units-tens of milliseconds) transfer of a compressed liquid to the supercritical temperature region along a supercritical isobar.