bluuebunny/crossref_metadata_2025 huggingface dataset:
Research experimental design for the construction and identification of the pGEX-BCKD-E4A recombinant point-mutant plasmid
Authors: Zhou Tiannan , Wei Huixian , Wang Jinjun
Published: February 2023

Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that eventually develops into cirrhosis and even liver cancer. In recent years, the incidence rate has been increasing, and the early diagnosis and treatment of PBC are crucial. In the early diagnosis method of PBC, anti-mitochondrial antibodies (AMAs) are an important diagnostic basis, especially the M2 subtype (AMA-M2) with almost 100% specificity. We selected the BCOADC-E2 protein, a mitochondrial autoantigen that reacts specifically with AMA-M2 antibodies, and carried out DNA recombination and protein mutation experiments by cloning in vitro the homologous target gene sequence BCKD that expresses the antigenic epitope of BCOADC-E2 protein, to provide experience for later exploring the effect of mutations of amino acids around the lysine in the active center of BCOADC-E2 protein on its specific binding to AMA-M2, and to lay the foundation for determining the key amino acids of BCOADC-E2 for the diagnosis and treatment of PBC. In addition, we apply this scientific research content to graduate course teaching. Experimental technology of microbial molecular ecology is a course with the cross-integration of multidisciplinary knowledge and experimental skills offered at our college since 2018. This article derives from the part of this course on the construction of recombinant plasmids. The students first constructed the recombinant plasmid pGEX-BCKD using the vector plasmid pGEX-4T1 and the target gene fragment BCKD provided by the laboratory and used this as a template to construct the pGEX-BCKD-E4A point mutation plasmid by the overlap extension PCR (SOE PCR) technique to achieve the effect of mutating the fifth amino acid glutamate in front of lysine, the active centre of the BCOADC-E2 lipid acyl binding domain, to alanine for subsequent studies. Through the research experiment, combining theoretical knowledge and experimental operation, we aim to deepen the student’s understanding of DNA recombination technology, let them feel the practical application prospect of experimental technology, stimulate students’ interest in professional knowledge learning, and cultivate students’ scientific thinking and innovation consciousness. We examined the quality of the teaching through the process and summative evaluation of the students. In this study, the students successfully completed the construction of pGEX-BCKD-E4A point mutant plasmid, and the average test score increased from 40.4% before teaching to 91.1%. The teaching effect was remarkable. This kind of research experimental teaching mode has good application prospects, and other education and teachers can refer to and reference it.
Research on dual-output port on-board charging system based on CLLC resonant converter
Authors: Zhou Kai , Song Hao , Jin Ningzhi , Sun Dongyang
Published: February 2023

This paper proposes a dual-output port on-board charging system based on a CLLC resonant converter, which can realize the function of simultaneously charging high-voltage power batteries and low-voltage batteries. The system topology is composed of a front-stage PFC and a latter-stage CLLC resonant converter. The system uses a three-port transformer to couple the resonant converter, the high-voltage charging circuit, and the low-voltage charging circuit. The system also realizes soft switching through resonant components. According to the design requirements of the charging system, the control strategy of the dual-output ports is determined by analyzing the working mode and gain characteristics of the system and the dual closed-loop control structure is designed to realize the functions of power factor correction and wide-range voltage regulation. Simulation and experimental results verify the correctness of theoretical analysis and structural design.
Implementing PERFECT-ER with Plan-Do-Study-Act on acute orthopaedic hospital wards: Building knowledge from an implementation study using Normalization Process Theory
Authors: Fox Chris , Hammond Simon P. , Backhouse Tamara , Poland Fiona , Waring Justin , Penhale Bridget , Cross Jane L.
Published: February 2023

Background

Delivering care to growing numbers of patients with increasingly ‘complex’ needs is currently compromised by a system designed to treat patients within organizational clinical specialties, making this difficult to reconfigure to fit care to needs. Problematic experiences of people with cognitive impairment(s) admitted to hospitals with a hip fracture, exemplify the complex challenges that result if their care is not tailored. This study explored whether a flexible, multicomponent intervention, adapting services to the needs of this patient group, could be implemented in acute hospital settings.

Methods

We used action research with case study design to introduce the intervention using a Plan-Do-Study-Act (PDSA) model to three different hospital sites (cases) across England. The qualitative data for this paper was researcher-generated (notes from observations and teleconference meetings) and change agent-generated (action plans and weekly reflective reports of change agents’ activities). Normalization Process Theory (NPT) was used to analyze and explain the work of interacting actors in implementing and then normalizing (embedding) the intervention across contexts and times. Data analysis was abductive, generating inductive codes then identified with NPT constructs. Across the three cases, change agents had to work through numerous implementation challenges: needing to make sense of the intervention package, the PDSA model as implementation method, and their own role as change agents and to orientate these within their action context (coherence). They had to work to encourage colleagues to invest in these changes (cognitive participation) and find ways to implement the intervention by mobilising changes (collective action). Finally, they created strategies for clinical routines to continue to self-review, reconfiguring actions and future plans to enable the intervention to be sustained (reflexive monitoring).

Conclusions

Successful implementation of the (PERFECT-ER) intervention requires change agents to recognize and engage with local values, and then to enable its fit with practice and wider contextual goals. A context of constant change fragments normalization. Thus, sustaining practice change over time is fragile and requires change agents to continue a recursive two-way sense-making process. This enables implementation and normalization to re-energize and overcome barriers to change.
Public health supply chain for iron and folic acid supplementation in India: Status, bottlenecks and an agenda for corrective action under Anemia Mukt Bharat strategy
Authors: Ahmad Khobaib , Singh Jitendra , Singh Ruby Alambusha , Saxena Abhimanyu , Varghese Mini , Ghosh Sebanti , Roy Sumitro , Yadav Kapil , Joe William , Patel Narendra
Published: February 2023

Purpose

The IFA supplementation program under the Anemia Mukt Bharat (AMB) program is one of the most ambitious nutrient supplementation programs in India. The delivery of services often suffers due to frequent stock outs and shortages. It is critical to understand the bottleneck in the supply chain adversely affecting the performance and coverage of the program. The paper attempts to identify the bottlenecks of the IFA supply chain in key areas of supply chain i.e., forecasting, procurement, warehousing and inventory management, transportation, distribution, logistic information system and suggests a plan of action aimed at ensuring uninterrupted supplies to the end beneficiaries.

Design/methodology/approach

The data source for the present paper is the nationwide IFA Supply Chain Assessment (2018–19) conducted across 29 Indian states with a total of 58 districts, 116 blocks, 232 Sub-Centres, 232 Anganwadi centres and 232 schools covered under the assessment as a multi-partner collaborative initiative. Field insights from supply chain strengthening interventions under different public health programs in India and other developing countries were taken to arrive at corrective actions and recommendations. Findings were disseminated to government and an action plan was suggested for connecting service delivery points through an app-based system, developing a micro plan for ensuring fixed distribution schedule, followed by continuous monitoring and review meetings identified for follow up.

Findings

The average lead time across states was 35 weeks with top three performing states being Goa, Sikkim, and Telangana. The average per unit cost of procurement was Rs 0.35 for IFA Red, Rs 0.25 for IFA Blue, Rs 0.31 for IFA Pink and Rs 7.30 for IFA syrup. Out of the 704 districts in India, only 213 has IFA Red, only 140 had IFA Blue, 152 had IFA Pink and 163 had IFA Syrup available in four quarters of 2018–19. The key issues identified in the assessment were–a lack of standardized forecasting process, absence of inventory management techniques, no fixed distribution schedule, inadequate availability of transport vehicles and an absence of an integrated MIS.

Originality/value

The identification of bottlenecks in the IFA supply chain and its impact on the performance of the supply chain would provide policy guidelines for the government as well as development partner agencies to design an effective and efficient supply chain. It would also enable the policy planners to understand the challenges associated with managing different components of a supply chain, their interrelation and impact on the overall performance of the supply chain. The suggested recommendations would equip program managers with the tool to devise and implement field level solutions.
Renal impairment associated with tenofovir disoproxil fumarate for antiretroviral therapy and HIV pre-exposure prophylaxis: An observational cohort study
Authors: Heron Jack E. , McManus Hamish , Vickers Tobias , Ryan Kathleen , Wright Edwina , Carter Allison , Stoove Mark , Asselin Jason , Grulich Andrew , Donovan Basil , Guy Rebecca , Varma Rick , Chen Marcus , Ryder Nathan , Lewis David A. , Templeton David J. , O’Connor Catherine C. , Gracey David M. ,   for the ACCESS Collaboration
Published: February 2023

Background

Tenofovir disoproxil fumarate (TDF) is associated with adverse renal outcomes when prescribed for HIV infection. There are few data concerning real-world renal outcomes amongst patients prescribed TDF for pre-exposure prophylaxis (PrEP).

Methods and findings

Data were extracted from 52 sexual health clinics across Australia from 2009–2019. All patients prescribed TDF-containing antiretroviral therapy and PrEP were included. Rates of renal impairment (a fall in eGFR to <60 ml/min/1·73m2) were calculated for people living with HIV (PLWHIV) prescribed TDF and HIV negative PrEP-users. Risk factors were assessed using Cox-proportional hazards models. Sensitivity analysis of risk using 1:1 propensity-score matching to adjust for potential imbalance in HIV and PrEP cohorts was conducted. 5,973 patients on PrEP and 1,973 PLWHIV were included. There were 39 (0.7%) instances of renal impairment in the PrEP group and 81 (4.1%) in the PLWHIV cohort (hazard ratio [HR]:0.35 95% confidence interval [CI]: 0.22–0.56). Rates of renal impairment were 4.01/1000 person-years (95%CI:2.93–5.48) in the PrEP cohort and 16.18/1000 person-years (95%CI:13.01–20.11) in the PLWHIV cohort (p<0.001). Predictors of renal impairment were: older age (40–49 years (HR:5.09 95%CI: 2.12–12.17) and 50–82 years (HR:13.69 95%CI: 5.92–31.67) (compared with 30–39 years) and baseline eGFR<90ml/min (HR:61.19 95%CI: 19.27–194.30). After adjusting for age and baseline eGFR the rate of renal impairment remained lower in the PrEP cohort (aHR:0.62 95%CI: 0.40–0.94, p = 0.023). In propensity-matched analysis using 1,622 patients per cohort the risk of renal impairment remained higher in the PLWHIV cohort (log-rank p = 0.001).

Conclusion

Patients prescribed TDF-based PrEP had lower rates of renal impairment than patients prescribed TDF for HIV infection. In propensity analysis, after matching for some risk factors, rates of renal impairment remained higher amongst patients with HIV.
Bayesian network modeling of risk and prodromal markers of Parkinson’s disease
Authors: Sood Meemansa , Suenkel Ulrike , von Thaler Anna-Katharina , Zacharias Helena U. , Brockmann Kathrin , Eschweiler Gerhard W. , Maetzler Walter , Berg Daniela , Fröhlich Holger , Heinzel Sebastian
Published: February 2023

Parkinson’s disease (PD) is characterized by a long prodromal phase with a multitude of markers indicating an increased PD risk prior to clinical diagnosis based on motor symptoms. Current PD prediction models do not consider interdependencies of single predictors, lack differentiation by subtypes of prodromal PD, and may be limited and potentially biased by confounding factors, unspecific assessment methods and restricted access to comprehensive marker data of prospective cohorts. We used prospective data of 18 established risk and prodromal markers of PD in 1178 healthy, PD-free individuals and 24 incident PD cases collected longitudinally in the Tübingen evaluation of Risk factors for Early detection of NeuroDegeneration (TREND) study at 4 visits over up to 10 years. We employed artificial intelligence (AI) to learn and quantify PD marker interdependencies via a Bayesian network (BN) with probabilistic confidence estimation using bootstrapping. The BN was employed to generate a synthetic cohort and individual marker profiles. Robust interdependencies were observed for BN edges from age to subthreshold parkinsonism and urinary dysfunction, sex to substantia nigra hyperechogenicity, depression, non-smoking and to constipation; depression to symptomatic hypotension and excessive daytime somnolence; solvent exposure to cognitive deficits and to physical inactivity; and non-smoking to physical inactivity. Conversion to PD was interdependent with prior subthreshold parkinsonism, sex and substantia nigra hyperechogenicity. Several additional interdependencies with lower probabilistic confidence were identified. Synthetic subjects generated via the BN based representation of the TREND study were realistic as assessed through multiple comparison approaches of real and synthetic data. Altogether our work demonstrates the potential of modern AI approaches (specifically BNs) both for modelling and understanding interdependencies between PD risk and prodromal markers, which are so far not accounted for in PD prediction models, as well as for generating realistic synthetic data.
Production of multimodal signals to assert social dominance in white-lipped peccary (Tayassu pecari)
Authors: Alencar Raimundo N. , Nogueira-Filho Sérgio L. G. , Nogueira Selene S. C.
Published: February 2023

In this study we aimed to examine whether the ‘redundancy’ (a backup function to ensure the signal transmission) or ‘multiple messages’ (sensory communication system in combination) hypothesis would explain the function of multimodal communication of white-lipped peccaries (Tayassu pecari–WLPs). We also aimed to assess the individual factors (the social rank and sex of the sender) influencing the production of, and responses to unimodal and multimodal signals. We determined the social rank of 21 WLPs living in two captive groups and quantified the production of unimodal and multimodal signals when displaying threatening and submissive behaviors. WLPs most often produce multimodal signals independent of a previous unimodal signal failure, which suggests that they were adding more information, such as the sender’s size, rather than merely increasing efficacy by engaging a different receiver’s sensory channel. There was no effect of the sender’s sex in the production of, and responses to, multimodal signals. However, the higher the sender’s social rank, the greater the production of multimodal signals when WLPs were displaying threatening behaviors; whereas the lower the sender’s social rank, the greater the production of multimodal signals when displaying submission behaviors. Multimodal signals elicited more non-aggressive responses than did the unimodal signals when displaying a threat. Moreover, the higher the sender’s social rank, the greater the occurrence of non-aggressive responses to multimodal signals when displaying a threat; whereas the opposite occurred when displaying submission. Our findings support the ‘multiple messages’ hypothesis to explain the function of multimodal signaling during agonistic interactions in WLPs. Additionally, both the production of, and responses to, multimodal signals are related to the sender’s social rank. These results allow us to suggest that the production of multimodal signals may have a key role in mitigating conflict and thus promoting group cohesion among white-lipped peccaries.
Transient binding sites at the surface of haloalkane dehalogenase LinB as locations for fine-tuning enzymatic activity
Authors: Raczyńska Agata , Kapica Patryk , Papaj Katarzyna , Stańczak Agnieszka , Shyntum Divine , Spychalska Patrycja , Byczek-Wyrostek Anna , Góra Artur
Published: February 2023

The haloalkane dehalogenase LinB is a well-known enzyme that contains buried active site and is used for many modelling studies. Using classical molecular dynamics simulations of enzymes and substrates, we searched for transient binding sites on the surface of the LinB protein by calculating maps of enzyme-ligand interactions that were then transformed into sparse matrices. All residues considered as functionally important for enzyme performance (e.g., tunnel entrances) were excluded from the analysis to concentrate rather on non-obvious surface residues. From a set of 130 surface residues, twenty-six were proposed as a promising improvement of enzyme performance. Eventually, based on rational selection and filtering out the potentially unstable mutants, a small library of ten mutants was proposed to validate the possibility of fine-tuning the LinB protein. Nearly half of the predicted mutant structures showed improved activity towards the selected substrates, which demonstrates that the proposed approach could be applied to identify non-obvious yet beneficial mutations for enzyme performance especially when obvious locations have already been explored.
Multi-phase attention network for face super-resolution
Authors: Hu Tao , Chen Yunzhi
Published: February 2023

Previous general super-resolution methods do not perform well in restoring the details structure information of face images. Prior and attribute-based face super-resolution methods have improved performance with extra trained results. However, they need an additional network and extra training data are challenging to obtain. To address these issues, we propose a Multi-phase Attention Network (MPAN). Specifically, our proposed MPAN builds on integrated residual attention groups (IRAG) and a concatenated attention module (CAM). The IRAG consists of residual channel attention blocks (RCAB) and an integrated attention module (IAM). Meanwhile, we use IRAG to bootstrap the face structures. We utilize the CAM to concentrate on informative layers, hence improving the network’s ability to reconstruct facial texture features. We use the IAM to focus on important positions and channels, which makes the network more effective at restoring key face structures like eyes and mouths. The above two attention modules form the multi-phase attention mechanism. Extensive experiments show that our MPAN has a significant competitive advantage over other state-of-the-art networks on various scale factors using various metrics, including PSNR and SSIM. Overall, our proposed Multi-phase Attention mechanism significantly improves the network for recovering face HR images without using additional information.
Scientific modelling can be accessible, interoperable and user friendly: A case study for pasture and livestock modelling in Spain
Authors: Marquez Torres Alba , Balbi Stefano , Villa Ferdinando
Published: February 2023

This article describes the adaptation of a non-spatial model of pastureland dynamics, including vegetation life cycle, livestock management and nitrogen cycle, for use in a spatially explicit and modular modelling platform (k.LAB) dedicated to make data and models more interoperable. The aim is to showcase to the social-ecological modelling community the delivery of an existing, monolithic model, into a more modular, transparent and accessible approach to potential end users, regional managers, farmers and other stakeholders. This also allows better usability and adaptability of the model beyond its originally intended geographical scope (the Cantabrian Region in the North of Spain). The original code base (written in R in 1,491 lines of code divided into 13 files) combines several algorithms drawn from the literature in an opaque fashion due to lack of modularity, non-semantic variable naming and implicit assumptions. The spatiotemporal rewrite is structured around a set of 10 namespaces called PaL (Pasture and Livestock), which includes 198 interoperable and independent models. The end user chooses the spatial and temporal context of the analysis through an intuitive web-based user interface called k.Explorer. Each model can be called individually or in conjunction with the others, by querying any PaL-related concepts in a search bar. A scientific dataflow and a provenance diagram are produced in conjunction with the model results for full transparency. We argue that this work demonstrates key steps needed to create more Findable, Accessible, Interoperable and Reusable (FAIR) models beyond the selected example. This is particularly essential in environments as complex as agricultural systems, where multidisciplinary knowledge needs to be integrated across diverse spatial and temporal scales in order to understand complex and changing problems.
Ganglioside GM3 prevents high fat diet-induced hepatosteatosis via attenuated insulin signaling pathway
Authors: Tajima Orie , Fujita Yuki , Ohmi Yuhsuke , Furukawa Koichi , Furukawa Keiko
Published: February 2023

Gangliosides, sialic acid-containing glycosphingolipids, are widely involved in regulations of signal transductions to control cellular functions. It has been suggested that GM3, the simplest structure among gangliosides, is involved in insulin resistance, whereas it remains unclear whether insulin signaling diminished by GM3 actually aggravates the pathological conditions in metabolic disorders. Moreover, the functional roles of gangliosides in the regulation of insulin signaling have not yet been fully elucidated in liver or hepatocytes despite that it is one of the major insulin-sensitive organs. To understand physiological roles of GM3 in metabolic homeostasis in liver, we conducted a high fat diet (HFD) loading experiment using double knockout (DKO) mice of GM2/GD2 synthase and GD3 synthase, which lack all gangliosides except GM3, as well as wild-type (WT) mice. DKO mice were strikingly resistant to HFD-induced hepatosteatosis, and hepatic lipogenesis-related molecules including insulin signaling components were down-regulated in HFD-fed DKO. Furthermore, we established primary hepatocyte cultures from DKO and WT mice, and examined their responses to insulin in vitro. Following insulin stimulation, DKO hepatocytes expressing GM3 showed attenuated expression and/or activations in the downstream components compared with WT hepatocytes expressing GM2. While insulin stimulation induced lipogenic proteins in hepatocytes from both genotypes, their expression levels were lower in DKO than in WT hepatocytes after insulin treatment. All our findings suggest that the modified gangliosides, i.e., a shift to GM3 from GM2, might exert a suppressive effect on lipogenesis by attenuating insulin signaling at least in mouse hepatocytes, which might result in protection of HFD-induced hepatosteatosis.
Little fast, little slow, should I stay or should I go? Adapting cognitive control to local-global temporal prediction across typical development
Authors: Del Popolo Cristaldi Fiorella , Toffoli Lisa , Duma Gian Marco , Mento Giovanni
Published: February 2023

Adaptive cognitive control (CC), the ability to adjust goal-directed behavior according to changing environmental demand, can be instantiated bottom-up by implicit knowledge, including temporal predictability of task-relevant events. In S1-S2 tasks, either local (trial-by-trial hazard expectation) or global (block-by-block expectation) temporal information can induce prediction, allowing for proactive action control. Recent developmental evidence showed that adaptive CC based on global temporal prediction emerges earlier than when it is based on the local one only. However, very little is known about how children learn to dynamically adjust behavior on the fly according to changing global predictive information. Addressing this issue is nevertheless crucial to unravel the mechanisms underlying adaptive CC flexibility. Here we used a modified version of the Dynamic Temporal Prediction task to investigate how typically developing younger (6–8 years) and older children (9–11 years), adolescents (12–15 years) and adults (21–31 years) use global prediction to shape adaptive CC over time. Specifically, the short-long percentage of S2 preparatory intervals was manipulated list-wide to create a slow-fast-slow-fast fixed block sequence and test how efficiently the response speed adapted accordingly. Overall, results revealed that in all groups behavioral performance is successfully adjusted as a function of global prediction in the late phase of the task (block 3 to 4). Remarkably, only adolescents and adults exhibit an early adaptation of adaptive CC (block 1 to 2), while children younger than 11 show sluggish ability in inferring implicit changes in global predictive rules. This age-related dissociation suggests that, although being present from an early age, adaptive CC based on global predictive information needs more developmental space to become flexible in an efficient way. In the light of a neuroconstructivist approach, we suggest that bottom-up driven implicit flexibility may represent a key prerequisite for the development of efficient explicit cognitive control
Epidemiologic transition and the double burden of disease in Ghana: What do we know at the neighborhood level?
Authors: Konkor Irenius , Kuuire Vincent Z.
Published: February 2023

Many developing countries including Ghana are currently experiencing dual disease burdens emerging from an unprecedented risk overlap that drive their epidemiological transitions. Yet, siloed and disintegrated approaches continue to take precedence in health research and policy programs that drive competition for limited resources to address competing health problems. The objective of this study was to offer empirical evidence in support of a cogent argument for an integrated framework for the study and management of infectious and chronic health conditions in Ghana. We did so by examining the prevalence, determinants, and neighborhoods trajectories of the double burden of disease using data from a cross-sectional neighborhood-based study in Ghana. We fitted multinomial multilevel multivariate models to a sample of 1377 individual surveys and the results presented as odds ratios. Findings show that amidst a rising burden of NCDs, infectious diseases remain the most common health condition and participants in deprived neighborhoods were significantly more likely to report poor health outcomes. Risk factors such as tobacco and alcohol consumption were significantly associated with NCDs and infectious diseases and respondents who reported being diagnosed with NCDs and infectious diseases in the past year were likely to engage in leisure time physical activities and eat healthy. Based on our findings, we recommend health reforms in Ghana and argue for the design and implementation of an integrated framework for the study and management of the double burden of disease in Ghana and similar developing country settings.
Birth asphyxia related mortality in Northwest Ethiopia: A multi-centre cohort study
Authors: Ketema Daniel Bekele , Aragaw Fantu Mamo , Wagnew Fasil , Mekonnen Misganaw , Mengist Abeba , Alamneh Alehegn Aderaw , Belay Yihalem Abebe , Kibret Getiye Dejenu , Leshargie Cheru Tesema , Birhanu Molla Yigzaw , Hibstie Yitbarek Tenaw , Temesgen Belisty , Alebel Animut
Published: February 2023

Background

Birth asphyxia is the second leading cause of neonatal death in Ethiopia, next to preterm-associated infections. Understanding the causes of death in asphyxiated newborns will help to design appropriate care. This study identifies predictors of neonatal mortality in asphyxiated newborns in selected hospitals in Northwest Ethiopia.

Methods

An institution-based prospective cohort study of 480 newborns with birth asphyxia was conducted at Debre Markos Comprehensive Specialized Hospital, Shegaw Motta District Hospital, and Injibara General Hospital. All newborns with asphyxia admitted to the neonatal critical care unit from the first of November 2018 to the first of November 2019 were included. Data were obtained prospectively from mothers using an interviewer’s administered questionnaire. The Kaplan-Meier survival curve was used to estimate survival time, and Log rank test was used to compare the survival curves. Bivariable and multivariable Cox proportional hazards models were fitted to identify the independent predictors of mortality in asphyxiated newborns. Adjusted hazard Ratios (AHRs) with 95% Cis (Confidence Intervals) were used to measure the strength of association and test statistical significance.

Results

The overall cumulative incidence of mortality among asphyxiated newborns was 42.29% (95% CI: 38%, 46). Asphyxiated neonates with other comorbidities (sepsis, neonatal anemia) (AHR = 2.63, 95% CI:1.69, 4.10), oxygen saturation of 50–69 (AHR = 4.62, 95% CI:2.55, 8.37), oxygen saturation of 70–89 (AHR = 2.82, 95% CI: 1.80, 4.42), severe Apgar score at one minute (AHR = 1.59, 95% CI:1.12, 2.25), neonates with Hypoxic Ischemic Encephalopathy (HIE) (AHR = 6.12, 95% CI:2.23, 16.75) were at higher risk of mortality.

Conclusions

The mortality rate among asphyxiated neonates remains high, and slightly higher than previous studies. Asphyxiated newborns with other comorbidities, severe Apgar score at one minute, who develop HIE, and low oxygen saturation were at higher risk of death. Therefore, designing appropriate interventions and prevention methods should be considered for identified variables.
Can use of the serum anti-PLA2R antibody negate the need for a renal biopsy in primary membranous nephropathy?
Authors: Ragy Omar , Rautemaa Vilma , Smith Alison , Brenchley Paul , Kanigicherla Durga , Hamilton Patrick
Published: February 2023

Background

Since the emergence of the anti-PLA2R antibody (PLA2R-Ab) test, nephrology practice has not changed dramatically, with most nephrologists still relying on a kidney biopsy to diagnose membranous nephropathy. In this study, we examined the clinical accuracy of the anti-PLA2R antibody test using ELISA in routine clinical care.

Methods

We conducted a retrospective analysis of PLA2R-Ab testing in 187 consecutive patients seen at a single UK centre between 2003 and 2020. We compared the kidney biopsy findings with the PLA2R-ab antibody test. Patients’ demography, urine protein creatinine ratios, serum albumin, and treatment characteristics including supportive and immunosuppressive treatment were recorded. The clinical accuracy of the test (e.g. sensitivity and specificity, positive [PPV] and negative [NPV] predictive values) was calculated using the kidney biopsy findings as the diagnostic reference.

Results

Mean levels of PLA2R-Ab titre in primary membranous nephropathy were 217RU/ml in comparison to 3RU/ml for both secondary membranous nephropathy and other diagnoses. Most patients with a positive PLA2R-Ab test had a confirmed renal biopsy diagnosis of primary membranous nephropathy with: PPV of 97.3%, sensitivity 75.5%, NPV was 79.8% and specificity was 97.8% at a cut-off threshold of >20 RU/ml.

Conclusion

The anti-PLA2R antibody test is a highly specific test for diagnosing membranous nephropathy, and the test has the potential to allow for the diagnosis and treatment in up to 75% of PMN cases without the need for a renal biopsy. Nevertheless, patients with negative PLA2R-Ab tests will still require a biopsy to confirm their diagnosis.
Development of a tool to assess HIV prevention readiness of adolescent girls and young women in HPTN 082 study
Authors: Beauchamp Geetha , Hosek Sybil , Donnell Deborah J. , Chan Kwun C. G. , Flaherty Brian P. , Anderson Peter L. , Dye Bonnie J. , Mgodi Nyaradzo , Bekker Linda-Gail , Delany-Moretlwe Sinead , Celum Connie ,   for the HPTN 082 study team
Published: February 2023

Background

African adolescent girls and young women (AGYW) represent a large proportion of new HIV infections, a priority population for pre-exposure prophylaxis (PrEP), but adherence remains a challenge. A reliable, valid readiness tool would help identify AGYW motivated to take PrEP who need adherence support.

Methods

In the HPTN 082 open-label PrEP study (2016–2019), South African and Zimbabwean women ages 16–25 were administered an HIV prevention readiness measure (HPRM). The 25 items in the HPRM included medication beliefs, connection with care, disclosure of PrEP use, social support, and housing stability using a 5-point Likert scale. Exploratory factor analysis (EFA) using polychoric correlations, scale reliability, and predictive validity were performed on data from 315 participants who responded to all items. We assessed the predictive value of HPRM scores with PrEP adherence, defined as tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots, as a continuous measure and dichotomized as high PrEP adherence (≥700 fmol/punch).

Results

EFA yielded 23 items with three subscales: self-efficacy (16 items), PrEP disclosure (4 items), and social support (3 items). Cronbach’s α ranged from 0.71 to 0.92 for the overall scale and the subscales. The average overall scale and the subscales were predictive of 3-month PrEP adherence for TFV-DP concentrations: for each unit increase of the HPRM score, TFV-DP concentration increased by 103 fmol/punch (95% CI: 16, 189, p = 0.02); the highest HPRM score equated with 608 fmol/punch on average. For the self-efficacy subscale, TFV-DP increased by 90 fmol/punch (95% CI: 7, 172, p = 0.03); PrEP disclosure, 68 fmol/punch (95% CI: 19, 117 p = 0.01); and social support, 58fmol/punch (95% CI: 2, 113, p = 0.04). Higher PrEP disclosure suggests high adherence (OR 1.36, 95% CI: 1.00, 1.86, p = 0.05) and predicted persistent high adherence at both months three and six (OR: 1.50, 95% CI: 1.03, 2.21, p = 0.04).

Conclusions

The HPRM scale overall and the subscales individually demonstrated good internal consistency among African young women. PrEP disclosure subscale exhibiting significant association with persistent high PrEP adherence is an important finding for PrEP adherence support programs. Future work will assess replicability and expand self-efficacy and social-support subscales after item revision.

Trial registration

ClinicalTrials.gov NCT02732730.
Preparation of noninfectious scRNAseq samples from SARS-CoV-2-infected epithelial cells
Authors: Osborn Raven M. , Leach Justin , Zanche Michelle , Ashton John M. , Chu ChinYi , Thakar Juilee , Dewhurst Stephen , Rosenberger Sonia , Pavelka Martin , Pryhuber Gloria S. , Mariani Thomas J. , Anderson Christopher S.
Published: February 2023

Coronavirus disease (COVID-19) is an infectious disease caused by the SARS coronavirus 2 (SARS-CoV-2) virus. Direct assessment, detection, and quantitative analysis using high throughput methods like single-cell RNA sequencing (scRNAseq) is imperative to understanding the host response to SARS-CoV-2. One barrier to studying SARS-CoV-2 in the laboratory setting is the requirement to process virus-infected cell cultures, and potentially infectious materials derived therefrom, under Biosafety Level 3 (BSL-3) containment. However, there are only 190 BSL3 laboratory facilities registered with the U.S. Federal Select Agent Program, as of 2020, and only a subset of these are outfitted with the equipment needed to perform high-throughput molecular assays. Here, we describe a method for preparing non-hazardous RNA samples from SARS-CoV-2 infected cells, that enables scRNAseq analyses to be conducted safely in a BSL2 facility–thereby making molecular assays of SARS-CoV-2 cells accessible to a much larger community of researchers. Briefly, we infected African green monkey kidney epithelial cells (Vero-E6) with SARS-CoV-2 for 96 hours, trypsin-dissociated the cells, and inactivated them with methanol-acetone in a single-cell suspension. Fixed cells were tested for the presence of infectious SARS-CoV-2 virions using the Tissue Culture Infectious Dose Assay (TCID50), and also tested for viability using flow cytometry. We then tested the dissociation and methanol-acetone inactivation method on primary human lung epithelial cells that had been differentiated on an air-liquid interface. Finally, we performed scRNAseq quality control analysis on the resulting cell populations to evaluate the effects of our virus inactivation and sample preparation protocol on the quality of the cDNA produced. We found that methanol-acetone inactivated SARS-CoV-2, fixed the lung epithelial cells, and could be used to obtain noninfectious, high-quality cDNA libraries. This methodology makes investigating SARS-CoV-2, and related high-containment RNA viruses at a single-cell level more accessible to an expanded community of researchers.
Beyond shallow feelings of complex affect: Non-motor correlates of subjective emotional experience in Parkinson’s disease
Authors: Carricarte Naranjo Claudia , Sánchez Luaces Claudia , Pedroso Ibáñez Ivonne , Machado Andrés , Sahli Hichem , Bobes María Antonieta
Published: February 2023

Affective disorders in Parkinson’s disease (PD) concern several components of emotion. However, research on subjective feeling in PD is scarce and has produced overall varying results. Therefore, in this study, we aimed to evaluate the subjective emotional experience and its relationship with autonomic symptoms and other non-motor features in PD patients. We used a battery of film excerpts to elicit Amusement, Anger, Disgust, Fear, Sadness, Tenderness, and Neutral State, in 28 PD patients and 17 healthy controls. Self-report scores of emotion category, intensity, and valence were analyzed. In the PD group, we explored the association between emotional self-reported scores and clinical scales assessing autonomic dysregulation, depression, REM sleep behavior disorder, and cognitive impairment. Patient clustering was assessed by considering relevant associations. Tenderness occurrence and intensity of Tenderness and Amusement were reduced in the PD patients. Tenderness occurrence was mainly associated with the overall cognitive status and the prevalence of gastrointestinal symptoms. In contrast, the intensity and valence reported for the experience of Amusement correlated with the prevalence of urinary symptoms. We identified five patient clusters, which differed significantly in their profile of non-motor symptoms and subjective feeling. Our findings further suggest the possible existence of a PD phenotype with more significant changes in subjective emotional experience. We concluded that the subjective experience of complex emotions is impaired in PD. Non-motor feature grouping suggests the existence of disease phenotypes profiled according to specific deficits in subjective emotional experience, with potential clinical implications for the adoption of precision medicine in PD. Further research on larger sample sizes, combining subjective and physiological measures of emotion with additional clinical features, is needed to extend our findings.
Determinants of time to first marriage and birth intervals among women of child bearing age in Dabat Health and demographic surveillance system site, Northwest Ethiopia
Authors: Alazbih Nega Mihret , Kaya Assefa Hailemariam , Mengistu Mezgebu Yitayal , Gelaye Kassahun Alemu
Published: February 2023

Background

Event histories such as marriage and birth have been used to study fertility behavior of women. Understanding the timing of these events provide insight to reproductive patterns of the population. Thus, the aim of this study was to assess the timing of marriage and durations of birth intervals and their associated factors, and and to examine their effects on the current fertility among women in Dabat health and demographic surveillance system site, Northwest Ethiopia.

Methods

A community based cross-sectional survey was carried out in the beginning of 2020 among 1649 women of reproductive age group. Data were collected using structured and interviewer administered questionnaire. The parametric survival analysis was employed to estimate the relationships among socioeconomic and demographic variables with outcome variables, the timing of age at first marriage and duration of birth intervals.

Results

This study confirmed that median age at first marriage was the lowest estimated at 15 years which was below the national and regional average. The result of the study also revealed that married women waited almost a median duration of three years for their first, second, third and fourth child which was increased to nearly four years for three years preceding the survey. The parametric survival analysis showed woman’s education, occupation, and current age were the predictors of age at first marriage. divorce experience, women empowerment and marriage cohort were the determinant factors of first birth interval; women education, child death, and ideal number of children were the predictors of second and third birth intervals; and media exposure and child death experience of women were predictors of fourth birth interval.

Conclusion

The study indicated that median age at first marriage was the lowest though the successive birth intervals were longer. The survival analysis identified women’s education, occupation, child death and ideal number of children affected the timing of age at first marriage and duration of birth intervals. Hence, encouraging women for higher education and giving opportunity to women in employments may contribute for delaying age at first marriage and increasing the duration of birth intervals which in turn slowing down the fertility of women.
Exploratory clinical trial to evaluate the efficacy and safety of transdermal electrical stimulation in patients with central retinal artery occlusion
Authors: Miura Gen , Fujiwara Tadami , Iwase Takayuki , Ozawa Yoshihito , Shiko Yuki , Kawasaki Yohei , Nizawa Tomohiro , Tatsumi Tomoaki , Baba Takayuki , Kurimoto Takuji , Mori Sotaro , Nakamura Makoto , Hanaoka Hideki , Yamamoto Shuichi
Published: February 2023

Purpose

To evaluate the efficacy and safety of transdermal electrical stimulation (TdES) using skin electrodes in patients with central retinal artery occlusion (CRAO).

Methods

Five eyes of five patients with CRAO underwent TdES (10-ms biphasic pulses, 20 Hz, 30 min) six times at 2-week intervals. Only the affected eye was stimulated with 1.0-mA pulses in all patients. The primary endpoint was the best-corrected logMAR visual acuity. The secondary endpoints were changes in the best-corrected logMAR visual acuity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, mean deviation of the Humphrey field analyzer (HFA) 10–2, and HFA Esterman test score. We also evaluated its safety.

Results

The logMAR visual acuity at 12 weeks was improved by 0.1 or more in two patients and was maintained in two patients compared to the baseline. No obvious changes in the mean logMAR visual acuity, ETDRS visual acuity, mean deviation, and HFA Esterman score were observed at 12 weeks compared to the baseline. All five enrolled patients completed the study according to the protocol. No treatment-related adverse events were observed during this study.

Conclusion

In this study, logMAR visual acuity was slightly improved in two patients, confirming the safety of TdES. Since CRAO has no established treatment method, further research into the effects of TdES treatment in CRAO patients may be beneficial.
Does papillary muscle free strain has predictive value in risk stratification of patients with hypertrophic cardiomyopathy?
Authors: Koyuncu Atilla , Yildiz Cennet , Ocal Lutfu , Kalkan Sedat , Kılıçgedik Alev , Gürsoy Mustafa Ozan , Oflar Ersan , Kahveci Gökhan
Published: February 2023

Background

Papillary muscle free strain has not been evaluated previously in hypertrophic cardiomyopathy (HCMP) patients. Our aim was to evaluate free papillary muscle free strain in HCMP patients and to find whether it has a value for prediction of sudden cardiac death (SCD) risk score.

Methods

Transthoracic echocardiography with tissue Doppler imaging, 2-D speckle tracking imaging (STI) of 55 HCMP patients and 45 controls were performed. HCMP patients were further divided into two groups according to their SCD risk score. Patients with risk score of less than 6 points constituted low/intermediate risk group, whereas patients with risk score of greater or equal to 6 points constituted high risk group.

Results

Interventricular septum, posterior wall, and left ventricular mass index were significantly higher, whereas mitral E/A ratio was significantly lower in HCMP patients compared to controls. Longitudinal apical 4C, 2C, 3C, global longitudinal LV strain, anterolateral papillary muscle (ALPM), posteromedial papillary muscle (PMPM) free strain were significantly reduced in HCMP group compared to control group. Global longitudinal strain and ALPM free strain were significantly lower in patients with high SCD risk score (-14.6 (-17.4 - -13.1) vs -11.6 (-13.2 - -10.1), p = 0.001 and -17.1 (-20.3 - -14.0) vs -9.2 (-12.6 - -7.5), p<0.001, respectively. Global longitudinal strain and ALPM free strain were statistically significantly correlated with SCD risk score (r = 0.480, p<0.001 and r = 0.462, p<0.001, respectively). Global longitudinal strain value of -12.60% had a sensitivity of 73.3% and specificity of 82.5% for predicting high SCD risk score (AUC: 0.787, 95% CI: 00.643–0.930, p = 0.001). ALPM free strain value of -12.95% had 66.7% sensitivity and 77.5% specificity for predicting high SCD risk score (AUC: 0.766, 95% CI: 0.626–0.905, p = 0.003).

Conclusion

Papillary muscle free strain was reduced in HCMP patients. It might be used in risk stratification of these patients.