bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanosecond pulsed electric field ablates rabbit VX2 liver tumors in a non-thermal manner
Authors: Li Qing-Gang , Liu Zhen-Guo , Dong Gang , Sun Ying , Zou Ya-Wen , Chen Xiao-Long , Wu Bin , Chen Xin-Hua , Ren Zhi-Gang
Published: March 2023

Background

Liver tumor remains an important cause of cancer-related death. Nanosecond pulsed electric fields (nsPEFs) are advantageous in the treatment of melanoma and pancreatic cancer, but their therapeutic application on liver tumors need to be further studied.

Methods

Hep3B cells were treated with nsPEFs. The biological behaviors of cells were detected by Cell Counting Kit-8, 5-ethynyl-20-deoxyuridine, and transmission electron microscopy (TEM) assays. In vivo, rabbit VX2 liver tumor models were ablated by ultrasound-guided nsPEFs and radiofrequency ablation (RFA). Contrast-enhanced ultrasound (CEUS) was used to evaluate the ablation effect. HE staining and Masson staining were used to evaluate the tissue morphology after ablation. Immunohistochemistry was performed to determine the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin at different time points after ablation.

Results

The cell viability of Hep3B cells was continuously lower than that of the control group within 3 days after pulse treatment. The proliferation of Hep3B cells was significantly affected by nsPEFs. TEM showed that Hep3B cells underwent significant morphological changes after pulse treatment. In vivo, CEUS imaging showed that nsPEFs could completely ablate model rabbit VX2 liver tumors. After nsPEFs ablation, the area of tumor fibrosis and the expression of Ki67, proliferating cell nuclear antigen, and α-smooth muscle actin were decreased. However, after RFA, rabbit VX2 liver tumor tissue showed complete necrosis, but the expression of PCNA and α-smooth muscle actin did not decrease compared to the tumor group.

Conclusions

nsPEFs can induce Hep3B cells apoptosis and ablate rabbit VX2 liver tumors in a non-thermal manner versus RFA. The ultrasound contrast agent can monitor immediate effect of nsPEF ablation. This study provides a basis for the clinical study of nsPEFs ablation of liver cancer.
Notre-Dame de Paris: The first iron lady? Archaeometallurgical study and dating of the Parisian cathedral iron reinforcements
Authors: L’Héritier Maxime , Azéma Aurélia , Syvilay Delphine , Delqué-Kolic Emmanuelle , Beck Lucile , Guillot Ivan , Bernard Mathilde , Dillmann Philippe
Published: March 2023

The study of iron reinforcements used in the construction of Notre-Dame de Paris offers a glimpse into the innovation that took place on this building site in the mid-12thcentury, adapting metal to create a novel architecture. The restoration of the monument after the 2019 fire offered unique possibilities to investigate its iron armatures and to sample 12 iron staples from different locations (tribunes, nave aisles and upper walls). Six of them were dated thanks to the development of an innovative methodology based on radiocarbon dating. They reveal that Notre-Dame is the first known Gothic cathedral where iron was massively used as a proper construction material to bind stones throughout its entire construction, leading to a better understanding of the master masons’ thinking. Moreover, a metallographic study and slag inclusion chemical analyses of the staples provide the first study of iron supply for a great medieval Parisian building yard, renewing our understanding of iron circulation, trade and forging in the 12thand 13thcentury capital of the French kingdom. The highlighting of numerous welds in all iron staples and the multiple provenances sheds light on the activity of the iron market in this major medieval European city and the nature of the goods that circulated, and questions the possible importance of recycling.
Metabolic, inflammatory and adipokine differences on overweight/obese children with and without metabolic syndrome: A cross-sectional study
Authors: Cura–Esquivel Idalia , Perales-Quintana Marlene Marisol , Torres-González Liliana , Guzmán-Avilán Katia , Muñoz-Espinosa Linda , Cordero-Pérez Paula
Published: March 2023

Background

Obesity is associated with low-grade inflammation and metabolic syndrome (MetS) in both children and adults. Our aim was to describe metabolic, inflammatory and adipokine differences on overweight/obese children with and without MetS.

Methods

This was an observational study. A total of 107 children and adolescents aged 6–18 years were included. Among this sample, n = 21 had normal body weight, n = 22 had overweight/obesity without MetS, and n = 64 had overweight/obesity with MetS. Anthropometric data and biochemical, adipokine, and inflammatory markers were measured. Different ratios were then assessed for estimate the probability of MetS. ROC analysis was used to estimate the diagnostic accuracy and optimal cutoff points for ratios.

Results

Serum CRP levels were higher among children with overweight/obesity with MetS. Adipokines like PAI-1 and leptin were significantly lower in children with normal body weight. The Adipo/Lep ratio was highest in the group with normal body weight. TG/HDL-C and TC/HDL-C ratios were significantly correlated with BMI, DBP, PCR, and PAI-1. TC/HDL-C ratio was significantly correlated with SBP and resistin. TGL/HDL-C ratio was significantly correlated with waist and hip circumferences, fasting glucose, and MCP-1. The AUC for TG/HDL-C at the optimal cutoff of 2.39 showed 85.71% sensitivity and 71.43% specificity. CT/HDL-C at the optimal cutoff of 3.70 showed 65.08% sensitivity and 81.82% specificity. Levels of both ratios increased significantly as additional MetS criteria were fulfilled.

Conclusion

Low-grade inflammation is correlated with MetS in children with overweight/obesity. TGL, HDL-C and TGL/HDL-C ratio, obtainable from routine lab tests, allows identification of MetS in children with overweight or obesity.
Negative and positive self-beliefs in social anxiety: The strength of believing mediates the affective response
Authors: Golde Sabrina , Ludwig Sophie , Lippoldt Sven , Rimpel Jérôme , Schulze Lars , Haucke Matthias , Renneberg Babette , Heinzel Stephan
Published: March 2023

Background and objectives

Current cognitive models of social anxiety disorder (SAD) propose that individual, situation-specific self-beliefs are central to SAD. However, the role of differences in the degree to which individuals with social anxiety are convinced of self-beliefs, in particular positive ones, is still not fully understood. We compared how much high and low socially anxious individuals agree with their own negative and positive self-beliefs. Furthermore, we investigated whether agreeing with one’s self-belief can explain the relation between negative affect in response to self-beliefs and social anxiety. Specifically, we were interested whether social anxiety increases negative affect in response to self-beliefs through an increase in agreement.

Methods

We developed a new experimental self-belief task containing positive and negative semi-idiosyncratic, situation specific self-beliefs typical of high social anxiety and included a direct measure of agreement with these beliefs. Using extreme group sampling, we a-priori selected high (n = 51) and low (n = 50) socially anxious individuals. By multi-level mediation analysis, we analyzed agreement with self-beliefs in both groups and its association with affect.

Results

High and low socially anxious individuals chose similar self-beliefs. However, high socially anxious individuals (HSA) agreed more with negative self-beliefs and less with positive self-beliefs compared to low socially anxious individuals (LSA). HSA individuals reported increased negative affect after both, exposition to negative and positive self-beliefs compared to LSA. We found that social anxiety increases affective responses towards negative-self beliefs through an increase in agreeing with these self-beliefs.

Conclusions

These findings suggest that cognitive models of social anxiety can be improved by including not only the content of a self-belief but also the strength of such a belief. In addition, they emphasize the relevance of positive self-beliefs in social anxiety, which has frequently been overlooked.
Conversion to belatacept after lung transplantation: Report of 10 cases
Authors: Brugière Olivier , Vallée Alexandre , Raimbourg Quentin , Peraldi Marie-Noelle , de Verdière Sylvie Colin , Beaumont Laurence , Hamid Abdulmonem , Zrounba Mathilde , Roux Antoine , Picard Clément , Parquin François , Glorion Matthieu , Oniszczuk Julie , Hertig Alexandre , Mal Hervé , Bunel Vincent
Published: March 2023

Background

Calcineurin inhibitors (CNIs) remain the cornerstone of maintenance immunosuppression (IS) after lung transplantation (LTx), although CNI-related life-threatening toxic effects may occur. Belatacept, a novel immunosuppressant that blocks a T-cell co-stimulation pathway, is a non-nephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, there are only a few reports of belatacept conversion as a CNI-free or CNI-sparing IS treatment.

Methods

We reviewed a series of 10 LTx recipients with conversion to a CNI-free belatacept IS regimen within the first year post-LTx (n = 7) or a belatacept/low-dose CNI combination after the first year (n = 3).

Results

Use of belatacept was triggered by severe renal failure in 9 patients and under-IS with previous other IS-related toxicities in 1 patient. Mean estimated glomerular filtration rate after starting belatacept significantly improved at 6 months after initiation and at the last-follow-up (p = 0.006, and p = 0.002 respectively). The incidence of recurrent and/or severe acute cellular rejection (ACR) episodes was high in patients with CNI-free belatacept-based IS (n = 4/7). Chronic graft allograft dysfunction developed in 2 of 9 recipients under belatacept IS. Belatacept was stopped in 6 patients because of recurrent/severe ACR (n = 3), recurrent opportunistic infections (n = 1), center modified policy (n = 1), or other cause (n = 1).

Conclusion

Early conversion to CNI-free belatacept-based IS improved renal function in this series but was counterbalanced by a high incidence of recurrent ACR, including life-threatening episodes. Other studies are needed to better determine the indications for its use after LTx, possibly with lower immunological risk IS regimens, such as CNI-sparing belatacept.
Social preferences in the public goods game–An Agent-Based simulation with EconSim
Authors: Bühren Christoph , Haarde Jan , Hirschmann Christian , Kesten-Kühne Janis
Published: March 2023

Using a reinforcement-learning algorithm, we model an agent-based simulation of a public goods game with endogenous punishment institutions. We propose an outcome-based model of social preferences that determines the agent’s utility, contribution, and voting behavior during the learning procedure. Comparing our simulation to experimental evidence, we find that the model can replicate human behavior and we can explain the underlying motives of this behavior. We argue that our approach can be generalized to more complex simulations of human behavior.
A single session of mindfulness meditation may acutely enhance cognitive performance regardless of meditation experience
Authors: Sleimen-Malkoun Rita , Devillers-Réolon Louise , Temprado Jean-Jacques
Published: March 2023

The present study investigated acute cognitive effects of mindfulness meditation (MM) compared to an active control intervention in meditators (n = 22) and novices (n = 20) using a within-subject design. We analyzed reaction times in a digitized Stroop task at baseline, after a 10-minute MM session with a fundamental breathing exercise, and after a 10-minute attentive listening intervention. Interventions order was randomized and a 10 min delay was respected before testing. Relative to baseline, meditators and novices showed faster reaction times after both interventions, but more so after MM for the congruent and incongruent Stroop task conditions that are associated with attention, inhibition and cognitive flexibility. Although the two interventions showed cognitive effects independent of previous meditation experience, MM appeared to induce larger benefits. Our findings are encouraging and support MM’s potential as a means to enhance cognitive performance on the short-term without the need of any previous practice.
Identification of social groups and waiting pedestrians at railway platforms using trajectory data
Authors: Küpper Mira , Seyfried Armin
Published: March 2023

To investigate the impact of social groups on waiting behaviour of passengers at railway platforms a method to identify social groups through the monitoring of distances between pedestrians and the stability of those distances over time is introduced. The method allows the recognition of groups using trajectories only and thus opens up the possibility of studying crowds in public places without constrains caused by privacy protection issues. Trajectories from a railway platform in Switzerland were used to analyse the waiting behaviour of passengers in dependence of waiting time as well as the size of social groups. The analysis of the trajectories shows that the portion of passengers travelling in groups reaches up to 10% during the week and increases to 20% on the weekends. 60% of the groups were pairs, larger groups were less frequent. With increasing group size, the mean speed of the members decreases. Individuals and pairs often choose waiting spots at the sides of the stairs and in vicinity of obstacles, while larger groups wait close to the platform entries. The results indicate that passengers choose waiting places according to the following criteria and ranking: shortest ways, direction of the next intended action, undisturbed places and ensured communication. While individual passengers often wait in places where they are undisturbed and do not hinder others, the dominating comfort criterion for groups is to ensure communication. The results regarding space requirements of waiting passengers could be used for different applications. E.g. to enhance the level of service concept assessing the comfort of different types of users, to avoid temporary bottlenecks to improve the boarding and alighting process or to increase the robustness of the performance of railway platforms during peak loads by optimising the pedestrian distribution.
Exploring the structural basis to develop efficient multi-epitope vaccines displaying interaction with HLA and TAP and TLR3 molecules to prevent NIPAH infection, a global threat to human health
Authors: Srivastava Sukrit , Verma Sonia , Kamthania Mohit , Saxena Ajay Kumar , Pandey Kailash C. , Pande Veena , Kolbe Michael
Published: March 2023

Nipah virus (NiV) is an emerging zoonotic virus that caused several serious outbreaks in the south asian region with high mortality rates ranging from 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific and effective vaccine has yet been reported against NiV. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have designed two Multi-Epitope Vaccines (MEVs) composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Out of those CTL and HTL combined 71 epitopes, 61 novel epitopes targeting nine different NiV proteins were not used before for vaccine design. Codon optimization for the cDNA of both the designed MEVs might ensure high expression potential in the human cell line as stable proteins. Both MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-γ inducing epitopes. Additional criteria such as sequence consensus amongst CTL, HTL and B Cell epitopes was implemented for the design of final constructs constituting MEVs. Hence, the designed MEVs carry the potential to elicit cell-mediated as well as humoral immune response. Selected overlapping CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles and in case of CTL epitopes with human Transporter Associated with antigen Processing (TAP) cavity. The structure based epitope cross validation for interaction with TAP cavity was used as another criteria choosing final epitopes for NiV MEVs. Finally, human Beta-defensin 2 and Beta-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. Molecular dynamics simulation studies of MEVs-TLR3 ectodomain (Human Toll-Like Receptor 3) complex indicated the stable molecular interaction. We conclude that the MEVs designed andin silicovalidated here could be highly potential vaccine candidates to combat NiV infections, with great effectiveness, high specificity and large human population coverage worldwide.
Progress in scale up of HIV viral load testing in select sub-Saharan African countries 2016–2018
Authors: Fonjungo Peter N. , Lecher Shirley , Zeh Clement , Rottinghaus Erin , Chun Helen , Adje-Toure Christiane , Lloyd Spencer , Mwangi Jane W. , Mwasekaga Michael , Eshete Yohannes Mengistu , Pati Rituparna , Mots’oane Tsietso , Mitruka Kiren , Beukes Anita , Mwangi Christina , Bowen Nancy , Hamunime Ndapewa , Beard Rachel S. , Kabuje Anyelwisye , Nabadda Susan , Auld Andrew F. , Balachandra Shirish , Zungu Innocent , Kandulu James , Alemnji George , Ehui Eboi , Alexander Heather , Ellenberger Dennis
Published: March 2023

Introduction

We assessed progress in HIV viral load (VL) scale up across seven sub-Saharan African (SSA) countries and discussed challenges and strategies for improving VL coverage among patients on anti-retroviral therapy (ART).

Methods

A retrospective review of VL testing was conducted in Côte d’Ivoire, Kenya, Lesotho, Malawi, Namibia, Tanzania, and Uganda from January 2016 through June 2018. Data were collected and included the cumulative number of ART patients, number of patients with ≥ 1 VL test result (within the preceding 12 months), the percent of VL test results indicating viral suppression, and the mean turnaround time for VL testing.

Results

Between 2016 and 2018, the proportion of PLHIV on ART in all 7 countries increased (range 5.7%–50.2%). During the same time period, the cumulative number of patients with one or more VL test increased from 22,996 to 917,980. Overall, viral suppression rates exceeded 85% for all countries except for Côte d’Ivoire at 78% by June 2018. Reported turnaround times for VL testing results improved in 5 out of 7 countries by between 5.4 days and 27.5 days.

Conclusions

These data demonstrate that remarkable progress has been made in the scale-up of HIV VL testing in the seven SSA countries.
Implementation and outcomes of a comprehensive emergency care curriculum at a low-resource referral hospital in Liberia: A novel approach to application of the WHO Basic Emergency Care toolkit
Authors: Epps Lane , Ramachandran Anu , Yi Sojung , Mayah Alexander , Burkholder Taylor , Jaung Michael , Haider Ahson , Wesseh Paul , Shakpeh John , Bills Corey , Enriquez Kayla
Published: March 2023

Background

Emergency care is vital in low- and middle-income countries (LMICs) but many frontline healthcare workers in low-resource settings have no formal training in emergency care. To address this gap, the World Health Organization (WHO) developed Basic Emergency Care (BEC): Approach to the acutely ill and injured, a multi-day, open-source course for healthcare workers in low-resource settings. Building on the BEC foundation, this study uses an implementation science (IS) lens to develop, implement, and evaluate a comprehensive emergency care curriculum in a single emergency facility in Liberia.

Methods

A six-month emergency care curriculum consisting of BEC content, standardized WHO clinical documentation forms, African Federation of Emergency Medicine (AFEM) didactics, and clinical mentorship by visiting emergency medicine (EM) faculty was designed and implemented using IS frameworks at Redemption Hospital, a low-resource public referral hospital in Monrovia, the capital of Liberia. Healthcare worker performance on validated knowledge-based exams during pre- and post-intervention testing, post-course surveys, and patient outcomes were used to evaluate the program.

Results

Nine visiting EM physicians provided 1400 hours of clinical mentorship and 560 hours of didactic training to fifty-six Redemption Hospital staff over six-months. Median test scores improved 20.0% (p<0.001) among the forty-three healthcare workers who took both the pre- and post-intervention tests. Participants reported increased confidence in caring for medical and trauma patients and comfort performing emergency care tasks on post-course surveys. Emergency unit (EU)/Isolation unit (IU) mortality decreased during the six-month implementation period, albeit non-significantly. Course satisfaction was high across multiple domains.

Discussion

This study builds on prior research supporting WHO efforts to improve emergency care globally. BEC implementation over a six-month timeframe using IS principles is an effective alternative strategy for facilities in resource-constrained environments wishing to strengthen emergency care delivery.
The magnitude and associated factors of immediate postpartum anemia among women who gave birth in east Gojjam zone hospitals, northwest- Ethiopia, 2020
Authors: Agmassie Getachew Altaseb , Alamneh Genet Degu , Ayicheh Moges Wubie , Getahun Worku Taye , Abneh Aysheshim Asnake
Published: March 2023

Background

Globally around half a million maternal death occurred annually related to labor and delivery of which twenty percent is contributed by post-partum anemia. Postpartum anemia contributes about two percent of total maternal mortality in Ethiopia. Immediate postpartum anemia is a common public health problem in most parts of the globe, being frequent in low and middle-income countries including in the developed world. The previous studies cut off point for immediate postpartum Anemia is 11mg/dl which is the cutoff point of anemia after one week of postpartum, environmental factors like barefoot were not addressed in the previous studies and the previous studies were conducted in a single facility This study aimed to assess the magnitude and associated factors of immediate post-partum anemia among women who gave birth in East Gojjam zone hospitals, Northwest Ethiopia.

Methods

Institutional based cross-sectional study was conducted from October 20-November 20 2020 on immediate post-partum anemia. During the study 467 study participants were included by using systematic random sampling method Data were collected using a structured interviewer-administered questionnaire and a blood sample was used for hemoglobin determination. Data were checked, coded, and entered into Epi-Data Version 4.2 and then exported to SPSS version 25 for analysis. Binary logistic regressions were done to identify predictors of immediate post-partum anemia and a 95% confidence interval of odds ratio at a p-value less than was taken as a significance level.

Results

The overall magnitude of immediate postpartum anemia among mothers who gave birth in East Gojjam Zone Hospitals were found to be 21.63% (95% CI:18.12%, 25.11%), not having antenatal care follow-up (Adjusted Odds Ratio (AOR) = 2.92;95% CI:1.20,7.06), assisted instrumental delivery (AOR = 2.72; 95% CI:1.08,6.78),mid-upper arm circumferences less than 23cm (AOR = 5.75;95% CI:3.38, 9.79), antepartum hemorrhage (AOR = 4.51; 95% CI:2.42, 8.37), never wearing shoes (AOR = 2.60; 95% CI:1.10, 6.14) were found to be significantly associated with immediate postpartum anemia.

Conclusion

This study indicates that immediate postpartum anemia is a moderate public health problem in the study area. A more careful strategy is ideal to increase antenatal care follow-up that sticks to national guideline contact schedule, safe reduction of instrumental and cesarean deliveries to the minimum, quick and timely linkage and treatment of malnourished pregnant mothers to the center where they get adequate health care services, along with a high index of suspicion in mothers diagnosed with antepartum hemorrhage, wise and vigilant advice on consistent use of the shoe for pregnant mothers are recommended to tackle the burden of immediate post-partum anemia.
Conceptual approaches in combating health inequity: A scoping review protocol
Authors: Amri Michelle , Mohamood Liban , Mansilla Cristián , Barrett Kathryn , Bump Jesse B.
Published: March 2023

Introduction

What are the different ways in which health equity can be sought through policy and programs? Although there is a central focus on health equity in global and public health, we recognize that stakeholders can understand health equity as taking different approaches and that there is not a single conceptual approach. However, information on conceptual categories of actions to improve health equity and/or reduce health inequity is scarce. Therefore, this study asks the research question: “what conceptual approaches exist in striving for health equity and/or reducing health inequity?” with the aim of presenting a comprehensive overview of approaches.

Methods

A scoping review will be undertaken following the PRISMA guidelines for Scoping Reviews (PRISMA-ScR) and in consultation with a research librarian. Both the peer-reviewed and grey literatures will be searched using: Ovid MEDLINE, Scopus, PAIS Index (ProQuest), JSTOR, Canadian Public Documents Collection, the World Health Organization IRIS (Institutional Repository for Information Sharing), and supplemented by a Google Advanced Search. Screening will be conducted by two independent reviewers and data will be charted, coded, and narratively synthesized.

Discussion

We anticipate developing a foundational document compiling categories of approaches and discussing the nuances inherent in each conceptualization to promote clarified and united action.
Spatial spillover and impacting factors of green development: A study based on China’s provincial data
Authors: Huang Jie , Chen Juan
Published: March 2023

Green development, an essential part of sustainable development transformation, is spatially correlated intra- and inter-regionally. However, previous research has not fully addressed the spatial characteristics of green development. This study investigates the spatial correlation structures, core–peripheral positions, and factors impacting the spatial network formation of China’s green development. Based on the green development evaluation index system modified by the entropy method, this study applies social network analysis, block model analysis, and quadratic assignment procedure analysis to data from 30 provinces in China. The results confirm the spatial spillover effect is overwhelmingly present in China’s green development. The findings further distinguish the core roles of provinces including Hunan, Tianjin, Zhejiang, Henan, and Xinjiang, and underline factors of green economic growth, governmental policy support, spatial adjacency, and geographic distance as significantly affecting the spatial network formation of China’s green development. Policy recommendations for green development are then put forward.
Increased levels of immature and activated low density granulocytes and altered degradation of neutrophil extracellular traps in granulomatosis with polyangiitis
Authors: Lipka Spyridon , Ostendorf Lennard , Schneider Udo , Hiepe Falk , Apel Falko , Alexander Tobias
Published: March 2023

Granulomatosis with Polyangiitis (GPA) is a small vessel vasculitis typically associated with release of neutrophil extracellular traps (NETs) by activated neutrophils. In this study, we further aimed to investigate the contributions of neutrophils and NETs to the complex disease pathogenesis. We characterized the phenotype of neutrophils and their capacity to induce NETs. In addition, the level of circulating NETs, determined by neutrophil elastase/DNA complexes, and the capacity of patient sera to degrade NETs were investigated from blood samples of 12 GPA patients, 21 patients with systemic lupus erythematosus (SLE) and 21 healthy donors (HD). We found that GPA patients had significantly increased levels of low-density granulocytes (LDGs) compared to HD, which displayed an activated and more immature phenotype. While the propensity of normal-density granulocytes to release NETs and the levels of circulating NETs were not significantly different from HD, patient sera from GPA patients degraded NETs less effectively, which weakly correlated with markers of disease activity. In conclusion, increased levels of immature and activated LDGs and altered degradation of circulating NETs may contribute to pathogenesis of GPA, potentially by providing a source of autoantigens that trigger or further enhance autoimmune responses.
“Stabilise-reduce, stabilise-reduce”: A survey of the common practices of deprescribing services and recommendations for future services
Authors: Cooper Ruth E. , Ashman Michael , Lomani Jo , Moncrieff Joanna , Guy Anne , Davies James , Morant Nicola , Horowitz Mark
Published: March 2023

Background

Public Health England recently called for the establishment of services to help people to safely stop prescribed drugs associated with dependence and withdrawal, including benzodiazepines, z-drugs, antidepressants, gabapentinoids and opioids. NICE identified a lack of knowledge about the best model for such service delivery. Therefore, we performed a global survey of existing deprescribing services to identify common practices and inform service development.

Methods

We identified existing deprescribing services and interviewed key personnel in these services using an interview co-produced with researchers with lived experience of withdrawal. We summarised the common practices of the services and analysed the interviews using a rapid form of qualitative framework analysis.

Results

Thirteen deprescribing services were included (8 UK, 5 from other countries). The common practices in the services were: gradual tapering of medications often over more than a year, and reductions made in a broadly hyperbolic manner (smaller reductions as total dose became lower). Reductions were individualised so that withdrawal symptoms remained tolerable, with the patient leading this decision-making in most services. Support and reassurance were provided throughout the process, sometimes by means of telephone support lines. Psychosocial support for the management of underlying conditions (e.g. CBT, counselling) were provided by the service or through referral. Lived experience was often embedded in services through founders, hiring criteria, peer support and sources of information to guide tapering.

Conclusion

We found many common practices across existing deprescribing services around the world. We suggest that these ingredients are included in commissioning guidance of future services and suggest directions for further research to clarify best practice.
The effects of nearby trees on the positional accuracy of GNSS receivers in a forest environment
Authors: Lee Taeyoon , Bettinger Pete , Merry Krista , Cieszewski Chris
Published: March 2023

Global Navigational Satellite System (GNSS) technologies are actively being developed to address the demand for enhanced positional accuracy. Smartphones are the most prevalent GNSS receiver today and have garnered attention thanks to improved positional accuracy and usability that can be accessed at an affordable price. In a forested environment, multipath error can deteriorate the positional accuracy, depending on the state of nearby vegetation. Therefore, this study was conducted to investigate the impacts of the size and location of vegetation on positional accuracy of GNSS receivers to determine whether the errors observed are systematic. Twenty-six control points within the Whitehall Forest GPS Test site in Athens, Georgia were used to evaluate positional accuracy of three different GNSS receivers (two traditional handheld GNSS receivers (including Garmin and Trimble receivers) and a smartphone). Thirty-five forest variables were developed from information around each control point to conduct a correlation analysis with observed horizontal position error in the positions determined by each device. In this study, we confirmed that the positional error of the smartphone was significantly lower than the Garmin receiver, and similar, but significantly different than the positional error observed by the Trimble receiver. It was confirmed that correlations between forest variables and horizontal position error regardless of the GNSS receiver employed were significant, yet trends were not consistent. The effect of the size of nearby trees on horizontal position error could not be generalized; however, the location of nearby trees on horizontal position error could.
How message appeals and prior product use influence information processing, risk perceptions, trust, attitudes, and genetic test purchase intentions
Authors: VanDyke Matthew S. , Lee Nicole M. , Abitbol Alan , Rush Stephen W.
Published: March 2023

Within the direct-to-consumer (DTC) genetic test industry, attracting customers can be difficult especially due to the highly sensitive nature of these products. How these tests are communicated to consumers may be one avenue in which companies can impact customer purchase intentions. A 2 (message sidedness: one-way vs. two-way refutational) x 2 (hedging: present vs. absent) between-subjects experiment was conducted to understand how message features and prior product use influence information processing, risk and trust perceptions, and attitude toward the genetic test, which in turn, may influence direct-to-consumer (DTC) genetic test purchase intentions. Results demonstrated that having used a genetic test in the past predicted participants’ trust in the company, information processing, and risk judgments; however, among those who used a genetic test, viewing a message that included hedging tended to increase their trust in the message. Trust in the message and company, information processing, and risk judgments significantly predicted participants’ attitudes toward genetic testing, which in turn predicted their purchase intentions. The results suggest that in the context of DTC genetic test messaging, practitioners should strive to increase consumer trust in the message and the company and facilitate information processing, and they should work to diminish perceived risk. These results suggest opportunities for identifying other message features that may influence message and company trust, information processing, risk judgments, and attitudes related to DTC genetic testing.
Glucosylceramide is essential for Heartland and Dabie bandavirus glycoprotein-induced membrane fusion
Authors: Xia Tian , Wu Xin , Hong Eunjin , Jung Kyle , Lai Chih-Jen , Kwak Mi-Jeong , Seo Hogyu , Kim Stephanie , Jiang Zhongyi , Cha Inho , Jung Jae U.
Published: March 2023

Due to climate changes, there has been a large expansion of emerging tick-borne zoonotic viruses, including Heartland bandavirus (HRTV) and Dabie bandavirus (DBV). As etiologic agents of hemorrhagic fever with high fatality, HRTV and DBV have been recognized as dangerous viral pathogens that likely cause future wide epidemics. Despite serious health concerns, the mechanisms underlying viral infection are largely unknown. HRTV and DBV Gn and Gc are viral surface glycoproteins required for early entry events during infection. Glycosphingolipids, including galactosylceramide (GalCer), glucosylceramide (GlcCer) and lactosylceramide (LacCer), are a class of membrane lipids that play essential roles in membrane structure and viral lifecycle. Here, our genome-wide CRISPR/Cas9 knockout screen identifies that glycosphingolipid biosynthesis pathway is essential for HRTV and DBV infection. The deficiency of UDP-glucose ceramide glucosyltransferase (UGCG) that produces GlcCer resulted in the loss of infectivity of recombinant viruses pseudotyped with HRTV or DBV Gn/Gc glycoproteins. Conversely, exogenous supplement of GlcCer, but not GalCer or LacCer, recovered viral entry of UGCG-deficient cells in a dose-dependent manner. Biophysical analyses showed that GlcCer targeted the lipid-head-group binding pocket of Gc to form a stable protein-lipid complex, which allowed the insertion of Gc protein into host lysosomal membrane lipid bilayers for viral fusion. Mutagenesis showed that D841 residue at the Gc lipid binding pocket was critical for GlcCer interaction and thereby, viral entry. These findings reveal detailed mechanism of GlcCer glycosphingolipid in HRTV and DBV Gc-mediated membrane fusion and provide a potential therapeutic target for tickborne virus infection.
Saúde mental, conexão de afetos e a pandemia
Authors: Dentz René
Published: March 2023

O contexto da pandemia trouxe de volta o desamparo fundante do sujeito, retomando o conceito afirmado por Freud em O mal-estar na civilização. Nele, o psicanalista austríaco enuncia a angústia real tendo como consequência um impacto traumático. Para além disso, a marca psíquica do masoquismo é igualmente reativada, pela fantasia de se imputar o sofrimento, que se torna quase um imperativo social. É evidente que se nesse contexto o sujeito crê ainda em uma espécie de apelo ao Outro — por meio da dimensão de cuidado e de segurança, a vulnerabilidade e a ausência dessa instância de proteção conduzem o indivíduo à condição subjetiva do desalento e, porta, como consequência, uma sensação de fragmentação e de desconstrução (mais profunda ainda do que aquela advinda da pós-modernidade).
Patient with adrenal insufficiency due to a de novo mutation in the NR0B1 gene
Authors: Bravo Nieto Daniel , García Fernández Alba S. , Díaz Troyano Noelia , Arnaiz Marina Giralt , Arias García Andrea , Fernández Álvarez Paula , Campos Martorell Ariadna , Ferrer Costa Roser , Clemente León María
Published: March 2023

Objectives

Congenital X-linked adrenal hypoplasia is a rare disease with a known genetic basis characterized by adrenal insufficiency, hypogonadotropic hypogonadism, and a wide variety of clinical manifestations.

Case presentation

We present the case of a 26-day old male newborn with symptoms consistent with adrenal insufficiency, hyponatremia, and hyperkalemia. Following NaCl and fludrocortisone supplementation, the patient remained clinically stable. 17-OH-progesterone testing excluded congenital adrenal hyperplasia. The rest of hormones were within normal limits, except for adrenocorticotropic hormone (ACTH), which was significantly elevated, and aldosterone, which was below the reference value. Further testing included very long chain fatty acids to exclude adrenoleukodystrophy, the CYP11B2 gene (aldosterone synthase), and an MRI to screen for other morphological abnormalities. All tests yielded normal results. Finally, after cortisol deficiency was detected, expanded genetic testing revealed a mutation in the NR0B1 gene, which led to a diagnosis of congenital adrenal hypoplasia.

Conclusions

Diagnosis of congenital adrenal hypoplasia is challenging due to the heterogeneity of both clinical manifestations and laboratory abnormalities. As a result, diagnosis requires close monitoring and genetic testing.
Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs
Authors: Charrière Karine , Pazart Lionel
Published: March 2023

In May 2022, the European Regulation 2017/746 (IVDR) came into force. It changes the approach of in vitro medical devices (IVD-MDs) for industry and institutions. It reinforces the clinical evidence requirements to improve performance, safety and transparency. Despite extended transition periods and existing guides, IVDR remains difficult to interpret and bringing devices into compliance requires efforts. The generation of clinical evidence is essential to demonstrate compliance with IVDR, and encompasses scientific validity, analytical performance and clinical performance. It is required to demonstrate, per intended use in the target population and clinical care pathway, IVD-MDs clinical performance (compared to a predefined clinical performance). Thus, there is a need for IVD-manufacturers and end-users in health care institutions, to obtain guidance on how to generate this clinical evidence. This article aims industrials and clinicians to identify key steps imposed by the IVDR for bringing IVD-MDs to the EU-market. We propose a general view of performance evaluation requirements for IVD-MDs and provide key references, including how to establish study design that will enable to document clinical performance of existing, refined or emerging medical tests. Finally, we propose a roadmap to address the relevant questions and studies in relation to the documents requested in the IVDR.
Mathematical model for conversion of groundwater flow from confined to unconfined aquifers with power law processes
Authors: Morakaladi Makosha Ishmaeline Charlotte , Atangana Abdon
Published: March 2023

In this work, we propose a mathematical model to depict the conversion of groundwater flow from confined to unconfined aquifers. The conversion problem occurs due to the heavy pumping of confined aquifers over time, which later leads to the depletion of an aquifer system. The phenomenon is an interesting one, hence several models have been developed and used to capture the process. However, one can point out that the model has limitations of its own, as it cannot capture the effect of fractures that exist in the aquitard. Therefore, we suggest a mathematical model where the classical differential operator that is based on the rate of change is substituted by a non-conventional one including the differential operator that can represent processes following the power law to capture the memory effect. Moreover, we revise the properties of the aquitard to evaluate and capture the behaviors of flow during the process in a different aquitard setting. Numerical analysis was performed on the new mathematical models and numerical solutions were obtained, as well as simulations for various fractional order values.
An 11-year-old girl with Autoimmune Polyglandular Syndrome (APS) type 2: a case report and review of literature
Authors: Bonataki Myrto , Dikaiakou Eirini , Anastasopoulou Panagiota , Fakiolas Stefanos , Kafetzi Maria , Vlachopapadopoulou Elpis Athina
Published: March 2023

Objectives

Autoimmune polyglandular syndrome type 2 (APS2) is characterized by autoimmune adrenal insufficiency (AI) in conjunction with autoimmune thyroid disease (AITD) and/or type 1 diabetes mellitus (T1DM). The aim is to report an 11-year-old girl with concurrence of Addison disease, celiac disease and thyroid autoimmunity.

Case presentation

She initially presented at the age of 5 with vomiting, dehydration, hyponatremia, hyperkalemia and low glucose. She recovered with intravenous hydration but the diagnosis was not established. She presented again at the age of 11 with hyperpigmentation, weakness and signs of impending adrenal crisis. Diagnosis of autoimmune AI was established together with celiac disease and thyroid autoimmunity. Thus, she met criteria for APS, being the third pediatric case report of APS2 with this combination.

Conclusions

This case is notable for the atypical age of onset, given that APS2 is rare in the pediatric population. Furthermore, it depicts the insidious course of Addison disease with symptoms fluctuating for years before diagnosis.
On the Origin of Transculturalism: A Study Into the Western Academic Context and its Chinese Translation
Authors: Zhang Xiaoying , Sheng Yang , Jiang Duo
Published: March 2023

The concept of transculturalism has often been used to describe the increasingly complicated interactions between different cultures under the circumstances of globalization. It is also widely used in international communication and intercultural studies in China, and is often translated into different Chinese concepts such as “跨文化” “超越文化” “转文化.” How can we better understand the meaning of this concept in different academic contexts? This paper discovered that this concept was developed as criticism of post-colonialism and that of Western cultural studies reflecting a worldview that is centered on Euro-centrism. The Chinese translation of transculturalism should accordingly vary in different academic discourses. The concept is of great significance to promote cultural equality, cultural connection and respect, cultural exchange and mutual learning. However, cultural competition and western-centrism embedded in Welsch’s definition of transculturalism is worthy of attention.
Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
Authors: Li Yachen , Duan Junjun , Lin Weicheng , Liu Jie
Published: March 2023

Osteoarthritis (OA) is a type of common degenerative joint disorder, in which adipose mesenchymal stem cells (ADSCs) and the secreted exosomes play an important role. The purpose of this study was to investigate the role and mechanism of exosomes derived from ADSCs (ADSC-exos) in OA. The gradient of IL-1β concentration was designed to construct the articular chondrocyte model of arthritic mice. The expression of miR-93-5p and ADAMTS9 in articular chondrocytes was detected by reverse transcription quantitative polymerase chain reaction. Dual luciferase reporter gene assay was performed to verify the interaction between them. Monodansylcadaverine staining was used to visualize the autophagosome formation and cell apoptosis was analyzed by flow cytometry. ADSC-exos were authenticated by transmission electron microscope and western blot assay. miR-93-5p was found to be downregulated in IL-1β-treated articular chondrocytes compared with OA cartilage while ADAMTS9 was upregulated, which was identified as a direct target gene of miR-93-5p. Silencing of ADAMTS9 attenuated the effects of miR-93-5p. Exosomal miR-93-5p can reduce the release of inflammatory factors in mouse arthritis cell models. This study first described the mechanism under that ADSC-exos inhibited inflammation and alleviated OA through the innovative targets miR-93-5p/ADAMTS9 signal axis. This provided a new method for the treatment of OA.
Narrowband photoblinking InP/ZnSe/ZnS quantum dots for super-resolution multifocal structured illumination microscopy enhanced by optical fluctuation
Authors: Zhou Liangliang , Cao Huiqun , Huang Lilin , Jing Yingying , Wang Meiqin , Lin Danying , Yu Bin , Qu Junle
Published: March 2023

Cadmium-free quantum-dot (QD) fluorophores can bridge the gap between the macroscopic and microscopic domains in fluorescence super-resolution bioimaging. InP/ZnSe/ZnS QD photoblinking fluorescent probes can improve the performance of reactive super-resolution imaging techniques and spontaneously switch fluorophores between at least two states (open and close) without depending on intense laser light and specialized buffers for bioimaging. Multifocal structured illumination microscopy (MSIM) provides a two-fold resolution enhancement in sub-diffraction imaging, but higher resolutions are limited by the pattern frequency and signal-to-noise ratio. We exploit the synergy between MSIM and spontaneously switching InP/ZnSe/ZnS QD fluorophores to further increase the imaging resolution. We demonstrate the experimental combination of optical-fluctuation-enhanced super-resolution MSIM using ultrasonic-oscillation-assisted organic solvothermal synthesis of narrowband photoblinking InP/ZnSe/ZnS QDs. The InP/ZnSe/ZnS QDs show a monodisperse grain size of approximately 9 nm, fluorescence quantum yields close to 100%, and full width at half maximum below 30 nm. The structural, electronic, and optical properties are characterized through experiments and first-principles calculations. The enhanced MSIM imaging achieves an approximate fourfold improvement in resolution for fixed cells compared with widefield imaging. The proposed InP/ZnSe/ZnS QD fluorescent probes seem promising for super-resolution imaging using MSIM.