bluuebunny/crossref_metadata_2025 huggingface dataset:
Coding undiagnosed rare disease patients in health information systems: recommendations from the RD-CODE project
Authors: Angin Céline , Mazzucato Monica , Weber Stefanie , Kirch Kurt , Abdel Khalek Waed , Ali Houda , Maiella Sylvie , Olry Annie , Jannot Anne-Sophie , Rath Ana
Published: January 2024

Background

In European Union countries, any disease affecting less than 5 people in 10,000 is considered rare. As expertise is scarce and rare diseases (RD) are complex, RD patients can remain undiagnosed for many years. The period of searching for a diagnosis, called diagnostic delay, sometimes leads to a diagnostic dead end when the patient’s disease is impossible to diagnose after undergoing all available investigations. In recent years, extensive efforts have been made to support the implementation of ORPHA nomenclature in health information systems (HIS) so as to allow RD coding. Until recently, the nomenclature only encompassed codes for specific RD. Persons suffering from a suspected RD who could not be diagnosed even after full investigation, could not be coded with ORPHAcodes. The recognition of the RD status is necessary for patients, even if they do not have a precise diagnosis. It can facilitate reimbursement of care, be socially and psychologically empowering, and grant them access to scientific advances.

Results

The RD-CODE project aimed at making those patients identifiable in HIS in order to produce crucial epidemiological data. Undiagnosed patients were defined as patients for whom no clinically-known disorder could be confirmed by an expert center after all reasonable efforts to obtain a diagnosis according to the state-of-the-art and diagnostic capabilities available. Three recommendations for the coding of undiagnosed RD patients were produced by a multi-stakeholder panel of experts: 1/ Capture the diagnostic ascertainment for all rare disease cases; 2/ Use the newly created ORPHAcode (ORPHA:616874 “Rare disorder without a determined diagnosis after full investigation”), available in the Orphanet nomenclature: as the code is new, guidelines are essential to ensure its correct and homogeneous use for undiagnosed patients’ identification in Europe and beyond; 3/ Use additional descriptors in registries.

Conclusions

The recommendations can now be implemented in HIS (electronic health records and/or registries) and could be a game-changer for patients, clinicians and researchers in the field, enabling assessment of the RD population, including undiagnosed patients, adaptation of policy measures including financing for care and research programs, and to improved access of undiagnosed patients to research programs.
Review of published 467 achondroplasia patients: clinical and mutational spectrum
Authors: Zhang XinZhong , Jiang Shan , Zhang Rui , Guo Siyi , Sheng Qiqi , Wang Kaili , Shan Yuanyuan , Liao Lin , Dong Jianjun
Published: January 2024

Aim

Achondroplasia is the most common of the skeletal dysplasias that cause fatal and disabling growth and developmental disorders in children, and is caused by a mutation in the fibroblast growth factor receptor, type 3 gene(FGFR3). This study aims to analyse the clinical characteristics and gene mutations of ACH to accurately determine whether a patient has ACH and to raise public awareness of the disease.

Methods

The database of Pubmed, Cochrane Library, Wanfang and CNKI were searched with terms of “Achondroplasias” or “Skeleton-Skin-Brain Syndrome” or “Skeleton Skin Brain Syndrome” or “ACH” and “Receptor, Fibroblast Growth Factor, Type 3” or “FGFR3”.

Results

Finally, four hundred and sixty-seven patients with different FGFR3 mutations were enrolled. Of the 138 patients with available gender information, 55(55/138, 40%) were female and 83(83/138, 60%) were male. Among the patients with available family history, 47(47/385, 12%) had a family history and 338(338/385, 88%) patients were sporadic. The age of the patients ranged from newborn babies to 36 years old. The mean age of their fathers was 37 ± 7 years (range 31–53 years). Patients came from 12 countries and 2 continents, with the majority being Asian (383/432, 89%), followed by European (49/432, 11%). Short stature with shortened arms and legs was found in 112(112/112) patients, the abnormalities of macrocephaly in 94(94/112) patients, frontal bossing in 89(89/112) patients, genu valgum in 64(64/112) patients and trident hand were found in 51(51/112) patients. The most common mutation was p.Gly380Arg of the FGFR3 gene, which contained two different base changes, c.1138G > A and c.1138G > C. Ten rare pathogenic mutations were found, including c.831A > C, c.1031C > G, c.1043C > G, c.375G > T, c.1133A > G, c.1130T > G, c.833A > G, c.649A > T, c.1180A > T and c.970_971insTCTCCT.

Conclusion

ACH was caused by FGFR3 gene mutation, and c.1138G > A was the most common mutation type. This study demonstrates the feasibility of molecular genetic testing for the early detection of ACH in adolescents with short stature, trident hand, frontal bossing, macrocephaly and genu valgum.
Transpalpebral electrical stimulation for the treatment of retinitis pigmentosa: study protocol for a series of N-of-1 single-blind, randomized controlled trial
Authors: Zhou Wei , Huang Ziyang , Xu Kai , Li Yamin , Li Xiaoyu , Li Jiaxian , Jin Yu , Snellingen Torkel , Liang Lina
Published: January 2024

Background

Retinitis pigmentosa (RP) is an inherited disease characterized by a progressive loss of rod photoreceptors of the eye, leading to irreversible blindness. To date, to our knowledge, no clinical prospective studies have been undertaken that could document the effect of interventions that could reverse or reduce the progression of this disease. The application of microcurrent stimulation (ES) of the eye in the treatment of chronic eye diseases such as glaucoma and age-related macular degeneration has been used over several decades and has been reported to have beneficial effects to reduce the progression of these blinding diseases and has been supported by animal studies and smaller clinical studies, but to date, no large randomized clinical trials on the use of microcurrent therapy have been published. More recent clinical reports have also shown beneficial effects of ES on slowing the progression of RP but also lacks data from robust prospective clinical outcome studies. To our knowledge, this is the first prospective randomized study to evaluate the safety and clinical effectiveness of transpalpebral electrical stimulation (TpES) on the progression of RP.

Methods

Randomized prospective study using N-of-1 trial 3 single-blind, crossover comparisons. The intervention period of each comparison is divided into treatment period and control period which are randomized arranged. Twelve participants will be strictly recruited in N-of-1 trial by the researcher in accordance with the inclusion and exclusion criteria. The main outcome of interest examined after each cycle of the 8-week intervention period is the assessment of the visual field (VF). Other variables of interest are best corrected visual acuity (BCVA), retinal function using electroretinogram (ERG), and visual function using NEI VFQ-25 questionnaire. Objective assessments of retinal changes will be undertaken using optical coherence tomography (OCT) and fundus autofluorescence (FAF).

Discussion

The trial will evaluate the efficacy and safety of microcurrent stimulation on RP and provide high-quality evidence for clinical application through N-of-1 trial.

Trial registration

Chinese Clinical Trial Registry; ChiCTR2300067357; https://www.chictr.org.cn/showproj.html?proj=174635. Registered on 5 January 2023
Associate Principal Investigators and the HEAL-COVID trial: good for trainees, good for trials
Authors: Newman Joseph , Wild Philip ,   HEAL-COVID Collaboration, Summers Charlotte , Toshner Mark
Published: January 2024

Background

The NIHR’s Associate Principal Investigator (API) Scheme in the United Kingdom was expanded nationally in 2020 with the aim of training clinicians to become Principal Investigators for clinical research in the future. The HEAL-COVID adaptive platform trial is an urgent public health study registered with the API Scheme. Within eighteen months of opening, the trial had recruited almost 1200 patients with over 100 active sites. Here we describe our experiences of APIs working on the trial with two broad objectives. Firstly, we aim to explore through qualitative methods the impact that the scheme has had on the APIs’ professional development. Secondly, we aim to quantify the impact that the APIs have had on the recruitment of patients into the trial.

Methods

The professional backgrounds of the APIs are described from data from their application forms to the scheme. The HEAL-COVID API Network is described from records of the monthly meetings. The APIs’ experiences are reviewed from data from the NIHR exit surveys at 6 months and from a reflective practice exercise at the final network meeting. Data of patient recruitment to HEAL-COVID was analysed for centres with and without APIs via a multivariate analysis.

Results

Forty-two APIs were registered with the HEAL-COVID trial with a diversity of backgrounds in terms of gender, country, profession, grade and specialty. Eleven monthly network meetings took place with the dual objectives of facilitating trial activity and providing educational content. Fourteen APIs completed the NIHR survey with all reporting Good Clinical Practice completion, local promotional activity of the trial, patient recruitment and support from their respective PI. Sites with at least one API recruited over 3.5 times more patients than sites without an API (medians 4 vs 14.5, p < 0.05), independent of factors including type of hospital or number of inpatient beds.

Discussion

This study adds to the growing literature that the NIHR’s API Scheme is effective in meeting its objectives in providing research training to clinicians, thus building a workforce of future clinical researchers. Moreover, data from the HEAL-COVID trial shows that sites with an API are associated with higher recruitment. Overall, registering a trial with the API Scheme not only trains future clinical researchers, but it is also likely to increase the number of patients recruited (amongst other benefits), increasing the efficiency of trials and improving access for patients.
Development of chromatographic methods to determine multivitamins formulation depending on their solubility and polarity: comparative study using three greenness assessment tools
Authors: Galal Sara Abdel Basset , Elzanfaly Eman Saad , Hussien Emad Mohamed , Amer Enas Abdel Hakim , Zaazaa Hala Elsayed
Published: January 2024

High performance liquid chromatography is one of the techniques of choice for the separation and quantitative determination of drugs in mixture form. Ipriflavone, ascorbic acid, pyridoxine, vitamin D3, and lysine are formulated together as an adjuvant combination in osteoporosis. In this work, we developed and validated two complementary high performance liquid chromatographic methods to determine the five compounds in their pharmaceutical dosage form. The first method (method A) was capable of determining ipriflavone, ascorbic acid, pyridoxine, and vitamin D3 in their bulk and combined pharmaceutical formulation. The method is based on Liquid Chromatographic separation with UV detection at 254 nm using Agilent Eclipse XDB-C18 column with a mobile phase consisting of 25 mM ammonium acetate buffer (pH 4.2): methanol in gradient mode. Due to the high polarity of lysine, it was difficult to achieve satisfactory retention on reversed phase columns. So, we separated it on a strong cation exchange column (Exsil 100 SCX) without derivatization with a mobile phase consisting of 10 mM sodium dihydrogen phosphate and 200 mM sodium chloride (pH 6) with UV detection at 210 nm (method B). Validation of the proposed methods was performed according to ICH guidelines Q2(R1). The proposed methods proved to be valid for selective analysis of the stated drugs in their bulk and combined pharmaceutical formulation. Greenness assessment of the developed methods was evaluated using three assessment tools: ESA, GAPI and the most recently developed tool AGREE, showing a satisfactory comprehensive guide of the greenness of the developed methods.
Chromatographic analysis of triple cough therapy; bromhexine, guaiafenesin and salbutamol and pharmaceutical impurity: in-silico toxicity profile of drug impurity
Authors: Sharkawi Marco M. Z. , Safwat Mark T. , Abdelaleem Eglal A. , Abdelwahab Nada S.
Published: January 2024

Bromhexine (BR), guaiafenesin (GUF) and salbutamol (SAL) are formulated as Ventocough syrup® (with and without sugar), labeled to contain propyl paraben and sodium benzoate as inactive ingredients. They are used to make coughing more productive and easier. A crucial element and a major issue in the pharmaceutical industry is the control of organic related impurities to obtain safe and effective treatment. Guaiacol (GUL) is reported to be GUF related impurity that was proved to be extremely toxic (toxic rating class 5), and its use should be banned. In this work, In-Silico study and ADMET estimation were conducted to predict GUL pharmacokinetic properties and its toxicity profile. Additionally, two chromatographic methods were conducted to analyze the studied components along with GUF impurity in the presence of the labeled dosage form excipients. The In-Silico study assured that GUL has oral rat acute toxicity and it is considered to be skin sensitizer. On the other hand, the developed TLC- densitometeric method depended on using a mobile phase mixture of hexane: methylene chloride: triethylamine (5.0:6.0:0.3, by volume) as a developing system. UV-Scanning was performed immediately at 275 nm for SAL, GUF and GUL, while scanning at 310 nm was used for scanning BR. Linearity was established in the ranges of 0.25–4.0, 0.25–4.0, 0.5–8.0 and 0.1–1.6 µg/band for BR, SAL, GUF and GUL, respectively. In the developed HPLC method, separation was performed on X-Bridge® C18 column (250 × 4.6 mm, 5 μm) using a solvent mixture of 0.05M disodium hydrogen phosphate pH 3 with aqueous phosphoric acid: methanol (containing 0.3%, v/v triethylamine) (40:60, v/v). Detection was done at 225 nm and separation was achieved within 10 min. Linearity was proved in the range of 2–50 µg/mL for the proposed drugs. Validation of the developed methods was done and all the calculated parameters were within the acceptable limits recommended by ICH guidelines. After that, methods were used to examine the potency of the selected marketed dosage forms and concentrations of all drugs were within the acceptable limits. Additionally, complete separation between the studied drugs and the additives were observed. The developed methods can be used during routine quality control analysis of the proposed drugs when the required issues concern on sensitivity, selectivity and analysis time.

Graphical Abstract
A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau
Authors: Jiang Zhouquan , Wang Jing , Qin Yongpeng , Liu Shanggong , Luo Bin , Bai Fan , Wei Huiyi , Zhang Shaojuan , Wei Junjie , Ding Guoyu , Ma Long , He Shu , Chen Rongjie , Sun Ying , Chen Yi , Wang Lu , Xu Hao , Wang Xiangyu , Chen Gong , Lei Wenliang
Published: January 2024

Background

Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys.

Methods

Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests.

Results

We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents.

Conclusions

This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.
Treatment strategy for heart failure complicated with complete left bundle branch block and atrial tachycardia: a case report
Authors: Wang Jian , Zhang Qing-Qing , Lin Jie , Yuan Wei , Wang Li-Chun , Wu Yu-Cheng
Published: January 2024

Background

For patients with heart failure combined with complete left bundle branch block, cardiac resynchronization therapy is an important therapeutic method. If these patients also have atrial tachycardia, how to choose a treatment strategy deserves discussion.

Case presentation

A Chinese woman in her early 70s was admitted due to recurrent episodes of chest distress and asthma for 1 year. Physical and laboratory examinations showed filling of the jugular vein, lung rales, left enlargement of the heart boundary, edema of the lower limbs and elevation of N-terminal pro b-type natriuretic peptide. An electrocardiogram showed atrial tachycardia and a left bundle branch block. An echocardiography revealed enlargement of the left ventricle and left ventricular systolic dysfunction. After obtaining informed consent, the treatment strategy decided upon by the team was to use biventricular cardiac resynchronization therapy treatment and to not intervene for the atrial tachycardia, with left bundle branch area pacing as a backup. Due to twisted and narrow coronary vein branches, traditional biventricular pacing failed, and then, left bundle branch area pacing was attempted successfully. A follow-up echocardiography at 1 year showed improved systolic function. The outcomes for this patient are favorable, but the choice of interventional strategy is worthy of discussion in this case.

Conclusion

For patients with heart failure combined with left bundle branch block and atrial tachycardia, left bundle branch area pacing can replace traditional biventricular pacing for cardiac resynchronization therapy treatment, and the therapeutic effect is significant. However, multiple factors need to be considered when formulating strategies, including whether there is bundle branch block under sinus rhythm, the success and recurrence rate of atrial tachycardia ablation, the response of cardiac resynchronization therapy, the costs of different strategies, and instrument implantation issues.
Impact of direct ICU admission of pneumococcal meningitis in France: a retrospective analysis of a French medico-administrative (PMSI) database
Authors: Thy Michael , Dupuis Claire , Mageau Arthur , Mourvillier Bruno , Bouadma Lila , Ruckly Stéphane , Perozziello Anne , Strukov Andrey , Van-Gysel Damien , de Montmollin Etienne , Sonneville Romain , Timsit Jean-François
Published: January 2024

Background

Current guidelines for adult patients with pneumococcal meningitis (PM) recommend initial management in intermediate or intensive care units (ICU), but evidence to support these recommendations is limited. We aimed to describe ICU admission practices of patients with PM.

Methods

We conducted a retrospective analysis of the French medico administrative database of consecutive adult patients with PM and sepsis criteria hospitalized between 2011 and 2020. We defined two groups, “Direct ICU” corresponding to a direct ICU admission and “Delayed ICU” corresponding to a secondary ICU admission.

Results

We identified 4052 patients hospitalized for a first episode of PM, including 2006 “Direct ICU” patients (50%) and 2046 “delayed ICU” patients (50%). The patients were mainly males [n = 2260 (56%)] with median age of 61 years [IQR 50–71] and a median Charlson index of 1 [0–3]. Among them, median SAPS II on admission was 46 [33–62], 2173 (54%) had a neurological failure on admission with 2133 (53%) in coma, 654 (16%) with brainstem failure, 488 (12%) with seizures and 779 (19%) with focal signs without coma. PM was frequently associated with pneumonia [n = 1411 (35%)], and less frequently with endocarditis [n = 317 (8%)]. The median ICU length of stay and hospital length of stay were 6 days [2–14] and 21 days [13–38], respectively. In-hospital mortality was 27% (n = 1100) and 640 (16%) patients were secondarily transferred to rehabilitation care unit. Direct ICU group was significantly more severe but after adjustment for age, sex, comorbidities, organ failures on admission and admission from home, direct ICU admission was significantly associated with a lower mortality (Odds ratio 0.67 [0.56–0.80], p < 0.01). This corresponded to one death avoided for 11 PM directly admitted in ICU.

Conclusions

Among patients with PM and sepsis, direct ICU admission was associated with lower mortality rates when compared to delayed admission.
How to improve the structural stabilities of halide perovskite quantum dots: review of various strategies to enhance the structural stabilities of halide perovskite quantum dots
Authors: Kim Dokyum , Yun Taesun , An Sangmin , Lee Chang-Lyoul
Published: January 2024

Halide perovskites have emerged as promising materials for various optoelectronic devices because of their excellent optical and electrical properties. In particular, halide perovskite quantum dots (PQDs) have garnered considerable attention as emissive materials for light-emitting diodes (LEDs) because of their higher color purities and photoluminescence quantum yields compared to conventional inorganic quantum dots (CdSe, ZnSe, ZnS, etc.). However, PQDs exhibit poor structural stabilities in response to external stimuli (moisture, heat, etc.) owing to their inherent ionic nature. This review presents recent research trends and insights into improving the structural stabilities of PQDs. In addition, the origins of the poor structural stabilities of PQDs and various methods to overcome this drawback are discussed. The structural degradation of PQDs is mainly caused by two mechanisms: (1) defect formation on the surface of the PQDs by ligand dissociation (i.e., detachment of weakly bound ligands from the surface of PQDs), and (2) vacancy formation by halide migration in the lattices of the PQDs due to the low migration energy of halide ions. The structural stabilities of PQDs can be improved through four methods: (1) ligand modification, (2) core–shell structure, (3) crosslinking, and (4) metal doping, all of which are presented in detail herein. This review provides a comprehensive understanding of the structural stabilities and opto-electrical properties of PQDs and is expected to contribute to future research on improving the device performance of perovskite quantum dot LEDs (PeLEDs).
Local site effects and seismic microzonation around Suban Area, Curup Rejang Lebong, Bengkulu deduced by ambient noise measurements
Authors: Siburian Brecya Isa , Marzuki Marzuki , Lubis Ashar Muda
Published: January 2024

Background

The Suban area of Curup Rejang Lebong is a tourist region in Bengkulu Province, Indonesia, close to the active Ketaun and Musi faults, which are segments of the Sumatra Fault System (SFS). However, no studies have been conducted in this area to assess how geological structures affect seismic ground motions and contribute to seismic hazard and risk assessment.

Methods

The first study of seismic microzonation in the Suban area of Curup City by ambient noise measurements was conducted at 100 sites, spaced ~ 1 km apart, with 60 min of data acquisition for each site. All microseismic data were processed using the Horizontal to Vertical Spectral Ratios (HVSR) method.

Results

The HVSR method revealed the amplification factors (A0) ranging from 1.23 to 8.26 times, corresponding to natural frequency (f0) variations between 1.24 and 9.67 Hz. About 13% and 55% of the sites show high (6 ≤ A0 ≤ 9) and medium (3 ≤ A0 ≤ 6) amplifications, respectively, predominantly in the western parts of the study area, consistent with a high seismic vulnerability index (Kg). Furthermore, we also estimated the ground shear strain (GSS) of the region using the Kanai method with two large historical earthquakes at the Ketahun segment in 1943 (Mw 7.4) and the Musi segment in 1979 (Mw 6.0). The Kg value is consistent with the GSS values and indicates areas of severe damage during the historic earthquakes.

Conclusions

Thus, the western parts of the Suban region are vulnerable to severe damage from an earthquake. These findings could provide valuable insights for future planning and risk management efforts aimed at minimizing the impact of earthquakes in the Suban region.
Treatment of glucocorticoid- induced hyperglycemia in hospitalized patients - a systematic review and meta- analysis
Authors: Struja Tristan , Nitritz Neele , Alexander Islay , Kupferschmid Kevin , Hafner Jason F. , Spagnuolo Carlos C. , Schuetz Philipp , Mueller Beat , Blum Claudine A.
Published: January 2024

Purpose

Glucocorticoid (GC)-induced hyperglycemia is a frequent issue, however there are no specific guidelines for this diabetes subtype. Although treat-to-target insulin is recommended in general to correct hyperglycemia, it remains unclear which treatment strategy has a positive effect on outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess whether treating GC-induced hyperglycemia improves clinical outcomes.

Methods

MEDLINE and EMBASE were systematically searched for RCTs on adults reporting treatment and outcomes of GC-induced hyperglycemia since the beginning of the data bases until October 21, 2023. Glucose-lowering strategies as compared to usual care were investigated.

Results

We found 17 RCTs with 808 patients and included seven trials in the quantitative analysis. Patients with an intensive glucose-lowering strategy had lower standardized mean glucose levels of – 0.29 mmol/l (95%CI -0.64 to -0.05) compared to usual care group patients. There was no increase in hypoglycemic events in the intensively treated groups (RR 0.91, 95%CI 0.70–1.17). Overall, we did not have enough trials reporting clinical outcomes for a quantitative analysis with only one trial reporting mortality.

Conclusion

In GC-induced hyperglycemia, tight glucose control has a moderate effect on mean glucose levels with no apparent harmful effect regarding hypoglycemia. There is insufficient data whether insulin treatment improves clinical outcomes, and data on non-insulin based treatment regimens are currently too sparse to draw any conclusions.

Systematic review registration

Registered as CRD42020147409 at PROSPERO (https://www.crd.york.ac.uk/prospero/) on April 28, 2020
The implication of cryptocurrency volatility on five largest African financial system stability
Authors: Joseph Tonuchi E. , Jahanger Atif , Onwe Joshua Chukwuma , Balsalobre-Lorente Daniel
Published: January 2024

This study examined the interconnectedness and volatility correlation between cryptocurrency and traditional financial markets in the five largest African countries, addressing concerns about potential spillover effects, especially the high volatility and lack of regulation in the cryptocurrency market. The study employed both diagonal BEKK-GARCH and DCC-GARCH to analyze the existence of spillover effects and correlation between both markets. A daily time series dataset from January 1, 2017, to December 31, 2021, was employed to analyze the contagion effect. Our findings reveal a significant spillover effect from cryptocurrency to the African traditional financial market; however, the percentage spillover effect is still low but growing. Specifically, evidence is insufficient to suggest a spillover effect from cryptocurrency to Egypt and Morocco’s financial markets, at least in the short run. Evidence in South Africa, Nigeria, and Kenya indicates a moderate but growing spillover effect from cryptocurrency to the financial market. Similarly, we found no evidence of a spillover effect from the African financial market to the cryptocurrency market. The conditional correlation result from the DCC-GARCH revealed a positive low to moderate correlation between cryptocurrency volatility and the African financial market. Specifically, the DCC-GARCH revealed a greater integration in both markets, especially in the long run. The findings have policy implications for financial regulators concerning the dynamics of both markets and for investors interested in portfolio diversification within the two markets.
Researcher and patient experiences of co-presenting research to people living with systemic sclerosis at a patient conference: content analysis of interviews
Authors: Wurz Amanda , Ellis Kelsey , Nordlund Julia , Carrier Marie-Eve , Cook Vanessa , Gietzen Amy , Adams Claire , Nassar Elsa-Lynn , Rice Danielle B. , Fortune Catherine , Guillot Genevieve , Mieszczak Tracy , Richard Michelle , Sauve Maureen , Thombs Brett D.
Published: January 2024

Background

Patient engagement in research is important to ensure research questions address problems important to patients, that research is designed in a way that can effectively answer those questions, and that findings are applicable, relevant, and credible. Yet, patients are rarely involved in the dissemination stage of research. This study explored one way to engage patients in dissemination, through co-presenting research.

Methods

Semi-structured, one-on-one, audio-recorded interviews were conducted with researchers and patients who co-presented research at one patient conference (the 2022 Canadian National Scleroderma Conference) in Canada. A pragmatic orientation was adopted, and following verbatim transcription, data were analyzed using conventional content analysis.

Results

Of 8 researchers who were paired with 7 patients, 5 researchers (mean age = 28 years, SD = 3.6 years) and 5 patients (mean age = 45 years, SD = 14.2 years) participated. Researcher and patient perspectives about their experiences co-presenting and how to improve the experience were captured across 4 main categories: (1) Reasons for accepting the invitation to co-present; (2) Degree that co-presenting expectations were met; (3) The process of co-presenting; and (4) Lessons learned: recommendations for co-presenting.

Conclusions

Findings from this study suggest that the co-presenting experience was a rewarding and enjoyable way to tailor research dissemination to patients. We identified a patient-centred approach and meaningful and prolonged patient engagement as essential elements underlying co-presenting success.
A human rights-based approach for effective criminal justice response to human trafficking
Authors: Demeke Saba
Published: January 2024

Human trafficking is a complex, multifaceted, and deeply layered issue. Consequently, any mitigation strategy employed against it must also be layered and target the distinct aspects of the issue. For long, the obvious and perhaps the most visible practice to deal with cases of trafficking has been employing a criminal justice approach where the focus largely lies on the persecution of the criminal instead of the protection of the survivors. More nuanced approaches, such as anti-trafficking clauses that protect human rights and focus on removing root causes that directly or indirectly have an impact on trafficking patterns, including labor, migration, and sexual exploitation issues, have emerged to successfully tackle human trafficking as a global issue. The principles and guidelines for such a multi-sectoral, human rights-based approach are primarily aimed at trafficking prevention, protection, assistance to survivors of trafficking, criminalization, punishment, and redressal. This article aims to evaluate this approach and its intersections with the traditional criminal justice approach. It will further discuss the approach that is currently in practice and argue for further improvements and efforts. Finally, it will also discuss the impact of COVID-19 on trafficking in persons.
Safety and feasibility study of a novel robotic system in an in vivo porcine vascular model
Authors: Moschovaki-Zeiger Ornella , Arkoudis Nikolaos-Achilleas , Spiliopoulos Stavros
Published: January 2024

Purpose

The goal of this preclinical study is to assess the functionality, technical feasibility, and safety of a new vascular robotic LIBERTYR3 System, in the microcatheterization of vascular targets using a range of guidewires and microcatheters.

Material and methods

An anesthetized pig served as an arterial model for the robotic device (LIBERTYR3; Microbot Medical Ltd, Yoqneam, IL). The primary efficacy endpoint was the evaluation of its capability to selectively catheterize predetermined distal arterial branches in the liver, kidneys, and mesenteric arteries (technical success), under fluoroscopy guidance. The primary safety endpoint was the occurrence of angiographic acute catheterization-related complications (dissection, thrombosis, embolism, perforation). The catheterizations were conducted by two interventional radiologists that present different work experience in endovascular procedures (18 and 2 years respectively), using a variety of microcatheters and wires. Various procedural parameters such as functionality, practicality, ease of use, and time required for selective catheterization, were evaluated, and recorded.

Results

All pre-determined arteries were successfully selectively catheterized (100% technical success), by both operators. No angiographic acute complications occurred. The microcatheters and wires were manipulated using the remote portable console in an effortless manner that maintained a high level of accuracy. Mean time for selective catheterization was 131 ± 82 s. The robot's conversion function to manual operation was successfully demonstrated.

Conclusion

Robotic navigation and catheterization of selected target arteries were accomplished without observable vascular damage, suggesting that the LIBERTYR3 robotic system is a reliable and safe tool for robotic-assisted endovascular navigation. Further experimental studies are required to evaluate safety and efficacy prior to introduction into clinical practice.
Emerging biomarkers and potential therapeutics of the BCL-2 protein family: the apoptotic and anti-apoptotic context
Authors: Saddam Md. , Paul Shamrat Kumar , Habib Mohammad Ahsan , Fahim Md. Abrar , Mimi Afsana , Islam Saiful , Paul Bristi , Helal Md Mostofa Uddin
Published: January 2024

Apoptosis, also known as the programmed death of cells, is responsible for maintaining the homeostasis of tissues, and this function is carried out by caspases. The process of apoptosis is carried out via two distinct pathways: the extrinsic pathway, which is governed by death receptors, and the intrinsic pathway, also known as the mitochondrial pathway. The BCL-2 protein family encoded by the BCL-2 gene, located at the 18q21.33 chromosomal location, is in charge of regulating the intrinsic pathway, which is responsible for inducing cell death via the permeabilization of the mitochondrial membrane and the release of apoptosis-inducing components. The BCL-2 homology (BH1, BH2, BH3, BH4) domains of this family proteins are crucial for their functioning, and their common BH domains allow interactions between members of the same family and can also serve as indications of pro- or anti-apoptotic activity. A direct correlation may be shown between the overexpression of BCL-2 and the postponement of cell death. It has been determined that a change in the expression of BCL-2 is the root cause of a variety of malignancies, including lung, breast, melanoma, and chronic lymphocytic leukemia, multiple sclerosis, diabetes. In this review, we addressed the genetic information and structural homology of BCL-2 family members. Further, we elucidate the pro-apoptotic and anti-apoptotic roles of the family members. This review highlights the most recent developments in the BCL-2 protein family and presents evidence that targeting this family proteins may have a positive impact on the treatment of medical problems that are still underserved.
A case report of left circumflex stent infection and mycotic aneurysm: a rare but life-threatening complication of percutaneous coronary intervention
Authors: Kumar Swasthi S. , Suresh Sumanyu , Iliyas Mohamed , Vijay Jyothi , Pillai Vivek
Published: January 2024

Background

Coronary stent infections are an uncommon but deadly complication of percutaneous coronary intervention. Mortality remains as high as 40–60% even with adequate treatment. We report such an interesting case of left circumflex stent (LCX) infection and mycotic aneurysm that was successfully managed with antibiotics and surgery.

Case presentation

A middle-aged man who underwent percutaneous coronary intervention (PCI) to the left circumflex artery four weeks prior was referred as a case of pyrexia of unknown origin, not responding to antibiotics, and colchicine started for suspected Dressler syndrome. Although the inflammatory markers were elevated, the results of the blood culture did not show any growth. Echocardiography showed a doubtful echogenic structure in the left atrioventricular groove and mild pericardial effusion, and a stent infection was suspected. PET scan showed focal metabolic activity in the region of the LCX stent, with metabolically active supraclavicular and paratracheal lymph nodes, and a coronary angiogram revealed an aneurysm arising distal to the stented LCX. A diagnosis of stent infection and associated mycotic aneurysm was made, and the patient underwent surgery which included aneurysm repair, stent retrieval, and coronary artery bypass graft (CABG) to the major and terminal OM. The postoperative course was uneventful, and the patient was discharged without complications.

Conclusions

It is important to investigate the possibility of coronary stent infection in individuals experiencing prolonged fever following PCI. PET scans and coronary angiograms can aid in diagnosis when echocardiograms are inconclusive. Adequate antibiotic therapy and timely surgery are crucial for successfully managing coronary stent infections.
Examining the relationship of career crafting, perceived employability, and subjective career success: the moderating role of job autonomy
Authors: Diaa Naglaa Mohamed , Abidin Ali Zain Ul , Roller Marvin
Published: January 2024

Career crafting has emerged as a significant construct in the field of career development, with the potential to significantly boost individuals’ overall work satisfaction. This study aimed to examine whether career crafting could improve individual’s subjective career success and perceived employability. Career crafting is an inevitable course of career-related actions to achieve career satisfaction. Based on proactive behavior theory, it is hypothesized that career crafting would have an impact on individuals’ subjective career success and perceived employability through the moderating role of job autonomy. Using cross-sectional study design, data were collected via Google Forms survey from 224 employees working in various fields in Pakistan and data were analyzed using structural equation modeling (SEM) via AMOS. The results indicate that career crafting has a significant positive relationship with subjective career success and perceived employability. Furthermore, job autonomy also has significant positive relationship with subjective career success and perceived employability. However, the moderation of job autonomy was not supported. This study provides robust insights to career practitioners, academicians, and individuals. Overall, the study expands the literature of the novel notion of career crafting and career outcomes; additionally, the study advocates organizations to include career crafting in HR policies and helping them to enhance the well-being of employees in their career development.
Robust joint adaptive multiparameter waveform inversion with attenuation compensation in viscoacoustic media
Authors: Li Chao , Liu Guochang , Li Fang , Wang Zhiyong
Published: January 2024

Full-waveform inversion (FWI) has been proven as an effective method to estimate subsurface parameters by iteratively reducing the data residual between the predictions and the observations. Nevertheless, FWI is greatly dependent on the initial model, and a poor initial model will lead to an incorrect solution. Furthermore, owing to the anelasticity of the earth, seismic waves will attenuate during propagation, which results in an attenuated gradient and makes the convergence rate of FWI even worse in viscoacoustic medium. Commonly, multiparameter (e.g. velocity and Q) waveform inversion can be used to mitigate these problems. Benefiting from the theory of Q-compensated wavefield propagation, we develop a Q-compensated joint multiparameter waveform inversion method to weaken the nonlinearity of the FWI objective function, which enables it to cope with challenges related with attenuation-induced gradient energy loss and cycle skipping simultaneously. We refer to our Q-compensated joint multiparameter FWI scheme as QJMFWI. The main contributions of QJMFWI are as follows: (1) given the difficulty associated with the estimation of velocity and Q simultaneously in viscoacoustic media, QJMFWI provides a straightforward waveform inversion method for velocity and Q model construction, by which we can obtain velocity and Q information with improved accuracy and resolution; and (2) compared with conventional FWI methods, QJMFWI relaxes the requirement for a good initial velocity and Q model, which can avoid trapping into local minima. Numerical and field data examples demonstrate that QJMFWI is an effective method to invert for accurate subsurface parameters in viscoacoustic media.
Remission of Ectopic Cushing Syndrome Secondary to Medullary Thyroid Cancer With Vandetanib and Selpercatinib
Authors: Jazdarehee Aria , Abdel-Rahman Omar , Jacquier Jennifer E
Published: January 2024

Medullary thyroid cancer (MTC) is a neuroendocrine tumor associated with activating mutations of the rearranged during transfection (RET) proto-oncogene. These tumors may rarely secrete adrenocorticotropin or corticotropin-releasing hormone, resulting in a paraneoplastic ectopic Cushing syndrome (ECS). Paraneoplastic ECS carries a high risk of mortality, and management is difficult due to the lack of response to antiadrenal therapies. We report on a 37-year-old man who was diagnosed with metastatic MTC and reported symptoms of cortisol excess with laboratory testing in keeping with ECS. He began treatment with vandetanib, a multitargeted tyrosine kinase inhibitor, which resulted in decreased tumor burden as well as clinical and biochemical resolution of ECS. Due to progressive structural disease 10 months later, he was switched to the selective RET inhibitor selpercatinib, which was followed by a rapid reduction of cortisol nearing the threshold of adrenal insufficiency. Tumor markers were also improved, and repeat imaging showed decreased tumor burden. Our case highlights the efficacy of tyrosine kinase inhibitors in the management of paraneoplastic ECS. Selective RET inhibitors may emerge as preferred targeted treatment options due to better efficacy and toxicity profiles compared to multitargeted inhibitors. Clinicians should monitor for adrenal insufficiency with the use of selective RET inhibitors.
A Case of an Ectopic ACTH-Producing Tumor With Adrenal Shrinkage During Osilodrostat Administration
Authors: Sawabe Fumikazu , Hayafusa Ryo , Kosugi Rieko , Ariyasu Hiroyuki
Published: January 2024

Ectopic adrenocorticotropin (ACTH)-secreting tumors are among the causes of ACTH-dependent Cushing syndrome. When surgical resection of the primary lesion is not feasible, medications such as metyrapone, mitotane, and ketoconazole have been used to control hypercortisolism. This report presents a case treated with the novel drug osilodrostat, wherein the patient's adrenal glands exhibited shrinkage following the initiation of this drug. The case involves a 68-year-old man diagnosed with small cell lung cancer and ectopic ACTH-producing Cushing syndrome. Initially, metyrapone was administered to manage hypercortisolism, but its effect proved insufficient. Subsequently, osilodrostat was initiated while gradually decreasing metyrapone, leading to full suppression of blood cortisol levels. With continued osilodrostat treatment, the adrenal glands reduced in size, suggesting the potential to reduce the osilodrostat dosage.
Understanding of Eosinophilic Esophagitis in Children - A Comprehensive Study on Epidemiology, Clinical Manifestations, Diagnosis and Innovative Treatment Modalities
Authors: Zarzycka Marta , Sikora Marcelina , Plewniok Ines , Maj-Dziedzic Monika , Dubiel Jeremiasz , Brzozowska Anna , Maj Adrian , Śmietana Greta , Warno Martyna , Kozik Wiktor
Published: January 2024

Introduction:

In the late 1960s, probable cases of eosinophilic esophagitis (EoE) emerged, initially linked to esophageal rings and congenital causes or gastroesophageal reflux disease (GERD). Doubts about the GERD association arose due to poor responses to antisecretory therapy. EoE is now a significant pediatric health concern, impacting 1 to 7 cases per 10,000 children.

Purpose of the Study:

This study aims to comprehensively explore EoE's epidemiology, etiology, subtypes, clinical manifestations, diagnostic methods, and treatment modalities.

Materials and Methods:

The study employs a cross-sectional analysis of pediatric EoE patients, utilizing endoscopic evaluation and histological assessment. Three distinct EoE subtypes are identified based on pathogenic characteristics. Clinical manifestations, diagnostic methods, and treatments, including endoscopy, are examined.

Results:

Clinical manifestations span a broad spectrum in the pediatric population. Diagnostic methods include endoscopy, esophageal manometry, impedance-pH monitoring, capsule endoscopy, and string tests. Three distinct EoE subtypes are identified with unique characteristics. Treatment modalities involve dietary management, proton pump inhibitors, topical corticosteroids, biologic therapies, allergen immunotherapy, and endoscopic interventions.

Conclusion:

Formerly associated with GERD, EoE is now a significant pediatric health concern. The study underscores the importance of comprehensive diagnostic approaches and diverse treatment modalities, including promising biologic therapies and allergen immunotherapy. Understanding these aspects is crucial for effective management and improved outcomes in patients.
We need to talk about dialysis away from base
Authors: Palmer Nick
Published: January 2024

Nick Palmer discusses the importance of dialysis access on holiday for kidney care patients
British Transplantation Society/UKKA guidance on shingles vaccination
Authors: Nimmo Ailish , Mallindine Charlotte , Morlidge Clare , Ravanan Rommel
Published: January 2024

This article outlines the importance of the UK shingles vaccination programme and who is elgible for the vaccine
Ketogenic diets for polycystic kidney disease
Authors: Ellis Peter
Published: January 2024

This article outlines the potential benefits of ketogenic diets for people with polycystic kidney disease