bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Ambient Air Mercury Levels in The Mercury Laboratory and Metrology Centre for Environmental Quality Instrumentation Standardization
Authors: Nurjaya  , Ardiansyah W , Syofyan Y
Published: June 2023

Today the use of heavy metals can be found in almost all aspects of life. However, the use of heavy metals causes a process of bioaccumulation of toxins from heavy metals into the body. One type of heavy metal that is very toxic is Mercury (Hg). According to the list of hazardous substances published by the Agency for Toxic Substances and Disease Registry (ATSDR), mercury occupies the third position among 275 substances harmful to human health. The mercury and metrology laboratory is a laboratory that functions to test mercury levels in both water, soil and air matrix samples. In carrying out a test or measurement of Mercury levels, employees at the Mercury and Metrology Laboratory of Centre for Environmental Quality Instrumentation Standardization (PSIKLH) always use Mercury in the process, so there is a possibility that the air in the Mercury and Metrology laboratory of PSIKLH is contaminated with Mercury because of the activities in it. That is the reason of researchers to test mercury levels in the ambient air around the Mercury laboratory and Metrology PSIKLH. This study aims to determine the level of mercury in the ambient air around the mercury and metrology laboratory of PSIKLH. The method used in this study is a quantitative analysis method using the Mercury Analyzer WA-5F from Nippon Instruments Corporation (NIC) which includes curve making, sampling, and measuring mercury levels in the sample. This research was conducted at the Mercury and Metrology Laboratory of PSIKLH. Based on research that was conduct, it shows that the highest concentration of mercury in the ambient air around the PSIKLH Mercury and Metrology Laboratory is found in the Atomic Absorption Spectrophotometer (AAS) room, the sampling equipment room, and the Hg tool room. Mercury levels contained in the three rooms were more than 0.01 mg/m3. However, mercury levels in the Mercury and Metrology Laboratory are still classified as normal because they have not passed the threshold of 0.05 mg/m3.
Factor and Barrier Implementing Building Information Modelling (BIM) in Green Construction in Indonesia
Authors: Susanti Riza , Fauziyah Shifa , Aziz Sheva Alviano
Published: June 2023

Building Information Modelling (BIM) is a technology that potential to increase effectiveness and productivity in projects. Implementing BIM in the project not only can simultaneously represent the physical modelling of a building but also can reduce waste and optimize time and resources as the aims of green construction. Nevertheless, unfortunately the level of BIM adoption in Indonesia is lower than other developing countries. The aim of this research is to analyse factors and barriers to implementing BIM to support green construction in Indonesia. This study uses a quantitative research method in a questionnaire survey of 20 construction projects in Indonesia to determine the factors driving BIM adoption and barrier to BIM adoption on construction projects in Indonesia. The result finds five factors driving the implementation of BIM in Indonesia i.e requirements from the government, BIM is believed to improve performance, BIM is believed better than existing method, technology and resources readiness, and support from top management. Despite the driving factors, the implementation of BIM also has barriers i.e lack of information, lack of BIM training for workers, reluctance to change, lack of owner requirement, and high the initial cost.
Analysis of the effect of motorcycle parking attendants on parking space unit Case Study : Poncol Station and Tawang Station
Authors: Narendra A , Widyadi M I
Published: June 2023

The movement or activities that take place in an area will undoubtedly be impacted by how developed it is. The city of Semarang experiences the same thing. With such high mobility, transportation modalities and related services are necessary. In Semarang City, there are two train stations: Tawang Station and Poncol Station. The purpose of this study is to measure the effect of motorcycle parking attendants on station parking spaces. The measurement is based on descriptive statistics on parking space unit’s width. Tawang Station has parking attendants, and Poncol Station does not. A primary survey was conducted at the Poncol and Tawang station. The survey calculating the number of active cars and the area utilised during peak, early, and late hours. Google Maps were used to predict peak hour. The presence of parking attendants shows 120% more effective than without parking attendants. Moreover on averagethe width, and degree of saturation are 106% and 110% respectively better than standard.
Adaptive Cruise Control tuned by Genetic Algorithm for Safe Distance of Automated Vehicle
Authors: Prastiyanto D , Apriaskar E , Ibrahim R F , Rumanda A , Manaf A A , Amelia I
Published: June 2023

The importance of safety in transportation has forced developments in automated vehicles. Many control methods have been introduced to ensure safe distance between automated vehicle and another car. This article presents an adaptive cruise control whose parameters are tuned by genetic algorithm for the case study of safe distance in automated vehicle. Two genetic algorithms with two different objective functions, i.e., integral square error (ISE) and integral absolute error (IAE), were evaluated. The results show that genetic algorithms could work well using both functions indicated by the obtained best fitness values through generations. The optimal controller parameter obtained by them also seems to be similar each other, including the distance, velocity and acceleration response of the automated vehicle. It is only the standard deviation that differs them. After 20 running tests, IAE produced 0.0288, 0.0439, and 0.0134 in standard deviation for verr_gain, xerr_gain, vx_gain, respectively, while ISE got 0.0169, 0.0755, and 0.0101. From the total values of standard deviation, we can conclude that GA with IAE performs slightly better since it has smaller value indicating that it has better repeatability.
Evaluation of Soil Liquefaction Using SPT Data at Boyolali Regency, Central Java
Authors: Askaviolita  , Ismanti Sito , Fathani Teuku Faisal
Published: June 2023

On 27 May 2006 at 05:54 local time, a major earthquake with a moment magnitude (Mw) of 6.3 occurred in Yogyakarta Province. This earthquake was widespread causing several damages in Yogyakarta Province and Central Java Province. One of the regencies in Central Java Province impacted was Boyolali Regency. This research aims to evaluate soil liquefaction based on the Standard Penetration Tests (SPT) in Boyolali Regency. Evaluation of soil liquefaction was necessary to minimize the damage as a preliminary in determining mitigation methods that can be applied. Besides Mw 6.3 earthquakes, according to SPT Data, several factors that triggered liquefaction were found in this study area such as a shallow groundwater table and the existence of a poorly graded sandy soil layer. The liquefaction was evaluated by comparing the Liquefaction Severity Index (LSI) and the Liquefaction Risk Index (LRI) using the simplified method. Based on the analysis, the result showed that Boyolali Regency had a value of LSI in the range of very low until low severity and a value of LRI in the range of low until the high risk.
Identifying Growth Pattern as Regional Classification in Central Java and Yogyakarta
Authors: Rahadini A
Published: June 2023

This study is the preliminary research of spatial inequality in Central Java. The regional differences are substantively irrepressible. The perception of north-south regions of Java exists and persist. As many of north regions have specialized in non-agriculture, the northern had been assumed as dynamic regions. This assumption has led to the differentiation of regional policy focused on north-south unbalance development. This study aims to evaluate the spatial pattern of Central Java and Yogyakarta based on economic growth from 1990-2010. The pattern indicates the relation of urban and its surrounding and no longer the contest of north and south region. Some current facts define that spread effects from the prime regions is beneficial for its surroundings. In this study, Semarang, Solo, and Yogyakarta, has been identified as the predominant cities toward their surroundings creating a cluster of growth pattern. The nearby surroundings obtain economic growth spill-over from those cities. On the other side, the regions locate away from prime cities have experienced lower growth. Consequently, the spatial inequality may occur across the regions.
Effects of Eudrilus eugeniae Worms and Cow Manure on the Vermicompost Process of Household Organic Waste
Authors: Pradnya I N , Am A I , Pradani H R
Published: June 2023

High population growth in developing countries also increases the amount of waste. Indonesia produces large amount of household solid waste production, namely 2.5 kg per day. Vermicompost is the best alternatives, the cheapest and does not harm the environment. In this study, the vermicompost method was used, worm weight and ratio affected the N, P, and K content in the fertilizer. The results of the sample test, namely the vermicompost time variable, the highest content was obtained at week 7 with N of 0.45%; P of 0.25%; and K by 0.23%. In the variable weight of worms, the highest weight of 300 grams of worms with N of 0.41%; P of 0.34%; and K by 0.23%; and the last variable is the ratio of cow dung and vegetable waste, where the highest content is at a ratio of 1:3 with N of 0.42%; P of 0.27%, and K of 0.22%. The test in this study was taken with 2 samples of the same variable and 1 different variable to determine the effect of these different variables on the N, P, and K content of liquid compost. Then the samples were tested for content using the macro-Kjedahl method to determine the nitrogen content, UV/Vis spectrophotometry to determine the phosphorus content, and AAS to determine the total potassium content.
Physical activity and injurious falls in older Australian women: adjusted associations and modification by physical function limitation and frailty in the Australian Longitudinal Study on Women’s Health
Authors: Kwok Wing S , Dolja-Gore Xenia , Khalatbari-Soltani Saman , Byles Julie , Oliveira Juliana S , Pinheiro Marina B , Naganathan Vasi , Tiedemann Anne , Sherrington Catherine
Published: June 2023

Objectives

To investigate associations between leisure-time physical activity (LPA) and injurious falls in older women and explore modification of associations by physical function and frailty.

Methods

Women born during 1946–51 from the Australian Longitudinal Study on Women’s Health, injurious falls (self-reported fall with injury and/or medical attention) and self-reported weekly LPA (duration and type). We undertook cross-sectional and prospective analyses using data from 2016 [n = 8,171, mean (SD) age 68 (1)] and 2019 surveys (n = 7,057). Associations were quantified using directed acyclic graph-informed logistic regression and effect modification examined using product terms.

Results

Participation in LPA as recommended by World Health Organization (150–300 min/week) was associated with lower odds of injurious falls in cross-sectional (adjusted Odds Ratio (OR) 0.74, 95% CI 0.61–0.90) and prospective analyses (OR 0.75, 95% CI 0.60–0.94). Compared with those who reported no LPA, cross-sectionally, odds of injurious falls were lower in those who reported brisk walking (OR 0.77, 95% CI 0.67–0.89) and vigorous LPA (OR 0.86, 95% CI 0.75–1.00). No significant association was found between different types of LPA and injurious falls prospectively. Only cross-sectionally, physical function limitation and frailty modified the association between LPA and injurious falls, with tendencies for more injurious falls with more activity in those with physical limitation or frailty, and fewer injurious falls with more activity among those without physical function limitation or frailty.

Conclusion

Participation in recommended levels of LPA was associated with lower odds of injurious falls. Caution is required when promoting general physical activity among people with physical limitation or frailty.
Gemini: memory-efficient integration of hundreds of gene networks with high-order pooling
Authors: Woicik Addie , Zhang Mingxin , Xu Hanwen , Mostafavi Sara , Wang Sheng
Published: June 2023

Motivation

The exponential growth of genomic sequencing data has created ever-expanding repositories of gene networks. Unsupervised network integration methods are critical to learn informative representations for each gene, which are later used as features for downstream applications. However, these network integration methods must be scalable to account for the increasing number of networks and robust to an uneven distribution of network types within hundreds of gene networks.

Results

To address these needs, we present Gemini, a novel network integration method that uses memory-efficient high-order pooling to represent and weight each network according to its uniqueness. Gemini then mitigates the uneven network distribution through mixing up existing networks to create many new networks. We find that Gemini leads to more than a 10% improvement in F1 score, 15% improvement in micro-AUPRC, and 63% improvement in macro-AUPRC for human protein function prediction by integrating hundreds of networks from BioGRID, and that Gemini’s performance significantly improves when more networks are added to the input network collection, while Mashup and BIONIC embeddings’ performance deteriorates. Gemini thereby enables memory-efficient and informative network integration for large gene networks and can be used to massively integrate and analyze networks in other domains.

Availability and implementation

Gemini can be accessed at: https://github.com/MinxZ/Gemini.
Genome-wide scans for selective sweeps using convolutional neural networks
Authors: Zhao Hanqing , Souilljee Matthijs , Pavlidis Pavlos , Alachiotis Nikolaos
Published: June 2023

Motivation

Recent methods for selective sweep detection cast the problem as a classification task and use summary statistics as features to capture region characteristics that are indicative of a selective sweep, thereby being sensitive to confounding factors. Furthermore, they are not designed to perform whole-genome scans or to estimate the extent of the genomic region that was affected by positive selection; both are required for identifying candidate genes and the time and strength of selection.

Results

We present ASDEC (https://github.com/pephco/ASDEC), a neural-network-based framework that can scan whole genomes for selective sweeps. ASDEC achieves similar classification performance to other convolutional neural network-based classifiers that rely on summary statistics, but it is trained 10× faster and classifies genomic regions 5× faster by inferring region characteristics from the raw sequence data directly. Deploying ASDEC for genomic scans achieved up to 15.2× higher sensitivity, 19.4× higher success rates, and 4× higher detection accuracy than state-of-the-art methods. We used ASDEC to scan human chromosome 1 of the Yoruba population (1000Genomes project), identifying nine known candidate genes.
Sperm induce macrophage extracellular trap formation via phagocytosis-dependent mechanism
Authors: Lu Chuncheng , Wu Zhao , Gao Hongbin , Li Haiyuan , Deng Renbin , Luo Ning , Fan Shipeng , Li Xi , He Danpeng , Zhao Hui
Published: June 2023

Infertility is a public health concern worldwide. Asthenozoospermia is a common cause of male infertility and is characterized by decreased motility. Sperm motility ensures that sperm migrate to complete fertilization. Macrophages are an essential component of innate immunity in the female reproductive tract. Macrophage extracellular traps are induced by various microorganisms to capture and mediate the clearance of microorganisms. The relationship between sperm and macrophage extracellular traps is unclear. The human monocyte leukemia (THP-1) cells differentiated by phorbol myristate acetate (PMA) are widely used as surrogate of human macrophages. This study investigated sperm-induced macrophage extracellular trap formation and clarified some of the mechanisms affecting macrophage extracellular trap production. Sperm-induced macrophage extracellular traps were visualized and components of macrophage extracellular traps were identified by immunofluorescence analyses and scanning electron microscopy. By inhibiting macrophage extracellular trap production and macrophage phagocytosis, the relationship between macrophage phagocytosis and macrophage extracellular trap production was analyzed. Sperm could trigger PMA-differentiated THP-1 macrophages to produce extracellular traps. Sperm-triggered macrophage extracellular traps are dependent on phagocytosis and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Sperm from asthenozoospermia donors are more likely to be phagocytosed by macrophages than sperm from healthy donors, which induce more macrophage extracellular trap release. These data confirm the phenomenon and partial mechanism of sperm-induced macrophage extracellular trap formation in vitro. These may partly provide evidence to explain the mechanisms of clearing abnormally morphological or hypomotile sperm in the female reproductive tract and the rationale for the decreased probability of successful fertilization in asthenozoospermia.
Healthcare experiences among patients with hidradenitis suppurativa: a qualitative study
Authors: Sow Yacine , Salame Nicole , Siira Meron R , Flowers Nyla , Garg Amit , Patzer Rachel E , Kavalieratos Dio , Curseen Kimberly A , Chen Suephy C , Orenstein Lauren A V
Published: June 2023

In this qualitative study, 21 adults living with hidradenitis suppurativa (HS) were interviewed about their healthcare experiences. Participants detailed how delay in diagnosis, lack of provider knowledge, inadequate pain management, poor access to care and stigmatization negatively affected their interactions with the healthcare system. Improving disease knowledge among providers, proactively addressing HS-related pain and coordinating access to multidisciplinary care may improve healthcare experiences among individuals living with HS.
O027 Less is more: extensive cardiac investigations add little value in waitlisting patients for kidney transplantation
Authors: Chow BJ , Khurram MA , Capuano E , Pugliese F , Yaqoob MM , Mohamed IH
Published: June 2023

Introduction

The utility and reliability of extensive cardiac investigations to aid waitlisting for kidney transplantation has been debated. This study assessed the prognostic power of coronary artery calcium scoring (CACS) using computed tomography coronary angiogram (CTCA) and myocardial perfusion scintigraphy (MPS) in predicting major adverse cardiac events (MACE).

Methods

We conducted a retrospective study of all ESRD patients considered for kidney transplantation and referred for MPS and/or CTCA for CACS between October 2012 to March 2014 and assessed MACE occurrences (heart failure, cardiac arrest, myocardial infarction, angina, CVA, PVD and transient ischaemic attack) over a 9-year follow-up period.

Results

Among 131 patients in our study, 91.6% had a MPS (76.7% Negative MPS result, 23.3% Positive MPS) and 92.4% had a CTCA (75.2% CACS <400 (Low Score), 24.8% CACS>400 (High Score)). Sensitivity, specificity, positive and negative predictive values were poor for CTCA (38.8%, 84.7%, 63.3%, 67.0%) and MPS (34.8%, 82.4%, 55.2%, 67.0%). There was no statistical significance in MACE when stratified by CACS and MPS in transplanted patients (log-rank p=0.155); statistical significance observed when stratified by transplant status in all patients (p=<0.0001). No statistical difference in MACE observed when stratified by MPS (p=0.749) or CACS (p=0.706) in non-transplanted patients.

Conclusion

This challenges the value of extensive cardiac assessments (MPS, CTCA) in predicting MACE. Candidates conventionally considered low-risk by these methods had similar risk of MACE when transplanted against higher-risk groups. Transplantation confers an advantage in MACE-free years. Such tests are best used for risk stratification and counselling for shared decision-making.

Take-home message

Extensive cardiac investigations such as MPS and CTCA are poor predictors of MACE in end-stage renal disease patients. These tests should not be used as key determinants in waitlisting patients for kidney transplantation.
O048 Levosimendin use in high-risk cardiac patients - is it about timing?
Authors: Peacock T , Anderson B
Published: June 2023

Introduction

Use of levosimendan pre-operatively has had mixed outcomes for cardiac patients with low ventricular ejection fraction (EF). Whilst studies have examined the effects of immediate preoperative and intraoperative administration, outcomes of administration one week prior to surgical intervention have not been evaluated. The aims of this study were to compare cardiac parameters pre and post administration of levosimendan one week prior to surgery.

Method

A retrospective analysis was conducted of high-risk patients undergoing cardiac surgery. Patients with an EF of <50% were included. Baseline EF, pulmonary artery pressures (PAP), cardiac output (CO) and cardiac index (CI) were measured utilising transthoracic echocardiogram. A weight-based dose of levosimendan was administered one week prior to intervention. Measures were repeated pre-operatively, one week after administration of levosimendan (0.2mg/Kg).

Results

A total of 100 patients were included in this study. The mean time from dose of levosimendan to operative time was 11 days. Mean EF, systolic PAP, mean PAP, CO, and CI were 43.63%, 48.71mmHg, 29.97mmHg, 4.84L/min, and 2.47L/min/m2 respectively. Each parameter showed significant improvement one week post levosimendan; 48.42% (p=0.011, SE 4.7, 1.8–1.2 95% CI), 35.06mmHg (p= <0.001, SE 13.65, 11.2–16.0 95% CI), 21.58mmHg (p= <0.001, SE 8.4, 6.6–10.1 95% CI), 5.64L/min (p= <0.001, SE 0.8, 0.6 to 1 95% CI), and 2.88L/min/m2 (p<0.001, SE 0.4, 0.3–0.5 95% CI) respectively. Overall, 30-day mortality was 3% (n=3), compared to an expected mortality of 5.02%.

Take-home message

Levosimendan shows promise in improving pre-operative cardiac function when given one week prior to intervention in high-risk cardiac patients.
EP-601 Biodegradable stents for benign oesophageal strictures- a single centre experience
Authors: Obuobi Reece-Bolton , Viswanath Yirupaiahgari
Published: June 2023

Biodegradable (BD) stents have been used for the management of various oesophageal strictures (ES). The present study aim to evaluate our experience and efficacy of BD stents in benign ES at the endoscopic unit at the James Cook University Hospital, Middlesbrough, UK.

Methods

A retrospective review of case notes of 9 patients who have undergone endoscopically placement of BD stent for benign ES between March 2010 and November 2020. All 9 patients underwent successful stent placement. None of the patients had previous surgery for their condition. All patients, prior to stenting had oesophageal dilatations, some multiple times.

Results

Stent placement was successful in all 9 patients. Some patients had stent migration and subsequent re stenting. All patients had benign ES as the cause of dysphagia. One patient had caustic oesophageal stricture, remaining eight had peptic ulceration and GORD as the cause of dysphagia. The median number of dilatations prior to stent placement was 4 (IQR 7), more than the median number of dilatations post stent placement which was 2.0 (IQR: 3.5).

Conclusion

BD stents offers prolonged dilatation-free interval and reduces the number dilatations in patients with benign oesophageal strictures.
1023 Utilisation of Plastic Surgery Theatres During the Covid-19 Pandemic at a Teaching Hospital
Authors: Murtaza A , Sarwar U
Published: June 2023

Aim

Method

Results

Conclusions
251 Use of Harmonic Focus Shears in Plastic Surgery Literature Review and Future Recommendations
Authors: Bahadori D , Eiben I , Eiben P , Never PL
Published: June 2023

Introduction

Harmonic Focus Shears (HFS) (Ethicon Endo-Surgery, USA) is an ultrasonic device specifically designed through its curved clips and hand activated trigger system to be precise and minimise the impact on tissues. Initially designed for head and neck dissection and proved to be effective without increasing risk of complications in thyroidectomy procedure it is surprisingly rarely mentioned in the field of plastic surgery.

We performed a literature search to established current uses of ultrasonic devices in plastic surgery and determine its effectiveness, and future uses.

Method

Literature search was performed in accordance with guidelines for Preferred Reporting Items for Systemic Reviews and Metanalysis.

Discussion

Use of ultrasonic devices as harmonic prove to be a useful tool in precise large tissue dissection surgery including pedicled flap and free flap dissection. Described benefits embrace upgraded operative time, blood loss, tissue discharge and morbidity.

Initially described to be superior to traditional electrocauthery in facelift procedure, ultrasonic devices then evolved to be advantageous when considering outcomes in breast reduction surgery, implant-based breast reconstruction and capsulectomy.

HFS as a novel and improved ultrasonic device allows for focused forceps dissection, haemostasis and tissue coagulation without the need to swap instruments that is safe to the surrounding tissues. Learning curve is expected, and pitfalls include additional staff training, multiple wire device setup, single use and possible overheating. On balance however improved timings and therefore operative efficiency, low risks of complications and optimal patient outcomes make this method of tissue handling a favourable tool to introduce to common plastic surgical practice.
Outcomes of Bariatric Surgery in People With Human Immunodeficiency Virus: A Retrospective Analysis From the ATHENA Cohort
Authors: Zino Leena , Wit Ferdinand , Rokx Casper , den Hollander Jan G , van der Valk Mark , Richel Olivier , Burger David M , Colbers Angela
Published: June 2023

Background

The implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) are unknown.

Methods

Here, we report a retrospective analysis up to 18 months post-BS in PWH from the AIDS Therapy evaluation in The Netherlands (ATHENA) cohort with data from all dutch HIV treating Centers. Primary end points were a confirmed virologic failure (2 consecutive HIV-RNA measurements >200 copies/mL) and the percentage of patients who achieved >20% total body weight loss up to 18 months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS.

Results

Fifty-one patients were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18 months post-BS. Eighty-five percent of patients achieved >20% total body weight loss at 18 months post-BS, with a mean difference from baseline (95% confidence interval) of −33.5% (−37.7% to −29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except for 1 sample of darunavir. Lipid profiles, but not serum creatinine and blood pressure, improved significantly (P < .01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 and from 62 to 25, respectively, at 18 months post-BS.

Conclusions

BS was an effective intervention for weight loss and lipid control in PWH using ART in this cohort with no clear link to poor virologic outcomes.
RYR2-ryanodinopathies: from calcium overload to calcium deficiency
Authors: Steinberg Christian , Roston Thomas M , van der Werf Christian , Sanatani Shubhayan , Chen S R Wayne , Wilde Arthur A M , Krahn Andrew D
Published: June 2023

The sarcoplasmatic reticulum (SR) cardiac ryanodine receptor/calcium release channel RyR2 is an essential regulator of cardiac excitation–contraction coupling and intracellular calcium homeostasis. Mutations of the RYR2 are the cause of rare, potentially lethal inherited arrhythmia disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) was first described more than 20 years ago and is the most common and most extensively studied cardiac ryanodinopathy. Over time, other distinct inherited arrhythmia syndromes have been related to abnormal RyR2 function. In addition to CPVT, there are at least two other distinct RYR2-ryanodinopathies that differ mechanistically and phenotypically from CPVT: RYR2 exon-3 deletion syndrome and the recently identified calcium release deficiency syndrome (CRDS). The pathophysiology of the different cardiac ryanodinopathies is characterized by complex mechanisms resulting in excessive spontaneous SR calcium release or SR calcium release deficiency. While the vast majority of CPVT cases are related to gain-of-function variants of the RyR2 protein, the recently identified CRDS is linked to RyR2 loss-of-function variants. The increasing number of these cardiac ‘ryanodinopathies’ reflects the complexity of RYR2-related cardiogenetic disorders and represents an ongoing challenge for clinicians.

This state-of-the-art review summarizes our contemporary understanding of RYR2-related inherited arrhythmia disorders and provides a systematic and comprehensive description of the distinct cardiac ryanodinopathies discussing clinical aspects and molecular insights. Accurate identification of the underlying type of cardiac ryanodinopathy is essential for the clinical management of affected patients and their families.
Real-Lab-Day: undergraduate scientific hands-on activity as an authentic learning opportunity in microbiology education
Authors: Moreno Ana Carolina Ramos , Pasternak Taschner Natalia , Piantola Marco Aurélio Floriano , Armellini Bárbara Rodrigues Cintra , Lellis-Santos Camilo , Ferreira Rita de Cássia Café
Published: June 2023

Traditional lab classes in microbiology are common in several educational institutions, which can provide a learning experience disconnected from the myriad of experiments performed in research laboratories. Attempting to promote an authentic learning opportunity of the functioning of a bacteriology research laboratory, we developed the “Real-Lab-Day,” a multimodal learning experience to develop competencies, abilities, critical analysis, and teamwork skills for undergraduate students. Students were divided into groups and assigned to research laboratories to be mentored by graduate students, to design and carry out scientific assays. Undergraduate students were introduced to methods such as cellular and molecular assays, flow cytometry, and fluorescence microscopy, as tools to address scientific questions about bacterial pathogenicity, bacterial resistance, and other topics. To consolidate their learning, students created and presented a poster in a rotational panel of peer learning. The perceived learning and interest in microbiology research were improved by the Real-Lab-Day experience, and >95% of the students approved the Real-Lab-Day as a teaching tool in microbiology. Students exposed to a research laboratory had a positive experience with the teaching method, and over 90% saw it as beneficial to improve their understanding of the scientific concepts discussed during lectures. Likewise, their interest in pursuing a career in microbiology was stimulated by the Real-Lab-Day experience. In conclusion, this educational initiative depicts an alternative methodology to connect students to the research and offers an opportunity to be in close contact with experts and graduate students, who gain teaching experience.
Identification of a novel transport system inBorrelia burgdorferithat links the inner and outer membranes
Authors: Bowen Hannah G , Kenedy Melisha R , Johnson David K , MacKerell Alexander D , Akins Darrin R
Published: June 2023

Borrelia burgdorferi, the spirochete that causes Lyme disease, is a diderm organism that is similar to Gram-negative organisms in that it contains both an inner and outer membrane. Unlike typical Gram-negative organisms, however, B. burgdorferi lacks lipopolysaccharide (LPS). Using computational genome analyses and structural modeling, we identified a transport system containing six proteins in B. burgdorferi that are all orthologs to proteins found in the lipopolysaccharide transport (LPT) system that links the inner and outer membranes of Gram-negative organisms and is responsible for placing LPS on the surface of these organisms. While B. burgdorferi does not contain LPS, it does encode over 100 different surface-exposed lipoproteins and several major glycolipids, which like LPS are also highly amphiphilic molecules, though no system to transport these molecules to the borrelial surface is known. Accordingly, experiments supplemented by molecular modeling were undertaken to determine whether the orthologous LPT system identified in B. burgdorferi could transport lipoproteins and/or glycolipids to the borrelial outer membrane. Our combined observations strongly suggest that the LPT transport system does not transport lipoproteins to the surface. Molecular dynamic modeling, however, suggests that the borrelial LPT system could transport borrelial glycolipids to the outer membrane.
Generation of advanced cerebellar organoids for neurogenesis and neuronal network development
Authors: Chen Ya , Bury Luke A , Chen Fu , Aldinger Kimberly A , Miranda Helen C , Wynshaw-Boris Anthony
Published: June 2023

Neurons within the cerebellum form temporal–spatial connections through the cerebellum, and the entire brain. Organoid models provide an opportunity to model the early differentiation of the developing human cerebellum, which is difficult to study in vivo, and affords the opportunity to study neurodegenerative and neurodevelopmental diseases of the cerebellum. Previous cerebellar organoid models focused on early neuron generation and single cell activity. Here, we modify previous protocols to generate more mature cerebellar organoids that allow for the establishment of several classes of mature neurons during cerebellar differentiation and development, including the establishment of neural networks during whole-organoid maturation. This will provide a means to study the generation of several more mature cerebellar cell types, including Purkinje cells, granule cells and interneurons expression as well as neuronal communication for biomedical, clinical and pharmaceutical applications.
Old World Medieval Treponema pallidum Complex Treponematosis: A Case Report
Authors: Oumarou Hama Hamadou , Boualam Mahmoud A , Levasseur Anthony , Ardagna Yann , Adalian Pascal , Chaix Annie-Claire , Drancourt Michel
Published: June 2023

Background

Introduction of 1 Treponema pallidum complex pathogen in naive European populations following the return of Christopher Columbus’ troops from Central America in 1493 is a central dogma in venereology.

Methods

Among skeletal elements from the seventh or eighth century uncovered in Roquevaire, France, individual RS-1003 femur macroscopically suspected of having an infectious disease was investigated by means of paleoautoimmunohistochemistry, direct metagenomics, and paleoserology, along with 1 control femur from an apparently healthy individual (R-1003) and experimental negative controls.

Results

RS-1003 femur showed infectious bone; paleoautoimmunohistochemistry of the lesions led to microscopic detection of a T. pallidum complex pathogen. Phylogenetic analyses comprising 71 T. pallidum complex–specific reads covering 2.37% of the T. pallidum subsp. pallidum reference genome sequence revealed an ancestral T. pallidum complex pathogen in the lesion. Paleoserology detecting T. pallidum–specific antigens confirmed positive serological findings in individual RS-1003. Individual R-1003 and the negative controls remained negative.

Conclusions

This case, predating by 8 centuries previous detections of T. pallidum complex treponematosis in Europe, indicated that European populations were not naive to these pathogens before the 1493 introduction of a Central American T. pallidum complex pathogen overwhelming the T. pallidum ones previously circulating in the Old World. These data break a century-old dogma in medical microbiology.
Oral antimicrobial agents in patients with short bowel syndrome: worth a try!
Authors: Korzilius Julia W , Gompelman Michelle , Wezendonk Guus T J , Jager Nynke G L , Rovers Chantal P , Brüggemann Roger J M , Wanten Geert J A
Published: June 2023

Background

The use of oral antimicrobial agents in patients with short bowel syndrome (SBS) is challenging due to the changes in gastrointestinal anatomy that may result in diminished absorption and altered drug bioavailability. Prospective studies evaluating bioavailability of antimicrobial agents after oral administration in SBS patients are lacking.

Objectives

To determine the bioavailability of orally administered antimicrobial agents commonly used for treatment in SBS patients to guide clinical decision making when faced with infections.

Methods

We performed an explorative, clinical study investigating the pharmacokinetics (PK) of clindamycin, ciprofloxacin, flucloxacillin and fluconazole in SBS patients with intestinal failure. Participants received a combination of two antimicrobial agents simultaneously. To determine the oral bioavailability, participants received a single oral and IV dose of both agents on two occasions, after which they underwent intensive PK sampling on six predefined time points up to 12 hours after administration. Primary outcome was the oral bioavailability of these antimicrobial agents. Secondary outcomes were intravenous PK characteristics following non-compartmental analysis.

Results

Eighteen SBS patients were included: the mean (SD) age was 59 (17) years and 61% of participants were female. The median observed (IQR) bioavailability of ciprofloxacin, clindamycin, flucloxacillin and fluconazole were 36% (24–50), 93% (56–106), 50% (32–76) and 98% (61–107), respectively.

Conclusion

The bioavailability of selected antimicrobial agents in certain patients with SBS appeared to be better than expected, providing a feasible treatment option. Due to the large observed differences between patients, therapeutic drug monitoring should be part of the treatment to safeguard adequate exposure in all patients.

Trial registration

Registered in the Dutch Trial Register (NL7796) and EudraCT number 2019-002587-28
Friendship, markets, and companionate robots for children
Authors: Healy Mary
Published: June 2023

The aim of this article is to examine how markets enable companionship to be disconnected from the concept of friendship thus enabling an illusion of companionship without the demands of friendship. As friendship is a crucial early relationship for children, this is particularly germane to the world of education. It recognizes the previous lack of philosophical attention to the idea of companionship—a key factor in friendship—and that this omission contributes to a lack of clarity on a variety of issues. Starting with a brief outline of companion friendship, the article examines the idea of the ‘intimate work’ of friendship within the market domain by considering three illustrative examples: firstly, rent-a-friend; secondly paid companionship; ending with companionate robots for children. It then concludes by contending that this is an important issue for children and their development and thus for education.
Cinobufagin: a promising therapeutic agent for cancer
Authors: Dai Chun-Lan , Zhang Run-jing , An Pei , Deng Yi-Qing , Rahman Khalid , Zhang Hong
Published: June 2023

Objectives

Cinobufagin is a natural active ingredient isolated from the traditional Chinese medicine Venenum Bufonis (Chinese: Chansu), which is the dried secretion of the postauricular gland or skin gland of the Bufo gargarizans Cantor or Bufo melanostictus Schneider. There is increasing evidence indicating that cinobufagin plays an important role in the treatment of cancer. This article is to review and discuss the antitumor pharmacological effects and mechanisms of cinobufagin, along with a description of its toxicity and pharmacokinetics.

Methods

The public databases including PubMed, China National Knowledge Infrastructure and Elsevier were referenced, and ‘cinobufagin’, ‘Chansu’, ‘Venenum Bufonis’, ‘anticancer’, ‘cancer’, ‘carcinoma’, and ‘apoptosis’ were used as keywords to summarize the comprehensive research and applications of cinobufagin published up to date.

Key findings

Cinobufagin can induce tumour cell apoptosis and cycle arrest, inhibit tumour cell proliferation, migration, invasion and autophagy, reduce angiogenesis and reverse tumour cell multidrug resistance, through triggering DNA damage and activating the mitochondrial pathway and the death receptor pathway.

Conclusions

Cinobufagin has the potential to be further developed as a new drug against cancer.
A design utility approach for preferentially sampled spatial data
Authors: Gray Elizabeth J , Evangelou Evangelos
Published: June 2023

Spatial preferential sampling occurs when the choice of sampling locations depends stochastically on the process of interest. Ignoring this dependence leads to inaccurate inferences. Our framework models experimenter preferences jointly with the spatial process to adjust for this. We dispense with the unrealistic assumption (required by existing methods) of conditional independence of sampling locations by defining a whole design distribution proportional to a utility function on the space of designs. The proposed model likelihood is generally intractable. We provide fitting techniques based on the noisy Markov chain Monte Carlo and demonstrate their usage on a data set of spatially distributed ammonia concentrations.
Deciphering the genetic architecture of fruit color in strawberry
Authors: Denoyes Béatrice , Prohaska Alexandre , Petit Johann , Rothan Christophe
Published: June 2023

Fruits of Fragaria species usually have an appealing bright red color due to the accumulation of anthocyanins, water-soluble flavonoid pigments. Octoploid cultivated strawberry (Fragaria × ananassa) is a major horticultural crop for which fruit color and associated nutritional value are main breeding targets. Great diversity in fruit color intensity and pattern is observed not only in cultivated strawberry but also in wild relatives such as its octoploid progenitor F. chiloensis or the diploid woodland strawberry F. vesca, a model for fruit species in the Rosaceae. This review examines our understanding of fruit color formation in strawberry and how ongoing developments will advance it. Natural variations of fruit color as well as color changes during fruit development or in response to several cues have been used to explore the anthocyanin biosynthetic pathway and its regulation. So far, the successful identification of causal genetic variants has been largely driven by the availability of high-throughput genotyping tools and high-quality reference genomes of F. vesca and F. × ananassa. The current completion of haplotype-resolved genomes of F. × ananassa combined with QTL mapping will accelerate the exploitation of the untapped genetic diversity of fruit color and help translate the findings into strawberry improvement.
Regulation of climacteric fruit ripening in melon: recent advances and future challenges
Authors: Pujol Marta , Garcia-Mas Jordi
Published: June 2023

Fruit ripening is a complex and highly regulated process where tomato and strawberry have been the model species classically used for studying climacteric and non-climacteric fleshy fruit ripening types, respectively. Melon has emerged as an alternative ripening model because climacteric and non-climacteric cultivars exist, which makes it possible to dissect the regulation of ripening using a genetic approach. Several quantitative trait loci that regulate climacteric fruit ripening have been identified to date, and their combination in both climacteric and non-climacteric genetic backgrounds resulted in lines with different ripening behaviors, demonstrating that the climacteric intensity can be genetically modulated. This review discusses our current knowledge of the physiological changes observed during melon climacteric fruit ripening such as ethylene production, fruit abscission, chlorophyll degradation, firmness, and aroma, as well as their complex genetic control. From pioneer experiments in which ethylene biosynthesis was silenced, to the recent genetic edition of ripening regulators, current data suggest that the climacteric response is determined by the interaction of several loci under quantitative inheritance. The exploitation of the rich genetic diversity of melon will enable the discovery of additional genes involved in the regulation of the climacteric response, ultimately leading to breeding aromatic melon fruits with extended shelf life.
Opaque cell-specific proteome ofCandida albicansATCC 10231
Authors: Abdulghani Mazen , Telang Saraswati , Desai Manisha , Kadam Shivdas , Kazi Rubina , Shelar Amruta , Patil Rajendra , Maurya Radheshyam , Zore Gajanan
Published: June 2023

Candida albicans, a polymorphic opportunistic pathogen of humans, can exist in different morphological forms like yeast, hyphae, pseudohyphae, chlamydospores, and white and opaque cells. Proteomic analysis of opaque form of C. albicans ATCC 10231 is carried out in the present study using microflow liquid chromatography–tandem mass spectrometry and validated using expression analysis of selected genes using reverse transcription quantitative real-time PCR and mitochondrial membrane potential assay. This is the first report identifying opaque cell-specific proteins of C. albicans. A total of 188 proteins were significantly modulated under opaque form compared to white cells, of which 110 were upregulated, and 78 were downregulated. It was observed that oxidative phosphorylation (OxPhos) and oxidative stress are enhanced in C. albicans cells growing under opaque form as proteins involved in OxPhos (Atp1, Atp3, Atp16, Atp7, Cox6, Nuc2, Qcr7, and Sdh12) and oxidative stress response (Gcs1, Gtt11, Gpx2, Sod1, Ccp1, and Lys7) were significantly upregulated. The maximum upregulation of 23.16- and 13.93-fold is observed in the cases of Ccp1 and Nuc2, respectively. The downregulation of proteins, namely Als1, Csh1, Sap9, and Rho1, determining cell surface chemistry indicates modulation in cell wall integrity and reduced adhesion of opaque cells compared to white cells. This study is significant as it is the first draft of the proteomic profile of opaque cells that suggests enhanced OxPhos, oxidative stress, and modulation in cell surface chemistry indicating reduced adhesion and cell wall integrity, which could be associated with reduced virulence in opaque form. However, a deeper investigation is needed to explore it further.