bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic symbiosis between oxygenated and hypoxic tumour cells: An agent-based modelling study
Authors: Jayathilake Pahala Gedara , Victori Pedro , Pavillet Clara E. , Lee Chang Heon , Voukantsis Dimitrios , Miar Ana , Arora Anjali , Harris Adrian L. , Morten Karl J. , Buffa Francesca M.
Published: March 2024

Deregulated metabolism is one of the hallmarks of cancer. It is well-known that tumour cells tend to metabolize glucose via glycolysis even when oxygen is available and mitochondrial respiration is functional. However, the lower energy efficiency of aerobic glycolysis with respect to mitochondrial respiration makes this behaviour, namely the Warburg effect, counter-intuitive, although it has now been recognized as source of anabolic precursors. On the other hand, there is evidence that oxygenated tumour cells could be fuelled by exogenous lactate produced from glycolysis. We employed a multi-scale approach that integrates multi-agent modelling, diffusion-reaction, stoichiometric equations, and Boolean networks to study metabolic cooperation between hypoxic and oxygenated cells exposed to varying oxygen, nutrient, and inhibitor concentrations. The results show that the cooperation reduces the depletion of environmental glucose, resulting in an overall advantage of using aerobic glycolysis. In addition, the oxygen level was found to be decreased by symbiosis, promoting a further shift towards anaerobic glycolysis. However, the oxygenated and hypoxic populations may gradually reach quasi-equilibrium. A sensitivity analysis using Latin hypercube sampling and partial rank correlation shows that the symbiotic dynamics depends on properties of the specific cell such as the minimum glucose level needed for glycolysis. Our results suggest that strategies that block glucose transporters may be more effective to reduce tumour growth than those blocking lactate intake transporters.
P53 and BCL-2 family proteins PUMA and NOXA define competitive fitness in pluripotent cell competition
Authors: Valverde-Lopez Jose A. , Li-Bao Lin , Sierra Rocío , Santos Elisa , Giovinazzo Giovanna , Díaz-Díaz Covadonga , Torres Miguel
Published: March 2024

Cell Competition is a process by which neighboring cells compare their fitness. As a result, viable but suboptimal cells are selectively eliminated in the presence of fitter cells. In the early mammalian embryo, epiblast pluripotent cells undergo extensive Cell Competition, which prevents suboptimal cells from contributing to the newly forming organism. While competitive ability is regulated by MYC in the epiblast, the mechanisms that contribute to competitive fitness in this context are largely unknown. Here, we report that P53 and its pro-apoptotic targets PUMA and NOXA regulate apoptosis susceptibility and competitive fitness in pluripotent cells. PUMA is widely expressed specifically in pluripotent cells in vitro and in vivo. We found that P53 regulates MYC levels in pluripotent cells, which connects these two Cell Competition pathways, however, MYC and PUMA/NOXA levels are independently regulated by P53. We propose a model that integrates a bifurcated P53 pathway regulating both MYC and PUMA/NOXA levels and determines competitive fitness.
Prevalence, regional patterns and socio-demographic factors associated with poly-tobacco use in India: A secondary data analysis
Authors: Bantwal Priyanka , Kulkarni Muralidhar M. , Kamath Veena G. , Naik Ashwath K. , Fogarty Andrew W. , Dhar Murali , Ahankari Anand S.
Published: March 2024

Background

Tobacco use is associated with early, intermediate and long-term complications throughout the life course. With an influx of newer products containing nicotine, poly-tobacco use is slowly emerging as a public health concern, that is defined as existing tobacco users currently using two or more tobacco or nicotine products. While many studies have investigated single use tobacco, there is a paucity of research on regional patterns and socio-demographic factors associated with poly-tobacco use in India.

Objectives

To assess prevalence of poly-tobacco use and determine the socio-demographic factors associated with poly-tobacco use in India.

Methods

Data from the Global Adult Tobacco Survey 2 (GATS, 2016–17) was analysed, which included information on tobacco use among people aged >15 years. The pattern of current tobacco status was described using descriptive statistics. Multiple logistic regression models were estimated to determine factors associated with poly-tobacco use.

Results

The prevalence of poly-tobacco use in India was found to be 9.8%. Among the current tobacco users, the prevalence was 33%. Significant socio-demographic factors associated with poly-tobacco use included younger age, male gender, religion and backward caste. North-eastern region reported highest prevalence of poly-tobacco use in the country, followed by the central region.

Conclusion

The number of poly-tobacco users in India is considerably high and a matter of concern, more so in north east and central regions of the country. There is a need to create awareness about dangerous effects of all types of tobacco products and strengthen implementation of tobacco control policies with special focus on regions with high burden.
Cross-sectional serosurvey of Leptospira species among slaughter pigs, goats, and sheep in Uganda
Authors: Alinaitwe Lordrick , Aturinda Christopher Joshua , Lubega Ashiraf , Kivali Velma , Bugeza James , Wainaina Martin , Richter Martin H. , Hoona Jolly Justine , Roesel Kristina , Mayer-Scholl Anne , Cook Elizabeth Anne Jessie , Kankya Clovice , Dürr Salome
Published: March 2024

Introduction

Leptospira are a group of bacteria, including pathogenic types that cause leptospirosis. In Uganda, Leptospira exposure has been reported in humans, with domesticated animals being speculated as the source. However, comparable evidence of Leptospira prevalence and circulating serovars/serogroups in animals is only documented for cattle, and dogs. Our study determined Leptospira seroprevalence, associated risk factors and serogroups circulating among slaughtered pigs, goats, and sheep in Uganda.

Methods

During an 11-month cross-sectional survey in selected slaughter facilities in three regions of Uganda, we collected blood from 926 pigs, 347 goats, and 116 sheep. The age, sex, breed, and origin of each sampled animal were noted. The samples were tested for anti-Leptospira antibodies using the microscopic agglutination test, based on a panel of 12 serovars belonging to 12 serogroups.

Results

Leptospira seroprevalence was 26.67% (247/926, 95%CI 23.92–29.61) among pigs, and 21.81% (101/463, 95%CI 18.29–25.80) in goats and sheep (small ruminants). L. interrogans Australis and L. kirschneri Grippotyphosa were the commonest serovars among pigs, as was L. borgpetersenii Tarassovi in small ruminants. Pigs sourced from the Eastern (Odds Ratio [OR] = 2.82, 95%CI 1.84–4.30) and Northern (OR = 3.56, 95%CI 2.52–5.02) regions were more likely to be seropositive, compared to those from the Central region. For small ruminants, being female (OR 2.74, 95% CI 1.69–4.57) and adult (OR 4.47, 95% CI 1.57–18.80) was significantly more associated with Leptospira seropositivity.

Conclusion/significance: Detection of a moderate seroprevalence, and several Leptospira serogroups among pigs, sheep, and goats from all regions of Uganda, supports existing reports in cattle and dogs, and implies widespread Leptospira exposure in domestic animals in Uganda. These findings may inform future programs for the control of leptospirosis in livestock in Uganda.
The allocation of carbon resources in marine capture fisheries
Authors: Li Guangliang , Zhang Weikun , Qiu Hailan , Tan Chunlan , Niu Juanjuan
Published: March 2024

Marine fishery carbon emissions play a significant role in agricultural carbon emissions, making resource allocation a crucial topic for the overall marine ecological protection. This paper evaluates the dynamic iteration method as a research approach with the factors of resource allocation consisting of value assessment, optimization objective, difference between value assessment and objective, and optimization calculation. The paper selects the shadow price from the Super-SBM model as the judgment function for the goal value, aiming for the fairness criterion. From an equity standpoint, the allocation of carbon resources in marine capture fisheries proves to be unreasonable. The fishery model exhibits an excessive supply of carbon resources, resulting in wastage, while the green fishery model faces a relatively limited supply, with a focus on energy conservation and environmental protection. To address this issue, this paper proposes a new method and discusses the corrective results. This result shows that the stabilization point achieved is a short-term equilibrium rather than a long-term one. By rectifying the social contradiction of profit-oriented approaches, this research provides a fresh perspective for economic studies and applications, particularly in industrial layout and resource utilization optimization.
Judicial improvement, market integration, and export technical complexity-a quasi-natural experiments based on the creation of circuit courts
Authors: Gao Xin , Kong Shuo
Published: March 2024

Judicial improvement and trade structure optimization are important elements in achieving a high level of openness. This paper develops a theoretical framework on the impact of local protectionism on market integration and export technical complexity, and then empirically analyses the effect of judicial improvement on the technical complexity of urban product exports and its mechanism of action based on a quasi-natural experiment with the establishment of circuit courts. The study finds that the establishment of circuit courts significantly increases the technical complexity of product exports, and the findings remain valid after a series of robustness tests. Further analysis shows that the technology enhancement effect of the establishment of circuit courts is more pronounced in the group of cities with higher administrative levels, better location advantages, and less advanced rule of law. Mechanism Analysis shows that a superior institutional environment can have a two-sided effect on different types of firms. Overall, however, the productivity-enhancing effect of low-productivity firms exiting the market is lower than the productivity-reducing effect of higher-productivity firms’ increased compliance costs, which in turn weakens the positive promotional effect of circuit courts. The above theoretical and empirical findings provide policy implications for maximizing the technology enhancement effect of the establishment of circuit courts on product exports, thereby promoting a high level of openness in China.
Risk factors for intubation and mortality in patients treated with high flow nasal cannula due to COVID-19 infection. Survival Analysis Study in a Northern Mexican Population
Authors: Luviano-García José Antonio , Loose-Esparza Alejandro , Hernández-Ruíz Yodira Guadalupe , Sanz-Sánchez Miguel Ángel , Maheda-García Hector Jeovanny , Sosa-Medellin Miguel Angel , Garza-Silva Arnulfo , Romero-Ibarguengoitia Maria Elena
Published: March 2024

Background

COVID-19-related acute hypoxic respiratory failure patients often use high-flow nasal cannula (HFNO) oxygen therapy. COVID-19 HFNO intubation and mortality risk factors are understudied in the Mexican population, so the aim was to study them.

Methods

This retrospective study searched electronic medical records from March 2020 to June 2022 for patients with COVID-19 who required hospitalization and HFNO. Descriptive statistics, a survival curve analysis, and Cox proportional hazard models were used to determine predictor factors for intubation and mortality in patients with HFNO and COVID-19, respectively.

Results

A total of 134 patients received HFNO treatment. Ninety-one (67.9%) were men with a mean (SD) age of 54.5 (17.9) years. Common medical history included obesity (n = 89, 66.4%) with a Body Mass Index (BMI) mean (SD) of 31.8 (5.9), hypertension (n = 67, 50.0%), type 2 diabetes (n = 55, 41.0%), and dyslipidemias (n = 43, 32.1%). The variables associated with a greater risk of requiring intubation after high-flow therapy were age (HR = 1.018, 95% CI 1.003–1.034, p = 0.022) and BMI (HR = 1.071, 95% CI 1.024–1.120, p = 0.003). No variables were associated with lower risk. Increased mortality was associated with increasing age (HR = 1.151, 95% CI 1.102–1.201, p = <0.001), hypertension (HR = 4.092, 95% CI 1.369–12.236, p = 0.012), and dyslipidemia (HR = 3.954, 95% CI 1.395–11.209, p = 0.010). Patients with type 2 diabetes had a lower risk of mortality (HR = 0.235, 95% CI 0.080–0.688, p = 0.008).

Conclusions

A higher age and BMI were associated with an increased risk of intubation in patients with HFNO and COVID-19. Hypertension and dyslipidemias were associated with a higher risk of mortality.
Use of business model potential in Dutch academic medical centres—A case study
Authors: Cardinaal Ester M. M. , Truijens Joey , Jeurissen Patrick P. T. , Berden Hubert
Published: March 2024

Academic Medical Centres (AMCs) are large organisations with a complex structure due to various intertwined missions and (public) roles that can be conflicting. This complexity makes it difficult to adapt to changing circumstances. The literature points to the use of business models to address such challenges. A business model describes the resources, processes, and cost assumptions that an organisation makes in order to the delivery of a unique value proposition to a customer/patient. Do AMC business operations managers actually use business models to address challenges and operate in a way that enables AMCs to adapt to changing circumstances? This study explored whether the use of a business model is a starting point for bringing about change in AMC operations. A case study design was considered appropriate to explore the knowledge and experience of business models among business operations managers of Dutch AMCs. Through purposive sampling, participants were invited to participate in a questionnaire to provide in-depth and detailed information about the use of business models in AMCs. Our research showed that a business model can support the complex organisation of an AMC, but the design and use of business models varies. In general, respondents attribute more potential to the use of a business model than they experience in daily practice. The majority consider a business model to be suitable for bringing about change, but see it only sparingly used in their own AMC. This is the first study to provide some initial insights into the use of business models in Dutch AMCs. We can assume that improvements are possible in order to optimise the change potential of business models in AMCs worldwide. In order to successfully implement an innovative business model, the interpretation of the concept of a business model and the creation of a framework of preconditions should be taken into account. Healthcare providers, policy makers or researchers should explicitly identify the environment in which the model will operate. In particular, by identifying the level of readiness for change readiness at all levels of the organisation.
The impact of the COVID-19 pandemic on frail older people ageing in place alone in two Italian cities: Functional limitations, care arrangements and available services
Authors: Melchiorre Maria Gabriella , Cerea Stefania , Socci Marco , Lamura Giovanni
Published: March 2024

The study aimed to explore and compare effects of lockdown, due to the COVID-19 pandemic in 2020, on frail older people living alone at home in Brescia and Ancona, two urban cities located respectively in Northern and Central Italy. This country was the Western epicenter of the first wave of the pandemic (February-May 2020), which affected the two cities differently as for infections, with a more severe impact on the former. A follow-up study of the IN-AGE research project (2019) was carried out in July-September 2020, by means of telephone interviews, involving 41 respondents. Semi-structured questions focused on the effects of the first wave of the pandemic on their mobility and functional limitations, available care arrangements, and access to health services. The lockdown and social distancing measures overall negatively impacted on frail older people living alone, to a different extent in Ancona and Brescia, with a better resilience of home care services in Brescia, and a greater support from the family in Ancona, where however major problems in accessing health services also emerged. Even though the study was exploratory only, with a small sample that cannot be considered as representative of the population, and despite differences between the two cities, findings overall suggested that enhancing home care services, and supporting older people in accessing health services, could allow ageing in place, especially in emergency times.
Momordica charantia fruit reduces plasma fructosamine whereas stems and leaves increase plasma insulin in adult mildly diabetic obese Göttingen Minipigs
Authors: Koopmans Sietse Jan , Binnendijk Gisabeth , Ledoux Allison , Choi Young Hae , Mes Jurriaan J. , Guan Xiaonan , Molist Francesc , Thị Minh Tâm Phạm , van der Wielen Nikkie
Published: March 2024

Background

Traditionally Momordica charantia (Bitter gourd) is known for its blood glucose lowering potential. This has been validated by many previous studies based on rodent models but human trials are less convincing and the physiological mechanisms underlying the bioactivity of Bitter gourd are still unclear. The present study compared the effects of whole fruit or stems-leaves from five different Bitter gourd cultivars on metabolic control in adult diabetic obese Göttingen Minipigs.

Methods

Twenty streptozotocin-induced diabetic (D) obese Minipigs (body weight ~85 kg) were subdivided in mildly and overtly D pigs and fed 500 g of obesogenic diet per day for a period of three weeks, supplemented with 20 g dried powdered Bitter gourd or 20 g dried powdered grass as isoenergetic control in a cross-over, within-subject design.

Results

Bitter gourd fruit from the cultivars “Palee” and “Good healthy” reduced plasma fructosamine concentrations in all pigs combined (from 450±48 to 423±53 and 490±50 to 404±48 μmol/L, both p<0.03, respectively) indicating improved glycemic control by 6% and 17%. These effects were statistically confirmed in mildly D pigs but not in overtly D pigs. In mildly D pigs, the other three cultivars of fruit showed consistent numerical but no significant improvements in glycemic control. The composition of Bitter gourd fruit was studied by metabolomics profiling and analysis identified three metabolites from the class of triterpenoids (Xuedanoside H, Acutoside A, Karaviloside IX) that were increased in the cultivars “Palee” (>3.9-fold) and “Good healthy” (>8.9-fold) compared to the mean of the other three cultivars. Bitter gourd stems and leaves from the cultivar “Bilai” increased plasma insulin concentrations in all pigs combined by 28% (from 53±6 to 67±9 pmol/L, p<0.03). The other two cultivars of stems and leaves showed consistent numerical but no significant increases in plasma insulin concentrations. The effects on plasma insulin concentrations were confirmed in mildly D pigs but not in overtly D pigs.

Conclusions

Fruits of Bitter gourd improve glycemic control and stems-leaves of Bitter gourd increase plasma insulin concentrations in an obese pig model for mild diabetes. The effects of Bitter gourd fruit on glycemic control seem consistent but relatively small and cultivar specific which may explain the varying results of human trials reported in the literature.
Oncolytic vaccinia virus immunotherapy antagonizes image-guided radiotherapy in mouse mammary tumor models
Authors: Umer Brittany A. , Noyce Ryan S. , Kieser Quinten , Favis Nicole A. , Shenouda Mira M. , Rans Kim J. , Middleton Jackie , Hitt Mary M. , Evans David H.
Published: March 2024

Ionizing radiation (IR) and oncolytic viruses are both used to treat cancer, and the effectiveness of both agents depends upon stimulating an immune response against the tumor. In this study we tested whether combining image guided ionizing radiation (IG-IR) with an oncolytic vaccinia virus (VACV) could yield a better therapeutic response than either treatment alone. ΔF4LΔJ2R VACV grew well on irradiated human and mouse breast cancer cells, and the virus can be combined with 4 or 8 Gy of IR to kill cells in an additive or weakly synergistic manner. To test efficacy in vivo we used immune competent mice bearing orthotopic TUBO mammary tumors. IG-IR worked well with 10 Gy producing 80% complete responses, but this was halved when the tumors were treated with VACV starting 2 days after IG-IR. VACV monotherapy was ineffective in this model. The antagonism was time dependent as waiting for 21 days after IG-IR eliminated the inhibitory effect but without yielding any further benefits over IR alone. In irradiated tumors, VACV replication was also lower, suggesting that irradiation created an environment that did not support infection as well in vivo as in vitro. A study of how four different treatment regimens affected the immune composition of the tumor microenvironment showed that treating irradiated tumors with VACV altered the immunological profiles in tumors exposed to IR or VACV alone. We detected more PD-1 and PD-L1 expression in tumors exposed to IR+VACV but adding an αPD-1 antibody to the protocol did not change the way VACV interferes with IG-IR therapy. VACV encodes many immunosuppressive gene products that may interfere with the ability of radiotherapy to induce an effective anti-tumor immune response through the release of danger-associated molecular patterns. These data suggest that infecting irradiated tumors with VACV, too soon after exposure, may interfere in the innate and linked adaptive immune responses that are triggered by radiotherapy to achieve a beneficial impact.
Optimization of RNAi efficiency in PVD neuron of C. elegans
Authors: Singh Pallavi , Selvarasu Kavinila , Ghosh-Roy Anindya
Published: March 2024

PVD neuron of C. elegans has become an attractive model for the study of dendrite development and regeneration due to its elaborate and stereotype dendrite morphology. RNA interference (RNAi) by feeding E. coli expressing dsRNA has been the basis of several genome wide screens performed using C. elegans. However, the feeding method often fails when it comes to knocking down genes in nervous system. In order to optimize the RNAi conditions for PVD neuron, we fed the worm strains with E. coli HT115 bacteria expressing dsRNA against mec-3, hpo-30, and tiam-1, whose loss of function are known to show dendrite morphology defects in PVD neuron. We found that RNAi of these genes in the available sensitive backgrounds including the one expresses sid-1 under unc-119 promoter, although resulted in reduction of dendrite branching, the phenotypes were significantly modest compared to the respective loss of function mutants. In order to enhance RNAi in PVD neurons, we generated a strain that expressed sid-1 under the promoter mec-3, which exhibits strong expression in PVD. When Pmec-3::sid-1 is expressed in either nre-1(-)lin-15b(-) or lin-15b(-) backgrounds, the higher order branching phenotype after RNAi of mec-3, hpo-30, and tiam-1 was significantly enhanced as compared to the genetic background alone. Moreover, knockdown of genes playing role in dendrite regeneration in the nre-1(-)lin-15b(-), Pmec-3-sid-1[+] background resulted in significant reduction in dendrite regeneration following laser injury. The extent of dendrite regrowth due to the RNAi of aff-1 or ced-10 in our optimized strain was comparable to that of aff-1 and ced-10 mutants. Essentially, our strain expressing sid-1 in PVD neuron, provides an RNAi optimized platform for high throughput screening of genes involved in PVD development, maintenance and regeneration.
Description of the fasted serum metabolomic signature of lean and obese cats at maintenance and of obese cats under energy restriction
Authors: Grant Caitlin E. , Godfrey Hannah , Tal Moran , Bakovic Marica , Shoveller Anna K. , Blois Shauna L. , Hesta Myriam , Verbrugghe Adronie
Published: March 2024

This study aimed to investigate the serum metabolomic profile of obese and lean cats as well as obese cats before and after energy restriction for weight loss. Thirty cats, 16 obese (body condition score 8 to 9/9) and 14 lean (body condition score 4 to 5/9), were fed a veterinary weight loss food during a 4-week period of weight maintenance (L-MAINT and O-MAINT). The 16 obese cats were then energy restricted by a 60% energy intake reduction with the same food for a 10-week period (O-RESTRICT). Fasted serum metabolites were measured using nuclear magnetic resonance and direct infusion mass spectrometry after the maintenance period for L-MAINT and O-MAINT cats and after the energy restriction period for O-RESTRICT and compared between groups using a two-sided t-test. Obese cats lost 672 g ± 303 g over the 10-week restriction period, representing a weight loss rate of 0.94 ± 0.28% per week. Glycine, l-alanine, l-histidine, l-glutamine, 2-hydroxybutyrate, isobutryric acid, citric acid, creatine, and methanol were greater in O-RESTRICT compared to O-MAINT. There was a greater concentration of long-chain acylcarnitines in O-RESTRICT compared to both O-MAINT and L-MAINT, and greater total amino acids compared to O-MAINT. Glycerol and 3-hydroxybutyric acid were greater in O-MAINT compared to L-MAINT, as were several lysophosphatidylcholines. Thus, energy restriction resulted in increased dispensable amino acids in feline serum which could indicate alterations in amino acid partitioning. An increase in lipolysis was not evident, though greater circulating acylcarnitines were observed, suggesting that fatty acid oxidation rates may have been greater under calorie restriction. More research is needed to elucidate energy metabolism and substrate utilization, specifically fatty acid oxidation and methyl status, during energy restriction in strict carnivorous cats to optimize weight loss.
Good psychiatric management for borderline personality disorder: A qualitative study of its implementation in a supported employment team
Authors: Dunand Noëllie , Golay Philippe , Bonsack Charles , Spagnoli Danièle , Pomini Valentino
Published: March 2024

Introduction

People with borderline personality disorder have difficulties with work. The Individual Placement and Support model has shown its worldwide effectiveness in terms of vocational rehabilitation for individuals with psychiatric disorders. However, only a few recent studies have explored its results for people with personality disorders, and the findings were mitigated. Additionally, Individual Placement and Support job coaches reported difficulties in supporting this population. An evidence-based psychotherapeutic method, also applicable in a case management context, called Good Psychiatric Management for borderline personality disorder, could potentially overcome these obstacles. This study aimed to evaluate the initial integration of Good Psychiatric Management in Individual Placement and Support practice.

Methods

Individual Placement and Support practitioners of Lausanne University Hospital, Switzerland, were trained in Good Psychiatric Management in January 2022. Five of them participated in a focus group to collect their impressions about the training, and six were interviewed 9 months later to assess the initial adoption of Good Psychiatric Management into their practice. Thematic analyses were conducted.

Results

Job coaches were positive about this new tool. All of them found it useful and beneficial both for them and their patients. They were able to follow the main Good Psychiatric Management principles in their practice However, the findings also suggested some additional improvements in the implementation process.

Conclusions

Integrating Good Psychiatric Management in Individual Placement and Support seems feasible, and the team who appreciated it adopted it. The method offers new perspectives in community support for people living with borderline personality disorder.
BetaBuddy: An automated end-to-end computer vision pipeline for analysis of calcium fluorescence dynamics in β-cells
Authors: Alsup Anne M. , Fowlds Kelli , Cho Michael , Luber Jacob M.
Published: March 2024

Insulin secretion from pancreatic β-cells is integral in maintaining the delicate equilibrium of blood glucose levels. Calcium is known to be a key regulator and triggers the release of insulin. This sub-cellular process can be monitored and tracked through live-cell imaging and subsequent cell segmentation, registration, tracking, and analysis of the calcium level in each cell. Current methods of analysis typically require the manual outlining of β-cells, involve multiple software packages, and necessitate multiple researchers—all of which tend to introduce biases. Utilizing deep learning algorithms, we have therefore created a pipeline to automatically segment and track thousands of cells, which greatly reduces the time required to gather and analyze a large number of sub-cellular images and improve accuracy. Tracking cells over a time-series image stack also allows researchers to isolate specific calcium spiking patterns and spatially identify those of interest, creating an efficient and user-friendly analysis tool. Using our automated pipeline, a previous dataset used to evaluate changes in calcium spiking activity in β-cells post-electric field stimulation was reanalyzed. Changes in spiking activity were found to be underestimated previously with manual segmentation. Moreover, the machine learning pipeline provides a powerful and rapid computational approach to examine, for example, how calcium signaling is regulated by intracellular interactions.
LEDT and Idebenone treatment modulate autophagy and improve regenerative capacity in the dystrophic muscle through an AMPK-pathway
Authors: Silva Heloina Nathalliê Mariano da , Fernandes Evelyn Mendes , Pereira Valéria Andrade , Mizobuti Daniela Sayuri , Covatti Caroline , Rocha Guilherme Luiz da , Minatel Elaine
Published: March 2024

Purpose

Considering the difficulties and challenges in Duchenne muscular dystrophy (DMD) treatment, such as the adverse effects of glucocorticoids, which are the main medical prescription used by dystrophic patients, new treatment concepts for dystrophic therapy are very necessary. Thus, in this study, we explore the effects of photobiomodulation (PBM; a non-invasive therapy) and Idebenone (IDE) treatment (a potent antioxidant), applied alone or in association, in dystrophic muscle cells and the quadriceps muscle, with special focus on autophagy and regenerative pathways.

Methods

For the in vitro studies, the dystrophic primary muscle cells received 0.5J LEDT and 0.06μM IDE; and for the in vivo studies, the dystrophic quadriceps muscle received 3J LEDT and the mdx mice were treated with 200mg/kg IDE.

Results

LEDT and IDE treatment modulate autophagy by increasing autophagy markers (SQSTM1/p62, Beclin and Parkin) and signaling pathways (AMPK and TGF-β). Concomitantly, the treatments prevented muscle degeneration by reducing the number of IgG-positive fibers and the fibers with a central nucleus; decreasing the fibrotic area; up-regulating the myogenin and MCH-slow levels; and down-regulating the MyoD and MHC-fast levels.

Conclusion

These results suggest that LEDT and IDE treatments enhance autophagy and prevented muscle degeneration in the dystrophic muscle of the experimental model. These findings illustrate the potential efficacy of LEDT and IDE treatment as an alternative therapy focused on muscle recovery in the dystrophic patient.
The efficacy of pediatric elbow radiographic guidance in diagnosis of lateral humeral condyle fracture
Authors: Vasaruchapong Satetha , Woratanarat Patarawan , Patathong Tanyaporn , Woratanarat Thira , Jaovisidha Supaneewan , Angsanunsukh Chanika
Published: March 2024

Although lateral humeral condyle fracture is common, the incidence of missed diagnosis is very high. Delayed and missed diagnosis led to significant morbidities and loss of functions. We designed a pediatric elbow radiographic guidance aiming to improve the accuracy of diagnosis. This study was aimed to evaluate the efficacy of the radiographic guidance for the diagnosis of lateral condyle fracture. A cross-sectional study was conducted after defining the essential parameters as a guidance for assessing the pediatric elbow radiographs. We included medical students, emergency medicine, orthopedic, and radiology residents and fellows into this study. A questionnaire was used to evaluate the efficacy of the guidance. All participants underwent a pretest evaluation, followed by studying the guidance, and then finished a posttest evaluation. Baseline characteristics, diagnostic scores, and parameter evaluation scores were collected. The pretest and posttest scores were analyzed using paired t-test. Association between baseline characteristics and diagnostic scores were analyzed using multiple regression analysis. We included 177 participants. Average diagnostic score was significantly increased after using the guidance, from 12.2 ± 1.9 to 13.0 ± 1.7 (p < 0.0001). Medical students showed the most improvement, from 11.9 ± 1.9 to 13.1 ± 1.3 (p <0.001). All means of essential parameter evaluation scores were significantly improved in overall participants.The pediatric elbow radiographic guidance is useful for evaluation and diagnosis of lateral condyle fracture, especially for young physicians and trainees. Therefore, this should be recommended in routine medical education and general practice.
Group peer mentoring is effective for different demographic groups of biomedical research faculty: A controlled trial
Authors: Pololi Linda H. , Evans Arthur T. , Civian Janet T. , McNamara Tay , Brennan Robert T.
Published: March 2024

Introduction

Improved mentoring of midcareer researchers in medical schools has been identified as an important potential avenue for addressing low vitality and high burnout rates in faculty, and the scarcity of both underrepresented minority (URM) faculty and women in biomedical research. To address the need for widescale effective mentoring, we sought to determine whether a group peer mentoring intervention (C-Change Mentoring and Leadership Institute) for early midcareer research faculty was effective for different demographic groups in a controlled trial.

Methods and materials

Thirty-five diverse early midcareer faculty and 70 propensity-matched (PM) control subjects matched to intervention subjects on a) study inclusion criteria; b) gender, race, and ethnicity, degree, rank, years of experience, publications, grants; and c) pretest survey outcome variables, participated in the intervention. The C-Change Participant Survey assessed vitality, self-efficacy in career advancement, research success, mentoring others, valuing diversity, cognitive empathy, and anti-sexism/anti-racism skills at pretest and intervention completion. Analysis using multiple regression models included outcome pretest values and indicator variables for intervention, gender, URM status, and MD vs. PhD. Hypotheses regarding differential effectiveness of the intervention by demographic group were tested by including cross-product terms between the demographic indicator variables and the intervention indicator. Missing data were addressed using chained equations to create 100 data sets.

Results and discussion

The intervention participants had significantly higher (favorable) scores than PM controls for: self-assessed change in vitality; self-efficacy for career advancement, research, and mentoring others; cognitive empathy; and anti-sexism/racism skills. The benefits of the intervention were nearly identical across: gender, URM vs non-URM faculty, and degree MD/PhD, except vitality significantly increased for non-URM subjects, and not for URM faculty. Self-assessed change in vitality increased for URM and non-URM.

Conclusion

The intervention worked successfully for enhancing vitality, self-efficacy and cross-cultural engagement across different demographic groups of biomedical research faculty.
Stationary stable cross-correlation pattern and task specific deviations in unresponsive wakefulness syndrome as well as clinically healthy subjects
Authors: Apablaza-Yevenes David E. , Corsi-Cabrera María , Martinez-Guerrero Antonieta , Northoff Georg , Romaniello Caterina , Farinelli Marina , Bertoletti Erik , Müller Markus F. , Muñoz-Torres Zeidy
Published: March 2024

Brain dynamics is highly non-stationary, permanently subject to ever-changing external conditions and continuously monitoring and adjusting internal control mechanisms. Finding stationary structures in this system, as has been done recently, is therefore of great importance for understanding fundamental dynamic trade relationships. Here we analyse electroencephalographic recordings (EEG) of 13 subjects with unresponsive wakefulness syndrome (UWS) during rest and while being influenced by different acoustic stimuli. We compare the results with a control group under the same experimental conditions and with clinically healthy subjects during overnight sleep. The main objective of this study is to investigate whether a stationary correlation pattern is also present in the UWS group, and if so, to what extent this structure resembles the one found in healthy subjects. Furthermore, we extract transient dynamical features via specific deviations from the stationary interrelation pattern. We find that (i) the UWS group is more heterogeneous than the two groups of healthy subjects, (ii) also the EEGs of the UWS group contain a stationary cross-correlation pattern, although it is less pronounced and shows less similarity to that found for healthy subjects and (iii) deviations from the stationary pattern are notably larger for the UWS than for the two groups of healthy subjects. The results suggest that the nervous system of subjects with UWS receive external stimuli but show an overreaching reaction to them, which may disturb opportune information processing.
A randomised controlled trial of Pre-Operative Oncotype DX testing in early-stage breast cancer (PRE-DX study) – Study protocol
Authors: Northgraves Matthew , Cohen Judith , Harvey James , Huang Chao , Palmieri Carlo , Pinder Sarah , Roy Pankaj , Reynia Sarah , Soares Marta , Cain Henry
Published: March 2024

Background

The Oncotype DX® Breast Recurrence Score assay can guide recommendations made to patients with oestrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer regarding post-surgery adjuvant therapy. Standard practice is to order the test in the post-operative setting on a specimen from the excised invasive carcinoma. However, it has been shown to be technically possible to perform the test on the diagnostic core biopsy. By testing the diagnostic core biopsy in the pre-operative setting, the wait for excised invasive carcinoma Recurrence Score results could be reduced allowing patients to be more accurately counselled regarding their treatment pathway sooner with any adjuvant treatment recommendations expedited. This would allow for more efficient streaming of follow up appointments. The aim of this study is to compare the impact on the patient treatment pathway of performing the Oncotype DX® test on the diagnostic core biopsy pre-operatively (intervention) as opposed to the excised invasive carcinoma (control).

Methods and analysis

This parallel group randomised controlled trial aims to recruit 330 newly diagnosed patients with grade 2 or grade 3, ER+, HER2-, invasive intermediate risk early-stage breast cancer. Participants will be randomised 2:1 to the preoperative testing of the diagnostic core biopsy compared to the post-operative testing of the excision specimen. The primary endpoint is number of clinical touchpoints between treating team and patient from initial approach until offer and prescription of the first adjuvant treatment. Secondary endpoints include time from diagnosis to offer and prescription of the first adjuvant treatment, patient-reported anxiety scores and health cost impact analysis collected at baseline, following the post-operative clinic and following the offer of adjuvant treatment, and number of alterations in treatment sequence from original planned surgical treatment to neoadjuvant therapy.

Trial registration

The study was registered on ISRCTN (ISRCTN14337451) on the 16th August 2022.
A single base pair substitution in zebrafish distinguishes between innate and acute startle behavior regulation
Authors: Ortiz Elelbin A. , Campbell Philip D. , Nelson Jessica C. , Granato Michael
Published: March 2024

Behavioral thresholds define the lowest stimulus intensities sufficient to elicit a behavioral response. Establishment of baseline behavioral thresholds during development is critical for proper responses throughout the animal’s life. Despite the relevance of such innate thresholds, the molecular mechanisms critical to establishing behavioral thresholds during development are not well understood. The acoustic startle response is a conserved behavior whose threshold is established during development yet is subsequently acutely regulated. We have previously identified a zebrafish mutant line (escapist) that displays a decreased baseline or innate acoustic startle threshold. Here, we identify a single base pair substitution on Chromosome 25 located within the coding sequence of the synaptotagmin 7a (syt7a) gene that is tightly linked to the escapist acoustic hypersensitivity phenotype. By generating animals in which we deleted the syt7a open reading frame, and subsequent complementation testing with the escapist line, we demonstrate that loss of syt7a function is not the cause of the escapist behavioral phenotype. Nonetheless, escapist mutants provide a powerful tool to decipher the overlap between acute and developmental regulation of behavioral thresholds. Extensive behavioral analyses reveal that in escapist mutants the establishment of the innate acoustic startle threshold is impaired, while regulation of its acute threshold remains intact. Moreover, our behavioral analyses reveal a deficit in baseline responses to visual stimuli, but not in the acute regulation of responses to visual stimuli. Together, this work eliminates loss of syt7a as causative for the escapist phenotype and suggests that mechanisms that regulate the establishment of behavioral thresholds in escapist larvae can operate independently from those regulating acute threshold regulation.
Alterations in stride-to-stride fluctuations in patients with chronic obstructive pulmonary disease during a self-paced treadmill 6-minute walk test
Authors: Liu Wai-Yan , Spruit Martijn A. , Delbressine Jeannet M. , Willems Paul J. , Yentes Jennifer M. , Bruijn Sjoerd M. , Franssen Frits M. E. , Wouters Emiel F. M. , Meijer Kenneth
Published: March 2024

Evaluating variability and stability using measures for nonlinear dynamics may provide additional insight into the structure of the locomotor system, reflecting the neuromuscular system’s organization of gait. This is in particular of interest when this system is affected by a respiratory disease and it’s extrapulmonary manifestations. This study assessed stride-to-stride fluctuations and gait stability in patients with chronic obstructive pulmonary disease (COPD) during a self-paced, treadmill 6-minute walk test (6MWT) and its association with clinical outcomes. In this cross-sectional study, eighty patients with COPD (age 62±7y; forced expiratory volume in first second 56±19%predicted) and 39 healthy older adults (62±7y) were analyzed. Gait parameters including stride-to-stride fluctuations (coefficient of variation (CoV), predictability (sample entropy) and stability (Local Divergence Exponent (LDE)) were calculated over spatiotemporal parameters and center of mass velocity. Independent t-test, Mann-Whitney U test and ANCOVA analyses were conducted. Correlations were calculated between gait parameters, functional mobility using Timed Up and Go Test, and quadriceps muscle strength using dynamometry. Patients walked slower than healthy older adults. After correction for Speed, patients demonstrated increased CoV in stride length (F(1,116) = 5.658, p = 0.019), and increased stride length predictability (F(1,116) = 3.959, p = 0.049). Moderate correlations were found between mediolateral center of mass velocity LDE and normalized maximum peak torque (ρ = -0.549). This study showed that patients with COPD demonstrate alterations in stride length fluctuations even when adjusted for walking speed, highlighting the potential of nonlinear measures to detect alterations in gait function in patients with COPD. Association with clinical outcomes were moderate to weak, indicating that these clinical test are less discriminative for gait alterations.
Investigating animal reservoirs for hepatitis E virus in Bangui, Central African Republic
Authors: Nombot-Yazenguet Marina Prisca de Marguerite , Modiyinji Abdou Fatawou , Tricou Vianney , Manirakiza Alexandre , Njouom Richard , Komas Narcisse Patrice Joseph
Published: March 2024

Background

Hepatitis E virus (HEV) is a major cause of enterotropic viral hepatitis, a major public health problem in many developing countries. In Central African Republic (CAR), HEV genotypes 1, 2, and 3 have been found to have an impact on human health. However, data on HEV in animal reservoirs are still lacking for CAR. Here, we investigated the presence of HEV in farmed pigs and goats in Bangui, the capital city of CAR, using molecular methods.

Methodology

In a prospective study, fecal samples from 61 pigs and 39 goats from farms in five districts (2nd, 4th, 6th, 7th, 8th) of Bangui were collected and tested for HEV RNA by real-time RT-PCR. The samples were further analyzed by nested-PCR and sequenced to determine the genotype and subtype to which the virus belong.

Results

In total, 22/100 (22.0%) feces samples were successfully amplified for HEV RNA by real time RT-PCR. All positive samples were from pigs (22/61; 36.1%), while all goat samples were negative (0/39). Twelve HEV RNA samples (12/22 or 54.5%) were successfully amplified by nested RT-PCR, and subsequently sequenced. Phylogenetic analysis revealed that the obtained sequences clustered with subtype 3h and were genetically related to the human HEV sequences from CAR.

Conclusion

This study confirms that pigs constitute an HEV reservoir, with genotype 3 being the major circulating strain. Further studies are needed to investigate other local reservoirs and to improve knowledge of the molecular epidemiology of HEV in CAR.
David Cronenberg: Interviews, David Schwartz, ed. (2021)
Authors: Smith Yaakov “Jacob”
Published: March 2024

Review of: David Cronenberg: Interviews, David Schwartz, ed. (2021)

Jackson, MS: University Press of Mississippi, 239pp., ISBN: 9781496832252 (pbk), $25.00, ISBN: 9781496832245 (hbk), $99.99