bluuebunny/crossref_metadata_2025 huggingface dataset:
P.131 Comparison of interhemispheric and transcortical approaches for resection of colloid cysts of the third ventricle
Authors: Benchekroun S , Champagne P , Côté M
Published: May 2024

Background: Colloid cysts are rare benign lesions of the third ventricle that can cause hydrocephalus and intracranial hypertension. Their primary treatment is surgical removal. Although open surgery presents the best opportunity for total resection of the cyst, there is no consensus regarding the optimal choice between the interhemispheric and the transcortical approaches. We aim to compare these two approaches in regard of the radicality of excision, the recurrence rate, and the surgical imprint. Methods: Retrospective cohort study on all patients who underwent surgical resection of colloid cyst between 2003 and 2023 at CHU de Québec. Data on demographics, symptoms, complications, and imaging was gathered. Results: In a cohort of 28 patients (17 interhemispheric, 11 transcortical), the preliminary results demonstrate prolonging operative time (270min. vs. 187min.) and increasing blood loss (193cc vs 100cc) associated with the interhemispheric approach. Despite these results, the hospitalization duration remains similar (p=0.734). However, the interhemispheric approach results in significantly lower surgery-induced encephalomalacia (1.1cc vs. 4.4cc, p=0.006). Conclusions: The interhemispheric approach could lead to potentially lesser consequences due to the reduced volume of encephalomalacia left by the surgical intervention, at the cost of prolonged operating time and higher blood loss.
Sociocultural Factors Influence on Burden and Stress of Caregivers of Children with Epilepsy
Authors: Schiller Katharina , Dassi Christelle , Berrahmoune Saoussen , Frauscher Birgit , Myers Kenneth A.
Published: May 2024

We evaluated stress and burden in epilepsy patient caregivers in a pediatric neurology clinic. Caregivers of 102 children with epilepsy completed the Caregivers’ Assessment of Difficulty Index and a questionnaire regarding caregiver sociocultural characteristics. A multiple linear regression statistical analysis found that caregiver burden was significantly increased for those who had a second child with a chronic disease, sole caregivers and for those with children with drug-resistant epilepsy. Caregiver stress was significantly increased for caregivers with a native language other than English or French, caregivers who had a second child with a chronic disease and sole caregivers.
C.1 Utility of genetic testing in the pre-surgical evaluation of children with drug-resistant epilepsy
Authors: Alsubhi S
Published: May 2024

Background: All patients with drug-resistant focal epilepsy, should undergo an evaluation to determine if non-medical options, including surgical intervention, are appropriate. This evaluation involves a thorough work-up, typically including some or all of neuropsychological evaluation, prolonged video EEG monitoring, and advanced neuroimaging. The utility of genetic testing as part of this evaluation has not been thoroughly investigated. Methods: In this retrospective study, we reviewed the charts of pediatric patients referred for epilepsy surgery evaluation over a 5-year period. We extracted and analyzed results of genetic testing as well as clinical, EEG, and neuroimaging data. Results: 125 patients were referred for epilepsy surgical evaluation, 86 of whom had some form of genetic testing. Of these, 18 had a pathogenic or likely pathogenic variant identified. Genes affected included NPRL3, TSC2, KCNH1, CHRNA4, SPTAN1, DEPDC5, SCN2A, ARX, SCN1A, DLG4, and ST5. One patient had ring chromosome 20, one a 7.17p12 duplication, and one a 15q13 deletion. A specific medical therapy choice was allowed due to genetic diagnosis in three patients who did not undergo surgery. Conclusions: Obtaining a molecular diagnosis may dramatically alter management in children with drug-resistant focal epilepsy. Genetic testing should be incorporated as part of standard investigations in the pre-surgical work-up of such patients.
D.6 Neurological care and outcomes of pregnant patients with epilepsy in a Canadian tertiary care center (2014-2020)
Authors: Chan S , Iyengar Y , Snelgrove J , Hebert J , Bui E
Published: May 2024

Background: Limited data exists on neurological care and outcomes of Canadian pregnant patients with epilepsy (PPWE). This study provides Canadian data to inform practice patterns and observed outcomes for PPWE at a tertiary care center. Methods: PPWE receiving care at the University Health Network (Toronto, Canada) epilepsy clinic from January 1, 2014 to November 20 2020 were retrospectively identified with demographics and neurological data and outcomes collected. Results: A total of 195 cases were identified, with a median maternal age of 32 years (SD 4.58), a median age at first seizure of 17 years (range 1 month – 36 years old), 52% were diagnosed with genetic generalized epilepsy and 50% endorsed 6 months of seizure freedom prior to conception. In pregnancy, 93% took ASM(s) with 77% receiving therapeutic drug monitoring (TDM) and drug dose adjustments reported in 69%. Most cases (73%) maintained a stable seizure frequency. Conclusions: This study provides new Canadian data on PPWE at a tertiary care center. PPWE are overall well controlled, more likely to have young adult onset, genetic generalized epilepsy with nearly all taking ASM(s) during pregnancy. While high rates of TDM and drug dose adjustments were observed, most experienced seizure stability in pregnancy.
Generalized transport characterizations for short oceanic internal waves in a sea of long waves
Authors: Lvov Yuri V. , Polzin Kurt L.
Published: May 2024

Wave turbulence provides a conceptual framework for weakly nonlinear interactions in dispersive media. Dating from five decades ago, applications of wave turbulence theory to oceanic internal waves assigned a leading-order role to interactions characterized by a near equivalence between the group velocity of high-frequency internal waves with the phase velocity of near-inertial waves. This scale-separated interaction leads to a Fokker–Planck (generalized diffusion) equation. More recently, starting four decades ago, this scale-separated paradigm has been investigated using ray tracing methods. These ray methods characterize spectral transport of energy by counting the amplitude and net velocity of wave packets in phase space past a high-wavenumber gate prior to ‘breaking’. This explicitly advective characterization is based on an intuitive assignment and lacks theoretical underpinning. When one takes an estimate of the net spectral drift from the wave turbulence derivation and makes the corresponding assessment, one obtains a prediction of spectral transport that is an order of magnitude larger than either observations or reported ray tracing estimates. Motivated by this contradiction, we report two parallel derivations for transport equations describing the refraction of high-frequency internal waves in a sea of random inertial waves. The first uses standard wave turbulence techniques and the second is an ensemble-averaged packet transport equation characterized by the dispersion of wave packets about a mean drift in the spectral domain. The ensemble-averaged transport equation for ray tracing differs in that it contains the intuitively motivated advective term. We conclude that the aforementioned contradiction between theory, numerics and observations needs to be taken at face value and present a pathway for resolving this contradiction.
Evaluating NMT using the non-inferiority principle
Authors: do Campo Bayón María , Sánchez-Gijón Pilar
Published: May 2024

The aim of this article is to propose a new neural machine translation (NMT) evaluation method based on the non-inferiority principle. In order to do that, we evaluate raw machine translation (MT) in terms of naturalness, which for this research is defined as not just the lack of fluency errors but also meeting the linguistic expectations of Galician end users when reading original texts in Galician. Our main objective is, in the first place, to validate the new methodology presented in our previous study by evaluating an NMT engine from Spanish into Galician for the social media domain that was retrained with a new Twitter corpus. This new methodology and NMT engine were applied after analyzing the conclusions of a pilot survey conducted among Twitter users to evaluate their perception of tweets translated from Spanish into Galician with our NMT engine created with a corpus of tweets. As in our preliminary study, our aim is to propose a robust quality approximation method based on the reception parameters of end users’ perceptions. This new survey was conducted in December of 2022 with the participation of 228 Galician-speaking Twitter users. Among the main changes proposed are the inclusion of more information about the participant profile, so the non-inferiority principle can be also evaluated according to these parameters; the inclusion of a new typology of tweets, the threads; the provision of context by means of presenting the tweets in their original display as shown in the Twitter app; a change in the number of tweets evaluated and the number of different questionnaires; the change in the distribution of the questionnaires; and the inclusion of an error classification human evaluation conducted by professional linguists to correlate the findings. We will present the steps carried out following the conclusions of the pilot study, describe the new study’s design, analyze the new findings, and present the final conclusions regarding the engine and the evaluation method based on the non-inferiority principle. Finally, we will also provide some examples of the use of this new methodology in the translation industry.
The prophylactic and therapeutic impact of Trichinella spiralis larvae excretory secretory antigens- loaded Ca-BTC metal organic frameworks on induced murine colitis
Authors: Fawzy E.M. , Selim M.A. , Mostafa N. E. , Abdelhameed R.M. , Darwish A.M. , Yousef A.M. , Alabiad M.A. , Ibrahim M.N. , Fawzy H.M. , Abdel Hamed E.F.
Published: May 2024

Background: Inflammatory bowel disease is an autoimmune disease that affects the gut. T. spiralis larvae (E/S Ags) loaded on calcium-benzene-1,3,5-tricarboxylate metal-organic frameworks (Ca-BTC MOFs) were tested to determine whether they might prevent or cure acetic acid-induced murine colitis. Methods: T. spiralis larvae E/S Ags/Ca-BTC MOFs were used in prophylactic and therapeutic groups to either precede or follow the development of murine colitis. On the seventh day after colitis, mice were slaughtered. The effect of our target antigens on the progress of the colitis was evaluated using a variety of measures, including survival rate, disease activity index, colon weight/bodyweight, colon weight/length) ratios, and ratings for macroscopic and microscopic colon damage. The levels of inflammatory cytokines (interferon-γ and interleukin-4), oxidative stress marker malondialdehyde, and glutathione peroxidase in serum samples were evaluated. Foxp3 T-reg expression was carried out in colonic and splenic tissues. Results: T. spiralis larvae E/S Ags/Ca-BTC MOFs were the most effective in alleviating severe inflammation in murine colitis. The survival rate, disease activity index score, colon weight/length and colon weight/bodyweight ratios, and gross and microscopic colon damage scores have all considerably improved. A large decrease in proinflammatory cytokine (interferon-γ) and oxidative stress marker (malondialdehyde) expression and a significant increase in interleukin-4 and glutathione peroxidase expression were obtained. The expression of Foxp3+ Treg cells was elevated in colonic and splenic tissues. Conclusion: T. spiralis larvae E/S Ags/Ca-BTC MOFs had the highest anti-inflammatory, antioxidant, and cytoprotective capabilities against murine colitis and might be used to develop new preventative and treatment strategies.
Ectoparasite and bacterial population genetics and community structure indicate extent of bat movement across an island chain
Authors: McKee Clifton D. , Peel Alison J. , Hayman David T. S. , Suu-Ire Richard , Ntiamoa-Baidu Yaa , Cunningham Andrew A. , Wood James L. N. , Webb Colleen T. , Kosoy Michael Y.
Published: May 2024

Few studies have examined the genetic population structure of vector-borne microparasites in wildlife, making it unclear how much these systems can reveal about the movement of their associated hosts. This study examined the complex host–vector–microbe interactions in a system of bats, wingless ectoparasitic bat flies (Nycteribiidae), vector-borne microparasitic bacteria (Bartonella) and bacterial endosymbionts of flies (Enterobacterales) across an island chain in the Gulf of Guinea, West Africa. Limited population structure was found in bat flies and Enterobacterales symbionts compared to that of their hosts. Significant isolation by distance was observed in the dissimilarity of Bartonella communities detected in flies from sampled populations of Eidolon helvum bats. These patterns indicate that, while genetic dispersal of bats between islands is limited, some non-reproductive movements may lead to the dispersal of ectoparasites and associated microbes. This study deepens our knowledge of the phylogeography of African fruit bats, their ectoparasites and associated bacteria. The results presented could inform models of pathogen transmission in these bat populations and increase our theoretical understanding of community ecology in host–microbe systems.
The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium
Authors: John Carol J. , Engler Meghan , Zaki Hania , Crooker Anna , Cabrera Maria , Golden Cassidy , Whitehill Robert , Xiang Yijin , Liu Katie , Fundora Michael P.
Published: May 2024

Objective:

Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation.

Design:

Retrospective study, July 1, 2017–May 31, 2022.

Setting:

Tertiary children’s hospital.

Patients:

Included were patients admitted to the paediatric cardiac ICU at Children’s Healthcare of Atlanta.

Interventions:

None.

Measurements and Main Results:

ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65–32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5–7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002).

Conclusions:

The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.
Cycles and their important shocks: completing the investigation
Authors: Gillman Max , Pagan Adrian
Published: May 2024

The paper looks at the question of measuring the importance of shocks to cycles. We consider two types of cycles - oscillations and those summarized by the NBER that require a study of growth in activity to establish turning points in the level of activity. The latter demarcate expansions and contractions. We establish a connection between these two concepts of cycles that shows shocks may have very different effects on each. As an application we look at a question that has often been asked over how important technology shocks are to cycles in activity? Some recent research concludes that total factor productivity (TFP) shocks are not important for oscillations and therefore models should be designed to reflect that. Using the same data we show that TFP shocks are very important to both types of cycles.
Inequality in iron and folic acid consumption and dietary diversity in pregnant women following exposure to maternal nutrition interventions in three low- and middle-income countries
Authors: Godha Deepali , Remancus Sandra , Sanghvi Tina
Published: May 2024

Objective:

Research is available on improved coverage and practices from several large-scale maternal nutrition programmes, but not much is known on change in inequalities. This study analyses wealth and education inequality using Erreygers and Concentration indices for four indicators: adequate iron and folic acid (IFA) consumption, women’s dietary diversity, and counselling on IFA and dietary diversity.

Design:

A pre-test–post-test, control group design.

Setting:

Maternal nutrition intervention programmes conducted in Bangladesh, Burkina Faso and Ethiopia during 2015–2022.

Participants:

Recently delivered women (RDW) and pregnant women (PW).

Results:

Statistically significant reductions in education inequality were observed for adequate IFA consumption, counselling on IFA and dietary diversity in intervention areas of Bangladesh and for adequate IFA consumption in intervention areas of Burkina Faso.

A significant decrease in wealth inequality was observed for adequate IFA consumption in the intervention areas of Bangladesh, whereas a significant increase was observed in the non-intervention areas for counselling on IFA in Ethiopia and for dietary diversity in Burkina Faso.

Conclusion:

The results can be attributed to the extensive delivery system at community level in Bangladesh and being predominantly facility-based in Burkina Faso and Ethiopia. COVID-19 disruptions (in Burkina Faso and Ethiopia) and indicator choice also had a role in the results.

The main takeaways for nutrition programmes are as follows: (a) assessing inequality issues through formative studies during designing, (b) monitoring inequality indicators during implementation, (c) diligently addressing inequality through targeted interventions, setting aside resources and motivating frontline workers to reduce disparities and (d) making inequality analysis a routine part of impact evaluations.
ELECTRO-OSMOTIC EFFECT ON PERISTALTIC FLOW OF PHAN–THIEN–TANNER FLUID IN A PLANAR CHANNEL
Authors: CHANNAKOTE MAHADEV M. , M. SHEKAR , DILIPKUMAR V. K.
Published: May 2024

There are several factors that can cause the excessive accumulation of biofluid in human tissue, such as pregnancy, local traumas, allergic responses or the use of certain therapeutic medications. This study aims to further investigate the shear-dependent peristaltic flow of Phan–Thien–Tanner (PTT) fluid within a planar channel by incorporating the phenomenon of electro-osmosis. This research is driven by the potential biomedical applications of this knowledge. The non-Newtonian fluid features of the PTT fluid model are considered as physiological fluid in a symmetric planar channel. This study is significant, as it demonstrates that the chyme in the small intestine can be modelled as a PTT fluid. The governing equations for the flow of the ionic liquid, thermal radiation and heat transfer, along with the Poisson–Boltzmann equation within the electrical double layer, are discussed. The long-wavelength (
$\delta \ll 1$
) and low-Reynolds-number approximations (
$Re \to 0$
) are used to simplify the simultaneous equations. The solutions analyse the Debye electronic length parameter, Helmholtz–Smoluchowski velocity, Prandtl number and thermal radiation. Additionally, streamlines are used to examine the phenomenon of entrapment. Graphs are used to explain the influence of different parameters on the flow and temperature. The findings of the current model have practical implications in the design of microfluidic devices for different particle transport phenomena at the micro level. Additionally, the noteworthy results highlight the advantages of electro-osmosis in controlling both flow and heat transfer. Ultimately, our objective is to use these findings as a guide for the advancement of lab-on-a-chip systems.
Enhanced labour protection for prisoners of war
Authors: Via Balole Christian , van Steenberghe Raphaël
Published: May 2024

The principle of prohibiting forced labour exists in both treaty and customary international law. However, there are limits to this prohibition, in that certain types of forced labour are actually permitted; this is the case for forced labour performed by prisoners of war (PoWs). This paper examines the legal regime applicable to such labour. It starts by setting out the current rules, following a brief historical review. It then explains the shortcomings of those rules, which are open to abuse and are not focused exclusively on the rights and interests of the PoWs, before proposing two possible ways of improving the situation by means of a systemic approach. The first is based on international humanitarian law itself, while the second is based on the complementary relationship between that body of law and international human rights law. Such improvements would give PoWs the right to perform any available work while continuing to require them to carry out work exclusively dedicated to running the PoW camp.
The Paradoxical Effects of High Work Methods and Work Scheduling Autonomy
Authors: Bipp Tanja , Walczok Marvin
Published: May 2024

Abstract: Job autonomy is traditionally seen as a core job characteristic with positive effects on work outcomes. However, in today’s world of work, excessive levels of job autonomy have also been suggested to lead to demands with negative downstream effects. We investigated paradoxical effects of high levels of two autonomy facets with regard to work engagement. In an experimental vignette study ( N = 228 German employees), we manipulated two autonomy facets in a 2×2 between-subject design (high vs. low work methods autonomy vs. work scheduling autonomy). We found evidence for paradoxical effects for one facet: High levels of work scheduling autonomy directly stimulated work engagement but led to higher levels of work intensification therefore also (indirectly) hindering work engagement. To our knowledge, our findings are the first to provide evidence of the simultaneous paradoxical effects of work scheduling autonomy and an explanation for detrimental effects on work engagement via the intensification of work.
Confined at Sea at the End of the World
Authors: Moutinho Sofia
Published: May 2024

Embedded on a research cruise in the Antarctic, a journalist joins a scientists’ “summer camp.”
Mechanisms of neuromodulatory volume transmission
Authors: Özçete Özge D. , Banerjee Aditi , Kaeser Pascal S.
Published: May 2024

A wealth of neuromodulatory transmitters regulate synaptic circuits in the brain. Their mode of signaling, often called volume transmission, differs from classical synaptic transmission in important ways. In synaptic transmission, vesicles rapidly fuse in response to action potentials and release their transmitter content. The transmitters are then sensed by nearby receptors on select target cells with minimal delay. Signal transmission is restricted to synaptic contacts and typically occurs within ~1 ms. Volume transmission doesn’t rely on synaptic contact sites and is the main mode of monoamines and neuropeptides, important neuromodulators in the brain. It is less precise than synaptic transmission, and the underlying molecular mechanisms and spatiotemporal scales are often not well understood. Here, we review literature on mechanisms of volume transmission and raise scientific questions that should be addressed in the years ahead. We define five domains by which volume transmission systems can differ from synaptic transmission and from one another. These domains are (1) innervation patterns and firing properties, (2) transmitter synthesis and loading into different types of vesicles, (3) architecture and distribution of release sites, (4) transmitter diffusion, degradation, and reuptake, and (5) receptor types and their positioning on target cells. We discuss these five domains for dopamine, a well-studied monoamine, and then compare the literature on dopamine with that on norepinephrine and serotonin. We include assessments of neuropeptide signaling and of central acetylcholine transmission. Through this review, we provide a molecular and cellular framework for volume transmission. This mechanistic knowledge is essential to define how neuromodulatory systems control behavior in health and disease and to understand how they are modulated by medical treatments and by drugs of abuse.
Surgical treatment of peri-implantitis
Authors: Roccuzzo Mario , Mirra Davide , Roccuzzo Andrea
Published: May 2024

As utilisation of dental implants continues to rise, so does the incidence of biological complications. When peri-implantitis has already caused extensive bone resorption, the dentist faces the dilemma of which therapy is the most appropriate to maintain the implant. Since non-surgical approaches of peri-implantitis have shown limited effectiveness, the present paper describes different surgical treatment modalities, underlining their indications and limitations. The primary goal in the management of peri-implantitis is to decontaminate the surface of the infected implant and to eliminate deep peri-implant pockets. For this purpose, access flap debridement, with or without resective procedures, has shown to be effective in a large number of cases. These surgical treatments, however, may be linked to post-operative recession of the mucosal margin. In addition to disease resolution, reconstructive approaches also seek to regenerate the bone defect and to achieve re-osseointegration.
EGFR inhibits TNF-α-mediated pathway by phosphorylating TNFR1 at tyrosine 360 and 401
Authors: Nam Young Woo , Shin June-Ha , Kim Seongmi , Hwang Chi Hyun , Lee Choong-Sil , Hwang Gyuho , Kim Hwa-Ryeon , Roe Jae-Seok , Song Jaewhan
Published: May 2024

Tumour necrosis factor receptor 1 (TNFR1) induces the nuclear factor kappa-B (NF-κB) signalling pathway and regulated cell death processes when TNF-α ligates with it. Although mechanisms regulating the downstream pathways of TNFR1 have been elucidated, the direct regulation of TNFR1 itself is not well known. In this study, we showed that the kinase domain of the epidermal growth factor receptor (EGFR) regulates NF-κB signalling and TNF-α-induced cell death by directly phosphorylating TNFR1 at Tyr 360 and 401 in its death domain. In contrast, EGFR inhibition by EGFR inhibitors, such as erlotinib and gefitinib, prevented their interaction. Once TNFR1 is phosphorylated, its death domain induces the suppression of the NF-κB pathways, complex II-mediated apoptosis, or necrosome-dependent necroptosis. Physiologically, in mouse models, EGF treatment mitigates TNF-α-dependent necroptotic skin inflammation induced by treatment with IAP and caspase inhibitors. Our study revealed a novel role for EGFR in directly regulating TNF-α-related pathways.
Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals
Authors: Louvrou Varvara , Solianik Rima , Brazaitis Marius , Erhardt Sophie
Published: May 2024

Background/objectives

Prolonged fasting triggers a stress response within the human body. Our objective was to investigate the impact of prolonged fasting, in conjunction with stress, on kynurenine pathway metabolites.

Subjects/methods

Healthy males were divided into fasting group (zero-calorie-restriction) for 6 days (FAST, n = 14), and control group (CON, n = 10). Blood and saliva samples were collected at baseline, Day 2, Day 4, Day 6 during fasting period, and 1 week after resuming regular diet. Plasma levels of kynurenine pathway metabolites were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Plasma and salivary samples were analyzed for stress markers.

Results

A pronounced activation of the kynurenine pathway in individuals on FAST trial was revealed. Concentrations of picolinic acid (PIC), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were significantly increased, with peak levels observed on Day 6 (P < 0.0001). Conversely, concentrations of tryptophan (TRP) and quinolinic acid (QUIN) decreased (P < 0.0001), while kynurenine (KYN) and nicotinamide (NAM) levels remained stable. Cortisol and noradrenaline concentrations remained unchanged. However, adrenaline levels significantly increased on Day 4 within FAST compared to CON (P = 0.005). Notably, all deviations in kynurenine pathway metabolite levels returned to baseline values upon resuming regular diet following the 6-day fasting regimen, even when weight and BMI parameters were not restored.

Conclusions

Extended fasting over 6 days induces the kynurenine pathway and has minimal effects on stress markers. Restoration of metabolite concentrations upon regular feeding implies rapid adaptation of the kynurenine pathway synthetic enzymes to maintain homeostasis when faced with perturbations.
Treating myasthenia gravis beyond the eye clinic
Authors: Jacob Saiju
Published: May 2024

Myasthenia gravis (MG) is one of the most well characterised autoimmune disorders affecting the neuromuscular junction with autoantibodies targeting the acetylcholine receptor (AChR) complex. The vast majority of patients present with ocular symptoms including double vision and ptosis, but may progress on to develop generalised fatiguable muscle weakness. Severe involvement of the bulbar muscles can lead to dysphagia, dysarthria and breathing difficulties which can progress to myasthenic crisis needing ventilatory support. Given the predominant ocular onset of the disease, it is important that ophthalmologists are aware of the differential diagnosis, investigations and management including evolving therapies. When the disease remains localised to the extraocular muscles (ocular MG) IgG1 and IgG3 antibodies against the AChR (including clustered AChR) are present in nearly 50% of patients. In generalised MG this is seen in nearly 90% patients. Other antibodies include those against muscle specific tyrosine kinase (MuSK) and lipoprotein receptor related protein 4 (LRP4). Even though decremental response on repetitive nerve stimulation is the most well recognised neurophysiological abnormality, single fibre electromyogram (SFEMG) in experienced hands is the most sensitive test which helps in the diagnosis. Initial treatment should be using cholinesterase inhibitors and then proceeding to immunosuppression using corticosteroids and steroid sparing drugs. Patients requiring bulbar muscle support may need rescue therapies including plasma exchange and intravenous immunoglobulin (IVIg). Newer therapeutic targets include those against the B lymphocytes, complement system, neonatal Fc receptors (FcRn) and various other elements of the immune system.
Repurposing a plant peptide cyclase for targeted lysine acylation
Authors: Rehm Fabian B. H. , Tyler Tristan J. , Zhou Yan , Huang Yen-Hua , Wang Conan K. , Lawrence Nicole , Craik David J. , Durek Thomas
Published: May 2024

Transpeptidases are powerful tools for protein engineering but are largely restricted to acting at protein backbone termini. Alternative enzymatic approaches for internal protein labelling require bulky recognition motifs or non-proteinogenic reaction partners, potentially restricting which proteins can be modified or the types of modification that can be installed. Here we report a strategy for labelling lysine side chain ε-amines by repurposing an engineered asparaginyl ligase, which naturally catalyses peptide head-to-tail cyclization, for versatile isopeptide ligations that are compatible with peptidic substrates. We find that internal lysines with an adjacent leucine residue mimic the conventional N-terminal glycine–leucine substrate. This dipeptide motif enables efficient intra- or intermolecular ligation through internal lysine side chains, minimally leaving an asparagine C-terminally linked to the lysine side chain via an isopeptide bond. The versatility of this approach is demonstrated by the chemoenzymatic synthesis of peptides with non-native C terminus-to-side chain topology and the conjugation of chemically modified peptides to recombinant proteins.
Prediction of recurrence risk in endometrial cancer with multimodal deep learning
Authors: Volinsky-Fremond Sarah , Horeweg Nanda , Andani Sonali , Barkey Wolf Jurriaan , Lafarge Maxime W. , de Kroon Cor D. , Ørtoft Gitte , Høgdall Estrid , Dijkstra Jouke , Jobsen Jan J. , Lutgens Ludy C. H. W. , Powell Melanie E. , Mileshkin Linda R. , Mackay Helen , Leary Alexandra , Katsaros Dionyssios , Nijman Hans W. , de Boer Stephanie M. , Nout Remi A. , de Bruyn Marco , Church David , Smit Vincent T. H. B. M. , Creutzberg Carien L. , Koelzer Viktor H. , Bosse Tjalling
Published: May 2024

Predicting distant recurrence of endometrial cancer (EC) is crucial for personalized adjuvant treatment. The current gold standard of combined pathological and molecular profiling is costly, hampering implementation. Here we developed HECTOR (histopathology-based endometrial cancer tailored outcome risk), a multimodal deep learning prognostic model using hematoxylin and eosin-stained, whole-slide images and tumor stage as input, on 2,072 patients from eight EC cohorts including the PORTEC-1/-2/-3 randomized trials. HECTOR demonstrated C-indices in internal (n = 353) and two external (n = 160 andn = 151) test sets of 0.789, 0.828 and 0.815, respectively, outperforming the current gold standard, and identified patients with markedly different outcomes (10-year distant recurrence-free probabilities of 97.0%, 77.7% and 58.1% for HECTOR low-, intermediate- and high-risk groups, respectively, by Kaplan–Meier analysis). HECTOR also predicted adjuvant chemotherapy benefit better than current methods. Morphological and genomic feature extraction identified correlates of HECTOR risk groups, some with therapeutic potential. HECTOR improves on the current gold standard and may help delivery of personalized treatment in EC.
Construction and optimization of Green Infrastructure Network in mountainous cities: a case study of Fuzhou, China
Authors: Huang He , Fu Danling , Ding Guochang , Yan Chen , Xie Xiangcai , Gao Yaling , Liu Qunyue
Published: May 2024

Green infrastructure networks enhance the protection and improvement of urban ecological environments, augment the efficiency and quality of ecosystem services, and furnish residents with healthier and more comfortable living conditions. Although previous research has investigated the construction or optimization methods of green infrastructure networks, these studies have been relatively isolated and lacking in case studies for mountainous cities. In the development of green infrastructure, mountainous cities must specifically consider the impact of terrain on network construction. Taking Fuzhou, a mountainous city in China, as an example, this study constructs and optimizes the green infrastructure network by employing morphological spatial pattern analysis, connectivity analysis, the Minimum Cumulative Resistance model, and circuit theory. These methodologies increase the connectivity of the Green Infrastructure within the study area, thereby promoting the health of the local ecosystem and creating conducive circumstances for the city’s sustainable development. The findings reveal that: (1) Green infrastructure in Fuzhou takes up 5366.38 ha, constituting 21.76% of the study area, primarily situated in the northwest and south; (2) Fuzhou’s Green Infrastructure network comprises 10 hubs and 17 corridors with a hub area of 1306.98 ha, predominantly distributed in the mountains encircling the city, including Meifeng Mountain, Gaogai Mountain, and Qingliang Mountain; (3) Based on optimization, the circuit centrality index categorizes hub importance into three protection levels, pinpointing nine crucial protected areas in the corridors and 680 areas requiring enhancement, including 68 areas for first-level improvement, 149 areas for second-level improvement, and 463 areas for third-level improvement. This research offers a methodological reference for constructing and optimizing green infrastructure networks in mountainous cities, providing both theoretical and practical foundations for optimizing green infrastructure networks in Fuzhou City.
FFF print defect characterization through in-situ electrical resistance monitoring
Authors: Jonkers Heime , Dijkshoorn Alexander , Stramigioli Stefano , Krijnen Gijs
Published: May 2024

Fused filament fabrication is a popular fabrication technique. Currently there is a need for in-situ monitoring modalities to gather real-time information on prints, both for quality control and closed-loop control. Despite current advancements, effective and affordable in-situ monitoring techniques for non-destructive defect detection of voids and bonding quality are still limited. This work demonstrates in-situ monitoring of fused filament fabrication through electrical resistance measurements as an alternative to thermal and optical methods. A new, easy-to-implement setup is demonstrated which measures the electrical resistance of a conductively doped filament between the nozzle and single or multi-electrodes on the bed. Defects can be located in an unprecedented way with the use of encoded axes in combination with the observed resistance variations throughout the part. A model of the anisotropic electrical conduction is used to interpret the measurements, which matches well with the data. Warping, inter-layer adhesion, under-extrusion and overhang sagging print defects can be observed in the measurements of parts with a complex geometry, which would be difficult to measure otherwise. Altogether in-situ electrical resistance monitoring offers a tool for optimising prints by online studying the influence of the print parameters for quality assessment and it opens up possibilities for closed-loop control.
Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease in Indians: a pilot study
Authors: Choudhury Raj Rajeshwar , Gupta Harshi , Bhushan Sudha , Singh Archna , Roy Ambuj , Saini Neeru
Published: May 2024

Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.
Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages
Authors: Flores-Valdez Mario Alberto , Peterson Eliza J. R. , Aceves-Sánchez Michel de Jesús , Baliga Nitin S. , Morita Yasu S. , Sparks Ian L. , Saini Deepak Kumar , Yadav Rahul , Lang Roland , Mata-Espinosa Dulce , León-Contreras Juan Carlos , Hernández-Pando Rogelio
Published: May 2024

We have previously reported the transcriptomic and lipidomic profile of the first-generation, hygromycin-resistant (HygR) version of the BCGΔBCG1419c vaccine candidate, under biofilm conditions. We recently constructed and characterized the efficacy, safety, whole genome sequence, and proteomic profile of a second-generation version of BCGΔBCG1419c, a strain lacking the BCG1419c gene and devoid of antibiotic markers. Here, we compared the antibiotic-less BCGΔBCG1419c with BCG. We assessed their colonial and ultrastructural morphology, biofilm, c-di-GMP production in vitro, as well as their transcriptomic and lipidomic profiles, including their capacity to activate macrophages via Mincle and Myd88. Our results show that BCGΔBCG1419c colonial and ultrastructural morphology, c-di-GMP, and biofilm production differed from parental BCG, whereas we found no significant changes in its lipidomic profile either in biofilm or planktonic growth conditions. Transcriptomic profiling suggests changes in BCGΔBCG1419c cell wall and showed reduced transcription of some members of the DosR, MtrA, and ArgR regulons. Finally, induction of TNF-α, IL-6 or G-CSF by bone-marrow derived macrophages infected with either BCGΔBCG1419c or BCG required Mincle and Myd88. Our results confirm that some differences already found to occur in HygR BCGΔBCG1419c compared with BCG are maintained in the antibiotic-less version of this vaccine candidate except changes in production of PDIM. Comparison with previous characterizations conducted by OMICs show that some differences observed in BCGΔBCG1419c compared with BCG are maintained whereas others are dependent on the growth condition employed to culture them.
Efficacy of melatonin in alleviating disorders arising from repeated exposure to sevoflurane in males and females of the Wistar rats during preadolescence
Authors: Heydari Fatemeh , Nasiri Mahdieh , Haroabadi Arash , Fahanik Babaei Javad , Pestehei Seyed Khalil
Published: May 2024

Pediatricians use sevoflurane due to its fast action and short recovery time. However, studies have shown that repeated exposure to anesthesia can affect learning and memory. Melatonin, an indole-type neuroendocrine hormone, has significant anti-inflammatory, and neuroprotective properties. Melatonin’s impact on cognitive behavior in sevoflurane-anesthetized males and females of the Wistar rats during preadolescence was examined in this research. The cognitive function was evaluated by shuttle box and morris water maze tests, while interleukin-10, Catalase (CAT), Malondialdehyde (MDA), and Tumor Necrosis Factor-α (TNF-α) were evaluated using ELISA kits. The expression levels of the apoptosis-linked proteins, Bax, Bcl-2, and caspase-3, were determined using the western blotting technique. The learning and memory latencies of the rats were more significant in the sevoflurane groups than in the control group; however, the latencies were significantly shorter in the sevoflurane and melatonin groups than in the control group. The levels of MDA, TNF-α, Bax, and caspase-3 were significantly higher in the sevoflurane groups than in the control group. We also found that the levels of CAT and Bcl-2 were significantly reduced in the sevoflurane groups compared to the control group. Increasing levels of CAT, Bcl-2, and decreasing levels of MDA, TNF-α, Bax, and caspase-3 in response to melatonin indicate a possible contribution to the recovery from the sevoflurane impairment. Melatonin shows neuroprotective effects in male and female rats with sevoflurane-induced cognitive impairment. This suggests melatonin could be a valuable treatment for learning and memory deficits resulting from repeated exposure to sevoflurane, possibly by controlling apoptosis, oxidative stress, and inflammation.
Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates
Authors: Atkinson-Clement Cyril , Alkhawashki Mohammad , Ross James , Gatica Marilyn , Zhang Chencheng , Sallet Jerome , Kaiser Marcus
Published: May 2024

Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.
Body mass index is associated with clinical outcomes in idiopathic pulmonary fibrosis
Authors: Yoon Hee-Young , Kim Hoseob , Bae Yoonjong , Song Jin Woo
Published: May 2024

Association between body mass index (BMI) and prognosis in patients with idiopathic pulmonary fibrosis (IPF) remains uncertain. We investigated the association between BMI and clinical outcomes in patients with IPF using national health claims data. The study included 11,826 patients with IPF and rare incurable disease exemption codes (mean age: 68.9 years, male: 73.8%) and available BMI data who visited medical institutions between January 2002 and December 2018. Multivariable Cox proportional hazard models were used to evaluate the association of BMI with all-cause mortality and hospitalization. Based on BMI, 3.1%, 32.8%, 27.8%, and 36.4% were classified as underweight, normal, overweight, and obese, respectively. Multivariable analysis showed independent associations of overweight (hazard ratio [HR] 0.856, 95% confidence interval [CI] 0.801–0.916) and underweight (HR 1.538, 95% CI 1.347–1.757) with mortality in patients with IPF. Similarly, overweight (HR 0.887, 95% CI 0.834–0.943) and underweight (HR 1.265, 95% CI 1.104–1.449) were also associated with hospitalization in patients with IPF in the multivariable analysis. Spline HR curve analysis adjusted for all covariates revealed a non-linear relationship between BMI and mortality in patients with IPF. Our data suggest that BMI is associated with clinical outcomes in patients with IPF.