bluuebunny/crossref_metadata_2025 huggingface dataset:
KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in Children and Adults: a commentary from the European Renal Best Practice (ERBP)
Authors: Iatridi Fotini , Carrero Juan Jesus , Gall Emilie Cornec-Le , Kanbay Mehmet , Luyckx Valerie , Shroff Rukshana , Ferro Charles J
Published: September 2024

The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guideline for Identification and Management of Chronic Kidney Disease (CKD) is a welcome development, coming 12 years after the paradigm-changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists, now being proven in multiple randomized controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD Guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and the fact that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such, the KDIGO 2024 CKD Guideline should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it.
Baseline factors relating to depressive symptoms at one year postoperative in patients with diffuse glioma
Authors: Belgers Vera , Tolver Anders , Klein Martin , Douw Linda , Niers Johanna M , Piil Karin , de Witt Hamer Philip C
Published: September 2024

Background

Depressive symptoms are common in patients with diffuse glioma, potentially reducing their quality of life. Understanding baseline factors associated with the development of depressive symptoms is important for psychoeducation and early intervention. This study investigates the associations of baseline patient- and tumor-related characteristics and depressive symptoms 1 year after surgery.

Methods

We combined retrospective longitudinal datasets from Amsterdam UMC and Rigshospitalet Copenhagen. Several characteristics of patients and tumors were retrieved, in particular items of their mood and functioning status. Depression instruments were harmonized to the Patient-Reported Outcomes Measurement Information System Depression scale through previously developed item response theory. Functioning items were harmonized to the International Classification of Functioning, Disability, and Health (ICF) domains using linking methods published previously. We analyzed the associations of 25 baseline factors with depressive symptoms one year after surgery by multivariable stepwise backward linear regression models and verified model robustness using best subset selection.

Results

We included 118 patients with diffuse glioma with a mean age of 48 years and a glioblastoma in 29%. Baseline depressive symptoms, lower ICF energy, and impaired ICF language functioning were associated with more depressive symptoms at follow-up in the multivariable model (R-squared: 0.379).

Conclusions

We identified 3 key baseline factors associated with depressive symptoms one year after surgery. Clinically, our findings contribute to the comprehension of predictive factors for depressive symptoms, aiding healthcare providers and patients in understanding and possibly allowing for early intervention.
Reporting standards in randomized controlled trials involving neuro-oncology caregivers: A systematic review report from the RANO-Cares working group
Authors: Boele Florien W , Hertler Caroline , Sherwood Paula , Cachia David , Dirven Linda , Young Jacob S , Walbert Tobias , Stockdill Macy , Rodriguez Almaraz Eduardo , Piil Karin
Published: September 2024

Background

Family caregivers in neuro-oncology (eg, spouse, family member, friend to a patient) have high unmet support needs, yet intervention trials and effective support options are scarce. The Response Assessment in Neuro-Oncology (RANO)-Cares working group investigated the methodological quality of neuro-oncology caregiver outcomes reporting in randomized controlled trials (RCTs).

Methods

A systematic review was performed to evaluate to what extent RCTs assessing outcomes of caregivers of adult primary brain tumor patients adhere to minimum reporting standards. A 33-item checklist (23 applicable to secondary analysis reports) based on the International Society for Quality of Life Research (ISOQOL) criteria for patient-reported outcome reporting was used. Risk of bias was assessed per RCT.

Results

Fifteen publications from 11 unique RCTs included 676 neuro-oncology caregivers, with low overall risk of bias. Ten publications (66%) reported on caregiver outcomes as a primary aim, of which 8 (80%) satisfied ≥2/3 of the key methodological criteria. Of the 5 secondary analysis reports (33%), 2 (40%) met ≥2/3 of applicable key criteria. Criteria often not reported adequately included sample size calculations (reported adequately in n = 8, 53%), participant flow (n = 9, 60%) window for data collection (n = 1, 6%), and extent of (n = 10, 66%), reasons for (n = 9, 60%), and statistical approaches in dealing with (n = 4, 26%) missing data.

Conclusions

Whilst there are opportunities to enhance reporting standards, RCTs that include neuro-oncology caregiver outcomes generally adhere to high-quality reporting standards and have low risk of bias, indicating good potential to impact clinical practice.
Recent advances in microenvironment regulation for electrocatalysis
Authors: Xu Zhiyuan , Tan Xin , Chen Chang , Wang Xingdong , Sui Rui , Zhuang Zhongbin , Zhang Chao , Chen Chen
Published: September 2024

High-efficiency electrocatalysis could serve as the bridge that connects renewable energy technologies, hydrogen economy and carbon capture/utilization, promising a sustainable future for humankind. It is therefore of paramount significance to explore feasible strategies to modulate the relevant electrocatalytic reactions and optimize device performances so as to promote their large-scale practical applications. Microenvironment regulation at the catalytic interface has been demonstrated to be capable of effectively enhancing the reaction rates and improving the selectivities for specific products. In this review we summarize the latest advances in microenvironment regulation in typical electrocatalytic processes (including water electrolysis, hydrogen–oxygen fuel cells, and carbon dioxide reduction) and the related in situ/operando characterization techniques and theoretical simulation methods. At the end of this article, we present an outlook on development trends and possible future directions.
Effect of Severe Fever With Thrombocytopenia Syndrome Virus Genotype on Disease Severity, Viral Load, and Cytokines in South Korea
Authors: Kwon Ji-Soo , Kim Ji Yeun , Jang Choi Young , Son Ju Yeon , Kim Woori , Kim Taeeun , Park Se Yoon , Kim Min-Chul , Park Seong Yeon , Cha Hye Hee , Jang Hyeon Mu , Kim Min-Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Kim Sung-Han
Published: September 2024

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by Bandavirus dabieense (SFTS virus [SFTSV]). Recently, at least 6 different genotypes of SFTSV have been identified, with genotypes A, D, and F dominant in China and B dominant in Japan and Korea. This study investigated the effect of SFTSV genotypes circulating in South Korea on disease severity, viral load, and cytokine profile.

Methods

We prospectively enrolled 70 patients with SFTS from July 2015 to June 2022. Serial plasma samples were obtained during hospitalization and analyzed. Viral load was measured by real-time reverse-transcription polymerase chain reaction. Partial sequences of the viral genome were analyzed for genotyping. Plasma concentrations of 17 cytokines were measured by multiplex-bead immunoassay.

Results

Of 70 samples, 51 could be genotyped. Genotype B was predominant (80.4%) and other genotypes were uncommon. Intensive care unit admission rates (51.2% vs 50.0%) and mortality rates (26.8% vs 40.0%) did not show any significant differences between genotype B and non-B genotypes. The initial viral load did not show any significant differences (3.59 vs 3.64 log copies/μL), whereas viral load measured at hospital day 3–4 tended to be higher in genotype B than non-B genotypes (3.83 vs 1.83 log copies/μL, P = .07). Additionally, the plasma concentrations of interferon-α, interleukin 10, and interferon-γ–induced protein 10, which are closely related to mortality in cases of SFTS, did not show any significant differences.

Conclusions

SFTSV genotype B was the prevalent genotype in South Korea, with no genotype-specific difference in clinical outcomes, initial viral load, or cytokine profiles.
Mortality risk assessment using deep learning-based frequency analysis of electroencephalography and electrooculography in sleep
Authors: Kristjánsson Teitur Óli , Stone Katie L , Sorensen Helge B D , Brink-Kjaer Andreas , Mignot Emmanuel , Jennum Poul
Published: September 2024

Study Objectives

To assess whether the frequency content of electroencephalography (EEG) and electrooculography (EOG) during nocturnal polysomnography (PSG) can predict all-cause mortality.

Methods

Power spectra from PSGs of 8716 participants, including from the MrOS Sleep Study and the Sleep Heart Health Study, were analyzed in deep learning-based survival models. The best-performing model was further examined using SHapley Additive Explanation (SHAP) for data-driven sleep-stage specific definitions of power bands, which were evaluated in predicting mortality using Cox Proportional Hazards models.

Results

Survival analyses, adjusted for known covariates, identified multiple EEG frequency bands across all sleep stages predicting all-cause mortality. For EEG, we found an all-cause mortality hazard ratio (HR) of 0.90 (CI: 95% 0.85 to 0.96) for 12–15 Hz in N2, 0.86 (CI: 95% 0.82 to 0.91) for 0.75–1.5 Hz in N3, and 0.87 (CI: 95% 0.83 to 0.92) for 14.75–33.5 Hz in rapid-eye-movement sleep. For EOG, we found several low-frequency effects including an all-cause mortality HR of 1.19 (CI: 95% 1.11 to 1.28) for 0.25 Hz in N3, 1.11 (CI: 95% 1.03 to 1.21) for 0.75 Hz in N1, and 1.11 (CI: 95% 1.03 to 1.20) for 1.25–1.75 Hz in wake. The gain in the concordance index (C-index) for all-cause mortality is minimal, with only a 0.24% increase: The best single mortality predictor was EEG N3 (0–0.5 Hz) with a C-index of 77.78% compared to 77.54% for confounders alone.

Conclusions

Spectral power features, possibly reflecting abnormal sleep microstructure, are associated with mortality risk. These findings add to a growing literature suggesting that sleep contains incipient predictors of health and mortality.
In vitro transcription-based biosensing of glycolate for prototyping of a complex enzyme cascade
Authors: Barthel Sebastian , Brenker Luca , Diehl Christoph , Bohra Nitin , Giaveri Simone , Paczia Nicole , Erb Tobias J
Published: September 2024

In vitro metabolic systems allow the reconstitution of natural and new-to-nature pathways outside of their cellular context and are of increasing interest in bottom-up synthetic biology, cell-free manufacturing, and metabolic engineering. Yet, the analysis of the activity of such in vitro networks is very often restricted by time- and cost-intensive methods. To overcome these limitations, we sought to develop an in vitro transcription (IVT)-based biosensing workflow that is compatible with the complex conditions of in vitro metabolism, such as the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle, a 27-component in vitro metabolic system that converts CO2 into glycolate. As proof of concept, we constructed a novel glycolate sensor module that is based on the transcriptional repressor GlcR from Paracoccus denitrificans and established an IVT biosensing workflow that allows us to quantify glycolate from CETCH samples in the micromolar to millimolar range. We investigate the influence of 13 (shared) cofactors between the two in vitro systems to show that Mg2+, adenosine triphosphate , and other phosphorylated metabolites are critical for robust signal output. Our optimized IVT biosensor correlates well with liquid chromatography–mass spectrometry–based glycolate quantification of CETCH samples, with one or multiple components varying (linear correlation 0.94–0.98), but notably at ∼10-fold lowered cost and ∼10 times faster turnover time. Our results demonstrate the potential and challenges of IVT-based systems to quantify and prototype the activity of complex reaction cascades and in vitro metabolic networks.
Innovation in viruses: fitness valley crossing, neutral landscapes, or just duplications?
Authors: Banse Paul , Elena Santiago F , Beslon Guillaume
Published: September 2024

Viruses evolve by periods of relative stasis interleaved with sudden, rapid series of mutation fixations, known as evolutionary bursts. These bursts can be triggered by external factors, such as environmental changes, antiviral therapies, or spill-overs from reservoirs into novel host species. However, it has also been suggested that bursts may result from the intrinsic evolutionary dynamics of viruses. Indeed, bursts could be caused by fitness valley crossing, or a neutral exploration of a fitness plateau until an escape mutant is found. In order to investigate the importance of these intrinsic causes of evolutionary bursts, we used a simulation software package to perform massive evolution experiments of viral-like genomes. We tested two conditions: (i) after an external change and (ii) in a constant environment, with the latter condition guaranteeing the absence of an external triggering factor. As expected, an external change was almost systematically followed by an evolutionary burst. However, we also observed bursts in the constant environment as well, albeit much less frequently. We analyzed how many of these bursts are triggered by deleterious, quasi-neutral, or beneficial mutations and show that, while bursts can occasionally be triggered by valley crossing or traveling along neutral ridges, many of them were triggered by chromosomal rearrangements and, in particular, segmental duplications. Our results suggest that combinatorial differences between the different mutation types lead to punctuated evolutionary dynamics, with long periods of stasis occasionally interrupted by short periods of rapid evolution, akin to what is observed in virus evolution.
Is there a place for dorsal hemiepiphysiodesis of the first metatarsal in the treatment of pes cavovarus?
Authors: Domingues Liliana S. , Norte Susana , Thusing Mónika , Neves Manuel C.
Published: September 2024

The objective of this study is to describe and evaluate dorsal hemiepiphysodesis of the first metatarsal as an osteotomy replacement technique. Retrospective analysis of patients with pes cavovarus (PCV) treated in our center with dorsal hemiepiphysodesis of the first metatarsal. Meary’s angle, calcaneal pitch, and Moreau Costa Bartani were compared pre and post-operatively and the ratio between width and foot length was monitored. Between May 2012 and May 2022, eight patients (14 feet) with PCV underwent dorsal hemiepiphysiodesis of the first metatarsal combined with the Steindler procedure. Four patients (50%) were male. The average age for boys at surgery was 10.75 years (10–11) and for girls was 9.75 years (8–11). Most patients (87.5%) had idiopathic PCV and 12.5% had a neurological PCV. Median follow-up was 4.3 years (1.5–10) and a benefit was seen in all patients in Moreau Costa Bartani angle (112.64° vs. 120.59°; P value = 0.003), calcaneal pitch (26.48° vs. 25.36°; P value = 0.091) and Meary’s angle (10.60° vs. 5.36°; P value = 0.008) after surgery. Supination improvement was also shown (0.21 vs. 0.24; P value = 0.039). Despite the limited number of patients, the results demonstrated that dorsal hemiepiphysiodesis of the first metatarsal can be a valid alternative to osteotomy of the base of the first metatarsal, with less morbidity and a gradual and dynamic correction throughout growth.
Weight, height, waist circumference: association with knee osteoarthritis findings from the osteoarthritis initiative
Authors: Antoine Lisa H. , Watts Kristen Allen , Rumble Deanna D. , Buchanan Taylor , Sims Andrew , Goodin Burel R.
Published: September 2024

Introduction:

Global prevalence of knee osteoarthritis is more than 300 million. Uncontrollable risk factors include age, sex, and height. Controllable risk factors include trauma, weight, and waist circumference.

Objectives:

Our goal was to determine the association between knee osteoarthritis and anthropometric measures that include weight, height, and waist circumference.

Methods:

Using 4,602 participants (45–79 years) from the Osteoarthritis Initiative, we analyzed the association between knee osteoarthritis and anthropometry collectively and by sex. We calculated female and male tertiles (3 groups) for anthropometry.

Results:

Anthropometric measures were correlated with knee osteoarthritis (P ≤ 0.05) except the correlation between height and activities and height and quality of life. When comparing female weight tertiles, there were associations (P's < 0.001) between knee osteoarthritis and weight, but when comparing male weight tertiles, these associations were primarily between the lowest weight and highest weight groups. There were significant associations between knee osteoarthritis and height among female tertiles, with no differences among male tertiles. There were knee osteoarthritis/waist circumference tertile associations (P's < 0.001) for the lowest and highest waist circumference groups.

Conclusion:

Higher weight in female participants was a stronger predictor of increases in knee osteoarthritis discomforts when compared to waist circumference, while weight and waist circumference were almost equivalent in predicting increases in knee osteoarthritis for male participants. Height did not predict increases in knee osteoarthritis with the exception of female symptoms and quality of life. Quality of life for both sexes was the most unfavorable with female participants reporting a more unfavorable quality of life than male participants.
Blood folate level needed for fully effective neural tube defect prevention
Authors: Wald Nicholas J. , Vale Stephen H. , Bestwick Jonathan P. , Morris Joan K.
Published: September 2024

Introduction

Neural tube defects (NTDs) are a folate deficiency disorder. NTDs are preventable; increasing folic acid intake through food fortification or use of supplements increases serum and red blood cell folate and reduces the risk of a woman having an NTD pregnancy. There is controversy over whether there is a blood folate level needed to achieve the full preventive effect because of discrepant conclusions from studies investigating the relationship between folate levels and NTD risk. Resolving the controversy is important in determining public health policy.

Methods

Data from two studies conducted in Ireland and China were used to determine the relationship between serum folate and NTD risk. The relationship from each study was compared with the observed result in a randomised trial of folic acid that increased serum folate from 5 ng/ml to 44 ng/ml among the women who took the daily folic acid supplement before and during early pregnancy.

Results

Data from both studies showed a proportional (logarithmic) relationship between serum folate and NTD risk with no evidence of a folate threshold above which there is no further NTD risk reduction. Both studies accurately predicted the observed result from the randomised trial that achieved serum folate levels beyond the average levels found in the general population with an 83% preventive effect. This is higher than can be achieved with current levels of folic acid food fortification or with the recommended peri-conceptional use of 0.4mg supplements. The suggestion of a threshold is not due to discrepant data but the incorrect interpretation of the folate-NTD risk association when plotted on arithmetic scales which conceals the proportional relationship between the two.

Conclusion

To achieve fully effective fortification serum folate levels need to be about 44ng/ml.

Key Messages

What is already known on this topic

Neural tube defects (NTDs), among the most common serious birth defects worldwide, are a folate deficiency disorder. Increasing folic acid (vitamin B9) intake increases serum folate and reduces the risk of an NTD pregnancy. There is a difference of opinion on the serum folate level needed for fully effective NTD prevention.

What this study adds

There is no threshold above which NTD risk does not decrease and population folate levels need to be substantially increased to have the expected potential achieve effect on the prevention of NTDs.

How this study might affect research, practice or policy

A serum folate level of about 44ng/ml is a reasonable target to achieve an approximate 83% reduction in the prevalence of NTD pregnancies. This result can be used to help influence folic acid fortification policy.
Towards large-scale museomics projects: a cost-effective and high-throughput extraction method for obtaining historical DNA from museum insect specimens
Authors: Holmquist Anna J. , Tavris Holly , Kim Grace , Esposito Lauren A. , Fisher Brian L. , Lam Athena
Published: September 2024

Natural history collections serve as invaluable repositories of biodiversity data. Large-scale genomic analysis would greatly expand the utility and accessibility of museum collections but the high cost and time-intensive nature of genomic methods limit such projects, particularly for invertebrate specimens. This paper presents an innovative, cost-effective and high-throughput approach to extracting genomic DNA from diverse insect specimens using single-phase reverse immobilization (SPRI) beads. We optimized PEG-8000 and NaCl concentrations to balance DNA yield and purity, reducing reagent cost to 6-11 cents per sample. Our method was validated against three widely used extraction protocols, and showed comparable DNA yield and amplification success to the widely used Qiagen DNeasy kit. We successfully applied the protocol in a high-throughput manner, extracting DNA from 3,786 insect specimens across a broad range of ages, taxonomies, and tissue types. A detailed protocol is provided to facilitate the adoption of the method by other researchers. By improving one of the most crucial steps in any molecular project, this SPRI bead-based DNA extraction approach has significant potential for enabling large-scale museomics projects, thereby increasing the utility of historical collections for biodiversity research and conservation efforts.
The diverse diet of southern Alaska resident killer whales changes across spatiotemporally distinct foraging aggregations
Authors: Myers Hannah , Olsen Daniel , Van Cise Amy , Parsons Kim , Wells Abigail , Matkin Craig
Published: September 2024

Top predators influence ecological communities in part through the prey they consume, which they often track through cycles of seasonal and geographic abundance. Killer whales are top predators in the marine ecosystem. In the North Pacific, they have diverged into three distinct lineages with different diets, of which the fish-eating type is most abundant. In this study, we examine the diet of the southern Alaska resident killer whale population across three major foraging aggregations. We take advantage of two unique sampling methods to reveal strong spatiotemporal patterns in diet from May through September. Chinook, chum, and coho salmon were each dominant in different locations and times, with substantial dietary contributions from Pacific halibut, arrowtooth flounder, and sablefish. The diverse, location-specific, and seasonal nature of the feeding habits of this marine top predator highlights the importance of diet sampling across broad spatiotemporal and population-level scales.
The H3K4me3 binding ALFIN-LIKE proteins recruit SWR1 for gene-body deposition of H2A.Z
Authors: Xu Linhao , Wang Yafei , Li Xueying , Hu Qin , Adamkova Vanda , Xu Junjie , Harris C. Jake , Ausin Israel
Published: September 2024

The H2A.Z histone variant is highly enriched over gene bodies, playing an essential role in several genome-templated processes, including transcriptional regulation and epigenetic patterning across eukaryotes. The SWR1 chromatin remodeling complex deposits H2A.Z. How SWR1 is directed to gene bodies is largely unknown. Here, we show that ALFIN-LIKE (AL) proteins are responsible for H2A.Z gene body patterning inArabidopsis. AL proteins encode H3K4me3-binding PHD domains, and by ChIP-seq, we confirm preferential binding of AL5 to H3K4me3 over H3K4me1/2in planta. We observe a global reduction in H2A.Z inalseptuple mutants (al7m), especially of over H3K4me3-enriched genic regions. While MBD9 recruits SWR1 to nucleosome-free regions, ALs act non-redundantly with MBD9 for deposition of H2A.Z. Notably,al7mmutants show severe developmental abnormalities and upregulation of H2A.Z gene body-enriched responsive genes. Therefore, we propose a model whereby AL proteins direct gene body enrichment of H2A.Z by recruiting SWR1 to H3K4me3-containing responsive genes.
PEARL: Protein Eluting Alginate with Recombinant Lactobacilli
Authors: Tadimarri Varun Sai , Blanch-Asensio Marc , Deshpande Ketaki , Baumann Jonas , Baumann Carole , Müller Rolf , Trujillo Sara , Sankaran Shrikrishnan
Published: September 2024

Engineered living materials (ELMs) made of bacteria in hydrogels have shown considerable promise for therapeutic applications through controlled and sustained release of complex biopharmaceuticals at low costs and with reduced wastage. While most therapeutic ELMs useE. colidue to its large genetic toolbox, most live biotherapeutic bacteria in development are lactic acid bacteria due to native health benefits they offer. Among these, lactobacilli form the largest family of probiotics with therapeutic potential in almost all sites of the body with a microbiome. A major factor limiting the use of lactobacilli in ELMs is their limited genetic toolbox.

In this study, we build upon our recent work to expand the genetic programmability of probioticLactiplantibacillus plantarumWCFS1 for protein secretion and encapsulate it in a simple, cost-effective, and biocompatible core-shell alginate bead to develop an ELM. We demonstrate the controlled release of recombinant proteins, even up to 14 days from this ELM, thereby terming it PEARL - Protein Eluting Alginate with Recombinant Lactobacilli. Notably, lactobacillus encapsulation offered benefits like bacterial containment, protein release profile stabilization, and metabolite-induced cytotoxicity prevention. These findings demonstrate the mutual benefits of combining recombinant lactobacilli with alginate for the controlled and sustained release of proteins.
Qing-Luo-Yin-induced SIRT1 inhibition contributes to the immune improvement of adjuvant-induced arthritis rats
Authors: Wang Dan-Dan , Song Meng-Ke , Yin Qin , Chen Wen-Gang , Olatunji Opeyemi Joshua , Yang Kui , Zuo Jian
Published: September 2024

The herbal formula Qing-Luo-Yin (QLY) was proved containing SIRT1 inhibitors. Whether they contribute to the anti-rheumatic effects is to be confirmed. Adjuvant-induced arthritis (AIA) rats were treated by QLY or/and nicotinamide mononucleotide (NMN) for 38 days. After sacrifice, main tissues were collected for histological and western-blot experiments. Levels of rheumatoid arthritis (RA)-related indictors in blood or tissue homogenates were detected by commercial kits. Normal pre-adipocytes were cultured by the relevant rat serums, and the medium was collected for monocytes culture. In replicate experiments, some pre-adipocytes received additional compounds or SIRT1 silencing/overexpression treatments. Due to spontaneous remission of inflammation, QLY didn’t further improve immune milieu in AIA rats, but greatly eased paw edema and joint injuries. Besides, it reversed triglyceride/glucose depletion in liver and adipose tissues, and inhibited the expression and function of SIRT1, causing concomitant changes of related signals and adipkines production. All the effects were weakened by NMN, which activated SIRT1 by increasing NAD production. The serum from QLY-treated rats improved AIA rat serum-induced metabolism and secretion changes of pre-adipocytes, and reduced the secretion of IL-1β, IL-6 and TNF-α in the monocytes cultured with the corresponding medium. A mixture of matrine, sinomenine, sophocarpine, dioscin, berberine showed the similar effects on pre-adipocytes to QLY-containing serum. eNAMPT decrease was especially notable, which was obviously weakened by SIRT1 overexpression but overshadowed SIRT1-silencing. SIRT1 inhibitors in QLY reshaped metabolism and secretion profiles of adipose tissues. It consequently mitigated eNAMPT-mediated inflammation and eased AIA in rats.
Yttrium-90-doped metal-organic frameworks (MOFs) for low-dose rate intratumoral radiotherapy
Authors: Qi Xiaoli , Fedotova Anzhelika , Yu Zhihao , Polyanskaya Anna , Shen Ningfei , Egorova Bayirta , Bagrov Dmitry , Slastnikova Tatiana , Rosenkranz Andrey , Patriarche Gilles , Nevolin Yurii , Permyakova Anastasia , Fedotov Stanislav , Lepoitevin Mathilde , Kalmykov Stepan , Serre Christian , Durymanov Mikhail
Published: September 2024

Brachytherapy, or intratumoral radiation therapy, is a highly effective treatment option for localized tumors. Herein, we engineered injectable and biodegradable metal-organic frameworks (MOFs) to deliver the therapeutic radioisotope yttrium-90 (90Y). Particles of bimetallic MIL-100(Fe,Y) and Y-BTC, doped with90Y and88Y, were synthesized in a single step and retained radioyttrium in various buffer solutions. Tumor injectability and radioisotope retention were evaluated using tumor-bearing mice.In vivoanalysis and calculations showed that radiolabeled MIL-100(Fe,Y) emitted more than 38% of its radioactivity, while Y-BTC emitted greater than 75% of its radioactivity, through 7 days at the tumor site upon intratumoral injection, without significant yttrium accumulation in off-target tissues. The anticancer effects of MIL-100(Fe,Y,90Y) and90Y,Y-BTC particles were assessed using 3D multicellular tumor spheroids and a tumor-bearing mouse model, respectively.90Y-doped MIL-100(Fe,Y) particles penetrated A549 tumor spheroids and caused superior cytotoxic effects compared to non-radioactive particles or90YCl3, added at the same dose. Brachytherapy with90Y-doped Y-BTC MOFs induced inhibition of B16F1 melanoma tumor growth and resulted in an increased median survival of 8.5 days compared to 4.5 days in untreated mice. This study exhibits the feasibility to prepare radioactive90Y-containing biodegradable, non-toxic MOF particles that are advantageous for low-dose rate internal radiotherapy.
Heterogeneous responses to embryonic critical period perturbations among different components of theDrosophilalarval locomotor circuit
Authors: Krick Niklas , Davies Jacob , Coulson Bramwell , Sobrido-Cameán Daniel , Miller Michael , Oswald Matthew C. W. , Zarin Aref A. , Baines Richard , Landgraf Matthias
Published: September 2024

As developing neural circuits become functional, they undergo a phase of heightened plasticity in response to intrinsic and/or extrinsic stimuli. These developmental windows are termed critical periods (CPs), because perturbations during the CP can lead to lasting and significant change in subsequent development, such as sub-optimal and/or unstable networks. By contrast, the same manipulations before or after the CP does not create lasting changes. Here, we have used theDrosophilalarval locomotor network to study how different identified, connected elements respond to a CP perturbation, from pre-motor interneuron to motoneuron, to neuromuscular junction. Using heat stress as an ecologically relevant stimulus, we show that increasing temperature causes increased network activity that, when applied during the CP, leads to larvae that crawl more slowly and that require longer to recover from electroshock-induced seizures, indicative of decreased network stability. Within the central nervous system, we find CP perturbation leads to pre-motor interneurons delivering increased synaptic drive to motoneurons, which in turn display reduced excitability. The peripheral neuromuscular junction, on the other hand, maintains normal synaptic transmission, despite significant structural changes of synaptic terminal overgrowth and altered postsynaptic receptor field composition. Overall, our data demonstrate that different connected elements within a network respond differentially to a CP perturbation. Our results suggest an underlying sequence, or hierarchy, of network adjustment during developmental CPs, and present the larval locomotor network as a highly tractable experimental model system with which to study CP biology.
Thorax temperature and niche characteristics as predictors of abundance of Amazonian Odonata
Authors: Calvão Lenize Batista , Faria Ana Paula J. , de Paiva Carina Kaory Sasahara , Oliveira-Junior José Max Barbosa , Muzón Javier , Córdoba-Aguillar Alex , Juen Leandro
Published: September 2024

Environmental architecture and body temperature drive the distribution of ectothermic species, especially those with specific ecophysiological requirements or narrow ecological niches. In this study, we evaluated the connection between thorax temperature and niche specialization concerning the abundance and species contribution to the beta diversity of adult Odonata in Amazonian streams, employing the Species Contribution to Beta Diversity (SCBD). Our hypotheses were (i) Odonata species’ thorax temperature is positively correlated with both morphology (thorax width) and air temperature, and (ii) the thorax temperature of the Odonata assemblage serves as a more influential predictor than niche specialization in determining species abundance and SCBD. We sampled 46 streams in an anthropized landscape in the Northeastern and Southeastern regions of Pará state, Brazil. Notably, niche breadth emerged as the variable influencing the abundance and SCBD of the Odonata assemblage. Niche position is a predictor for Odonata SCBD and not suborders, and predictor for abundance, except for Anisoptera. Both suborders exhibited a negative relationship between abundance and thoracic temperature. In summary, our results underscore the necessity of considering both niche and ecophysiological predictors to comprehensively assess the Odonata assemblage in Amazonian streams. This holistic approach has implications for conservation efforts and bioassessment practices, offering valuable insights into the collective response of Odonata as a group.
The digestion time for salmon louse (Lepeoptheirus salmonis) in lumpfish (Cyclopterus lumpus)in relation to freshness, developmental stage, and temperature
Authors: Eliasen Kirstin , Østerø Sandra L. , Johannesen Tróndur T. , Patursson Esbern J. , Jacobsen Ása , Mortensen Agnes M. , Nolsøe Marner , Johannesen Ása
Published: September 2024

Sea lice infestations cause significant economic losses in the Atlantic salmon aquaculture industry. To biologically control sea lice at farming sites, cleaner fish such as lumpfish are employed. However, the efficacy of lumpfish is under constant debate, primarily due to limited knowledge of digestion times, which makes it difficult to interpret the number of salmon lice found in the stomach contents of dissected lumpfish.

The aim of this study was to provide quantitative estimates of the degradation of salmon lice over a period of 12 days. After an acclimation period of approximately one week, batches of eight lumpfish (average weight 94.3 g, SD ± 33.2) were fed salmon lice and arranged in tanks.

Each batch received six large mobile lice and two adult female lice. Samplings were conducted at 24-hour intervals during the first four days and at 48-hour intervals over the remaining eight days. The experiment was conducted twice, each at a different temperature regime (6°C and 9°C), using live lice in both trials. To investigate if the freshness of the louse influenced degradation and digestion, the setup was replicated in the 9°C experiment with lice that had been stored frozen at -80°C, with an additional 12-hour sampling point for comprehensive observation.

The analysis of salmon lice revealed expected digestion times of 6.8 days and 12 days for large mobile and adult female salmon lice, respectively. Temperature and lice freshness did not seem to influence digestion times, but the developmental stage of the lice did. The findings of this study can be used to estimate the cleaning efficacy of lumpfish based on the stomach contents.
Voltage imaging reveals circuit computations in the raphe underlying serotonin-mediated motor vigor learning
Authors: Kawashima Takashi , Wei Ziqiang , Haruvi Ravid , Shainer Inbal , Narayan Sujatha , Baier Herwig , Ahrens Misha B.
Published: September 2024

As animals adapt to new situations, neuromodulation is a potent way to alter behavior, yet mechanisms by which neuromodulatory nuclei compute during behavior are underexplored. The serotonergic raphe supports motor learning in larval zebrafish by visually detecting distance traveled during swims, encoding action effectiveness, and modulating motor vigor. We found that swimming opens a gate for visual input to cause spiking in serotonergic neurons, enabling encoding of action outcomes and filtering out learning-irrelevant visual signals. Using light-sheet microscopy, voltage sensors, and neurotransmitter/modulator sensors, we tracked millisecond-timescale neuronal input-output computations during behavior. Swim commands initially inhibited serotonergic neurons via GABA, closing the gate to spiking. Immediately after, the gate briefly opened: voltage increased consistent with post-inhibitory rebound, allowing swim-induced visual motion to evoke firing through glutamate, triggering serotonin secretion and modulating motor vigor. Ablating GABAergic neurons impaired raphe coding and motor learning. Thus, serotonergic neuromodulation arises from action-outcome coincidence detection within the raphe, suggesting the existence of similarly fast and precise circuit computations across neuromodulatory nuclei.
Aquaporin-4 expression levels and mis-localization are inversely linked to peritumoral edema in gliomas of varying aggressiveness
Authors: Valente Onofrio , Abbrescia Pasqua , Signorile Gianluca , Messina Raffaella , de Gennaro Luigi , Bozzi Maria Teresa , Ingravallo Giuseppe , D’amati Antonio , Zimatore Domenico Sergio , Palazzo Claudia , Nicchia Grazia Paola , Frigeri Antonio , Signorelli Francesco
Published: September 2024

Aquaporin-4 (AQP4) and its extended isoform, AQP4ex, are crucial for regulating brain water homeostasis. Mis-localization of these isoforms is implicated in various brain tumors, including glioblastoma multiforme (GBM).

This study explores AQP4 isoform expression and localization in Pilocytic Astrocytomas (PA), a circumscribed astrocytic low-grade glioma, compared to GBM, an adult-type diffuse high grade glioma.

We found significant upregulation of AQP4 and AQP4ex in PA, with notable mis-localization deviating from the typical perivascular localization seen in healthy tissue. This mis-localization mirrors the phenotype observed in AQP4ex knockout models, where impaired AQP4 localization is linked to disrupted water homeostasis and reduced waste clearance, despite overall increased AQP4 levels. Interestingly, PA shows minimal peritumoral edema and a relatively intact blood-brain barrier (BBB), with elevated phosphorylated AQP4ex (pAQP4ex) suggesting a role in stabilizing AQP4 function. In contrast, GBM exhibits reduced AQP4/AQP4ex expression, significant peritumoral edema, and BBB disruption.

GFAP isoforms, GFAPκ and GFAPδ, are upregulated in PA, associated with Rosenthal fibers, indicating a stabilizing astrocytic response. GBM, however, shows generalized GFAP increase, reflecting aggressive gliosis and disrupted water homeostasis.

In conclusion, both AQP4 expression levels and mis-localization are important factors influencing peritumoral edema and tumor aggressiveness in gliomas. This study positions AQP4 as a potential biomarker for glioma progression, offering insights into astrocytic function and paving the way for targeted therapies.
PREDICTION OF SINGLE NUCLEOTIDE VARIANT EFFECTS RELATED TO SEX DETERMINATION INCarica papaya (Caricaceae)
Authors: Bôas Spelta João Victor Villas , Sakamoto Tetsu
Published: September 2024

Papaya (Carica papaya) produces one of the most consumed fruits worldwide, holding great economic importance, especially in tropical regions. Papaya trade mainly involves gynodioecious cultivars with a ratio of 1:1 or 2:1 of hermaphrodites to females. For commercial reasons and also inherent to cultivation, it is preferable to have as many hermaphrodites as possible. In general, it is still not possible to produce only hermaphrodite seeds, so the sex of the plant is usually identified by conventional methods after the first flowering of the papaya plant. This occurs about 4-6 months after planting the seedling, with the females typically being discarded at the end. To avoid wasting resources and achieve higher harvest yields, producers may also resort to molecular methods using sex markers. However, this alternative also has its limitations, including high costs. Given these challenges, many researchers have focused on studying the process of sex determination inC. papaya, but the factors directly influencing this process remain unknown. The elucidation of this mechanism is not only of great agronomic interest, but also represents a significant opportunity forC. papayato establish itself as a model organism for studying sexual chromosomes of recent evolutionary origin. Therefore, in this work, a bioinformatics strategy was used to address the topic. A genotype-phenotype association study was conducted to find possible genetic factors involved in sex determination using resequencing data from 36 individuals (24 male papaya plants and 12 hermaphrodites) obtained from public databases. The association study was preceded by a variant calling performed with BCFTOOLS, which found 75,607 variants, leaving 37,027 after filtering. Association studies were then carried out using the PLINK program with the filtered variants, and among these, 251 of the most statistically significant variants were applied to the SnpEff program for variant annotation, returning 449 effects, including 402 with a modifier level of impact, 22 with a low impact, and 25 with a moderate effect. Inferences and gene annotations were also performed using the Augustus software and BLASTP alignments with the gene sequences that had moderate effects predicted by SnpEff, as well as de novo genome assemblies of a male sample and its alignment with the hermaphrodite sex-determining region. These results were recorded and compared with previous studies in the literature. This allowed for the conclusion that the specific results obtained serve as a starting point for more robust studies to understand the molecular mechanisms of sex determination inC. papaya.
Positional information drives distinct traits in transcriptomically identified neuronal types
Authors: Shainer Inbal , Kappel Johannes M. , Laurell Eva , Donovan Joseph C. , Schneider Martin W. , Kuehn Enrico , Arnold-Ammer Irene , Stemmer Manuel , Larsch Johannes , Baier Herwig
Published: September 2024

Neuronal phenotypic traits such as morphology, connectivity, and function are dictated, to a large extent, by a specific combination of differentially expressed genes. Clusters of neurons in transcriptomic space correspond to distinct cell types and in some cases (e. g.,C. elegansneurons1and retinal ganglion cells2–4) have been shown to share morphology and function. The zebrafish optic tectum is composed of a spatial array of neurons that transforms visual inputs into motor outputs. While the visuotopic map is continuous, subregions of the tectum are functionally specialized5,6. To uncover the cell-type architecture of the tectum, we transcriptionally profiled its neurons, revealing more than 60 cell types that are organized in distinct anatomical layers. We then measured the visual responses of thousands of tectal neurons by two-photon calcium imaging and matched them with their transcriptional profile. Furthermore, we characterized the morphologies of transcriptionally identified neurons using specific transgenic lines. Surprisingly, we found that neurons that are transcriptionally similar can diverge functionally and morphologically. Incorporating the spatial coordinates of neurons within the tectal volume revealed functionally and morphologically defined anatomical subclusters within individual transcriptomic clusters. Our findings demonstrate that extrinsic, position-dependent factors expand the phenotypic repertoire of genetically similar neurons.
Filter bank common spatial pattern and envelope-based features in multimodal EEG-fTCD brain-computer interfaces
Authors: Essam Alaa-Allah , Ibrahim Ammar , Zanqour Ashar , El-Saqa Mariam , Mohamed Sohila , Anwar Ayman , Eldeib Ayman , Akcakaya Murat , Khalaf Aya
Published: September 2024

Brain-computer interfaces (BCIs) exploit brain activity to bypass neuromuscular control with the aim of providing alternative means of communication with the surrounding environment. Such systems can significantly improve the quality of life for patients suffering from severe motor or speech impairment. Multimodal BCIs have been introduced recently to enhance the performance of BCIs utilizing single modality. In this paper, we aim to improve the performance of multimodal BCIs combining Electroencephalography (EEG) and functional transcranial Doppler ultrasound (fTCD). The BCIs included in the study utilized two different paradigms to infer user intent including motor imagery (MI) and flickering mental rotation (MR)/word generation (WG) paradigms. Filter Bank Common Spatial Pattern (FBCSP) algorithm was used to extract features from the EEG data. Several time series features were extracted from the envelope of the fTCD signals. Wilcoxon rank sum test and linear kernel Support vector machines (SVM) were used for feature selection and classification respectively. Additionally, a probabilistic Bayesian fusion approach was used to fuse the information from EEG and fTCD modalities. Average accuracies of 94.53%, 94.9% and 96.29% were achieved for right arm MI versus baseline, left arm MI versus baseline, and right arm MI versus left arm MI respectively. Whereas average accuracies of 95.27%, 85.93% and 96.97% were achieved for MR versus baseline, WG versus baseline, and MR versus WG respectively. Our results show that EEG- fTCD BCIs with the proposed analysis techniques outperformed the multimodal EEG-fNRIS BCIs in comparison.