bluuebunny/crossref_metadata_2025 huggingface dataset:
Web-based Tool Validation for Antimicrobial Resistance Prediction: An Empirical Comparative Analysis
Authors: Routray Sweta Padma , Sahoo Swayamprabha , Nayak Debasish Swapnesh Kumar , Shah Sejal , Swarnkar Tripti
Published: December 2022

Global public health is seriously threatened by Antimicrobial Resistance (AMR), and there is an urgent need for quick and precise AMR diagnostic tools. The prevalence of novel Antibiotic Resistance Genes (ARGs) has increased substantially during the last decade, owing to the recent burden of microbial sequencing. The major problem is extracting vital information from the massive amounts of generated data. Even though there are many tools available to predict AMR, very few of them are accurate and can keep up with the unstoppable growth of data in the present. Here, we briefly examine a variety of AMR prediction tools that are available. We highlighted three potential tools from the perspective of the user experience that is preferable web-based AMR prediction analysis, as a web-based tool offers users accessibility across devices, device customization, system integration, eliminating the maintenance hassles, and provides enhanced flexibility and scalability. By using thePseudomonas aeruginosaComplete Plasmid Sequence (CPS), we conducted a case study in which we identified the strengths and shortcomings of the system and empirically discussed its prediction efficacy of AMR sequences, ARGs, amount of information produced and visualisation. We discovered that ResFinder delivers a great amount of information regarding the ARGS along with improved visualisation. KmerResistance is useful for identifying resistance plasmids, obtaining information about related species and the template gene, as well as predicting ARGs. ResFinderFG does not provide any information about ARGs, but it predicts AMR determinants and has a better visualisation than KmerResistance.

Author summary

AMR is the capacity of microorganisms to survive or grow in the presence of drugs intended to stop them or kill them. Consequently, there is an increase in the Burden of disease, death rates, and the cost of healthcare, making it a serious global threat to both human and animal health. Next-Generation Sequencing (NGS) based molecular monitoring can be a real boon to phenotypic monitoring of AMR. Researchers face difficult challenges in terms of producing, managing, analysing, and interpreting massive amounts of sequence data. There are many tools available to predict AMR, but only a small number of them are reliable and able to keep up with the current rate of unstoppable data growth. Each tool has specific benefits and drawbacks of its own. Our research offers a comprehensive overview of the outcomes produced by three different tools, enabling users to choose the tool that best suits their requirements.
Randomised trial ofAureobasidium pullulans-produced beta 1,3-1,6-glucans in patients with Duchenne muscular dystrophy: Favourable changes in gut microbiota and clinical outcomes indicating their potential in epigenetic manipulation
Authors: Raghavan Kadalraja , Dedeepiya Vidyasagar Devaprasad , Yamamoto Naoki , Ikewaki Nobunao , Iwasaki Masaru , Dinassing Ashwamed , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK
Published: December 2022

Objective

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disorder that leads to increasing muscle weakening and early death. Steroids, the standard treatment of choice in slowing down disease progression, are plagued with adverse effects. Following anti-inflammatory and anti-fibrotic outcomes of anAureobasidium pullulansstrain N-163-produced beta 1,3-1,6-glucan food supplement in clinical and pre-clinical studies of DMD, herein we report their implications on the gut microbiome in patients with DMD.

Design

Twenty-seven patients with DMD were included in the pilot study (Control [n=9], N-163 [n=18]) which had previously reported the clinical decrease in inflammatory and fibrosis biomarkers. For the current study, whole genome metagenomic sequencing was performed in pre- and post N-163 intervention faecal samples of each of these participants.

Results

After N-163 beta-glucan administration, the constitution of the gut microbiome in all the participants was modified to one with positive outcomes on health. There was an increase in butyrate-producing species such asRoseburiaandFaecalibacterium prausnitzii. There was a decrease in harmful bacteria associated with inflammation such as enterobacteria andAlistipes.

Conclusion

Beneficial reconstitution of the gut microbiome after N-163 beta-glucan administration, in addition to their implications in anti-inflammatory and anti-fibrotic outcomes, require further in-depth exploration on their roles in epigenetic manipulation.
Ceramides as risk markers for future cardiovascular events and all-cause mortality in long-standing type 1 diabetes
Authors: Wretlind Asger , Curovic Viktor R. , Suvitaival Tommi , Theilade Simone , Tofte Nete , Winther Signe A. , Vilsbøll Tina , Vestergaard Henrik , Rossing Peter , Legido-Quigley Cristina
Published: December 2022

Background

Ceramides are lipid molecules involved in inflammation-related signaling. Recent studies have shown that higher amounts of specific circulating ceramides and ceramide ratios are associated with future development of cardiovascular (CV) disease (CVD). In persons with longstanding type 1 diabetes (T1D), we investigated if serum ceramide levels and ratios predicted CVD, kidney failure and all-cause mortality.

Methods

We included 662 participants with T1D from 2009-2011. Health registry data was obtained at a 6-year follow-up. Baseline serum samples were analyzed using liquid chromatography-mass spectrometry. Six predefined ceramide levels were measured and ratios calculated. Adjusted Cox regression analyses were carried out to investigate ceramide levels in relation to future CV events (CVE), kidney failure and all-cause mortality.

Results

Ceramide ratio cer(d18:1/18:0)/cer(d18:1/24:0) was significantly associated with risk of CVE (HR = 1.33, P = 0.01) and all-cause mortality (HR = 1,48, P = 0.01) before and after adjustments. All five investigated ceramide ratios were associated with kidney failure, before adjusting for the kidney markers estimated glomerular filtration rate and urinary albumin excretion rate.

Conclusions

Specific ceramides and ratios associated with 6-year cardiovascular risk and all-cause mortality in a T1D cohort. The ratio of cer(d18:1/18:0)/cer(d18:1/24:0) was an especially robust indicator. This highlights the strength of ceramide association with vascular complications and presents a new potential tool for early risk assessment if validated in other cohorts.

Trial Registration

ClinicalTrial.govidentifier:NCT01171248
Exploring the use of synthetic placebo populations in ALS randomized clinical trials
Authors: Bowles Harry , Opie-Martin Sarah , Shojaie Ali , Libonati Laura , Iacoangeli Alfredo , Al Khleifat Ahmad , Al-Chalabi Ammar
Published: December 2022

Objectives

The use of synthetic data to supplement clinical trial placebo groups or for trial planning is rapidly gaining interest. However, there is not yet an established framework for generating synthetic data for these purposes. In this work we test two approaches to generating synthetic placebo arms for ALS trials with survival being the primary outcome variable.

Methods

For the first approach, we extracted sample subsets from the UK MND register (n = 308) using an evolutionary algorithm such that the subset baseline variables matched a target trials group, either people enrolled in LiCALS (n = 106) or people included in the PRO-ACT database (n = 171). We also applied trial specific exclusion criteria where possible or alternatively we applied a custom ‘time filter’. For the second approach, survival was predicted for LiCALS participants using the ENCALS model. Survival probabilities from each method were compared to real placebo participants using Kaplan-Meier analysis and the log rank test.

Results

We found that the synthetic placebo groups derived from the MND register matched the target trials outcomes very well. The ENCALS model produces synthetic placebo groups that are significantly different to the real placebo groups. However, when participants are censored at 6 month intervals, the ENCALS synthetic group matches the target group very well between 24 and 48 months, indicating a possible timeframe that this method could be utilised.

Conclusion

Both the register based approach and the ENCALS prognostic model generated synthetic placebo groups that matched placebo groups from historical trials. These methods need to be validated in prospective trials.
De novo designed ice-binding proteins from twist-constrained helices
Authors: de Haas R.J. , Tas R.P. , van den Broek D. , Nguyen H. , Kang A. , Bera A.K. , King N.P. , Voets I. K. , de Vries R.
Published: December 2022

Attaining molecular-level control over solidification processes is a crucial aspect of materials science. To control ice formation, organisms have evolved bewildering arrays of ice-binding proteins (IBPs) but these have poorly understood structure-activity relationships. We propose that reverse engineering usingde novocomputational protein design can shed light on structureactivity relationships of IBPs. We hypothesized that the model alpha-helical winter flounder antifreeze protein (wfAFP) uses an unusual under-twisting of its alpha-helix to align its putative ice-binding threonine residues in exactly the same direction. We test this hypothesis by designing a series of straight three-helix bundles with an ice-binding helix projecting threonines and two supporting helices constraining the twist of the ice-binding helix. We find that ice recrystallization inhibition by the designed proteins increases with the degree of designed under-twisting, thus validating our hypothesis and opening up new avenues for the computational design of icebinding proteins.

Significance Statement

Ice-binding proteins (IBPs) modulate ice nucleation and growth in cold-adapted organisms so that they can survive in ice-laden environments at (sub)freezing temperatures. The functional repertoire of IBPs is diverse, ranging from inhibition of recrystallization and freezing point depression to shaping of ice crystals and ice nucleation. Precisely how these activities arise from the structure and ice-binding properties of IBPs is poorly understood. We demonstrate throughde novocomputational protein design that constraining the twist of an ice-binding helix is a key feature determining its ice-binding activity, opening new avenues for the design of synthetic IBPs with activities tailored to the requirements of specific applications, such as cell and tissue cryopreservation.
Urbanisation impacts the diversity, coloration, and body size of wild bees in a Mediterranean city
Authors: Badiane Arnaud , Ropars Lise , Flacher Floriane , Schurr Lucie , Zakardjian Marie , Affre Laurence , Deschamps-Cottin Magali , Gachet Sophie , Robles Christine , Geslin Benoît
Published: December 2022

Urbanisation is a growing phenomenon causing the decline of wild bees globally. Yet, bees manage to persist in the urban matrix thanks to islands of vegetation in public parks and private gardens. While we begin to comprehend the impact of urbanisation on bees’ diversity and abundance, our understanding of its impact on the functional diversity of wild bees is limited. Here, we use an integrative approach to investigate the response of wild bees to urbanisation at the community, species, and individual levels. To do so, we sampled wild bees in 24 public parks along an urbanisation gradient in the Mediterranean city of Marseille. We found that species richness and abundance decreased in more urbanised areas, but increased in larger city parks. Moreover, larger individuals within species, but not larger species, were found in larger city parks, suggesting that park size is crucial for the persistence of bees in cities. Interestingly, we show that brighter species were found in parks surrounded by a large amount of impervious surface, highlighting the importance of colour traits in the response to environmental changes. Finally, our results revealed that larger species, but not larger individuals, were also more colourful. In summary, our study not only confirmed that urbanisation negatively impacts community-level traits, but that it also affects species’ coloration and individuals’ body size, thus improving our understanding of the functional response of wild bees to urbanisation. We suggest that increasing park size may compensate for the negative effects of urbanisation on wild bees.
A survey of proteomic variation across two ethnic groups in Nigeria and its relationship to obesity risk
Authors: Biddanda Arjun , de Arce Karen Perez , Eze-Echesi Golibe , Nwuba Chiamaka , Ibrahim Yusuf , Oyedele Olubukunola , Joshi Esha , Alalade Boladale , Ajayi Olanrewaju , Nwatu Chidimma , Yakubu Aminu , Ene-Obong Abasi , Popoola Jumi , O’Dushlaine Colm , Fekkes Peter
Published: December 2022

Proteomic variation between individuals has immense potential for identifying novel drug targets and disease mechanisms. However, with high-throughput proteomic technologies still in their infancy, they have largely been applied in large majority European ancestry cohorts (e.g. the UK Biobank). An open question is the degree to which proteomic signatures seen in European and other groups mirror those seen in diverse populations, such as cohorts from Africa. Coupled with genetic information, we can also gain a better understanding of the role of genetic variants in the regulation of the proteome and subsequent disease mechanisms.

To address the gap in our understanding of proteomic variation in individuals of African ancestry, we collected proteomic data from 176 individuals across two ethnic groups (Igbo and Yoruba) in Nigeria. These individuals were also stratified into high BMI (BMI > 30 kg/m2) and normal BMI (20 kg/m2< BMI < 30 kg/m2) categories. We characterized differences in plasma protein abundance using the Olink Explore 1536 panel between high and normal BMI individuals, finding strong associations consistent with previously known signals in individuals of European descent. We additionally found 73 sentinel cis-pQTL in this dataset, with 21 lead cis-pQTL not observed in catalogs of variation from European-ancestry individuals. In summary, our study highlights the value of leveraging proteomic data in cohorts of diverse ancestry for investigating trait-specific mechanisms and discovering novel genetic regulators of the plasma proteome.
Origin, evolution and diversification of plant mechanosensitive channel of small conductance-like (MSL) proteins
Authors: Zhang Zaibao , Ye Fan , Xiong Tao , Chen Jiahui , Cao Jiajia , Chen Yurui , Luo Tian , Liu Sushuang
Published: December 2022

Mechanosensitive (MS) ion channels provide efficient molecular mechanism for transducing mechanical forces into intracellular ion fluxes in all kingdoms of life. The mechanosensitive channel of small conductance (MscS) was one of the best-studied MS channels and its homologs (MSL, MscS-like) were widely distributed in cell-walled organisms. However, the origin, evolution and expansion of MSL proteins in plants are still not clear. Here, we identified more than 2100 MSL proteins from 176 plants and conducted a broad-scale phylogenetic analysis. The phylogenetic tree showed that plant MSL proteins were divided into three groups (I, II and III) prior to the emergence of chlorophytae algae, which was consistent with their specific subcellular localization. MSL proteins were distributed unevenly into each of plant species, and four parallel expansion was identified in angiosperms. In Brassicaceae, most MSL duplicates were derived by whole-genome duplication (WGD)/segmental duplications. Finally, a hypothetical evolutionary model of MSL proteins in plants was proposed based on phylogeny. Our studies illustrate the evolutionary history of the MSL proteins and provide a guide for future functional diversity analyses of these proteins in plants.
Pseudomonasisolates from ponds populated with duckweed prevent disease caused by pathogenicPseudomonasspecies
Authors: Baggs E.L , Stark F.G , Tiersma M.B , Krasileva K.V
Published: December 2022

Duckweeds are notoriously invasive plants. They are successful in inhabiting diverse environments, despite their lack of conventional immune pathways that are essential for disease resistance in other plant species. It is unclear how duckweeds thrive in the absence of these immune pathways. In this study, we investigated the effect of bacteria from duckweeds’ natural habitat on disease progression utilizing the duckweed-Pseudomonaspathosystem. Through nanopore sequencing of 16S and ITS rDNA amplicons we identified duckweed-associated bacterial and fungal genera present at three environmental sites. The pond filtrate from one of the three environmental locations primed duckweed’s pathogen defenses leading to a reduction in disease symptoms. Furthermore, we were able to identify bacterial isolates from the filtrate that protect duckweed from disease symptoms uponPseudomonaspathogen inoculation. The isolated protective bacteria belong to thePseudomonasgenus, and we demonstrated antagonistic interactions between the pathogen and beneficial strainsin vitroandin vivo. The ability of our environmental isolates to protect againstPseudomonaspathogens appears to be plant/species specific as environmental strains showed no protective effect againstPseudomonaspathogens inArabidopsisassays. Genome sequencing of the beneficialPseudomonasstrains showed the presence of several genes involved in bacterial competition. We have thus demonstrated thatPseudomonasspecies from duckweeds natural habitat can successfully antagonize other plant pathogens.
Profile of the pregnant woman with Gestational Diabetes Mellitus in a private hospital in Joinville, Brazil
Authors: Baptista João Pedro Ribeiro , Schulz Matheus Augusto , Fleith Lehana , Kitzberger Israel , Hilário Wesley Feitosa , Neumann Dieter Alisson , da Silva Júlia Opolski Nunes , e Silva Rodrigo Ribeiro , Nascimento Iramar Baptistella do , Silva Jean Carl
Published: December 2022

Objective

To analyze the maternal-fetal characteristics of patients with gestational diabetes mellitus (GDM) attended in a private service.

Materials and Methods

This is a cross-sectional study. Data collection was carried out from the medical records of patients diagnosed with GDM at Centro Hospitalar UNIMED, in Joinville city, between 2011 and 2017. Maternal-fetal characteristics, therapeutics and complications of pregnant women diagnosed with GDM were analyzed.

Results

515 patients with GDM were reported. Of the maternal characteristics, the mean age was (31.77), BMI (27.82). The proportion of obese pregnant women was (55.6%), normal (42.4%) and low weight (2%). The preference for cesarean section was (81.4%) and Gestational Age (GA) of GDM diagnosis (26.85), with higher diagnosis in the third trimester (65.2%) than second (29.3%) and first (5.3%). Incidences of hypertension (7.4%), preeclampsia (0.6%) and pregnant women with previous abortions (16.5%) were found. The mean glycemic profile showed HbA1C (5.26), estimated glucose (104.30) and FPG fasting (86.38), in the first hour (144.46) and in the second hour (64.15). Treatment with diet and exercise (38.3%), metformin (40%), insulin (14.5%) and combined (7.8%). Regarding newborns, the mean weight was (3.123.46) and the GA at birth (37.46). Regarding the percentile, AGP (71.8%), SGP (28.2%) and no cases of LGP. In terms of adverse outcomes, hyperbilirubinemia was evidenced in (25.6%), prematurity (10.9%) and fetal hypoglycemia (9.9%).

Conclusion

Pregnant women diagnosed with GDM had a higher GA at diagnosis in the third trimester and more cesarean sections. Among the adverse outcomes related to newborns, there were more cases of hyperbilirubinemia, prematurity and fetal hypoglycemia.
Reduced mortality among COVID-19 ICU patients after treatment with HemoClear convalescent plasma in Suriname
Authors: Bihariesingh-Sanchit R. , Bansie R. , Ramdhani N. , Mangroo R. , Bustamente D. , Diaz E. , A Foek C. Fung , Thakoer I. , Vreden S. , Choudhry Z. , van ‘t Wout A.B. , Diavatopoulos D.A. , Nierich A.P.
Published: December 2022

Convalescent plasma is a promising therapy for coronavirus disease 2019 (COVID-19), but its efficacy in intensive care unit (ICU) patients in a low and middle income country setting such as Suriname is unknown. Bedside plasma separation using the HemoClear device made convalescent plasma therapy accessible as treatment option in Suriname. Two hundred patients with severe SARS-CoV-2 infection requiring intensive care were recruited. Fifty eight patients (29%) received COVID-19 convalescent plasma (CCP) treatment in addition to standard of care (SOC). The CCP treatment and SOC groups were matched by age, sex, and disease severity scores. Mortality in the CCP treatment group was significantly lower than in the SOC group (21% versus 39%; Fisher’s exactP= 0.0133). Multivariate analysis using ICU days showed that CCP treatment reduced mortality (hazard ratio [HR], 0.35; 95% CI, 0.18–0.66;P= 0.001), while complication of acute renal failure (creatinine levels >110 mol/L; HR, 4.45; 95%CI, 2.54-7.80;P< 0.0001) was independently associated with death. Decrease in chest X-ray score in the CCP treatment group (median -3 points, IQR -4 to -1) was significantly greater than in the SOC group (median -1 point, IQR -3 to 1, Mann WhitneyP= 0.0004). Improvement in PaO2/FiOs ratio was also significantly greater in the CCP treatment group (median 83, IQR 8 to 140) than in the SOC group (median 35, IQR -3 to 92, Mann WhitneyP= 0.0234). Further research is needed for HemoClear-produced CCP as therapy in SARS-CoV-2 infections together with adequately powered, randomized controlled trials.

Importance

This study compares mortality and other endpoints between intensive care unit (ICU) COVID-19 patients treated with convalescent plasma plus standard of care (CCP), and a control group of patients hospitalized in the same medical ICU facility treated with standard of care alone (SOC) in a low and middle income country (LMIC) setting using bedside donor whole blood separation by gravity (HemoClear) to produce the CCP. It demonstrates a significant 65% survival improvement in HemoClear-produced CCP recipients (HR 0.35; 95% CI, 0.19–0.66; P = 0.001). Although this is an exploratory study, it clearly shows the benefit of using the HemoClear-produced CCP in ICU patients in the Suriname LMIC setting. Additional studies can further substantiate our findings and their applicability to both LMICs and high income countries and the use of CCP as a prepared readiness method to combat new viral pandemics.
New phenotype discovery method by unsupervised deep representation learning empowers genetic association studies of brain imaging
Authors: Patel Khush , Xie Ziqian , Yuan Hao , Islam Sheikh Muhammad Saiful , Zhang Wanheng , Gottlieb Assaf , Chen Han , Giancardo Luca , Knaack Alexander , Fletcher Evan , Fornage Myriam , Ji Shuiwang , Zhi Degui
Published: December 2022

Understanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6,130 UK Biobank (UKBB) participants’ T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as endophenotypes (ENDOs). GWAS of these ENDOs in held-out UKBB subjects (n = 22,962 discovery and n = 12,848/11,717 replication cohorts for T1/T2) identified 658 significant replicated variant-ENDO pairs involving 43 independent loci. Thirteen loci were not reported in earlier T1 and T2 IDP-based UK Biobank GWAS. We developed a perturbation-based decoder interpretation approach to show that these loci are associated with ENDOs mapped to multiple relevant brain regions. Our results established unsupervised deep learning can derive robust, unbiased, heritable, and interpretable endophenotypes from imaging data.
RNA-Chrom: a manually-curated analytical database of RNA–chromatin interactome
Authors: Ryabykh G. K. , Kuznetsov S. V. , Korostelev Y. D , Sigorskikh A. I. , Zharikova A. A. , Mironov A. A.
Published: December 2022

Every year there is more and more evidence that non-coding RNAs play an important role in biological processes affecting various levels of organisation of living systems: from the cellular (regulation of gene expression, remodeling and maintenance of chromatin structure, co-transcriptional suppression of transposons, splicing, post-transcriptional RNA modifications, etc.), to cell populations and even organismal ones (development, aging, cancer, cardiovascular and many other diseases). The development and creation of mutually complementary databases that will aggregate, unify and structure different types of data can help to reach the system-level of studying non-coding RNAs. Here we present the RNA-Chrom manually-curated analytical database, which contains the coordinates of billions of contacts of thousands of human and mouse RNAs with chromatin. Through the user-friendly web interface (https://rnachrom2.bioinf.fbb.msu.ru/), two approaches to the analysis of the RNA–chromatin interactome were implemented. Firstly, to find out whether the RNA of interest to a user contacts with chromatin, and if so, with which genes or DNA loci? Secondly, to find out which RNAs are in contact with the DNA locus of interest to a user (and probably participate in its regulation), and if there are such, what is the nature of their interaction? For a more detailed study of contact maps and their comparison with other data, the web interface allows a user to view them in the UCSC Genome Browser.
Chronomodulated administration of chemotherapy in advanced colorectal cancer. A systematic review and meta-analysis
Authors: Nassar Ahmed , Abdelhamid Amir , Ramsay George , Bekheit Mohamed
Published: December 2022

Aim

In this systematic review, the efficacy and safety of chronomodulated chemotherapy, defined as delivery of chemotherapy timed according to the human circadian rhythm, were assessed, and compared to continuous infusion chemotherapy for patients with advanced colorectal cancer.

Methods

Electronic English-language studies published until October 2020 were searched. Randomised Controlled Trials (RCTs) compared chronomodulated chemotherapy with non-chronomodulated (Conventional) chemotherapy for management of advanced colorectal cancer were included. Main outcomes were the objective response rate (ORR) and system-specific and overall toxicity related to chemotherapy. Electronic database search in Ovid Medline, Ovid Embase, Cochrane CENTRAL and the Cochrane Database of Systematic Review (CDSR).

Results

In total, 7 RCTs including 1137 patients were analysed. Males represented 684 (60%) of the study population. The median age was 60.5 (range: 47.2 - 64) years.

There is no significant difference between chronomodulated and conventional chemotherapy in ORR ((risk ratio (RR) 1.15; 95%CI [0.87-1.53]). There was no significant difference in gastrointestinal toxicity under the random effect model RR 1.02; CI 95% [0.68 – 1.51]. No significant difference was found regarding neurological and skin toxicities, (RR 0.64,95%CI [0.32 – 1.27]) and (RR 2.11, 95%CI [0.33-13.32]), respectively. However, patients who received chronomodulated chemotherapy had fewer haematological toxicity, (RR 0.36, 95%CI [0.27-0.48]).

Conclusion

There was no overall difference in ORR or toxicity but haematologic, between chronomodulated and non-chronomodulated chemotherapy used for patients with advanced colorectal cancer. Chronomodulated chemotherapy could be considered in patients at high risk of haematological toxicities.
Frailty increases the risk of adverse outcomes among 38,950 UK Biobank participants with prediabetes: A prospective cohort study
Authors: Cao Xingqi , Li Xueqin , Zhang Jingyun , Sun Xiaoyi , Yang Gan , Zhao Yining , Li Shujuan , Hoogendijk Emiel O. , Wang Xiaofeng , Zhu Yimin , Allore Heather , Gill Thomas M. , Liu Zuyun
Published: December 2022

Background

We aimed to systematically evaluate the associations of frailty, a simple health indicator, with risks of multiple adverse outcomes in late life among adults with prediabetes.

Methods

We evaluated 38,950 adults aged 40-64 years with prediabetes from the baseline survey of the UK Biobank. Frailty was assessed using the frailty phenotype (FP, 0-5), and participants were grouped into non-frail (FP =0), pre-frail (1≤ FP ≤2), and frail (FP ≥3). Multiple health outcomes were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations.

Results

At baseline, 49.1% and 5.9% of adults with prediabetes were identified as pre-frail and frail, respectively. Both pre-frailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <0.001). For instance, compared with their non-frail counterparts, frail participants with prediabetes had a significantly higher risk (P <0.001) of type 2 diabetes mellitus (T2DM) (hazard ratio [HR]: 1.73), diabetes-related microvascular disease (HR: 1.89), cardiovascular disease (HR: 1.66), chronic kidney disease (HR: 1.76), eye disease (HR: 1.31), dementia (HR: 2.03), depression (HR: 3.01), and all-cause mortality (HR: 1.81) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%.

Conclusions

In UK adults with prediabetes, both pre-frailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into the routine care for middle-aged adults with prediabetes, to improve the allocation of healthcare resources and reduce diabetes-related burdens.
Lateral diffusion of NKCC1 contributes to neuronal chloride homeostasis and is rapidly regulated by the WNK signaling pathway
Authors: Côme Etienne , Blachier Simon , Gouhier Juliette , Russeau Marion , Lévi Sabine
Published: December 2022

An upregulation of the Na+-K+-2Cl-co-transporter NKCC1, the main chloride importer in mature neurons, can lead to depolarizing/excitatory responses mediated by GABAAreceptors and thus to hyperactivity. Understanding the regulatory mechanisms of NKCC1 would help prevent intra-neuronal chloride accumulation that occurs in pathologies with defective inhibition. The cellular and molecular regulatory mechanisms of NKCC1 are poorly understood. Here, we report in mature hippocampal neurons that GABAergic activity controls the membrane diffusion and clustering of NKCC1 via the chloride-sensitive WNK1 kinase and the downstream SPAK kinase that directly phosphorylates NKCC1 on key threonine residues. At rest, this signaling pathway has little effect on intracellular Cl-concentration but it participates to the elevation of intraneuronal Cl-concentration in hyperactivity condition associated with an up-regulation of NKCC1. The fact that the chloride exporter KCC2 is also regulated in mature neurons by the WNK1 pathway indicates that this pathway will be a target of choice in the pathology.
Non-Local Conceptual Combination
Authors: Parrish Alicia , Rodriguez Amilleah , Pylkkänen Liina
Published: December 2022

It is uncontroversial that the syntax of an expression largely determines its meaning. For example, there is no way to interpret a sentence like “the blue hat has a white bow” as telling you that there is a white hat that has blue bow. But to what extent are the brain’s combinatory interpretive routines exclusively locked into the structures given by syntax? Consider another example: “The blue color of his hat is pretty.” This sentence tells us that a color is pretty, that the color is blue and that the color belongs to a hat. What the syntax of this sentence does not give us is a combination of “blue” and “hat.” But clearly, if we were to draw a picture of the meaning of this sentence, it would have a blue hat in it. We asked: upon encountering “hat” in this sentence, do our brains combine the features of “blue” with the features of “hat,” despite the long distance between them and no direct syntactic relation? By using a known neural measure of conceptual combination in the left anterior temporal lobe, we obtained evidence using MEG that our brains appear to perform such a long-distance conceptual combination that does not track the syntax. Intriguingly, word (or rather concept) order affected the directionality of the effect. While the effect of concept order remains a topic for future work, our results overall suggest that the meaning composition system of language is likely richer than the combinatory steps predicted from syntactic structures.
3D Graph Contrastive Learning for Molecular Property Prediction
Authors: Moon Kisung , Im Hyeon-Jin , Kwon Sunyoung
Published: December 2022

Motivation

Self-supervised learning (SSL) is a method that learns the data representation by utilizing supervision inherent in the data. This learning method is in the spotlight in the drug field, lacking annotated data due to time-consuming and expensive experiments. SSL using enormous unlabeled data has shown excellent performance for molecular property prediction, but a few issues exist. (1) Existing SSL models are large-scale; there is a limitation to implementing SSL where the computing resource is insufficient. (2) In most cases, they do not utilize 3D structural information for molecular representation learning. The activity of a drug is closely related to the structure of the drug molecule. Nevertheless, most current models do not use 3D information or use it partially. (3) Previous models that apply contrastive learning to molecules use the augmentation of permuting atoms and bonds. Therefore, molecules having different characteristics can be in the same positive samples. We propose a novel contrastive learning framework, small-scale 3D Graph Contrastive Learning (3DGCL) for molecular property prediction, to solve the above problems.

Results

3DGCL learns the molecular representation by reflecting the molecule’s structure through the pre-training process that does not change the semantics of the drug. Using only 1,128 samples for pre-train data and 0.5 million model parameters, we achieved state-of-the-art or comparable performance in six benchmark datasets. Extensive experiments demonstrate that 3D structural information based on chemical knowledge is essential to molecular representation learning for property prediction.

Availability

Data and codes are available inhttps://github.com/moonkisung/3DGCL.

Contact

sy.kwon@pusan.ac.kr
Heat wave, COVID-19, and mortality excess in the 2022 summer: a cohort study on data from Italian surveillances
Authors: Venturelli Francesco , Mancuso Pamela , Vicentini Massimo , Ottone Marta , Storchi Cinzia , Roncaglia Francesca , Bisaccia Eufemia , Ferrarini Chiara , Pezzotti Patrizio , Rossi Paolo Giorgi
Published: December 2022

We aimed to assess differences in the summer excess of mortality by COVID-19 history using data from the mortality and COVID-19 surveillances. We found 4% excess risk in 2022 summer, compared to 2015-2019. A mortality rate ratio of 1.59 (95%CI 1.39-1.82) for COVID-19 survivors compared to naïve, was found. Both were higher in people aged ≥75 years. During the July heat wave, the excess for COVID-19 survivors decreased and disappeared when excluding people living in nursing homes.

Funding statement

This study was partially supported by the Italian Ministry of Health –CCM 2020 - “Sorveglianza epidemiologica e controllo del COVID-19 in aree urbane metropolitane e per il contenimento della circolazione del Sars-CoV-2 nella popolazione immigrata in Italia” and by the Ricerca Corrente 2023

Highlights

the excess of mortality in COVID-19 survivors is not exacerbated by heatwaves

an excess of mortality during the whole summer in COVID-19 survivors aged over 75 suggest that no harvesting effect is appreciable in the older population that survived COVID-19

For COVID-19 survivors aged over 75, a lower mortality than the naïve population was observed only during the July heat wave when we stratified by residency
Comparable in vivo joint kinematics between self-reported stable and unstable knees after TKA can be explained by muscular adaptation strategies: a retrospective observational study
Authors: Rao Longfeng , Horn Nils , Meister Nadja , Preiss Stefan , Taylor William R. , Santuz Alessandro , Schütz Pascal
Published: December 2022

Background

Postoperative knee instability is one of the major reasons accounting for unsatisfactory outcomes, as well as a major failure mechanism leading to total knee arthroplasty (TKA) revision. Nevertheless, subjective knee instability is not well defined clinically, plausibly because the relationships between instability and implant kinematics during functional activities of daily living remain unclear. Although muscles play a critical role in supporting the dynamic stability of the knee joint, the influence of joint instability on muscle synergy patterns is poorly understood. Therefore, this study aimed to understand the impact of self-reported joint instability on tibiofemoral kinematics and muscle synergy patterns after TKA during functional gait activities of daily living.

Methods

Tibiofemoral kinematics and muscle synergy patterns were examined during level walking, downhill walking, and stair descent in eight self-reported unstable knees after TKA (3M:5F, 68.9±8.3 years, BMI 26.1±3.2 kg/m2, 31.9±20.4 months postoperatively), and compared against ten stable TKA knees (7M:3F, 62.6±6.8 years, 33.9±8.5 months postoperatively, BMI 29.4±4.8 kg/m2). For each knee joint, clinical assessments of postoperative outcome were performed, while joint kinematics were evaluated using moving video-fluoroscopy, and muscle synergy patterns were recorded using electromyography.

Results

Our results reveal that average condylar A-P translations, rotations, as well as their ranges of motion were comparable between stable and unstable groups. However, the unstable group exhibited more heterogeneous muscle synergy patterns and prolonged activation of knee flexors compared to the stable group. In addition, subjects who reported instability events during measurement showed distinct, subject-specific tibiofemoral kinematic patterns in the early/mid-swing phase of gait.

Conclusions

Our findings suggest that accurate movement analysis is sensitive for detecting acute instability events, but might be less robust in identifying general joint instability. Conversely, muscle synergy patterns seem to be able to identify muscular adaptation associated with underlying chronic knee instability.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Estimating Subnational Excess Mortality in Times of Pandemic. An application to Frenchdépartementsin 2020
Authors: Bonnet Florian , Camarda Carlo Giovanni
Published: December 2022

The Covid-19 pandemic did not affect sub-national regions in a uniform way. Knowledge of the impact of the pandemic on mortality at the local level is therefore an important issue for better assessing its burden. Vital statistics are now available for an increasing number of countries for 2020 and 2021, and allow the calculation of sub-national excess mortality. However, this calculation faces two important methodological challenges: (1) it requires appropriate mortality projection models; (2) small populations implies important uncertainty in the estimates, commonly neglected. We address both issues by adopting a method to forecast mortality at sub-national level and by incorporating uncertainty in the computation of mortality measures. We illustrate our approach to Frenchdépartements(NUTS 3, 95 geographical units) and produce estimates for 2020 and both sexes. Nonetheless, the proposed approach is so flexibility to allow estimation of excess mortality during Covid-19 in most demographic scenarios as well as for past pandemics.
Neurogenetic Mechanisms of Risk for ADHD: Examining Associations of Functionally-Annotated Polygenic Scores and Brain Volumes in a Population Cohort
Authors: He Quanfa , Keding Taylor , Zhang Qi , Miao Jiacheng , Herringa Ryan J. , Lu Qiongshi , Travers Brittany G. , Li James J.
Published: December 2022

Background

ADHD polygenic scores (PGS) are reliably predictive of ADHD outcomes across studies. However, traditional PGS arestatisticalindices of genetic liability – predictive of ADHD but uninformed bybiologicalinformation. The objective of our study was to determine whether a novel, biologically-informed, functionally annotated ADHD PGS can reveal specific brain mechanisms of risk for ADHD.

Methods

Data were from the Philadelphia Neurodevelopmental Cohort (n=555). Multiple mediation models were tested to examine the indirect effects of ADHD PGS (including one using a functionally annotated approach, i.e.,AnnoPred) on ADHD inattention (IA) and hyperactivity-impulsivity (HI) symptoms, via gray matter volumes in the cingulate gyrus, angular gyrus, caudate, dorsolateral prefrontal cortex (DLPFC), and inferior temporal lobe. Age-stratified analyses (children, adolescents, and young adults) were also conducted to account for developmental differences.

Results

A direct effect was detected betweenAnnoPredPGS and IA symptoms in adolescents only. No indirect effects via brain volumes were detected for either IA or HI symptoms. However, ADHD PGS were consistently associated with the DLPFC.

Conclusions

A biologically-informed PGS yielded a more powerful (and developmentally-specific) signal in detecting a direct effect of ADHD PGS on adolescent IA symptoms. However, no indirect effects between ADHD PGS and ADHD symptomology via the brain emerged. ADHD will become increasing predictive as discovery sample sizes climb. Studies that integrate both genetic and neuroimaging information are critical to advancing our understanding of the biological mechanisms underlying ADHD.
Sporting tournaments and changed birth rates 9 months later: a systematic review
Authors: Masukume Gwinyai , Grech Victor , Ryan Margaret
Published: December 2022

Introduction

Emerging evidence suggests that major sporting tournaments are associated with increased birth rates 9 months afterwards. This increase has been attributed to the celebratory atmosphere encouraging more conception through increased sexual activity among the populace.

Methods

Studies that examined the relationship between a major sporting tournament and altered birth metrics (number of births and/or birth sex ratio, defined as male divided by total live births) 9(±1) months later were sought out systematically through searches of PubMed and Scopus. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed in conducting this study.

Results

Five major sporting tournaments were linked to noticeably increased birth metrics 9(±1) months later. The Super Bowl (increased United States birth sex ratio in multiple years, however, from 2004 to 2013 there were no observable birth increases in winning counties and losing was not associated with a changed number of births), the 2009 UEFA Champions League (16% increase in Solsonès and Bages births in Spain), the 2010 FIFA World Cup (increased birth sex ratio and over 1000 extra births in South Africa), the 2016 UEFA Euros (2% increase in Northern Ireland births) and the 2019 Rugby World Cup (increased birth sex ratio in some Japanese prefectures). Nine months after the most popular provincialla Ligasoccer teams unexpectedly lost matches, there were 0.8% fewer births in those provinces from 2001 to 2015; the number of births were unaffected by unexpected wins. After the 1998 FIFA World Cup a changed sex ratio at birth was not witnessed 9 months on. Nine months following a performance improvement of one standard deviation by a European national soccer team at the FIFA World Cup or UEFA Euro Championships, from 1960 to 2016, there was a 0.3% decline in births 9 months on.

Conclusions

With a few exceptions, major American football, Association football (soccer) and Rugby apex tournaments in Africa, North America, Asia and Europe were associated with increases in the number of babies born and/or in the birth sex ratio 9(±1) months following notable team wins and/or hosting the tournament. Related to this, unexpected losses by teams from a premier soccer league were associated with a decline in births 9 months on. In conclusion, Nelson Mandela was correct when he averred, “Sport has the power to change the world. It has the power to inspire, it has the power to unite people in a way that little else does.”

PROSPERO registration

CRD42022382971
The Impact of COVID-19 Pandemic on Mental Health: A Scoping Review
Authors: Josiah Blessing O. , Ncube France
Published: December 2022

Background

This scoping review assessed the COVID-19 impacts on mental health and associated risk factors.

Methods

A systematic literature search for relevant articles published in the period March 2020 to July 2022, was conducted in the APA PsychInfo, JBI Evidence Synthesis, Epistemonikos, PubMed, and Cochrane databases.

Results

A total of 72 studies met the inclusion criteria. Results showed that the commonly used mental health assessment tools were the Patient Health Questionnaire (41.7%), Generalized Anxiety Disorder Scale (36%), 21-item Depression, Anxiety, and Stress (13.9%), Impact of Event Scale (12.5%), Pittsburgh Sleep Quality Index (9.7%), Symptom Checklist and the General Health Questionnaire (6.9% each). The prevalence rate of depression ranged from 5-76.5%, 5.6-80.5% for anxiety, 9.1-65% for Post-Traumatic Stress Disorder, 8.3-61.7% for sleep disorders, 4.9-70.1% for stress, 7-71.5% for psychological distress, and 21.4-69.3% for general mental health conditions. The major risks included female gender, healthcare-related/frontline jobs, isolation/quarantine, poverty, lower education, COVID-19 risk, age, commodities, mental illness history, negative psychology, and higher social media exposure. The incidence of mental disorders increased along with the increasing cases of COVID-19 and the corresponding government restrictions.

Conclusion

Standard assessment tools were used for mental health assessment by the reviewed studies which were conducted during COVID-19. Mental health disorders like depression, anxiety, and stress increased during the COVID-19 pandemic and lockdowns. Various factors impacted the prevalence of mental health disorders. Policymakers need to provide social protective measures to improve coping capacities during critical health events to avoid negative impacts on the population. Further studies should investigate the effectiveness of interventions for reducing the prevalence and risk factors for mental health conditions during a public health challenge.

Background