bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Reporting, Quality of Management, and Financial Performance
Authors: Churet Cécile , Eccles Robert G.
Published: November 2023

Interest in integrated reporting continues to grow as its proponents cite a number of significant benefits to both companies and investors. But given the still‐early stages of development of this new management practice and the relative paucity of data, establishing empirical confirmation of these claims is difficult. Using RobecomSAM's proprietary database of over 2,000 companies surveyed during its annual Corporate Sustainability Assessment (CSA), the authors discuss the extent and recent growth of integrated reporting, and its likely effects on important indicators of both ESG quality of management and financial performance.

The authors begin by reporting that although only 12% of the companies in the survey dataset practiced some form of integrated reporting in 2012, that number represented a 50% increase from 2011. The authors also report a strong relationship between integrated reporting and ESG quality of management, which some studies suggest has become a useful indicator of the overall effectiveness of management in creating value over the long term. This relationship is particularly strong in certain sectors, notably healthcare. At the same time, the authors find a relationship between integrated reporting and financial performance for two sectors—healthcare and information technology—though not for the population as a whole. The authors suggest that this apparent lack of effect may be attributable to a time lag between integrated reporting's contribution to better ESG quality of management, and the eventual reflection of such management in financial performance.
The role of thriving in mental health among people with intellectual and developmental disabilities during the COVID‐19 pandemic in Canada
Authors: Sellitto Teresa , Fraser‐Thomas Jessica , Bassett‐Gunter Rebecca L. , Lee Vivian , Lunsky Yona , Balogh Robert , Weiss Jonathan A.
Published: November 2023

Background

The COVID‐19 pandemic has had a negative impact on the mental health of people with intellectual and developmental disabilities. Numerous pandemic‐related stressors experienced by people with intellectual and developmental disabilities may have impacted their ability to thrive, which has been linked to mental health outcomes. The current study examined the associations among COVID‐19 stressors, thriving, and mental health problems among youth and adults with intellectual and developmental disabilities.

Method

Caregivers of 159 people with intellectual and developmental disabilities between 12 and 35 years of age from Canada completed an online questionnaire.

Results

A mediation analysis revealed that COVID‐19 stressors were positively associated with mental health problems, and that thriving partially mediated this association.

Conclusion

Our findings suggest that experiences of thriving may be an important target for mental health support for people with intellectual and developmental disabilities.
Whole‐exome sequencing analysis of patent ductus arteriosus in a Japanese macaque (Macaca fuscata)
Authors: Jang Young‐Jin , Park Byung‐Yong , Tae Hyun‐Jin , Sim Jeoungha , Ahn Dongchoon
Published: November 2023

We performed whole‐exome sequencing using a human exome capture kit to analyze the potential genetic factors related to patent ductus arteriosus in Japanese macaques. Compared with the reference sequences of other primates, we identified potential missense variants in five genes: ADAM15, AZGP1, CSPG4, TNFRSF13B, and EPOR.
Synergistic effects of immune checkpoints and checkpoint inhibitors in inflammatory neuropathies: Implications and mechanisms
Authors: Sarkar Aritrani , Nagappa Madhu , Dey Saikat , Mondal Sandipan , Babu Gopika Suresh , Choudhury Saptamita Pal , Akhil Pokala , Debnath Monojit
Published: November 2023

Immune checkpoint molecules play pivotal roles in the regulation of immune homeostasis. Disruption of the immune checkpoints causes autoimmune/inflammatory as well as malignant disorders. Over the past few years, the immune checkpoint molecules with inhibitory function emerged as potential therapeutic targets in oncological conditions. The inhibition of the function of these molecules by using immune checkpoint inhibitors (ICIs) has brought paradigmatic changes in cancer therapy due to their remarkable clinical benefits, not only in improving the quality of life but also in prolonging the survival time of cancer patients. Unfortunately, the ICIs soon turned out to be a “double‐edged sword” as the use of ICIs caused multiple immune‐related adverse effects (irAEs). The development of inflammatory neuropathies such as Guillain–Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) as the secondary effects of immunotherapy appeared very challenging as these conditions result in significant and often permanent disability. The underlying mechanism(s) through which ICIs trigger inflammatory neuropathies are currently not known. Compelling evidence suggests autoimmune reaction and/or inflammation as the independent risk mechanism of inflammatory neuropathies. There is a lack of understanding as to whether prior exposure to the risk factors of inflammatory neuropathies, the presence of germline genetic variants in immune function‐related genes, genetic variations within immune checkpoint molecules, the existence of autoantibodies, and activated/memory T cells act as determining factors for ICI‐induced inflammatory neuropathies. Herein, we highlight the available pieces of evidence, discuss the mechanistic basis, and propose a few testable hypotheses on inflammatory neuropathies as irAEs of immunotherapy.
Plasma proteomic analysis on neuropathic pain in idiopathic peripheral neuropathy patients
Authors: van Doormaal Perry T. C. , Thomas Simone , Ajroud‐Driss Senda , Cole Robert N. , DeVine Lauren R. , Dimachkie Mazen M. , Geisler Stefanie , Freeman Roy , Simpson David M. , Singleton J. Robinson , Smith A. Gordon , Stino Amro ,   PNRR Study Group, Höke Ahmet
Published: November 2023

Background and Aims

Why only half of the idiopathic peripheral neuropathy (IPN) patients develop neuropathic pain remains unknown. By conducting a proteomics analysis on IPN patients, we aimed to discover proteins and new pathways that are associated with neuropathic pain.

Methods

We conducted unbiased mass‐spectrometry proteomics analysis on blood plasma from 31 IPN patients with severe neuropathic pain and 29 IPN patients with no pain, to investigate protein biomarkers and protein–protein interactions associated with neuropathic pain. Univariate modeling was done with linear mixed modeling (LMM) and corrected for multiple testing. Multivariate modeling was performed using elastic net analysis and validated with internal cross‐validation and bootstrapping.

Results

In the univariate analysis, 73 proteins showed a p‐value <.05 and 12 proteins showed a p‐value <.01. None were significant after Benjamini–Hochberg adjustment for multiple testing. Elastic net analysis created a model containing 12 proteins with reasonable discriminatory power to differentiate between painful and painless IPN (false‐negative rate 0.10, false‐positive rate 0.18, and an area under the curve 0.75). Eight of these 12 proteins were clustered into one interaction network, significantly enriched for the complement and coagulation pathway (Benjamini–Hochberg adjusted p‐value = .0057), with complement component 3 (C3) as the central node. Bootstrap validation identified insulin‐like growth factor‐binding protein 2 (IGFBP2), complement factor H‐related protein 4 (CFHR4), and ferritin light chain (FTL), as the most discriminatory proteins of the original 12 identified.

Interpretation

This proteomics analysis suggests a role for the complement system in neuropathic pain in IPN.
Evaluation of American College of Radiology Ovarian‐Adnexal Reporting and Data System ultrasound to predict malignancy risk in adnexal lesions
Authors: Li Ya , Shao Guangrui , Wu Mei , Zhang Feixue , Zhang Yuqing , Shao Chunchun
Published: November 2023

Aims

To validate the diagnostic performance of Ovarian‐Adnexal Reporting and Data System (O‐RADS) ultrasound for preoperative adnexal lesions in an external center. The secondary aim was to evaluate the performance of a strategy test including O‐RADS ultrasound evaluation and subjective assessment of higher malignant risk lesions.

Methods

One hundred thirty patients with 158 ovarian‐adnexal lesions were enrolled in the study. Each lesion was assigned an O‐RADS score after real‐time ultrasound examination by one experienced radiologist. A second subjective assessment by an expert was performed for O‐RADS 4 and O‐RADS 5 lesions. The histopathological diagnosis was used as the reference standard.

Results

A total of 126 benign and 32 malignant adnexal masses were included in the study. The area under the receiver operating characteristic curve of O‐RADS ultrasound was 0.950, with a cutoff value > O‐RADS 3. The sensitivity, specificity, and negative and positive predictive values were 100% (95% confidence interval [CI], 0.867–1), 83.3% (95% CI, 0.754–0.892), 60.4% (95% CI, 0.460–0.732), and 100% (95% CI, 0.956–1), respectively. For the strategy test, the sensitivity, specificity, negative and positive predictive values were 100% (95% CI, 0.867–1), 92.1% (95% CI, 0.855–0.959), 76.2% (95% CI, 0.602–0.874), and 100% (95% CI, 0.960–1), respectively. In comparison with O‐RADS ultrasound, the specificity and negative predictive value of the strategy test were slightly higher (p < 0.05).

Conclusions

Good diagnostic performance of the O‐RADS ultrasound in adnexal lesions can be achieved by experienced radiologists in clinical practice. A second subjective assessment of sonographic findings can be applied to O‐RADS 4 and 5 lesions.
Dynamic Capabilities and MNE Global Strategy: A Systematic Literature Review‐Based Novel Conceptual Framework
Authors: Pitelis Christos N. , Teece David J. , Yang Hongyi
Published: November 2023

Global strategy cannot be fully understood without consideration of dynamic capabilities (DCs). This is because the three key constituents of DCs – the sensing and seizing of opportunities and the reconfiguration of the resource base – are essential preconditions for strategy development, within nations and cross‐border. We investigate the aspects of DCs that are most suitable for global strategy and those that need to be revisited and developed. We discuss theory and evidence on DCs and global strategy, present a systematic literature review, compare theory and evidence, and identify gaps between the two as well as opportunities to align them more closely and to develop both. To help guide future research, we develop a novel conceptual framework and provide suggestions for more theory‐congruent empirical research.
Diaporthe melongenae sp. nov, a new fungal species causing leaf blight in eggplant
Authors: Aumentado Herbert Dustin , Balendres Mark Angelo
Published: November 2023

Eggplant is a vegetable crop of the Solanaceae family. In November 2021, leaf blights of eggplant were observed from an eggplant field with an approximate disease incidence of 10%–30% in Cavite, Philippines. The infected leaves had typical symptoms of Phomopsis blight disease. Two fungal isolates were obtained, and morphological characteristics resemble those of a Diaporthe species. Based on the combined multi‐gene phylogenetic analysis, Diaporthe melongenae sp. nov. formed a separate clade from closely related species: D. guangdongensis, D. melonis and D. moriniae with high bootstrap support values of 99/1.0 ML/PP. Moreover, the morphological characteristics of D. melongenae have differences from the closely related species. D. melongenae differs by having a slightly smaller average alpha conidial size than D. guangdongensis and absence of beta conidia. Diaporthe melonis is distinct from D. melongenae by having slightly constricted middle alpha conidia. Together, based on morphology, multi‐locus phylogeny, GCPSRA and ecology (lifestyle, host and pathogenicity) herein we introduce D. melongenae as a novel species. Furthermore, this study presented the current phylogenetic tree of D. sojae species complex based on accepted Diaporthe species.
The MT1 receptor as the target of ramelteon neuroprotection in ischemic stroke
Authors: Zhang Xinmu , Peng Bin , Zhang Shenqi , Wang Jian , Yuan Xiong , Peled Sharon , Chen Wu , Ding Jinyin , Li Wei , Zhang Andrew , Wu Qiaofeng , Stavrovskaya Irina G. , Luo Chengliang , Sinha Bharati , Tu Yanyang , Yuan Xiaojing , Li Mingchang , Liu Shuqing , Fu Jianfang , Aziz‐Sultan Ali , Kristal Bruce S. , Alterovitz Gil , Du Rose , Zhou Shuanhu , Wang Xin
Published: November 2023

Stroke is the leading cause of death and disability worldwide. Novel and effective therapies for ischemic stroke are urgently needed. Here, we report that melatonin receptor 1A (MT1) agonist ramelteon is a neuroprotective drug candidate as demonstrated by comprehensive experimental models of ischemic stroke, including a middle cerebral artery occlusion (MCAO) mouse model of cerebral ischemia in vivo, organotypic hippocampal slice cultures ex vivo, and cultured neurons in vitro; the neuroprotective effects of ramelteon are diminished in MT1‐knockout (KO) mice and MT1‐KO cultured neurons. For the first time, we report that the MT1 receptor is significantly depleted in the brain of MCAO mice, and ramelteon treatment significantly recovers the brain MT1 losses in MCAO mice, which is further explained by the Connectivity Map L1000 bioinformatic analysis that shows gene‐expression signatures of MCAO mice are negatively connected to melatonin receptor agonist like Ramelteon. We demonstrate that ramelteon improves the cerebral blood flow signals in ischemic stroke that is potentially mediated, at least, partly by mechanisms of activating endothelial nitric oxide synthase. Our results also show that the neuroprotection of ramelteon counteracts reactive oxygen species‐induced oxidative stress and activates the nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 pathway. Ramelteon inhibits the mitochondrial and autophagic death pathways in MCAO mice and cultured neurons, consistent with gene set enrichment analysis from a bioinformatics perspective angle. Our data suggest that Ramelteon is a potential neuroprotective drug candidate, and MT1 is the neuroprotective target for ischemic stroke, which provides new insights into stroke therapy. MT1‐KO mice and cultured neurons may provide animal and cellular models of accelerated ischemic damage and neuronal cell death.
Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment
Authors: Zhao Handan , Lu Yanqiu , Li Shan , Qin Jiangying , Xu Miaomiao , Ye Hui , Yang Zongxing , Rao Jianfeng , Chen Guochun , Su Feifei , Hu Zhiliang , Xu Lijun
Published: November 2023

Background

The efficacy and side effects of voriconazole plus 5‐flucytosine (Vori + 5‐FC) versus amphotericin B deoxycholate plus 5‐flucytosine (AmBd + 5‐FC) as an induction treatment for cryptococcal meningitis are unknown.

Methods

Forty‐seven patients treated with Vori + 5‐FC and 92 patients treated with AmBd + 5‐FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two‐week laboratory test results and 90‐day mortality were compared between the two groups.

Results

After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5‐FC group and 76.5% in the AmBd + 5‐FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5‐FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2‐week induction treatment. The Vori + 5‐FC group and AmBd + 5‐FC group had similar 90‐day cumulative survival rates (89.9% vs. 87.8%, p = .926).

Conclusion

The Vori + 5‐FC regimen was associated with low 2‐week CSF sterile culture and was not superior to AmBd + 5‐FC as induction therapy in terms of the 90‐day cumulative survival rate of CM patients.
A machine learning–based generalized approach for predicting unauthorized immigration flow considering dynamic border security nexus
Authors: Aziz Ridwan Al , Ahmed Tanvir , Zhuang Jun
Published: November 2023

Unauthorized immigration has been a long‐standing and contentious challenge for developed and developing countries. Numerous continually evolving push and pull factors across international borders, such as economy, employment, population density, unrest, corruption, and climate have driven this migration. Large‐scale pandemics such as COVID‐19, causing further instability in countries' financial well‐being, can initiate or alter emigration flow from different countries. In light of such a complex confluence of factors, climate change, and demographic shifts in migrant communities, it is high time to shift toward machine learning–reinforced generalized approaches from the traditional parametric approaches based on migrant community–specific localized surveys. To our best knowledge, no literature has explored the nonparametric approach and developed a comprehensive database independent of localized surveys to analyze unauthorized migration. This article fills this gap by deploying nine nonparametric machine learning algorithms for predicting unauthorized immigration flow considering the dynamic border security nexus. This framework considers the Seasonal Autoregressive Integrated Moving Average model as the null model. The proposed novel framework removes the dependency on localized survey‐based studies and provides a more cost‐effective, faster, and big data–friendly approach. This study finds the Bayesian Additive Regression Tree model as the best predictive model.
The ‘European City’ at the Crossroads: Four Analytical Elements for Understanding Convergence and Differentiation
Authors: Kazepov Yuri , Ahn Byeongsun , Cucca Roberta
Published: November 2023

This theoretical contribution explores the use of four analytical elements to understand European cities' commonalities and distinctive characteristics in the face of the challenges presented by structural global changes and supra‐national governance mechanisms: sovereignty, policy, politics, context. The article shows how institutional and contextual opportunities mediate globalization's repercussions to varying degrees at the urban level, according to national and regional dynamics and institutional frameworks as well as urban governance structures. Additionally, the article argues that the local policy capacity of cities and their ability to innovate and deal with new social challenges are shaped by the interplay among the four specific elements mentioned before.
In vitro quality parameters of whole blood‐derived platelets pooled using two different platelet pooling sets and stored up to 7 days are similar
Authors: Vandenbroeke Tania , Gloor Christina , Wingfield Tyler , Leite Caroline , Carr Kathlynn , Turner Chris , Ngamsuntikul Samantha , Sutor Laurie , Compton Frances , Nestheide Shawnagay , Rugg Neeta , Cancelas Jose A. , Dumont Larry J.
Published: November 2023

Background

Increasing the number of collections of whole blood‐derived platelets (WBDP) and lengthening the allowable storage time may alleviate platelet (PLT) shortages. There is a need for new PLT pooling sets that can provide acceptable quality on Day 7 of storage.

Study Design and Methods

This pool‐and‐split study compared WBDP prepared using the platelet‐rich plasma method with the novel IMUGARD WB PLT pooling set and a control pooling set. After pooling and filtration, PLT products were tested on Days 1, 5, and 7. Large volume delayed sampling (LVDS) cultures were taken on Day 2.

Results

The median postfiltration residual white blood cell (rWBC) content was 0.18 million per product (maximum 1.26 million; n = 69) with mean PLT recovery of 88.5 ± 2.8% for the new set and median 0.23 million (maximum 1.83 million) rWBC with 87.5 ± 2.5% recovery for the control. Day 5 mean pH22°C were 7.18 ± 0.12 and 7.13 ± 0.10 for the new and control set, respectively. Day 5 in vitro quality parameters were within 20% between the two pooling sets. The new set Day 7 pH22°C was acceptable (7.07 ± 0.17, 100% ≥ 6.3), and most parameters were within 20% of Day 5 values.

Conclusion

WBDP quality for the new pooling set is acceptable across a battery of in vitro tests when stored up to 7 days and meets FDA regulatory criteria. The quality parameters were similar between the new pooling set and the control set on Day 5. This new set is compatible with LVDS.
Prime tuples and Siegel zeros
Authors: Wright Thomas
Published: November 2023

Under the assumption of infinitely many Siegel zeroes with for a sufficiently large value of , we prove that there exist infinitely many ‐tuples of primes that are apart. This ‘improves’ (in some sense) on the bounds of Maynard–Tao, Baker–Irving, and Polymath 8b, who found bounds of unconditionally and assuming the Elliott–Halberstam conjecture; it also generalizes a 1983 result of Heath–Brown that states that infinitely many Siegel zeroes would imply infinitely many twin primes. Under this assumption of Siegel zeroes, we also improve the upper bounds for the gaps between prime triples, quadruples, quintuples, and sextuples beyond the bounds found via Elliott–Halberstam.
A new approach to twisted homological stability with applications to congruence subgroups
Authors: Putman Andrew
Published: November 2023

We introduce a new method for proving twisted homological stability, and use it to prove such results for symmetric groups and general linear groups. In addition to sometimes slightly improving the stable range given by the traditional method (due to Dwyer), it is easier to adapt to nonstandard situations. As an illustration of this, we generalize to of many rings a theorem of Borel that says that passing from of a number ring to a finite‐index subgroup does not change the rational cohomology. Charney proved this generalization for trivial coefficients, and we extend it to twisted coefficients.
Passive Design Strategies in Focus: Implications of Climate Change on New Buildings and Renovations
Authors: Ganem-Karlen Carolina , Barea-Paci Gustavo Javier
Published: November 2023

Climate change is happening, and there is a general consensus that measures to drastically reduce emissions must be taken. Nevertheless, its implications on new buildings and renovations are not fully understood yet. Bioclimatic building design is based on the knowledge of passive design strategies potential for a location. However, traditionally used passive strategies may no longer be the correct design approach in the future. A methodological contribution for the assessment of the influence of climate change on passive building strategies in temperate climates is presented. Based on the top priority Intergovernmental Panel on Climate Change scenarios of the 6th assessment report (AR6) the shared socio-economic pathways (SSP) and their equivalences with the prior representative concentration pathways (RCP), the effects of climate change on different cooling and heating strategies are examined for a continental temperate-cold desert climate with significant daily and annual variation. The results are integrated directly into a selected case study with the intention of exemplifying a concrete application. The findings of this study showed that the shading season is expanding even toward the transitional months, such as April and October. Future climate-adapted buildings in temperate climatic zones will have to confront overheating. Moreover, in the particular studied case, present and future total energy requirements seem similar and variations are perceived as low between scenarios. The main discussion focuses on the type of energy required that will turn from natural gas (net to primary energy conversion factor = 1.25) to electricity (net to primary energy conversion factor = 3.30).
Augmenting L3MBTL2-induced condensates suppresses tumor growth in osteosarcoma
Authors: Zhong Li , Wang Jingxuan , Chen Wanqi , Lv Dongming , Zhang Ruhua , Wang Xin , Zeng Cuiling , He Xiaobo , Zheng Lisi , Gao Ying , Wang Shang , Li Miao , Wu Yuanzhong , Yin Junqiang , Kang Tiebang , Liao Dan
Published: November 2023

Osteosarcoma is a highly aggressive cancer and lacks effective therapeutic targets. We found that L3MBTL2 acts as a tumor suppressor by transcriptionally repressing
IFIT2
in osteosarcoma. L3MBTL2 recruits the components of Polycomb repressive complex 1.6 to form condensates via both Pho-binding pockets and polybasic regions within carboxyl-terminal intrinsically disordered regions; the L3MBTL2-induced condensates are required for its tumor suppression. Multi-monoubiquitination of L3MBTL2 by UBE2O results in its proteasomal degradation, and the UBE2O/L3MBTL2 axis was crucial for osteosarcoma growth. There is a reverse correlation between L3MBTL2 and UBE2O in osteosarcoma tissues, and higher UBE2O and lower L3MBTL2 are associated with poorer prognosis in osteosarcoma. Pharmacological blockage of UBE2O by arsenic trioxide can enhance L3MBTL2-induced condensates and consequently suppress osteosarcoma growth. Our findings unveil a crucial biological function of L3MBTL2-induced condensates in mediating tumor suppression, proposing the UBE2O-L3MBTL2 axis as a potential cancer therapeutic target in osteosarcoma.
Therapeutic targeting of CPSF3-dependent transcriptional termination in ovarian cancer
Authors: Shen Peiye , Ye Kaiyan , Xiang Huaijiang , Zhang Zhenfeng , He Qinyang , Zhang Xiao , Cai Mei-Chun , Chen Junfei , Sun Yunheng , Lin Lifeng , Qi Chunting , Zhang Meiying , Cheung Lydia W. T. , Shi Tingyan , Yin Xia , Li Ying , Di Wen , Zang Rongyu , Tan Li , Zhuang Guanglei
Published: November 2023

Transcriptional dysregulation is a recurring pathogenic hallmark and an emerging therapeutic vulnerability in ovarian cancer. Here, we demonstrated that ovarian cancer exhibited a unique dependency on the regulatory machinery of transcriptional termination, particularly, cleavage and polyadenylation specificity factor (CPSF) complex. Genetic abrogation of multiple CPSF subunits substantially hampered neoplastic cell viability, and we presented evidence that their indispensable roles converged on the endonuclease CPSF3. Mechanistically, CPSF perturbation resulted in lengthened 3′-untranslated regions, diminished intronic polyadenylation and widespread transcriptional readthrough, and consequently suppressed oncogenic pathways. Furthermore, we reported the development of specific CPSF3 inhibitors building upon the benzoxaborole scaffold, which exerted potent antitumor activity. Notably, CPSF3 blockade effectively exacerbated genomic instability by down-regulating DNA damage repair genes and thus acted in synergy with poly(adenosine 5'-diphosphate–ribose) polymerase inhibition. These findings establish CPSF3-dependent transcriptional termination as an exploitable driving mechanism of ovarian cancer and provide a promising class of boron-containing compounds for targeting transcription-addicted human malignancies.
Halogen bonding–driven chiral amplification of a bimetallic gold-copper cluster through hierarchical assembly
Authors: Wang Ya-Jie , Shi Xiao-Yan , Xing Pengyao , Dong Xi-Yan , Zang Shuang-Quan
Published: November 2023

Understanding the fundamentals and applications of chirality relies substantially on the amplification of chirality through hierarchical assemblies involving various weak interactions. However, a notable challenge remains for metal clusters chiral assembly driven by halogen bonding, despite their promising applications in lighting, catalysis, and biomedicine. Here, we used halogen bonding–driven assembly to achieve a hierarchical degree of achiral emissive

Au
2
Cu
2

clusters. From single crystals to one-dimensional ribbons and then to helixes, the morphologies were primarily modulated by intermolecular halogen bonding that evoked by achiral or/and chiral iodofluorobenzene (IFBs) molecules. Concomitantly, the luminescence and circularly polarized luminescence (CPL) changed a lot, ultimately leading to a substantial increase in the luminescence dissymmetry
g
-factor (
g
lum
) of 0.036 in the supramolecular helix. This work opens an avenue for hierarchical assemblies using predesigned metal clusters as building blocks though directional halogen bonding. This achievement marks a noteworthy advancement in the field of nanosized inorganic functional blocks.
Algorithmic encoding of adaptive responses in temperature-sensing multimaterial architectures
Authors: Li Weichen , Wang Yue , Chen Tian , Zhang Xiaojia Shelly
Published: November 2023

We envision programmable matters that can alter their physical properties in desirable manners based on user input or autonomous sensing. This vision motivates the pursuit of mechanical metamaterials that interact with the environment in a programmable fashion. However, this has not been systematically achieved for soft metamaterials because of the highly nonlinear deformation and underdevelopment of rational design strategies. Here, we use computational morphogenesis and multimaterial polymer 3D printing to systematically create soft metamaterials with arbitrarily programmable temperature-switchable nonlinear mechanical responses under large deformations. This is made possible by harnessing the distinct glass transition temperatures of different polymers, which, when optimally synthesized, produce local and giant stiffness changes in a controllable manner. Featuring complex geometries, the generated structures and metamaterials exhibit fundamentally different yet programmable nonlinear force-displacement relations and deformation patterns as temperature varies. The rational design and fabrication establish an objective-oriented synthesis of metamaterials with freely tunable thermally adaptive behaviors. This imbues structures and materials with environment-aware intelligence.
Translating models of obesity to tackle common obesity
Authors: Ulijaszek Stanley
Published: November 2023

Tackling common obesity rests on having models of obesity that can be effectively translated into models for intervention; are we nearly there yet?
A comprehensive overview of the Chloroflexota community in wastewater treatment plants worldwide
Authors: Petriglieri Francesca , Kondrotaite Zivile , Singleton Caitlin , Nierychlo Marta , Dueholm Morten K. D. , Nielsen Per H.
Published: November 2023

Filamentous Chloroflexota are abundant in activated sludge wastewater treatment plants (WWTPs) worldwide and are occasionally associated with poor solid-liquid separation or foaming, but most of the abundant lineages remain undescribed. Here, we present a comprehensive overview of Chloroflexota abundant in WWTPs worldwide, using high-quality metagenome-assembled genomes (MAGs) and 16S rRNA amplicon data from 740 Danish and global WWTPs. Many novel taxa were described, encompassing 4 families, 13 genera, and 29 novel species. These were widely distributed across most continents, influenced by factors such as climate zone and WWTP process design. Visualization by fluorescence
in situ
hybridization (FISH) confirmed their high abundances in many WWTPs based on the amplicon data and showed a filamentous morphology for nearly all species. Most formed thin and short trichomes integrated into the floc structure, unlikely to form the typical inter-floc bridging that hinders activated sludge floc settling. Metabolic reconstruction of 53 high-quality MAGs, representing most of the novel genera, offered further insights into their versatile metabolisms and suggested a primary role in carbon removal and involvement in nitrogen cycling. The presence of glycogen reserves, detected by FISH-Raman microspectroscopy, seemed widespread across the phylum, demonstrating that these bacteria likely utilize glycogen as energy storage to survive periods with limited resources. This study gives a broad overview of the Chloroflexota community in global activated sludge WWTPs and improves our understanding of their roles in these engineered ecosystems.

IMPORTANCE

Chloroflexota are often abundant members of the biomass in wastewater treatment plants (WWTPs) worldwide, typically with a filamentous morphology, forming the backbones of the activated sludge floc. However, their overgrowth can often cause operational issues connected to poor settling or foaming, impairing effluent quality and increasing operational costs. Despite their importance, few Chloroflexota genera have been characterized so far. Here, we present a comprehensive overview of Chloroflexota abundant in WWTPs worldwide and an in-depth characterization of their morphology, phylogeny, and ecophysiology, obtaining a broad understanding of their ecological role in activated sludge.
In vitro
optimization of crushed drug-sensitive antituberculosis medication when administered via a nasogastric tube
Authors: Phogole Cassius M. , de Jong Jocelyn , Lalla Usha , Decloedt Eric , Kellermann Tracy
Published: November 2023

In low-resource settings, access to intravenous formulations of antituberculosis drugs is lacking or absent. Thus, critically ill patients with tuberculosis (TB) are often treated with readily available tablets which are crushed, mixed with water, and administered via a nasogastric tube (NGT). This has been associated with plasma concentrations below the recommended target, particularly of rifampicin (RIF) and isoniazid (INH), leading to clinical failure and development of drug resistance. We aimed to identify physiochemical factors contributing to lower plasma concentrations of antituberculosis drugs when administered in this manner using laboratory-based techniques, including the addition of ascorbic acid (AA) for optimum administration. Aqueous solubility of crushed medication using the inversion mixing method was evaluated against easily implementable mixing methods (sonication/vortexing) with or without AA. Stability of crushed medication in simulated-gastrointestinal fluids was evaluated with or without AA. Drug loss via NGT surface adsorption was quantitatively determined. RIF demonstrated poor aqueous solubility of 5.2%. Incorporation of AA improved the solubility to 29.7%, and with the addition of mixing techniques, solubility improved to 86.3%. Mixing methods with AA further improved the solubilities of both INH (80%) and pyrazinamide (PZA, 64%) to over 90%. AA also showed protective effects against unstable RIF in simulated-gastric fluid. Conventional flushing of NGT after drug administration with 10 mL of water resulted in drug losses of 1.5%, 0.13%, and 1.4% for RIF, INH, and PZA, respectively. An additional flushing step halved this amount. These interventions may improve the poor plasma concentrations of crushed antituberculosis drugs in critically ill patients.

IMPORTANCE

The incidence of tuberculosis (TB) in intensive care units (ICUs) can be as high as 3% in high-burden settings, translating to more than 7,500 patients admitted to the ICU annually. In resource-limited settings, the lack or absence of intravenous formulations of drug-sensitive antituberculosis medications necessitates healthcare practitioners to crush, dissolve, and administer the drugs to critically ill patients via a nasogastric tube (NGT). This off-label practice has been linked to plasma concentrations below the recommended target concentrations, particularly of rifampicin and isoniazid, leading to clinical failure and the development of drug resistance. Optimizing the delivery of crushed drug-sensitive antituberculosis medication via the NGT to critically ill patients is of utmost importance.
Blood cell differential count discretisation modelling to predict survival in adults reporting to the emergency room: a retrospective cohort study
Authors: Fumagalli Riccardo Mario , Chiarelli Marco , Cazzaniga Massimo , Bonato Claudio , D'Angelo Luciano , Cavalieri D'Oro Luca , Cerino Mario , Terragni Sabina , Lainu Elisa , Lorini Cristina , Scarazzati Claudio , Tazzari Sara Elisabetta , Porro Francesca , Aldé Simone , Burati Morena , Brambilla William , Nattino Stefano , Locatelli Matteo , Valsecchi Daria , Spreafico Paolo , Tantardini Valter , Schiavo Gianpaolo , Zago Mauro Pietro , Fumagalli Luca Andrea Mario
Published: November 2023

Objectives

To assess the survival predictivity of baseline blood cell differential count (BCDC), discretised according to two different methods, in adults visiting an emergency room (ER) for illness or trauma over 1 year.

Design

Retrospective cohort study of hospital records.

Setting

Tertiary care public hospital in northern Italy.

Participants

11 052 patients aged >18 years, consecutively admitted to the ER in 1 year, and for whom BCDC collection was indicated by ER medical staff at first presentation.

Primary outcome

Survival was the referral outcome for explorative model development. Automated BCDC analysis at baseline assessed haemoglobin, mean cell volume (MCV), red cell distribution width (RDW), platelet distribution width (PDW), platelet haematocrit (PCT), absolute red blood cells, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets. Discretisation cut-offs were defined by benchmark and tailored methods. Benchmark cut-offs were stated based on laboratory reference values (Clinical and Laboratory Standards Institute). Tailored cut-offs for linear, sigmoid-shaped and U-shaped distributed variables were discretised by maximally selected rank statistics and by optimal-equal HR, respectively. Explanatory variables (age, gender, ER admission during SARS-CoV2 surges and in-hospital admission) were analysed using Cox multivariable regression. Receiver operating curves were drawn by summing the Cox-significant variables for each method.

Results

Of 11 052 patients (median age 67 years, IQR 51–81, 48% female), 59% (n=6489) were discharged and 41% (n=4563) were admitted to the hospital. After a 306-day median follow-up (IQR 208–417 days), 9455 (86%) patients were alive and 1597 (14%) deceased. Increased HRs were associated with age >73 years (HR=4.6, 95% CI=4.0 to 5.2), in-hospital admission (HR=2.2, 95% CI=1.9 to 2.4), ER admission during SARS-CoV2 surges (Wave I: HR=1.7, 95% CI=1.5 to 1.9; Wave II: HR=1.2, 95% CI=1.0 to 1.3). Gender, haemoglobin, MCV, RDW, PDW, neutrophils, lymphocytes and eosinophil counts were significant overall. Benchmark-BCDC model included basophils and platelet count (area under the ROC (AUROC) 0.74). Tailored-BCDC model included monocyte counts and PCT (AUROC 0.79).

Conclusions

Baseline discretised BCDC provides meaningful insight regarding ER patients’ survival.
Feasibility interventional study investigating PAIN in neurorehabilitation through wearabLE SensorS (PAINLESS): a study protocol
Authors: Moscato Serena , Orlandi Silvia , Di Gregorio Francesco , Lullini Giada , Pozzi Stefania , Sabattini Loredana , Chiari Lorenzo , La Porta Fabio
Published: November 2023

Introduction

Millions of people survive injuries to the central or peripheral nervous system for which neurorehabilitation is required. In addition to the physical and cognitive impairments, many neurorehabilitation patients experience pain, often not widely recognised and inadequately treated. This is particularly true for multiple sclerosis (MS) patients, for whom pain is one of the most common symptoms. In clinical practice, pain assessment is usually conducted based on a subjective estimate. This approach can lead to inaccurate evaluations due to the influence of numerous factors, including emotional or cognitive aspects. To date, no objective and simple to use clinical methods allow objective quantification of pain and the diagnostic differentiation between the two main types of pain (nociceptive vs neuropathic). Wearable technologies and artificial intelligence (AI) have the potential to bridge this gap by continuously monitoring patients’ health parameters and extracting meaningful information from them. Therefore, we propose to develop a new automatic AI-powered tool to assess pain and its characteristics during neurorehabilitation treatments using physiological signals collected by wearable sensors.

Methods and analysis

We aim to recruit 15 participants suffering from MS undergoing physiotherapy treatment. During the study, participants will wear a wristband for three consecutive days and be monitored before and after their physiotherapy sessions. Measurement of traditionally used pain assessment questionnaires and scales (ie, painDETECT, Doleur Neuropathique 4 Questions, EuroQoL-5-dimension-3-level) and physiological signals (photoplethysmography, electrodermal activity, skin temperature, accelerometer data) will be collected. Relevant parameters from physiological signals will be identified, and AI algorithms will be used to develop automatic classification methods.

Ethics and dissemination

The study has been approved by the local Ethical Committee (285-2022-SPER-AUSLBO). Participants are required to provide written informed consent. The results will be disseminated through contributions to international conferences and scientific journals, and they will also be included in a doctoral dissertation.

Trial registration number

NCT05747040.
Feasibility of linking universal child and family healthcare and financial counselling: findings from the Australian Healthier Wealthier Families (HWF) mixed-methods study
Authors: Price Anna M H , White Natalie , Burley Jade , Zhu Anna , Contreras-Suarez Diana , Wang Si , Stone Melissa , Trotter Kellie , Mrad Mona , Caldwell Jane , Bishop Rebecca , Chota Sumayya , Bui Lien , Sanger Debbie , Roles Rob , Watts Amy , Samir Nora , Grace Rebekah , Raman Shanti , Kemp Lynn , Lingam Raghu , Eapen Valsamma , Woolfenden Susan , Goldfeld Sharon
Published: November 2023

Objectives

‘Healthier Wealthier Families’ (HWF) seeks to reduce financial hardship in the early years by embedding a referral pathway between Australia’s universal child and family health (CFH) services and financial counselling. This pilot study investigated the feasibility and short-term impacts of HWF, adapted from a successful Scottish initiative.

Methods

Setting: CFH services in five sites across two states, coinciding with the COVID-19 pandemic. Participants: Caregivers of children aged 0–5 years experiencing financial hardship (study-designed screen). Design: Mixed methods. With limited progress using a randomised trial (RCT) design in sites 1–3 (March 2020–November 2021), qualitative interviews with service providers identified implementation barriers including stigma, lack of knowledge of financial counselling, low financial literacy, research burden and pandemic disruption. This informed a simplified RCT protocol (site 4) and direct referral model (no randomisation, pre–post evaluation, site 5) (June 2021–May 2022). Intervention: financial counselling; comparator: usual care (sites 1–4). Feasibility measures: proportions of caregivers screened, enrolled, followed up and who accessed financial counselling. Impact measures: finances (quantitative) and other (qualitative) to 6 months post-enrolment.

Results

355/434 caregivers completed the screen (60%–100% across sites). In RCT sites (1–4), 79/365 (19%–41%) reported hardship but less than one-quarter enrolled. In site 5, n=66/69 (96%) caregivers reported hardship and 44/66 (67%) engaged with financial counselling; common issues were utility debts (73%), and obtaining entitlements (43%) or material aid/emergency relief (27%). Per family, financial counselling increased income from government entitlements by an average $A6504 annually plus $A784 from concessions, grants, brokerage and debt waivers. Caregivers described benefits (qualitative) including reduced stress, practical help, increased knowledge and empowerment.

Conclusions

Financial hardship screening via CFH was acceptable to caregivers, direct referral was feasible, but individual randomisation was infeasible. Larger-scale implementation will require careful, staged adaptations where CFH populations and the intervention are well matched and low burden evaluation.

Trial registration number

ACTRN12620000154909.
Outcomes of first emergency admissions for alcohol-related liver disease in England over a 10-year period: retrospective observational cohort study using linked electronic databases
Authors: Bodger Keith , Mair Thomas , Schofield Peità , Silberberg Benjamin , Hood Steve , Fleming Kate M
Published: November 2023

Objectives

To examine time trends in patient characteristics, care processes and case fatality of first emergency admission for alcohol-related liver disease (ARLD) in England.

Design

National population-based, retrospective observational cohort study.

Setting

Clinical Practice Research Datalink population of England, 2008/2009 to 2017/2018. First emergency admissions were identified using the Liverpool ARLD algorithm. We applied survival analyses and binary logistic regression to study prognostic trends.

Outcome measures

Patient characteristics; ‘recent’ General Practitioner (GP) consultations and hospital admissions (preceding year); higher level care; deaths in-hospital (including certified cause) and within 365 days. Covariates were age, sex, deprivation status, coding pattern, ARLD stage, non-liver comorbidity, coding for ascites and varices.

Results

17 575 first admissions (mean age: 53 years; 33% women; 32% from most deprived quintile). Almost half had codes suggesting advanced liver disease. In year before admission, only 47% of GP consulters had alcohol-related problems recorded; alcohol-specific diagnostic codes were absent in 24% of recent admission records. Overall, case fatality rate was 15% in-hospital and 34% at 1 year. Case-mix-adjusted odds of in-hospital death reduced by 6% per year (adjusted OR (aOR): 0.94; 95% CI: 0.93 to 0.96) and 4% per year at 365 days (aOR: 0.96; 95% CI: 0.95 to 0.97). Exploratory analyses suggested the possibility of regional inequalities in outcome.

Conclusions

Despite improving prognosis of first admissions, we found missed opportunities for earlier recognition and intervention in primary and secondary care. In 2017/2018, one in seven were still dying during index admission, rising to one-third within a year. Nationwide efforts are needed to promote earlier detection and intervention, and to minimise avoidable mortality after first emergency presentation. Regional variation requires further investigation.
Challenges of developing a green gastroenterology evidence base and how trainee research networks can fill the gaps
Authors: Tavabie Oliver , Clough Jennifer , King Jonathan , Nicholas Victoria , Kumar Aditi
Published: November 2023

Trainee research networks are a collaborative effort to enable high-quality multicentre audits or research that is more widely accessible to trainees. Such networks lead, design and deliver research at a far higher scale than could be achieved locally and are carried out solely by trainees. There is an increasing focus on delivering research that is not only environmentally sustainable but also focuses on areas that can reduce the carbon footprint of service provision in gastroenterology and hepatology. In this manuscript, we performed a scoping review to understand the current evidence base of the impact of gastroenterology and hepatology services on the environment as well as exploring any association between pollution and climate change with gastrointestinal and liver disease. We further discuss the barriers that researchers face in delivering environmentally sustainable research, the limitation in clinical guidelines related to practicing environmentally sustainable gastroenterology and hepatology and how the trainee research networks are ideally placed to initiate change by developing, disseminating and implementing best practice in ‘green Gastroenterology’.