bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust and flexible learning of a high-dimensional classification rule using auxiliary outcomes
Authors: Liang Muxuan , Park Jaeyoung , Lu Qing , Zhong Xiang
Published: December 2024

Correlated outcomes are common in many practical problems. In some settings, one outcome is of particular interest, and others are auxiliary. To leverage information shared by all the outcomes, traditional multi-task learning (MTL) minimizes an averaged loss function over all the outcomes, which may lead to biased estimation for the target outcome, especially when the MTL model is misspecified. In this work, based on a decomposition of estimation bias into two types, within-subspace and against-subspace, we develop a robust transfer learning approach to estimating a high-dimensional linear decision rule for the outcome of interest with the presence of auxiliary outcomes. The proposed method includes an MTL step using all outcomes to gain efficiency and a subsequent calibration step using only the outcome of interest to correct both types of biases. We show that the final estimator can achieve a lower estimation error than the one using only the single outcome of interest. Simulations and real data analysis are conducted to justify the superiority of the proposed method.
Minimal important difference of pain numeric rating scale in patients with hidradenitis suppurativa: results from THESEUS
Authors: Pickles Tim , Ingram John R
Published: December 2024

Patient-reported outcomes collected in THESEUS study can be used to estimate a minimal important difference of 1 for a current pain numeric rating scale in a sample of patients with hidradenitis suppurativa.
Comprehensive phylogenetic analysis of tribe Psoraleeae (Fabaceae) supports segregation of the South American Otholobium as a New Genus Grimolobium
Authors: Egan Ashley N , Bello Abubakar , Stirton Charles H , Chimphango Samson B M , Muasya A Muthama
Published: December 2024

Tribe Psoraleeae (Fabaceae) is a clade nested within the Millettioid/Phaseoloid legumes, yet set apart by its single-seeded fruit. With a cosmopolitan distribution, the tribe is currently recognized as having 10 genera: Bituminaria, Cullen, Hoita, Kartalinia, Ladeania, Orbexilum, Otholobium, Pediomelum, Psoralea, and Rupertia. Several previous molecular systematic works have shown the non-monophyly of species within Otholobium, with lineages separating geographically between members distributed in South America vs. Africa. However, previous sampling was sparse regarding species sampled from South America. Here, we increase our sampling of South American Otholobium species and estimate phylogenies based on four DNA regions (ITS, rpoB-trnC, trnS-trnG, trnL-trnF) to provide conclusive evidence that South American species of Otholobium should be segregated and recognized as a new genus, Grimolobium A.N.Egan, C.H.Stirt. & A.Bello, chosen to honour the work of James Grimes, a botanist whose seminal work on New World Psoraleeae improved the taxonomic evolutionary understanding of this plant group. We describe this new genus based on a new phylogenetic analysis of the tribe Psoraleeae and our exploration of morphology within this phylogenetic context and provide the necessary new combinations and keys.
Theoretical study on single-molecule electron conductivity of paddlewheel-type dichromium(II,II) tetracarboxylate complexes
Authors: Amamizu Naoka , Sasaki Keisuke , Nishida Mitsuhiro , Masuda Koki , Inoue Ren , Taka Kaito , Tada Kohei , Kishi Ryohei , Kitagawa Yasutaka
Published: December 2024

A relationship between the single-molecule electron conductivity, spin states, and substituents is investigated on the paddlewheel-type dichromium(II,II) tetracarboxylate complexes as the simplest model of the extended metal atom chains. The electronic structures and single-molecule electron conductivity of some model complexes with different substituents are calculated by the broken-symmetry density functional theory and elastic scattering Green's functions methods, respectively. The calculated results indicate that the electron conductivity of the complexes is changed by the electron-donating/withdrawing groups introduced into the bridging ligands. In addition, it is also found that a ratio of the electron conductivities between the antiferromagnetic and ferromagnetic coupling states in the Cr(II)2 unit can be changed by these substituents. These results suggest that the electron conductivity of these complexes can be controlled by changing the spin state.
Solvent-free mechanochemical synthesis of zinc glutarate for the heterogeneous catalysis of propylene oxide and CO2 copolymerization
Authors: Saito Norio , Honda Masayoshi , Sugimoto Hiroshi , Takei Takahiro , Kumada Nobuhiro
Published: December 2024

Zinc glutarate (ZnGA) is used as a solid-state heterogeneous catalyst for the synthesis of aliphatic polycarbonate from the alternating copolymerization of CO2 and epoxide. However, the conventional synthesis of ZnGA involves the use of a large amount of toluene, which is a toxic substance. In the present study, we developed a solvent-free, environmentally friendly synthesis for ZnGA using a mechanochemical process. This accelerated the formation of flake-like ZnGA microcrystals in a shorter reaction time than that of the conventional method. X-ray diffraction, X-ray photoelectron spectroscopy, X-ray absorption fine structure analyses, and Fourier-transform infrared spectroscopy revealed that ZnO is the most effective source of Zn. This catalyst selectively produced poly(propylene carbonate) from CO2 and propylene oxide, with a molecular weight (Mn) of 25,000 and a molecular weight distribution (Mw/Mn) of 5.27. We believe that this mechanochemical synthesis is a sustainable alternative to conventional approaches.
Bilateral lower limb ulceration in a patient with a malignancy
Authors: Riley Callum , Butt Sanaa , Mathe Nomathamsanqa , Cain Owen , Kaushal Ghazia
Published: December 2024

An 81-year-old woman presented with a 5-week history of progressive and painful bilateral lower limb ulcers. The patient denied any trauma to the areas. The larger ulcer of the right leg had first appeared 5 weeks previously as two small, painful blisters that subsequently coalesced and ulcerated.
A widespread chronic pruritic varioliform ulcerating eruption
Authors: McGrath Conn , Tull Thomas J , Markiewicz Dorota , DeAnta Natalie , Calonje Eduardo , Grattan Clive , Lebas Eglantine
Published: December 2024

We present the case of a 70-year-old woman with a 7-year history of widespread pruritic varioliform lesions recalcitrant to topical therapy.
The need for a shared definition of the atopic dermatitis ‘super responder’ in the ‘treat-to-target’ era
Authors: Mastorino Luca , Mendes-Bastos Pedro , Ribero Simone , Ortoncelli Michela
Published: December 2024

In the last few years, the introduction of monoclonal antibody and Janus kinase inhibitors in the treatment of atopic dermatitis has revolutionized and elevated the therapeutic targets of this disease. Recently, several proposals for treat-to-target strategies have been published, the most important of which converge on achieving specific clinical and quality-of-life outcomes.
Exploring the relation between TGF-β pathway activity and response to checkpoint inhibition in patients with metastatic melanoma
Authors: van Ravensteijn Stefan G , Amir Avital L , Tauriello Daniele V F , van Herpen Carla M L , Boers-Sonderen Marye J , Wesseling Yvonne J W , van Brussel Anne G C , Keizer Diederick M , Verheul Henk M W , Bol Kalijn F
Published: December 2024

Introduction

Immune checkpoint inhibition (ICI) is highly effective for the treatment of melanoma, but intrinsic resistance is present in a subgroup of patients. TGF-β pathway activity may play a role in this resistance by preventing T-cells from entering the tumor microenvironment, causing immune escape. We investigated the association of TGF-β signal transduction pathway activity with resistance to ICI treatment in advanced melanoma. Furthermore, other pathway activities were analyzed to better understand their potential role in ICI resistance.

Method

The activity of 8 signaling pathways (TGF-β, Hedgehog, MAPK, AR, NOTCH, PI3K, JAK/STAT1-2, and NFkB) was analyzed from tumor tissue from patients with advanced melanoma. Pathway activity scores (PAS) were explored for associations with survival and response to ICI in 34 patients (19 non-responders and 15 responders). A second, independent method to investigate the predictive value of TGF-β pathway activation was conducted by determining levels of phosphorylated SMAD2.

Results

The mean TGF-β PAS of responders vs non-responders was 53.9 vs 56.8 (P = 0.265). No significant relation with progression-free survival was detected for TGF-β activity (P = 0.078). No association between pSMAD2 staining and treatment response or survival was identified. In contrast, Hedgehog scores of responders versus non-responders were 35.7 vs 41.6 (P = 0.038). High Hedgehog PAS was the sole significant predictor of resistance to ICI (OR 0.88, P = 0.033) and worse progression-free survival (HR 1–1.1, P = 0.012).

Conclusion

TGF-β pathway activation showed no significant relation with treatment response to ICI or survival in patients with advanced melanoma. Hedgehog PAS was identified as a possible biomarker associated with both treatment response and survival.
Effect of pupation environment on pupal development and eclosion of chilli thrips (Thysanoptera: Thripidae)
Authors: Han Dongyin , Ye Zhengpei , Fu Yueguan , Zhang Fangping , Zhan Canlan , Li Lei
Published: December 2024

In recent years, the damage caused by thrips has become a key factor impacting the winter and spring production of fruits and vegetables in Hainan Province, China. This study aimed to elucidate the effects of different pupation environments on pupal development and eclosion of chilli thrips (Scirtothrips dorsalis Hood) by analyzing pupal development and eclosion of chilli thrips in an indoor environment with simulated natural soils and water content. Soil type, soil water content, and temperature substantially affected the eclosion of chilli thrips during the pupal stage. Both a low soil water content of 1% and a high soil water content of 15% were not conducive to the pupation and eclosion of chilli thrips. Moreover, the results indicated an interaction between soil type and soil water and temperature and soil water content, affecting the eclosion of chilli thrips. Chilli thrips not only pupated in soil but also completed pupation and eclosion in other soil-less environments, such as tender mango leaves, stalks, plastic mulch, and weed fabric. This study suggests that in addition to adopting pest control measures that target the canopy layer of crops, appropriate measures such as increasing soil water content can also be implemented in the ground layer to enhance the overall effectiveness of pest control.
Atrial and ventricular functional mitral regurgitation: prevalence, characteristics, outcomes, and disease progression
Authors: Chen Qin-Fen , Zhou Xi , Katsouras Christos S , Ni Chao , Zhu Han , Liu Chenyang , Peng Yangdi , Ge Hang-Bin , Hong Chenglv , Lin Wei-Hong , Zhou Xiao-Dong
Published: December 2024

Aims

Limited data exist on the natural history of functional mitral regurgitation (FMR), including atrial (AFMR), ventricular (VFMR), and dual FMR. This study examined the prevalence, characteristics, outcomes, and progression of these FMR subtypes.

Methods and results

Consecutive patients with ≥mild to moderate FMR were included and classified as AFMR, VFMR, or dual FMR. AFMR is characterized by left atrial enlargement, while VFMR involves left ventricular enlargement or reduced left ventricular ejection fraction. Dual FMR combines features of both. Clinical outcome was all-cause mortality and heart failure (HF) hospitalization. Echocardiographic outcome was the progression from mild-moderate/moderate to severe FMR and from AFMR/VFMR to dual FMR. Of 22 814 patients, AFMR, VFMR, and dual FMR were identified in 39%, 14%, and 47%, respectively. Most (84%) had mild-moderate to moderate FMR. Over a median clinical follow-up of 4.7 years, dual FMR has the highest risk of all-cause mortality and HF hospitalization. Compared with AFMR, patients with VFMR have a higher incidence of all-cause mortality (adjusted HR = 1.73, 95%CI 1.54–1.94, P < 0.001) and HF hospitalization (adjusted HR = 1.23, 95%CI 1.15–1.32, P < 0.001). In the serial cohort with 2.4 (1.0–4.9) years echocardiogram follow-up, VFMR was associated with a 1.51-fold and 3.08-fold increase in the risk of progressing to severe FMR and dual FMR than AFMR (both P < 0.001). Sensitivity analyses did not change these findings.

Conclusion

AFMR and VFMR have significant differences in survival and disease progression. Dual FMR is a common and distinct disease process that occurs in the progression of AFMR or VFMR and is associated with a poor prognosis.
‘It’s what we should be doing anyway’: using financial incentives to promote relational continuity in Australian General Practice—a nested case study analysis
Authors: Russell Grant , Westbury Susannah , Advocat Jenny , Zwar Nicholas , Metusela Christine , Batterham Marijka , Peterson Gregory M , Mullan Judy , Mazza Danielle , Radford Jan , Eckermann Simon , Bonney Andrew
Published: December 2024

Background

Relational continuity is a fundamental component of primary care. The ‘Quality in General Practice Trial’ (EQuIP-GP), was a 12-month cluster randomized trial, designed to investigate whether financial incentives can improve relational continuity in primary care.

Aim

To examine (i) how financial incentives are perceived and experienced by primary care patients, providers, and practice staff, and (ii) how clinical and organizational routines related to relational continuity are influenced by the introduction of a financial model designed to incentivize relational continuity.

Design and setting

We used a mixed methods case study approach with six of the intervention arm practices participating in the EQuIP-GP trial.

Method

Semi-structured interviews were conducted with patients, providers, practice staff, and intervention facilitators. Intervention facilitators kept structured diaries to capture reflective notes. To contextualize results, practices completed a modified practice attributes survey and patients completed the Primary Care Assessment Tool at baseline and 12 months.

Results

Patient-perceived relational continuity was not impacted by the intervention. Financial incentives were preferred for rewarding, as opposed to incentivizing, quality care; however, they were perceived as a blunt and inflexible instrument. The introduction of the incentive model increased attention to pre-existing organizational routines rather than creating new ones.

Conclusion

Incentive models should be suitably flexible to accommodate diversity in patient and practice needs. Small changes can be made to existing practice routines that will improve awareness and conscientiousness of relational continuity. Further research should examine how feasible these routine changes would be in practices that do not already focus on continuity.
A high copy suppressor screen identifies factors enhancing the allotopic production of subunit II of cytochrome c oxidase
Authors: Nieto-Panqueva Felipe , Vázquez-Acevedo Miriam , Barrera-Gómez David F , Gavilanes-Ruiz Marina , Hamel Patrice P , González-Halphen Diego
Published: December 2024

Allotopic expression refers to the artificial relocation of an organellar gene to the nucleus. Subunit 2 (Cox2) of cytochrome c oxidase, a subunit with 2 transmembrane domains (TMS1 and TMS2) residing in the inner mitochondrial membrane with a Nout-Cout topology, is typically encoded in the mitochondrial cox2 gene. In the yeast Saccharomyces cerevisiae, the cox2 gene can be allotopically expressed in the nucleus, yielding a functional protein that restores respiratory growth to a Δcox2 null mutant. In addition to a mitochondrial targeting sequence followed by its natural 15-residue leader peptide, the cytosol synthesized Cox2 precursor must carry one or several amino acid substitutions that decrease the mean hydrophobicity of TMS1 and facilitate its import into the matrix by the TIM23 translocase. Here, using a yeast strain that contains a COX2W56R gene construct inserted in a nuclear chromosome, we searched for genes whose overexpression could facilitate import into mitochondria of the Cox2W56R precursor and increase respiratory growth of the corresponding mutant strain. A COX2W56R expressing strain was transformed with a multicopy plasmid genomic library, and transformants exhibiting enhanced respiratory growth on nonfermentable carbon sources were selected. We identified 3 genes whose overexpression facilitates the internalization of the Cox2W56R subunit into mitochondria, namely: TYE7, RAS2, and COX12. TYE7 encodes a transcriptional factor, RAS2, a GTP-binding protein, and COX12, a non-core subunit of cytochrome c oxidase. We discuss potential mechanisms by which the TYE7, RAS2, and COX12 gene products could facilitate the import and assembly of the Cox2W56R subunit produced allotopically.
High-resolution GPU-based simulations of quasi-static poroelasticity: seismic attenuation and modulus dispersion in three-dimensional stochastic fracture networks
Authors: Alkhimenkov Yury
Published: December 2024

Fractures significantly impact the elastic and hydraulic properties of geological structures, influencing fields like geothermal energy, hydrocarbon exploration, nuclear waste disposal and $\mathrm{ \mathrm{CO}}_2$ storage. Characterizing these formations is challenging due to the scale disparity between seismic wavelengths and fracture sizes. This study leverages decades of analytical and numerical advancements to evaluate the effective mechanical properties of fractured solids at the mesoscopic scale. A novel numerical method for modelling quasi-static Biot’s poroelastic equations using graphics processing units (GPUs) is introduced for simulating hydromechanically coupled systems. Capable of handling up to 133 million voxel elements on a single GPU, this method offers unprecedented spatial resolution to model complex fracture networks. The GPU-accelerated solver, FastBiot_QS, delivers exceptional performance, achieving a computational speedup of approximately 520 times compared to central processing unit-based methods. The solver’s accuracy is rigorously validated in 1-D and 3-D setups. Simulations reveal that fracture clustering and spatial distribution significantly affect seismic attenuation and modulus dispersion. Clusters of interconnected fractures lead to higher attenuation at higher frequencies, while sparsely distributed fractures result in higher attenuation at lower frequencies. Simulations with log-normal and uniform distributions present intermediate behaviours between densely clustered and sparsely distributed fractures. The study can improve interpretations of seismic data and hydraulic properties in fractured media.
Gender and Sex Differences in Abdominal Pain, Fatigue, And Psychological Symptoms Among Adults with Inflammatory Bowel Disease: A Network Analysis
Authors: Kamp Kendra , Yang Pei-Lin , Tsai Chi-Shan , Zhang Xiaoyu , Yoo Linda , Altman Molly R , Heitkemper Margaret , Conley Samantha , Kane Sunanda , Winders Samantha
Published: December 2024

Background and Aims

Individuals with inflammatory bowel disease (IBD) experience a high symptom burden, including abdominal pain, fatigue, anxiety, depression, and sleep disturbances; yet, little is known regarding the relationship between sex and gender on symptoms. We sought to report symptom severity for cisgender men, cisgender women, and transgender and gender-diverse (TGD) individuals. In addition, we used network analysis to identify core symptoms and explore if symptoms and their relationships differ between cisgender men and cisgender women.

Methods

This was a cross-sectional study. We recruited adults with IBD online through ResearchMatch. Individuals responded to Patient-Reported Outcomes Measurement Information symptom questionnaires, as well as demographic and clinical questionnaires. Network analysis was used to identify the core symptoms driving the symptom structure.

Results

One-hundred and fifty-seven (63.3%) participants identified as cisgender women, 84 (33.9%) as cisgender men, and 7 (2.8%) as TGD. Cisgender men (M = 61.8) and TGD (M = 61.3) groups reported higher abdominal pain levels compared with cisgender women (M = 57.8; P = .02). Transgender and gender-diverse individuals reported higher depression levels (M = 64.8) compared with cisgender men (M = 56.7) and cisgender women (M = 54.4; P = .01). Using a network analysis approach, anxiety and fatigue emerged as core symptoms for the entire sample (clinically active and inactive disease), and among only those with active clinical disease. Fatigue was a top core symptom for cisgender women; anxiety emerged as a top core symptom for cisgender men.

Conclusions

This study highlights that fatigue and anxiety are core symptoms among individuals with IBD and demonstrates a potential sex and/or gender difference in core symptoms. Replication of this study is needed with further consideration of inclusion of TGD patients.
Estimating Standard-Dose and High-Dose Fluzone Vaccine Efficacies for Influenza A Based on Hemagglutination Inhibition Titers
Authors: Hammerton Savannah M , Billings W Zane , Hemme Hayley , Ross Ted M , Shen Ye , Handel Andreas
Published: December 2024

Background

The high-dose (HD) Fluzone influenza vaccine is recommended for individuals aged ≥65 years due to its improved antibody responses and vaccine efficacy (VE) over the standard-dose (SD) formulation. Since influenza vaccines are frequently reformulated, monitoring VE changes is crucial. Traditional efficacy trials are costly and time-consuming, but immunogenicity studies using hemagglutination inhibition (HAI) titers—a reliable correlate of protection—can be used to estimate VE more efficiently.

Methods

We analyzed data from a human vaccine cohort who received either the SD or HD Fluzone split-inactivated influenza vaccine during influenza seasons 2013–2014 to 2021–2022. We used a previously developed statistical model to map pre- and postvaccination HAI titers to protection probabilities, and computed differences in VE of the HD vaccine in older (≥65 years) populations compared to SD vaccines in the same age group and in younger (<65 years) adults.

Results

We found that the HD vaccine generally improved the estimated VE in older adults. We also found that HD recipients often had a lower estimated VE than younger SD recipients.

Conclusions

While HD vaccines lead to a small increase in estimated VE compared to SD in older adults, further increases in dose or other developments to improve VE should be considered.
Protracted Tuberculosis Outbreak in a Pasifika Diaspora in Western Sydney, Australia: The Importance of Community Engagement
Authors: Koirala Archana , Smith Katherine , Britton Philip N , Howard-Jones Annaleise R , Sintchenko Vitali , Donnan Ellen J , Ulbricht Evan , Martinez Elena , Toma Reta , Marais Ben J
Published: December 2024

A prolonged tuberculosis outbreak, linked by whole-genome sequencing, occurred in a Pasifika extended family over 10 years (2013–2022) in Sydney, Australia. Despite Australia's low tuberculosis incidence, social and cultural complexities, and coronavirus disease 2019 (COVID-19) disruptions exacerbated transmission. Control required culturally sensitive, family-centered care and robust health system engagement.
Multi-Devotionalism and Mono-Devotionalism: Beyond the Problems of Polytheism and Monotheism
Authors: Hedges Paul
Published: December 2024

It is argued that the terms polytheism and monotheism are both problematically rhetorical and analytically weak, while they are typically applied in essentializing ways. Noting the history of these terms, especially in relation to such terms as idolatry, this article makes the argument that more analytical language is needed. The terms mono-devotionalism and multi-devotionalism are introduced, not as replacements, but as a reconceptualization. Pointing to trends and tendencies within traditions, it is argued that this pair of terms provides a preferable way to talk about how singular or multiple ends, modes of devotion, and practices may occur both within and across traditions. Particular attention is paid to Christianity and Hinduism as traditions intimately bound up with the history of how the terms monotheism and polytheism have been deployed.
Safety, tolerability and pharmacokinetics of subcutaneous cefazolin as an alternative to intravenous administration
Authors: Murray Fionnuala , Yoo Okhee , Brophy-Williams Samuel , Rawlins Matthew , Wallis Steven C , Roberts Jason A , Raby Edward , Salman Sam , Manning Laurens
Published: December 2024

Background

Subcutaneous (SC) administration of antibiotics is a practical alternative to IV administration. Cefazolin is widely used for skin and soft tissue infections and other complex infections by IV administration.

Methods

In this prospective, cross-over self-controlled study, a single dose of SC cefazolin was administered to 15 stable inpatients established on IV cefazolin as part of their management plan. The equivalent dose of cefazolin was diluted in 50 mL of normal saline via gravity feed over 30 min. Venous blood samples were collected at baseline and 0.5, 1, 2, 4 and 8 h following both the SC and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were evaluated.

Results

SC cefazolin was well tolerated. The bioavailability of SC administration was 74.8% (95% CI 66.7%–81.7%). Slower absorption from SC tissue was associated with a BMI of ≥30. Lower peak, and higher trough concentrations were observed with SC administration. Although lower bioavailability was observed with SC administration, the PTA for unbound drug concentrations greater than the MIC for more than 90% of the time between doses was higher for SC compared with IV administration at MICs between 0.25 and 4 mg/L. Simulated SC doses of 3 g twice daily had similar PTA to standard IV dosing of 2 g three times daily. A simulated 6 g continuous 24 h infusion of SC cefazolin had a favourable pharmacokinetic profile.

Conclusion

SC cefazolin appears to be well tolerated, with an improved pharmacokinetic profile compared with IV administration. Either 3 g twice daily, or 6 g as a 24 h SC infusion could be considered for future evaluation.
Patterns of genotype-specific interactions in an obligate host-specific insect pathogenic fungus
Authors: Edwards Sam , Naundrup Andreas , Becher Paul G , De Fine Licht Henrik H
Published: December 2024

Host–pathogen infections and possible effects on co-evolutionary patterns depend on the genotypes of both host and pathogen. Obligate fungal pathogens of plants are often characterized by host–pathogen genotype-by-genotype (GxG) interactions, but whether these patterns exist in obligate insect fungal pathogens is unclear. We take advantage of the obligate insect pathogenic fungus Entomophthora muscae, where individual isolates are specific to different dipteran host species in nature but can cross-infect multiple fly species in the laboratory. We collected three new isolates of E. muscae from Drosophila species. Phylogenetic analysis showed that Drosophila-isolated E. muscae represents a distinct geographically widespread Drosophila lineage compared to the house fly (Musca domestica) or Delia species-isolated E. muscae. We used the three new E. muscae isolates from Drosophila spp. together with a genetically distinct E. muscae isolate from house flies and assessed their virulence in a cross-infection experiment using one house fly, three Drosophila suzukii, and two D. melanogaster genotypes as hosts. All fungal isolates successfully infected hosts, induced behavioural manipulation, sporulated in all fly hosts, and differed in virulence between host genotypes, revealing GxG interactions. While house flies were most susceptible to fungal infection with 99% mortality, we found a lower virulence of 49% and 25% mortality in D. melanogaster and D. suzukii genotypes, respectively. Furthermore, all isolates harboured a specific mycovirus (family Iflaviridae), but co-phylogenetic branching patterns did not support fungus–virus co-speciation. We show that the genetic makeup of both fungal pathogen and fly host influence E. muscae infectivity, confirming GxG interactions in obligate fly fungal pathogens.
Cold storage of Ganaspis kimorum (Hymenoptera: Figitidae) immature stages for optimized classical biological control of Drosophila suzukii (Diptera: Drosophilidae)
Authors: Lisi Fabrizio , Biondi Antonio , Hogg Brian N , Rossi Stacconi Marco Valerio , Wang Xingeng , Daane Kent M
Published: December 2024

Programs to mass rear and release Ganaspis kimorum Buffington (Hymenoptera: Figitidae) are ongoing in many countries to manage its host Drosophila suzukii (Matsumura) (Diptera: Drosophilidae). To optimize parasitoid production and synchronize field releases with pest outbreaks, we investigated a cold storage protocol by exposing different immature G. kimorum stages to 2 storage temperatures (10 or 15°C) for 2, 4, 6, or 8 wk. We further studied those temperature/exposure time combinations that allowed survival but prevented parasitoid emergence before the end of each cold exposure, or the cold storage suitability (CSS). The impact of cold storage on G. kimorum emergence time, total development time, and emergence rate was then evaluated for temperature/exposure time combinations with CSS > 60%. We also assessed fitness costs in terms of longevity and parasitism rates of emerging parasitoids. Results showed that only G. kimorum larvae and pupae were suitable for cold storage under this methodology. Cold exposure significantly delayed the emergence time and total development time of larvae and pupae, whereas the emergence rate was significantly reduced only for larvae at 10°C for 6 wk. The longevity of emerging male and female parasitoids was significantly reduced when stored cold as larvae, while no effects were reported for the parasitism rate by emerged females. These findings provide new insights into G. kimorum cold sensitivity and offer valuable options to better schedule mass rearing and wasp releases for biological control of D. suzukii.
Prospects for PARG inhibitors in cancer therapy
Authors: Hu Yangchan , Meng Yuxin , Zhuang Zirui , Li Yuancong , Nan Junjun , Xu Ning , Ye Zu , Jing Ji
Published: December 2024

Poly(ADP-ribose) glycosylhydrolase (PARG) is an enzyme involved in hydrolyzing the ribose–ribose bonds present in poly(ADP-ribose) (PAR), which are primarily found in the nucleus. Along with poly(ADP-ribose) polymerase (PARP), PARG regulates the level of PAR in cells, playing a crucial role in DNA maintenance and repair processes. Recent studies have revealed elevated levels of PARG in various cancers, such as breast, liver, prostate, and esophageal cancers, indicating a link to unfavorable cancer outcomes. PARG is a significant molecular target for treating PAR-related cancers. This review provides a comprehensive overview of the physiological role of PARG and the development of its inhibitors, highlighting its potential as an innovative target for cancer treatment.
Competence by default: do listeners assume that speakers are knowledgeable when computing conversational inferences?
Authors: Bale Alan , Noguchi Hisako , Rolland Marguerite , Barner David
Published: December 2024

When engaged in conversation, do listeners make default assumptions about the epistemic states of speakers? According to some accounts, when listeners hear a sentence like “Sarah solved some of the math problems,” they infer by default that speakers believe that the stronger statement involving “all” is false (i.e. that Sarah did not solve all of the problems). However, drawing on tests of reading time, eye tracking, and manipulations of cognitive load, multiple studies have argued that this form of inference (i.e. strong scalar implicature) is not computed by default. In this study, while acknowledging this claim, we explore whether important subprocesses of implicature might nevertheless involve default inferences. In particular, we tested whether listeners assume by default that speakers are knowledgeable about alternative utterances that are left unsaid—a critical precondition for computing strong scalar implicatures. To do this, we tested 60 English-speaking participants who heard utterances made by either knowledgeable speakers or ignorant speakers. In addition, half of these participants were placed under cognitive load using a dot-array memory task. We found that participants placed under load over-computed implicatures when speakers were ignorant, as though assuming that they were knowledgeable by default.
Comprehensive surgical management of a severe 270-degree circumferential penetrating neck injury from an industrial accident: a case report
Authors: Jaber Jana , Al Jebawi Kholoud , Nasrallah Jamil , Al Shoufy Mira , Mehta Shubh , Hashim Hashim Talib , AL-Mukhtar Mahmoud Mussleh
Published: December 2024

Penetrating neck injury (PNI), involving disruption of the platysma muscle, accounts for 10% of trauma cases and poses significant morbidity and mortality risks. This case report details the management of a 45-year-old male who sustained a 270-degree circumferential neck incision from an industrial accident. The patient presented with a deep neck laceration, severe blood loss, and hypovolemic shock. Pre-hospital care included intubation, oxygen supplementation, and fluid resuscitation. At the hospital, under general anesthesia, surgical interventions involved ligation of posterior neck vessels, hemostasis, muscle repair with Vicryl 1–0, drainage tube placement, and skin closure. Postoperative care included intensive monitoring, neurological assessments, and pain management. Effective management of severe PNI requires a multidisciplinary approach, combining prompt pre-hospital care, meticulous surgical techniques, and comprehensive postoperative management. Future research should focus on standardizing PNI management protocols and advancing surgical and diagnostic techniques to improve outcomes in similar critical cases.
Alleviation of Helicobacter pylori- or aspirin-induced gastritis and neuroinflammation in mice by Lactococcus lactis and Bifidobacterium longum
Authors: Shin Jung-Woo , Shin Yoon-Jung , Lee Dong-Yun , Kim Dong-Hyun
Published: December 2024

Helicobacter pylori (HP) causes gastritis and peptic ulcer. Therefore, we examined whether probiotics Lactococcus lactis P135 and Bifidobacterium longum P142, which inhibited HP growth by 37.9% and 35.3%, respectively, and HP-induced IL-8 expression in KATO III cells by 68.6% and 63.1%, respectively, compared to those of normal controls, could mitigate HP-induced gastritis and psychiatric disorder in mice. Oral administration of P135 and/or P142 alleviated HP- or aspirin-induced gastritis, colitis, neuroinflammation, and depression/cognitive impairment-like behavior. They also suppressed HP infection, neutrophil infiltration, and NF-κB activation in the stomach and TNF-α expression and NF-κB activation in the colon and hippocampus. of P135 and/or P142 alleviated HP- or aspirin-induced gut dysbiosis: they decreased Lachnospiracease, Helicobacteriaceae, and Akkermansiaceae populations and increased Bacteroidaceae and Muribaculaceae populations. These findings suggest that HP growth/inflammation-inhibitory P135 and/or P142 may alleviate gut inflammation (gastritis and colitis) and neuroinflammation through the suppression of neutrophil infiltration, NF-κB activation, and HP growth, thereby leading to the attenuation of systemic inflammation and psychiatric disorder.
Bioremediation of polyaromatic hydrocarbon polluted sewage sludge soil employing a bacterial consortium and phytotoxicity evaluation
Authors: Khan Gulfishan , Tiwari Anshul , Patel Devendra K , Anbumani Sadasivam , Manickam Natesan
Published: December 2024

A consortium of five distinct bacterial strains was evaluated for their ability to biodegrade multiple polyaromatic hydrocarbons (PAHs) in sewage sludge under microcosm studies. The presence of PAHs was determined from the sludge samples collected during pre- and post-monsoon seasons from three different wastewater treatment plants (WWTPs). Among the 16 PAHs found, the lowest concentration detected was 1.75 ng g−1 of benz(k)fluoranthene, and the highest concentration of 5.41 mg g−1 indeno(1,2,3-cd) pyrene was found in both dry and wet samples, perhaps owing to its multiple origin of contamination. A bacterial consortium comprising of well characterized bacteria Stenotrophomonas maltophilia IITR87, Ochrobactrum anthropi IITR07, Microbacterium esteraromaticum IITR47, Pseudomonas aeruginosa IITR48, and Pseudomonas mendocina IITR46 employed for PAHs bioremediation in a microcosm study. In 20 days, 65%–70% of PAHs were remediated, and low molecular weight PAHs such as naphthalene, phenanthrene, and pyrene showed enhanced degradation. Bioremediated samples showed a significant reduction in phytotoxicity using plant germination of wheat (Triticum aestivum), black chickpea (Cicer arietinum), and mustard (Brassica juncea), whereas the contaminated soil showed severe inhibition of plant growth. The results comprehensively suggest a possible remediation option for PAHs occurring in complex sewage sludge, preventing further contamination into other environmental compartments.
Tailoring disjoint belief structures to the AGM framework
Authors: Aravanis Theofanis
Published: December 2024

The belief-structures model of Chopra and Parikh is perfectly suitable for representing the statics and dynamics of the beliefs of resource-bounded agents. Nevertheless, despite its favourable properties, it lies outside the AGM framework, the well-established paradigm for codifying rational belief revision of belief sets (i.e. logical theories), proposed by Alchourrón, Gärdenfors and Makinson. This feature can be attributed to two primary reasons: firstly, a multivalued logic is utilized for evaluating queries relative to a belief structure, and secondly, the objects under revision in the context of the belief-structures model are belief structures, rather than belief sets. Against this background, we present, in this article, a natural approach for adapting the revision of belief structures to an AGM-style revision while retaining the favourable properties of the belief-structures model. Under certain realistic assumptions, including the mutual disjointness of sublanguages of belief structures, a collection of interesting properties of the proposed method are identified, by investigating the satisfiability and violation of principal postulates of the belief-revision theory. Overall, it is demonstrated that the introduced approach constitutes a meaningful relevance-sensitive tool for integrating disjoint belief structures within the AGM framework, with potential applications in emerging fields such as digital twins, where precise and dynamic belief changes are essential for maintaining accurate simulations of real-world systems.
The kinematics of massive high-redshift dusty star-forming galaxies
Authors: Amvrosiadis A , Wardlow J L , Birkin J E , Smail I , Swinbank A M , Nightingale J , Bertoldi F , Brandt W N , Casey C M , Chapman S C , Chen C -C , Cox P , da Cunha E , Dannerbauer H , Dudzevičiūtė U , Gullberg B , Hodge J A , Knudsen K K , Menten K , Walter F , van der Werf P
Published: December 2024

We present a new method for modelling the kinematics of galaxies from interferometric observations by performing the optimization of the kinematic model parameters directly in visibility space instead of the conventional approach of fitting velocity fields produced with the clean algorithm in real-space. We demonstrate our method on Atacama Large Millimeter/submillimeter Array (ALMA) observations of $^{12}$CO (2–1), (3–2), or (4–3) emission lines from an initial sample of 30 massive 850 $\mu$m-selected dusty star-forming galaxies with far-infrared luminosities $\gtrsim$$\, 10^{12}$ L$_{\odot }$ in the redshift range $z \sim$ 1.2–4.7. Using the results from our modelling analysis for the 12 of the 20 sources with the highest signal-to-noise emission lines that show disc-like kinematics, we conclude the following: (i) our sample prefers a CO-to-$H_2$ conversion factor, of $\alpha _{\rm CO} = 0.74 \pm 0.37$; (ii) these far-infrared luminous galaxies follow a similar Tully–Fisher relation between the circular velocity, $V_{\rm circ}$, and baryonic mass, $M_{\rm b}$, as less strongly star-forming samples at high redshift, but extend this relation to much higher masses – showing that these are some of the most massive disc-like galaxies in the Universe; (iii) finally, we demonstrate support for an evolutionary link between massive high-redshift dusty star-forming galaxies and the formation of local early-type galaxies using the both the distributions of the baryonic and kinematic masses of these two populations on the $M_{\rm b}$ – $\sigma$ plane and their relative space densities.
IgG4-related disease with epithelioid granulomas: A case and a review of the literature
Authors: Kachi Shion , Oka Hideki , Sumitomo Shuji , Hara Shigeo , Ohmura Koichiro
Published: December 2024

IgG4-related disease (IgG4-RD) is a systemic, immune-mediated, fibroinflammatory disorder that affects multiple organs. Histopathologically, the supportive findings of IgG4-RD include dense lymphocytic infiltrates, obliterative phlebitis, storiform fibrosis, and elevated numbers of IgG4-positive plasma cells. However, the presence of granulomatous inflammation is generally considered highly atypical, suggesting alternative diagnoses such as sarcoidosis and lymphoma. Here, we present a case of IgG4-RD involving granulomatous lymphadenopathy. Labial salivary gland biopsy findings were consistent with IgG4-related sialadenitis. Elevated serum IgG4 levels, hypocomplementemia, and abnormal imaging findings in the kidneys and pancreas indicated an association with IgG4-RD. The patient was treated with prednisolone, which resulted in a significant improvement in the serum IgG4 and complement levels and a notable reduction in lymph node swelling. Although granulomatous inflammation is rare, integrating clinical, serological, radiological, and pathological parameters can ensure an accurate assessment within the appropriate clinicopathological context.
Sonic hedgehog medulloblastoma cells in co-culture with cerebellar organoids converge towards in vivo malignant cell states
Authors: van Essen Max J , Nicheperovich Alina , Schuster-Böckler Benjamin , Becker Esther B E , Jacob John
Published: December 2024

Background

In the malignant brain tumor sonic hedgehog medulloblastoma (SHH-MB) the properties of cancer cells are influenced by their microenvironment, but the nature of those effects and the phenotypic consequences for the tumor are poorly understood. The aim of this study was to identify the phenotypic properties of SHH-MB cells that were driven by the nonmalignant tumor microenvironment.

Methods

Human induced pluripotent cells (iPSC) were differentiated to cerebellar organoids to simulate the nonmaliganant tumor microenvironment. Tumor spheroids were generated from 2 distinct, long-established SHH-MB cell lines which were co-cultured with cerebellar organoids. We profiled the cellular transcriptomes of malignant and nonmalignant cells by performing droplet-based single-cell RNA sequencing (scRNA-seq). The transcriptional profiles of tumor cells in co-culture were compared with those of malignant cell monocultures and with public SHH-MB datasets of patient tumors and patient-derived orthotopic xenograft (PDX) mouse models.

Results

SHH-MB cell lines in organoid co-culture adopted patient tumor-associated phenotypes and showed increased heterogeneity compared to monocultures. Subpopulations of co-cultured SHH-MB cells activated a key marker of differentiating granule cells, NEUROD1 that was not observed in tumor monocultures. Other subpopulations expressed transcriptional determinants consistent with a cancer stem cell-like state that resembled cell states identified in vivo.

Conclusions

For SHH-MB cell lines in co-culture, there was a convergence of malignant cell states towards patterns of heterogeneity in patient tumors and PDX models implying these states were non-cell autonomously induced by the microenvironment. Therefore, we have generated an advanced, novel in vitro model of SHH-MB with potential translational applications.
Un guide pour la prise en charge communautaire des troubles des conduites alimentaires en pédiatrie
Authors: Coret Marian , Vyver Ellie , Harrison Megan , Toulany Alene , Vandermorris Ashley , Agostino Holly
Published: December 2024

Les troubles des conduites alimentaires (TCA) désignent un groupe de maladies graves au potentiel mortel qui se déclarent généralement pendant l’adolescence et peuvent être associés à de graves complications médicales et psychosociales. Ils peuvent avoir d’importantes répercussions sur les proches et les autres membres de la famille. Les professionnels de la santé jouent un rôle important pour les dépister et les prendre en charge chez les adolescents et les jeunes adultes. Le présent document de principes aide les professionnels de la santé en milieu communautaire à dépister, diagnostiquer et traiter les TCA dans la population pédiatrique. Les modalités de dépistage, les indications d’hospitalisation, les complications médicales et la surveillance des jeunes ayant un TCA sont résumées. Les données probantes à jour appuient le recours au traitement familial comme modalité thérapeutique psychologique de première ligne auprès des adolescents ayant un TCA restrictif. Les traitements familiaux dépassent peut-être la portée de pratique de certains médecins en milieu communautaire, mais le présent document de principes en examine les éléments fondamentaux. Au diagnostic d’un TCA, les professionnels de la santé qui mettent rapidement ces éléments à exécution en milieu communautaire peuvent ralentir l’évolution de la maladie et donner des conseils aux familles.
Diagnosis and management of congenital syphilis: Avoiding missed opportunities
Authors: Fanella Sergio , Bitnun Ari , Barton Michelle , Sauvé Laura
Published: December 2024

Congenital syphilis can result in pregnancy loss and substantial morbidity in newborns. The current epidemic of congenital syphilis in Canada (especially Western Canada) is a preventable public health emergency. Rates indicate a lack of control of syphilis within the community and insufficient public health resources to prevent spread that predate the COVID-19 pandemic. Risk factors include lack of prenatal care, methamphetamine and other substance use, and unstable housing. The cornerstone of prevention is identification, treatment, and follow-up during pregnancy, including of partners. Clinicians caring for newborns need to consider aspects of maternal treatment, reinfection risk, the results of paired maternal and infant syphilis serology, and infant clinical assessment. A complete risk assessment will guide effective management and follow-up of infants exposed in utero to syphilis.