bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of psychosocial aftercare following pediatric chronic pain treatment withstand the coronavirus disease 2019 pandemic: long-term outcomes of a randomized controlled trial
Authors: Rau Lisa-Marie , Dogan Meltem , Hirschfeld Gerrit , Blankenburg Markus , Frühwald Michael C. , Ahnert Rosemarie , Braun Sarah , Marschall Ursula , Zernikow Boris , Wager Julia 
Published: December 2024

Abstract

Introduction:
Intensive interdisciplinary pain treatment (IIPT) is the best therapy available for children and adolescents affected by severe chronic pain. Psychosocial aftercare (PAC) offered for 6 months after IIPT can improve treatment outcomes for up to 12 months.

Objectives:
The current study is the first to explore whether PAC is superior to treatment as usual at a long-term follow-up of 18 to 33 months after discharge—including when facing the coronavirus disease 2019 (COVID-19) pandemic.

Methods:
A multicenter randomized controlled trial investigated the impact of PAC with follow-up assessments in 2021 during the COVID-19 pandemic (N = 209). Multilevel models and regression analyses explored long-term treatment effects on pain characteristics and psychological outcomes, associations of pandemic-related burden with these outcomes, and whether pandemic-related burden moderates those effects.

Results:
Patients who received PAC significantly improved treatment outcomes concerning pain characteristics and psychological well-being 18 to 33 months after IIPT discharge. A COVID-19 infection among family members or peers was associated with a lower probability of having chronic pain at long-term follow-up, whereas having missed or rescheduled health care appointments was associated with a higher probability. Positive evaluations of family time during the pandemic were associated with better psychological well-being. Regardless of pandemic-related burdens, PAC had similarly better outcomes than treatment as usual. Only for anxiety, greater burdens mitigated the advantages of PAC.

Conclusion:
Despite adverse circumstances, PAC retained its superiority long-term. Integrating PAC into routine health care to support families after IIPT should be prioritized to yield enduring treatment effects, acting as a buffer against the impacts of unpredictable adverse events.
What do ultrasound vocalizations really mean in rats with different origins of pain?
Authors: Yu Yang , Li Chun-Li , Du Rui , Wang Xiao-Liang , Chen Jun 
Published: December 2024

Abstract

Objectives:
This study is to assess how 22 kHz and 50 kHz spontaneous ultrasound vocalization (USV) calls would be affected by different origins of pain so as to validate the use of USV in pain studies.

Methods:
Five well-established rat models of pain were used to evaluate various parameters of spontaneous 22 kHz and 50 kHz calls in adult male rats in terms of both acute and chronic or inflammatory and neuropathic or somatic and visceral origins. The effects of local lidocaine blockade of the injection site and intraperitoneal administration of antidepressant (amitriptyline) and anticonvulsant (gabapentin) were examined as well in typical inflammatory and neuropathic pain models, respectively.

Results:
The major new gains were as follows: (1) naive rats staying alone and engaging dyadic social interaction with a naive or a conspecific in pain emitted similar power and amounts of both 22 kHz and 50 kHz spontaneous USV calls; however, rats suffering from various origins of pain emitted significantly less USV calls of both 22 kHz and 50 kHz in terms of both number and time. (2) Local blockade of the injury sites of inflammatory pain could reverse the impaired emission of both 22 kHz and 50 kHz spontaneous calls, so did the treatment of the rats with neuropathic pain by amitriptyline and gabapentin.

Conclusions:
Emissions of both 22 kHz and 50 kHz spontaneous calls were impaired by acute and chronic pain conditions regardless of inflammatory and neuropathic or somatic and visceral origins.
A significant role for maternal genetic nurture in the risk architecture of attention-deficit/hyperactivity disorder
Authors: Mahjani Behrang , Kępińska Adrianna P. , Smout Shelby , Cohen Lily , Caballero Madison , Buxbaum Joseph D. , Grice Dorothy E. 
Published: December 2024

AbstractObjectivePrevious studies have shown that parental factors are associated with an increased risk for attention-deficit/hyperactivity disorder (ADHD). However, the pathways by which parental factors are associated with risk of ADHD in offspring are not well understood. These associations can arise directly from parental genotypes inherited by offspring, and/or via environmental effects, some of which may themselves be influenced by the parental genotype (i.e., parental genetic nurture). This study specifically examines the impact of the maternal phenotype on offspring ADHD risk, above and beyond the direct genetic effect of maternally-inherited genes.MethodsThe study population consisted of 982,544 individuals from the Swedish Medical Birth Register. We partitioned the liability of ADHD into direct additive genetic effect, maternal genetic nurture effect, and maternal common environment effect.ResultsWe identified 66,707 (7%) individuals in the birth cohort with an ADHD diagnosis. Maternal half-siblings were associated with a higher ADHD risk compared to paternal half-siblings, suggesting maternal effect. We estimated 66.1% direct additive genetic effect (95% credible interval, 0.647%-0.676%) and 14.3% maternal genetic nurture effect (95% credible interval, 0.136%-0.151%). Additionally, we also observed evidence for substantial assortative mating among individuals with ADHD.ConclusionsOur findings indicate that maternal genotypes influence offspring’s risk of ADHD through environmental pathways beyond the effects of direct genetic transmission. Exploring the impact of the genetics of the mother beyond the maternally inherited genes can lead to new insights into ADHD risk. Future studies should also investigate paternal effects to provide a more comprehensive understanding of the ADHD risk architecture.
Artificial Intelligence Methods to Detect Heart Failure with Preserved Ejection Fraction (AIM-HFpEF) within Electronic Health Records: An equitable disease prediction model
Authors: Wu Jack , Biswas Dhruva , Brown Samuel , Ryan Matthew , Bernstein Brett , To Brian Tam , Searle Tom , Rizvi Maleeha , Fairhurst Natalie , Kaye George , Baral Ranu , Vijayakumar Dhanushan , Mehta Daksh , Melikian Narbeh , Sado Daniel , Carr-White Gerald , Chowienczyk Phil , Teo James , Dobson Richard JB , Bromage Daniel I , Lüscher Thomas F , Vazir Ali , McDonagh Theresa A , Webb Jessica , Shah Ajay M , O’Gallagher Kevin 
Published: December 2024

AbstractBackground and aimsHeart Failure with Preserved Ejection Fraction (HFpEF) accounts for approximately half of all heart failure cases, with high levels of morbidity and mortality. However, most cases of HFpEF are undiagnosed as conventional risk scores underestimate risk in non-White populations. Our aim was to develop and validate a diagnostic prediction model to detect undiagnosed HFpEF, AIM-HFpEF.MethodsWe applied natural language processing (NLP) and machine learning methods to routinely collected electronic health record (EHR) data from a tertiary centre hospital trust in London, UK, to derive the AIM-HFpEF model. We then externally validated the model and performed benchmarking against existing HFpEF prediction models (H2FPEF and HFpEF-ABA) for diagnostic power in patients of non-white ethnicity and patients from areas of increased socioeconomic deprivation.ResultsAn XGBoost model combining demographic, clinical and echocardiogram data showed strong diagnostic performance in the derivation dataset (n=3170, AUC=0.88, [95% CI, 0.86-0.91]) and validation cohort (n=5383, AUC: 0.88 [95% CI, 0.87-0.89]). Diagnostic performance was maintained in patients of non-White ethnicity (AUC=0.88 [95% CI, 0.84-0.93]) and patients from areas of high socioeconomic deprivation (AUC=0.89 [95% CI, 0.84-0.94]). and AIM-HFpEF performed favourably in comparison to H2FPEF and HFpEF-ABA models. AIM-HFpEF model probabilities were associated with an increased risk of death, hospitalisation and stroke in the external validation cohort (P<0.001, P=0.01, P<0.001 respectively for highest versus middle tertile).ConclusionAIM-HFpEF represents a validated equitable diagnostic model for HFpEF, which can be embedded within an EHR to allow for fully automated HFpEF detection.
Association Between Oral Microbiota and Close-Range Proximity in a Primary School
Authors: Dall’Amico Lorenzo , Bai Xiangning , Weltzien Sandra Marie , Rayner Simon , Paolotti Daniela , Budin Ljøsne Isabelle Sylvie , Matussek Andreas , Furberg Anne-Sofie , Cattuto Ciro , Nielsen Christopher Sivert 
Published: December 2024

AbstractThe microbiota is the ensemble of microorganisms inhabiting the human body and it deeply influences human health and well-being. Recent studies showed its interplay with social behavior, suggesting that part of the microbiota might be socially transmissible. In this work, we investigate the association between closerange proximity and the oral microbiota composition in a group of children attending primary school. Unlike most related studies, our cohort comprises non-cohabiting individuals, and we use high-resolution proximity sensors to objectively measure social interactions. Our analysis shows that prolonged interactions between children pairs correlate with a higher similarity between their microbiota. These findings complement what is known for co-habiting individuals, suggesting that microbiota might be transmitted in social settings.
Interaction of the wireworm speciesAgriotes obscurus,A. sputatorandA. lineatuswith a new granule formulation ofMetarhizium brunneum
Authors: Paluch Maximilian , Seib Tanja , Stephan Dietrich , Jürgens Andreas , Lehmhus Jörn 
Published: December 2024

AbstractThe attract-and-kill strategy is a promising approach in integrated pest management to increase the efficiency of plant protection products by pushing the required contact between target pest and active ingredient. Within the project AgriMet, a new soil granule of the entomopathogenic fungusMetarhizium brunneumwas developed to control wireworms of the genusAgriotes(Coleoptera: Elateridae) in potato cultivation. The formulation is based on autoclaved millet as a substrate to lure the larvae to the infectious conidia on its surface. However, no data existed about the interactions of wireworms with the AgriMet-Granule. Here, I examined the behavioural response of the wireworm speciesA. obscurus,A. sputatorandA. lineatusto the AgriMet-Granule using an olfactometric bioassay in the laboratory. The foraging behaviour ofA. obscurusandA. sputator,with regard to the AgriMet-Granule, was tested with a feed-choice-experiment using a horizontal arena set-up. The tested wireworms significantly preferred autoclaved millet compared to the control. Fungal colonisation on the surface of the AgriMet-Granule did not influence their preference in general. However, differences were observed depending on the respective wireworm species and the twoMetarhiziumspp. isolates used. The feeding bioassay showed that the acceptance of wireworms for the AgriMet-Granule, with a low conidia concentration on its surface, was high. A high conidia concentration on the surface of the AgriMet-Granule led to a decreased acceptance that differed between the wireworm species. However, the survival analysis of wireworms isolated after the feed choice experiment indicated that the wireworms came in contact with the infectious conidia. Overall, the data suggests that autoclaved millet is a suitable substrate for the AgriMet-Granule. It attracts larvae of the genusAgriotesto the biocontrol agent using the formulatedM. brunneumisolate.
Calcium dynamics tune developmental tempo to generate evolutionarily divergent axon tract lengths
Authors: Lindhout Feline W. , Szafranska Hanna M. , Imaz-Rosshandler Ivan , Guglielmi Luca , Moarefian Maryam , Voitiuk Kateryna , Zernicka-Glover Natalia K. , Boulanger Jerome , Schulze Ulrike , Lloyd-Davies Sánchez Daniel J. , Minnick John , Teodorescu Mircea , Lancaster Madeline A. 
Published: December 2024

ABSTRACTThe considerably slow pace of human brain development correlates with an evolutionary increase in brain size, cell numbers, and expansion of neuronal structures, with axon tracts undergoing an even greater evolutionary increase than other neuronal domains. However, whether tempo is responsible for these differences in magnitude, and how, remains to be determined. Here, we used brain organoids to investigate this and observed that human axon tracts spend more time growing and extend farther compared to those of mice, independent of their tissue environment. Single cell RNA sequencing analysis pointed to a subset of calcium-permeable ion channels expressed throughout neuron development, including during axon tract outgrowth. Calcium imaging during early neuron development consistently revealed a reduced calcium influx in human neurons compared to mouse neurons. Stimulating calcium influx and increasing cAMP levels resulted in premature halting of axon tract outgrowth and shorter axon tracts, mimicking the mouse phenotype, while abrogating calcium influx led to an even longer phase of axon tract outgrowth and longer axon tracts in humans. Thus, evolutionary differences in calcium regulation set the tempo of neuronal development, by extending the time window to foster the more elaborated human neuron morphology.
Single-cell transcriptome profiling of the myeloid cells repopulating after chemotherapy identifies a neutrophil-like monocyte subset with pro-tumor activities
Authors: Ding Zhi-chun , Zhou George I. , Okoko Ogacheko D. , Wang Xin , Bryan Locke J. , Zhou Gang , Shi Huidong 
Published: December 2024

AbstractPatients with cancer often receive chemotherapy to control tumor progression and reduce disease symptoms. Cytotoxic chemotherapeutic agents not only kill rapidly growing cancer cells but also reduce normal cells including myeloid cells, the main innate immune population involved in fighting infections and repairing tissue damages. Rapid loss of myeloid cells caused by chemotherapy triggers myelopoiesis, a process in which the hematopoietic stem and progenitor cells in the bone marrow regenerate myeloid cells, including monocytes, neutrophils, dendritic cells and macrophages, to reconstitute the myeloid cell compartment. We previously reported that chemotherapy with an alkylating agent cyclophosphamide (CTX) in mice leads to repopulation of myeloid cells that acquire immunosuppressive activities within the monocyte subset. However, detailed information on the cellular composition and molecular identity of these chemotherapy- induced immunosuppressive monocytes is lacking. Here, we investigated how the various myeloid cell subsets in the bone marrow of mice respond to CTX chemotherapy through single-cell RNA sequencing analysis (scRNAseq). We found that myeloid progenitor cells and monocytes were reduced 2 days after chemotherapy but rebounded and surpassed their pretreatment levels by day 7. Further scRNAseq analysis of pre-enriched monocytes revealed that the monocyte population was heterogenous, and that chemotherapy tilted myelopoiesis towards the production of neutrophil-like monocytes (NeuMo). We identified Cxcr4 and Cx3cr1 as suitable markers for isolation of chemotherapy-induced NeuMo and demonstrated that these cells were suppressive to T cells. Together with the evidence that CTX-induced monocytes can promote breast cancer metastasis in mice, our data reveal the heterogeneity of the monocytes reemerging after chemotherapy and identify the NeuMo subset as a potential therapeutic target for enhancing the efficacy of chemotherapy in cancer.
Construction of a drug sensitisedCandida aurisstrain
Authors: Hassan Mahnoor , Furner-Pardoe Jessica , Chen Yiyuan , Mason A. James , Rahman Khondaker Miraz , Sutton J. Mark , Hind Charlotte , Panaretou Barry 
Published: December 2024

AbstractCandida aurisis an emerging pathogenic fungus causing outbreaks of invasive disease in healthcare facilities worldwide with the majority of clinical isolates demonstrating intrinsic resistance to multiple drug classes. Therefore, there is a pressing need for new antifungals, but screening in wild-typeC. aurisstrains may miss scaffolds which would be good subjects for med-chem projects as antifungals. Work presented here indicates that deletion ofCDR1andMDR1inC. auris, respectively encoding an ATP-binding Cassette and a Major Facilitator Superfamily efflux pump, generates a strain that is hypersensitised to drugs and can act as a platform for antifungal drug screening. Thecdr1Δmdr1Δ mutant was 64- and 8- times more sensitive to fluconazole and voriconazole, respectively, compared with the wild-type strain. In a pilot study using a 2,000 compound library, use of thecdr1Δmdr1Δ mutant identified over twice as many compounds compared to wild-type. When assessing the capacity to form biofilms, there was a modest difference in biomass between the wild-type andcdr1Δmdr1Δ mutant, but there was little to no statistically significant difference observed when using a colorimetric dye that measured metabolic activity. Little to no statistically significant difference was observed between wild-type and the efflux pump mutant in virulence, as judged by the larvalGalleria mellonellainfectivity assay. Accordingly, thecdr1Δmdr1Δmutant will be useful when screening for drugs that limit formation of biofilms or limit fungal virulence, as these two properties are unaffected when drug efflux is compromised.
Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis
Authors: Lee Min-Ting , Tan Xiaoqing , Le Henry H. , Besler Kevin , Thompson Sharon , Harris-Tryon Tamia , Johnson Elizabeth L. 
Published: December 2024

ABSTRACTSphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood. Sphingolipid synthesis by prominent gut microbes has been shown to affect intestinal, hepatic and immune functions with the potential for sphingolipid-producing bacteria to affect skin biology through altering skin sphingolipid levels. To address this question, we used bioorthogonal chemistry to label lipids from the sphingolipid-producing bacteriaBacteroides thetaiotaomicronand trace these lipids to the skin epidermis. Exposing mice toB. thetaiotaomicronstrains mutant in the ability to produce sphingolipids resulted in significantly lower transfer of gut microbiome-derived lipids to the skin, while also altering skin biology and altering expression of skin barrier genes. Measurement of skin ceramide levels, a class of sphingolipids involved in skin barrier function, determined that skin sphingolipid levels were altered in the presence of gut sphingolipid-producing bacteria. Together this work demonstrates that gut bacterial lipids can transfer to the skin and provides a compelling avenue for modulating sphingolipid-dominant compartments of the skin using sphingolipid-producing bacteria of the gut microbiome.
Human Slip Control: Investigating the Role of Hand Acceleration Modulation in Preventing Slips
Authors: Nazari Kiyanoush , Mandil Willow , Santello Marco , Ghalamzan Amir 
Published: December 2024

AbstractEnsuring a stable grasp during manipulative movements is crucial for robotic applications. While grip force has been the primary means of slip control, our human study revealed that trajectory modulation is also an effective slip control policy during pick-and-place tasks. Motivated by these findings, we developed and compared a slip control policy based on trajectory modulation to one based on grip force control for robotic pick-and-place tasks. Our results show that trajectory modulation significantly outperforms grip force control in certain scenarios, highlighting its potential for slip control in robotics. Moreover, we demonstrate the importance of incorporating forward models in developing effective trajectory modulation slip control systems. Overall, our study provides insight into an alternative method for slip control and suggests that humans use trajectory modulation as an alternative to grip force control for slippage prevention. This insight helps design algorithm for improving robotic manipulation tasks to prevent slippage.
Beta cell dysfunction occurs independently of insulitis in type 1 diabetes pathogenesis
Authors: Huber Mollie K. , Widener Adrienne E. , Cuaycal Alexandra E. , Smurlick Dylan , Butterworth Elizabeth A. , Lenchik Nataliya I. , Chen Jing , Beery Maria , Hiller Helmut , Verney Ellen , Kusmartseva Irina , Rupnik Marjan Slak , Campbell-Thompson Martha , Gerling Ivan C. , Atkinson Mark A. , Mathews Clayton E. , Phelps Edward A. 
Published: December 2024

SummaryThe loss of insulin secretory function associated with type 1 diabetes (T1D) is attributed to the immune-mediated destruction of beta cells. Yet, at onset of T1D, patients often have a significant beta cell mass remaining while T cell infiltration of pancreatic islets is sporadic. Thus, we investigated the hypothesis that the remaining beta cells in T1D are largely dysfunctional using live human pancreas tissue slices prepared from organ donors with recently diagnosed T1D. Beta cells in slices from donors with T1D had significantly diminished Ca2+mobilization and insulin secretion responses to glucose. Beta cell function was equally impaired in T cell-infiltrated and non-infiltrated islets. Fixed tissue staining and gene expression profiling of laser-capture microdissected islets revealed significant decreases of proteins and genes in the glucose stimulus secretion coupling pathway. From these data, we posit that functional defects occur in the remaining mass of beta cells during human T1D pathogenesis.
Organ injury accelerates stem cell differentiation by modulating a fate-transducing lateral inhibition circuit
Authors: Sanders Erin N. , Sun Hsuan-Te , Tabatabaee Saman , Lang Charles F. , van Dijk Sebastian G. , Su Yu-Han , Labott Andrew , Idris Javeria , He Li , Marchetti Marco , Xie Shicong , O’Brien Lucy Erin 
Published: December 2024

AbstractInjured epithelial organs must rapidly replace damaged cells to restore barrier integrity and physiological function. In response, injury-born stem cell progeny differentiate faster compared to healthy-born counterparts, yet the mechanisms that expedite differentiation are unclear. Using the adultDrosophilaintestine, we find that injury accelerates differentiation by modulating the lateral inhibition circuit that transduces a fate-determining Notch signal. During routine intestinal turnover, balanced terminal (Notch-active) and stem (Notch-inactive) fates arise through lateral inhibition in which Notch-Delta signaling between two stem cell daughters resolves over time to activate Notch and extinguish Delta in one cell. When we feed flies a gut-damaging toxin, injury-induced cytokines cause Notch-activated cells to escape normal Delta suppression by inactivating the Notch co-repressor Groucho. Mathematical modeling predicts that this augmented Delta prompts faster Notch signaling; indeed,in vivolive imaging reveals that injury-born cells undergo markedly faster Notch signal transduction. Thus, Notch-Delta lateral inhibition—a switch that regulates fates during steady-state turnover—also serves as a throttle that tunes differentiation speed according to tissue need.