bluuebunny/crossref_metadata_2025 huggingface dataset:
P852 Metataxonomic and metabolomic profiling to predict response to anti-TNF therapy in Crohn’s Disease
Authors: Foyzul J , Alexander J L , Chappell K E , Ibraheim H A , Saifuddin A , Kennedy N A , Bewshea C , Lin S , Hart A L , Goodhand J R , Ahmad T , Powell N ,   UK Inflammatory Bowel Disease Pharmacogenetics Study Group
Published: January 2024

Background

The composition of the gut microbiota is associated with response to treatments in inflammatory bowel disease1. We sought to identify gut microbial and metabolomic biomarkers associated with response to anti-TNF therapy in Crohn’s disease.

Methods

Faecal and serum samples collected at baseline and week 14 of anti-TNF treatment in the "Predictors of anti-TNF treatment failure" (PANTS) study were used2. Response to treatment (defined clinically and biochemically) was determined at week 142. Faecal samples were processed by GA-map®, with targeted 16S rRNA PCR sequencing. Serum samples were analysed with targeted liquid chromatography tandem mass spectrometry for bile acids and tryptophan metabolites. Multivariate and univariate analyses, as well as Spearman’s rank test, were performed.

Results

Two-hundred and twenty-four patients with Crohn’s disease commencing anti-TNF therapy were included (54.1% anti-TNF responders, 48.6% female, median age 37.2 (26.5-50.0) years, 56.9% receiving immunomodulator-based treatment). A significantly higher proportion of non-responders received corticosteroid treatment compared to responders at baseline (p=0.0009).

Sixty-nine bacterial taxa were identified. Significantly lower abundances of Clostridium difficile and Mycoplasma were identified in responders relative to non-responders at baseline (q-value=0.046 and q-value=0.034, respectively). No significant differences in the abundances of Faecalibacterium prausnitzii, Shigella or Escherichia Coli were found (all q-values > 0.05).

Eighteen serum bile acids and thirteen tryptophan metabolites were identified. Significantly higher serum abundances of cholic acid, tryptophan and 3OH-kynurenine were identified in responders at baseline (q-values=0.049, 0.033, and 0.033, respectively). Exploration of microbial–metabolite associations revealed negative correlations between secondary bile acids and several bile salt hydrolase producing bacteria, such as Bifidobacterium (r ≤ -0.50). Positive correlations were also identified between xanthurenic acid and Bifidobacterium and Roseburia intestinalis (r ≥ 0.50). Increased abundances of short-chain fatty acid producing bacteria, such as Bifidobacterium and Bacteroides vulgatus, were noted in responders at week 14.

Conclusion

We have identified baseline differences in the faecal microbiota and serum metabolome of anti-TNF responders and non-responders. These findings require validation in larger cohorts to determine their robustness for potential use in treatment personalisation.

References

1. Radhakrishnan S. et al., Alimentary pharmacology & therapeutics vol. 55,1 (2022): 26-48. 10.1111/apt.16656.

2. Kennedy N. et al., The Lancet. Gastroenterology & Hepatology vol. 4,5 (2019): 341-353. 10.1016/S2468-1253(19)30012-3.
P1003 Dietary pattern can influence the level of fatigue in patients with Inflammatory Bowel Disease in remission
Authors: Stroie T G , Preda C M , Istratescu D , Nitescu M , Manuc T E , Manuc M , Meianu C G , Andrei A , Ciora C A , Louis E , Diculescu M M
Published: January 2024

Background

It is well known that dietary pattern can play an important role in the onset of inflammatory bowel diseases (IBD). In patients with established disease, they can influence the risk of relapse and the disease course.

The aim of the study is to explore the impact of dietary patterns on health-related quality of life (HR-QoL), fatigue, anxiety and depression in patients with IBD in corticosteroid-free clinical remission.

Methods

A total of 96 consecutive patients diagnosed with IBD that were in corticosteroid-free remission for at least 12 weeks were enrolled in this observational, cross-sectional study.

During an interview, patients were asked about their dietary patterns. Twelve categories of foods were identified, 6 of them being considered "healthy" (vegetables and fruits >4 portions/day, cereals >3 portions/day, seeds >4 portions/week, cheese >1 portion/day, yoghurt >1 portion/day, fish >2 portions/week) and the other 6 "unhealthy" (fatty red meat >1 portion/day, sweetened beverages >1L/day, cured meat >2 portions/day, fried food >1 portion/day, chips >1 portion/day, mayonnaise >1 portion/day) (see Figure 1).

An "unhealthy" dietary pattern was considered if the proportion of "unhealthy" food categories from the total food categories consumed by the patient exceeded 50%.

HR-QoL, fatigue, anxiety and depression were evaluated using the following self-administered questionnaires: IBDQ-32, FACIT-Fatigue and HADS.

Results

Out of the 96 patients included, 60 (62.5%) were men. The median patient age was 38 years (IQR 31.5 – 45.5). Sixty patients (62.5%) were diagnosed with CD, and 36 (37.5%) with UC. Most of the patients were treated with biologics (93.8%).

An unhealthy dietary pattern was identified in 58 (60.4%) patients.

Patients with an "unhealthy" dietary pattern experienced significantly more fatigue compared to patients with a "healthy" dietary pattern (mean FACIT-F score 40.3 vs. 44.4 points, p=0.02). Even though not statistically significant, patients with "unhealthy" dietary pattern had a trend towards a lower HR-QoL (mean IBDQ score 187.3 vs. 192.8, p=0.24). Anxiety and depression were less frequent among patients with "unhealthy" dietary pattern, but the differences were not statistically significant (anxiety: 24.1% vs. 31.6%, p=0.57; depression: 13.8% vs. 21.2%, p=0.51).

Conclusion

Patients with an "unhealthy" dietary pattern experience significantly higher levels of fatigue compared to patients that are eating "healthier" food. There is also a trend towards lower HR-QoL in this category of patients.
P1061 TEV-48574, an anti-TL1A antibody in development for use in IBD, is safe and well tolerated following 16 weeks of subcutaneous treatment in adults with severe uncontrolled T2-low/non T2 asthma
Authors: Raphael G , Damera G , Angeles T , Li S , Stoyanov S
Published: January 2024

Background

TEV-48574 is a human antibody that targets tumor necrosis factor (TNF)-like ligand 1A, also known as TNF superfamily member 15 (TNFSF15). It is in clinical development as a potential treatment for ulcerative colitis (UC) and Crohn’s disease (CD). TL1A signalling is believed to amplify immune-mediated inflammation in asthma and inflammatory bowel disease (IBD); thus, targeting TL1A may mitigate over-activation of immune responses. A proof-of-concept phase 2A study evaluated safety, tolerability and efficacy of TEV-48574 as treatment for adults with severe uncontrolled asthma (Clinicaltrials.gov NCT04545385). Although the study terminated (after meeting pre-specified criteria for futility at a preplanned interim analysis) the drug demonstrated favourable safety, tolerability and immunogenicity data, supporting the potential use of anti-TL1A treatment in patients with UC and CD.

Methods

TEV-48574 was administered as a loading dose followed by 7 maintenance doses given subcutaneously (sc) every 2 weeks for 16 weeks in adult patients (n = 65) with severe T2-low asthma with no/low inflammation at baseline. The primary efficacy endpoint was reduction in patients who experience loss of asthma control (LoAC). Patients were monitored for LoAC at bi-weekly visits and daily by use of a handheld spirometer/e-diary. Safety was assessed throughout the study.

Results

Of 65 randomized patients, 64 received at least one dose of study drug and were included in the safety analysis (33 active drug; 31 placebo). There were no severe AEs, treatment related SAEs, deaths, or withdrawals due to adverse events, and no medical device-related issues. There were no clinically meaningful changes in lab parameters, vital signs or ECGs. Furthermore, there was no evidence of immune suppression, opportunistic infections, or malignancies. Mild treatment-related adverse reactions occurred in both treatment groups (erythema and pruritus in two placebo patients; erythema in one TEV-48574 treated patient). Mild injection site reactions occurred more frequently (not statistically different) in the TEV-48574 group. Treatment-emergent anti-drug antibodies were reported in patients taking TEV-48574 (3 patients; 9.09%), with no anaphylactic or severe systemic reactions.

Conclusion

Overall, TEV-48574 administered every 2 weeks over 16 weeks demonstrated a favourable safety and tolerability profile with no emerging safety signals or evidence of immunosuppression. This is consistent with TL1A being an amplifier of inflammation. Treatment with TEV-48574 may dampen excessive inflammation without inducing a state of immunodeficiency in patients with conditions such as UC or CD, supporting further development in these indications.
P1079 Mindfulness-based cognitive therapy to reduce psychological distress in patients with Inflammatory Bowel Disease: first results of a multicentre randomised controlled trial (MindIBD)
Authors: Ter Avest M , Speckens A , Dijkstra G , Dresler M , Bosman S , Horjus C , Römkens T , Witteman E , Van Dop W , Nissen L , Huijbers M
Published: January 2024

Background

Many patients with Inflammatory Bowel Diseases (IBD) suffer from psychological distress and fatigue. Moreover they report a reduced quality of life. The availability of psychosocial treatment options is limited. As mindfulness-based cognitive therapy (MBCT) has been shown to reduce psychological distress and fatigue, and improve quality of life in other populations, MBCT might also be effective in patients with IBD.

Methods

The MindIBD study was a prospective, multicentre, randomised controlled trial, conducted in one academic and three general hospitals in the Netherlands. Patients of 16 years and older with a confirmed IBD diagnosis were eligible if the IBD was in remission (based on faecal calprotectin <250 mg/kg and no changes in IBD medication for at least three months) and they experienced at least mild psychological distress (based on Hospital Anxiety and Depression Scale (HADS) total score ≥ 11). Participants were allocated in the intervention group (MBCT plus treatment as usual) or control group (treatment as usual alone). Assessments were conducted at baseline, post-intervention (3 months) and at 6, 9 and 12 months after baseline. Primary outcome was the effect on psychological distress post-intervention. Secondary outcomes included fatigue, perceived disease control, disease activity, disease-specific quality of life and positive mental health. This trial was registered at ClinicalTrials.gov: NCT04646785.

Results

A total of 142 IBD patients were randomly assigned to the intervention group (n=70) or the control group (n=72). The study population had a median age of 50 years (IQR 39-59 years), consisted of 91 women (64%) and 68 participants (48%) were diagnosed with Crohn’s disease. Post-intervention, participants in the intervention group showed a mean decrease on the HADS total of 4.7 ± 6.3 points compared to a mean decrease of 1.2 ± 5.2 points in the control group. This difference in improvement of psychological distress was statistically significant (p<0.001), and this benefit was maintained during follow-up (p=0.005). MBCT did also result in a significant improvement on fatigue (p=0.022) and positive mental health (p=0.022) post-intervention. These improvements remained in favour of the intervention group during follow-up, although not significantly different. No differences were found on perceived disease control, disease activity and disease-specific quality of life.

Conclusion

MBCT reduces psychological distress and improves fatigue and positive mental health. Therefore MBCT can be considered as a valuable addition to the limited psychosocial interventions for patients with IBD to improve psychological distress, fatigue and positive mental health.
Tracing evolutionary trajectories in the presence of gene flow in South American temperate lizards (Squamata: Liolaemus kingii group)
Authors: Sánchez Kevin I , Recknagel Hans , Elmer Kathryn R , Avila Luciano J , Morando Mariana
Published: January 2024

Evolutionary processes behind lineage divergence often involve multidimensional differentiation. However, in the context of recent divergences, the signals exhibited by each dimension may not converge. In such scenarios, incomplete lineage sorting, gene flow, and scarce phenotypic differentiation are pervasive. Here, we integrated genomic (RAD loci of 90 individuals), phenotypic (linear and geometric traits of 823 and 411 individuals, respectively), spatial, and climatic data to reconstruct the evolutionary history of a speciation continuum of liolaemid lizards (Liolaemus kingii group). Specifically, we (a) inferred the population structure of the group and contrasted it with the phenotypic variability; (b) assessed the role of postdivergence gene flow in shaping phylogeographic and phenotypic patterns; and (c) explored ecogeographic drivers of diversification across time and space. We inferred eight genomic clusters exhibiting leaky genetic borders coincident with geographic transitions. We also found evidence of postdivergence gene flow resulting in transgressive phenotypic evolution in one species. Predicted ancestral niches unveiled suitable areas in southern and eastern Patagonia during glacial and interglacial periods. Our study underscores integrating different data and model-based approaches to determine the underlying causes of diversification, a challenge faced in the study of recently diverged groups. We also highlight Liolaemus as a model system for phylogeographic and broader evolutionary studies.
Using cash transfers to promote child health equity: an analysis of Lesotho’s Child Grants Program
Authors: Besnier Elodie , Finseraas Henning , Sieu Celine , Muthengi Kimanzi
Published: January 2024

Cash transfers (CTs) are increasingly popular tools for promoting social inclusion and equity in children in sub-Saharan Africa. However, less is known about their implications for reducing the health gap between the beneficiary and non-beneficiary children in the community. Using Lesotho’s Child Grants Program (CGP) as a case study, we aim to understand better the potential for CT programmes to reduce the gap in child health in the targeted communities. Using a triple difference model, we examine to what extent CGP improved child health outcomes in eligible households compared with non-eligible households in treatment communities vs control communities and to what extent this effect varied in different population subgroups. We find that the child health gap by beneficiary children’s health outcomes catching-up on the health of non-beneficiary children narrowed but that eduction was not statistically significant. However, such a ‘catch-up’ effect among beneficiaries was observed for selected nutrition outcomes amongst female-headed households and subjective child health assessment for comparatively more food-secure households. This study highlights the potential and limitations of CT programmes like the CGP to address health inequalities in preschool children for selected population subgroups in the community.
Historical Vistas on Sri Lanka’s 2022 People’s Uprising
Authors: Hemachandra Samal Vimukthi , Sivasundaram Sujit
Published: January 2024

Written in close proximity to Sri Lanka’s 2022 people’s uprising, this is a conversation between two historians, one from the University of Colombo and the other from the University of Cambridge, about the long roots of violence in Sri Lankan society. It is an account of the lived experience of violence on 9 May 2022, which was a defining event of the uprising. What occurred on this date is cast here within various alternative historical itineraries. The article experiments with groundedness and time travel; it acknowledges the positionality of the authors, creating a solidarity across borders. This approach responds to critiques of the political naivety and colonialist methodology of empiricist history, making history of political use and public value once again.
Evaluating the sensitivity of EQ-5D-5L in patients with brain metastases: a secondary analysis of NRG CC001
Authors: Cherng Hua-Ren R , Qu Melody , Zafari Zafar , Bentzen Søren M , Armstrong Terri S , Gondi Vinai , Brown Paul D , Mehta Minesh , Mishra Mark V
Published: January 2024

Background

EuroQoL EQ-5D-5L is a commonly used measure of health-related quality of life in clinical trials given the use of its index score as a measure of health utilities. It is unclear whether EQ-5D-5L is sensitive to changes in neurocognitive function and progression that occur following brain radiation. This study sought to evaluate the sensitivity of EQ-5D-5L in reflecting these changes.

Methods

A secondary analysis of NRG Oncology CC001 was performed. Mean EQ-5D-5L index and visual analog scale (VAS) score changes from baseline between groups of patients stratified by neurocognitive function and intracranial progression status were assessed. MD Anderson Symptom Inventory for brain tumor (MDASI-BT) symptom and interference items were also analyzed between groups.

Results

EQ-5D-5L mean index and VAS score changes between patients who had cognitive failure and those who had preserved cognition showed no statistically significant differences at any timepoint. In contrast, VAS changes at 4 months (1.61 vs -5.13, P = .05) and 6 months (8.17 vs −0.14, P = .04) were significantly improved in the patients who survived without intracranial progression. MDASI-BT cognitive factor scores were improved in the cohort of patients with preserved neurocognitive function at 2 months (1.68 vs 2.08, P = .05) and 4 months (1.35 vs 1.83, P = .04). MDASI-BT symptom interference was significantly associated with intracranial progression at 4 months, but not with neurocognitive status.

Conclusion

EQ-5D-5L index and VAS scores were not sensitive to neurocognitive changes that patients experienced, but VAS scores were sensitive to progression. This study challenges the routine use of EQ-5D as a quality of life metric in brain metastases clinical trials that are focused on preventing neurocognitive dysfunction.

Trial Registration

NCT# 02360215.
Bipolar Argumentation Frameworks with a dual relation between defeat and defence
Authors: Alcântara João , Cordeiro Renan
Published: January 2024

Bipolar Argumentation Frameworks ($\textit{BAF}$s) extend Dung’s Abstract Argumentation Frameworks ($\textit{AAF}$s) by incorporating an explicit notion of support between arguments. However, there is a price to pay: the semantics for $\textit{BAF}$s often involve more intricate definitions and computational procedures than those for $\textit{AAF}$s. In this paper, we establish a dual relation between defeat and defence. Taking profit from this dual perspective, we define conflict-free sets, acceptability, extension-based and labelling-based semantics as in $\textit{AAF}$s. We also show that our definitions collapse into the corresponding concepts proposed for $\textit{AAF}$s when the support relation is ignored. In particular, we prove the semantics $\beta $-admissible, $\beta $-complete, $\beta $-grounded, $\beta $-preferred, $\beta $-stable and $\beta $-semi-stable defined here for $\textit{BAF}$s are generalisations of the corresponding semantics for $\textit{AAF}$s. Besides generalising $\textit{AAF}$s semantics to $\textit{BAF}$s, our approach also preserves some of their most remarkable results, including Dung’s Fundamental Lemma.
The ongoing spin-down episode of 4U 1626-67
Authors: Tobrej Mohammed , Tamang Ruchi , Rai Binay , Ghising Manoj , Paul Bikash Chandra
Published: January 2024

We report the X-ray characteristics of the persistent X-ray pulsar 4U 1626-67 using simultaneous NuSTAR and NICER observations. The X-ray pulsar 4U 1626-67 has just encountered a torque reversal in 2023 and is presently in the spin-down state. We have examined the temporal and spectral characteristics of the source during its ongoing spin-down episode. The pulse profiles of the source are characterized by multiple substructures at lower energies and a wide asymmetric single-peaked structure at higher energies. The pulse fraction follows an overall increasing trend with energy. We confirm the existence of mHz quasi-periodic oscillation (QPO) exclusively during the current spin-down phase in all the observations. The source is spinning down at 0.00045(4) s yr−1. The broad-band spectrum during this phase is described by empirical NPEX model and a soft blackbody component with kT ∼ 0.25 keV. In addition to the iron emission line, we also confirm the presence of cyclotron line at ∼36 keV. The source flux continues to decrease during the current spin-down phase, and the corresponding luminosity ∼(3.3–4.9) × 1036 erg s−1 lies in the intermediate range of accreting X-ray pulsars that may be associated with a hybrid accretion geometry. The magnetic field strengths estimated using the cyclotron line measurements and QPO frequency are consistent. The evolution of the spectral parameters relative to the pulsed phase is examined using phase-resolved spectroscopy.
Rotational evolution of young-to-old stars with data-driven three-dimensional wind models
Authors: Evensberget D , Vidotto A A
Published: January 2024

Solar-type stars form with a wide range of rotation rates Ω. A wide Ω range persists until a stellar age of t ∼ 0.6 Gyr, after which solar-type stars exhibit Skumanich spin-down where Ω ∝ t−1/2. Rotational evolution models incorporating polytropic stellar winds struggle to simultaneously reproduce these two regimes, namely the initially wide Ω range and the Skumanich spin-down without imposing an a priori cap on the wind mass-loss rate. We show that a three-dimensional wind model driven by Alfvén waves and observational data yields wind torques that agree with the observed age distribution of Ω. In our models of the Sun and 27 open cluster stars aged from 0.04 to 0.6 Gyr that have observationally derived surface magnetic maps and rotation rates, we find evidence of exponential spin-down in young stars that are rapid rotators and Skumanich spin-down for slow rotators. The two spin-down regimes emerge naturally from our data-driven models. Our modelling suggests that the observed age distribution of stellar rotation rates Ω arises as a consequence of magnetic field strength saturation in rapid rotators.
Structural investigation of pathogenic RFC1 AAGGG pentanucleotide repeats reveals a role of G-quadruplex in dysregulated gene expression in CANVAS
Authors: Wang Yang , Wang Junyan , Yan Zhenzhen , Hou Jianing , Wan Liqi , Yang Yingquan , Liu Yu , Yi Jie , Guo Pei , Han Da
Published: January 2024

An expansion of AAGGG pentanucleotide repeats in the replication factor C subunit 1 (RFC1) gene is the genetic cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), and it also links to several other neurodegenerative diseases including the Parkinson's disease. However, the pathogenic mechanism of RFC1 AAGGG repeat expansion remains enigmatic. Here, we report that the pathogenic RFC1 AAGGG repeats form DNA and RNA parallel G-quadruplex (G4) structures that play a role in impairing biological processes. We determine the first high-resolution nuclear magnetic resonance (NMR) structure of a bimolecular parallel G4 formed by d(AAGGG)2AA and reveal how AAGGG repeats fold into a higher-order structure composed of three G-tetrad layers, and further demonstrate the formation of intramolecular G4s in longer DNA and RNA repeats. The pathogenic AAGGG repeats, but not the nonpathogenic AAAAG repeats, form G4 structures to stall DNA replication and reduce gene expression via impairing the translation process in a repeat-length-dependent manner. Our results provide an unprecedented structural basis for understanding the pathogenic mechanism of AAGGG repeat expansion associated with CANVAS. In addition, the high-resolution structures resolved in this study will facilitate rational design of small-molecule ligands and helicases targeting G4s formed by AAGGG repeats for therapeutic interventions.
Disease Progress and Detection of a California Resistance-Breaking Strain of Tomato Spotted Wilt Virus in Tomato with LAMP and CRISPR-Cas12a Assays
Authors: Shymanovich Tatsiana , Saville Amanda C. , Mohammad Noor , Wei Qingshan , Rasmussen David , Lahre Kirsten A. , Rotenberg Dorith , Whitfield Anna E. , Ristaino Jean Beagle
Published: January 2024

Use of tomato cultivars with the Sw-5 resistance gene cluster has led to the occurrence of resistance-breaking (RB) tomato spotted wilt virus (TSWV) strains globally, including California and, recently, North Carolina and Texas. We documented disease on tomato infected with either an RB strain from California (CA-RB) or a wild type (CA-WT) strain of TSWV on tomato with (cultivar Mountain Merit) or without (cultivar Mountain Fresh Plus) the Sw-5b resistance gene and detected virus incidence over time using microneedle RNA extractions and LAMP. We developed a LAMP/Cas12a assay for detection of the CA-C118Y mutation in a CA-RB strain and tested the assay with field samples. Disease in the susceptible cultivar was less severe with CA-RB than with the CA-WT strain. In contrast, the resistant cultivar had little disease when inoculated with the CA-WT strain but exhibited stunting of greater than 50% when inoculated with the CA-RB strain. In the susceptible tomatoes, the detection rates over time by LAMP reaction were higher in CA-WT than in CA-RB-inoculated plants. In resistant tomato, CA-RB remained detectable by TSWV LAMP over 14 days, whereas the WT strain was undetectable. A two-step LAMP/Cas12a assay differentiated the two strains in 1 h. Our methods were validated with samples from TSWV-infected North Carolina fields. A phylogeny of NSm gene sequences that included North Carolina field samples revealed two independent origins of the North Carolina RB isolates. The LAMP/Cas12 assay showed excellent detection of the CA-C118Y mutation. The TSWV LAMP/Cas12a assay is adaptable for in-field applications on either a smart phone platform or heat block.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Pregnancy-associated melanoma: characteristics and outcomes from 2002 to 2020
Authors: Davidson Tara M. , Hieken Tina J. , Glasgow Amy E. , Habermann Elizabeth B. , Yan Yiyi
Published: January 2024

Melanoma diagnosed within 1 year of pregnancy is defined as pregnancy-associated melanoma (PAM). No robust data on how pregnancy influences melanoma nor guidelines for PAM management exist. With IRB approval, female patients with a pathology-confirmed melanoma diagnosis within 1 year of pregnancy treated at our institution from 2000 to 2020 were identified. Controls from the cancer registry were matched 1 : 4 when available on decade of age, year of surgery (±5), and stage. We identified 83 PAM patients with median follow-up of 86 months. Mean age at diagnosis was 31 years. 80% AJCC V8 stage I, 2.4% stage II, 13% stage III, 4.8% stage IV. Mean Breslow thickness was 0.79 mm and 3.6% exhibited ulceration. The mean mitotic rate was 0.76/mm2. In terms of PAM management, 98.6% of ESD patients and 86.7% of LSD patients received standard-of-care therapy per NCCN guidelines for their disease stage. No clinically significant delays in treatment were noted. Time to treatment from diagnosis to systemic therapy for LSD patients was an average of 46 days (95% CI: 34–59 days). Comparing the 83 PAM patients to 309 controls matched on age, stage, and year of diagnosis, similar 5-year overall survival (97% vs. 97%, P = 0.95) or recurrence-free survival (96% vs. 96%, P = 0.86) was observed. The outcomes of PAM following SOC treatment at a highly specialized center for melanoma care were comparable to non-PAM when matched by clinical-pathologic features. Specialty center care is encouraged for women with PAM.
Injectable Weight Loss Medications in Plastic Surgery: What We Know, Perioperative Considerations, and Recommendations for the Future
Authors: O’Neill Elizabeth S. , Wiegmann Aaron L. , Parrella Naomi , Pittman Troy , Hood Keith , Kurlander David
Published: January 2024

Obesity is a major epidemic plaguing American society. Injectable subcutaneous medications initially designed for use in type 2 diabetes management, such as semaglutide and other glucagon-like peptide-1 receptor agonists, are rapidly gaining popularity for their effects on weight. These drugs (Ozempic, Wegovy, Saxenda, and Mounjaro) are ubiquitous on social media and are promoted by celebrities across all demographics. “Ozempic face” and “Ozempic butt” are now mainstream concepts highlighting the morphologic changes that occur with these medications. There is a paucity of literature available on the impact of these medications for plastic surgeons and their patients. As use becomes widespread, it is important for plastic surgeons to understand their indications, contraindications, appropriate perioperative management, and impact on plastic surgery procedures.
Pathology of knee osteoarthritis pain: contribution of joint structural changes and pain sensitization to movement-evoked pain in knee osteoarthritis
Authors: Hattori Takafumi , Ohga Satoshi , Shimo Kazuhiro , Matsubara Takako
Published: January 2024

Introduction:

Movement-evoked pain (MEP) is the primary symptom in patients with knee osteoarthritis (KOA).

Objectives:

This study aimed to investigate the contribution of joint structural changes and pain sensitization to the mechanisms of MEP in patients with KOA.

Methods:

A total of 86 patients were assessed for demographic characteristics, osteoarthritis severity, Whole-Organ Magnetic Resonance Imaging Score–Hoffa synovitis and bone marrow lesions, pressure pain threshold and temporal summation of pain at the knee and forearm, Central Sensitization Inventory-9, and MEP. In measure of MEP, knee pain was scored using a numerical rating scale (NRS, 0–10) before and every minute during a 6-minute walking test (6MWT), and the MEP index was defined as the change in NRS pain score from baseline to the sixth minute of walking.

Result:

On average, pain during 6MWT increased by 1.4 ± 1.5 points on the NRS relative to baseline, with 30.2% of patients showing an increase of 2 points or more. The hierarchical linear regression analysis revealed that Hoffa synovitis, pressure pain threshold at the forearm, and temporal summation of pain at the knee were associated with the MEP index.

Conclusion:

The findings of this study suggest that both synovitis and neural mechanisms, such as pain sensitization, play a role in the development of MEP in KOA.
Improving the Safety of Computed Tomography Through Automated Quality Measurement
Authors: Smith-Bindman Rebecca , Wang Yifei , Stewart Carly , Luong Jason , Chu Philip W. , Kohli Marc , Westphalen Antonio C. , Siegel Eliot , Ray Monika , Szczykutowicz Timothy P. , Bindman Andrew B. , Romano Patrick S.
Published: January 2024

Objectives

The Centers for Medicare and Medicaid Services funded the development of a computed tomography (CT) quality measure for use in pay-for-performance programs, which balances automated assessments of radiation dose with image quality to incentivize dose reduction without compromising the diagnostic utility of the tests. However, no existing quantitative method for assessing CT image quality has been validated against radiologists' image quality assessments on a large number of CT examinations. Thus to develop an automated measure of image quality, we tested the relationship between radiologists' subjective ratings of image quality with measurements of radiation dose and image noise.

Materials and Methods

Board-certified, posttraining, clinically active radiologists rated the image quality of 200 diagnostic CT examinations from a set of 734, representing 14 CT categories. Examinations with significant distractions, motion, or artifact were excluded. Radiologists rated diagnostic image quality as excellent, adequate, marginally acceptable, or poor; the latter 2 were considered unacceptable for rendering diagnoses. We quantified the relationship between ratings and image noise and radiation dose, by category, by analyzing the odds of an acceptable rating per standard deviation (SD) increase in noise or geometric SD (gSD) in dose.

Results

One hundred twenty-five radiologists contributed 24,800 ratings. Most (89%) were acceptable. The odds of an examination being rated acceptable statistically significantly increased per gSD increase in dose and decreased per SD increase in noise for most categories, including routine dose head, chest, and abdomen-pelvis, which together comprise 60% of examinations performed in routine practice. For routine dose abdomen-pelvis, the most common category, each gSD increase in dose raised the odds of an acceptable rating (2.33; 95% confidence interval, 1.98–3.24), whereas each SD increase in noise decreased the odds (0.90; 0.79–0.99). For only 2 CT categories, high-dose head and neck/cervical spine, neither dose nor noise was associated with ratings.

Conclusions

Radiation dose and image noise correlate with radiologists' image quality assessments for most CT categories, making them suitable as automated metrics in quality programs incentivizing reduction of excessive radiation doses.
The reproduction number and its probability distribution for stochastic viral dynamics
Authors: Williams Bevelynn , Carruthers Jonathan , Gillard Joseph J. , Lythe Grant , Perelson Alan S. , Ribeiro Ruy M. , Molina-París Carmen , López-García Martín
Published: January 2024

We consider stochastic models of individual infected cells. The reproduction number,R, is understood as a random variable representing the number of new cells infected by one initial infected cell in an otherwise susceptible (target cell) population. Variability inRresults partly from heterogeneity in the viral burst size (the number of viral progeny generated from an infected cell during its lifetime), which depends on the distribution of cellular lifetimes and on the mechanism of virion release. We analyse viral dynamics models with an eclipse phase: the period of time after a cell is infected but before it is capable of releasing virions. The duration of the eclipse, or the subsequent infectious, phase is non-exponential, but composed of stages. We derive the probability distribution of the reproduction number for these viral dynamics models, and show it is a negative binomial distribution in the case of constant viral release from infectious cells, and under the assumption of an excess of target cells. In a deterministic model, the ultimate in-host establishment or extinction of the viral infection depends entirely on whether the mean reproduction number is greater than, or less than, one, respectively. Here, the probability of extinction is determined by the probability distribution ofR, not simply its mean value. In particular, we show that in some cases the probability of infection is not an increasing function of the mean reproduction number.
Beneath the Surface:  A Case Report on Nonencapsulated Streptococcus pneumoniae-Associated Invasive Disease in an Immunocompromised Patient.

Authors: Zintgraff Jonathan Cristian , Sanchez Eluchans Nahuel , Gagetti Paula , Martinez Celeste , Dina Pedersen , Moscoloni María , Lewis Adrian , Lara Claudia , Corso Alejandra
Published: January 2024

Background: Streptococcus pneumoniae, a prominent human pathogen linked to various systemic diseases, includes non-typeable pneumococci marked by the absence of a detectable capsule. However, the majority of invasive infections are attributed to encapsulated strains. This case report details the first documented instance of invasive disease caused by non-typeable S. pneumoniae in Argentina since 2017.
Case Presentation: A 19-year-old woman presented with hemorrhagic injuries attributed to chronic oral mucosa irritation. Subsequent hospitalization revealed bone marrow aplasia. Two weeks later, she was readmitted with sepsis related to a respiratory focus. After ten days, ICU admission revealed additional infections: positive COVID-PCR test, fungal sinusitis, and S. pneumoniae bacteremia. Targeted treatments led to improvement, and the patient was subsequently discharged.
S. pneumoniae Characterization: Verification of the capsule's absence utilized traditional methods such as the Quellung reaction, transmission electron microscopy, molecular assays, and Whole Genome Sequencing. The isolate, identified as ST18335, displayed genetic features and antibiotic resistance patterns, concordant between WGS and the agar dilution method. It demonstrated non-susceptibility to penicillin and cefotaxime, based on meningitis breakpoints, as well as meropenem and cotrimoxazole.
Conclusion:  This case underscores the clinical significance of non-typeable S. pneumoniae, emphasizing the necessity for a comprehensive approach to identification and characterization. The findings contribute to ongoing discussions regarding the challenges posed by non-typeable strains in vaccine development, understanding clinical impacts, and addressing antibiotic resistance. This case serves as a valuable addition to the evolving knowledge surrounding non-typeable S. pneumoniae, highlighting the continued need for surveillance and research in infectious diseases.
Cutaneous tuberculosis an unusual localization: A case report
Authors: ZIAD Fatima , Benaissa Elmostafa , Ben lahlou Yassine , Maleb Adil , Chadli Mariama , Elouennass Mostafa
Published: January 2024

Tuberculosis is a major public health concern. Morocco is a tuberculosis endemic country; nearly 30000 cases are recorded each year, pulmonary tuberculosis represents 57%, extrapulmonary tuberculosis 43%.
Cutaneous localization is exceptional; it represents 0.5 to 2% of cases of tuberculosis. It is very difficult to diagnose, given the variability of clinical presentation, and is based on combining clinical, radiological and biological arguments.
In this study we report a rare case of cutaneous tuberculosis occurring in a patient with history of pulmonary and cutaneous sarcoidosis, with personal history of pulmonary tuberculosis treated in 2017, presenting for a month a mass on the left thigh in the form of an abscess. The patient benefited from drainage of the skin abscess, the research of Koch's bacillus (BK) by conventional and molecular methods was positive.
Direct examination remains a very simple and rapid tool, it allows the search for Acid-Fast Bacilli (AFB) in the sample, its sensitivity is variable, it does not exceed 20% for extra-pulmonary samples, and the detection threshold is order of 104 AFB of pathological product.
Polymerase chain reaction (PCR) using the GeneXpert MTB/RIF method offers an early diagnosis that identifies Mycobacterium tuberculosis DNA and the main mutations that confer rifampicin resistance to the bacteria.
Cutaneous tuberculosis is a rare entity, the polymorphism of the anatomo-clinical presentation and the multiplicity of differential diagnoses make the diagnosis difficult.
The present case encourages us to think about it when faced with abscessed and recurrent skin lesions, especially in an endemic country like ours.
Sporadic cases of chronic wasting disease in old moose – an epidemiological study
Authors: Hopp Petter , Rolandsen Christer Moe , Korpenfelt Sirkka-Liisa , Våge Jørn , Sörén Kaisa , Solberg Erling Johan , Averhed Gustav , Pusenius Jyrki , Rosendal Thomas , Ericsson Göran , Bakka Haakon Christopher , Mysterud Atle , Gavier-Widén Dolores , Hautaniemi Maria , Ågren Erik , Isomursu Marja , Madslien Knut , Benestad Sylvie Lafond , Nöremark Maria
Published: January 2024

Transmissible spongiform encephalopathies or prion diseases comprise diseases with different levels of contagiousness under natural conditions. The hypothesis has been raised that the chronic wasting disease (CWD) cases detected in Nordic moose (Alces alces) may be less contagious, or not contagious between live animals under field conditions. This study aims to investigate the epidemiology of CWD cases detected in moose in Norway, Sweden and Finland using surveillance data from 2016 to 2022.

In total, 18 CWD cases were detected in Nordic moose. All moose were positive for prion (PrPres) detection in the brain, but negative in lymph nodes, all were old (mean 16 years; range 12–20) and all except one, were female. Age appeared to be a strong risk factor, and the sex difference may be explained by few males reaching high age due to hunting targeting calves, yearlings and males.

The cases were geographically scattered, distributed over 15 municipalities. However, three cases were detected in each of two areas, Selbu in Norway and Arjeplog-Arvidsjaur in Sweden. A Monte Carlo simulation approach was applied to investigate the likelihood of such clustering occurring by chance, given the assumption of a non-contagious disease. The empirical P-value for obtaining three cases in one Norwegian municipality was less than 0.05, indicating clustering. However, the moose in Selbu were affected by different CWD strains, and over a 6 year period with intensive surveillance, the apparent prevalence decreased, which would not be expected for an ongoing outbreak of CWD. Likewise, the three cases in Arjeplog-Arvidsjaur could also indicate clustering, but management practices promotes a larger proportion of old females and the detection of the first CWD case contributed to increased awareness and sampling.

The results of our study show that the CWD cases detected so far in Nordic moose have a different epidemiology compared to CWD cases reported from North America and in Norwegian reindeer (Rangifer tarandus tarandus). The results support the hypothesis that these cases are less contagious or not contagious between live animals under field conditions. To enable differentiation from other types of CWD, we support the use of sporadic CWD (sCWD) among the names already in use.
Serotonin Promotes Vesicular Association and Fusion by Modifying Lipid Bilayers
Authors: Roy Debsankar Saha , Gupta Ankur , Vishvakarma Vicky , Krupa Pawel , Li Mai Suan , Maiti Sudipta
Published: January 2024

The primary event in chemical neurotransmission involves the fusion of a membrane-limited vesicle at the plasma membrane and the subsequent release of its chemical neurotransmitter cargo. The cargo itself is not known to have any effect on the fusion event. However, amphiphilic monoamine neurotransmitters (e.g. serotonin and dopamine) are known to strongly interact with lipid bilayers and to affect their mechanical properties, which can in principle impact membrane-mediated processes. Here we probe whether serotonin can enhance the association and fusion of artificial lipid vesiclesin vitro. We employ Fluorescence Correlation Spectroscopy and Total Internal Reflection Fluorescence microscopy to measure the attachment and fusion of vesicles whose lipid compositions mimic the major lipid components of synaptic vesicles. We find that association between vesicles and supported lipid bilayers are strongly enhanced in a serotonin dose-dependent manner, and this drives an increase in the rate of spontaneous fusion. Molecular dynamics simulations and fluorescence spectroscopy data show that serotonin insertion increases the water content of the hydrophobic part of the bilayer. This suggests that the enhanced membrane association is likely driven by an energetically favourable drying transition. Other monoamines such as dopamine and norepinephrine, but not other related species such as tryptophan, show similar effects on membrane association. Our results reveal a lipid bilayer-mediated mechanism by which monoamines can themselves modulate vesicle fusion, potentially adding to the control toolbox for the tightly regulated process of neurotransmissionin vivo.

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Quantification of local matrix deposition during muscle stem cell activation using engineered hydrogels
Authors: Duran Pamela , Yang Benjamin A. , Plaster Eleanor , Eiken Madeline , Loebel Claudia , Aguilar Carlos A.
Published: January 2024

Adult stem cells occupy a niche that contributes to their function, but how stem cells remodel their microenvironment remains an open-ended question. Herein, biomaterials-based systems and metabolic labeling were utilized to evaluate how skeletal muscle stem cells deposit extracellular matrix. Muscle stem cells and committed myoblasts were observed to generate less nascent matrix than muscle resident fibro-adipogenic progenitors. When cultured on substrates that matched the stiffness of physiological uninjured and injured muscles, the increased nascent matrix deposition was associated with stem cell activation. Reducing the ability to deposit nascent matrix in muscle stem cells attenuated function and mimicked impairments observed from muscle stem cells isolated from old aged muscles, which could be rescued with therapeutic supplementation of insulin-like growth factors. These results highlight how nascent matrix production is critical for maintaining healthy stem cell function.
Multimodal CustOmics: A Unified and Interpretable Multi-Task Deep Learning Framework for Multimodal Integrative Data Analysis in Oncology
Authors: Benkirane Hakim , Vakalopoulou Maria , Planchard David , Adam Julien , Olaussen Ken , Michiels Stefan , Cournède Paul-Henry
Published: January 2024

Characterizing cancer poses a delicate challenge as it involves deciphering complex biological interactions within the tumor's microenvironment. Histology images and molecular profiling of tumors are often available in clinical trials and can be leveraged to understand these interactions. However, despite recent advances in representing multimodal data for weakly supervised tasks in the medical domain, numerous challenges persist in achieving a coherent and interpretable fusion of whole slide images and multi-omics data. Each modality operates at distinct biological levels, introducing substantial correlations both between and within data sources. In response to these challenges, we propose a deep-learning-based approach designed to represent multimodal data for precision medicine in a readily interpretable manner. Demonstrating superior performance compared to state-of-the-art methods across multiple test cases, our approach not only provides robust results but also extracts various scores, shedding light on the activity of each modality and their interactions at the pathway and gene levels. The strengths of our method lie in its capacity to unravel pathway activation through multimodal relationships and extend enrichment analysis to spatial data for supervised tasks. We showcase the efficiency and robustness of its interpretations of our method through an extensive exploration of multiple TCGA datasets and validation cohorts, underscoring its value in advancing our understanding of cancer. The method is publicly available in Github: https://github.com/HakimBenkirane/Multimodal-CustOmics