bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic Drug Monitoring of Pazopanib in Renal Cell Carcinoma and Soft Tissue Sarcoma: A Systematic Review
Authors: Turjap Miroslav , Pelcová Marta , Gregorová Jana , Šmak Pavel , Martin Hiroko , Štingl Jan , Peš Ondřej , Juřica Jan 
Published: May 2024

Background:
Pazopanib, an anti-angiogenic multitarget tyrosine kinase inhibitor, has been approved for the treatment of metastatic renal cell carcinoma and soft tissue sarcoma. However, its recommended dose does not always produce consistent outcomes, with some patients experiencing adverse effects or toxicity. This variability is due to differences in the systemic exposure to pazopanib. This review aimed to establish whether sufficient evidence exists for the routine or selective therapeutic drug monitoring of pazopanib in adult patients with approved indications.

Methods:
A systematic search of the PubMed and Web of Science databases using search terms related to pazopanib and therapeutic drug monitoring yielded 186 and 275 articles, respectively. Ten articles associated with treatment outcomes or toxicity due to drug exposure were selected for review.

Results:
The included studies were evaluated to determine the significance of the relationship between drug exposure/Ctrough and treatment outcomes and between drug exposure and toxicity. A relationship between exposure and treatment outcomes was observed in 5 studies, whereas the trend was nonsignificant in 4 studies. A relationship between exposure and toxicity was observed in 6 studies, whereas 2 studies did not find a significant relationship; significance was not reported in 3 studies.

Conclusions:
Sufficient evidence supports the therapeutic drug monitoring of pazopanib in adult patients to improve its efficacy and/or safety in the approved indications.
Optimizing the Pedicled Latissimus Dorsi Myocutaneous Flap in Breast Reconstruction: Lessons Learned from 110 Consecutive Flaps
Authors: Doan Leandra , Sam Andre-Philippe , Li Wai-Yee 
Published: May 2024

Background:
The pedicled latissimus dorsi myocutaneous flap (LDMCF) in autologous breast reconstruction has been superseded by abdominal free tissue transfer. Common complaints of the LDMCF include the asymmetric back scar, need for prosthesis, and high seroma rates. We believe that the LDMCF remains versatile, with distinct advantages over other autologous options: the flap can be harvested unilaterally or bilaterally, not ‘burning any bridges’ for future reconstruction in unilateral breast reconstruction; the recovery is relatively easy, without complications such as risk of long-term abdominal wall weakness; and the aesthetic results are comparable, if not superior, leading to a more “youthful” result.

Methods:
We performed a retrospective review over an 8-year period.

Results:
A total of 106 patients underwent 110 breast reconstructions. Complications included four of 106 patients (3.8%) with seroma, three of 78 (3.8%) with periprosthetic implant infection, and one case of partial flap loss.

Conclusions:
We learned the following: (1) Direct-to-implant can be performed in most LDMCF patients, avoiding the use of tissue expanders; (2) High BMI patients may not require an implant; (3) Back donor site aesthetics can be improved using a “bra-line-back-lift” approach; (4) Use of liposomal bupivacaine intercostal blocks and modified enhanced recovery after surgery protocol can reduce length-of-stay to overnight; (5) We achieved low seroma rates using topical fibrin glue and closed suction drains; (6) Low and high BMI patients who may not qualify for free tissue transfer are usually still surgical candidates with LDMCF; and (7) Short and long-term recovery are faster than free tissue transfer, with minimal long-term deficit.
Small fibre neuropathy frequently underlies the painful long-COVID syndrome
Authors: Falco Pietro , Litewczuk Daniel , Di Stefano Giulia , Galosi Eleonora , Leone Caterina , De Stefano Gianfranco , Di Pietro Giuseppe , Tramontana Lorenzo , Ciardi Maria Rosa , Pasculli Patrizia , Zingaropoli Maria Antonella , Arendt-Nielsen Lars , Truini Andrea 
Published: May 2024

Abstract
Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case–control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. Clinical data, quantitative sensory testing, and skin biopsies were collected from 26 selected patients with painful long-COVID syndrome. We also examined 100 individuals with past COVID-19 infection, selecting 33 patients with painless long-COVID syndrome, characterized mainly by symptoms such as brain fog and fatigue, and 30 asymptomatic post–COVID-19 controls. Demographic and clinical variables were compared among these groups. Among the 26 patients with painful long-COVID syndrome, 12 had skin biopsy and/or quantitative sensory testing abnormalities compatible with small fibre neuropathy. Demographic and clinical data did not differ across patients with small fibre neuropathy, patients with painless long-COVID syndrome, and asymptomatic post–COVID-19 controls. This case–control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post–COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.
Inferior Long-Term Results of a Randomized Controlled Trial Initially Demonstrating Enhanced Sensory Nerve Recovery Using a Chitosan Nerve Tube
Authors: Aman Martin , Preisner Fabian , Mayrhofer- Schmid Maximilian , Eisa Amr , Schwarz Daniel , Kneser Ulrich , Harhaus Leila , Boecker Arne H. 
Published: May 2024

Background:
Traumatic peripheral nerve injuries can result in significant functional impairments and long-term sequelae. This study evaluated the long-term outcomes of a chitosan tube implant to protect epineural coaptation after peripheral nerve injuries using 2 different tube versions (different wall thicknesses and resorption characteristics), compared with a control group. The study focused on pain levels, sensory function, and overall functional outcomes.

Methods:
Patients who received a tube implant around direct coaptation sites of digital nerves were randomized and compared with control patients with no additional tube protection. Pain levels, sensory function, grip force, and functional scores were assessed at time points ranging from 3 months to 5 years postoperatively. Tube biodegradation was measured using high-resolution magnetic resonance neurography and categorized.

Results:
Patients with the first tube version had higher pain levels compared with the control group after 5 years, and reported more symptoms of numbness and hypersensitivity. Patients with the second version exhibited higher pain levels at 3 months that did not persist at 6 months, but they showed compromised sensory function, with higher 2-point discrimination values compared with the first and control groups. No differences were found in grip force or functional scores between the groups. Magnetic resonance imaging displayed remnants of implants even at long-term follow-up.

Conclusions:
The findings suggest potential limitations attributable to increased pain and impaired sensory function associated with tube implantation in the long term. In the short term, however, the material seemed to have a protective effect (as published previously). The resorption process was not complete at the end of the 5-year observation period. This might explain the prolonged scarring and inferior long-term results. Future research should focus on improving tube materials and design to minimize adverse effects and enhance functional outcomes.
Brief Report: Veterans Aging Cohort Study Index 2.0 Shows Improved Discrimination of Neurocognitive Impairment and Frailty in People With HIV
Authors: Yan Cynthia Y. , Cooley Sarah A. , Ances Beau M. 
Published: May 2024

Objective:
To examine whether the revised Veterans Aging Cohort Study (VACS2.0) index [including serum albumin, body mass index, and white blood cell count] had stronger correlations with cognitive function, brain volume, and frailty in persons with HIV (PWHs) ≥50 years compared with the VACS1.0.

Design and methods:
Neuropsychological performance (NP) Z-scores (learning, retention, executive functioning, psychomotor function/processing speed, language, and global cognition), and neuroimaging measures (brain volumetrics) were analyzed in PWHs (n = 162). A subset of the sample (n = 159) was defined as either frail (n = 18) or nonfrail (n = 141) according to the Fried phenotype criteria. Brain volumes, NP scores, and frailty subgroups were analyzed with VACS scores, albumin, body mass index, and white blood cell count using Pearson significance tests and independent T tests.

Results:
Higher VACS scores significantly correlated with lower brain volumes. Higher VACS2.0 scores were associated with lower NP in the executive functioning and psychomotor function/processing speed domains and were primarily driven by albumin. VACS1.0 scores did not correlate with cognition Z-scores. There was no relationship between frailty status and VACS1.0. PWHs who were frail had significantly greater VACS2.0 scores than nonfrail PWHs.

Conclusions:
The addition of albumin to the VACS index improved its correlations with NP and frailty in PWHs. While low albumin levels may contribute to cognitive decline or frailty, the reverse causality should also be considered. These findings suggest that the VACS2.0 index (especially albumin) is a valuable measure for clinicians to improve outcomes in PWHs.
Prelaminated Nose Reconstruction: Comparison of Forehead and Radial Donor Site and Review of the Literature
Authors: Spyropoulou Georgia-Alexandra , Demiri Efterpi , Antoniades Kostantinos , Vahtsevanos Konstantinos , Triaridis Stefanos , Markou Konstantinos , Cohen Mimis 
Published: May 2024

Introduction:
Total nose reconstruction is demanding as it is a 3-dimensional structure that needs lining, support and external coverage. Usually, several stages are needed to achieve a satisfactory result. The authors present 2 cases of prelaminated radial forearm and 2 prelaminated forehead nose reconstructions and compare both methods. According to our review of the literature, this is the first report of prelaminated forehead for total nose reconstruction.

Materials and Methods:
The last 5 years the authors have treated 4 patients with prelaminated flaps for total nose reconstruction. The age ranged from 50 to 75 years. There were 3 male patients and one female. Three patients underwent total nose amputation due to squamous cell carcinoma and one due to melanoma.

Results:
Two patients were treated with prelaminated radial forearm reconstruction and 2 with prelaminated forehead reconstruction. Both patients that were treated with prelaminated radial forearm reconstruction had the collapse of the nasal pyramid and had salvage procedures with replacement of the cartilaginous framework with iliac bone graft framework.

Conclusions:
Prelaminated nose reconstruction with either the radial forearm or forehead flap needs several stages. There is the possibility of infection-collapse of the cartilage framework, therefore, the authors recommend reconstruction of the nasal skeleton with an iliac bone graft. The flaps are stiff and difficult to handle. The authors don’t think that prelaminated nose reconstruction with the radial forearm flap has advantage compared with the classic several stages nose reconstruction with radial forearm flap. Possibly, prelaminated forehead reconstruction can be applied for aged patients who cannot undergo microsurgical reconstruction.
Concurrent validity, test-retest reliability, and normative properties of the Ignite app: a cognitive assessment for frontotemporal dementia
Authors: Convery Rhian S. , Adams-Carr Kerala , Nicholas Jennifer M. , Moore Katrina M. , Goldsmith Sophie , Bocchetta Martina , Russell Lucy L. , Rohrer Jonathan D. 
Published: May 2024

AbstractDigital biomarkers can provide frequent, real-time monitoring of health-related behaviour and could play an important role in the assessment of cognition in frontotemporal dementia (FTD). However, the validity and reliability of digital biomarkers as measures of cognitive function must first be determined. The Ignite computerised cognitive app contains several iPad-based measures of executive function, social cognition, and other domains known to be affected in FTD. Here we describe the normative properties of the Ignite tests, evaluate the associations with gold-standard neuropsychology tests, and investigate test-retest reliability through two healthy controls studies. Over 2,000 cognitively normal adults aged 20-80 years (mean=55.2, standard deviation=15.8) were recruited to complete the Ignite app through a remote data collection study. Significant associations were found between age and performance on several Ignite measures of processing speed (r=0.42 to 0.56,p<0.001) and executive function (r=0.43 to 0.62,p<0.001), suggesting the tests are sensitive to cognitive decline observed in normal ageing. A separate cohort of 98 healthy controls were recruited to an observational study (mean age=51.2 years, standard deviation=17.3), completing Ignite at two timepoints (7 days apart), a gold-standard pen and paper neuropsychology battery of corresponding tests, and a user experience questionnaire (10-items). The Ignite tests demonstrated moderate to excellent test-retest reliability (ICCs=0.54 to 0.92) and significantly correlated with their pen and paper counterparts (r=0.25 to 0.72,p<0.05). The majority of participants (>90%) also rated the app favourably, stating it was enjoyable and easy to complete unsupervised. These findings suggest the Ignite tests are valid measures of cognitive processes, capture a stable picture of performance over time and are well accepted in healthy controls, speaking to the feasibility of administering the app remotely. Therefore, the results have important implications for the utility of Ignite as a cognitive endpoint in upcoming FTD clinical trials.
Single Cell Sequencing of Human Langerhans Cells Identifies Altered Gene Expression Profiles in Patients with Atopic Dermatitis
Authors: Tamminga Sara M. , van der Wal M. Marlot , Saager Elise S. , van der Gang Lian F. , Boesjes Celeste M. , Hendriks Astrid , Pannekoek Yvonne , de Bruin Marjolein S. , van Wijk Femke , van Sorge Nina M. 
Published: May 2024

AbstractAtopic dermatitis (AD) is characterized by dysregulated T cell immunity and skin microbiome dysbiosis with predominance ofStaphylococcus aureus(S. aureus). Emerging evidence suggests a role forS. aureusin exacerbating AD skin inflammation. We have previously shown that specific glycosylation ofS. aureuscell wall structures amplifies skin inflammation through interaction with Langerhans cells (LCs). However, the role of LCs in AD remains poorly characterized. Here, we performed single cell RNA-sequencing of primary epidermal LCs and dermal T cells isolated from skin biopsies of AD patients and healthy controls, alongside specific glycoanalysis ofS. aureusstrains isolated from the AD lesions. Our findings reveal four LC subpopulations, including two steady-state clusters (LC1 and LC1H) and two pro-inflammatory/matured subsets (LC2 and migratory LCs). The latter two subsets were enriched in AD skin. AD LCs showed enhanced expression of C-type lectin receptors, the high-affinity IgE receptor (FcεR1), and activation of prostaglandin and leukotrienes biosynthesis pathways, as well as upregulated transcriptional signatures related to T cell activation pathways and increased expression of CCL17 (specifically LC2) compared to healthy LCs. Correspondingly, T helper 2 and regulatory T cell populations were increased in AD lesions. Our study provides proof-of-concept for a role of LCs in connecting theS. aureus-T cell axis in the AD inflammatory cycle.
Probing intratumoral metabolic compartmentalisation in fumarate hydratase-deficient renal cancer using clinical hyperpolarised13C-MRI and mass spectrometry imaging
Authors: Horvat-Menih Ines , Casey Ruth , Denholm James , Hamm Gregory , Hulme Heather , Gallon John , Khan Alixander S , Kaggie Joshua , Gill Andrew B , Priest Andrew N , Duarte Joao A G , Yong Cissy , Brodie Cara , Whitworth James , Barry Simon T , Goodwin Richard J A , Anand Shubha , Dodd Marc , Honan Katherine , Welsh Sarah J , Warren Anne Y , Aho Tevita , Stewart Grant D , Mitchell Thomas J , McLean Mary A , Gallagher Ferdia A 
Published: May 2024

AbstractBackgroundFumarate hydratase-deficient renal cell carcinoma (FHd-RCC) is a rare and aggressive renal cancer subtype characterised by increased fumarate accumulation and upregulated lactate production. Renal tumours demonstrate significant intratumoral metabolic heterogeneity, which may contribute to treatment failure. Emerging non-invasive metabolic imaging techniques have clinical potential to more accurately phenotype tumour metabolism and its heterogeneity.MethodsHere we have used hyperpolarised13C-pyruvate MRI (HP13C-MRI) to assess13C-lactate generation in a patient with an organ-confined FHd-RCC. Post-operative tissue samples were co-registered with imaging and underwent sequencing, IHC staining, and mass spectrometry imaging (MSI).ResultsHP13C-MRI revealed two metabolically distinct tumour regions. The13C-lactate-rich region showed a high lactate/pyruvate ratio and slightly lower fumarate on MSI compared to the other tumour region, as well as increased CD8+ T cell infiltration, and genetic dedifferentiation. Compared to the normal kidney, vascularity in tumour was decreased, while immune cell fraction was markedly higher.ConclusionsThis study shows the potential of metabolic HP13C-MRI to characterise FHd-RCC and how targeting of biopsies to regions of metabolic dysregulation could be used to obtain the tumour samples of greatest clinical significance, which in turn can inform on early and successful response to treatment.
Effects of HMGCR deficiency on skeletal muscle development
Authors: Gunasekaran Mekala , Littel Hannah R. , Wells Natalya M. , Turner Johnnie , Campos Gloriana , Venigalla Sree , Estrella Elicia A. , Ghosh Partha S. , Daugherty Audrey L. , Stafki Seth A. , Kunkel Louis M. , Foley A. Reghan , Donkervoort Sandra , Bönnemann Carsten G. , Toledo-Bravo de Laguna Laura , Nascimento Andres , Benito Daniel Natera-de , Draper Isabelle , Bruels Christine C. , Pacak Christina A. , Kang Peter B. 
Published: May 2024

AbstractPathogenic variants inHMGCRwere recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern. The mechanism linking pathogenic variants inHMGCRwith skeletal muscle dysfunction is unclear. We knocked downHmgcrin mouse skeletal myoblasts, knocked downhmgcrin Drosophila, and expressed three pathogenicHMGCRvariants (c.1327C>T, p.Arg443Trp; c.1522_1524delTCT, p.Ser508del; and c.1621G>A, p.Ala541Thr) inHmgcrknockdown mouse myoblasts.Hmgcrdeficiency was associated with decreased proliferation, increased apoptosis, and impaired myotube fusion. Transcriptome sequencing ofHmgcrknockdown versus control myoblasts revealed differential expression involving mitochondrial function, with corresponding differences in cellular oxygen consumption rates. Both ubiquitous and muscle-specific knockdown ofhmgcrin Drosophila led to lethality. Overexpression of referenceHMGCRcDNA rescued myotube fusion in knockdown cells, whereas overexpression of the pathogenic variants ofHMGCRcDNA did not. These results suggest that the three HMGCR-related muscle diseases share disease mechanisms related to skeletal muscle development.
The Brain Computes Dynamic Facial Movements for Emotion Categorization Using a Third Pathway
Authors: Yan Yuening , Zhan Jiayu , Garrod Oliver G. , Chen Chaona , Ince Robin A.A. , Jack Rachael E. , Schyns Philippe G. 
Published: May 2024

AbstractRecent theories suggest a new brain pathway dedicated to processing social movement is involved in understanding emotions from biological motion, beyond the well-known ventral and dorsal pathways. However, how this social pathway functions as a network that computes dynamic biological motion signals for perceptual behavior is unchartered. Here, we used a generative model of important facial movements that participants (N = 10) categorized as “happy,” “surprise,” “fear,” “anger,” “disgust,” “sad” while we recorded their MEG brain responses. Using new representational interaction measures (between facial features, MEGtsource, and behavioral responses), we reveal per participant a functional social pathway extending from occipital cortex to superior temporal gyrus. Its MEG sources selectively represent, communicate and compose facial movements to disambiguate emotion categorization behavior, while occipital cortex swiftly filters out task-irrelevant identity-defining face shape features. Our findings revealhowsocial pathway selectively computes complex dynamic social signals to categorize emotions in individual participants.
Circulating mitochondrial bioenergetics as fingerprint of the hepatic one: how to monitor genetic MASLD
Authors: Paolini Erika , Longo Miriam , Meroni Marica , Podini Paola , Maggioni Marco , Quattrini Angelo , Fracanzani Anna Ludovica , Dongiovanni Paola 
Published: May 2024

AbstractBackground & AimsMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) pathogenesis is shaped by genetics and mitochondrial dysfunction. Recently, we demonstrated that the co-presence of patatin- like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) and membrane bound o-acyltransferase domain-containing 7 (MBOAT7) polymorphisms predisposes to disease progression in MASLD patients and that their deletion contributes to mitochondrial (mt) maladaptation in anin- vitromodel. In this work we deepened the impact of genes silencing on mitochondrial dynamism. Then we restored TM6SF2 and/or MBOAT7 wild-type (WT) proteins in thein-vitromodel to evaluate the rescue of organelles’ morphology/function. Finally, we compared hepatic and peripheral mt-bioenrgetics in MASLD patients carrying PNPLA3, MBOAT7 and/or TM6SF2 loss-of-function variations.MethodsWT proteins were overexpressed through lentiviral transfection, mt-respiration was assessed by Seahorse.ResultsThe restore of MBOAT7 and/or TM6SF2 wild-type proteins resulted in the assembly ofspaghetti- shaped mitochondria with improved OXPHOS capacity. Mitochondrial activity was assessed in liver biopsies and peripheral blood mononuclear cells of biopsy-proven (n=44;Discovery cohort) and noninvasively assessed (n=45;Fibroscan-MASLD cohort) MASLD patients stratified according to the presence of the 3 at-risk variants alongside in unrelated liver disease patients (n=45;Unrelated liver disease cohort). In the Discovery cohort, the hepatic bioenergetic profile fully reflecting the circulating one, was impaired in carriers of the risk variants, more so when in combination. We confirmed the lowered serum respirometry in the Fibroscan-MASLD cohort. Finally, the circulating respiration did not change in unrelated liver disease patients, thus demonstrating that it was specifically impaired in MASLD.ConclusionsThese results boosted the relevance of mitochondrial circulating respirometry to outline genetically-based MASLD.