bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detangling the Structural Neural Correlates Associated with Resting versus Dynamic Phantom Limb Pain Intensity Using a Voxel-based Morphometry Analysis
Authors: Pinto Camila B , Pacheco-Barrios Kevin , Saleh Velez Faddi G , Gunduz Muhammed E , Münger Marionna , Fregni Felipe 
Published: December 2022

Abstract
The management of phantom limb pain (PLP) is still challenging due to a partial understanding of its neurophysiological mechanisms. Structural neuroimaging features are potential biomarkers. However, only a few studies assessed their correlations with clinical severity and treatment response. This study aims to explore the association between brain gray matter volume (GMV) with phantom limb manifestations severity and PLP improvement after neuromodulatory treatments (transcranial direct current stimulation and mirror therapy). Voxel-based morphometry analyses and functional decoding using a reverse inference term-based meta-analytic approach were used. We included 24 lower limb traumatic amputees with moderate to severe PLP. We found that alterations of cortical GMV were correlated with PLP severity but not with other clinical manifestations. Less PLP severity was associated with larger brain clusters GMV in the non-affected prefrontal, insula (non-affected mid-anterior region), and bilateral thalamus. However, only the insula cluster survived adjustments. Moreover, the reverse inference meta-analytic approach revealed that the found insula cluster is highly functionally connected to the contralateral insula and premotor cortices, and the decoded psychological processes related to this cluster were “rating,” “sustained attention,” “impulsivity, ” and “suffering.” Moreover, we found that responders to neuromodulatory treatment have higher GMV in somatosensory areas (total volume of S1 and S2) in the affected hemisphere at baseline, compared to non-responders, even after adjustments.
Effects of providing sensory attractants to suckling pigs during lactation and after weaning on post-weaning growth performance
Authors: Wensley Madie R , Tokach Mike D , Woodworth Jason C , Goodband Robert D , DeRouchey Joel M , Gebhardt Jordan T , McKilligan Denny , Upah Nathan 
Published: December 2022

Abstract
Three experiments were conducted to determine the effect of sensory attractants pre- and post-weaning on the growth performance of pigs after weaning. For each experiment, treatments were arranged as a 2 × 2 × 2 factorial with main effects of pre-weaning application (without or with), post-weaning application (without or with), and body weight category (representing the lightest or heaviest 50% of the population). In Exp. 1, 356 nursery pigs (initially 5.7 kg) were used in a 28-d trial with enrichment cubes used as the sensory attractant. A greater percentage of heavy pigs (P = 0.007) or pigs offered enrichment cubes pre-weaning (P = 0.044) lost BW from weaning to d 3 compared to light pigs or pigs not offered enrichment cubes pre-weaning. From weaning to d 7, a greater percentage of pigs lost weight when not offered cubes post-weaning (P = 0.002) compared to pigs offered cubes post-weaning. In Exp. 2, 355 nursery pigs (initially 5.6 kg) were used in a 29-d trial with a powder used as the sensory attractant. Providing a powder attractant both pre- and post-weaning reduced the percentage of pigs that lost weight from weaning to d 3 as compared with providing a powder either pre- or post-weaning only (interaction, P &lt; 0.05). In Exp. 3, 355 nursery pigs (initially 5.9 kg) were used in a 24-d trial with a liquid spray used as the sensory attractant. A greater percentage of heavy pigs that did not receive liquid attractant lost weight from weaning to d 3, whereas a greater percentage of light pigs lost weight when they received liquid attractant only pre-weaning (three-way interaction; P = 0.016). Across all three experiments, sensory attractant application had limited effects on the growth performance of pigs after weaning; however, varying responses were observed for the percentage of pigs that lost weight in the first 3 to 7 d immediately post-weaning. In summary, environmental enrichment with cubes (Exp. 1) appears to have the greatest effect when applied post-weaning whereas flavor attractants (Exp. 2 and 3) appear to have the greatest effect when applied both pre- and post-weaning.
Periostin increased by mechanical stress upregulates interleukin‐6 expression in the ligamentum flavum
Authors: Yabu Akito , Suzuki Akinobu , Hayashi Kazunori , Hori Yusuke , Terai Hidetomi , Orita Kumi , Habibi Hasibullah , Salimi Hamidullah , Kono Hiroshi , Toyoda Hiromitsu , Maeno Takafumi , Takahashi Shinji , Tamai Koji , Ozaki Tomonori , Iwamae Masayoshi , Ohyama Shoichiro , Imai Yuuki , Nakamura Hiroaki 
Published: December 2022

AbstractLigamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long‐term mechanical stress were analyzed using RNA‐seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor‐β1, α‐smooth muscle actin, collagen type 1 alpha 1, and interleukin‐6 (IL‐6) in LF cells. Periostin blockade suppressed the mechanical stress‐induced gene expression of IL‐6 while periostin treatment increased IL‐6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL‐6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.
LDHA deficiency inhibits trophoblast proliferation via the PI3K/AKT/FOXO1/CyclinD1 signaling pathway in unexplained recurrent spontaneous abortion
Authors: Zhu Yueyue , Wu Fan , Hu Jianing , Xu Yichi , Zhang Jinwen , Li Yan , Lin Yi , Liu Xiaorui 
Published: December 2022

AbstractDysregulated trophoblast proliferation, invasion, and apoptosis may cause several pregnancy‐associated complications, such as unexplained recurrent spontaneous abortion (URSA). Recent studies have shown that metabolic abnormalities, including glycolysis inhibition, may dysregulate trophoblast function, leading to URSA. However, the underlying mechanisms remain unclear. Herein, we found that lactate dehydrogenase A (LDHA), a key enzyme in glycolysis, was significantly reduced in the placental villus of URSA patients. The human trophoblast cell line HTR‐8/SVneo was used to investigate the possible LDHA‐mediated regulation of trophoblast function. LDHA knockdown in HTR‐8/SVneo cells induced G0/G1 phase arrest and increased apoptosis, whereas LDHA overexpression reversed these effects. Next, RNA sequencing combined with Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that the PI3K/AKT signaling pathway is potentially affected by downstream genes of LDHA. Especially, we found that LDHA knockdown decreased the phosphorylation levels of PI3K, AKT, and FOXO1, resulting in a significant downregulation of CyclinD1. In addition, treatment with an AKT inhibitor or FOXO1 inhibitor also verified that the PI3K/AKT/FOXO1 signaling pathway influenced the gene expression of CyclinD1 in trophoblast. Moreover, p‐AKT expression correlated positively with LDHA expression in syncytiotrophoblasts and extravillous trophoblasts in first‐trimester villus. Collectively, this study revealed a new regulatory pathway for LDHA/PI3K/AKT/FOXO1/CyclinD1 in the trophoblast cell cycle and proliferation.
Influenza virus replication is affected by glutaredoxin1‐mediated protein deglutathionylation
Authors: Checconi Paola , Coni Cristiana , Limongi Dolores , Baldelli Sara , Ciccarone Fabio , De Angelis Marta , Mengozzi Manuela , Ghezzi Pietro , Ciriolo Maria Rosa , Nencioni Lucia , Palamara Anna Teresa 
Published: December 2022

AbstractSeveral redox modifications have been described during viral infection, including influenza virus infection, but little is known about glutathionylation and this respiratory virus. Glutathionylation is a reversible, post‐translational modification, in which protein cysteine forms transient disulfides with glutathione (GSH), catalyzed by cellular oxidoreductases and in particular by glutaredoxin (Grx). We show here that (i) influenza virus infection induces protein glutathionylation, including that of viral proteins such as hemagglutinin (HA); (ii) Grx1‐mediated deglutathionylation is important for the viral life cycle, as its inhibition, either with an inhibitor of its enzymatic activity or by siRNA, decreases viral replication. Overall these data contribute to the characterization of the complex picture of redox regulation of the influenza virus replication cycle and could help to identify new targets to control respiratory viral infection.
Xanthine oxidoreductase mediates genotoxic drug‐induced autophagy and apoptosis resistance by uric acid accumulation and TGF‐β‐activated kinase 1 (TAK1) activation
Authors: Wang Jingxiang , Hu Yanhua , Liu Penggang , Xu Xiulong 
Published: December 2022

AbstractAutophagy is a highly conserved cellular process that profoundly impacts the efficacy of genotoxic chemotherapeutic drugs. TGF‐β‐activated kinase 1 (TAK1) is a serine/threonine kinase that activates several signaling pathways involved in inducing autophagy and suppressing cell death. Xanthine oxidoreductase (XOR) is a rate‐limiting enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid and hydrogen peroxide in the purine catabolism pathway. Recent studies showed that uric acid can bind to TAK1 and prolong its activation. We hypothesized that genotoxic drugs may induce autophagy and apoptosis resistance by activating TAK1 through XOR‐generated uric acid. Here, we report that gemcitabine and 5‐fluorouracil (5‐FU), two genotoxic drugs, induced autophagy in HeLa and HT‐29 cells by activating TAK1 and its two downstream kinases, AMP‐activated kinase (AMPK) and c‐Jun terminal kinase (JNK). XOR knockdown and the XOR inhibitor allopurinol blocked gemcitabine‐induced TAK1, JNK, AMPK, and Unc51‐like kinase 1 (ULK1)S555 phosphorylation and gemcitabine‐induced autophagy. Inhibition of the ATM‐Chk pathway, which inhibits genotoxic drug‐induced uric acid production, blocked gemcitabine‐induced autophagy by inhibiting TAK1 activation. Exogenous uric acid in its salt form, monosodium urate (MSU), induced autophagy by activating TAK1 and its downstream kinases JNK and AMPK. Gene knockdown or the inhibitors of these kinases blocked gemcitabine‐ and MSU‐induced autophagy. Inhibition of autophagy by allopurinol, chloroquine, and 5Z‐7‐oxozeaenol (5Z), a TAK1‐specific inhibitor, enhanced gemcitabine‐induced apoptosis. Our study uncovers a previously unrecognized role of XOR in regulating genotoxic drug‐induced autophagy and apoptosis and has implications for designing novel therapeutic strategies for cancer treatment.
The Utility of IR-Guided Biopsy in the Treatment of Pediatric Osteomyelitis
Authors: Gajewski Christopher R. , Chen Kevin , Upfill-Brown Alexander , Silva Mauricio , Thompson Rachel M. 
Published: December 2022

Background:
Accurate and efficient diagnosis, as well as a consistent and effective treatment of acute hematogenous osteomyelitis, are paramount to ensure successful clinical outcomes. Noninvasive measures of isolating the causative pathogen from blood cultures have low sensitivity, with published rates often <50%. The use of interventional radiology (IR)-guided percutaneous biopsy has gained traction as a nonsurgical means of obtaining tissue cultures with a reported increased sensitivity of >90%. This study aims to determine the utility of IR-guided biopsy in the management of pediatric patients with acute hematogenous pediatric osteomyelitis (OM).

Methods:
An IRB-approved retrospective review was completed of children younger than 18 years admitted to a single institution for treatment of magnetic resonance imaging or culture/biopsy-proven acute hematogenous OM. Patients were excluded for the diagnosis of chronic recurrent multifocal OM, incomplete documentation, treatment initiation at an outside institution, open surgical debridement, and concomitant septic arthritis. Patients who underwent IR-guided biopsy were compared with those treated empirically without biopsy.

Results:
Fifty patients were included for analysis. Fifteen (30%) had IR-guided biopsies; 35 (70%) were treated empirically. The average age at diagnosis was 11.8 years old (SD: 4.9). Of the 15 patients who underwent IR-guided biopsy, a pathogen was identified in 12 cases (80%); 14 of these patients had concomitant blood cultures with only 1 (7%) positive result (P<0.01). Of the 11 patients with positive IR-guided biopsy results in the setting of negative blood cultures, 9 (82%) had alterations in their antibiotic regimen as a result of the biopsy. The average time from blood sample collection to definitive antibiotic initiation was nearly double that of time from IR-guided biopsy collection to definitive antibiotic initiation (70.8 vs. 36 h; P<0.01).

Conclusion:
IR-guided biopsy increased pathogen identification by 47% over blood cultures alone and decreased the time to definitive antibiotics. As such, IR-guided biopsy is an effective and safe diagnostic tool for pathogen identification and appropriate antibiotic selection. Orthopaedic surgeons are encouraged to incorporate IR-guided biopsy early in the treatment pathway for patients with acute OM without an indication for open surgical intervention.

Level of Evidence:
Level III; retrospective comparative study.
Prognostic Factors Associated With Extubation Failure in Acutely Brain-Injured Patients: A Systematic Review and Meta-Analysis*
Authors: Taran Shaurya , Angeloni Natalia , Pinto Ruxandra , Lee Shawn , McCredie Victoria A. , Schultz Marcus J. , Robba Chiara , Taccone Fabio S. , Adhikari Neill K. J. 
Published: December 2022

Objective:
Extubation failure in brain-injured patients is associated with increased morbidity. Our objective was to systematically review prognostic factors associated with extubation failure in acutely brain-injured adult patients receiving invasive ventilation in an ICU.

Data Sources:
MEDLINE, Embase, and Cochrane Central were searched from inception to January 31, 2022.

Study Selection:
Two reviewers independently screened citations and selected English-language cohort studies and randomized trials examining the association of prognostic factors with extubation failure. Studies were considered if they included greater than or equal to 80% adult patients with acute brain injury admitted to the ICU and mechanically ventilated for greater than or equal to 24 hours.

Data Extraction:
Two reviewers extracted data on population, prognostic factors, extubation outcomes, and risk of bias (using the quality in prognostic factors tool).

Data Synthesis:
In the primary analysis, adjusted odds ratios (aOR) for each prognostic factor were pooled using random-effects models. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The search identified 7,626 citations, of which 21 studies met selection criteria. Moderate-certainty evidence suggested increased risk of extubation failure with older age (aOR, 3.0 for upper vs lower tertile; 95% CI, 1.78–5.07) and longer duration of mechanical ventilation (aOR, 3.47 for upper vs lower tertile; 95% CI, 1.68–7.19). Presence of cough (aOR, 0.40; 95% CI, 0.28–0.57) and intact swallow (aOR, 0.34; 95% CI, 0.21–0.54) probably decreased risk of extubation failure (moderate certainty). Associations of other factors with extubation failure were informed by low or very low certainty evidence.

Conclusions:
Patient age, duration of mechanical ventilation, and airway reflexes were associated with extubation failure in brain-injured patients with moderate certainty. Future studies are needed to determine the optimal application of these variables in clinical practice.
Molecular mechanisms and roles of pyroptosis in acute lung injury
Authors: Wei Tianchang , Zhang Cuiping , Song Yuanlin 
Published: December 2022

Abstract
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which are characterized by excessive inflammation and accompanied by diffuse injury of alveoli, can result in severe respiratory failures. The morbidity and mortality of patients remain high because the major treatments for ALI/ARDS are mainly supportive due to the lack of effective therapies. Numerous studies have demonstrated that the aggravation of coronavirus disease 2019 (COVID-19) leads to severe pneumonia and even ARDS. Pyroptosis, a biological process identified as a type of programed cell death, is mainly triggered by inflammatory caspase activation and is directly meditated by the gasdermin protein family, as well as being associated with the secretion and release of pro-inflammatory cytokines. Clinical and experimental evidence corroborates that pyroptosis of various cells in the lung, such as immune cells and structural cells, may play an important role in the pathogenesis of “cytokine storms” in ALI/ARDS, including those induced by COVID-19. Here, with a focus on ALI/ARDS and COVID-19, we summarized the recent advances in this field and proposed the theory of an inflammatory cascade in pyroptosis to identify new targets and pave the way for new approaches to treat these diseases.
Urine excretion of C3dg and sC5b-9 coincide with proteinuria and development of preeclampsia in pregnant women with type-1 diabetes
Authors: Isaksson Gustaf L. , Nielsen Lise H. , Palarasah Yaseelan , Jensen Dorte M. , Andersen Lise L. T. , Madsen Kirsten , Bistrup Claus , Jørgensen Jan S. , Ovesen Per G. , Jensen Boye L. 
Published: December 2022

Objective:
Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition.

Methods:
Stored urine and plasma samples from pregnant women with type-1 diabetes (n = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls.

Results:
Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg (r = 0.51, P < 0.001) and C9 neoantigen (r = 0.68, P < 0.001); urine albumin correlated to C3dg (r = 0.44, P < 0.001) and C9 (r = 0.59, P < 0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia.

Conclusion:
In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury.
Time of blood pressure in target range in acute ischemic stroke
Authors: Kakaletsis Nikolaos , Ntaios George , Milionis Haralampos , Protogerou Athanasios D. , Karagiannaki Anastasia , Chouvarda Ioanna , Dourliou Vasiliki , Ladakis Ioannis , Kaiafa Georgia , Daios Stylianos , Doumas Michael , Savopoulos Christos 
Published: December 2022

Objective:
The purpose of this study was to investigate the association of blood pressure (BP) time-in-target range (TTR) derived from 24-h ambulatory BP monitoring (ABPM) during the acute phase of ischemic stroke (AIS), with the severity of stroke and its predictive value for the 3 months outcome.

Methods:
A total of 228 AIS patients (prospective multicenter follow-up study) underwent ABPM every 20 min within 48 h from stroke onset using an automated oscillometric device. Clinical and laboratory findings were recorded. Mean BP parameters, BP variability and TTR for SBP (90–140 mmHg), DBP (60–90 mmHg), and mean arterial pressure (MAP) were calculated. Endpoints were death and disability/death at 3 months.

Results:
A total of 14 942 BP measurements were recorded (∼66 per AIS patient) within 72 h of stroke onset. Patient's 24-h TTR was 34.7 ± 29.9, 64.3 ± 24.2, and 55.3 ± 29.4% for SBP, DBP and MAP, respectively. In patients without prior hypertension, TTR was lower as stroke severity increased for both DBP (P = 0.031) and MAP (P = 0.016). In 175 patients without prior disability, increase in TTR of DBP and MAP associated significantly with a decreased risk of disability/death (hazard ratio 0.96, 95% CI 0.95–0.99, P = 0.007 and hazard ratio 0.97, 95% CI 0.96–0.99, P = 0.007). TTR of SBP in 130–180 mmHg and 110–160 mmHg ranges seems to be related with mortality and disability outcomes, respectively.

Conclusion:
TTR can be included for a more detailed description of BP course, according to stroke severity, and for the evaluation of BP predictive role, in addition to mean BP values, derived from ABPM during the acute phase of AIS.

Clinical Trial Registration-URL:

http://www.clinicaltrials.gov. Unique identifier: NCT01915862.
Unmasking left ventricular systolic dysfunction in masked hypertension: looking at myocardial strain. A review and meta-analysis
Authors: Cuspidi Cesare , Gherbesi Elisa , Faggiano Andrea , Sala Carla , Grassi Guido , Tadic Marijana 
Published: December 2022

Background and Aim:
A growing body of evidence supports the view that masked hypertension (MH) (i.e. normal office and elevated out-of-office BP) is a blood pressure (BP) phenotype associated with increased risk of subclinical organ damage, cardiovascular disease and death as compared to true normotension. Whether left ventricular (LV) systolic function is impaired in individuals with MH is still a poorly defined topic. Therefore, we aimed to provide a new piece of information on LV systolic dysfunction in the untreated MH setting, focusing on speckle tracking echocardiography (STE) studies investigating LV global longitudinal strain (GLS), a more sensitive index of systolic function than conventional LV ejection fraction (LVEF).

Methods:
A computerized search was performed using Pub-Med, OVID, EMBASE and Cochrane library databases from inception until June 30, 2022. Full articles reporting data on LV GLS in MH, as assessed by ambulatory BP monitoring (ABPM), and normotensive controls were considered suitable for the purposes of review and meta-analysis.

Results:
A total of 329 untreated individuals with MH and 376 normotensive controls were included in six studies. While pooled average LVEF was not different between groups [64.5 ± 1.5 and 64.5 ± 1.3%, respectively, standard means difference (SMD): −0.002 ± 0.08, confidence interval (CI): 0.15/−0.15, P = 0.98), LV GLS was worse in MH patients than in normotensive counterparts (−18.5 ± 0.70 vs. −20.0 ± 0.34%, SMD: 0.68 ± 0.28, CI: 0.12/1.24, P < 0.01).

Conclusions:
Our findings suggest that early changes in LV systolic function not detectable by conventional echocardiography in the MH setting can be unmasked by STE and that its implementation of STE in current practice may improve the detection of subclinical organ damage of adverse prognostic significance.