bluuebunny/crossref_metadata_2025 huggingface dataset:
Induced pluripotent stem cells derived from patients carrying mitochondrial mutations exhibit altered bioenergetics and aberrant differentiation potential
Authors: Meshrkey Fibi , Scheulin Kelly M. , Littlejohn Christopher M. , Stabach Joshua , Saikia Bibhuti , Thorat Vedant , Huang Yimin , LaFramboise Thomas , Lesnefsky Edward J. , Rao Raj R. , West Franklin D. , Iyer Shilpa
Published: November 2023

Background

Human mitochondrial DNA mutations are associated with common to rare mitochondrial disorders, which are multisystemic with complex clinical pathologies. The pathologies of these diseases are poorly understood and have no FDA-approved treatments leading to symptom management. Leigh syndrome (LS) is a pediatric mitochondrial disorder that affects the central nervous system during early development and causes death in infancy. Since there are no adequate models for understanding the rapid fatality associated with LS, human-induced pluripotent stem cell (hiPSC) technology has been recognized as a useful approach to generate patient-specific stem cells for disease modeling and understanding the origins of the phenotype.

Methods

hiPSCs were generated from control BJ and four disease fibroblast lines using a cocktail of non-modified reprogramming and immune evasion mRNAs and microRNAs. Expression of hiPSC-associated intracellular and cell surface markers was identified by immunofluorescence and flow cytometry. Karyotyping of hiPSCs was performed with cytogenetic analysis. Sanger and next-generation sequencing were used to detect and quantify the mutation in all hiPSCs. The mitochondrial respiration ability and glycolytic function were measured by the Seahorse Bioscience XFe96 extracellular flux analyzer.

Results

Reprogrammed hiPSCs expressed pluripotent stem cell markers including transcription factors POU5F1, NANOG and SOX2 and cell surface markers SSEA4, TRA-1-60 and TRA-1-81 at the protein level. Sanger sequencing analysis confirmed the presence of mutations in all reprogrammed hiPSCs. Next-generation sequencing demonstrated the variable presence of mutant mtDNA in reprogrammed hiPSCs. Cytogenetic analyses confirmed the presence of normal karyotype in all reprogrammed hiPSCs. Patient-derived hiPSCs demonstrated decreased maximal mitochondrial respiration, while mitochondrial ATP production was not significantly different between the control and disease hiPSCs. In line with low maximal respiration, the spare respiratory capacity was lower in all the disease hiPSCs. The hiPSCs also demonstrated neural and cardiac differentiation potential.

Conclusion

Overall, the hiPSCs exhibited variable mitochondrial dysfunction that may alter their differentiation potential and provide key insights into clinically relevant developmental perturbations.
Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes
Authors: Liu Mengyao , Ng Martin , Phu Tuan , Bouchareychas Laura , Feeley Brian T. , Kim Hubert T. , Raffai Robert L. , Liu Xuhui
Published: November 2023

Background

Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown.

Methods

We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration.

Results

Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle.

Conclusion

Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.
Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy
Authors: Lambert Matthias R. , Gussoni Emanuela
Published: November 2023

The tropomyosin genes (TPM1-4) contribute to the functional diversity of skeletal muscle fibers. Since its discovery in 1988, the TPM3 gene has been recognized as an indispensable regulator of muscle contraction in slow muscle fibers. Recent advances suggest that TPM3 isoforms hold more extensive functions during skeletal muscle development and in postnatal muscle. Additionally, mutations in the TPM3 gene have been associated with the features of congenital myopathies. The use of different in vitro and in vivo model systems has leveraged the discovery of several disease mechanisms associated with TPM3-related myopathy. Yet, the precise mechanisms by which TPM3 mutations lead to muscle dysfunction remain unclear. This review consolidates over three decades of research about the role of TPM3 in skeletal muscle. Overall, the progress made has led to a better understanding of the phenotypic spectrum in patients affected by mutations in this gene. The comprehensive body of work generated over these decades has also laid robust groundwork for capturing the multiple functions this protein plays in muscle fibers.
Prediction of pulmonary aspergillosis in patients with ventilator-associated pneumonia
Authors: Massart Nicolas , Plainfosse Emma , Benameur Yanis , Dupin Clarisse , Legall Florence , Cady Anne , Gourmelin Frederic , Legay François , Barbarot Nicolas , Magalhaes Eric , Fillatre Pierre , Frerou Aurélien , Reizine Florian
Published: November 2023

Background

Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP.

Methods

Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort.

Results

Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort.

Conclusions

We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings.
The influence of assistive technology and home modifications on falls in community-dwelling older adults: a systematic review protocol
Authors: Crosby Kathryn M. , Rodriguez Catarina A. , Canas Matthew A. , Kim Changki , Noroozi Shamim , Vis-Dunbar Mathew , Komisar Vicki , Sakakibara Brodie M. , Jakobi Jennifer M.
Published: November 2023

Background

Fall-related injuries can reduce older adults’ independence and result in economic burdens. The assistive technologies and home modifications explored in this review are suggested to reduce the risk of falls of community-dwelling older people. However, the location of the in-home assistive technology being used, and the in-home modification likely interact and influence fall reduction and injury prevention of community-dwelling older adults. This interactive effect is poorly understood. A better understanding of the impact of assistive technologies and modifications in the homes of older adults is needed to support the appropriate application of these devices.

Objective

The objective of this systematic review is to detail the contribution of assistive technology and home modification on falls, fall frequency, fall severity, and fall location within the homes of community-dwelling older adults.

Methods

We will source articles from 3 databases (MEDLINE, CINAHL, Web of Science Core Collection) and will assess them using a set of pre-defined inclusion and exclusion criteria. Reporting will be in accordance with PRISMA 2020. Two independent reviewers will screen each study at the title and abstract and full-text level. We are managing citations within the Covidence software. Data extraction and analysis will be reported in a systematic review.

Discussion

The outcome variables of interest are fall frequency, fall location, injury, mortality, and hospitalization. These variables of interest all relate to falls, their severity, and their locations in the home. We are seeking a better understanding of how these outcomes vary with the use of different assistive technologies and home modifications as reported in the literature. This will help us understand where falls occur which may inform how different assistive technologies can be used by community-dwelling older adults to prevent falls and adverse outcomes in different areas of their homes. Our review will provide a basis for more intentional prescription of ambulatory assistive technologies and evidence-based recommendations of home modifications. It may also inform adaptations to existing technologies to foster safer mobility in the homes of community-dwelling older adults.

Systematic review registration

This protocol has been submitted for registration in PROSPERO CRD42022370172 on October 24, 2022.
Effectiveness of single-session therapy for adult common mental disorders: a systematic review
Authors: Kim Jongtae , Ryu Namgil , Chibanda Dixon
Published: November 2023

Background

Common mental disorders (CMDs) impose significant socioeconomic impacts on the global community. Nevertheless, over 50% of individuals with CMDs do not receive proper treatment, indicating that the current treatment modalities do not adequately tackle this issue. Since single-session therapy (SST) is a potential method for reducing the treatment gap, it is crucial to evaluate its effectiveness. Therefore, this systematic review aimed to evaluate the effectiveness of SST on CMD symptoms in adults.

Methods

This systematic review included randomised and non-randomised studies assessing the clinical effectiveness of SST on CMD symptoms in adults. English-written, peer-reviewed studies or dissertations were included, while grey literature was excluded. MEDLINE, Embase, PsycINFO, and Cochrane’s CENTRAL were searched on December 13, 2022, from their inception dates. The risk of bias in the included studies was evaluated using RoB 2 and ROBINS-I. A narrative synthesis was performed. This systematic review was registered in the PROSPERO database on July 6, 2022 (CRD42022343925).

Results

Six randomised and three non-randomised studies were included after screening 2,130 records. Three non-randomised studies with a “critical” or “serious” risk of bias were excluded from the synthesis. Therefore, six randomised trials involving 298 participants were included in the synthesis. Four out of six studies had a “high” risk of bias. The participants had non-severe symptoms at baseline, and three intervention types (behavioural activation, DBT, and solution-focused psychotherapy) were evaluated. Five of six studies showed positive results for depression, with only one reporting a positive result for anxiety.

Conclusions

SST may be effective in improving CMD symptoms in adults, particularly depression. However, there is a limit to deriving definite conclusions due to a high risk of bias in included studies, insufficient sample size and research volume. Further research exploring the characteristics of clients who can benefit from SST is required to facilitate its widespread use.
EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma
Authors: Martija Antoni Andreu , Krauß Alexandra , Bächle Natalie , Doth Laura , Christians Arne , Krunic Damir , Schneider Martin , Helm Dominic , Will Rainer , Hartmann Christian , Herold-Mende Christel , von Deimling Andreas , Pusch Stefan
Published: November 2023

Epithelial membrane protein 3 (EMP3) is an N-glycosylated tetraspanin with a putative trafficking function. It is highly expressed in isocitrate dehydrogenase-wild-type glioblastoma (IDH-wt GBM), and its high expression correlates with poor survival. However, the exact trafficking role of EMP3 and how it promotes oncogenic signaling in GBM remain unclear. Here, we show that EMP3 promotes EGFR/CDK2 signaling by regulating the trafficking and enhancing the stability of EGFR. BioID2-based proximity labeling revealed that EMP3 interacts with endocytic proteins involved in the vesicular transport of EGFR. EMP3 knockout (KO) enhances epidermal growth factor (EGF)-induced shuttling of EGFR into RAB7 + late endosomes, thereby promoting EGFR degradation. Increased EGFR degradation is rescued by the RAB7 negative regulator and novel EMP3 interactor TBC1D5. Phosphoproteomic and transcriptomic analyses further showed that EMP3 KO converges into the inhibition of the cyclin-dependent kinase CDK2 and the repression of EGFR-dependent and cell cycle transcriptional programs. Phenotypically, EMP3 KO cells exhibit reduced proliferation rates, blunted mitogenic response to EGF, and increased sensitivity to the pan-kinase inhibitor staurosporine and the EGFR inhibitor osimertinib. Furthermore, EGFR-dependent patient-derived glioblastoma stem cells display a transcriptomic signature consistent with reduced CDK2 activity, as well as increased susceptibility to CDK2 inhibition upon EMP3 knockdown. Lastly, using TCGA data, we showed that GBM tumors with high EMP3 expression have increased total and phosphorylated EGFR levels. Collectively, our findings demonstrate a novel EMP3-dependent mechanism by which EGFR/CDK2 activity is sustained in GBM. Consequently, EMP3’s stabilizing effect provides an additional layer of tumor cell resistance against targeted kinase inhibition.
Changes in tibial cortical dimensions and density associated with long‐term locking plate fixation in goats
Authors: Bowers Kristin M. , Terrones Lori D. , Sun Xiaocun , Rifkin Rebecca , Croy Elizabeth , Adair Henry S. , Mulon Pierre‐Yves , Hecht Silke , Anderson David E.
Published: November 2023

Purpose

Cortical porosis, secondary to either vascular injury or stress‐shielding, is a comorbidity of fracture fixation using compression bone plating. Locking plate constructs have unique mechanics of load transmission and lack of reliance on contact pressures for fixation stability, so secondary cortical porosis adjacent to the plate has not been widely investigated. Therefore, this study aimed to assess the effects of long‐term locking plate fixation on cortical dimensions and density in a caprine tibial segmental ostectomy model.

Methods

Data was acquired from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over periods of 3, 6, 9, and 12 months. Quantitative data included tibial cortical width measurements and three‐dimensionally reconstructed slab density measurements, both assessed using computed tomographic examinations performed at the time of plate removal. Additional surgical and demographic variables were analyzed for effect on cortical widths and density, and all cis‐cortex measurements were compared to both the trans‐cortex and to the contralateral limbs.

Results

The tibial cis‐cortex was significantly wider and more irregular than the trans‐cortex at the same level. This width asymmetry differed in both magnitude and direction from the contralateral limb. The bone underlying the plate was significantly less dense than the trans‐cortex, and this cortical density difference was significantly greater than that of the contralateral limb. These cortical changes were independent of both duration of fixation and degree of ostectomy bone healing.

Conclusions

This study provides evidence that cortical bone loss consistent with cortical porosity is a comorbidity of locking plate fixation in a caprine tibial ostectomy model. Further research is necessary to identify risk factors for locking‐plate‐associated bone loss and to inform clinical decisions in cases necessitating long‐term locking plate fixation.
Pharmaceutical compounding and storage of faricimab in a syringe for intravitreal injection do not impair stability and bi-specific binding properties
Authors: Jørstad Øystein Kalsnes , Foss Stian , Gjølberg Torleif Tollefsrud , Mester Simone , Nyquist-Andersen Mari , Sivertsen Magne Sand , Fossum Dag , Gleditsch Espen , Moe Morten Carstens , Andersen Jan Terje
Published: November 2023

Background

Intravitreal injection (IVI) of antibody biologics is a key treatment approach in ophthalmology. Pharmaceutical compounding and storage of prefilled syringes for IVI must take place without impairing the structure and function of the biologics. This study investigated the effect of withdrawing and storing the therapeutic antibody faricimab (Vabysmo, Roche, Basel, Switzerland) in the Zero Residual silicone oil-free, 0.2-mL syringe (SJJ Solutions, The Hague, the Netherlands).

Methods

To assess the effect of syringe withdrawal on faricimab, we compared samples from syringes prepared at day 0 with samples taken directly from faricimab vials. To assess the effect of syringe storage on faricimab, we kept prefilled syringes in the dark at 4 oC for 7, 14, or 37 days and compared samples from these syringes with day 0. We measured protein concentration (with spectrophotometry), stability and integrity (with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size-exclusion chromatography (SEC), and melting temperature (Tm)), as well as binding of faricimab to its cognate antigens: vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2) (with enzyme-linked immunosorbent assay (ELISA)).

Results

Faricimab migrated in line with its expected molecular mass under both reducing and non-reducing conditions for all time points when analyzed with SDS-PAGE, without any sign of degradation products or aggregation. The SEC elution profiles were identical for all time points. There were slight variations in Tm for different time points compared to day 0 but without consistent relationship with storage time. ELISA did not detect differences in VEGF-A or Ang-2 binding between time points, and faricimab did not bind the neonatal Fc receptor.

Conclusions

Withdrawal and storage of faricimab in syringes for up to day 37 did not impair the structure and bi-specific binding properties of the therapeutic antibody.
Bilateral multiple stroke, left upper extremity ischemia, and transient complete atrioventricular block in transcatheter aortic valve implantation: a case report
Authors: Mitsuta Yuki , Nakamura Shingo , Uemura Yumiko , Tashima Koichiro , Oyoshi Takafumi , Hirata Naoyuki
Published: November 2023

Background

Transcatheter aortic valve implantation (TAVI) is a minimally invasive surgery. However, there is a risk of surgical manipulation causing detachment of a lesion of the aortic valve, which can result in various embolisms.

Case presentation

An 87-year-old woman with symptomatic severe aortic valve stenosis was scheduled for transfemoral TAVI under monitored anesthesia. Preoperative examination revealed severe calcification of the aortic valve, but there was no calcification in the ascending aorta. After a delivery catheter system passed the aortic valve, left radial arterial pressure dropped significantly, and complete atrioventricular block (CAVB) occurred. Catecholamine administration and ventricular pacing improved hemodynamics, and a self-expandable valve was implanted. CAVB resolved after surgery, but her state of consciousness was poor, and her left hand became ischemic. Imaging studies revealed multiple embolic infarcts in her bilateral cerebrum and cerebellum.

Conclusions

It should be noted that there is a risk of detachment of a calcified lesion of the aortic valve during TAVI, which can cause embolisms not only in the brain but also in the extremities and coronary arteries.
The mediating role of FoMO and the moderating role of narcissism in the impact of social exclusion on compulsive buying: a cross-cultural study
Authors: Mert Merve , Tengilimoğlu Dilaver
Published: November 2023

Background

There is an interrelationship between the concepts of social exclusion, compulsive buying behavior, fear of missing out (FoMO), and narcissism. Nevertheless, the extent to which these concepts mediate or moderate their relationships with each other has not been efficiently investigated.

Objective

This research aims to investigate how FoMO mediates and narcissism moderates the correlation between social exclusion and compulsive buying behavior. In addition, the research aims to test a conceptual model and highlight the differences that may occur in the conceptual model proposed in two different countries.

Methods

This model was analyzed among 1007 university students (Turkey = 506, Denmark = 501). The study used scales to measure social exclusion, compulsive buying behavior, FoMO, and narcissism. The study employed PROCESS Model 4 to analyze direct and indirect (mediation) effects and PROCESS Model 59 to assess conditional (moderation) effects. Furthermore, the Johnson-Neyman technique was utilized to investigate interaction terms.

Results

The findings indicate that those who face social exclusion tend to participate more in compulsive buying, and this connection is partly explained by FoMO. This suggests that individuals who encounter social exclusion may have an increased likelihood of experiencing FoMO, which may subsequently contribute to compulsive buying behavior. Furthermore, the moderating effect of narcissism differed between the Turkey and Danish samples. Specifically, in the Turkey sample, narcissism only modified the connection between social exclusion and FoMO, while in the Danish sample, it impacted both the connection between social exclusion and FoMO and the connection between FoMO and compulsive buying.

Conclusion

The obtained results show that the regulating role of narcissism is different in Turkey and Denmark within the conceptual model we studied.
Thermal ablation with configurable shapes: a comprehensive, automated model for bespoke tumor treatment
Authors: Paolucci Iwan , Bulatović Milica , Weber Stefan , Tinguely Pascale
Published: November 2023

Background

Malignant tumors routinely present with irregular shapes and complex configurations. The lack of customization to individual tumor shapes and standardization of procedures limits the success and application of thermal ablation.

Methods

We introduced an automated treatment model consisting of (i) trajectory and ablation profile planning, (ii) ablation probe insertion, (iii) dynamic energy delivery (including robotically driven control of the energy source power and location over time, according to a treatment plan bespoke to the tumor shape), and (iv) quantitative ablation margin verification. We used a microwave ablation system and a liver phantom (acrylamide polymer with a thermochromic ink) to mimic coagulation and measure the ablation volume. We estimated the ablation width as a function of power and velocity following a probabilistic model. Four representative shapes of liver tumors < 5 cm were selected from two publicly available databases. The ablated specimens were cut along the ablation probe axis and photographed. The shape of the ablated volume was extracted using a color-based segmentation method.

Results

The uncertainty (standard deviation) of the ablation width increased with increasing power by ± 0.03 mm (95% credible interval [0.02, 0.043]) per watt increase in power and by ± 0.85 mm (95% credible interval [0, 2.5]) per mm/s increase in velocity. Continuous ablation along a straight-line trajectory resulted in elongated rotationally symmetric ablation shapes. Simultaneous regulation of the power and/or translation velocity allowed to modulate the ablation width at specific locations.

Conclusions

This study offers the proof-of-principle of the dynamic energy delivery system using ablation shapes from clinical cases of malignant liver tumors.

Relevance statement

The proposed automated treatment model could favor the customization and standardization of thermal ablation for complex tumor shapes.

Key points

• Current thermal ablation systems are limited to ellipsoidal or spherical shapes.

• Dynamic energy delivery produces elongated rotationally symmetric ablation shapes with varying widths.

• For complex tumor shapes, multiple customized ablation shapes could be combined.

Graphical Abstract
Deep learning performance for detection and classification of microcalcifications on mammography
Authors: Pesapane Filippo , Trentin Chiara , Ferrari Federica , Signorelli Giulia , Tantrige Priyan , Montesano Marta , Cicala Crispino , Virgoli Roberto , D’Acquisto Silvia , Nicosia Luca , Origgi Daniela , Cassano Enrico
Published: November 2023

Background

Breast cancer screening through mammography is crucial for early detection, yet the demand for mammography services surpasses the capacity of radiologists. Artificial intelligence (AI) can assist in evaluating microcalcifications on mammography. We developed and tested an AI model for localizing and characterizing microcalcifications.

Methods

Three expert radiologists annotated a dataset of mammograms using histology-based ground truth. The dataset was partitioned for training, validation, and testing. Three neural networks (AlexNet, ResNet18, and ResNet34) were trained and evaluated using specific metrics including receiver operating characteristics area under the curve (AUC), sensitivity, and specificity. The reported metrics were computed on the test set (10% of the whole dataset).

Results

The dataset included 1,000 patients aged 21–73 years and 1,986 mammograms (180 density A, 220 density B, 380 density C, and 220 density D), with 389 malignant and 611 benign groups of microcalcifications. AlexNet achieved the best performance with 0.98 sensitivity, 0.89 specificity of, and 0.98 AUC for microcalcifications detection and 0.85 sensitivity, 0.89 specificity, and 0.94 AUC of for microcalcifications classification. For microcalcifications detection, ResNet18 and ResNet34 achieved 0.96 and 0.97 sensitivity, 0.91 and 0.90 specificity and 0.98 and 0.98 AUC, retrospectively. For microcalcifications classification, ResNet18 and ResNet34 exhibited 0.75 and 0.84 sensitivity, 0.85 and 0.84 specificity, and 0.88 and 0.92 AUC, respectively.

Conclusions

The developed AI models accurately detect and characterize microcalcifications on mammography.

Relevance statement

AI-based systems have the potential to assist radiologists in interpreting microcalcifications on mammograms. The study highlights the importance of developing reliable deep learning models possibly applied to breast cancer screening.

Key points

• A novel AI tool was developed and tested to aid radiologists in the interpretation of mammography by accurately detecting and characterizing microcalcifications.

• Three neural networks (AlexNet, ResNet18, and ResNet34) were trained, validated, and tested using an annotated dataset of 1,000 patients and 1,986 mammograms.

• The AI tool demonstrated high accuracy in detecting/localizing and characterizing microcalcifications on mammography, highlighting the potential of AI-based systems to assist radiologists in the interpretation of mammograms.

Graphical Abstract
Rare cause of bilateral basal ganglia calcifications: hemispheric AVM
Authors: Gozgec Elif , Ogul Hayri
Published: November 2023

Background

Intracranial calcifications may occur physiologically or pathologically for many reasons. In arteriovenous malformations (AVMs), calcification is not uncommon and is usually detected in the lesion vessel walls and surrounding parenchyma. However, rarely calcifications can also be seen in bilateral basal ganglia and especially in watershed areas, which are far from the lesion.

Case presentation

In this article, we present a 47-year-old case of hemispheric AVM accompanied by bilateral basal ganglia calcification.

Conclusions

Since the direct diagnosis of AVM in non-contrast brain-computed tomography (CT) is difficult, the detection of calcification in these regions requires the presence of AVM in the differential diagnosis.
Apolipoprotein D concentration in Parkinson’s disease patients
Authors: Shaheen Hala A. , Sobhy Sayed , El Mously Sherine , Eid Mohammed Mansour Abbas , Omirah Marwa Hanafy Abo , Abbas Asmaa , Gomaa Mohammed
Published: November 2023

Background

Parkinson’s disease (PD) is distinguished recently by an increase in inflammation and oxidative stress. Apolipoprotein D (Apo D) is a neuroprotective protein that was discovered to be increased in PD-affected brains. The aim of our study was to measure the ApoD serum level in individuals with PD and to correlate it with the clinical data of those individuals. Thirty individuals suffering from idiopathic PD were subjected to neurological examination, disease intensity by applying the Unified Parkinson’s Disease Rating Scale (UPDRS) and measurement of Apo D blood levels. Thirty age and sex matched controls were included for comparison of Apo D concentration.

Results

Apolipoprotein D levels were substantially greater in PD individuals than in controls. The correlation between Apo D serum level and PD severity determined by the UPDRS and its subscales was positive.

Conclusion

PD patients had increased blood level concentration of Apo D, which was associated positively with disease intensity. We suggest that Apo D serum level can be used as a predictor factor for PD severity. More studies are warranted to study how to target the Apo D in PD patients and thus helping to reduce the oxidative stress and inflammatory cascade involved in the pathogenesis of the disease.
Effect of hydroxyurea on SP1, LIN28B, IGF2BP3, COL4A5, BCL2, gamma globin genes expression: an in vitro study
Authors: Fashami Akram Agha-Amini , Alemzadeh Esmat , Safarpour Hossein , Miri-Moghaddam Ebrahim
Published: November 2023

Background

In some β-thalassemia intermedia patients, hydroxyurea (HU) increases hemoglobin and HbF levels. However, HUs’ effects molecular mechanism is still unclear.

Methods

In this study, a weighted gene co-expression network analysis was conducted on the GSE109186 dataset. The genes LIN28A, COL4A5, SP1, BCL2, and IGF2BP3 were identified as hub genes involved in the γ-gene switching process. The effect of HU treatment at doses of 50, 100, and 150 μM for 12, 24, and 48 h on the K562 cell line was examined by using qRT-PCR to measure the expression levels of these hub genes.

Results

SP1 gene expression decreased after treatment with 50, 100, and 150 μM HU for 12, 24, and 48 h. The expression of the LIN28A gene was tripled at three concentrations of 50, 100, and 150 μM for 12 h. The IGF2BP3 gene expression was doubled after 24 and 48 h at a concentration of 150 μM HU. Regarding COL4A5 gene expression, except at 12 h after treatment at a concentration of 50 μM, a significant increase was observed in other concentrations and times. The BCL2 gene expression pattern at all concentrations decreased significantly after 12 h. The γ gene showed a significant increase compared to the control group after 24 and 48 h at the different concentrations.

Conclusion

The results showed that in HU-treated cells, changes in the expression of LIN28A, COL4A5, SP1, and IGF2BP3 genes were accompanied by an increase in γ-gene expression. By elucidating precisely the mechanism of γ-to-β gene switching, we can hope for less complicated drugs.
A rare presentation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) as acute hemorrhagic longitudinally extensive transverse myelitis
Authors: Nerlekar Aniket , Malvadkar Sharad , Patil Dhairyasheel , Bhoir Bhagyashree , Shaikh Neha , Sambare Jagdish
Published: November 2023

Background

Myelin oligodendrocyte glycoprotein antibody-associated disease is usually associated with optic neuritis, acute disseminated encephalomyelitis or transverse myelitis. We are presenting a rare case report wherein myelin oligodendrocyte glycoprotein antibody seropositivity was associated with hemorrhagic longitudinally extensive transverse myelitis. To our knowledge, no such cases were found to be published.

Case presentation

A 15-year-old female came with complaints of sudden onset paraparesis. MRI was performed within 48 h from the episode of paraparesis, which revealed a long-segment, intramedullary, expansile and heterogeneously enhancing spinal cord lesion extending from T1 vertebral level up to conus medullaris. Few foci of blooming were also noted within the spinal cord on gradient sequences. Laboratory evaluation of cerebrospinal fluid analysis revealed no significant abnormality. Neuromyelitis optica antibodies were negative, and myelin oligodendrocyte glycoprotein antibodies (MOG) showed seropositivity. The patient was started on methylprednisolone and plasmapheresis for the same after which the patient gradually improved and regained her ability to walk. Follow-up MRI was performed after 4 weeks, which revealed significant reduction in the extent of the intramedullary lesion described earlier.

Conclusions

Hemorrhagic longitudinally extensive transverse myelitis without any involvement of optic nerves and brain may show MOG seropositivity, and it should be considered as one of the differential diagnosis in acute myelopathy.
Process development and quality attributes for the freeze-drying process in pharmaceuticals, biopharmaceuticals and nanomedicine delivery: a state-of-the-art review
Authors: Pardeshi Sagar R. , Deshmukh Nilesh S. , Telange Darshan R. , Nangare Sopan N. , Sonar Yogesh Y. , Lakade Sameer H. , Harde Minal T. , Pardeshi Chandrakantsing V. , Gholap Amol , Deshmukh Prashant K. , More Mahesh P.
Published: November 2023

Background

Process intensification is a major hurdle in pharmaceutical process scale-up. Solvent removal strategies have limited the effectiveness of the overall stability of pharmaceutical formulations. The main aim of present review article is to focus on the use of the freeze-drying process in pharmaceuticals, biopharmaceuticals and nanoderived therapeutics and their translation into commercial viable products. Unwavering efforts of scientists in the process intensification of lyophilization promote unique features of products for commercialization. Regulatory agencies are promoting the utilization of a quality-by-design approach to improve product characteristics. Among 300 FDA-approved pharmaceutical industries, 50% of products are freeze-dried. The freeze-drying process is costlier and requires more time than other drying methodologies. Unstable pharmaceutical dispersions and solutions can be preferably stabilized by using the freeze-drying method.

Main text

This review highlights the utilization of critical quality attributes and process parameters for the freeze-drying process, which helps to improve the integrity and stability of the formulation. The quality-by-design approach possibly cuts the cost of the process and saves money, time, and laborious work. The present review focuses preliminarily on the applications of freeze-drying in the development of biopharmaceuticals, including vaccines, proteins and peptides, and injectable products. In addition, a separate section demonstrating the potential of freeze-drying in nanoderived therapeutics has been illustrated briefly. The present clinical scenario of freeze-dried pharmaceuticals and biopharmaceuticals has also been described in later sections of the review.

Conclusions

This review underscores the value of integrating Quality by Design into the development of lyophilization processes for pharmaceutical and biopharmaceutical products. By identifying critical process parameters, delineating a design space, and leveraging advanced monitoring techniques, manufacturers can effectively address the intricacies of lyophilization. This approach empowers them to produce stable, superior quality products with confidence and consistency.

Graphical abstract
Vestibular evoked myogenic potentials and videonystagmography findings in type 2 diabetes mellitus patients with and without polyneuropathy
Authors: Koura Rabab Ahmed , El-Badry Mohamed Mohamed , Othman Asmaa Mohamed , Anwar Rehab Hassan El , Elsharkawy Sara Ahmed Mahmoud , Basiouny Iman Mostafa
Published: November 2023

Background

Vestibular impairment is a common pathology in patients with type 2 diabetes mellitus (DM) due to ischemia of the vestibular end organs and lysis of the myelin of the vestibular nerve. We aimed to evaluate function of the vestibular end organs and vestibular nerve in patients with type 2 DM with polyneuropathy and compare results to those of the patients without polyneuropathy.

Method

The participants consisted of three groups: thirty patients with type 2 diabetes mellitus without polyneuropathy (DM), thirty patients with type 2 diabetes mellitus with polyneuropathy (DPN), and thirty healthy non-diabetic individuals as the control group. Clinical examination, videonystagmography, cervical vestibular evoked myogenic potential(cVEMP), ocular vestibular evoked myogenic potential (oVEMP), Gans Sensory Organization Performance (SOP) test, and nerve conduction study were all performed on all groups.

Results

P1 and N1 cVEMP latencies and n1 and p1 oVEMP latencies were statistically significantly delayed in both the DM and DPN groups than the control. Also, amplitudes of P1-N1 and n1-p1 were statistically significantly lower in the DM and DPN groups than the control group. DPN patients had longer latencies and lower amplitude of the cVEMP and oVEMP response compared to diabetes patients without neuropathy. There was a statistically significant prevalence of BPPV in the DPN group compared to the control and DM groups. DPN included the following: 4 (13.3%) had vestibular pattern, 12 had polyneuropathic pattern, and 5 (16.7%) had vestibular and polyneuropathic pattern as regards the Gans Sensory Organization Performance (SOP) test.

Conclusion

VEMP is considered a promising objective tool in the assessment of the vestibular end organ disorders in patients with type 2 DM with and without polyneuropathy. Diabetics with prominent diabetic polyneuropathy showed higher vestibular impairment than diabetics without DPN, which may increase the risk of falling.
Impact of comorbid pulmonary disease on COVID-19 disease severity and outcome: a retrospective cohort study
Authors: Magdy Sally , Elkorashy Reem , Elsebaie Eman Hany , Assal Hebatallah Hany , Abdel-Hamid Hoda M.
Published: November 2023

Background

Identifying patients with comorbid pulmonary disease may guide prognosis and aid in developing strategies regarding who would benefit the most from vaccines. This study was designed to clarify the influence of comorbid lung disease on COVID-19 severity and outcome.

Methods

This is a retrospective cohort analysis of 587 COVID-19 patients. The clinical, laboratory, and imaging data and comorbidities as reported by the patients were obtained from the Kasr Alainy Hospital medical records. Also, data regarding whether the patient is hospitalized or not, the length of hospital stay, complications, and mortality are gathered from the records.

Results

The patients’ mean ages are 51 ± 15 years (63.9% are males with the remaining 36.1% which are females). Patients with chronic comorbid pulmonary diseases represented 113 patients among the whole study population. with the COPD being 11.4%. Patients with comorbid lung diseases associated or not with other comorbidities were at higher risk of acquiring severe COVID-19 and had higher complication and mortality rates compared to patients without comorbidities (p-value < 0.001). Patients with preexisting diabetes, hypertension, COPD, and chronic kidney disease have a significantly higher risk of severe infection (p-value < 0.001, 0.001, 0.001, < 0.001), complications (p-value 0.038, 0.005, < 0.001, < 0.001), and mortality (p-value 0.021, 0.001, < 0.001, < 0.001), respectively.

Conclusion

This study provides a better understanding of COVID-19 patients with comorbid lung disease and highlights the importance of the data deduced from our study and similar studies in aiding the designation of vaccination programs for those patients if needed.
Robust and efficient waveform-based velocity model building by optimal transport in the pseudotime domain: An ocean-bottom cable case study in the North Sea
Authors: Provenzano Giuseppe , Brossier Romain , Métivier Ludovic
Published: November 2023

Full-waveform inversion (FWI) in the North Sea has demonstrated its imaging power starting from low-resolution models obtained by traveltime tomography, enriching them with geologically interpretable fine-scale details. However, building a traveltime-based kinematically accurate starting model for FWI is a time-consuming and rather subjective process requiring phase identification and selection. The two main problems faced by FWI starting from noninformative initial models are the susceptibility to cycle skipping and a lack of sensitivity to low wavenumbers in the deep subsurface not sampled by turning waves. On a North Sea ocean-bottom cable 3D data set, a novel [Formula: see text] building methodology is applied that addresses those issues by jointly inverting reflections and refractions (joint full-waveform inversion [JFWI]) using a robust misfit function in the vertical traveltime domain (pseudotime). Pseudotime addresses reflectivity-velocity coupling and attenuates phase ambiguities at short offsets, whereas a graph-space optimal transport (GSOT) objective function with dedicated data windowing averts cycle skipping at intermediate-to-long offsets. A fast and balanced reflectivity reconstrution is obtained prior to JFWI thanks to an asymptotic-preconditioned impedance waveform inversion ([Formula: see text]WI). Starting from a linearly increasing one-dimensional model, GSOT-pseudotime JFWI is effective at obtaining a meaningful P-wave velocity macromodel down to depths sampled by reflections only, without phase identification and picking. P-wave FWI, starting from the JFWI-based model, injects the high wavenumbers missing in the JFWI solution, attaining apparent improvements in shallow and deep model reconstruction and imaging compared with the previous studies in the literature, and a satisfactory prediction of the ground-truth logs.
Changes in sleep and the prevalence of probable insomnia in undergraduate university students over the course of the COVID-19 pandemic: findings from the U-Flourish cohort study
Authors: King Nathan , Pickett William , Keown-Stoneman Charles D. G. , Miller Christopher B. , Li Melanie , Duffy Anne
Published: November 2023

Background

Sleep problems associated with poor mental health and academic outcomes may have been exacerbated by the COVID-19 pandemic.

Aims

To describe sleep in undergraduate students during the COVID-19 pandemic.

Method

This longitudinal analysis included data from 9523 students over 4 years (2018–2022), associated with different pandemic phases. Students completed a biannual survey assessing risk factors, mental health symptoms and lifestyle, using validated measures. Sleep was assessed with the Sleep Condition Indicator (SCI-8). Propensity weights and multivariable log-binomial regressions were used to compare sleep in four successive first-year cohorts. Linear mixed-effects models were used to examine changes in sleep over academic semesters and years.

Results

There was an overall decrease in average SCI-8 scores, indicating worsening sleep across academic years (average change −0.42 per year; P-trend < 0.001), and an increase in probable insomnia at university entry (range 18.1–29.7%; P-trend < 0.001) before and up to the peak of the pandemic. Sleep improved somewhat in autumn 2021, when restrictions loosened. Students commonly reported daytime sleep problems, including mood, energy, relationships (36–48%) and concentration, productivity, and daytime sleepiness (54–66%). There was a consistent pattern of worsening sleep over the academic year. Probable insomnia was associated with increased cannabis use and passive screen time, and reduced recreation and exercise.

Conclusions

Sleep difficulties are common and persistent in students, were amplified by the pandemic and worsen over the academic year. Given the importance of sleep for well-being and academic success, a preventive focus on sleep hygiene, healthy lifestyle and low-intensity sleep interventions seems justified.