bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA circLOC101928570 suppresses systemic lupus erythematosus progression by targeting the miR-150-5p/c-myb axis
Authors: Zhao Xingwang , Dong Rui , Tang Zhongwei , Wang Juan , Wang Chunyou , Song Zhiqiang , Ni Bing , Zhang Longlong , He Xiaochong , You Yi 
Published: November 2022

AbstractBackgroundAccumulating evidence supports the implication of circular RNAs (circRNAs) in systemic lupus erythematosus (SLE). However, little is known about the detailed mechanisms and roles of circRNAs in the pathogenesis of SLE.MethodsQuantitative real-time PCR was used to determine the levels of circLOC101928570 and miR-150-5p in peripheral blood mononuclear cells of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization, RNA immunoprecipitation, luciferase reporter assays, Western blot, flow cytometry analysis and enzyme-linked immunosorbent assay were used to investigate the molecular mechanisms underlying the function of circLOC101928570.ResultsThe results showed that the level of circLOC101928570 was significantly downregulated in SLE and correlated with the systemic lupus erythematosus disease activity index. Functionally, circLOC101928570 acted as a miR-150-5p sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promoted the transcriptional level of IL2RA by directly regulating the miR-150-5p/c-myb axis.ConclusionOverall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The downregulation of circLOC101928570 suppressed SLE progression through the miR-150-5p/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serves as a potential biomarker for the diagnosis and therapy of SLE.
Unilateral acute lung injury in pig: a promising animal model
Authors: Geilen Johannes , Kainz Matthias , Zapletal Bernhard , Geleff Silvana , Wisser Wilfried , Bohle Barbara , Schweiger Thomas , Schultz Marcus J. , Tschernko Edda 
Published: November 2022

Abstract
Background
Acute lung injury (ALI) occurs in 23% unilateral. Models of unilateral ALI were developed and used previously without clearly demonstrating the strictly unilateral nature and severity of lung injury by the key parameters characterizing ALI as defined by the American Thoracic Society (ATS). Thus, the use of unilateral ALI remained rare despite the innovative approach. Therefore, we developed a unilateral model of ALI and focused on the crucial parameters characterizing ALI. This model can serve for direct comparisons between the injured and intact lungs within single animals, thus, reducing the number of animals required for valid experimental conclusions.

Methods
We established the model in nine pigs, followed by an evaluation of key parameters in six pigs (main study). Pigs were ventilated using an adapted left double-lumen tube for lung separation and two ventilators. ALI was induced in the left lung with cyclic rinsing (NaCl 0.9% + Triton® X-100), after which pigs were ventilated for different time spans to test for the timing of ALI onset. Ventilatory and metabolic parameters were evaluated, and bronchoalveolar lavage (BAL) was performed for measurements of inflammatory mediators. Finally, histopathological specimens were collected and examined in respect of characteristics defining the lung injury score (LIS) as suggested by the ATS.

Results
After adjustments of the model (n = 9) we were able to induce strictly left unilateral ALI in all six pigs of the evaluation study. The median lung injury score was 0.72 (IQR 0.62–0.79) in the left lung vs 0.14 (IQR 0.14–0.16; p < 0.05) in the right lung, confirming unilateral ALI. A significant and sustained drop in pulmonary compliance (Cdyn) of the left lung occurred immediately, whereas Cdyn of the right lung remained unchanged (p < 0.05). BAL fluid concentrations of interleukin-6 and -8 were increased in both lungs.

Conclusions
We established a model of unilateral ALI in pigs, confirmed by histopathology, and typical changes in respiratory mechanics and an inflammatory response. This thoroughly evaluated model could serve as a basis for future studies and for comparing pathophysiological and pharmacological changes in the uninjured and injured lung within the same animal.
Targeting HSP47 and HSP70: promising therapeutic approaches in liver fibrosis management
Authors: Abd El-Fattah Eslam E. , Zakaria Amr Y. 
Published: November 2022

AbstractLiver fibrosis is a liver disease in which there is an excessive buildup of extracellular matrix proteins, including collagen. By regulating cytokine production and the inflammatory response, heat shock proteins (HSPs) contribute significantly to a wider spectrum of fibrotic illnesses, such as lung, liver, and idiopathic pulmonary fibrosis by aiding in the folding and assembly of freshly synthesized proteins, HSPs serve as chaperones. HSP70 is one of the key HSPs in avoiding protein aggregation which induces its action by sending unfolded and/or misfolded proteins to the ubiquitin–proteasome degradation pathway and antagonizing influence on epithelial-mesenchymal transition. HSP47, on the other hand, is crucial for boosting collagen synthesis, and deposition, and fostering the emergence of fibrotic disorders. The current review aims to provide light on how HSP70 and HSP47 affect hepatic fibrogenesis. Additionally, our review looks into new therapeutic approaches that target HSP70 and HSP47 and could potentially be used as drug candidates to treat liver fibrosis, especially in cases of comorbidities.
Comparison of clinical outcomes of frozen-thawed D5 and D6 blastocysts undergoing preimplantation genetic testing
Authors: Yu Guanling , Ma Shuiying , Liu Hui , Liu Yujin , Zhang Haozhen , Zhang Wenjia , Wu Keliang 
Published: November 2022

Abstract
Background
This study aimed to analyze the clinical outcomes of blastocyst which undergo the preimplantation genetic testing (PGT) transplantation from frozen-thawed D5 and D6. In addition, the effect of blastocyst grade on clinical and neonatal outcomes was also investigated in this study.

Methods
The pregnancy and miscarriage rates of 1130 cycles of frozen embryo transfer, including 784 D5 frozen embryos and 346 D6 frozen embryos in the Reproductive Hospital of Shandong University from January to December 2020 were analyzed. Gardner blastocyst scoring was used for blastocyst evaluation.

Results
The pregnancy rate of D5 blastocyst was significantly higher, whereas the miscarriage rate of D5 blastocyst was lower, than that of D6 blastocyst tissue biopsy. No significant difference was observed in birth weight and low birth weight of D5 blastocyst and D6 blastocyst, preterm birth, gestational age, and neonatal sex. Frozen-thawed D5 blastocysts have higher pregnancy success rates and lower miscarriage rates compared to D6 blastocysts.

Conclusion
Therefore, both blastocyst grade and embryo biopsy date must be considered when transferring frozen embryos.
Paxlovid accelerates cartilage degeneration and senescence through activating endoplasmic reticulum stress and interfering redox homeostasis
Authors: Kong Keyu , Chang Yongyun , Qiao Hua , Zhao Chen , Chen Xuzhuo , Rong Kewei , Zhang Pu , Jin Minghao , Zhang Jingwei , Li Huiwu , Zhai Zanjing 
Published: November 2022

Abstract
Background
The COVID-19 pandemic has become a huge threat to human health, infecting millions of people worldwide and causing enormous economic losses. Many novel small molecule drugs have been developed to treat patients with COVID-19, including Paxlovid, which block the synthesis of virus-related proteins and replication of viral RNA, respectively. Despite satisfactory clinical trial results, attention is now being paid to the long-term side effects of these antiviral drugs on the musculoskeletal system. To date, no study has reported the possible side effects, such as osteoarthritis, of Paxlovid. This study explored the effects of antiviral drug, Paxlovid, on chondrocyte proliferation and differentiation.

Methods
In this study, both in vitro and in vivo studies were performed to determine the effect of Paxlovid on chondrocyte degeneration and senescence. Furthermore, we explored the possible mechanism behind Paxlovid-induced acceleration of cartilage degeneration using transcriptome sequencing and related inhibitors were adopted to verify the downstream pathways behind such phenomenon.

Results
Paxlovid significantly inhibited chondrocyte extracellular matrix protein secretion. Additionally, Paxlovid significantly induced endoplasmic reticulum stress, oxidative stress, and downstream ferroptosis, thus accelerating the senescence and degeneration of chondrocytes. In vivo experiments showed that intraperitoneal injection of Paxlovid for 1 week exacerbated cartilage abrasion and accelerated the development of osteoarthritis in a mouse model.

Conclusions
Paxlovid accelerated cartilage degeneration and osteoarthritis development, potentially by inducing endoplasmic reticulum stress and oxidative stress. Long-term follow-up is needed with special attention to the occurrence and development of osteoarthritis in patients treated with Paxlovid.
Realizing the promise of long-acting antiretroviral treatment strategies for individuals with HIV and adherence challenges: an illustrative case series
Authors: Kilcrease Christin , Yusuf Hasiya , Park Joan , Powell Aaron , RN Leon James , RN Jacob Oates , LMSW Brittany Davis , Weld Ethel D. , Dooley Kelly E. , Arrington-Sanders Renata , Agwu Allison L. 
Published: November 2022

Abstract
Background
Adherence to antiretroviral treatment (ART) remains the cornerstone of optimal HIV outcomes, including viral suppression (VS), immune recovery, and decreased transmission risk. For many people with HIV (PWH), particularly those with early-acquired HIV, structural, behavioral, and cognitive barriers to adherence and competing priorities related to life events may be difficult to overcome, resulting in nonadherence. Long-acting injectable antiretroviral therapies (LAI-ART) may be a useful strategy to overcome some of these barriers. However, to date, the approved LAI-ART strategies (e.g., cabotegravir and rilpivirine (CAB/RPV)) have targeted those who have already attained viral suppression, precluding their use in the 40% of adolescents and young adults (AYA) that VS has eluded.

Case presentation
Ms. X is a 30-year-old woman with perinatally-acquired HIV and barriers to adherence. Despite many interventions, she remained persistently viremic, with resultant immune suppression and multiple comorbid opportunistic conditions, and viral load (VL) > 10,000,000 copies/ml. Given her longstanding history of poor adherence to an oral regimen, a switch to monthly intramuscular (IM) injections and biweekly infusions of ibalizumab were initiated leading to decreased viral load to 8,110 copies/ml within two weeks. Ms. H is a 33-year-old woman with cognitive limitations due to childhood lead poisoning. Her viral load trajectory took a downward turn, precipitated by various life events, remaining elevated despite intensive case management. Initiation of LAI-ART (CAB/RPV) in this patient led to an undetectable VL (< 20 copies/ml) within two months of treatment initiation. Miss Y. is a 37-year-old woman with perinatally-acquired HIV and chronic challenges with nonadherence and longstanding immunosuppression with CD4 < 200 cells/mm3 for > 5 years. She received a 1-month oral lead-in (OLI) of cabotegravir/rilpivirine, followed by the injectable loading dose. She has since adhered to all her monthly dosing appointments, sustained VS, and transitioned to a bi-monthly injection schedule.

Conclusion
These three individuals with HIV (perinatally and non-perinatally acquired) with longstanding nonadherence and persistent viremia were successfully initiated on LAI-ART through the process of care coordination and the collective efforts of the care team, highlighting the barriers, challenges, and the multidisciplinary coordination needed to assure successful implementation of this strategy for the most vulnerable of patients.
Modulation of striatal glutamatergic, dopaminergic and cholinergic neurotransmission pathways concomitant with motor disturbance in rats with kaolin-induced hydrocephalus
Authors: Chen Li-Jin , Chen Jeng-Rung , Tseng Guo-Fang 
Published: November 2022

Abstract
Background
Hydrocephalus is characterized by abnormal accumulation of cerebrospinal fluid in the cerebral ventricles and causes motor impairments. The mechanisms underlying the motor changes remain elusive. Enlargement of ventricles compresses the striatum of the basal ganglia, a group of nuclei involved in the subcortical motor circuit. Here, we used a kaolin-injection juvenile rat model to explore the effects of acute and chronic hydrocephalus, 1 and 5 weeks post-treatment, respectively on the three major neurotransmission pathways (glutamatergic, dopaminergic and cholinergic) in the striatum.

Methods
Rats were evaluated for motor impairments. Expressions of presynaptic and postsynaptic protein markers related to the glutamatergic, dopaminergic, and cholinergic connections in the striatum were evaluated. Combined intracellular dye injection and substance P immunohistochemistry were used to distinguish between direct and indirect pathway striatal medium spiny neurons (d and i-MSNs) for the analysis of their dendritic spine density changes.

Results
Hydrocephalic rats showed compromised open-field gait behavior. However, male but not female rats displayed stereotypic movements and compromised rotarod performance. Morphologically, the increase in lateral ventricle sizes was greater in the chronic than acute hydrocephalus conditions. Biochemically, hydrocephalic rats had significantly decreased striatal levels of synaptophysin, vesicular glutamate transporter 1, and glutamatergic postsynaptic density protein 95, suggesting a reduction of corticostriatal excitation. The expression of GluR2/3 was also reduced suggesting glutamate receptor compositional changes. The densities of dendritic spines, morphological correlates of excitatory synaptic foci, on both d and i-MSNs were also reduced. Hydrocephalus altered type 1 (DR1) and 2 (DR2) dopamine receptor expressions without affecting tyrosine hydroxylase level. DR1 was decreased in acute and chronic hydrocephalus, while DR2 only started to decrease later during chronic hydrocephalus. Since dopamine excites d-MSNs through DR1 and inhibits i-MSNs via DR2, our findings suggest that hydrocephalus downregulated the direct basal ganglia neural pathway persistently and disinhibited the indirect pathway late during chronic hydrocephalus. Hydrocephalus also persistently reduced the striatal choline acetyltransferase level, suggesting a reduction of cholinergic modulation.

Conclusions
Hydrocephalus altered striatal glutamatergic, dopaminergic, and cholinergic neurotransmission pathways and tipped the balance between the direct and indirect basal ganglia circuits, which could have contributed to the motor impairments in hydrocephalus.
A comparative study of paranasal sinus and nasal cavity anatomic variations between the Polish and Turkish Cypriot Population with CBCT
Authors: Gruszka Katarzyna , Aksoy Seçil , Różyło-Kalinowska Ingrid , Gülbeş Melis Mısırlı , Kalinowski Paweł , Orhan Kaan 
Published: November 2022

Abstract
Background
Genetic and environmental factors especially climatic conditions are thought to influence the shape and size of the paranasal sinuses and anatomic variations may create both a diagnostic and therapeutic challenge. However, no study has been published about the climatic adaptation of the paranasal sinus region in different populations. This study aimed to compare the prevalence of anatomical variants in the paranasal sinus and nasal cavity using Cone-Beam Computed Tomography (CBCT) between Polish and Turkish Cypriot populations.

Methods
The material consisted of volumes acquired utilizing Galileos (Sirona, Germany) as well as Newtom 3G (QR Verona, Newtom, Italy) CBCT units. There were examined 356 Polish and 359 Turkish Cypriot patients in whom paranasal sinuses were included in the field of view. Paranasal sinus anatomic variations were assessed in both populations.

Results
In the Polish population, the most common anatomic variation was septum deviation followed by the Agger nasi cell and concha bullosa with a prevalence of 87.7%, 83.2%, and 54.8% respectively. For the Turkish Cypriot population, the most common anatomic variation was Agger nasi cell followed by concha bullosa and supraorbital ethmoid cells with a prevalence of 81.6%, 68%, and 57.8% respectively. Many anatomic variations were found to show substantial differences among both populations. Incidence rates of hyperpneumatization of the frontal sinus, septum pneumatization, supraorbital ethmoid cells, concha bullosa, uncinate bulla, and internal carotid artery protrusion into the sphenoid sinus were significantly higher in the Turkish Cypriot group, while the incidence of Haller cell, frontal sinus hypoplasia, maxillary sinus hypoplasia, ethmomaxillary sinus, sphenomaxillary plate, and septum deviation were significantly higher in Polish population.

Conclusion
According to the Köppen-Geiger world climatic map, the climate is warmer and drier in Turkish Cypriote populations than in the Polish population. These climatic differences influence the paranasal sinus variations between the Turkish Cypriot and Polish populations that must be taken into account by rhinologic surgeons especially when performing frontal and sphenoid sinus surgery.
Multiple system atrophy: α-Synuclein strains at the neuron-oligodendrocyte crossroad
Authors: Reddy Kreesan , Dieriks Birger Victor 
Published: November 2022

AbstractThe aberrant accumulation of α-Synuclein within oligodendrocytes is an enigmatic, pathological feature specific to Multiple system atrophy (MSA). Since the characterization of the disease in 1969, decades of research have focused on unravelling the pathogenic processes that lead to the formation of oligodendroglial cytoplasmic inclusions. The discovery of aggregated α-Synuclein (α-Syn) being the primary constituent of glial cytoplasmic inclusions has spurred several lines of research investigating the relationship between the pathogenic accumulation of the protein and oligodendrocytes. Recent developments have identified the ability of α-Syn to form conformationally distinct “strains” with varying behavioral characteristics and toxicities. Such “strains” are potentially disease-specific, providing insight into the enigmatic nature of MSA. This review discusses the evidence for MSA-specific α-Syn strains, highlighting the current methods for detecting and characterizing MSA patient-derived α-Syn. Given the differing behaviors of α-Syn strains, we explore the seeding and spreading capabilities of MSA-specific strains, postulating their influence on the aggressive nature of the disease. These ideas culminate into one key question: What causes MSA–specific strain formation? To answer this, we discuss the interplay between oligodendrocytes, neurons and α-Syn, exploring the ability of each cell type to contribute to the aggregate formation while postulating the effect of additional variables such as protein interactions, host characteristics and environmental factors. Thus, we propose the idea that MSA strain formation results from the intricate interrelation between neurons and oligodendrocytes, with deficits in each cell type required to initiate α-Syn aggregation and MSA pathogenesis.
Graphical Abstract
Somatic cell count in bovine quarter milk samples culture positive for various Staphylococcus species
Authors: Taponen Suvi , Myllys Vesa , Pyörälä Satu 
Published: November 2022

Abstract
Background
Non-aureus staphylococci (NAS) are the most prevalent group of bacteria isolated in bovine mastitis milk in Finland and many other countries. They usually cause subclinical or mild clinical mastitis. The increase in milk somatic cell count (SCC) during NAS intramammary infection varies from slight to marked, reflecting the severity of infection in the quarter. Limited evidence has indicated that NAS species may have different impact on milk SCC. We used a large data set originating from a prevalence study, including isolates from quarter milk samples and the SCCs of the respective quarters, to study the effect of different NAS species on quarter milk SCC.

Results
Staphylococcal species of a total of 1265 isolates, originally identified as NAS, were analysed with MALDI-TOF MS. The most prevalent NAS species were S. epidermidis, S. simulans, S. chromogenes and S. haemolyticus. Forty-two isolates appeared to be S. aureus. Geometric mean milk SCC of all quarter samples was 114,000 cells/mL and median 126,000 cells/mL. Staphylococcus species had a significant effect on the SCC of the quarter. The highest SCCs were caused by S. aureus, S. agnetis/S. hyicus (these two species cannot be distinguished with MALDI-TOF MS) and S. simulans. The mean SCCs of milk samples that were culture positive for these three species did not differ significantly from each other but were significantly higher than the mean SCCs of milk samples positive for any other species. The mean SCC of milk samples positive for S. chromogenes was significantly higher than those of milk samples positive for S. epidermidis or S. warneri.

Conclusion
Our results confirm that different Staphylococcus species have different impacts on milk SCC, as shown in previous studies. S. aureus caused the highest SCC, as expected, but the SCCs caused by S. agnetis/S. hyicus and S. simulans did not differ significantly from that of S. aureus. Other Staphylococcus species may also cause high SCC but are often isolated also from quarters with SCC on the level of healthy quarters.
Cerebellar abiotrophy in an Icelandic horse
Authors: Hansen Sanni , Olsen Emil , Raundal Marie , Agerholm Jørgen Steen 
Published: November 2022

Abstract
Background
Cerebellar abiotrophy (CA) is an uncommon hereditary neurodegenerative disorder affecting the cerebellar Purkinje cells. Equine CA has been reported in several breeds, but a genetic etiology has only been confirmed in the Arabian breed, where CA is caused by an autosomal recessive mutation.
Case presentation.
Clinical and histological findings consistent with CA are reported in an 8.5-month-old Icelandic filly. The filly showed a perceived sudden onset of marked head tremor, incoordination, ataxia, lack of menace response and a broad-based stance. Cerebrospinal fluid, hematological and biochemical findings were all within the normal range, ruling out several differential diagnoses. Post mortem histopathological examination revealed Purkinje cell degeneration accompanied by astrogliosis. Assessment of the filly’s pedigree revealed that its parents shared a common ancestor.

Conclusions
To the authors’ knowledge, this is the first report of CA in the Icelandic breed. The identification of a common parental ancestor makes autosomal recessive inheritance of CA in this filly possible, but this would need to be confirmed by further studies. Veterinarians and breeders working with Icelandic horses should be aware of this condition and report suspected cases in order to support genetic investigation.
New insights in pediatrics in 2021: choices in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine
Authors: Caffarelli Carlo , Santamaria Francesca , Piro Ettore , Basilicata Simona , Delle Cave Valeria , Cipullo Marilena , Bernasconi Sergio , Corsello Giovanni 
Published: November 2022

AbstractIn this review, we report the developments across pediatric subspecialties that have been published in the Italian Journal of Pediatrics in 2021. We highlight advances in allergy and immunology, critical care, endocrinology, gastroenterology, genetics, hematology, infectious diseases, neonatology, neurology, nutrition, palliative care, respiratory tract illnesses and telemedicine.