bluuebunny/crossref_metadata_2025_split huggingface dataset:
CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR
Authors: Wang Xiaolong , Chen Tong , Li Chen , Li Wenhao , Zhou Xianyong , Li Yaming , Luo Dan , Zhang Ning , Chen Bing , Wang Lijuan , Zhao Wenjing , Fu Shanji , Yang Qifeng 
Published: August 2022

Abstract
Background
Circular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers and therapeutic targets for a variety of malignancies. However, the regulatory functions and underlying mechanisms of circRNAs in triple-negative breast cancer (TNBC) are largely unknown.

Methods
By using RNA high-throughput sequencing technology, qRT-PCR and in situ hybridization assays, we screened dysregulated circRNAs in breast cancer and TNBC tissues. Then in vitro assays, animal models and patient-derived organoids (PDOs) were utilized to explore the roles of the candidate circRNA in TNBC. To investigate the underlying mechanisms, RNA pull-down, RNA immunoprecipitation (RIP), co immunoprecipitation (co-IP) and Western blotting assays were carried out.

Results
In this study, we demonstrated that circRNA-CREIT was aberrantly downregulated in doxorubicin resistant triple-negative breast cancer (TNBC) cells and associated with a poor prognosis. The RNA binding protein DHX9 was responsible for the reduction in circRNA-CREIT by interacting with the flanking inverted repeat Alu (IRAlu) sequences and inhibiting back-splicing. By utilizing in vitro assays, animal models and patient-derived organoids, we revealed that circRNA-CREIT overexpression significantly enhanced the doxorubicin sensitivity of TNBC cells. Mechanistically, circRNA-CREIT acted as a scaffold to facilitate the interaction between PKR and the E3 ligase HACE1 and promoted proteasomal degradation of PKR protein via K48-linked polyubiquitylation. A reduced PKR/eIF2α signaling axis was identified as a critical downstream effector of circRNA-CREIT, which attenuated the assembly of stress granules (SGs) to activate the RACK1/MTK1 apoptosis signaling pathway. Further investigations revealed that a combination of the SG inhibitor ISRIB and doxorubicin synergistically inhibited TNBC tumor growth. Besides, circRNA-CREIT could be packaged into exosomes and disseminate doxorubicin sensitivity among TNBC cells.

Conclusions
Our study demonstrated that targeting circRNA-CREIT and SGs could serve as promising therapeutic strategies against TNBC chemoresistance.
Multiple genome alignment in the telomere-to-telomere assembly era
Authors: Kille Bryce , Balaji Advait , Sedlazeck Fritz J. , Nute Michael , Treangen Todd J. 
Published: August 2022

AbstractWith the arrival of telomere-to-telomere (T2T) assemblies of the human genome comes the computational challenge of efficiently and accurately constructing multiple genome alignments at an unprecedented scale. By identifying nucleotides across genomes which share a common ancestor, multiple genome alignments commonly serve as the bedrock for comparative genomics studies. In this review, we provide an overview of the algorithmic template that most multiple genome alignment methods follow. We also discuss prospective areas of improvement of multiple genome alignment for keeping up with continuously arriving high-quality T2T assembled genomes and for unlocking clinically-relevant insights.
Right-side fixation of the sigmoid colon causing internal herniation with closed-loop obstruction of both small and large bowel: a case report and review of the literature
Authors: Bertelli G. , Patauner S. , Gorgatti T. , Frena A. 
Published: August 2022

Abstract
Background
Right-side fixation of the sigmoid colon is a rare anatomical variant associated with intestinal malrotation (Choi et al. in J Korean Surg Soc. 84(4):256–60,
2013). Differently from other forms of malrotation, this variant has not been associated thus far with acute surgical conditions.

Case presentation
In this report, we present a 65-year-old Caucasian patient admitted for bowel obstruction symptoms. Computed tomography scan revealed right-side fixation of the sigmoid colon extended to the subhepatic recess complicated by obstructed internal herniation of the ileum. In this patient, the sigmoid colon occupied a recess posterior to the ascending colon and right Toldt’s fascia. Within this narrow anatomical space, an ileal loop was trapped causing internal herniation with resultant close-bowel obstruction of both ileum and sigmoid colon. The ileal loop was released surgically and the anatomical abnormality corrected.

Conclusions
To our knowledge, this is the first case of right-side fixation of the sigmoid colon causing acute obstruction secondary to internal herniation of the small intestine. Early recognition and precise anatomical definition of such anatomical variants are essential to optimize their surgical approach.
Giant desmoid tumour mimicking recurrent uterine myoma in a nulliparous young Nigerian: a case report
Authors: Njoku Obinna Chukwunwike , Umezurike Chisara Cyprian 
Published: August 2022

AbstractBackgroundDesmoid tumors are rare lesions. Although they demonstrate tumor characteristics, such as infiltrative growth and tendency towards local recurrence, they lack the ability to metastasize. To date, the cause of desmoid tumors is unknown. They can occur in both sexes, but predominant slightly in women, including nulliparous women, of reproductive age, but mostly during and after pregnancy.Case presentationA 36-year-old nulliparous Nigerian woman presented with a large desmoid tumor of the anterior abdominal wall, mimicking recurrent leiomyoma. At presentation, she had a painless abdominal mass for 1 year, which was first noticeable as a small induration that progressively increased in size. The patient had a previous surgical history of open myomectomy for symptomatic fibroids of 3 years duration, prior to presentation. Treatment comprised a complete excision of the tumor with a wide margin and partial omentectomy and the anterior abdominal wall closed in layers, though without prosthesis. The patient subsequently developed incisional hernia.ConclusionsLarge desmoid tumors may be misdiagnosed or mistaken for uterine leiomyoma or other abdominal or pelvic tumors. Attention should therefore be paid to detailed patient history and systematic clinical evaluation. To guard against incisional hernia associated with surgical resection of huge desmoid tumors, mesh reconstruction is recommended.
Detecting inappropriate total duration of antimicrobial therapy using semi-automated surveillance
Authors: van den Broek Annemieke K. , de la Court Jara R. , Groot Thomas , van Hest Reinier M. , Visser Caroline E. , Sigaloff Kim C. E. , Schade Rogier P. , Prins Jan M. 
Published: August 2022

Abstract
Objectives
Evaluation of the appropriateness of the duration of antimicrobial treatment is a cornerstone of antibiotic stewardship programs, but it is time-consuming. Furthermore, it is often restricted to antibiotics prescribed during hospital admission. This study aimed to determine whether mandatory prescription-indication registration at the moment of prescribing antibiotics enables reliable automated assessment of the duration of antibiotic therapy, including post-discharge duration, limiting the need for manual chart review to data validation.

Methods
Antibiotic prescription and admission data, from 1-6-2020 to 31-12-2021, were electronically extracted from the Electronic Medical Record of two hospitals using mandatory indication registration. All consecutively prescribed antibiotics of adult patients who received empiric therapy in the first 24 h of admission were merged to calculate the total length of therapy (LOT) per patient, broken down per registered indication. Endpoints were the accuracy of the data, evaluated by comparing the extracted LOT and registered indication with the clinical notes in 400 randomly selected records, and guideline adherence of treatment duration. Data were analysed using a reproducible syntax, allowing semi-automated surveillance.

Results
A total of 3,466 antibiotic courses were analysed. LOT was accurately retrieved in 96% of the 400 evaluated antibiotic courses. The registered indication did not match chart review in 17% of antibiotic courses, of which only half affected the assessment of guideline adherence. On average, in 44% of patients treatment was continued post-discharge, accounting for 60% (± 19%) of their total LOT. Guideline adherence ranged from 26 to 75% across indications.

Conclusions
Mandatory prescription-indication registration data can be used to reliably assess total treatment course duration, including post-discharge antibiotic duration, allowing semi-automated surveillance.
GM-CSF-mediated inducement of bone marrow MDSCs by TSA and effect on survival of graft in mice
Authors: Zhao Shuguang , Li Shaohua , Yang Jingci , Gao Weinian , Chen Ziying 
Published: August 2022

Abstract
Objective
This study analyzed the effect of HDAC inhibitor, trichostatin A (TSA), in inducing granulocyte–macrophage colony-stimulating factor (GM-CSF)-mediated bone marrow (BM) cell differentiation to myeloid-derived suppressor cells (MDSCs) in vitro and in vivo.

Methods
BM cell differentiation to CD11b + GR-1 + MDSCs was achieved by in vitro culture with TSA and GM-CSF, and the collected cells were analyzed by mixed lymphocyte culture to identify suppressive actions against effector T cells. RT-PCR and ELISA were conducted to analyze the CCL5 mRNA and protein levels in TSA + GM-CSF + BM, GR-1 + MDSCs and GR-1 + MDSC + CCL5 groups. The survival of cardiac grafts was compared between groups.

Results
TSA was beneficial for the GM-CSF-mediated BM differentiation to CD11b + GR-1 + MDSCs. Adoptive transfer of GR-1 + MDSCs was powerful in suppressing CD4 + CD25-T cell proliferation and the effect was mediated by iNOS and HO-1; it also increased CCL5 gradient concentration between grafts and plasma to recruit Treg to grafts and prolong the survival of the grafts. Survival analysis revealed that the survival of grafts after adoptive transfer of GR-1 + MDSCs could be prolonged.

Conclusion
This study helps in further research on the application value of MDSCs in the field of transplant, and may provide a new thought for the cell therapy in inducing immune tolerance in organ transplant.
Plasma volume expansion reveals hidden metabolic acidosis in patients with diabetic ketoacidosis
Authors: Svensson Robert , Hahn Robert G. , Zdolsek Joachim H. , Bahlmann Hans 
Published: August 2022

Abstract
Background
Hyperchloremic metabolic acidosis that develops during the treatment of diabetic ketoacidosis is usually attributed to the chloride content of resuscitation fluids. We explored an alternative explanation, namely that fluid-induced plasma volume expansion alters the absolute differences in the concentrations of sodium and chloride (the Na–Cl gap) enough to affect the acid–base balance. We analyzed data from a prospective single-center cohort study of 14 patients treated for diabetic ketoacidosis. All patients received 1 L of 0.9% saline over 30 min on two consecutive days. Blood gases were sampled before and after the infusions.

Results
The initial plasma volume was estimated to be 25 ± 13% (mean ± SD) below normal on admission to the intensive care unit. At that time, most patients had an increased actual Na–Cl gap, which counteracts acidosis. However, the correction of the plasma volume deficit revealed that these patients would have had a decreased Na–Cl gap upon admission if they had been normovolemic at that time; the estimated “virtual Na–Cl gap” of 29 ± 5 mmol/L was significantly lower than the uncorrected value, which was 39 ± 5 mmol/L (P < 0.001). On Day 2, most patients had a decreased actual Na–Cl gap (33 ± 5 mmol/L), approaching the corrected value on Day 1.

Conclusions
The hyperchloremic acidosis commonly seen in diabetic ketoacidosis may not be primarily caused by the chloride content of resuscitation fluids but, rather, by the restoration of plasma volume, which reveals the hidden metabolic acidosis caused by a decreased Na–Cl gap.
Trial registration Clinical Trials Identifier NCT02172092, registered June 24, 2014, https://www.clinicaltrials.gov/NCT02172092
Vitamin combination promotes ex vivo expansion of NK-92 cells by reprogramming glucose metabolism
Authors: Fu Yan , Chen Yuying , Xie Zhepei , Huang Huimin , Tan Wen-Song , Cai Haibo 
Published: August 2022

AbstractRobust ex vivo expansion of NK-92 cells is essential for clinical immunotherapy. The vitamin B group is critical for the expansion and function of immune cells. This study optimized a vitamin combination by response surface methodology based on an in-house designed chemically defined serum-free medium EM. The serum-free medium EM-V4 with an optimal vitamin combination favoured ex vivo expansion of NK-92 cells. The characteristics of glucose metabolism of NK-92 cells in EM-V4 and the relationships between cell expansion and metabolism were investigated. NK-92 cells in EM-V4 underwent metabolic reprogramming. An elevated ratio of glucose-6-phosphate dehydrogenase/phosphofructokinase (G6PDH/PFK) indicated that NK-92 cells shifted towards the pentose phosphate pathway (PPP). An increase in the ratio of pyruvate dehydrogenase/lactate dehydrogenase (PDH/LDH) suggested that the cells shifted towards the Krebs (TCA) cycle, i.e., from glycolysis to aerobic metabolism. The enhanced ratio of oxygen consumption rate/extracellular acidification rate (OCR/ECAR) indicated that NK-92 cells were more reliant on mitochondrial respiration than on glycolysis. This shift provided more intermediate metabolites and energy for biosynthesis. Thus, EM-V4 accelerated biomass accumulation and energy production to promote NK-92 cell expansion by regulating the metabolic distribution. Our results provide valuable insight for the large-scale ex vivo expansion of clinically available NK-92 cells.
Graphical Abstract
Occurrence of claw asymmetries in fattening pigs and potential impact on the development of sole ulcerations
Authors: Seufert Sarah , Volkmann Nina , Schmidt-Mosig Johannes , Kemper Nicole 
Published: August 2022

AbstractBackgroundClaw abnormalities, particularly claw asymmetries, are associated with lameness in pigs and can be a welfare issue. However, the prevalence and development of claw asymmetries in pigs of different age is unknown. Therefore, the aim of this study was to analyze the claw symmetry over the pig lifetime from birth to slaughter as well as the occurrence of sole ulcerations in fattening pigs possibly caused by such asymmetric claws.ResultsFrom third day of life until slaughtering, asymmetric growth of the claws was detected more frequently and more severely with increasing age as determined by three-step scoring. Sole ulcerations were detected in slaughtered pigs only with a prevalence of 64.2% (197/307 examined animals). The risk for a sole ulceration was 3.6-fold higher for pigs with strongly asymmetric claws (≥ 30% size difference of the claw footing area) compared to slightly asymmetric claws (≥ 5–15% size difference of the claw footing area) (odds ratio (OR) = 3.6). It was even higher for pigs showing intermediately asymmetric claws (≥ 15–30% size difference of the claw footing area) (OR = 2.7).ConclusionsThe study showed a significant increase in the prevalence of claw asymmetries over the pigs’ lifetime, which can lead to serious pathologic findings with increasing age such as sole ulcerations. Most likely, the unbalanced weight load on single claws in combination with hard flooring can result in claw damages. Moreover, a genetic component cannot be excluded because claw asymmetries were already detected in suckling piglets.
Role of endoanal ultrasound in the assessment of perianal fistula in correlation with MRI fistulography
Authors: Sayed Alaa , El-azizi Hatem Mohamed Said , El-barmelgi Mohamed Yehia Ahmed , Azzam Heba 
Published: August 2022

Abstract
Background
Perianal fistula is a considered as chronic recurrent inflammatory condition that requires proper surgical treatment and may require repeated intervention. Therefore, adequate pre-operative radiological diagnosis plays a critical role.
In this study, we aimed at comparing the role of endoanal ultrasonography with MRI fistulography in evaluating the primary fistula's tract, internal opening, secondary extensions, and complications of the perianal fistula.

Results
The study was carried over 108 males (90%) and 12 females (10%) presenting with clinically diagnosed perianal fistula. Ultrasound was found superior to MRI in the localization of the internal opening with estimated K value (0.44), P value (0.001). Regarding the type of fistula, ultrasound was found in agreement with MRI in 112 cases (93.3%) with estimated K value of about (0.7). Ultrasound was found equally effective as MRI in the detection of complication with estimated agreement K value of about 1. Regarding assessment of the secondary extensions, the agreement between the two modalities was about 50% with estimated k value of about 0.65. Conversely, MRI was found superior to ultrasound in the characterization of the fibrotic tracts.

Conclusions
Both EAUS and MRI have a crucial role in the evaluation and detection of perianal fistulas. EAUS was preferable to MRI in the localization of the internal opening; ,conversely, in the evaluation of extra-sphincteric fistulas and fibrotic tracts characterization MRI was preferable to EAUS.
Comparison of Turbo Flash and dual-energy modes of third-generation dual-source CT in pre-transplant renal angiography: a prospective observational study
Authors: Christopher Navya , Periaswamy Gopinath , Arunachalam Venkatesh Kasi , Pilli Vandana , Renganathan Rupa , Rajasekaran Sriman , Mehta Pankaj , Cherian Mathew 
Published: August 2022

Abstract
Background
The purpose of this study was to compare the Image Quality, Contrast Medium Volume, and Radiation dose in renal angiography performed using Turbo Flash mode and dual-energy (DE) mode in the third-generation dual-source dual-energy CT.
This prospective observational study was performed on renal donors who underwent CTA imaging as a pre-transplant workup. The study population was divided into two groups. Group A underwent DECT renal angiography. Group B underwent Turbo Flash Mode CT renal angiography. For group A, a contrast volume of 1 ml/kg and for group B at 0.5 ml/kg was administered. Image Quality was evaluated objectively by calculating CNR and SNR and subjectively by a 5-point scale. Radiation Dose analysis was done by noting CTDIvol and DLP on the scanner system and calculating effective radiation dose (ED).

Results
The subjective image quality scores for the Turbo Flash group were comparable with the DE group in qualitative image analysis. Additionally, in the Turbo Flash group, there was a reduction in contrast media and effective radiation dose by 47.5% and 32.7%, respectively. Nevertheless, mean attenuation of the abdominal arteries, CNR, SNR, and Noise (S.D) showed statistical significance between the two groups (p value < 0.01).

Conclusions
To our knowledge, no previous study compared Turboflash mode with DE protocol in CT renal angiography in a donor group of patients. Turbo Flash CT is an excellent modality that is faster and has an added advantage of decreased radiation dose and contrast media volume reduction, which can be recommended for screening of voluntary kidney donors but needs further clinical studies, validation, and standardization with tailored protocols.
Production of low wear friction lining material from agro-industrial wastes
Authors: Mgbemena Chinedum Ogonna , Esigie Richard U. , Mgbemena Chika Edith , Ata Chike M. 
Published: August 2022

AbstractThis research aims at producing and characterizing a low-wear friction lining material using a hybrid mixture of burnt vehicle tyres, pulverized palm kernel shell (PKS), pulverized coconut shell (CS), iron and brass filings obtained from the machine shop floor. The Taguchi method was used to determine the optimum parameter settings to obtain a friction lining with a low wear rate by exploring the signal-to-noise ratios (S/N) of the smaller-the-better. The developed friction lining was subjected to the scanning electron microscopy-energy dispersive spectroscopy (SEM-EDX) and X-ray fluorescence (XRF) to ascertain the functional groups present in the friction lining, their elemental composition and finally the morphology. The control factors used in the Taguchi analysis are the moulding temperature, cure time and heat treatment. The optimum parameter settings for a low wear rate were obtained as follows: moulding temperature of 175 °C, cure time of 8 min and heat treatment time of 3 h. The XRF spectroscopy indicated that the developed friction lining materials contained the following compounds in large proportions: CaO, SiO2, Al2O3 and Fe2O3. The SEM-EDX results for the two image scans reported show that carbon and oxygen were the predominant elements observed in the micrograph.
Hawking radiation from acoustic black holes in hydrodynamic flow of electrons
Authors: Dave Shreyansh S. , Ganguly Oindrila , Saumia P. S. , Srivastava Ajit M. 
Published: August 2022

Abstract
Acoustic black holes are formed when a fluid flowing with subsonic velocities accelerates and becomes supersonic. When the flow is directed from the subsonic to supersonic region, the surface on which the normal component of fluid velocity equals the local speed of sound acts as an acoustic horizon. This is because no acoustic perturbation from the supersonic region can cross it to reach the subsonic part of the fluid. One can show that if the fluid velocity is locally irrotational, the field equations for acoustic perturbations of the velocity potential are identical to that of a massless scalar field propagating in a black hole background. One, therefore, expects Hawking radiation in the form of a thermal spectrum of phonons. There have been numerous investigations of this possibility, theoretically, as well as experimentally, in systems ranging from cold atom systems to quark-gluon plasma formed in relativistic heavy-ion collisions. Here we investigate this possibility in the hydrodynamic flow of electrons. The resulting Hawking radiation in this case should be observable in terms of current fluctuations. Further, current fluctuations on both sides of the acoustic horizon should show correlations expected for pairs of Hawking particles.
Exploring Visceral and Subcutaneous Adipose Tissue Secretomes in Human Obesity: Implications for Metabolic Disease
Authors: Kahn Darcy , Macias Emily , Zarini Simona , Garfield Amanda , Zemski Berry Karin , MacLean Paul , Gerszten Robert E , Libby Andrew , Solt Claudia , Schoen Jonathan , Bergman Bryan C 
Published: August 2022

Abstract
Adipose tissue secretions are depot-specific and vary based on anatomical location. Considerable attention has been focused on visceral (VAT) and subcutaneous (SAT) adipose tissue with regard to metabolic disease, yet our knowledge of the secretome from these depots is incomplete. We conducted a comprehensive analysis of VAT and SAT secretomes in the context of metabolic function. Conditioned media generated using SAT and VAT explants from individuals with obesity were analyzed using proteomics, mass spectrometry, and multiplex assays. Conditioned media were administered in vitro to rat hepatocytes and myotubes to assess the functional impact of adipose tissue signaling on insulin responsiveness. VAT secreted more cytokines (IL-12p70, IL-13, TNF-α, IL-6, and IL-8), adipokines (matrix metalloproteinase-1, PAI-1), and prostanoids (TBX2, PGE2) compared with SAT. Secretome proteomics revealed differences in immune/inflammatory response and extracellular matrix components. In vitro, VAT-conditioned media decreased hepatocyte and myotube insulin sensitivity, hepatocyte glucose handling, and increased basal activation of inflammatory signaling in myotubes compared with SAT. Depot-specific differences in adipose tissue secretome composition alter paracrine and endocrine signaling. The unique secretome of VAT has distinct and negative impact on hepatocyte and muscle insulin action.