bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional assessment of homozygous ALDH18A1 variants reveals alterations in amino acid and antioxidant metabolism
Authors: Colonna Maxwell B , Moss Tonya , Mokashi Sneha , Srikanth Sujata , Jones Julie R , Foley Jackson R , Skinner Cindy , Lichty Angie , Kocur Anthony , Wood Tim , Stewart Tracy Murray , Casero Jr. Robert A , Flanagan-Steet Heather , Edison Arthur S , Lyons Michael J , Steet Richard 
Published: September 2022

Abstract
Mono- and bi-allelic variants in ALDH18A1 cause a spectrum of human disorders associated with cutaneous and neurological findings that overlap with both cutis laxa and spastic paraplegia. ALDH18A1 encodes the bifunctional enzyme pyrroline-5-carboxylate synthetase (P5CS) that plays a role in the de novo biosynthesis of proline and ornithine. Here we characterize a previously unreported homozygous ALDH18A1 variant (p.Thr331Pro) in four affected probands from two unrelated families, and demonstrate broad-based alterations in amino acid and antioxidant metabolism. These four patients exhibit variable developmental delay, neurological deficits and loose skin. Functional characterization of the p.Thr331Pro variant demonstrated a lack of any impact on the steady-state level of the P5CS monomer or mitochondrial localization of the enzyme, but reduced incorporation of the monomer into P5CS oligomers. Using an unlabeled NMR-based metabolomics approach in patient fibroblasts and ALDH18A1-null human embryonic kidney cells expressing the variant P5CS, we identified reduced abundance of glutamate and several metabolites derived from glutamate, including proline and glutathione. Biosynthesis of the polyamine putrescine, derived from ornithine, was also decreased in patient fibroblasts, highlighting the functional consequence on another metabolic pathway involved in antioxidant responses in the cell. RNA sequencing of patient fibroblasts revealed transcript abundance changes in several metabolic and extracellular matrix-related genes, adding further insight into pathogenic processes associated with impaired P5CS function. Together these findings shed new light on amino acid and antioxidant pathways associated with ALDH18A1-related disorders, and underscore the value of metabolomic and transcriptomic profiling to discover new pathways that impact disease pathogenesis.
Trileaflet semilunar valve reconstruction: pulsatile in vitro evaluation
Authors: Carlson Hanse Lisa , Tjørnild Marcell J , Sørensen Simon G , Johansen Peter , Lugones Ignacio , Hjortdal Vibeke E 
Published: September 2022

Abstract

OBJECTIVES
Residual regurgitation is common after congenital surgery for right ventricular outflow tract malformation. It is accepted as there is no competent valve solution in a growing child. We investigated a new surgical technique of trileaflet semilunar valve reconstruction possessing the potential of remaining sufficient and allowing for some growth with the child. In this proof-of-concept study, our aim was to evaluate if it is achievable as a functional pulmonary valve reconstruction in vitro.

METHODS
Explanted pulmonary trunks from porcine hearts were evaluated in a pulsatile flow-loop model. First, the native pulmonary trunk was investigated, after which the native leaflets were explanted. Then, trileaflet semilunar valve reconstruction was performed and investigated. All valves were initially investigated at a flow output of 4 l/min and subsequently at 7 l/min. The characterization was based on hydrodynamic pressure and echocardiographic measurements.

RESULTS
Eight pulmonary trunks were evaluated. All valves are competent on colour Doppler. There is no difference in mean pulmonary systolic artery pressure gradient at 4 l/min (P = 0.32) and at 7 l/min (P = 0.20). Coaptation length is increased in the neo-valve at 4 l/min (P &lt; 0.001, P &lt; 0.001, P = 0.008) and at 7 l/min (P &lt; 0.001, P = 0.006, P = 0.006). A windmill shape is observed in all neo-valves.

CONCLUSIONS
Trileaflet semilunar valve reconstruction is sufficient and non-stenotic. It resulted in an increased coaptation length and a windmill shape, which is speculated to decrease with the growth of the patient, yet remains sufficient as a transitional procedure until a long-term solution is feasible. Further in vivo investigations are warranted.
Feasibility and long-term outcomes of surgery for primary thoracic synovial sarcoma
Authors: Pieropan Sara , Mercier Olaf , Mitilian Delphine , Pradère Pauline , Fabre Dominique , Ion Daniela Iolanda , Mir Olivier , Galbardi Barbara , Thomas De Montpreville Vincent , Fadel Elie 
Published: September 2022

Abstract

OBJECTIVES
Primary thoracic synovial sarcoma (SS) is a rare, high-grade, malignancy. Involvement of vital organs is frequent and may decrease the benefits of surgical resection. We reviewed our practice at a highly experienced thoracic-surgery centre to assess early- and long-term outcomes after surgery.

METHODS
We conducted a retrospective, observational, single-centre study of patients undergoing curative-intent surgery for primary thoracic SS between 1 January 2000 and 31 January 2021 as part of a multidisciplinary management. We assessed demographics, medical history, histopathology and follow-up information.

RESULTS
We enrolled 20 patients (13 males) with a median age of 40 years old and a median tumour size of 11 cm. Neoadjuvant chemotherapy was administered to 13 patients. Surgery consisted in extrapleural pneumonectomy (n = 7), extrapleural lobectomy (n = 5), chest wall resection (n = 4) or tumour resection (n = 4). R0 resection was achieved in 16 (80%) patients. Adjuvant therapy was given to 13 patients. 6 patients developed postoperative complications. The median hospital stay was 11.5 days. Overall survival at 2 and 5 years was 51% and 22%, respectively; median overall survival was 25 months and median disease-free survival was 8.5 months. Relapses occurred in 15 patients. By univariate analysis, incomplete resection was the only significant predictor of survival (P = 0.01).

CONCLUSIONS
Primary thoracic SS is an aggressive disease. Surgery included in a multimodal treatment may contribute to achieving a good outcome, providing that an R0 resection is obtained. Given the considerable technical challenges of surgery, patient selection and referral to an experienced centre are crucial to minimize morbidity and mortality.
Chain destruction of methane–hydrogen explosion in utility tunnel to adjacent space
Authors: Zhang Shuhao , Yao Yanchen , Yang Xinying , Du Jianmei 
Published: September 2022

Abstract
Hydrogen is clean energy possible be transported in pipelines under utility tunnels in the future. Current research about gas explosions in the utility tunnel ignored the damage in the adjacent zones, the fire-proof wall, the above ventilated mezzanine and the escape room. The numerical simulation of methane–hydrogen explosion considering the chain destruction is conducted. The results show that the maximum overpressure peak is 6 MPa under 100% H2, and the fire-proof wall will increase the explosive intensity, so the length of one gas compartment should increase to 400 m or 600 m. The maximum overpressure sometimes presents in the adjacent zone rather than the explosive center, and the shock wave will not influence the ventilated mezzanine much. However, the flame will influence ventilated mezzanine, even the ground, so the adjacent zones, ventilated mezzanine and escape room are also dangerous. Therefore, a novel emergency system should be discussed for high-proportion-hydrogen transportation in utility tunnels.
Universality for Low-Degree Factors of Random Polynomials over Finite Fields
Authors: He Jimmy , Tuan Pham Huy , Wenqiang Xu Max 
Published: September 2022

Abstract
We show that the counts of low-degree irreducible factors of a random polynomial $f$ over $\mathbb {F}_q$ with independent but nonuniform coefficients behave like that of a uniform random polynomial, exhibiting a form of universality for random polynomials over finite fields. Our strongest results require various assumptions on the parameters, but we are able to obtain results requiring only $q=p$ a prime with $p\leq \exp ({n^{1/13}})$ where $n$ is the degree of the polynomial. Our proofs use Fourier analysis and rely on tools recently applied by Breuillard and Varjú to study the $ax+b$ process, which show equidistribution for $f(\alpha )$ at a single point. We extend this to handle multiple roots and the Hasse derivatives of $f$, which allow us to study the irreducible factors with multiplicity.
Efficient approach to automated pavement manhole cover detection with modified faster R-CNN
Authors: Zhang Hang , Dong Zishuo , He Anzheng , Zhang Allen A , Wang Kelvin C P , Liu Yang , Xu Jie , Shang Jing , Ai Changfa 
Published: September 2022

Abstract
At the present time, increasing attention is being paid to the detection of road facilities, such as manhole covers— an important type of road facility which can have tangible impacts on driving safety and comfort. This paper proposes a robust method based on a modification of the Faster Region Convolutional Neural Network (Faster R-CNN) to automatically detect pavement manhole covers. We establish a manually annotated image library that consists of 1,245 manhole cover images collected by 1 mm laser imaging system, and implement the modified Faster R-CNN architecture to locate manhole covers exclusively under realistic and complex environments. Compared with the original Faster R-CNN, the proposed modification is to replace the feature extractor used in the original Faster R-CNN with a more-efficient backbone ResNet50, and implement a Feature Pyramid Network (FPN) to fuse multi-scale features. The experimental results demonstrate that the modified Faster R-CNN outperforms the original Faster R-CNN and other state-of-the-art models, including YOLOv4, EfficientDet, and YOLOX. The F1-score and Overall-IOU achieved by the modified Faster R-CNN on 250 test images are 98.15 per cent and 92.07 per cent respectively. To further verify the robustness of the proposed method, the modified Faster R-CNN is applied to process manhole cover images which are taken randomly by a smartphone and thus very different to the manhole cover images acquired by the laser imaging system. It is found that the modified Faster R-CNN can also yield similar detection efficiency even for images representing highly dissimilar viewing angles and unforeseen scenarios, implying the benefits of deep-learning-based object detection algorithms to intelligent investigation of pavement manhole covers.
Relevance of the Consensus Principles for Appropriate Antibiotic Prescribing in 2022
Authors: Cantón Rafael , Akova Murat , Langfeld Karen , Torumkuney Didem 
Published: September 2022

AbstractBackgroundIn the late 1990s, as a response to rising antimicrobial resistance (AMR), an independent multinational, interdisciplinary group was formed specifically targeting primary care antibiotic prescribing for community-acquired respiratory tract infections (CA-RTIs). The group comprised senior clinicians from Canada, Israel, Spain, Sweden, UK and USA. The group’s objectives were to provide recommendations for antibiotic stewardship in the community because, whilst it was widely accepted that inappropriate antibiotic use was contributing to AMR, it remained difficult to change prescribing behaviour. The group aimed to identify principles underlying appropriate antibiotic prescribing and guideline formulation to reduce morbidity from CA-RTIs, limit therapeutic failure and, importantly, curb AMR emergence. The group published a report in 2002, which has become known as the Consensus Principles.Objectives(i) To consider the relevance of the Consensus Principles in 2022 by reviewing current global approaches to rising AMR. A wide range of factors, such as antibiotic overuse, most recently seen in COVID-19 patients, are still driving rising AMR even though there has been a high-level international response to the AMR threat; and (ii) as an introduction to this Supplement, which reports the findings of analyses of how AMR is being addressed in nine disparate countries (Brazil, India, Kuwait, Mexico, Pakistan, Russia, Saudi Arabia, Türkiye and Vietnam). Understanding how these initiatives are being pursued in different countries helps identify areas where more information is needed.ConclusionsAdherence to the Consensus Principles remains as important now as it was in 2002. Achieving appropriate antibiotic prescribing is a vital objective in order that the right patient receives the right antibiotics at the right time to ensure optimal clinical outcomes while at the same time helping to limit further increases in AMR.
Country data on AMR in Türkiye in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome
Authors: Torumkuney Didem , Aktas Zerrin , Unal Serhat , van Hasselt James , Seyhun Yalcin , Keles Nergis 
Published: September 2022

Abstract

Background
Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action.

Objectives
To review AMR in Türkiye and initiatives addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Türkiye and to improve patient outcomes.

Methods
National AMR initiatives, antibiotic use and prescribing, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs (community-acquired pneumonia, acute otitis media, acute bacterial rhinosinusitis) were also reviewed, plus local antibiotic availability. Insights from both a local clinician and local clinical microbiologist were sought to contextualize this information.

Conclusions
Türkiye developed an antibiotic stewardship programme, The Rational Drug Use National Action Plan 2014–2017, prioritizing appropriate antibiotic prescription in the community. Public campaigns discouraging inappropriate antibiotic use were also initiated. Türkiye has a high level of antibiotic resistance and a high level of consumption, however, in 2015 over-the-counter antibiotic sales were prohibited, resulting in a declining trend in overall consumption. There is still a need for physician education on current developments in antibiotic use. Several ongoing global surveillance studies provide antibiotic susceptibility data in Türkiye. Clinicians in Türkiye use several country-specific guidelines for common CA-RTIs plus a range of international guidelines. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data on isolates from community-acquired infections in Türkiye, could make guideline use more relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve patient outcome.
Country data on AMR in Kuwait in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome
Authors: Torumkuney Didem , Behbehani Naser , van Hasselt James , Hamouda Mohamed , Keles Nergis 
Published: September 2022

Abstract

Background
Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action.

Objectives
To review AMR in Kuwait and initiatives underway addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Kuwait and to improve patient outcomes.

Methods
National initiatives to address AMR, antibiotic use and prescribing, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs (community-acquired pneumonia, acute otitis media and acute bacterial rhinosinusitis) were also reviewed, plus local antibiotic availability. Insights from a clinician in Kuwait were sought to contextualize this information.

Conclusions
In Kuwait there have been some initiatives addressing AMR such as annual campaigns for proper use of antibiotics. Antibiotic use is high but there appears to be a low understanding in the general public about their appropriate use. However, there is legislation in place prohibiting over-the-counter purchase of antibiotics. Only international guidelines for CA-RTIs are used. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data of isolates from community-acquired infections in Kuwait, could make management guideline use more locally relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve clinical patient outcomes.
(Pro)renin receptor and insulin signalling regulate cell proliferation in MCF-7 breast cancer cells
Authors: Sato Shigemitsu , Hirose Takuo , Ohba Koji , Watanabe Fumihiko , Watanabe Tomoki , Minato Kazuya , Endo Akari , Ito Hiroki , Mori Takefumi , Takahashi Kazuhiro 
Published: September 2022

Abstract
(Pro)renin receptor [(P)RR] is related to both the renin-angiotensin system and V-ATPase with various functions including stimulation of cell proliferation. (P)RR is implicated in the pathophysiology of diabetes mellitus and cancer. Hyperinsulinemia is observed in obesity-related breast cancer. However, the relationship between (P)RR and insulin has not been clarified. We have therefore studied the effect of insulin on (P)RR expression, cell viability and AKT phosphorylation under the conditions with and without (P)RR knockdown. Effects of insulin were studied in a human breast cancer cell line, MCF-7. Cell proliferation assay was performed by WST-8 assay. (P)RR expression was suppressed by (P)RR-specific siRNAs. The treated cells were analysed by western blotting and reverse transcriptase-quantitative polymerase chain reaction analysis. Insulin stimulated proliferation of MCF-7 cells and increased (P)RR protein expression, but not (P)RR mRNA levels. Moreover, autophagy flux was suppressed by insulin. Suppression of (P)RR expression reduced cell number of MCF-7 cells and AKT phosphorylation significantly in both the presence and the absence of insulin, indicating that (P)RR is important for cell viability and AKT phosphorylation. In conclusion, insulin upregulates the level of (P)RR protein, which is important for cell viability, proliferation, AKT phosphorylation and autophagy in breast cancer cells.
Influence of nitrogen sources on the tolerance of Lacticaseibacillus rhamnosus to heat stress and oxidative stress
Authors: Zhang Chenchen , Han Yuemei , Gui Ya , Wa Yunchao , Chen Dawei , Huang Yujun , Yin Boxing , Gu Ruixia 
Published: September 2022

Abstract
It has been found that 32 genes related to nitrogen source metabolism in Lacticaseibacillus rhamnosus are downregulated under both heat stress and oxidative stress. In this study, the influence of different nitrogen sources within the growth medium on the tolerance of L. rhamnosus to heat stress and oxidative stress was investigated. Tryptone-free MRS was found to enhance the tolerance of L. rhamnosus hsryfm 1301 to heat stress and oxidative stress during the whole growth period, and this result was universal for all L. rhamnosus species analyzed. The strongest strengthening effect occurred when the OD600 value reached 2.0, at which the survival rates under heat stress and oxidative stress increased 130-fold and 40-fold, respectively. After supplementing phenylalanine, isoleucine, glutamate, valine, histidine, or tryptophan into the tryptone-free MRS, the tolerance of L. rhamnosus to heat stress and oxidative stress exhibited a sharp drop. The spray drying survival rate of L. rhamnosus hsryfm 1301 cultured in the tryptone-free MRS rose to 75% (from 30%), and the spray dried powder also performed better in the experimentally simulated gastrointestinal digestion. These results showed that decreasing the intake of amino acids is an important mechanism for L. rhamnosus to tolerate heat stress and oxidative stress. When L. rhamnosus is cultured for spray drying, the concentration of the nitrogen source's components should be an important consideration.
U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3′ end processing core factors
Authors: Hu Zhijie , Li Mengxia , Huo Zhanfeng , Chen Liutao , Liu Susu , Deng Ke , Lu Xin , Chen Shangwu , Fu Yonggui , Xu Anlong 
Published: September 2022

ABSTRACTIn eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3′ end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level. SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate, which may reduce the repressive effects of PABPN1 on the proximal APA sites. Additionally, SNRNP70 can also promote the proximal APA sites by recruiting CPSF6, suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent. Consequently, these results reveal that, on the contrary to U1 snRNP complex, the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3′ end processing machinery.