bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous attenuation of hyperglycemic memory-induced retinal, pulmonary, and glomerular dysfunctions by proinsulin C-peptide in diabetes
Authors: Jeon Hye-Yoon , Moon Chan-Hee , Kim Eun-Bin , Sayyed Nilofar Danishmalik , Lee Ah-Jun , Ha Kwon-Soo 
Published: February 2023

Abstract
Background
Hyperglycemic memory (HGM) is a pivotal phenomenon in the development of diabetic complications. Although coincident diabetic complications are reported, research on their development and treatment is limited. Thus, we investigated whether C-peptide can simultaneously inhibit HGM-induced retinal, pulmonary, and glomerular dysfunctions in diabetic mice supplemented with insulin.

Methods
Insulin-treated diabetic mice were supplemented with human C-peptide by subcutaneous implantation of K9-C-peptide depots for 4 weeks, and reactive oxygen species (ROS) generation, transglutaminase (TGase) activity, and vascular leakage were examined in the retina, lung, and kidney.

Results
We found hyperglycemia-induced persistent ROS generation and TGase activation after blood glucose normalization in the retina, lung, and kidney of insulin-supplemented diabetic mice. These pathological events were inhibited by systemic supplementation of human C-peptide via subcutaneous implantation of a thermosensitive biopolymer-conjugated C-peptide depot. ROS generation and TGase activation were in a vicious cycle after glucose normalization, and C-peptide suppressed the vicious cycle and subsequent endothelial permeability in human retinal endothelial cells. Moreover, C-peptide supplementation ameliorated HGM-induced retinal vascular leakage and neurodegeneration, pulmonary vascular leakage and fibrosis, and glomerular adherens junction disruption and vascular leakage.

Conclusions
Overall, our findings demonstrate that C-peptide supplementation simultaneously attenuates vascular and neuronal dysfunctions in the retina, lung, and glomerulus of insulin-supplemented diabetic mice.
Single-port robot-assisted perineal radical prostatectomy with the da Vinci XI system: initial experience and learning curve using the cumulative sum method
Authors: Yu Chenhao , Xu Li , Ye Liyin , Zheng Qiming , Hu Haiyi , Ni Kangxin , Zhou Chenghao , Xue Dingwei , Cheng Sheng , Wang Hui , Pak Raymond Wei , Li Gonghui 
Published: February 2023

Abstract
Background
To evaluate the early functional and oncological outcomes of single-port robot-assisted perineal radical prostatectomy (sp-pRARP) using the da Vinci XI system and analyze its learning curve using the cumulative sum (CUSUM) method.

Methods
The clinical data of 50 patients who underwent sp-pRARP for localized prostate cancer between May 2020 and May 2022 in our center by a single surgeon were analyzed retrospectively. Demographic information, preoperative and postoperative variables, complications, early functional and oncological outcomes of patients were recorded. The CUSUM method was used to illustrate the learning curve based on operation time.

Results
All surgeries were completed without conversion. The median (interquartile range, IQR) operation time was 205.0 (82.5) min, whereas the median (IQR) docking time was 30.0 (15.0) min and the console time was 120.0 (80.5) min. The median (IQR) estimated blood loss (EBL) was 50.0 (137.5) mL. Positive surgical margins were detected in five patients (10.0%). The continence rate was 40.9%, 63.6%, 88.4%, and 97.7% at the 1, 3, 6, and 12 months after surgery. According to the CUSUM plot, the inflection points of the learning curve were 20 cases, splitting the case series into “early phase” and “late phase.” In “late phase” cases, there was less time spent on each step of the operation and less EBL.

Conclusions
Sp-pRARP using the da Vinci XI system was verified to be a feasible and reliable surgical approach. According to the CUSUM plot, 20 cases was considered the turning point for surgeons to master the novel technique.
Essential emergency and critical care as a health system response to critical illness and the COVID19 pandemic: what does it cost?
Authors: Guinness Lorna , Kairu Angela , Kuwawenaruwa August , Khalid Karima , Awadh Khamis , Were Vincent , Barasa Edwine , Shah Hiral , Baker Peter , Schell Carl Otto , Baker Tim 
Published: February 2023

AbstractEssential Emergency and Critical Care (EECC) is a novel approach to the care of critically ill patients, focusing on first-tier, effective, low-cost, life-saving care and designed to be feasible even in low-resourced and low-staffed settings. This is distinct from advanced critical care, usually conducted in ICUs with specialised staff, facilities and technologies. This paper estimates the incremental cost of EECC and advanced critical care for the planning of care for critically ill patients in Tanzania and Kenya.The incremental costing took a health systems perspective. A normative approach based on the ingredients defined through the recently published global consensus on EECC was used. The setting was a district hospital in which the patient is provided with the definitive care typically provided at that level for their condition. Quantification of resource use was based on COVID-19 as a tracer condition using clinical expertise. Local prices were used where available, and all costs were converted to USD2020.The costs per patient day of EECC is estimated to be 1 USD, 11 USD and 33 USD in Tanzania and 2 USD, 14 USD and 37 USD in Kenya, for moderate, severe and critical COVID-19 patients respectively. The cost per patient day of advanced critical care is estimated to be 13 USD and 294 USD in Tanzania and USD 17 USD and 345 USD in Kenya for severe and critical COVID-19 patients, respectively.EECC is a novel approach for providing the essential care to all critically ill patients. The low costs and lower tech approach inherent in delivering EECC mean that EECC could be provided to many and suggests that prioritizing EECC over ACC may be a rational approach when resources are limited.
Graphical Abstract
LINC00478-derived novel cytoplasmic lncRNA LacRNA stabilizes PHB2 and suppresses breast cancer metastasis via repressing MYC targets
Authors: Guo Rong , Su Yonghui , Zhang Qi , Xiu Bingqiu , Huang Sheng , Chi Weiru , Zhang Liyi , Li Lun , Hou Jianjing , Wang Jia , Chen Jiajian , Chi Yayun , Xue Jingyan , Wu Jiong 
Published: February 2023

Abstract
Background
Metastasis is the predominant cause of mortality in patients with breast cancer. Long noncoding RNAs (lncRNAs) have been shown to drive important phenotypes in tumors, including invasion and metastasis. However, the lncRNAs involved in metastasis and their molecular and cellular mechanisms are still largely unknown.

Methods
The transcriptional and posttranscriptional processing of LINC00478-associated cytoplasmic RNA (LacRNA) was determined by RT-qPCR, semiquantitative PCR and 5′/3′ RACE. Paired-guide CRISPR/cas9 and CRISPR/dead-Cas9 systems was used to knock out or activate the expression of LacRNA. Cell migration and invasion assay was performed to confirm the phenotype of LacRNA. Tail vein model and mammary fat pad model were used for in vivo study. The LacRNA-PHB2-cMyc axis were screened and validated by RNA pulldown, mass spectrometry, RNA immunoprecipitation and RNA-seq assays.

Results
Here, we identified a novel cytoplasmic lncRNA, LacRNA (LINC00478-associated cytoplasmic RNA), derived from nucleus-located lncRNA LINC00478. The nascent transcript of LINC00478 full-length (LINC00478_FL) was cleaved and polyadenylated, simultaneously yielding 5′ ends stable expressing LacRNA, which is released into the cytoplasm, and long 3′ ends of nuclear-retained lncRNA. LINC00478_3′RNA was rapidly degraded. LacRNA significantly inhibited breast cancer invasion and metastasis in vitro and in vivo. Mechanistically, LacRNA physically interacted with the PHB domain of PHB2 through its 61–140-nt region. This specific binding affected the formation of the autophagy degradation complex of PHB2 and LC3, delaying the degradation of the PHB2 protein. Unexpectedly, LacRNA specifically interacted with PHB2, recruited c-Myc and promoted c-Myc ubiquitination and degradation. The negatively regulation of Myc signaling ultimately inhibited breast cancer metastasis. Furthermore, LacRNA and LacRNA-mediated c-Myc signaling downregulation are significantly associated with good clinical outcomes, take advantage of these factors we constructed a prognostic predict model.

Conclusion
Therefore, our findings propose LacRNA as a potential prognostic biomarker and a new therapeutic strategy.
Lifestyle and environmental risk factors for unexplained male infertility: study protocol for Australian Male Infertility Exposure (AMIE), a case–control study
Authors: Biggs Sarah N. , Kennedy Joanne , Lewis Sharon L. , Hearps Stephen , O’Bryan Moira K. , McLachlan Robert , von Saldern Simon , Chambers Georgina , Halliday Jane 
Published: February 2023

Abstract
Background
Approximately 1 in 20 men are sub-fertile or infertile yet the aetiologies of male infertility remain largely unexplained. It is suggested that lifestyle choices and environmental factors contribute but research is limited. In particular, no study has evaluated early life exposures and subsequent male infertility. To address this knowledge gap, this study aims to characterise a cohort of men with idiopathic infertility and compare their general health, lifestyle choices and environmental exposures from teenage years onwards to men without reproductive abnormalities.

Methods
Two groups of men (N = 500 cases; N = 500 controls), matched for age and socio-economic status, will be recruited from fertility clinics around Australia between June 2021 and June 2024. Men will be eligible if they are between 18 and 50 years, with a female partner less than 42 years, and have identified idiopathic male infertility (case) or are part of a couple with diagnosed female factor infertility but with no indication of compromised male fertility (control). Participants will complete an in-depth survey on general health, lifestyle and environmental exposures, reporting from teenage years onwards. An online medical data capture form will be used to gather fertility assessment information from participant medical records. Biological specimens of saliva (all study participants), blood and urine (optional) will be collected and stored for future genetic and epigenetic analysis. Differences in outcome measures between cases and controls will be determined using appropriate between groups comparisons. The relationship between explanatory variables and infertility will be analysed using multilevel modelling to account for clustering within fertility clinics.

Discussion
This study addresses an important gap in research on the aetiology of male infertility and will provide a comprehensive profile of the lifestyle and environmental risk factors for male infertility, leading to provision of up-to-date health advice for male teenagers and adults about optimising their fertility.
GVHD occurrence does not reduce AML relapse following PTCy-based haploidentical transplantation: a study from the ALWP of the EBMT
Authors: Baron Frédéric , Labopin Myriam , Tischer Johanna , Raiola Anna Maria , Vydra Jan , Blaise Didier , Chiusolo Patrizia , Stölzel Friedrich , Fanin Renato , Chevallier Patrice , Nagler Arnon , Ciceri Fabio , Mohty Mohamad 
Published: February 2023

AbstractThe association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence. However, grade I acute GVHD was associated with better LFS (HR = 0.71, 95% CI 0.51–0.99, P = 0.04). In contrast, grade III–IV acute (HR = 3.09, 95% CI 1.87–5.12, P < 0.0001) as well as extensive chronic (HR = 3.3, 95% CI 1.81–6.04, P = 0.0001) GVHD correlated with higher nonrelapse mortality leading to lower LFS (HR = 1.36, 95% CI 0.99–1.86, P = 0.056 and HR = 1.97, 95% CI 1.35–2.89, P = 0.0004, respectively). In conclusion, these data suggest a dissociation of graft-versus-leukemia effects from GVHD in patients with active AML treated with PTCy-based Haplo-HCT.
Rate of tarsal and metatarsal bone mineral density change in adults with diabetes mellitus and peripheral neuropathy: a longitudinal study
Authors: Youmans Nicholas J. , Vaidya Rachana S. , Chen Ling , Jeong Hyo‐Jung , York Alexa , Commean Paul K. , Hastings Mary K. , Zellers Jennifer A. 
Published: February 2023

AbstractBackgroundIn people with diabetes (DM) and peripheral neuropathy (PN), loss of bone mineral density (BMD) in the tarsals and metatarsals contribute to foot complications; however, changes in BMD of the calcaneal bone is most commonly reported. This study reports rate of change in BMD of all the individual bones in the foot, in participants with DM and PN. Our aim was to investigate whether the rate of BMD change is similar across all the bones of the foot.MethodsParticipants with DM and PN (n = 60) were included in this longitudinal cohort study. Rate of BMD change of individual bones was monitored using computed tomography at baseline and 6 months, 18 months, and 3–4 years from baseline. Personal factors (age, sex, medication use, step count, sedentary time, and PN severity) were assessed. A random coefficient model estimated rate of change of BMD in all bones and Pearson correlation tested relationships between personal factor variables and rate of BMD change.ResultsMean and calcaneal BMD decreased over the study period (p < 0.05). Individual tarsal and metatarsal bones present a range of rate of BMD change (‐0.3 to ‐0.9%/year) but were not significantly different than calcaneal BMD change. Only age showed significant correlation with BMD and rate of BMD change.ConclusionThe rate of BMD change did not significantly differ across different foot bones at the group level in people with DM and PN without foot deformity. Asymmetric BMD loss between individual bones of the foot and aging may be indicators of pathologic changes and require further investigation.Trial registrationMetatarsal Phalangeal Joint Deformity Progression—R01. Registered 25 November 2015, https://clinicaltrials.gov/ct2/show/NCT02616263
“It's like a swan, all nice and serene on top, and paddling like hell underneath”: community first responders’ practices in attending patients and contributions to rapid emergency response in rural England, United Kingdom—a qualitative interview study
Authors: Patel Gupteswar , Phung Viet-Hai , Trueman Ian , Pattinson Julie , Botan Vanessa , Parvin Hosseini Seyed Mehrshad , Ørner Roderick , Asghar Zahid , Smith Murray D. , Rowan Elise , Spaight Robert , Evans Jason , Brewster Amanda , Mountain Pauline , Siriwardena Aloysius Niroshan 
Published: February 2023

Abstract
Background
Community First Responder (CFR) schemes are a long-established service supplementing ambulance trusts in their local community in the United Kingdom. CFRs are community members who volunteer to respond to people with life-threatening conditions. Previous studies highlighted the motivations for becoming CFRs, their training, community (un)awareness and implications of their work on themselves and others. The practices of CFRs in prehospital care remain underexplored. Therefore, we aimed to explore real-world practice of Community First Responders and their contribution to prehospital emergency care.

Methods
We conducted 47 interviews with CFRs (21), CFR leads (15), ambulance clinicians (4), commissioners (2) and patients and relatives (5) from six ambulance services and regions of England, United Kingdom. Thematic analysis enabled identification of themes and subthemes, with subsequent interpretation built on the theory of practice wisdom.

Results
Our analysis revealed the embeddedness of the concept of doing the right thing at the right time in CFR practice. CFRs’ work consisted of a series of sequential and interconnected activities which included: identifying patients’ signs, symptoms and problems; information sharing with the ambulance control room on the patient’s condition; providing a rapid emergency response including assessment and care; and engaging with ambulance clinicians for patient transfer. The patient care sequence began with recognising patients’ signs and symptoms, and validation of patient information provided by the ambulance control room. The CFRs shared patient information with ambulance control who in turn notified the ambulance crew en-route. The practices of CFRs also included delivery of emergency care before ambulance clinicians arrived. Following the delivery of a rapid emergency response, CFRs engaged with the ambulance crew to facilitate patient transfer to the nearest medical facility.

Conclusion
The sequential CFR practices supported ambulance services in delivering prehospital and emergency care in rural areas. CFR practices were founded on the principle of practice wisdom where CFRs constructed their practice decisions based on the patient’s condition, their training, availability of equipment and medications and their scope of practice.
Optimization of Cr (VI) removal from aqueous solution with activated carbon derived from Eichhornia crassipes under response surface methodology
Authors: Fito Jemal , Tibebu Solomon , Nkambule Thabo T. I. 
Published: February 2023

AbstractTannery industries’ effluent contains a high concentration of Cr (VI) which has the potential to affect the environment and public health. Therefore, this study aimed to investigate the optimization of Cr (VI) adsorption by activated carbon (AC) derived from Eichhornia crassipes from an aqueous solution. The adsorbent was activated with dilute sulfuric acid followed by thermal activation. AC was characterized using proximate analysis, SEM, FTIR, X-ray diffraction, and the BET method. The Cr (VI) removal optimization process was performed using a central composite design under the response surface methodology. The proximate analysis showed that the moisture content, volatile matter, ash content, and fixed carbon of the activated carbon were 5.6%, 18.2%, 14.4%, and 61.8% respectively. The surface areas of the Eichhornia crassipes before activation, after activation, and after adsorption were 60.6 g/m2, 794.2 g/m2, and 412.6 g/m2 respectively. A highly porous structure with heterogeneous and irregular shapes was observed in the SEM micrograph. In the FTIR analysis, different peaks are indicated with various functional groups. The intensity of XRD peaks decreased as 2 theta values increased, which indicates the presence of an amorphous carbon arrangement. The point of zero charge (pHpzc) of the activated carbon was found to be 5.20. A maximum Cr (VI) removal of 98.4% was achieved at pH 5, contact time 90 min, adsorbent dose 2 g, and initial Cr (VI) concentration of 2.25 mg/L. Statistically significant interactions (P < 0.05) were observed between the initial Cr (VI) concentration and adsorbent dose as well as the initial Cr (VI) concentration and contact time. Langmuir adsorption isotherm fitted the experimental data best, with an R2 value of 0.99. The separation constant (RL) indicates that the adsorption process is favorable. The kinetic experimental data were best fitted with the pseudo-second-order model with an R2 value of 0.99 whereas the adsorption rate is controlled by intraparticle and extragranular diffusion processes. Generally, the AC has the potential to be a strong adsorbent candidate for wastewater treatment at the industrial level.
Biodegradable functionalized magnetite nanoparticles as binary-targeting carrier for breast carcinoma
Authors: Akl Magda Ali , Kamel Amira Mostafa , El-Ghaffar Mahmoud Ahmed Abd 
Published: February 2023

AbstractIn this study, Superparamagnetic magnetite nanoparticles (SPMNPs) are used in a new way as direct nanocarrier for Doxorubicin hydrochloride (DOX) via the functionalization of their surface with tri-sodium citrate through ligand exchange to conjugate DOX with imine bond to form tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (DOX/Cit-MNPs). The DOX/Cit-MNPs were coated with chitosan to form chitosan coated citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) to offer biodegradability and pH-sensitive drug release features. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed functionalization of SPMNPs, DOX-conjugation, and chitosan coating. The trans electron microscopy (TEM) show spherical nanostructures with average size 40 nm for coated nanocarriers. The saturation magnetization value of carrier was 59 emu/g.The in-vitro release of DOX from the chitosan coated tri-sodium citrate functionalized magnetite loaded DOX nanoparticles (Cs/DOX/Cit-MNPs) was studied to be 75% at pH 5.5 and 28.6% at pH 7.4 which proves the pH sensitivity of encapsulated Cs/DOX/Cit-MNPs. The effect of Cs/DOX/Cit-MNPs toward Human Breast Cancer Cell lines (MCF7) was studied and found to be 76% without magnet and 98% with external magnet after 72 h. With increasing DOX concentration and treatment time, the cell inhibition (IR%) of DOX solution and Cs/DOX-Cit-MNPs suspension to all cells is increased. Cs/DOX/Cit-MNPs showed sustained release and good inhibition to cancer cells and offer a protective mode for normal cells (WISH) compared to the free DOX.
Graphical Abstract
Genomic analysis of the international high-risk clonal lineage Klebsiella pneumoniae sequence type 395
Authors: Shaidullina Elvira R. , Schwabe Michael , Rohde Thomas , Shapovalova Valeria V. , Dyachkova Marina S. , Matsvay Alina D. , Savochkina Yuliya A. , Shelenkov Andrey A. , Mikhaylova Yulia V. , Sydow Katharina , Lebreton François , Idelevich Evgeny A. , Heiden Stefan E. , Becker Karsten , Kozlov Roman S. , Shipulin German A. , Akimkin Vasiliy G. , Lalk Michael , Guenther Sebastian , Zautner Andreas E. , Bohnert Jürgen A. , Mardanova Ayslu M. , Bouganim Ruth , Marchaim Dror , Hoff Katharina J. , Schaufler Katharina , Edelstein Mikhail V. 
Published: February 2023

AbstractBackgroundKlebsiella pneumoniae, which is frequently associated with hospital- and community-acquired infections, contains multidrug-resistant (MDR), hypervirulent (hv), non-MDR/non-hv as well as convergent representatives. It is known that mostly international high-risk clonal lineages including sequence types (ST) 11, 147, 258, and 307 drive their global spread. ST395, which was first reported in the context of a carbapenemase-associated outbreak in France in 2010, is a less well-characterized, yet emerging clonal lineage.MethodsWe computationally analyzed a large collection ofK. pneumoniaeST395 genomes (n = 297) both sequenced in this study and reported previously. By applying multiple bioinformatics tools, we investigated the core-genome phylogeny and evolution of ST395 as well as distribution of accessory genome elements associated with antibiotic resistance and virulence features.ResultsClustering of the core-SNP alignment revealed four major clades with eight smaller subclades. The subclades likely evolved through large chromosomal recombination, which involved differentK. pneumoniaedonors and affected,inter alia, capsule and lipopolysaccharide antigen biosynthesis regions. Most genomes contained acquired resistance genes to extended-spectrum cephalosporins, carbapenems, and other antibiotic classes carried by multiple plasmid types, and many were positive for hypervirulence markers, including the siderophore aerobactin. The detection of “hybrid” resistance and virulence plasmids suggests the occurrence of the convergent ST395 pathotype.ConclusionsTo the best of our knowledge, this is the first study that investigated a large international collection ofK. pneumoniaeST395 genomes and elucidated phylogenetics and detailed genomic characteristics of this emerging high-risk clonal lineage.