bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic characterization of colistin-resistant Klebsiella pneumoniae isolated from intensive care unit patients in Egypt
Authors: Attalla Eriny T. , Khalil Amal M. , Zakaria Azza S. , Baker Dave J. , Mohamed Nelly M. 
Published: September 2023

Abstract
Background
Egypt has witnessed elevated incidence rates of multidrug-resistant Klebsiella pneumoniae infections in intensive care units (ICUs). The treatment of these infections is becoming more challenging whilst colistin-carbapenem-resistant K. pneumoniae is upsurging. Due to the insufficiently available data on the genomic features of colistin-resistant K. pneumoniae in Egypt, it was important to fill in the gap and explore the genomic characteristics, as well as the antimicrobial resistance, the virulence determinants, and the molecular mechanisms of colistin resistance in such a lethal pathogen.

Methods
Seventeen colistin-resistant clinical K. pneumoniae isolates were collected from ICUs in Alexandria, Egypt in a 6-month period in 2020. Colistin resistance was phenotypically detected by modified rapid polymyxin Nordmann/Poirel and broth microdilution techniques. The isolates susceptibility to 20 antimicrobials was determined using Kirby-Bauer disk diffusion method. Whole genome sequencing and bioinformatic analysis were employed for exploring the virulome, resistome, and the genetic basis of colistin resistance mechanisms.

Results
Out of the tested K. pneumoniae isolates, 82.35% were extensively drug-resistant and 17.65% were multidrug-resistant. Promising susceptibility levels towards tigecycline (88.24%) and doxycycline (52.94%) were detected. Population structure analysis revealed seven sequence types (ST) and K-types: ST383-K30, ST147-K64, ST17-K25, ST111-K63, ST11-K15, ST14-K2, and ST525-K45. Virulome analysis revealed yersiniabactin, aerobactin, and salmochelin siderophore systems in ˃ 50% of the population. Hypervirulence biomarkers, iucA (52.94%) and rmpA/A2 (5.88%) were detected. Extended-spectrum β-lactamase- and carbapenemase-producers accounted for 94.12% of the population, with blaCTX-M-15, blaNDM-5, and blaOXA-48 reaching 64.71%, 82.35%, and 82.35%, respectively. Chromosomal alterations in mgrB (82.35%) were the most prevailing colistin resistance-associated genetic change followed by deleterious mutations in ArnT (23.53%, L54H and G164S), PmrA (11.76%, G53V and D86E), PmrB (11.76%, T89P and T134P), PmrC (11.76%, S257L), PhoQ (5.88%, L322Q and Q435H), and ArnB (5.88%, G47D) along with the acquisition of mcr-1.1 by a single isolate of ST525.

Conclusions
In this study, we present the genotypic colistin resistance mechanisms in K. pneumoniae isolated in Egypt. More effective antibiotic stewardship protocols must be implemented by Egyptian health authorities to restrain this hazard and safeguard the future utility of colistin. This is the first characterization of a complete sequence of mcr-1.1-bearing IncHI2/IncHI2A plasmid recovered from K. pneumoniae clinical isolate belonging to the emerging high-risk clone ST525.
circEIF3I facilitates the recruitment of SMAD3 to early endosomes to promote TGF-β signalling pathway-mediated activation of MMPs in pancreatic cancer
Authors: Zhao Zhongjie , Yang Wenbo , Kong Rui , Zhang Yangyang , Li Le , Song Zengfu , Chen Hongze , Luo Yan , Zhang Tao , Cheng Chundong , Li Guanqun , Liu Danxi , Geng Xinglong , Chen Hua , Wang Yongwei , Pan Shangha , Hu Jisheng , Sun Bei 
Published: September 2023

Abstract
Background
Among digestive tract tumours, pancreatic ductal adenocarcinoma (PDAC) shows the highest mortality trend. Moreover, although PDAC metastasis remains a leading cause of cancer-related deaths, the biological mechanism is poorly understood. Recent evidence demonstrates that circular RNAs (circRNAs) play important roles in PDAC progression.

Methods
Differentially expressed circRNAs in normal and PDAC tissues were screened via bioinformatics analysis. Sanger sequencing, RNase R and actinomycin D assays were performed to confirm the loop structure of circEIF3I. In vitro and in vivo functional experiments were conducted to assess the role of circEIF3I in PDAC. MS2-tagged RNA affinity purification, mass spectrometry, RNA immunoprecipitation, RNA pull-down assay, fluorescence in situ hybridization, immunofluorescence and RNA–protein interaction simulation and analysis were performed to identify circEIF3I-interacting proteins. The effects of circEIF3I on the interactions of SMAD3 with TGFβRI or AP2A1 were measured through co-immunoprecipitation and western blotting.

Results
A microarray data analysis showed that circEIF3I was highly expressed in PDAC cells and correlated with TNM stage and poor prognosis. Functional experiments in vitro and in vivo revealed that circEIF3I accelerated PDAC cells migration, invasion and metastasis by increasing MMPs expression and activity. Mechanistic research indicated that circEIF3I binds to the MH2 domain of SMAD3 and increases SMAD3 phosphorylation by strengthening the interactions between SMAD3 and TGFβRI on early endosomes. Moreover, AP2A1 binds with circEIF3I directly and promotes circEIF3I-bound SMAD3 recruitment to TGFβRI on early endosomes. Finally, we found that circEif3i exerts biological functions in mice similar to those of circEIF3I in humans PDAC.

Conclusions
Our study reveals that circEIF3I promotes pancreatic cancer progression. circEIF3I is a molecular scaffold that interacts with SMAD3 and AP2A1 to form a ternary complex, that facilitates the recruitment of SMAD3 to early endosomes and then activates the TGF-β signalling pathway. Hence, circEIF3I is a potential prognostic biomarker and therapeutic target in PDAC.
“It’s like a safety net for when things go wrong”: key stakeholder and program user perspectives on a peer-led safe space program in Sydney, Australia
Authors: Wadds Phillip , Doran Christopher M. , Shakeshaft Anthony , Tran Dam Anh 
Published: September 2023

Abstract
Background
Safe Spaces are a harm reduction approach commonly utilised in nightlife and festival settings to address alcohol and other drug-related harms. Despite increasing use, there has been little independent evaluation of safe space programs. This study aimed to explore (1) program user satisfaction with and use of a safe space program implemented in Sydney, Australia (The Take Kare Safe Space (TKSS)), and (2) the strengths and weaknesses of TKSS from the perspective of key stakeholders.

Methods
Semi-structured, in-depth, interviews lasting between 30 min to 1 h were conducted with 38 key program stakeholders, including staff from police (n = 4), ambulance (n = 4), a local hospital accident and emergency room (n = 4), local council (n = 2), city ‘rangers’ (n = 2), the TKSS program (n = 4), licensed venues and other nightlife service providers (n = 4), and program users (n = 14). Purposive sampling was used to identify key stakeholders to participate in interviews.

Results
Stakeholders stated that the TKSS program had a number of core benefits, including that it filled a service gap in nightlife settings; improved the efficiency and effectiveness of emergency services and other stakeholders operating in nightlife precincts; provided welfare services through proactive and non-judgmental interventions; and facilitated a means to de-escalate conflict without engaging police. Perceived weaknesses of the program included a lack of public awareness about the program; staff and volunteer levels; and misunderstandings regarding the scope and function of the TKSS program by some stakeholders.

Conclusion
This study demonstrates the complex relationships that exist around the delivery of harm reduction in nightlife settings. In particular, it highlights the relative lack of servicing of public nightlife settings and the value of safe spaces/peer-to-peer safety ambassador programs in linking up care and filling this service gap. Further, it documents the extended benefit across key stakeholder groups of delivering proactive and non-judgemental harm reduction services and, in doing so, provides critical evidence around their efficacy in reducing AOD-related harms in the night-time economy.
Establishment of a high-fidelity patient-derived xenograft model for cervical cancer enables the evaluation of patient’s response to conventional and novel therapies
Authors: Liu Liting , Wu Min , Huang Anni , Gao Chun , Yang Yifan , Liu Hong , Jiang Han , Yu Long , Huang Yafei , Wang Hui 
Published: September 2023

Abstract
Background
Recurrent or metastatic cervical cancer (r/m CC) often has poor prognosis owing to its limited treatment options. The development of novel therapeutic strategies has been hindered by the lack of preclinical models that accurately reflect the biological and genomic heterogeneity of cervical cancer (CC). Herein, we aimed to establish a large patient-derived xenograft (PDX) biobank for CC, evaluate the consistency of the biologic indicators between PDX and primary tumor tissues of patients, and explore its utility for assessing patient’s response to conventional and novel therapies.

Methods
Sixty-nine fresh CC tumor tissues were implanted directly into immunodeficient mice to establish PDX models. The concordance of the PDX models with their corresponding primary tumors (PTs) was compared based on the clinical pathological features, protein biomarker levels, and genomic features through hematoxylin & eosin staining, immunohistochemistry, and whole exome sequencing, respectively. Moreover, the clinical information of CC patients, RNA transcriptome and immune phenotyping of primary tumors were integrated to identify the potential parameters that could affect the success of xenograft engraftment. Subsequently, PDX model was evaluated for its capacity to mirror patient’s response to chemotherapy. Finally, PDX model and PDX-derived organoid (PDXO) were utilized to evaluate the therapeutic efficacy of neratinib and adoptive cell therapy (ACT) combination strategy for CC patients with human epidermal growth factor receptor 2 (HER2) mutation.

Results
We established a PDX biobank for CC with a success rate of 63.8% (44/69). The primary features of established PDX tumors, including clinicopathological features, the expression levels of protein biomarkers including Ki67, α-smooth muscle actin, and p16, and genomics, were highly consistent with their PTs. Furthermore, xenograft engraftment was likely influenced by the primary tumor size, the presence of follicular helper T cells and the expression of cell adhesion-related genes in primary tumor tissue. The CC derived PDX models were capable of recapitulating the patient’s response to chemotherapy. In a PDX model, a novel therapeutic strategy, the combination of ACT and neratinib, was shown to effectively inhibit the growth of PDX tumors derived from CC patients with HER2-mutation.

Conclusions
We established by far the largest PDX biobank with a high engraftment rate for CC that preserves the histopathological and genetic characteristics of patient’s biopsy samples, recapitulates patient’s response to conventional therapy, and is capable of evaluating the efficacy of novel therapeutic modalities for CC.
Integration of proprioception in upper limb prostheses through non-invasive strategies: a review
Authors: Papaleo Ermanno Donato , D’Alonzo Marco , Fiori Francesca , Piombino Valeria , Falato Emma , Pilato Fabio , De Liso Alfredo , Di Lazzaro Vincenzo , Di Pino Giovanni 
Published: September 2023

AbstractProprioception plays a key role in moving our body dexterously and effortlessly. Nevertheless, the majority of investigations evaluating the benefits of providing supplemental feedback to prosthetics users focus on delivering touch restitution. These studies evaluate the influence of touch sensation in an attempt to improve the controllability of current robotic devices. Contrarily, investigations evaluating the capabilities of proprioceptive supplemental feedback have yet to be comprehensively analyzed to the same extent, marking a major gap in knowledge within the current research climate. The non-invasive strategies employed so far to restitute proprioception are reviewed in this work. In the absence of a clearly superior strategy, approaches employing vibrotactile, electrotactile and skin-stretch stimulation achieved better and more consistent results, considering both kinesthetic and grip force information, compared with other strategies or any incidental feedback. Although emulating the richness of the physiological sensory return through artificial feedback is the primary hurdle, measuring its effects to eventually support the integration of cumbersome and energy intensive hardware into commercial prosthetic devices could represent an even greater challenge. Thus, we analyze the strengths and limitations of previous studies and discuss the possible benefits of coupling objective measures, like neurophysiological parameters, as well as measures of prosthesis embodiment and cognitive load with behavioral measures of performance. Such insights aim to provide additional and collateral outcomes to be considered in the experimental design of future investigations of proprioception restitution that could, in the end, allow researchers to gain a more detailed understanding of possibly similar behavioral results and, thus, support one strategy over another.
A deep learning model for rapid classification of tea coal disease
Authors: Xu Yang , Mao Yilin , Li He , Sun Litao , Wang Shuangshuang , Li Xiaojiang , Shen Jiazhi , Yin Xinyue , Fan Kai , Ding Zhaotang , Wang Yu 
Published: September 2023

Abstract
Background
The common tea tree disease known as “tea coal disease” (Neocapnodium theae Hara) can have a negative impact on tea yield and quality. The majority of conventional approaches for identifying tea coal disease rely on observation with the human naked eye, which is labor- and time-intensive and frequently influenced by subjective factors. The present study developed a deep learning model based on RGB and hyperspectral images for tea coal disease rapid classification.

Results
Both RGB and hyperspectral could be used for classifying tea coal disease. The accuracy of the classification models established by RGB imaging using ResNet18, VGG16, AlexNet, WT-ResNet18, WT-VGG16, and WT-AlexNet was 60%, 58%, 52%, 70%, 64%, and 57%, respectively, and the optimal classification model for RGB was the WT-ResNet18. The accuracy of the classification models established by hyperspectral imaging using UVE-LSTM, CARS-LSTM, NONE-LSTM, UVE-SVM, CARS-SVM, and NONE-SVM was 80%, 95%, 90%, 61%, 77%, and 65%, respectively, and the optimal classification model for hyperspectral was the CARS-LSTM, which was superior to the model based on RGB imaging.

Conclusions
This study revealed the classification potential of tea coal disease based on RGB and hyperspectral imaging, which can provide an accurate, non-destructive, and efficient classification method for monitoring tea coal disease.
One-hole split endoscopy technique versus unilateral biportal endoscopy technique for L5-S1 lumbar disk herniation: analysis of clinical and radiologic outcomes
Authors: Zhang Yuhong , Feng Bo , Hu Peng , Dai Guohua , Su Weiliang 
Published: September 2023

Abstract
Background
Lumbar disk herniation (LDH) is one of the most common diseases of the spine, especially occurring in L4-5 and L5-S1 intervertebral disks, and surgery is a choice when conservative treatment is ineffective. The purpose of this study is to investigate the clinical efficacy and radiologic outcomes of one-hole split endoscopy (OSE) technique versus unilateral biportal endoscopy (UBE) technique in the treatment of L5-S1 lumbar disk herniation (LDH).

Methods
A total of 133 patients of a single center surgically treated for L5-S1 LDH between 2019 and 2021 were retrospectively included in this study, of which 70 were treated by UBE technique and the rest were treated by OSE technique. Hospitalization time, operative time, intraoperative blood loss, fluoroscopy times, incision length and related complications were recorded. Bone resection area (BRA), articular process resection rate, range of motion (ROM), sagittal translation (ST), disk height (DH), Visual Analog Score (VAS), Oswestry Disability Index (ODI) and Macnab criteria were used to evaluated the clinical efficacy.

Results
There was no statistically significant difference in hospitalization time or fluoroscopy times between the two groups. The operation time was shorter in the UBE group than that in the OSE group; however, the incision length was longer. Intraoperative blood loss and BRA were larger in the UBE group than in the OSE group. There was no significant difference in ROM, ST, DH, or postoperative facet resection rate between the two groups. There was no significant difference in ROM, ST, or postoperative facet resection rate compared with preoperative indicators in each group, but there was a significant difference in DH among distinct groups. At any time point, the lower back and leg VAS and ODI in each group were significantly improved compared to those before the operation, with no significant difference between the two groups. There was one case of dural tear in the UBE group. One case of transient hypoesthesia occurred in each of the two groups. The excellent–good rates of the UBE group and the OSE group were 88.6% and 90.5%, respectively.

Conclusion
The OSE technique is an effective minimally invasive surgical option as well as the UBE technique in the treatment of L5-S1 LDH.
Surgical options for distal radius fractures of type C in elderly patients over 65 years old: a comparison of external fixation with Kirschner wires and volar locking plate
Authors: Zhang He , Liu Man , Duan Si-Yu , Liang Hai-Rui , Xu Rong-Da , Cai Zhen-Cun 
Published: September 2023

Abstract
Background
ue to the lack of consensus on the optimal surgical treatment for distal radius fractures (DRF) in elderly patients over 65 years old, the purpose of this study was to compare the efficacy of external fixation (EF) with Kirschner wires and volar locking plate (VLP) in the treatment of DRF through a retrospective cohort study. We hypothesized that there would be no significant difference in overall complications and functional recovery between the two methods.

Methods
We retrospectively analyzed 62 patients over 65 years old who underwent surgical treatment for C-type DRF between 2019 and 2022. Based on the different treatment methods, they were divided into the EF group and the VLP group. General data, inpatient data, and postoperative complications during follow-up were recorded. The X-ray images before surgery, after surgery, and at the last follow-up were analyzed, and the results of wrist motion range, Gartland–Werley wrist joint score, and DASH score were evaluated 6 months after surgery for both groups.

Result
Thirty patients underwent closed reduction and external fixation combined with Kirschner wire fixation, while 32 underwent open reduction and VLP fixation. The EF group had significantly shorter operation time, intraoperative blood loss, injury-to-surgery time, and hospital stay compared to the VLP group (all p < 0.001). At the last follow-up, the radiographic parameters (ulnar variance and radial inclination) and wrist joint function (wrist dorsiflexion and forearm supination) were better in the VLP group than in the EF group (p = 0.04, p = 0.01, p = 0.001, p = 0.02, respectively). However, there was no significant difference in overall Gartland-Werley wrist joint score, DASH score, and incidence of postoperative complications between the two groups (p = 0.31, p = 0.25, p = 0.47, respectively).

Conclusion
For patients aged 65 and above with distal radius fractures (DRF) of type C, VLP and external fixation with Kirschner wires yield comparable functional outcome and complications rate at the short term. However, VLP allowed restoration of better radiological parameters.
ApoC3 is expressed in oocytes and increased expression is associated with PCOS progression
Authors: Zhou Jiahe , Mo Hui , Feng Qian , Li Li , La Jiahui 
Published: September 2023

Abstract
Background
Polycystic ovary syndrome (PCOS) is a lifelong metabolic disorder and the most common cause of anovulatory infertility affecting women in reproductive age. Our recent study reported that apolipoprotein C3 (ApoC3) could be a potential diagnostic serum marker for metabolism disturbance in PCOS patients, but whether it is present in the ovaries and what role it plays has not yet been described.

Objective
Aimed to investigate ApoC3 expression in ovary of PCOS, and to discuss its potential role in PCOS progression.

Methods
ApoC3 expression in ovarian tissue samples from 12 PCOS patients along with 12 healthy controls were measured via immunohistochemistry (IHC). Also, the level of ApoC3 in follicular fluid from 14 patients diagnosed with PCOS and 13 control subjects were detected by ELISA. The expression and location of ApoC3 in ovaries of PCOS mice were tested weekly for three consecutive weeks during PCOS formation using real time PCR, Western Blot, IHC and immunofluorescence. The relation of ApoC3 and sex hormones was analyzed in mouse plasma. Additionally, the dynamic changes of ApoC3 level in ovaries of healthy mice during postnatal development was also investigated.

Results
ApoC3 levels in ovarian tissue and follicular fluid were significantly higher in PCOS patients than in controls (33.87 ± 4.11 vs. 27.71 ± 3.65, P < 0.01; 0.87 ± 0.09 vs. 0.51 ± 0.32 ng/mL, P < 0.05), respectively. In ovary, ApoC3 was found to be located in the cytoplasm of oocyte, and its expression gradually increased with PCOS progression (P < 0.05). Furthermore, correlation analysis showed that plasma ApoC3 level was closely associated with luteinizing hormone (r = 0.709, P = 0.001), testosterone (r = 0.627, P = 0.005) and anti-mullerian hormone (r = 0.680, P = 0.002) in PCOS mice. In addition, ApoC3 level in oocyte was physiologically increased and peaked on postnatal age 21 (P21), then decreased following P21 in healthy mice.

Conclusions
We identified ApoC3 expression in oocyte. It may be involved in PCOS progression and possibly participate in the regulation of oocyte development.
A small clinical trial of vaporized cannabis for PTSD: suggestive results and directions for future study
Authors: Walsh Zach , Mitchell Ian , Crosby Kim , St. Pierre Michelle , DeClerck Drew , Ong Kaye , Lucas Philippe 
Published: September 2023

AbstractThe last few decades have seen increasing interest in the use of cannabis for post-traumatic stress disorder (PTSD). Recent attempts to evaluate the clinical efficacy of cannabis for PTSD were inconclusive and generalizability was limited by undesirable features of the study drug. The present clinical trial evaluated the effects of a commercially available chemovar that was delivered by vaporization. The study was designed as a randomized placebo-controlled cross-over study with three conditions; however, only five individuals completed the trial, and analysis of the placebo effect was not possible. Results identified positive changes consistent with medium-sized within-subject effects for cannabis in the treatment of PTSD. Positive trending results and high patient need mandate future studies of cannabis for the treatment of PTSD.