bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of grayscale values of hypoechoic lesions matched with target lesions observed on magnetic resonance imaging for the prediction of clinically significant prostate cancer
Authors: Kim Dong Gyun , Yoo Jeong Woo , Koo Kyo Chul , Chung Byung Ha , Lee Kwang Suk 
Published: October 2022

AbstractBackgroundTo analyze grayscale values for hypoechoic lesions matched with target lesions evaluated using prebiopsy magnetic resonance imaging (MRI) according to the Prostate Imaging-Reporting and Data System (PI-RADS).MethodsWe collected data on 420 target lesions in patients who underwent MRI/transrectal ultrasound fusion-targeted biopsies between January 2017 and September 2020. Images of hypoechoic lesions that matched the target lesions on MRI were stored in a picture archiving and communication system, and their grayscale values were estimated using the red/green/blue scoring method through an embedded function. We analyzed imaging data using grayscale values.ResultsOf the 420 lesions, 261 (62.1%) were prostate cancer lesions. There was no difference in the median grayscale values between benign and prostate cancer lesions. However, grayscale ranges (41.8–98.5 and 42.6–91.8) were significant predictors of prostate cancer and clinically significant prostate cancer (csPC) in multivariable logistic regression analyses. Area under the curve for detecting csPC using grayscale values along with conventional variables (age, prostate-specific antigen levels, prostate volume, previous prostate biopsy results, and PI-RADS scores) was 0.839, which was significantly higher than that for detecting csPC using only conventional variables (0.828;P = 0.036). Subgroup analysis revealed a significant difference for PI-RADS 3 lesions between grayscale values for benign and cancerous lesions (74.5 vs. 58.8,P = 0.008). Grayscale values were the only significant predictive factor (odds ratio = 4.46,P = 0.005)for csPC.ConclusionsDistribution of grayscale values according to PI-RAD 3 scores was potentially useful, and the grayscale range (42.6–91.8) was a potential predictor for csPC diagnosis.
Cosmesis and feasibility of transvaginal natural orifice Specimen extraction (NOSE) for large organ specimen: a prospective pilot study
Authors: Hwang Woo Yeon , Suh Dong Hoon , Lee Sangchul 
Published: October 2022

Abstract
Background
This study aimed to evaluate cosmetic outcomes and feasibility of transvaginal natural orifice specimen extraction (NOSE) in patients who underwent laparoscopic or robotic surgery for the treatment of benign or malignant diseases of the kidney, liver, stomach, adrenal gland, and bladder.

Methods
This prospective study was conducted at a tertiary hospital between March 2015 and May 2020. The main outcome was cosmetic outcomes of scars assessed using the Patient and Observer Scar Assessment Scale (POSAS) 1 and 8 weeks after surgery. The secondary outcomes were postoperative pain, operating time, and complications. Sexual function was assessed using the Female Sexual Function Index (FSFI) questionnaire 6 months after surgery in 17 patients who were sexually active at the time of surgery.

Results
A total of 38 transvaginal NOSE procedures were performed for the extraction of 33 kidneys, 2 livers, 1 stomach, 1 adrenal gland, and 1 bladder. Observers rated pigmentation and relief scores as most deviant from normal skin (2.9 ± 1.7, 3.0 ± 2.1 at postoperative 1 week; 3.6 ± 1.9, 3.5 ± 2.2 at postoperative 8 weeks, respectively), but the overall scores of each item were low. The patients’ overall satisfaction with postoperative scars was high, and the mean scores for pain and itching were low, with significant improvement from the first week to the eighth week (P = 0.014 and P = 0.006, respectively). Patients also reported low scores on vaginal assessment items, indicating better symptoms, and bleeding improved significantly between the two time points (P = 0.001). Postoperative pain was reduced from moderate during the first 24 h after surgery to mild after 24 h. The mean operative time of the transvaginal NOSE procedure was 28.3 ± 13.3 min. No postoperative complications were associated with the procedure. The mean FSFI total score was 21.2 ± 8.7 (cutoff score for dysfunction is 21), with higher scores indicating better sexual functioning.

Conclusion
Transvaginal NOSE seems to be a feasible procedure with promising cosmetic benefits, for patients who undergo minimally invasive surgery for large organs including the kidney, liver, stomach, adrenal gland, and bladder. A prospective randomized clinical trial is needed to provide solid evidence to support transvaginal NOSE.

Trial registration:
This trial is registered at ClinicalTrials.gov (NCT05113134).
Hospital-based prostate cancer screening in vietnamese men with lower urinary tract symptoms: a classification and regression tree model
Authors: Cuong Nguyen Chi , Vien Nguyen Truong , Thien Nguyen Minh , Hai Phan Thanh , Dang Tran Ngoc 
Published: October 2022

Abstract
Background
Prostate cancer (PCa) is a common disease in men over 65 years of age, and should be detected early, while reducing unnecessary biopsies. This study aims to construct a classification and regression tree (CART) model (i.e., risk stratification algorithm) using multivariable approach to select Vietnamese men with lower urinary tract symptoms (LUTS) for PCa biopsy.

Methods
We conducted a case-control study on 260 men aged ≥ 50 years who visited MEDIC Medical Center, Vietnam in 2017–2018 with self-reported LUTS. The case group included patients with a positive biopsy and the control group included patients with a negative biopsy diagnosis of PCa. Bayesian Model Averaging (BMA) was used for selecting the most parsimonious prediction model. Then the CART with 5-fold cross-validation was constructed for selecting men who can benefit from PCa biopsy in steps by steps and intuitive way.

Results
BMA suggested five potential prediction models, in which the most parsimonious model including PSA, I-PSS, and age. CART advised the following cut-off points in the marked screening sequence: 18 < PSA < 33.5 ng/mL, I-PSS ≥ 19, and age ≥ 71. Patients with PSA ≥ 33.5 ng/mL have a PCa risk was 91.2%; patients with PSA < 18 ng/mL and I-PSS < 19 have a PCa risk was 7.1%. Patient with 18 ≤ PSA < 33.5ng/mL and I-PSS < 19 have a PCa risk is 70% if age ≥ 71; and is 16% if age < 71. In overall, CART reached high predictive value with AUC = 0.915. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CART at the 20% diagnosis probability threshold were 91.5%, 86.2%, 86.9%, 91.2%, and 88.9% respectively; at 80% diagnosis probability threshold were 79.2%, 92.3%, 91.2%, 81.6%, and 85.8% respectively.

Conclusion
CART combining PSA, I-PSS, and age has practical use in hospital-based PCa screening in Vietnamese men with lower urinary tract symptoms.
Novel protein-repellent and antibacterial polymethyl methacrylate dental resin in water-aging for 6 months
Authors: Cao Li , Xie Xianju , Yu Wenqi , Xu Hockin H. K. , Bai Yuxing , Zhang Ke , Zhang Ning 
Published: October 2022

Abstract
Background
The present study aimed to develop a novel protein-repellent and antibacterial polymethyl methacrylate (PMMA) dental resin with 2-methacryloyloxyethyl phosphorylcholine (MPC) and quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM), and to investigate the effects of water-aging for 6 months on the mechanical properties, protein adsorption, and antibacterial activity of the dental resin.

Methods
Four groups were tested: PMMA control; PMMA + 3% MPC; PMMA + 1.5% DMAHDM; and PMMA + 3% MPC + 1.5% DMADDM in acrylic resin powder. Specimens were water-aged for 1 d, 3 months, and 6 months at 37 ℃. Their mechanical properties were then measured using a three-point flexure test. Protein adsorption was measured using a micro bicinchoninic acid (BCA) method. A human saliva microcosm model was used to inoculate bacteria on water-aged specimens and to investigate the live/dead staining, metabolic activity of biofilms, and colony-forming units (CFUs).

Results
The flexural strength and elastic modulus showed a significant loss after 6 months of water-ageing for the PMMA control (mean ± SD; n = 10); in contrast, the new protein repellent and antibacterial PMMA resin showed no strength loss. The PMMA–MPC–DMAHDM-containing resin imparted a strong antibacterial effect by greatly reducing biofilm viability and metabolic activity. The biofilm CFU count was reduced by about two orders of magnitude (p < 0.05) compared with that of the PMMA resin control. The protein adsorption was 20% that of a commercial composite (p < 0.05). Furthermore, the PMMA–MPC–DMAHDM-containing resin exhibited a long-term antibacterial performance, with no significant difference between 1 d, 3 months and 6 months (p > 0.05).

Conclusions
The flexural strength and elastic modulus of the PMMA–MPC–DMAHDM-containing resin were superior to those of the PMMA control after 6 months of water-ageing. The novel PMMA resin incorporating MPC and DMAHDM exhibited potent and lasting protein-repellent and antibacterial properties.
Estimating the burden of diseases attributable to lead exposure in the North Africa and Middle East region, 1990–2019: a systematic analysis for the Global Burden of Disease study 2019
Authors: Rezaee Malihe , Esfahani Zahra , Nejadghaderi Seyed Aria , Abbasi-Kangevari Mohsen , Saeedi Moghaddam Sahar , Ghanbari Ali , Ghamari Azin , Golestani Ali , Foroutan Mehr Elmira , Kazemi Ameneh , Haghshenas Rosa , Moradi Mahsa , Kompani Farzad , Rezaei Negar , Larijani Bagher 
Published: October 2022

Abstract
Background
Lead exposure (LE) and its attributable deaths and disability-adjusted life years (DALYs) have declined in the recent decade; however, it remains one of the leading public health concerns, particularly in regions with low socio-demographic index (SDI) such as the North Africa and Middle East (NAME) region. Hence, we aimed to describe the attributable burden of the LE in this region.

Methods
Data on deaths, DALYs, years of life lost (YLLs), and years lived with disability (YLDs) attributable to LE in the NAME region and its 21 countries from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) 2019 study.

Results
In 2019, the age-standardized death and DALY rates attributable to LE were 23.4 (95% uncertainty interval: 15.1 to 33.3) and 489.3 (320.5 to 669.6) per 100,000 in the region, respectively, both of which were higher among men than women. The overall age-standardized death and DALY rates showed 27.7% and 36.8% decreases, respectively, between 1990 and 2019. In this period, Bahrain, the United Arab Emirates, and Turkey had the highest decreases in the age-standardized death and DALY rates, while Afghanistan, Egypt, and Yemen had the lowest ones. Countries within high SDI quintile had lower attributable burden to LE compared with the low SDI quintile. Cardiovascular diseases and chronic kidney diseases accounted for the 414.2 (258.6 to 580.6) and 28.7 (17.7 to 41.7) LE attributable DALYs per 100,000 in 2019, respectively. The attributable YLDs was 46.4 (20.7 to 82.1) per 100,000 in 2019, which shows a 25.7% reduction (-30.8 to -22.5%) over 1990–2019.

Conclusions
The overall LE and its attributed burden by cause have decreased in the region from 1990–2019. Nevertheless, the application of cost-effective and long-term programs for decreasing LE and its consequences in NAME is needed.
An optimized exosome production strategy for enhanced yield while without sacrificing cargo loading efficiency
Authors: Zhang Rongxin , Bu Te , Cao Ruidan , Li Zhelong , Wang Chen , Huang Bing , Wei Mengying , Yuan Lijun , Yang Guodong 
Published: October 2022

Abstract
Background
Exosome mediated mRNA delivery is a promising strategy for the treatment of multiple diseases. However, the low yield of exosomes is a bottleneck for clinical translation. In this study, we boosted exosome production via simultaneously reducing the expression of genes inhibiting exosome biogenesis and supplementing the culture medium with red cell membrane components.

Results
Among the candidate genes, knocking down of Rab4 was identified to have the highest efficacy in promoting exosome biogenesis while without any obvious cytotoxicity. Additionally, supplementing red cell membrane particles (RCMPs) in the culture medium further promoted exosome production. Combination of Rab4 knockdown and RCMP supplement increased exosome yield up to 14-fold. As a proof-of-concept study, low-density lipoprotein receptor (Ldlr) mRNA was forced expressed in the exosome donor cells and passively encapsulated into the exosomes during biogenesis with this strategy. Though exosome production per cell increased, the booster strategy didn’t alter the loading efficiency of therapeutic Ldlr mRNA per exosome. Consistently, the therapeutic exosomes derived by the strategy alleviated liver steatosis and atherosclerosis in Ldlr−/− mice, similar as the exosomes produced by routine methods.

Conclusions
Together, the proposed exosome booster strategy conquers the low yield bottleneck to some extent and would certainly facilitate the clinical translation of exosomes.
Montelukast reduces grey matter abnormalities and functional deficits in a mouse model of inflammation-induced encephalopathy of prematurity
Authors: Yates Abi G. , Kislitsyna Elena , Alfonso Martin Carla , Zhang Jiaying , Sewell Amy L. , Goikolea-Vives Ane , Cai Valerie , Alkhader Lama F. , Skaland Aleksander , Hammond Basil , Dimitrova Ralica , Batalle Dafnis , Fernandes Cathy , Edwards A. David , Gressens Pierre , Thornton Claire , Stolp Helen B. 
Published: October 2022

AbstractEncephalopathy of prematurity (EoP) affects approximately 30% of infants born < 32 weeks gestation and is highly associated with inflammation in the foetus. Here we evaluated the efficacy of montelukast, a cysteinyl leukotriene receptor antagonist widely used to treat asthma in children, to ameliorate peripheral and central inflammation, and subsequent grey matter neuropathology and behaviour deficits in a mouse model of EoP. Male CD-1 mice were treated with intraperitoneal (i.p.) saline or interleukin-1beta (IL-1β, 40 μg/kg, 5 μL/g body weight) from postnatal day (P)1–5 ± concomitant montelukast (1–30 mg/kg). Saline or montelukast treatment was continued for a further 5 days post-injury. Assessment of systemic and central inflammation and short-term neuropathology was performed from 4 h following treatment through to P10. Behavioural testing, MRI and neuropathological assessments were made on a second cohort of animals from P36 to 54. Montelukast was found to attenuate both peripheral and central inflammation, reducing the expression of pro-inflammatory molecules (IL-1β, IL-6, TNF) in the brain. Inflammation induced a reduction in parvalbumin-positive interneuron density in the cortex, which was normalised with high-dose montelukast. The lowest effective dose, 3 mg/kg, was able to improve anxiety and spatial learning deficits in this model of inflammatory injury, and alterations in cortical mean diffusivity were not present in animals that received this dose of montelukast. Repurposed montelukast administered early after preterm birth may, therefore, improve grey matter development and outcome in EoP.
Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: a systematic approach to profiling neuropathic pain
Authors: Wang Lei , Gunduz Mehmet A. , Semeano Ana T. , Yılmaz Enis C. , Alanazi Feras A. H. , Imir Ozan B. , Yener Ulas , Arbelaez Christian A. , Usuga Esteban , Teng Yang D. 
Published: October 2022

Abstract
Background
People with spinal cord injury (SCI) frequently develop neuropathic pain (NP) that worsens disability and diminishes rehabilitation efficacy. Chronic NP is presently incurable due to poor understanding of underlying mechanisms. We hypothesized that multilocus neuroinflammation (NIF) might be a driver of SCI NP, and tested it by investigating whether NP coexisted with central NIF, neurotransmission (NTM), neuromodulation (NML) and neuroplasticity (NPL) changes post-SCI.

Methods
Female Sprague–Dawley rats (230–250 g) with T10 compression or laminectomy were evaluated for physical conditions, coordinated hindlimb functions, neurological reflexes, and mechanical/thermal sensitivity thresholds at 1 day post-injury (p.i.) and weekly thereafter. Eight weeks p.i., central nervous system tissues were histochemically and immunohistochemically characterized for parameters/markers of histopathology and NIF/NTM/NML/NPL. Also analyzed was the correlative relationship between levels of selected biomarkers and thermosensitivity thresholds via statistical linear regression.

Results
SCI impaired sensorimotor functions, altered reflexes, and produced spontaneous pain signs and hypersensitivity to evoked nociceptive, mechanical, and thermal inputs. Only injured spinal cords exhibited neural lesion, microglia/astrocyte activation, and abnormal expression of proinflammatory cytokines, as well as NIF/NTM/NML/NPL markers. Brains of SCI animals displayed similar pathophysiological signs in the gracile and parabrachial nuclei (GrN and PBN: sensory relay), raphe magnus nucleus and periaqueduct gray (RMN and PAG: pain modulation), basolateral amygdala (BLA: emotional-affective dimension of pain), and hippocampus (HPC: memory/mood/neurogenesis). SCI augmented sensory NTM/NPL (GrN and PBN); increased GAD67 (PAG) level; reduced serotonin (RMN) and fear-off neuronal NTR2 (BLA) expressions; and perturbed neurogenesis (HPC).

Conclusion
T10 compression caused chronic hyperalgesia that coexisted with NIF/NTM/NML/NPL responses at multilevel neuroaxis centers. The data have provided multidimensional biomarkers as new mechanistic leads to profile SCI NP for therapeutic/therapy development.
Olfactory marker protein is unlikely to be cleaved by calpain 5
Authors: Nakashima Noriyuki , Nakashima Kie , Nakashima Akiko , Takano Makoto 
Published: October 2022

AbstractOlfactory maturation marker protein (OMP) is expressed in olfactory receptor neurons and hypothalamic neurons. OMP is a nested gene located in the intron of calpain 5 (CAPN5), a Ca2+-dependent cysteine protease. Despite being located at the same genomic locus, genetic regulation of the reciprocal expression of OMP and CAPN5 has been suggested. By performing a motif search, we detected possible calpain cleavage sites in OMP. However, the direct proteolytic regulation of OMP by CAPN5 is unclear. Here, we generated OMP fused with Myc-tag and His-tag at its N- and C-termini and examined whether CAPN5 cleaves OMP into fragments by detecting immunoreactivity against Myc, OMP and His. Western blotting demonstrated that OMP was unlikely to be cleaved even in the presence of Ca2+ in vitro. We expressed OMP and CAPN5 in HEK293T cells and applied a calcium ionophore under physiological conditions in cellulo, which resulted in no apparent fragmentation of OMP. We also applied liquid chromatography/mass spectrometry to the electrophoresed fractions smaller than the uncut Myc-OMP-His signals, which demonstrated no significant fragmentation of OMP. These results collectively indicate that OMP is unlikely to be cleaved by CAPN5.
Expression of long noncoding RNAs in the ovarian granulosa cells of women with diminished ovarian reserve using high-throughput sequencing
Authors: Dong Li , Xin Xin , Chang Hsun-Ming , Leung Peter C. K. , Yu Chen , Lian Fang , Wu Haicui 
Published: October 2022

Abstract
Background
Infertility is a global reproductive-health problem, and diminished ovarian reserve (DOR) is one of the common causes of female infertility. Long noncoding RNAs (lncRNAs) are crucial regulators of numerous physiological and pathological processes in humans. However, whether lncRNAs are involved in the development of DOR remains to be elucidated.

Methods
Ovarian granulosa cells (OGCs) extracted from infertile women with DOR and from women with normal ovarian reserve (NOR) were subjected to high-throughput sequencing. Comprehensive bioinformatics analysis was conducted to identify the differential expression of messenger RNAs (mRNAs) and lncRNAs. Sequencing results were validated by the selection of lncRNAs and mRNAs using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results
Compared with the NOR group, a total of 244 lncRNAs were upregulated (53 known and 191 novel), and 222 lncRNAs were downregulated (36 known and 186 novel) in the DOR group. Similarly, 457 mRNAs had differential expression between the two groups. Of these, 169 were upregulated and 288 were downregulated. Bioinformatics analysis revealed that the differentially expressed genes of mRNA and lncRNAs were considerably enriched in “cell adhesion and apoptosis”, “steroid biosynthesis”, and “immune system”. A co-expression network comprising lncRNAs and their predicted target genes revealed the possible involvement of the “thyroid hormone signaling pathway” and “protein binding, digestion and absorption” in DOR pathogenesis. The expression of SLC16A10 was positively regulated by multiple lncRNAs. After RT-qPCR validation of seven differentially expressed lncRNAs and mRNAs, respectively, the expression of lncRNA NEAT1, GNG12, ZEB2-AS1, and mRNA FN1, HAS3, RGS4, SUOX were in accordance with RNA-sequencing.

Conclusions
We presented the first data showing that the expression profiles of lncRNA and mRNA in OGCs between NOR and DOR patients using RNA sequencing. The lncRNAs and mRNAs that we identified may serve as novel diagnostic biomarkers for patients with DOR.
Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures
Authors: Lai Benjamin , Yu Huang-Ping , Chang Yu-Jing , Wang Liang-Chin , Chen Che-Kai , Zhang Weiya , Doherty Michael , Chang Shang-Hung , Hsu Jun-Te , Yu Kuang-Hui , Kuo Chang-Fu 
Published: October 2022

Abstract
Objectives
Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension.

Methods
We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates.

Results
Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk [RR], 1.10; 95% confidence interval [CI], 1.03–1.19; p = 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02–1.19; p = 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout.

Conclusions
In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension.