bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study
Authors: Brocklebank Vicky , Walsh Patrick R. , Smith-Jackson Kate , Hallam Thomas M. , Marchbank Kevin J. , Wilson Valerie , Bigirumurame Theophile , Dutt Tina , Montgomery Emma K. , Malina Michal , Wong Edwin K. S. , Johnson Sally , Sheerin Neil S. , Kavanagh David 
Published: June 2023

Abstract
Historically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials of eculizumab with a short follow-up suggested efficacy. We prove, for the first time to our knowledge, in a genotype matched CaHUS cohort that the 5-year cumulative estimate of ESKD-free survival improved from 39.5% in a control cohort to 85.5% in the eculizumab-treated cohort (hazard ratio, 4.95; 95% confidence interval [CI], 2.75-8.90; P = .000; number needed to treat, 2.17 [95% CI, 1.81-2.73]). The outcome of eculizumab treatment is associated with the underlying genotype. Lower serum creatinine, lower platelet count, lower blood pressure, and younger age at presentation as well as shorter time between presentation and the first dose of eculizumab were associated with estimated glomerular filtration rate &gt;60 ml/min at 6 months in multivariate analysis. The rate of meningococcal infection in the treated cohort was 550 times greater than the background rate in the general population. The relapse rate upon eculizumab withdrawal was 1 per 9.5 person years for patients with a pathogenic mutation and 1 per 10.8 person years for those with a variant of uncertain significance. No relapses were recorded in 67.3 person years off eculizumab in those with no rare genetic variants. Eculizumab was restarted in 6 individuals with functioning kidneys in whom it had been stopped, with no individual progressing to ESKD. We demonstrated that biallelic pathogenic mutations in RNA-processing genes, including EXOSC3, encoding an essential part of the RNA exosome, cause eculizumab nonresponsive aHUS. Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may also present with thrombotic microangiopathy.
Trastuzumab-resistant breast cancer cells-derived tumor xenograft models exhibit distinct sensitivity to lapatinib treatment in vivo
Authors: Liu Hao , Ruan Sanbao , Larsen Margaret E. , Tan Congcong , Liu Bolin , Lyu Hui 
Published: June 2023

Abstract
Background
Resistance to HER2-targeted therapies, including the monoclonal antibody trastuzumab and tyrosine kinase inhibitor lapatinib, frequently occurs and currently represents a significant clinical challenge in the management of HER2-positive breast cancer. We previously showed that the trastuzumab-resistant SKBR3-pool2 and BT474-HR20 sublines were refractory to lapatinib in vitro as compared to the parental SKBR3 and BT474 cells, respectively. The in vivo efficacy of lapatinib against trastuzumab-resistant breast cancer remained unclear.

Results
In tumor xenograft models, both SKBR3-pool2- and BT474-HR20-derived tumors retained their resistance phenotype to trastuzumab; however, those tumors responded differently to the treatment with lapatinib. While lapatinib markedly suppressed growth of SKBR3-pool2-derived tumors, it slightly attenuated BT474-HR20 tumor growth. Immunohistochemistry analyses revealed that lapatinib neither affected the expression of HER3, nor altered the levels of phosphorylated HER3 and FOXO3a in vivo. Interestingly, lapatinib treatment significantly increased the levels of phosphorylated Akt and upregulated the expression of insulin receptor substrate-1 (IRS1) in the tumors-derived from BT474-HR20, but not SKBR3-pool2 cells.

Conclusions
Our data indicated that SKBR3-pool2-derived tumors were highly sensitive to lapatinib treatment, whereas BT474-HR20 tumors exhibited resistance to lapatinib. It seemed that the inefficacy of lapatinib against BT474-HR20 tumors in vivo was attributed to lapatinib-induced upregulation of IRS1 and activation of Akt. Thus, the tumor xenograft models-derived from SKBR3-pool2 and BT474-HR20 cells serve as an excellent in vivo system to test the efficacy of other HER2-targeted therapies and novel agents to overcome trastuzumab resistance against HER2-positive breast cancer.
Complete chloroplast genome structural characterization of two Phalaenopsis (Orchidaceae) species and comparative analysis with their alliance
Authors: Tao Lei , Duan Hanning , Tao Kaifeng , Luo Yan , Li Qingqing , Li Lu 
Published: June 2023

Abstract
Background
The taxonomy and infrageneric delimitation of Phalaenopsis Blume has been significantly disputed due to some overlapping morphological features between species related, which needed further evidence for clarification. The structural characterization of complete chloroplast genomes of P. storbatiana and P. wilsonii were analyzed and compared with those of related taxa to provide a better understanding of their genomic information on taxonomy and phylogeny.

Results
It was shown that chloroplast genomes of Phalaenopsis storbatiana and P. wilsonii had a typical quadripartite structure with conserved genome arrangements and moderate divergence. The chloroplast genomes of P. storbatiana and P. wilsonii were 145,885 bp and 145,445 bp in length, respectively, and shared a similar GC content of 36.8%. Gene annotations of two species revealed 109 single-copy genes consistently. In addition, 20 genes duplicated in the inverted regions, 16 genes each possessed one or more introns, and five ndh (NA (D)H dehydrogenase) genes were observed in both. Comparative analysis of the total cp genomes of P. storbatiana and P. wilsonii with those of other six related Phalaenopsis species confirmed the stable sequence identity for coding and non-coding regions and higher sequence variation in SC regions than IR regions. Most of their protein-coding genes had a high degree of codon preference. Moreover, 45 genes were discovered with significantly positive selection. However, different amplifications in IR regions were observed in these eight species. Phylogenetic analysis based on CDS from 60 species representing main clades in Orchidaceae indicated that Phalaenopsis species including P. stobartiana and P. wilsonii formed a monophyletic clade with high bootstrap nested in tribe Vandeae of Epidendroideae, which was consistent with those from previous studies.

Conclusions
The results could provide insight into understanding the plastome evolution and phylogenetic relationships of Phalaenopsis.
Oxalate nephropathy in an elderly patient with newly diagnosed celiac disease – a case report
Authors: Zijlstra Hendrik W. , Stegeman Coen A. 
Published: June 2023

AbstractOxalate nephropathy, due to secondary hyperoxaluria has widely been described in gastrointestinal diseases. However, reports of oxalate nephropathy in newly diagnosed celiac disease are rare.A 72-year-old Caucasian male presented to the hospital with abdominal discomfort and acute renal insufficiency with a creatinine of 290 µmol/L.The clinical course, laboratory results and urinalysis were suspect for tubular injury. Renal biopsy showed calcium oxalate depositions. Elevated plasma and urine oxalate levels established the diagnosis oxalate nephropathy.The abdominal complaints with steatorrhea and positive anti-tissue transglutaminase antibodies were diagnosed as celiac disease, which was confirmed after duodenal biopsies.Treatment with prednisone, and gluten-free, low oxalate and normal calcium diet, lowered the plasma oxalate levels and improved his renal function.Decreased absorption of free fatty acids can lead to increased free oxalate in the colon due to the binding of free fatty acids to calcium, preventing the formation of the less absorbable calcium oxalate in the colon.Oxalate dispositions in the kidney can lead to acute tubular injury and chronic renal insufficiency. Celiac disease is therefore one of the intestinal diseases that can lead to hyperoxaluria and oxalate nephropathy.
A novel nomogram based on cell cycle-related genes for predicting overall survival in early-onset colorectal cancer
Authors: Xiang Meijuan , Gao Yuan , Zhou Yue , Wang Muqing , Yao Xueqing 
Published: June 2023

Abstract
Background
Although the incidence of late-onset colorectal cancer (LOCRC) has decreased, the incidence of early-onset colorectal cancer (EOCRC) is still rising dramatically. Heterogeneity in the genomic, biological, and clinicopathological characteristics between EOCRC and LOCRC has been revealed. Therefore, the previous prognostic models based on the total CRC patient population might not be suitable for EOCRC patients. Here, we constructed a prognostic classifier to enhance the precision of individualized treatment and management of EOCRC patients.

Methods
EOCRC expression data were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The regulatory pathways were explored by gene set enrichment analysis (GSEA). The prognostic model was developed by univariate Cox-LASSO-multivariate Cox regression analyses of GEO samples. TCGA samples were used to verify the model. The expression and mutation profiles and immune landscape of the high-risk and low-risk cohorts were analyzed and compared. Finally, the expression and prognostic value of the model genes were verified by immunohistochemistry and qRT‒PCR analysis.

Results
The cell cycle was identified as the most significantly enriched oncological signature of EOCRC. Then, a 4-gene prognostic signature comprising MCM2, INHBA, CGREF1, and KLF9 was constructed. The risk score was an independent predictor of overall survival. The area under the curve values of the classifier for 1-, 3-, and 5-year survival were 0.856, 0.893, and 0.826, respectively, in the training set and 0.749, 0.858, and 0.865, respectively, in the validation set. Impaired DNA damage repair capability (p < 0.05) and frequent PIK3CA mutations (p < 0.05) were found in the high-risk cohort. CD8 T cells (p < 0.05), activated memory CD4 T cells (p < 0.01), and activated dendritic cells (p < 0.05) were clustered in the low-risk group. Finally, we verified the expression of MCM2, INHBA, CGREF1, and KLF9. Their prognostic value was closely related to age.

Conclusion
In this study, a robust prognostic classifier for EOCRC was established and validated. The findings may provide a reference for individualized treatment and medical decision-making for patients with EOCRC.
High glucose promotes the progression of colorectal cancer by activating the BMP4 signaling and inhibited by glucagon-like peptide-1 receptor agonist
Authors: Ma Bingwei , Wang Xingchun , Ren Hui , Li Yingying , Zhang Haijiao , Yang Muqing , Li Jiyu 
Published: June 2023

Abstract
Background
The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM.

Methods
We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People’s Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4.

Results
BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4.

Conclusions
BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes.
SARS-CoV-2 incidence in secondary schools; the role of national and school-initiated COVID-19 measures
Authors: Jonker L. , Linde K. J. , de Boer A. R. , Ding E. , Zhang D. , de Hoog M. L. A. , Herfst S. , Heederik D. J. J. , Fraaij P. L. A. , Bluyssen P. M. , Wouters I. M. , Bruijning-Verhagen P. C. J. L. 
Published: June 2023

Abstract
Introduction
Our aim was to gain insight into the effect of COVID-19 measures on SARS-CoV-2 incidence in secondary schools and the association with classroom CO2 concentration and airborne contamination.

Methods
Between October 2020—June 2021, 18 schools weekly reported SARS-CoV-2 incidence and completed surveys on school-initiated COVID-19 measures (e.g. improving hygiene or minimizing contacts). CO2 was measured in occupied classrooms twice, and SARS-CoV-2 air contamination longitudinally using electrostatic dust collectors (EDC) and analyzed using RT-qPCR. National COVID-19 policy measures varied during pre-lockdown, lockdown and post-lockdown periods. During the entire study, schools were recommended to improve ventilation. SARS-CoV-2 incidence rate ratios (IRR) were estimated by Generalized Estimating Equation (GEE) models.

Results
During 18 weeks follow-up (range: 10–22) SARS-CoV-2 school-incidence decreased during national lockdown (adjusted IRR: 0.41, 95%CI: 0.21–0.80) and post-lockdown (IRR: 0.60, 0.39–0.93) compared to pre-lockdown. School-initiated COVID-19 measures had no additional effect. Pre-lockdown, IRRs per 10% increase in time CO2 exceeded 400, 550 and 800 ppm above outdoor level respectively, were 1.08 (1.00–1.16), 1.10 (1.02–1.19), and 1.08 (0.95–1.22). Post-lockdown, CO2-concentrations were considerably lower and not associated with SARS-CoV-2 incidence. No SARS-CoV-2 RNA was detected in any of the EDC samples.

Conclusion
During a period with low SARS-CoV-2 population immunity and increased attention to ventilation, with CO2 levels most of the time below acceptable thresholds, only the national policy during and post-lockdown of reduced class-occupancy, stringent quarantine, and contact testing reduced SARS-CoV-2 incidence in Dutch secondary schools. Widespread SARS-CoV-2 air contamination could not be demonstrated in schools under the prevailing conditions during the study.
Feasibility of artificial intelligence assisted quantitative muscle ultrasound in carpal tunnel syndrome
Authors: Kim Sun Woong , Kim Sunwoo , Shin Dongik , Choi Jae Hyeong , Sim Jung Sub , Baek Seungjun , Yoon Joon Shik 
Published: June 2023

Abstract
Background
In case of focal neuropathy, the muscle fibers innervated by the corresponding nerves are replaced with fat or fibrous tissue due to denervation, which results in increased echo intensity (EI) on ultrasonography. EI analysis can be conducted quantitatively using gray scale analysis. Mean value of pixel brightness of muscle image defined as EI. However, the accuracy achieved by using this parameter alone to differentiate between normal and abnormal muscles is limited. Recently, attempts have been made to increase the accuracy using artificial intelligence (AI) in the analysis of muscle ultrasound images. CTS is the most common disease among focal neuropathy. In this study, we aimed to verify the utility of AI assisted quantitative analysis of muscle ultrasound in CTS.

Methods
This is retrospective study that used data from adult who underwent ultrasonographic examination of hand muscles. The patient with CTS confirmed by electromyography and subjects without CTS were included. Ultrasound images of the unaffected hands of patients or subjects without CTS were used as controls. Ultrasonography was performed by one physician in same sonographic settings. Both conventional quantitative grayscale analysis and machine learning (ML) analysis were performed for comparison.

Results
A total of 47 hands with CTS and 27 control hands were analyzed. On conventional quantitative analysis, mean EI ratio (i.e. mean thenar EI/mean hypothenar EI ratio) were significantly higher in the patient group than in the control group, and the AUC was 0.76 in ROC analysis. In the analysis using machine learning, the AUC was the highest for the linear support vector classifier (AUC = 0.86). When recursive feature elimination was applied to the classifier, the AUC value improved to 0.89.

Conclusion
This study showed a significant increase in diagnostic accuracy when AI was used for quantitative analysis of muscle ultrasonography. If an analysis protocol using machine learning can be established and mounted on an ultrasound machine, a noninvasive and non-time-consuming muscle ultrasound examination can be conducted as an ancillary tool for diagnosis.
Patterns and predictors of periodontal disease and tooth loss among users of smokeless tobacco
Authors: Nasir Syed Muazzam , Sultana Tajwer , Hashmi Shahkamal , Ahmed Mansoor 
Published: June 2023

AbstractBackgroundSmokeless tobacco (SLT) products of several different types are widely used in several South Asian countries including Pakistan. These products are consumed in different forms and with different names. The study aims to determine adverse effects of the SLT consumption on periodontal tissues.MethodsThis cross sectional study was conducted in Karachi, Pakistan. It recruited 377 users of (SLT) with 231 males (61.3%) and 146 females (38.7%) of age 15 to 45 years. After obtaining informed consent, quantitative data were collected via a questionnaire followed by intra oral clinical examination to determine presence of periodontal diseases using community periodontal index (CPI). To determine the association between periodontal diseases and smokeless tobacco consumption habits, Chi Square test was conducted.ResultsGingival recession (Class II-IV) (65.8%) was the most prevalent periodontal disease among SLT users. CPI score was high (CPI score 3 and 4) in 31.3% participants, whereas tooth loss was found in 21%. Among types of SLT products, gutka (28.6%) and betel quid (23.3%) were most commonly used. Using SLT for five or more years was found to be associated with a high CPI score, gingival recession (Class II-IV), moderate to severe tooth mobility, and presence of tooth loss.ConclusionsThe study found statistically significant association between duration in years of using SLT and periodontal disease including gingival recession, tooth mobility and tooth loss. However, no significant results were found between retention during single use and frequency of SLT use per day. However, the link of these factors with the periodontal disease cannot be eliminated.
Behaviors and practices of incarcerated women towards menstrual hygiene in a large urban prison in Uganda: a phenomenological qualitative study
Authors: Nabiryo Margaret , Ondia Miriam , Izudi Jonathan 
Published: June 2023

Abstract
Background
Deplorable and unconducive conditions in prisons present serious challenges to menstrual hygiene management. However, little is known about menstrual hygiene among incarcerated women in Uganda. Our study explored the behaviors and practices of incarcerated women regarding menstrual hygiene management in a large government prison in Uganda. In addition, we explored the barriers to menstrual hygiene management in this population.

Methods
In this phenomenological qualitative study, we conducted in-depth interviews with incarcerated women aged 20–49 years and key informant interviews with female prison officers (wardresses) at Luzira Prison in Kampala, Uganda. The data were analyzed using content analysis and the findings were presented using themes/sub-themes along with participant quotes.

Results
We interviewed 15 incarcerated women aged 20–49 years (mean age, 29.5 ± 8.7 years) and five key informants aged 30–50 years (mean, 42.6 ± 4.9) about menstrual hygiene behaviors and practices, including barriers to menstrual hygiene. Five sub-themes emerged concerning behaviors and practices of menstrual hygiene among incarcerated women. Findings reveal the behaviors and practices of menstrual hygiene management were characterized by infrequent change of menstrual pads, lack of privacy during menstrual hygiene practices, use of poor-quality menstrual hygiene materials, and improper disposal of used sanitary products. However, bathing with soap and water during menstruation was frequent and non-restricted. Three sub-themes emerged as barriers to menstrual hygiene practices, largely at the institutional level, and they included unhygienic sanitary facilities, unreliable access to clean water, and insufficient sanitary products.

Conclusions
Behaviors and practices of incarcerated women fall short of desired standards and they face several barriers to practicing menstrual hygiene. The prison authorities should provide sufficient sanitary products like pads, and knickers including soap, construct more sanitary facilities, educate about the safe disposal of used sanitary products, and provide sufficient clean water to promote good menstrual hygiene management among incarcerated women.