bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type 2B von Willebrand disease mutations differentially perturb autoinhibition of the A1 domain
Authors: Legan Emily R. , Liu Yi , Arce Nicholas A. , Parker Ernest T. , Lollar Pete , Zhang X. Frank , Li Renhao 
Published: December 2022

Abstract
Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder in which a subset of point mutations in the von Willebrand factor (VWF) A1 domain and recently identified autoinhibitory module (AIM) cause spontaneous binding to glycoprotein Ibα (GPIbα) on the platelet surface. All reported type 2B VWD mutations share this enhanced binding; however, type 2B VWD manifests as variable bleeding complications and platelet levels in patients, depending on the underlying mutation. Understanding how these mutations localizing to a similar region can result in such disparate patient outcomes is essential for detailing our understanding of VWF regulatory and activation mechanisms. In this study, we produced recombinant glycosylated AIM-A1 fragments bearing type 2B VWD mutations and examined how each mutation affects the A1 domain’s thermodynamic stability, conformational dynamics, and biomechanical regulation of the AIM. We found that the A1 domain with mutations associated with severe bleeding occupy a higher affinity state correlating with enhanced flexibility in the secondary GPIbα-binding sites. Conversely, mutation P1266L, associated with normal platelet levels, has similar proportions of high-affinity molecules to wild-type (WT) but shares regions of solvent accessibility with both WT and other type 2B VWD mutations. V1316M exhibited exceptional instability and solvent exposure compared with all variants. Lastly, examination of the mechanical stability of each variant revealed variable AIM unfolding. Together, these studies illustrate that the heterogeneity among type 2B VWD mutations is evident in AIM-A1 fragments.
Benchmarking full-length transcript single cell mRNA sequencing protocols
Authors: Probst Victoria , Simonyan Arman , Pacheco Felix , Guo Yuliu , Nielsen Finn Cilius , Bagger Frederik Otzen 
Published: December 2022

AbstractBackgroundSingle cell mRNA sequencing technologies have transformed our understanding of cellular heterogeneity and identity. For sensitive discovery or clinical marker estimation where high transcript capture per cell is needed only plate-based techniques currently offer sufficient resolution.ResultsHere, we present a performance evaluation of four different plate-based scRNA-seq protocols. Our evaluation is aimed towards applications taxing high gene detection sensitivity, reproducibility between samples, and minimum hands-on time, as is required, for example, in clinical use. We included two commercial kits, NEBNext® Single Cell/ Low Input RNA Library Prep Kit (NEB®), SMART-seq® HT kit (Takara®), and the non-commercial protocols Genome & Transcriptome sequencing (G&T) and SMART-seq3 (SS3). G&T delivered the highest detection of genes per single cell. SS3 presented the highest gene detection per single cell at the lowest price. Takara® kit presented similar high gene detection per single cell, and high reproducibility between samples, but at the absolute highest price. NEB® delivered a lower detection of genes but remains an alternative to more expensive commercial kits.ConclusionFor the tested kits we found that ease-of-use came at higher prices. Takara can be selected for its ease-of-use to analyse a few samples, but we recommend the cheaper G&T-seq or SS3 for laboratories where a substantial sample flow can be expected.
New insights into genome annotation in Podospora anserina through re-exploiting multiple RNA-seq data
Authors: Lelandais Gaëlle , Remy Damien , Malagnac Fabienne , Grognet Pierre 
Published: December 2022

Abstract
Background
Publicly available RNA-seq datasets are often underused although being helpful to improve functional annotation of eukaryotic genomes. This is especially true for filamentous fungi genomes which structure differs from most well annotated yeast genomes. Podospora anserina is a filamentous fungal model, which genome has been sequenced and annotated in 2008. Still, the current annotation lacks information about cis-regulatory elements, including promoters, transcription starting sites and terminators, which are instrumental to integrate epigenomic features into global gene regulation strategies.

Results
Here we took advantage of 37 RNA-seq experiments that were obtained in contrasted developmental and physiological conditions, to complete the functional annotation of P. anserina genome. Out of the 10,800 previously annotated genes, 5’UTR and 3’UTR were defined for 7554, among which, 3328 showed differential transcriptional signal starts and/or transcriptional end sites. In addition, alternative splicing events were detected for 2350 genes, mostly due alternative 3’splice sites and 1732 novel transcriptionally active regions (nTARs) in unannotated regions were identified.

Conclusions
Our study provides a comprehensive genome-wide functional annotation of P. anserina genome, including chromatin features, cis-acting elements such as UTRs, alternative splicing events and transcription of non-coding regions. These new findings will likely improve our understanding of gene regulation strategies in compact genomes, such as those of filamentous fungi. Characterization of alternative transcripts and nTARs paves the way to the discovery of putative new genes, alternative peptides or regulatory non-coding RNAs.
The impact of Helicobacter pylori infection and eradication therapy containing minocycline and metronidazole on intestinal microbiota
Authors: Cui Meng-Yan , Cui Zhen-Yu , Zhao Meng-Qi , Zhang Meng-Jie , Jiang Qiao-Li , Wang Jing-Jing , Lu Lun-Gen , Lu Ying-Ying 
Published: December 2022

Abstract
Background
Helicobacter pylori (H. pylori) infection is associated with remodeling of gut microbiota. Many studies have found H. pylori infection and eradication therapy can alter the gut microbiota. However, few studies explored the impact of eradication therapy containing minocycline and metronidazole on gut microbiota.

Aim
The objective of the present study was to explore the changes of gut microbiota after H. pylori infection. Besides, learn more about the dynamic changes of gut microbiota during different stages of eradication treatment containing minocycline, metronidazole, bismuth agents and proton pump inhibitors.

Methods
Sixty stool samples from the patients with H. pylori infection before eradication, 14 and 42 days after eradication, and ten stool samples from non-infected individuals were collected. Subsequently, we performed 16S rRNA gene amplicon sequencing to analyze these samples, and the results were evaluated by using alpha diversity, beta diversity and microbial composition analyses. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was also used to predict the metabolic pathways according to the Kyoto Encyclopedia of Genes and Genomes database.

Results
The alpha and beta diversity of the microbiota changed significantly in H. pylori infected individuals, but returned to baseline 42 days after eradication therapy. At the genus level, the abundances of Bacteroidetes, [Ruminococcus]_gnavus_group, Ruminococcaceae_Incertae_Sedis, Tuzzrealla, Butyricicoccus were significantly lower in the H. pylori infected group. Bacterial abundance was also dynamically changing during eradication treatment. In addition, PICRUST analysis found the levels of uronic acid metabolism, uncharacterized transport system, and biosynthesis of unsaturated fatty acids were higher in H. pylori infected individuals than in the non-infected group.

Conclusions
Intestinal microbiota diversity, composition, functional predictions altered significantly after H. pylori infection, and gradually returned to healthy control levels after the application of eradication therapy containing minocycline and metronidazole in one month and a half.
The minimum effective concentration (MEC90) of ropivacaine for ultrasound-guided quadratus lumborum block for analgesia after cesarean delivery: a dose finding study
Authors: Cao Rong , Li Xuehan , Yang Jing , Deng Lingmei , Cui Yu 
Published: December 2022

Abstract
Background
Quadratus lumborum block was recently proposed as an alternative technique for post-cesarean delivery analgesia. However, there is not a definite optimum concentration of local anesthetics. A biased coin design up-and-down method was used to explore the minimum effective concentration of ropivacaine in quadratus lumborum block for satisfactory analgesia after cesarean delivery.

Methods
Fifty-six patients weighing 60–80 kg after cesarean section and with ages between 18 and 40 years were recruited. For the posterior quadratus lumborum block, a volume of 25 ml of the assigned concentration of ropivacaine was injected bilaterally.
The concentration administered to each patient depended on the response to the previous dose. The first patient received 0.25%. If a successful block was observed, the next patient was randomized to receive the same ropivacaine concentration (with a probability of 0.89) or 0.025% less (with a probability of 0.11). After any block failure, the concentration was always increased by 0.025% for the next. The study ended when 45 successful blocks were obtained.
We defined effective quadratus lumborum block as a resting visual analog score ≤ 3 and the absence of a need for rescue anesthetics.

Results
The 90% minimum effective concentration of ropivacaine was 0.335% (95% CI 0.306 to 0.375%), and the 99% minimum effective concentration was 0.371% (95% CI 0.355 to 0.375%). The sufentanil consumption was 11 (11,13) and 24 (22,27) μg at 12 and 24 hours after quadratus lumborum block, respectively.

Conclusions
The optimum dosage of ropivacaine is a 25 ml volume of 0.335% for quadratus lumborum block after cesarean delivery.

Trial registration
The study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000040415).
Racial or ethnic differences on treatment adherence and persistence among patients with inflammatory bowel diseases initiated with biologic therapies
Authors: Cai Qian , Ding Zhijie , Fu Alex Z. , Patel Aarti A. 
Published: December 2022

Abstract
Background
Inflammatory bowel disease (IBD) is a chronic disease with the potential for significant morbidity in case of suboptimal treatment (e.g. low treatment adherence). In spite of immense research in IBD, literature on association of IBD with race/ethnicity is fragmented. In this study, we aimed to evaluate the association between race/ethnicity and treatment adherence and persistence among patients with Crohn’s disease (CD) or ulcerative colitis (UC) initiated with biologic therapies.

Methods
This observational, retrospective study utilized the Optum Clinformatics (Optum) Extended Data Mart Socioeconomic Status (SES) database. Adult patients with ≥ 2 medical claims for CD or UC diagnosis, ≥ 1 medical or pharmacy claim for corresponding FDA-approved biologic therapy, and a ≥ 12-month pre-index (index date: date of the first biologic medical/pharmacy claim) continuous health plan enrollment were included. Treatment adherence was measured as the proportion of days covered of ≥ 80% and treatment persistence by the number of days from the index date to the biologics discontinuation date. Switching among biologics was allowed for both treatment adherence and treatment persistence. Multivariable regression analyses were performed to evaluate the association between race/ethnicity and treatment adherence/persistence.

Results
Among patients with CD (N = 1430) and UC (N = 1059) included, majority were White (CD: 80.3%, UC: 78.3%), followed by African Americans (AA; CD: 10.5%, UC: 9.7%). Among patients with CD, AA were significantly less likely to adhere to biologics (adjusted OR [95%CI]: 0.61 [0.38; 0.99]) and more likely to discontinue biologics earlier (adjusted HR [95%CI]: 1.52 [1.16; 2.0]) during the follow-up period compared to Whites, after adjusting for other patient sociodemographic and clinical characteristics. Among patients with UC, no significant differences in the treatment adherence/persistence were observed between different races/ethnicities.

Conclusions
Patients with CD were found to display racial differences in the treatment adherence and persistence of biologics, with significantly lower adherence and earlier discontinuation in AA compared to Whites. Such differences were not observed in patients with UC. Future studies are warranted to understand the possible reasons for racial differences, particularly in patients with CD.
The company we keep. Using hemodialysis social network data to classify patients’ kidney transplant attitudes with machine learning algorithms
Authors: Aljurbua Rafaa , Gillespie Avrum , Obradovic Zoran 
Published: December 2022

AbstractBackgroundHemodialysis clinic patient social networks may reinforce positive and negative attitudes towards kidney transplantation. We examined whether a patient’s position within the hemodialysis clinic social network could improve machine learning classification of the patient’s positive or negative attitude towards kidney transplantation when compared to sociodemographic and clinical variables.MethodsWe conducted a cross-sectional social network survey of hemodialysis patients in two geographically and demographically different hemodialysis clinics. We evaluated whether machine learning logistic regression models using sociodemographic or network data best predicted the participant’s transplant attitude. Models were evaluated for accuracy, precision, recall, and F1-score.ResultsThe 110 surveyed participants’ mean age was 60 ± 13 years old. Half (55%) identified as male, and 74% identified as Black. At facility 1, 69% of participants had a positive attitude towards transplantation whereas at facility 2, 45% of participants had a positive attitude. The machine learning logistic regression model using network data alone obtained a higher accuracy and F1 score than the sociodemographic and clinical data model (accuracy 65% ± 5% vs. 61% ± 7%, F1 score 76% ± 2% vs. 70% ± 7%). A model with a combination of both sociodemographic and network data had a higher accuracy of 74% ± 3%, and an F1-score of 81% ± 2%.ConclusionSocial network data improved the machine learning algorithm’s ability to classify attitudes towards kidney transplantation, further emphasizing the importance of hemodialysis clinic social networks on attitudes towards transplant.
Eczema as a protective factor for brain cancer: a meta-analysis
Authors: Zhu Yun , Teng Yirong , Xu Shuangyan , Xu Yinde , Zhu Boheng , Yan Weimin , Liu Jie 
Published: December 2022

Abstract
Background
Brain cancer is one of the most aggressive cancer types owing to poor treatment effects. Epidemiological studies have demonstrated that allergies may increase the disease risk. Therefore, this study evaluated the association between eczema and the risk of various brain cancers.

Methods
We systematically searched the PubMed and Embase databases from their inception until June 23, 2022. Two reviewers independently reviewed and screened the articles, extracted data, assessed the study quality, and pooled the results. Stata software was used to generate pooled odds ratios and 95% confidence intervals (CIs).

Results
We included 20 studies comprising 5,117,222 patients that investigated the relationship between eczema and brain cancer. Eczema was significantly inversely associated with the risk of brain cancer (odds ratio [OR], 0.82; 95% CI, 0.77–0.87), glioma (OR, 0.53; 95% CI, 0.14–2.02), meningioma (OR, 0.74; 95% CI, 0.66–0.84), and acoustic neuroma (OR, 0.60; 95% CI, 0.41–0.88). Interesting, The strong correlation between eczema and the reduced risk of brain cancer was observed in people over 16 years old (OR, 0.79; 95% CI, 0.71–0.88), but not in those under 16 years old (OR, 0.94; 95% CI, 0.79–1.11). In addition, subgroup analyses found that eczema significantly decreased the glioma risk in Europeans (OR, 0.73; 95% CI, 0.65–0.82) but not Australians (OR, 0.53; 95% CI, 0.14–2.02) or Americans (OR, 1.01; 95% CI, 0.69–1.46).

Conclusion
Eczema may be considered as a potential protective factor of brain cancer in population aged over 16 years. However, this relationship requires verification using large-scale clinical data.
Splenic lymphangiomas as a common indication for splenectomy: a case series with literature review
Authors: Efared Boubacar , Bako Aïchatou Balaraba Abani , Younssa Hama , Boubacar Idrissa , Zabeirou Aliou , Koura Hamadou Halidou , Boureima Habiba Salifou , Amadou Soumaila , Coulibaly Idrissa Seriba , Lassey James Didier , Nouhou Hassan 
Published: December 2022

Abstract
Background
Splenic lymphangiomas (SL) are very rare benign cystic lesions found in pediatric population. Their occurrence in adults is exceptional. Splenectomy is the common management of splenic lesions for diagnostic and/or therapeutic purpose. Our aim is to report additional cases of SL diagnosed on splenectomy specimens at our Pathology laboratory with literature review.

Methods
This is a retrospective study including all cases of splenectomy recorded at our Pathology laboratory (June 2020–August 2022). We performed a comparison of clinicopathological features between patients with SL and those with other benign splenic diseases.

Results
Sixteen cases of splenectomy were included. The mean age was 30.25 years (range of 6–70 years). The final histopathological diagnoses were congestive spleens in all cases of sickle cell disease (SCD) (5/16 patients, 31.25%), splenic cystic lymphangiomas (4/16 patients, 25%), capsular splenic infiltration by gastric and colic cancers (3/16 cases, 18.75%), splenic abscess (2/16 cases, 12.5%) and splenic rupture with subcapsular hematoma (1/16 patients, 6.25%). 12/16 patients (75%) had benign splenic conditions (4/12 with SL, 5/12 with SCD, 2/12 with abscess and 1/12 with splenic trauma). Patients with SL were older than those with other benign splenic conditions (mean age of 28.27 years versus 20.87 years). Also patients with SL presented with massive splenomegaly (mean splenic weight of 1675 g versus 418.75 g, mean splenic size of 19.62 cm versus 14.63 cm). Open surgery was performed in 15/16 patients (93.75%).

Conclusion
Unlike previous studies, our series shows that SL are a common indication for splenectomy and occur in older patients with massive cystic splenomegaly. Open splenectomy is still an usual surgical practice in our country.
VEGF, EGFR and PSMA as possible imaging targets of lymph node metastases of urothelial carcinoma of the bladder
Authors: van der Fels Christa Anne Maria , Leliveld Annemarie , Buikema Henk , van den Heuvel Marius Christianus , de Jong Igle Jan 
Published: December 2022

Abstract
Background
In this study we investigated the expression of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and prostate-specific membrane antigen (PSMA) to analyze their potency as targets for the detection of lymph node (LN) metastases of urothelial carcinoma of the bladder.

Methods
Antigen expression was determined in 40 samples with urothelial carcinoma and compared to 17 matched samples without metastases by immunohistochemistry. The total immunostaining score (TIS 0–12) was determined as the product of a proportion score (PS 0–4) and intensity score (IS 0–3).

Results
VEGF expression was high in primary tumor and LN metastases (median TIS 8 in both) and VEGF expression was also seen in LNs without metastases (median TIS 6). EGFR expression was low in primary tumor and LN metastases (median TIS 3 and 2 respectively) and absent in LNs without metastases. PSMA expression was low in samples with urothelial carcinoma (median TIS 2).

Conclusion
VEGF shows moderate to high expression levels in both primary tumors and LN metastases and could be a candidate as a target agent for imaging modalities of urothelial carcinoma. EGFR and PSMA do show low staining levels in tumor tissue with urothelial carcinoma and do not seem suitable as target agents.
Trial registration: The Medical Ethics Review Board of the University Medical Center Groningen approved this study on 14 December 2017 (METc UMCG 2017/639). Trial registration number (UMCG Research Register): 201700868.
Pain Interventions for people with dementia: a quasi-experimental study
Authors: Spichiger Frank , Volken Thomas , Bosshard Georg , Zigan Nicole , Blanc Geneviève , Büscher Andreas , Nagl-Cupal Martin , Bernard Mathieu , Rubli Truchard Eve , Larkin Philip , Koppitz Andrea 
Published: December 2022

Abstract
Background
Due to the complexity of the provision of care for people with dementia, pain assessment and management is still considered to be lacking. An optimal way to support frontline staff in providing pain assessment and management for people with dementia living in nursing homes has not yet been identified. The success of supporting interventions seems dependent on contextual factors in the nursing homes. This study, therefore, analyzes the feasibility of a nurse-led training intervention, using repeated on-site case studies, in modifying pain intensity and frequency in people with dementia.

Methods
Using a quasi-experimental design, we undertook a multi-center study of nurse-led training in pain management, with subsequent on-site case studies. Healthcare workers from 3 nursing homes assessed pain in 164 residents with dementia over 147 days. We used mixed-effect growth curve models with spline regression to analyze the data.

Results
We found that on-site case studies support frontline staff with pain management and assessment. Repeated reflection in case studies led to significantly longer pain free intervals (from 4.7 at baseline to 37.1 days at second follow-up) and decreased frequency of pain events (OR 0.54 at first follow-up and 0.43 at second follow-up). However no trends regarding pain intensity could be found. Therefore, on-site case studies may be valuable for improving pain frequency and pain-free intervals over time.

Conclusion
This feasibility study shows the potential of on-site support for frontline nursing home staff. On-site case studies may also affect health outcomes in people with dementia. However, the complexity of dementia care necessitates the management of a broader range of needs.

Trial registration
The study was retrospectively registered on the tenth of January 2017 with the German registry of clinical trials (DRKS00009726).