bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid cast nephropathy: A rare presentation of multiple myeloma–associated light chain amyloidosis
Authors: Reis Marina , Rodrigues Ana , Cristovão Maques Joana , Góis Mário , Sousa Helena , Nolasco Fernando 
Published: December 2021

Introduction: Monoclonal immunoglobulins can cause a variety of histologic patterns of kidney injury, depending on the physicochemical properties. Multiple myeloma manifests more often as light-chain nephropathy. On the other hand, light-chain amyloidosis leads to glomerular and vascular amyloid deposits, but a less common presentation with amyloid casts has also been described. Rarely, more than one histologic pattern can be present in the same patient. Case report: We report a case of a 73-year-old man, diagnosed with multiple myeloma that 8 months after achieving partial response to chemotherapy develops acute kidney injury and nephrotic syndrome. Kidney biopsy revealed features of light-chain nephropathy, amyloid cast nephropathy, and glomerular and vascular amyloid deposits. Immunofluorescence was positive for IgA (++) and lambda chains (+++) and negative for kappa chains. After the diagnosis of multiple myeloma-associated light-chain amyloidosis, chemotherapy was initiated; unfortunately, the patient died 1 month after the diagnosis. Conclusion: Amyloid casts, isolated or accompanied by other renal or extra-renal amyloid deposits, are another form of tubular toxicity caused by dysproteinemias and should be systematically screened in kidney biopsies.
Primary adenocarcinoma of renal pelvis or ureter: an uncommon histopathological entity seen in three cases
Authors: Agrawal Shashank , Singh Abhishek G. , Sabnis Ravindra B. , Desai Mahesh R. 
Published: December 2021

Abstract
Background
Primary adenocarcinoma of renal pelvis or ureter is rarest (< 1%) among all urothelial tumors. Regrettably, no characteristic symptoms, radiological features and treatment for this tumor are reported. We report three cases of adenocarcinoma of renal pelvis and ureter.

Case presentation
Case 1 had grossly hydronephrotic non-functional right kidney and underwent percutaneous nephrostomy followed by laparoscopic simple nephrectomy. Incidentally, histopathological examination reported adenocarcinoma of renal pelvis. Whole-body positron emission tomography-CT (PET-CT) ruled out malignancy at other sites. Patient refused adjuvant chemotherapy. Case 2 presented with previous history of right pyelolithotomy, right ureteroscopic lithotripsy and right flank pain with intermittent discharge via previous percutaneous site. On biochemical and radiological investigations, right poorly functioning pyonephrotic kidney was confirmed. Patient underwent right open nephrectomy which incidentally reported adenocarcinoma of renal pelvis. Patient is disease-free at 18 months of follow-up. Case 3 had left ureteric wall thickening on CT scan when evaluated for hematuria. Ureteroscopic-guided biopsy showed villous adenoma. Laparoscopic left nephroureterectomy with bladder cuff excision specimen showed well-differentiated adenocarcinoma in ureter with extension into periureteric fat. Patient died 32 months after surgery.

Conclusion
Primary adenocarcinoma of renal pelvis or ureter is very rare and urologists should suspect it in patients with mucinous material in nephrostomy tube. We should have a low threshold for performing radical nephrectomy with complete ureterectomy in these unusual cases to improve the prognosis.
Integrative analysis of multimodal traffic data: addressing open challenges using big data analytics in the city of Lisbon
Authors: Lemonde Carlos , Arsenio Elisabete , Henriques Rui 
Published: December 2021

AbstractWorldwide cities are establishing efforts to collect urban traffic data from various modes and sources. Integrating traffic data, together with their situational context, offers more comprehensive views on the ongoing mobility changes and supports enhanced management decisions accordingly. Hence, cities are becoming sensorized and heterogeneous sources of urban data are being consolidated with the aim of monitoring multimodal traffic patterns, encompassing all major transport modes—road, railway, inland waterway—, and active transport modes such as walking and cycling. The research reported in this paper aims at bridging the existing literature gap on the integrative analysis of multimodal traffic data and its situational urban context. The reported work is anchored on the major findings and contributions from the research and innovation project Integrative Learning from Urban Data and Situational Context for City Mobility Optimization (ILU), a multi-disciplinary project on the field of artificial intelligence applied to urban mobility, joining the Lisbon city Council, public carriers, and national research institutes. The manuscript is focused on the context-aware analysis of multimodal traffic data with a focus on public transportation, offering four major contributions. First, it provides a structured view on the scientific and technical challenges and opportunities for data-centric multimodal mobility decisions. Second, rooted on existing literature and empirical evidence, we outline principles for the context-aware discovery of multimodal patterns from heterogeneous sources of urban data. Third, Lisbon is introduced as a case study to show how these principles can be enacted in practice, together with some essential findings. Finally, we instantiate some principles by conducting a spatiotemporal analysis of multimodality indices in the city against available context. Concluding, this work offers a structured view on the opportunities offered by cross-modal and context-enriched analysis of traffic data, motivating the role of Big Data to support more transparent and inclusive mobility planning decisions, promote coordination among public transport operators, and dynamically align transport supply with the emerging urban traffic dynamics.
The effect of post-fixation olecranon lengthening on range of motion of the elbow: a cadaveric study
Authors: Wong Khai Phang , Tan James Chung Hui 
Published: December 2021

Abstract
Background
Principles of fixation of comminuted olecranon fractures include anatomical reduction of the articular surface and restoration of ulnohumeral joint motion. However, comminution sometimes may not permit anatomical fixation of fracture fragments, resulting in inadvertent olecranon lengthening after plate fixation. The aim of our study is to investigate the relationship between olecranon lengthening following plate fixation and loss of elbow extension.

Materials and methods
Transverse olecranon osteotomies were performed on 8 cadaveric elbows. The osteotomy sites were then fixed with olecranon plates. Lengthening of the osteotomy sites were simulated by placement of 2mm, 4mm, 6mm and 8mm blocks. Lateral view photographs of the elbows were taken after each degree of lengthening. These photographs were then printed and measurements of elbow extension were performed with a goniometer with average values taken. The measurements were tabulated and statistical analysis performed to determine the relationship between degree of elbow extension loss and amount of olecranon lengthening.

Results
Average values of each degree of lengthening (at 2mm, 4mm, 6mm and 8mm) were taken and compared with the baseline measurement (at 0mm). Cluster analysis showed that for every increment in osteotomy length of 2mm, there is a corresponding increase of 0.79° of elbow extension loss (p<0.01, 95% confidence level 0.55°-1.03°).

Conclusion
Lengthening of olecranon by increments of 2mm correlates positively with loss of elbow extension. This shows that inadvertent intra-operative olecranon lengthening post-fixation may result in limited range of motion. However, it is reassuring to know that the small degree of extension loss may not translate to functional limitation.
Upregulated expression of transforming growth factor-β receptor I/II in an endemic Osteoarthropathy in China
Authors: Zhang Ying , Mu Yudong , He Ying , Li Zhengzheng , Mi Ge , Liu Yinan , Zhang Meng , Wang Hui , Feng Yiping , Fang Qian , Ma Tianyou , Deng Xianghua , Chen Jinghong 
Published: December 2021

Abstract
Background
Kashin–Beck disease (KBD) is a chronic, deforming, endemic osteochondropathy that begins in patients as young as 2–3 years of age. The pathogenesis of KBD remains unclear, although selenium (Se) deficiency and T-2 toxin food contamination are both linked to the disease. In the present study, we evaluated transforming growth factor-β receptor (TGF-βR I and II) levels in clinical samples of KBD and in pre-clinical disease models.

Methods
Human specimens were obtained from the hand phalanges of eight donors with KBD and eight control donors. Animal models of the disease were established using Sprague–Dawley rats, which were fed an Se-deficient diet for 4 weeks and later administered the T-2 toxin. Cartilage cellularity and morphology were examined by hematoxylin and eosin staining. Expression and localization of TGF-βRI and II were evaluated using immunohistochemical staining and western blotting.

Results
In the KBD samples, chondral necrosis was detected based on cartilage cell disappearance and alkalinity loss in the matrix ground substance. In the necrotic areas, TGF-βRI and II staining were strong. Positive percentages of TGF-βRI and II staining were higher in the cartilage samples of KBD donors than in those of control donors. TGF-βRI and II staining was also increased in cartilage samples from rats administered T-2 toxin or fed on Se-deficient plus T-2 toxin diets.

Conclusion
TGF-βRI and II may be involved in the pathophysiology of KBD. This study provides new insights into the pathways that contribute to KBD development.
Clinical feature-related single-base substitution sequence signatures identified with an unsupervised machine learning approach
Authors: Ji Hongchen , Li Junjie , Zhang Qiong , Yang Jingyue , Duan Juanli , Wang Xiaowen , Ma Ben , Zhang Zhuochao , Pan Wei , Zhang Hongmei 
Published: December 2021

AbstractBackgroundMutation processes leave different signatures in genes. For single-base substitutions, previous studies have suggested that mutation signatures are not only reflected in mutation bases but also in neighboring bases. However, because of the lack of a method to identify features of long sequences next to mutation bases, the understanding of how flanking sequences influence mutation signatures is limited.MethodsWe constructed a long short-term memory-self organizing map (LSTM-SOM) unsupervised neural network. By extracting mutated sequence features via LSTM and clustering similar features with the SOM, single-base substitutions in The Cancer Genome Atlas database were clustered according to both their mutation site and flanking sequences. The relationship between mutation sequence signatures and clinical features was then analyzed. Finally, we clustered patients into different classes according to the composition of the mutation sequence signatures by the K-means method and then studied the differences in clinical features and survival between classes.ResultsTen classes of mutant sequence signatures (mutation blots, MBs) were obtained from 2,141,527 single-base substitutions via LSTM-SOM machine learning approach. Different features in mutation bases and flanking sequences were revealed among MBs. MBs reflect both the site and pathological features of cancers. MBs were related to clinical features, including age, sex, and cancer stage. The class of an MB in a given gene was associated with survival. Finally, patients were clustered into 7 classes according to the MB composition. Significant differences in survival and clinical features were observed among different patient classes.ConclusionsWe provided a method for analyzing the characteristics of mutant sequences. Result of this study showed that flanking sequences, together with mutation bases, shape the signatures of SBSs. MBs were shown related to clinical features and survival of cancer patients. Composition of MBs is a feasible predictive factor of clinical prognosis. Further study of the mechanism of MBs related to cancer characteristics is suggested.
Role of Secretoglobin+ (club cell) NFκB/RelA-TGFβ signaling in aero-allergen-induced epithelial plasticity and subepithelial myofibroblast transdifferentiation
Authors: Skibba Melissa E. , Xu Xiaofang , Weiss Kurt , Huisken Jan , Brasier Allan R. 
Published: December 2021

AbstractRepetitive aeroallergen exposure is linked to sensitization and airway remodeling through incompletely understood mechanisms. In this study, we examine the dynamic mucosal response to cat dander extract (CDE), a ubiquitous aero-allergen linked to remodeling, sensitization and asthma. We find that daily exposure of CDE in naïve C57BL/6 mice activates innate neutrophilic inflammation followed by transition to a lymphocytic response associated with waves of mucosal transforming growth factor (TGF) isoform expression. In parallel, enhanced bronchiolar Smad3 expression and accumulation of phospho-SMAD3 was observed, indicating paracrine activation of canonical TGFβR signaling. CDE exposure similarly triggered epithelial cell plasticity, associated with expression of mesenchymal regulatory factors (Snai1 and Zeb1), reduction of epithelial markers (Cdh1) and activation of the NFκB/RelA transcriptional activator. To determine whether NFκB functionally mediates CDE-induced growth factor response, mice were stimulated with CDE in the absence or presence of a selective IKK inhibitor. IKK inhibition substantially reduced the level of CDE-induced TGFβ1 expression, pSMAD3 accumulation, Snai1 and Zeb1 expression. Activation of epithelial plasticity was demonstrated by flow cytometry in whole lung homogenates, where CDE induces accumulation of SMA+Epcam+ population. Club cells are important sources of cytokine and growth factor production. To determine whether Club cell innate signaling through NFκB/RelA mediated CDE induced TGFβ signaling, we depleted RelA in Secretoglobin (Scgb1a1)-expressing bronchiolar cells. Immunofluorescence-optical clearing light sheet microscopy showed a punctate distribution of Scgb1a1 progenitors throughout the small airway. We found that RelA depletion in Secretoglobin+ cells results in inhibition of the mucosal TGFβ response, blockade of EMT and reduced subepithelial myofibroblast expansion. We conclude that the Secretoglobin—derived bronchiolar cell is central to coordinating the innate response required for mucosal TGFβ1 response, EMT and myofibroblast expansion. These data have important mechanistic implications for how aero-allergens trigger mucosal injury response and remodeling in the small airway.
FPR2 participates in epithelial ovarian cancer (EOC) progression through RhoA-mediated M2 macrophage polarization
Authors: Xie Xiaohui , He Juan , Wang Qiong , Liu Yaqiong , Chen Weiwei , Shi Kun 
Published: December 2021

Abstract
Background
In our previous study, we found that formyl peptide receptor 2 (FPR2) promoted the invasion and metastasis of epithelial ovarian cancer (EOC) and could be a prognostic marker for EOC. In this study, we aimed to study the possible mechanism of FPR2 in promoting EOC progression.

Methods
EOC cell lines with ectopic FPR2 expression and knockdown as well as their control cell lines were established, and the expression change of RhoA in each cell line was evaluated by real time quantitative polymerase chain reaction (RT-qPCR) and Western blot. Wound healing and Transwell assays were performed to detect the migratory ability of EOCs affected by FPR2 and RhoA. The supernatant of each EOC cell line was used to coculture with macrophages, and then we tested M1 and M2 macrophage biomarkers in the supernatants by flow cytometry. The THP-1 cell line was also induced to differentiate into M1 and M2 macrophages, and FPR2 and RhoA expression in each macrophage cell line was detected by RT-qPCR and Western blot. A tumour xenograft model was established with SKOV3 and SKOV3−shFPR2 cell lines, and tumour volumes and weights were recorded.

Results
RhoA expression was significantly increased in EOCs along with the overexpression of FPR2, which showed a positive correlation by Pearson correlation analysis. Ectopic FPR2 expression contributes to the migratory ability of EOCs, and a RhoA inhibitor (C3 transferase) impairs EOC migration. Furthermore, FPR2 stimulated the secretion of Th2 cytokines by EOCs, which induced macrophages to differentiate to the M2 phenotype, while a RhoA inhibitor stimulated the secretion of Th1 cytokines and induced macrophages to differentiate to the M1 phenotype. Moreover, compared with M1 macrophages and THP-1 cells, FPR2 and RhoA expression was significantly upregulated in M2 macrophages.

Conclusion
FPR2 stimulated M2 macrophage polarization and promoted invasion and metastasis of ovarian cancer cells through RhoA.
Gene cascade analysis in human granulosa tumor cells (KGN) following exposure to high levels of free fatty acids and insulin
Authors: Tremblay Patricia G. , Fortin Chloé , Sirard Marc-André 
Published: December 2021

AbstractMaternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid and stearic acid reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of palmitic acid, oleic acid, and stearic acid at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.
Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines
Authors: Hawash Mohammed , Kahraman Deniz Cansen , Ergun Sezen Guntekin , Cetin-Atalay Rengul , Baytas Sultan Nacak 
Published: December 2021

Abstract
Background
Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, 1H-NMR and 13C-NMR spectroscopy and element analysis.

Results
The cytotoxic activity was performed against Huh7, MCF7 and HCT116 cancer cell lines using sulforhodamine B assay. Some compounds showed potent anticancer activities and three of them were chosen for further evaluation on liver cancer cell lines based on SRB assay and real-time cell growth tracking analysis. Compounds were shown to cause arrest in the G0/G1 phase in Huh7 cells and caused a significant decrease in CDK4 levels. A good correlation was obtained between the theoretical predictions of bioavailability using Molinspiration calculation, Lipinski’s rule of five, and experimental verification. These investigations reveal that indole-isoxazole hybrid system have the potential for the development of novel anticancer agents.

Conclusions
This study has provided data that will form the basis of further studies that aim to optimize both the design and synthesis of novel compounds that have higher anticancer activities.
Ecological surveillance of bat coronaviruses in Sarawak, Malaysian Borneo
Authors: Tan Cheng-Siang , Noni Vaenessa , Sathiya Seelan Jaya Seelan , Denel Azroie , Anwarali Khan Faisal Ali 
Published: December 2021

Abstract
Objective
Coronaviruses (CoVs) are natural commensals of bats. Two subgenera, namely Sarbecoviruses and Merbecoviruses have a high zoonotic potential and have been associated with three separate spillover events in the past 2 decades, making surveillance of bat-CoVs crucial for the prevention of the next epidemic. The study was aimed to elucidate the presence of coronavirus in fresh bat guano sampled from Wind Cave Nature Reserve (WCNR) in Sarawak, Malaysian Borneo. Samples collected were placed into viral transport medium, transported on ice within the collection day, and preserved at − 80 °C. Nucleic acid was extracted using the column method and screened using consensus PCR primers targeting the RNA-dependent RNA polymerase (RdRp) gene. Amplicons were sequenced bidirectionally using the Sanger method. Phylogenetic tree with maximum-likelihood bootstrap and Bayesian posterior probability were constructed.

Results
CoV-RNA was detected in ten specimens (47.6%, n  = 21). Six alphacoronavirus and four betacoronaviruses were identified. The bat-CoVs can be phylogenetically grouped into four novel clades which are closely related to Decacovirus-1 and Decacovirus-2, Sarbecovirus, and an unclassified CoV. CoVs lineages unique to the Island of Borneo were discovered in Sarawak, Malaysia, with one of them closely related to Sarbecovirus. All of them are distant from currently known human coronaviruses.
Improving research quality: the view from the UK Reproducibility Network institutional leads for research improvement
Authors: Stewart Andrew J. , Farran Emily K. , Grange James A. , Macleod Malcolm , Munafò Marcus , Newton Phil , Shanks David R. ,   the UKRN Institutional Leads
Published: December 2021

AbstractThe adoption and incentivisation of open and transparent research practices is critical in addressing issues around research reproducibility and research integrity. These practices will require training and funding. Individuals need to be incentivised to adopt open and transparent research practices (e.g., added as desirable criteria in hiring, probation, and promotion decisions, recognition that funded research should be conducted openly and transparently, the importance of publishers mandating the publication of research workflows and appropriately curated data associated with each research output). Similarly, institutions need to be incentivised to encourage the adoption of open and transparent practices by researchers. Research quality should be prioritised over research quantity. As research transparency will look different for different disciplines, there can be no one-size-fits-all approach. An outward looking and joined up UK research strategy is needed that places openness and transparency at the heart of research activity. This should involve key stakeholders (institutions, research organisations, funders, publishers, and Government) and crucially should be focused on action. Failure to do this will have negative consequences not just for UK research, but also for our ability to innovate and subsequently commercialise UK-led discovery.