bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental Disasters and Humanitarian Protection: A Fertile Ground for Litigating Climate Change and Human Rights in Italy?
Authors: Vona Fabrizio 
Published: October 2021

Abstract
On 24 February 2021, the Italian Corte Suprema di Cassazione delivered a landmark ordinance unequivocally establishing that the existence of a situation of environmental degradation in the country of origin of an international protection seeker, which entails grave human rights violations, justifies the recognition of the humanitarian protection status. In ruling that the assessment of vulnerability, for the purpose of granting humanitarian protection, must also be conducted in relation to environmental and climatic conditions which are capable of seriously affecting the enjoyment of human rights, the Supreme Court potentially paves the way for a first wave of rights-based climate lawsuits before Italian civil courts.
Risk assessment of eight metals and their mixtures to aquatic biota in sediments with diffusive gradients in thin films (DGT): a case study in Pearl River intertidal zone
Authors: Gu Yang-Guang 
Published: October 2021

Abstract
Background
The ecotoxicological risk posed by metals and their mixtures in sediments depends on their bioavailability. Many methods for evaluating the bioavailability of metals in sediments/soils are time-consuming and expensive, and frequently result in equivocal outcomes. The diffusive gradients in thin films (DGT) technique is a good measure of bioavailability for metals that can avoid the above drawbacks. Therefore, more effective approaches to this method should be developed that focus on metal bioavailability. No studies have been conducted using DGT to assess metal mixtures to aquatic biota in sediments. This study is therefore the first attempt to assess sediment toxicity of metals and their mixtures to aquatic biota based on the DGT technique. The intertidal zone of the Pearl River Estuary is selected as a case study.

Results
The bioavailable (DGT-labile) concentrations of metals range as follows (μg/L): Cd, 0.34–3.62; Pb, 1.35–1.92; Ni, 0.67–92.83; Cu, 0.74–10.30; Zn, 28.60–296.94; Co, 0.03–58.85; Fe, 7.23–4539.36; and Mn, 19.40–6626.83. The risk quotient (RQ), which is the ratio between the measured metal concentrations in the environment (MEC) and the predicted no-effect concentration (PNEC), is conducted to evaluate the single metal risk. The RQ based on summing up the MEC/PNEC ratios (RQMEC/PNEC) and the RQ based on sum of toxic units (RQSTU) are used to assess risk of metal mixture. TheRQ values of Cd, Pb, Ni, Cu, Zn, Fe, and Mn significantly exceed 1, indicating that the adverse effects of the metals are not negligible. Regarding the toxicity of metal mixtures, the values of RQMEC/PNEC and RQSTU are both between 62.45 and 743.48, revealing that the possible risk has already occurred in the study area.

Conclusions
The two methods of RQMEC/PNEC and RQSTU based on DGT-labile metal concentrations are effective and suitable to estimate the toxicity of metal mixtures in sediments.
End-to-end learning for compound activity prediction based on binding pocket information
Authors: Tanebe Toshitaka , Ishida Takashi 
Published: October 2021

AbstractBackgroundRecently, machine learning-based ligand activity prediction methods have been greatly improved. However, if known active compounds of a target protein are unavailable, the machine learning-based method cannot be applied. In such cases, docking simulation is generally applied because it only requires a tertiary structure of the target protein. However, the conformation search and the evaluation of binding energy of docking simulation are computationally heavy and thus docking simulation needs huge computational resources. Thus, if we can apply a machine learning-based activity prediction method for a novel target protein, such methods would be highly useful. Recently, Tsubaki et al. proposed an end-to-end learning method to predict the activity of compounds for novel target proteins. However, the prediction accuracy of the method was still insufficient because it only used amino acid sequence information of a protein as the input.ResultsIn this research, we proposed an end-to-end learning-based compound activity prediction using structure information of a binding pocket of a target protein. The proposed method learns the important features by end-to-end learning using a graph neural network both for a compound structure and a protein binding pocket structure. As a result of the evaluation experiments, the proposed method has shown higher accuracy than an existing method using amino acid sequence information.ConclusionsThe proposed method achieved equivalent accuracy to docking simulation using AutoDock Vina with much shorter computing time. This indicated that a machine learning-based approach would be promising even for novel target proteins in activity prediction.
adabmDCA: adaptive Boltzmann machine learning for biological sequences
Authors: Muntoni Anna Paola , Pagnani Andrea , Weigt Martin , Zamponi Francesco 
Published: October 2021

AbstractBackgroundBoltzmann machines are energy-based models that have been shown to provide an accurate statistical description of domains of evolutionary-related protein and RNA families. They are parametrized in terms of local biases accounting for residue conservation, and pairwise terms to model epistatic coevolution between residues. From the model parameters, it is possible to extract an accurate prediction of the three-dimensional contact map of the target domain. More recently, the accuracy of these models has been also assessed in terms of their ability in predicting mutational effects and generatingin silicofunctional sequences.ResultsOur adaptive implementation of Boltzmann machine learning, , can be generally applied to both protein and RNA families and accomplishes several learning set-ups, depending on the complexity of the input data and on the user requirements. The code is fully available athttps://github.com/anna-pa-m/adabmDCA. As an example, we have performed the learning of three Boltzmann machines modeling the Kunitz and Beta-lactamase2 protein domains and TPP-riboswitch RNA domain.ConclusionsThe models learned by are comparable to those obtained by state-of-the-art techniques for this task, in terms of the quality of the inferred contact map as well as of the synthetically generated sequences. In addition, the code implements both equilibrium and out-of-equilibrium learning, which allows for an accurate and lossless training when the equilibrium one is prohibitive in terms of computational time, and allows for pruning irrelevant parameters using an information-based criterion.
Transmission of multidrug-resistant tuberculosis in Shimen community in Shanghai, China: a molecular epidemiology study
Authors: Han Zhiying , Li Jing , Sun Guomei , Gu Kaikan , Zhang Yangyi , Yao Hui , Jiang Yuan 
Published: October 2021

Abstract
Background
Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015.

Methods
We used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation.

Results
The ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases.

Conclusions
The integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.
Dual Ureaplasma parvum arthritis: a case report of U. parvum septic arthritis following contralateral reactive arthritis in an immunosuppressed patient
Authors: Lemoine Lea , Le Brun Cecile , Maillot Francois , Thorey Camille , Boucaud Annaelle , Lemaignen Adrien , Bigot Adrien 
Published: October 2021

Abstract
Background
Ureaplasma parvum is usually part of the normal genital flora. Rarely can it cause invasive infections such as genitourinary infections, septic arthritis, or meningitis.

Case presentation
Here we present the first description of chronic ureterocystitis in a 56-year-old immunocompromised patient, complicated first by reactive arthritis and secondarily by contralateral septic arthritis due to U. parvum infection. U. parvum was detected in synovial fluid and in a urine sample. Treatment consisted of double-J stenting and targeted antibiotic therapy. Evolution showed resolution of urinary symptoms and clinical improvement of arthritis despite functional sequelae.

Conclusions
Given the high prevalence of U. parvum colonisation, this diagnosis should remain a diagnosis of exclusion. However, because of the difficulty in detecting this microorganism, it should be considered in unexplained subacute urethritis or arthritis, including reactive arthritis, especially in immunosuppressed patients. Real-time PCR positivity in the absence of a differential diagnosis should not be overlooked.
Xanthogranulomatous pyelonephritis infected with the Providencia stuartii: a case report and literature review
Authors: Xu Zhunan , Cai Tong , Zhang Xuebao , Wu Jitao , Liu Chu 
Published: October 2021

Abstract
Background
Xanthogranulomatous pyelonephritis (XGP) is a rare and severe chronic inflammatory disease of the renal parenchyma, which is most commonly associated with super-infections by bacteria such as E. coli, Proteus mirabilis, and occasionally Pseudomonas species.

Case presentation
Herein, we present a rare case of a patient with XGP infected with Providencia stuartii. Initially, the patient refused nephrectomy and underwent holmium laser lithotripsy and right ureteral stenting, followed by meropenem treatment of 7 days. Relapse occurred in the third month after discharge from the hospital, due to which she underwent a radical nephrectomy.

Discussion
The diagnosis of XGP is confirmed by histopathology. The standard treatment for XGP is antibiotic therapy and radical nephrectomy, but partial nephrectomy may be appropriate in select cases.
Hemichorea in a patient with ipsilateral cortical infarction: a case report
Authors: Wei Jie , Zhang Yue 
Published: October 2021

Abstract
Background
Hemichorea is usually caused by contralateral deep structures of brain. It rarely results from acute cortical ischemic stroke and that caused by ipsilateral brain lesions is even rarer.

Case presentation
A 64-year-old female presented with acute obtuseness and left-sided hemichorea. She had a history of right frontal lobe surgery and radiotherapy due to brain metastasis from lung cancer 8 years ago. MRI revealed acute left frontal lobe infarction in addition to an old right frontal lobe lesion. 18FDG PET-CT showed hypometabolism in the left frontal lobe and hypermetabolism in the right basal ganglia region and central sulcus. The choreatic movement remitted after antipsychotic treatment.

Conclusion
The mechanism of hemichorea after ipsilateral cortical infarction is poorly understood. We assume both previous contralateral brain lesion and recent ipsilateral ischemic stroke contributed to the strange manifestation in this case.
Cholinesterase inhibitor to prevent falls in Parkinson’s disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson’s disease
Authors: Neumann S. , Taylor J. , Bamford A. , Metcalfe C. , Gaunt D. M. , Whone A. , Steeds D. , Emmett S. R. , Hollingworth W. , Ben-Shlomo Y. , Henderson E. J. 
Published: October 2021

AbstractBackgroundFalls are a common complication of Parkinson’s disease. There is a need for new therapeutic options to target this debilitating aspect of the disease. Cholinergic deficit has been shown to contribute to both gait and cognitive dysfunction seen in the condition. Potential benefits of using cholinesterase inhibitors were shown during a single centre phase 2 trial. The aim of this trial is to evaluate the effectiveness of a cholinesterase inhibitor on fall rate in people with idiopathic Parkinson’s disease.MethodsThis is a multi-centre, double-blind, randomised placebo-controlled trial in 600 people with idiopathic Parkinson’s disease (Hoehn and Yahr stages 1 to 4) with a history of a fall in the past year. Participants will be randomised to two groups, receiving either transdermal rivastigmine or identical placebo for 12 months. The primary outcome is the fall rate over 12 months follow-up. Secondary outcome measures, collected at baseline and 12 months either face-to-face or via remote video/telephone assessments, include gait and balance measures, neuropsychiatric indices, Parkinson’s motor and non-motor symptoms, quality of life and cost-effectiveness.DiscussionThis trial will establish whether cholinesterase inhibitor therapy is effective in preventing falls in Parkinson’s disease. If cost-effective, it will alter current management guidelines by offering a new therapeutic option in this high-risk population.Trial registrationREC reference: 19/SW/0043.EudraCT: 2018–003219-23.ISCRTN:41639809(registered 16/04/2019).ClinicalTrials.gov Identifier:NCT04226248Protocol at time of publicationVersion 7.0, 20th January 2021.
Second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab for patients with metastatic colorectal cancer
Authors: Yamamoto Shun , Nagashima Kengo , Kawakami Takeshi , Mitani Seiichiro , Komoda Masato , Tsuji Yasushi , Izawa Naoki , Kawakami Kentaro , Yamamoto Yoshiyuki , Makiyama Akitaka , Yamazaki Kentaro , Masuishi Toshiki , Esaki Taito , Nakajima Takako Eguchi , Okuda Hiroyuki , Moriwaki Toshikazu , Boku Narikazu 
Published: October 2021

Abstract
Background
The ML18174 study, which showed benefits of bevacizumab (BEV) continuation beyond progression (BBP) for metastatic colorectal cancer (mCRC), excluded patients with first-line progression-free survival (PFS) shorter than 3 months. The present study was conducted to evaluate the efficacy of second-line chemotherapy after early disease progression during first-line chemotherapy containing bevacizumab.

Methods
The subjects of this study were mCRC patients who experienced disease progression < 100 days from commencement of first-line chemotherapy containing BEV initiated between Apr 2007 and Dec 2016. Second-line chemotherapy regimens were classified into two groups with and without BEV/other anti-angiogenic agents (BBP and non-BBP) and efficacy and safety were compared using univariate and multivariate analysis.

Results
Sixty-one patients were identified as subjects of this study. Baseline characteristics were numerically different between BBP (n = 37) and non-BBP (n = 25) groups, such as performance status (0–1/> 2/unknown: 89/8/3 and 56/40/4%), RAS status (wild/mutant/unknown: 32/54/16 and 76/16/8%). Response rate was 8.6% in BBP group and 9.1% in non-BBP group (p = 1.00). Median PFS was 3.9 months in BBP group and 2.8 months in non-BBP group (HR [95%CI]: 0.79 [0.46–1.34], p = 0.373, adjusted HR: 0.87 [0.41–1.82], p = 0.707). Median overall survival was 8.5 months in BBP group and 5.4 months in non-BBP group (HR 0.66 [0.38–1.12], p = 0.125, adjusted HR 0.53 [0.27–1.07], p = 0.078).

Conclusion
In mCRC patients who experienced early progression in first-line chemotherapy, second-line chemotherapy showed poor clinical outcomes regardless use of anti-angiogenic agents.
Development and validation of genomic and epigenomic signatures associated with tumor immune microenvironment in hepatoblastoma
Authors: Zhang Yanbing , Zhang Tian , Yin Qiang , Luo Haiyan 
Published: October 2021

Abstract
Background
This study aimed to probe and verify aberrantly methylated and expressed genes in hepatoblastoma and to analyze their interactions with tumor immune microenvironment.

Methods
Aberrantly methylated and expressed genes were obtained by comprehensively analyzing gene expression and DNA methylation profiles from GSE81928, GSE75271 and GSE78732 datasets. Their biological functions were predicted by the STRING and Metascape databases. CIBERSORT was utilized for inferring the compositions of tumor-infiltrating immune cells (TIICs) in each sample. Correlation between hub genes and immune cells was then analyzed. Hub genes were validated in hepatoblastoma tissues via western blot or immunohistochemistry. After transfection with sh-NOTUM, migration and invasion of HuH-6 and HepG2 cells were investigated. The nude mouse tumorigenesis model was constructed.

Results
Totally, 83 aberrantly methylated and expressed genes were determined in hepatoblastoma, which were mainly involved in metabolic and cancer-related pathways. Moreover, their expression was liver-specific. 13 hub genes were screened, which were closely related to immune cells in hepatoblastoma tissues. Among them, it was confirmed that AXIN2, LAMB1 and NOTUM were up-regulated and SERPINC1 was down-regulated in hepatoblastoma than normal tissues. NOTUM knockdown distinctly weakened migration and invasion of HuH-6 and HepG2 cells and tumor growth in vivo.

Conclusions
This study identified aberrantly methylated and expressed signatures that were in relation to immune microenvironment in hepatoblastoma. Targeting NOTUM hub gene could suppress migration and invasion of hepatoblastoma cells. Thus, these aberrantly methylated and expressed genes might act as therapeutic agents in hepatoblastoma therapy.
Treatment outcomes of acute postoperative infectious endophthalmitis
Authors: Peng Kai-Ling , Kung Ya-Hsin , Tsai Hui-Shuang , Wu Tsung-Tien 
Published: October 2021

Abstract
Background
Acute postoperative endophthalmitis is one of the most severe complications of modern ophthalmic procedures including cataract surgeries, vitrectomy and intravitreal injection (IVI). We evaluated the treatment outcomes of acute postoperative infectious endophthalmitis.

Methods
In this retrospective study, we collected data from 82 patients with acute infectious endophthalmitis within 6 weeks after intraocular surgeries, including cataract surgeries, vitreoretinal surgeries, and IVI, from January 2010 to December 2019. We analyzed the pre-treatment, treatment-related and post-treatment factors that affected visual outcomes.

Results
The mean age was 67.65 ± 9.52 years, the proportion of male patients was 56.1%. The mean baseline vision was 1.92 (Snellen Equivalent SE], counting finger [CF]) ± 0.54 logarithm of the minimum angle of resolution (log MAR) and the mean final vision was 0.71 (SE, 39/200) ± 0.80 logMAR. Visual improvement was significant (P < 0.001). The pre-treatment factors affecting final visual outcomes were diabetes, hemodialysis, baseline vision, signs of vitreous opacity, and different surgeries before endophthalmitis; the treatment-related factors affecting visual outcomes were the choice factors between IVI of antibiotics alone and vitrectomy combined with IVI of antibiotics, and the injection numbers of antibiotics; post-treatment factors affecting visual outcomes were complications such as retinal detachment (RD), glaucoma and macular pucker. Furthermore, prior cataract surgery was associated with a better mean final vision of 0.57 (SE, 54/200) ± 0.67 logMAR while prior vitrectomy resulted in the worst mean final vision of 1.38 (SE, 21/500) ± 0.75 logMAR.

Conclusions
The important factors that affected the final visual prognosis, included diabetes, hemodialysis, baseline vision, severity of vitritis, treatment strategies and complications. The treatment outcomes revealed better final vision in prior cataract surgery than vitrectomy.
The effects of antifungal therapy on the recurrence of aspergillus infection after pulmonary aspergilloma resection: a study protocol for a single-center, prospective, non-blind, randomized, 24-month, parallel group study
Authors: Chen Xianqiu , Zhou Yiming , Zhang Lijuan , Xu Jinfu , Liang Shuo 
Published: October 2021

Abstract
Background
In recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear.

Methods
In this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated.

Discussion
The study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma.
Trial registration: The trial was registered on the Chinese Clinical Trial Registry website (https://www.chictr.org.cn/showprojen.aspx?proj=33231). Registration number: ChiCTR1800019990.