tbuckley/cabot-search huggingface dataset:
Severe air pollution links to higher mortality in COVID-19 patients: The “double-hit” hypothesis.
Authors: Antonio Frontera, Lorenzo Cianfanelli, Konstantinos Vlachos, Giovanni Landoni, George Cremona
Journal: Journal of Infection (2020)

In areas of SARS-CoV-2 outbreak worldwide mean air pollutants concentrations vastly exceed the maximum limits. Chronic exposure to air pollutants have been associated with lung ACE-2 over-expression which is known to be the main receptor for SARS-CoV-2. The aim of this study was to analyse the relationship between air pollutants concentration (PM 2.5 and NO2) and COVID-19 outbreak, in terms of transmission, number of patients, severity of presentation and number of deaths.
Procedural Pain in Premature Infants (Poppi): A stopped blinded randomised placebo-controlled trial investigating the analgesic efficacy and safety of morphine
Authors: C Hartley, F Moultrie, A Hoskin, G Green, V Monk, J Bell, A King, M Buckle, M van der Vaart, D Gursul, S Goksan, E Juszczak, J Norman, R Roger, C Patel, E Adams, R Slater
Journal: The Lancet (2018)
Super-resolution observation of lysosomal dynamics with fluorescent gold nanoparticles
Authors: Kangqiang Qiu, Yang Du, Jiyan Liu, Jun-Lin Guan, Hui Chao, Jiajie Diao
Journal: Theranostics (2020)

Because lysosomes play critical roles in multiple cellular functions and are associated with many diseases, studying them at the subcellular level could elucidate their functionality and support the discovery of therapeutic drugs for treating those diseases.The commonly used dyes for super-resolution imaging of lysosomes are the commercial molecular LysoTrackers.But the tolerance to changes in the lysosomal microenvironment and to lysosomal membrane permeabilization (LMP) and the photostability of the LysoTrackers are worrisome.The purpose of our study was to evaluate the feasibility of performing a fluorescent gold nanoprobe for super-resolution observation of lysosomal dynamics in living cells and compare it to the commercial LysoTrackers.Methods: The nanoprobe Cy5@Au NP contained three parts: a bio-inert gold core, a biocompatible polyethylene glycol spacer, and a fluorophore cyanine 5. Structured illumination microscopy (SIM) was employed to capture the fluorescence of Cy5@Au NPs in cells.The tolerance assays to changes in the lysosomal microenvironment and to LMP, the photobleaching assay, and the long-term lysosomes labelling assay of Cy5@Au NPs were compared with commercial LysoTrackers.The super-resolution observation of lysosomal dynamics with Cy5@Au NPs was performed.Results: Cy5@Au NPs can light up lysosomes specifically under SIM.Compared with commercial lysosomal molecular probes, Cy5@Au NPs exhibited stronger tolerance in lysosomes during various treatments, and changes in the lysosomal microenvironment and LMP did not cause Cy5@Au NPs to lose track of their targets.Cy5@Au NPs demonstrated an excellent anti-photobleaching ability, and a long-term labelling assay revealed that they could label lysosomes more than 3 d.Biological events of lysosomes such as the kiss-and-run process, fusion, fission, and mitophagy were recorded with the fluorescent Cy5@Au NPs under SIM.Conclusions: The nanoprobe Cy5@Au NP was successfully used as a lysosomal probe for the super-resolution observation in living cells and found to overcome the limitations of commercial LysoTrackers.Our results thus confirm that nanoparticles can be useful tools for subcellular super-resolution imaging and highlight new avenues for using nanoparticles in biology.
Evolutionary Genomics at the Human–Environment Interface in Africa
Authors: Hannes Svardal, Bosco Rusuwa, Tyler Linderoth, Anmol Kiran, Anne Charmantier, H Michael G Lattorff, Alex Cagan, Sheila C Ommeh, Arox Kamng’ona, Cyprian Katongo, M Emília Santos, Richard Durbin, Benjamin Kumwenda, Peter M Visscher, Sophie von der Heyden
Journal: Molecular Biology and Evolution (2020)

We report on the first meeting of SMBE in Africa. SMBE Malawi was initiated to bring together African and international researchers who use genetics or genomics to study natural systems impacted by human activities. The goals of this conference were 1) to reach a world-class standard of science with a large number of contributions from Africa, 2) to initiate exchange between African and international researchers, and 3) to identify challenges and opportunities for evolutionary genomics research in Africa. As repored, we think that we have achieved these goals and make suggestions on the way forward for African evolutionary genomics research.
ABC of sexual health: Sexual problems associated with infertility, pregnancy, and ageing
Authors: J. Read
Journal: BMJ (1999)

Infertility may interact with a couple's or individual's sexuality and sexual expression in two main ways. Sexual problems may be caused or exacerbated by the diagnosis, investigation, and management of infertility (or subfertility), or they may be a contributory factor in childlessness. Any examination of a couple's difficulty in conceiving must include overt and clear questioning about their sexual activity. ### Responses to infertility In response to being unable to conceive, many people feel emotions such as anger, panic, despair, and grief, and these may have several effects on sexual activity. The stress of infertility and its treatment may be a cause of sexual difficulties for both the prospective father and mother. Intercourse may be avoided, with patterns of behaviour established, so that one or other partner is not reminded of the fertility problem. Postcoital tests or having to provide semen samples may result in a man feeling under pressure to perform, adversely affecting his erectile or ejaculatory ability. For some men, one or two failures during intercourse begins a vicious circle of fear of failure, with anxiety leading to further failures. Partners may also develop arousal difficulties because of anxiety or distress. Some individuals feel that their partner seems to want them only when there is a chance of conception, and sexual activity can then become a battleground for issues of power and control. #### Useful questions to elicit information
Genetic landscape and PD-L1 expression of Chinese patients with small cell lung cancer.
Authors: Meifang Chen, Ding Zhang, Guoqiang Wang, Bijiong Wang
Journal: Journal of Clinical Oncology (2020)

e21099 Background: Small cell lung cancer (SCLC) is a highly aggressive carcinoma of the lung. Whereas, precise treatment options for SCLC are limited. Genomic profiling would be essential to understand drug resistance related mechanism. So far, little is known about an in-depth molecular characterization for SCLC in Chinese patients. Here we described the mutational landscape and programmed cell death-1 (PD-L1) expression profile in Chinese patients with SCLC by next-generation sequencing (NGS) assay. Methods: Chinese patients with SCLC were included in this study. Genomic profiling of DNA was performed on formalin-fixed paraffin-embedded tumor samples and matched blood through a NGS with 381 cancer-related genes panel. PD-L1 expression status of tumor tissue was determined by immunohistochemistry. Results: In total, 115 patients with SCLC were included in the present study. We identified 2,948 mutations, spanning 434 genes, with TP53, RB1 and LRP1B being the most frequently mutated genes, occurring in 109(94.78%), 88(76.52%) and 48(41.74%) of SCLC patients, respectively. For somatic single nucleotide variant (SNV), TP53 (108/115, 93.91%), RB1 (82/115, 71.30%) and LRP1B (43/115, 37.39%) were frequently mutated, which exhibited the similar mutation frequencies with TCGA database. To be noted, 79 (68.70%) SCLC patients harbored both RB1 and TP53 mutations, which was comparable with TCGA data (84/110, 76.36%). Germline SNV spectrum varied significantly compare with somatic SNV. BLM, MSH2 and VEGFA were the most frequently germline mutated genes. In our dataset, the tumor mutation burden (TMB) of 108 patients, PD-L1 expression status of 95 patients and microsatellite stabilities/instabilities (MSS/MSI) status of 112 patients were also analyzed. The median TMB was 10.61/MB. The positive rate of PD-L1 expression was 12.63%. All patients were MSS. Conclusions: Our study revealed the genetic landscape and PD-L1 expression of SCLC. The data may provide the support on immunotherapy and targeted therapy research.
Research progress on the urotensin II receptor antagonist
Authors: 李海霞, 徐春琳, 吴文英
Journal: BMJ (2009)

尾加压素Ⅱ(urotemin Ⅱ,UⅡ)最早是自硬骨鱼的脊髓尾部下垂体中提取的一种生长抑素样环肽,主要分布于心血管系统与神经系统,是迄今最强的缩血管肽,与孤立G-蛋白耦联受体(the orphan G-protein coupled receptor 14,GPR14)结合后可引起一系列生物学效应.近年来研究发现,UⅡ受体拮抗剂可能在糖尿病、肾脏病、肺脏疾病的治疗中发挥重要作用[1-2]。
认识并延缓慢性肾脏病进展
Authors: 徐红, 刘伟竹
Journal: BMJ (2011)

徐红:慢性肾脏病(CKD)患者会缓慢进展为肾功能衰竭,最后至终末期肾病.CKD发病率、患病率明显上升,国外发病率为11.0%～16.2%;国内北京、广州、浙江三个城市的调查,发病率分别为11.3%、10.1%、13.5%,据此推算我国CKD患者人数在1.41亿.每年这些患者中都有一部分会进展到透析阶段,如果其中1%发展为终末期肾病,1个血液透析患者每年要花费10万元,即每年用于肾脏替代治疗的费用就高达1410亿元。
Technical validation of a high-sensitivity target capture NGS assay using unique molecular identifier approach.
Authors: Ruifang Mao, Shanshan Xiao, Rui Lin, Yuchen Wang, Tao Wang
Journal: Journal of Clinical Oncology (2020)

e13657 Background: Identification of a broad spectrum of somatic mutations is crucial to guide targeted therapy such as for non-small cell lung cancer (NSCLC) patients. In the clinical environment, it requires well validated NGS workflow both for the wet-lab and dry-lab procedures. Here we describe a high sensitivity target NGS assay to accurately capture single nucleotide variants (SNVs), short insertions and deletions (indels), copy number alterations and gene rearrangements for formalin-fixed paraffin-embedded (FFPE) NSCLC patient samples. Extensive analytical validation was performed following the checklists of College of American Pathologists. Methods: Next generation sequencing (NGS) libraries were prepared using extracted DNA from FFPE tissue NSCLC patient samples. The protocol for library generation was optimized in several steps and incorporated 10bp unique molecular identifiers (UMIs). The libraries were sequenced on Illumina HiSeq X-Ten platform. The sequence data was analyzed by an in-house bioinformatics pipeline to call somatic mutations at an average depth of 4000X. Results: We tested the accuracy of 68 clinical tumor samples that were also validated by conventional or alternative methods in the third party CAP accredited labs. We observed 100% sensitivity and 100% specificity compared with the other lab¡¯s validation results. To define the limit of detection (LOD) for different mutation types, clinical DNA samples containing different variants were diluted with normal DNA. The LODs for SNV (as in EGFR L858R) and indel (as in EGFR 19del) were 0.5% and 1%, respectively. Addressing the LOD of fusion and copy number alteration is usually challenging. Our NGS assay was able to achieve 2% LOD for gene rearrangement (fusion) and 3.5 copies for copy number amplification. The high reproducibility was also achieved by inter- and intra- replicate experiments. Our NGS assay showed better performance than other widely used commercial NGS assay panels. Conclusions: We have validated an NGS based approach with UMI technology that is able to achieve high accuracy and sensitivity as low as 0.5% for detection of somatic mutations, which will improve the clinical testing performance for NSCLC FFPE samples with low allele frequencies of driver mutations.
Clinical features of unilateral oculomotor nerve palsy related to multiple myeloma: a case report and literature review
Authors: Hongtao Hu, Mo Li, Ming Jiang, Xiaolei Guo, Jie Chen, Yanxia Bai, Rongjie Bai
Journal: BMJ (2016)

Objective
To analyze the clinical features of unilateral oculomotor nerve palsy caused by multiple myeloma(MM).


Methods
A 79-year-old female diagnosed MM for 3 years was admitted due to the disease relapse. The patient presented left oculomotor nerve palsy, bone marrow biopsy showed 4.5% of myeloma cells, the serum level of λ light chain was up to 18 g/L, and brain CT/MRI scan revealed left parasphenoidsinus lesion. A diagnosis of relapsing intramedullary and extramedullary MM, IgGλ type, stage ⅢA was made. Ten cases were retrieved from literature since 1990, the clinical features of 11 cases were analyzed as follows.


Results
Among 11 cases of unilateral oculomotor nerve palsy caused by MM, 7 were males and 4 females with a mean age of (60±12) years (40-79 years). The sub-types of MM were IgG type (7 cases), IgA type (2 cases), biclonal of IgG and IgA type (1 case), and IgD type (1 case). Oculomotor nerve palsy was presented as the initial manifestation of MM in 9 cases, as a sign of relapse of MM in 1 case, and during MM treatment in 1 case. In 7 cases, oculomotor nerve was the only cranial nerve involved, while in other 4 cases, the Ⅳ, Ⅴ, Ⅵ cranial nerves were also involved. Neuroimaging revealed parasphenoid sinus lesions in 9 cases, and myeloma meningitis in 2 cases. Most of the reviewed cases achieved significant clinical improvement after chemotherapy and/or radiotherapy, except 2 cases with myeloma meningitis. The case in our department was improved significantly and rapidly after receiving chemotherapy with bortezomib.


Conclusion
MM should be considered when unilateral oculomotor nerve palsy is presented with or without the history of MM, the disease is sensitive to chemotherapy in most circumstances.


Key words: 
Multiple myeloma; Oculomotor nerve diseases; Drug therapy; Bortezomib
Anaerobes in prostate cancer: New approaches to treatment and prevention.
Authors: Tim RTD Oliver, Roshni Bhudia, Frank Chinegwundoh, Mark Wilks
Journal: Journal of Clinical Oncology (2020)

e13606 Background: The sun-sensitive microaerophylic bacterium C. acnes, is linked with prostate cancer (PC) in 9 studies 3 of which are cohort studies of 289,043 men followed for 30 years from puberty. That circumcision reduces PC risk further supports a role for anaerobes as they are reduced on the circumcised glans penis. A 1988 study linked anaerobes with PC but considered them opportunists. Reports that H. pylori, linked to stomach cancer, is also a microaerophilic bacterium led us to reinvestigate the association of PC and anaerobes. Methods: The MOLDI-TOF methodology for analysing anaerobes in 18 post rectal exam urine samples has been previously reported ( https://www.nature.com/articles/s41598-017-13782-6 ). This report analyses outcome after a further 21 patients were recruited and follow up was extended from 1 month to a median of 43 months. In total there were 21 diagnosed as PC and 18 BPH. Results: Of the 29 anaerobic isolates, 19 were Chlostridiales family, 2 Prevotella and 7 Actinomycoses (includes C.acnes) family. 12 cases had obligate anaerobes, 7 microaerophylic bacteria and 20 none of these. In 27 patients with PSA &gt; 1.5, 56% had anaerobes, while in 12 with PSA = &lt; 1.5 it was 17% (p &lt; 0.037 Fisher’s exact test) In the 21 with prostate cancer, 7 (64%) of 11 without anaerobes and 2 of 10 (20% ) with anaerobes remain on Active Surveillance (p = 0.08 Fisher’s exact test) vs in 18 without cancer, 10/11 (91%) without and 5/7 (71%) with anaerobes remain without the need of TURP intervention. Conclusions: This is a small study and needs expanding. Given the rising incidence of antibiotic resistance more resources should be focused on the immune deficiency associated with chronic bacterial infection. Expansion of technology used to produce bacterial vaccines to treat women with recurrent cystitis could offer new approaches to prevention of PC and to treat patients with raised PSA and negative biopsy. Modern approaches to immunotherapy against these bacteria with checkpoint inhibitors could be used in combination with androgen suppression and chemotherapy.
Development and application of microscopy review criteria of urinalysis combination of dry chemistry and flow cytometry
Authors: Chuanbao Li, Jin Fan, Zhejun Dong, Wei Hong, Huan Qi
Journal: BMJ (2014)

Objective
To establish the review criteria of urinalysis combination of AX-4280 urine dry chemeical analyzer and UF-1000i urine particle analyzer at our laboratory.


Methods
A total of 4 049 samples were collected randomly from Beijing Hospital of Ministry of Health from December 2010 to December 2011. After analysis on automated analysis line, each sample was examined by two experienced technicians with double-blind method. Their mean results were regarded as the microscopic examination results. The automatic detection and microscopy results of 4 049 samples were analyzed by the UriAccess 3.0 software. The results included BLD LEU and PRO of AX-4280, RBC WBC and CAST of UF-1000i and microscopic examination. The microscopy results were set as the gold standard. And the values of true positive rate, false positive rate, true negative rate, false negative rate and review rate of different combinations of rules were calculated. Then 189 urine samples were examined to validate the feasibility of rules by false negative rate and review rate.


Results
After analysis, 47 rules were selected for microscopic review. The true positive rate of this review criteria was 32.38% (1 311/4 049), false positive rate 22.33% (904/4 049), true negative rate 43.12% (1 746/4 049), false negative rate 2.17% (88/4 049) and review rate 27.76% (1 124/4 049). The false negative rate of this review criteria was 1.06% (2/189) and review rate 26.46% (50/189). Two cases of missed diagnosis specimens came from renal outpatient department of internal medicine and department of traditional Chinese medicine, the microscopic results of RBC and WBC were 4/HP and 7/HP respectively. So this criteria would not cause a missed diagnosis for patients with severe kidney disease.


Conclusions
This review criteria can effectively screen the urine samples to diagnose patients with severe kidney disease. So this review criteria is suitable for the screening of urinalysis results at our laboratory.


Key words: 
Urinalysis; Chemistry, analytical; Microscopy; Autoanalysis
Application of atherogenic index of plasma and intima-media thickness of carotid artery in renal arteriolar sclerosis patients with chronic renal failure
Authors: Yapei Zhao, Cuijing Liu, Cuiying Yang, Shiying Fan, Yanqin Zhao, Lijian Zhang, Yingxin Xie
Journal: BMJ (2017)

Objective
To evaluate the application of atherogenic index of plasma (AIP) and intima-media thickness of carotid artery (CA-IMT) in renal arteriolar sclerosis patients with chronic renal failure.


Methods
One hundred and twenty nine patients with chronic renal failure patients underwent ultrasound-guided percutaneous renal biopsy from October 2013 to June 2014, the biopsy results showed that renal arteriolar sclerosis was identified in 72 patients (atherosclerosis group) and no renal arterioles sclerosis was detected in 57 patients (non-atherosclerosis group); 71 healthy adults were enrolled in the study as controls. The age, height, body weight, systolic and diastolic blood pressure, the indexes of blood lipid and renal function were documented and compared among three groups. The correlation of AIP and CBMmax of common carotid artery and carotid bifurcation with blood lipid level and renal function was analyzed.


Results
There was significant difference in body weight among patients with atherosclerosis [(70.77±14.27) kg], without atherosclerosis [(60.63±12.12) kg] and the controls [(64.20±8.13) kg] (t=3.071, 3.391, all P<0.05). The TG [(2.43±1.61) mmol/L vs.(1.02±0.37)mmol/L], TC[(7.40±8.80) mmol/L vs.(4.53±0.67)mmol/L], LDL-C[(4.40±2.13) mmol/L vs.(2.85±0.70)mmol/L], AIP[(0.15±0.351)vs.(-0.127±0.184)] of the atherosclerosis group were higher than those of control group (t=5.975, 2.252, 2.614, -5.467, all P<0.05). The HDL-C of atherosclerosis group was lower than that of control group [(0.78±0.16)mmol/L vs.(1.29±0.21)mmol/L, t=4.750, P<0.05]. The Scr[(117.24±94.27)mmol/L vs.(64.16±13.42)mmol/L], BUN[(6.73±3.58)mmol/L vs.(4.66±1.08)mmol/L] of the atherosclerosis group were higher, and the GFR was lower [(65.60±23.00)ml·min-1·1.73 m-2vs.(124.78±24.35)ml·min-11.73 m-2 , t=5.118] than those of control group (t=4.730, 4.702). The Scr of the atherosclerosis group was higher, and the GFR was lower [(65.60±23.00)ml·min-1·1.73 m-2vs.(95.60±53.00)ml·min-1·1.73 m-2, t=3.514] than those of the non-atherosclerosis group [(117.24±94.27)mmol/L vs.(71.35±42.18)mmol/L, t=3.690]. There were positive correlation between TG and LDL-C (r=0.828, 0.323, P<0.05) and negative correlation between AIP and HDL-C (r=-0.489, P<0.05). There was positive correlation of CBMmax with Scr, BUN and AIP (r=0.394, 0.289, 0.528, all P<0.05), and negative correlation between CBMmax and GFR (r=-0.277, P<0.05).


Conclusion
Body weight, GFR, AIP and CBMmax are useful indicators in evaluation of renal arteriolar sclerosis in patients with chronic renal failure. AIP is a sensitive index for abnormal blood lipid level. AIP and CBMmax are important risk factors in chronic renal failure patients with renal arteriolar sclerosis.


Key words: 
Kidney failure, chronic; Atherogenic index of plasma; Intima-media thickness of carotid artery
Lessons learned from clinical trial queries on small biopsy collections from an academic cancer center.
Authors: Jamie Voyten, Matthew Peter Holtzman, Liron Pantanowitz, Rajiv Dhir, H. Scott Beasley, Jackie Cuda, Sara Elizabeth Monaco
Journal: Journal of Clinical Oncology (2020)

e14016 Background: Small biopsies and cytology specimens are becoming increasingly important for clinical trials and biomarker testing. Thus, institutions must ensure that there is adequate lesional material meeting specifications for a multitude of different protocols, which can involve rapid on-site evaluation (ROSE). The aim of this study is to look at the recent clinical trial biopsy characteristics and feedback on these collections at our institution. Methods: Clinical trial biopsies performed at our institution and trial feedback (so called “queries”) were analyzed from the past two years (2017-2019). The query data was reviewed in detail, in addition to protocol modifications related to biopsy requirements and study protocol changes. Results: A total of 698 biopsy collections were performed for clinical trial purposes for 95 trials, with the majority of these requiring biopsies at more than 1 time point (63.2%), for phase 1 or 2 trials (92.6%), and for specific tumor types (67.4%). Only 18 (18.9%) of the 95 trials requiring fresh tissue biopsies provided feedback. This included 90 (12.9%) cases, of which 27 (30.0%) had queries regarding insufficient (10, 37.0%) or borderline (17, 63.0%) tumor, and only 1 (3.7%) of these had ROSE by cytology. ROSE was performed due to institutional guidelines (45.3%), requirement by study (1.1%), or trial modification (5.3%).(Table). Conclusions: This investigation shows the high volume of clinical trial biopsies managed at our academic cancer center. Feedback from trials is low at 18.9%, and frequently involves suboptimal cases without ROSE at acquisition, which has led to more widespread adoption of ROSE to mitigate insufficient biopsies and repeat procedures. The high volume of clinical trial biopsies and variability in trial needs necessitates a collaborative multi-disciplinary network to facilitate these important biopsies for cancer patients. [Table: see text]