dataesr/scientific-paragraphs-categorization huggingface dataset:
Data analysis All MRI examinations were independently and retrospectively reviewed for presence and severity of OA features in each joint, primarily by one radiologist (MJ) with 5-years of experience and adjudicated by a second radiologist (AG) with 25-years of experience in musculoskeletal radiology. Scoring of MRI abnormalities was performed without reference to the on-site clinical reports issued at the time of imaging. To define the presence of knee OA based on MRI, we used an MRI definition of knee OA based on a Delphi exercise including several experts in the field  [5]. This definition requires the presence of a definitive osteophyte AND full thickness cartilage loss, OR one of the aforementioned features PLUS two or more minor features such as subchondral bone marrow lesion, partial thickness cartilage loss, bone attrition, and/or meniscal degeneration/maceration/subluxation.
From all knees assessed on MRI during the 2016 Summer Olympics, 23. 4% had features of OA; this was true for only 2. 5% of hips. Because the data we collected is not comparable and we did not examine all athletes participating in the Olympics, it is difficult to compare and discuss the frequencies found in these joints in our study with most available studies. Given the high prevalence rates of peripheral OA in former athletes  [23] [24] [25] [26] , it is not surprising that most of the MRI-detected peripheral OA in the Olympic athletes was observed aged 30 years or older, including severe OA cases in our study. This reflects the repetitive stress and overload applied in peripheral joints, especially those from the inferior limbs when sports involve long-term weight-bearing activities. A previous study found an association between long-term weight-bearing sports and radiographic knee and hip OA in former middle-aged elite athletes  [28].
Our study has several limitations. Firstly, observed frequency of MRIdepicted OA is dependent on the MRI-based definition of OA, and thresholds between different severity grades are somewhat arbitrary. Secondly, we assessed a highly selected sub-sample of Olympian athletes that presented for an MRI examination for a multitude of reasons. Clinical data was not available in this retrospective analysis and we do not know if these athletes had symptomatic OA. In addition, we did not obtain follow up information regarding the possibility of competing in the games, and if this was not possible, data on return to sport. Information such as duration of elite athletic activity or whether they were registered in prior Olympic competitions was not available. Future studies would benefit from reassessing the site of injury after a set period of recovery Fig.
Ethics statement Our study was approved by the medical research ethics committee of the South-Eastern Norway Regional Health Authority (S-07196C). Because the information in this study was anonymized and deidentified, the need for informed consent was waived. The International Olympic Committee granted approval to use the anonymized imaging and demographic data for publication. An additional institutional review board approval was obtained from Boston University (H-36593). The athletes' information was collected, stored, and analyzed in strict compliance with data protection and confidentiality.
Then, to identify the constituents, 1µL of each fraction under study was injected on a GC Trace Ultra gas chromatograph (Thermo Scientific) equipped with a HP5 MS column (30 m x 0. 25 mm x 0. 1 µm) and a temperature programmable injector (PTV) linked to a TSQ Quantum GC mass spectrometer (Thermo Scientific). Helium was used as carrier gas (1. 1 mL min -1 , constant flow mode) and the oven was programmed as follows: 70 °C (1 min), 70 °C to 300 °C (5 °C/min), isothermal at 300 °C for 20 min. The mass spectrometer was operating in electron impact mode (70 eV) with a scan range of m/z 50-700. The temperature of the source and of the transfer line was set at 220 °C and 300 °C, respectively. Data were reprocessed using Thermo Xcalibur 2. 1 Qual Browser (Thermo Scientific) mass spectrometry software.
has research grants supported by  Uriach Pharma ,  Novartis  and has received grants from  Instituto Carlos III-FEDER. Ana M Giménez-Arnau  has participated in educational activities for Uriach Pharma,  Novartis ,  Genentech ,  Menarini ,  LEO-PHARMA ,  GSK ,  MSD ,  Almirall ,  Sanofi.
Based on the results, experts from the Asia-Pacific Alliance for the Control of Influenza (APACI) issued recommendations for the improvement of existing surveillance systems. Results: Australia demonstrated the broadest scope of influenza surveillance followed by China and Malaysia. In Australia, surveillance tools covered all sub-systems. In China, surveillance did not cover non-medically attended respiratory events, primary care consultations, and excess mortality modelling. In Malaysia, surveillance consisted of primary care and hospital sentinel schemes. There were disparities between the countries across the 5 evaluation criteria, particularly regarding data granularity from health authorities, information on data representativeness, and data communication, especially the absence of publicly available influenza epidemiological reports in Malaysia.
Selected samples from the NISN are processed by the WHO CC laboratory in the CNIC in Beijing (sub-system 2), which then provides the WHO FluNet with influenza type and subtype breakdown, and a phylogenetic and antigenic analysis are sent to GISA ID's EpiFlu database and used for influenza vaccine strain selection and recommendation. The NISN also played a vital role in the early detection of emerging novel influenza viruses. Built on the existing influenza surveillance network, the CNIC developed a novel influenza identification platform in order to detect zoonotic infections. This system enabled the CNIC to confirm China's first human infections with A(H7N9), A(H10N8) and A(H5N6) viruses just 1-3 days after receiving specimens. In parallel, the China Public Health Emergency Management Information System (CPHE MIS) reported ILI outbreaks of more than 10 cases within 5 days in all close settings to the local CDC and NIC (sub-system 4).
Malaysia In Malaysia, influenza surveillance focused mainly on influenza activity and virology. Figure  3 ). 15 sentinel clinics under ILI syndromic surveillance (sub-system 5) and 8 sentinel hospitals under SARI syndromic surveillance (sub-system 6) collect five samples per week each. Then, specimens are sent to two designated laboratories: the MKAK Sungai Buloh for the ILI specimens and the Virology Unit of Institute of Medical Research (WHO NIC) for SARI specimens (sub-system 2)  [34]. As a WHO NIC, the Department of Medical Microbiology in University of Malaya reports isolates separately to a WHO CC and laboratory test results are submitted to WHO FluNet database  [9]. Although respiratory virus outbreaks in close settings may be reported to the MOH, there was no reporting obligation as influenza is not a notifiable disease in Malaysia (sub system 4).
Adherence to WHO guidance Australia, China, and Malaysia contribute to WHO basic requirements in terms of monitoring of influenza virology and activity. All three countries provide the results from their sentinel schemes in primary and secondary care on a weekly basis to their respective NIC, supporting the identification of seasonality patterns and circulating subtypes. Compared to Malaysia, both China and Australia have developed more in-depth virological surveillance and both countries have a WHO CC reference and H5 reference laboratory, providing data on influenza virus genome sequencing, antigenic characterisation, antiviral resistance, and identification of pathogens with pandemic potential such as avian influenza viruses. These contribute to WHO FluNet, the Global Initiative on Sharing Avian Influenza Data (GISAID)'s EpiFlu database and the biannual WHO vaccine recommendations  [9, 39].
Data communication The Australian Department of Health publishes the national influenza surveillance report fortnightly during the season, and monthly otherwise  [28]. In China, the CNIC has generated online weekly influenza reports since 2005 to share when, where, and which influenza viruses were circulating using NISN and CPHEMIS surveillance data. The weekly reports, in both Chinese and English, are emailed to key stakeholders and are also made available on the CNIC website  [32]. The NIDRS notified influenza cases and deaths are shared with a breakdown by age and province on a monthly basis by the CCDC on the Public Health Science data platform  [31]. Hospital admission data are not available, except occasionally in scientific publications from observational studies  [41]. Although laboratory-confirmed influenza cases by subtype are available through the WHO FluNet website, weekly and annual influenza surveillance reports are not made publicly available by the Malaysia MOH.
Estimates of influenza incidence, associated hospitalization rate, and mortality rate could be produced on an annual basis at a minimum by province. It is also suggested to expand the current SARI network to cover all provinces and publish data on severe influenza cases using the existing weekly bulletin from the CNIC. To compensate for the limitations of influenza deaths notified under the NIDRS, the adoption of an excess-mortality model to estimate the mortality attributable to influenza or for all causes, as previously performed by Chinese research groups at national, provincial, and city levels would be useful  [40, [44] [45] [46]. Finally, the use of surveillance tools to monitor nonmedically attended events could be considered, so as to best anticipate the evolution of the epidemic, such as self-reported web-survey, medical phone line surveillance or monitoring of web queries.
Moreover, mandatory notification tools such as the NIDRS, that records the number of influenza cases and deaths across China, may have represented a conservative estimate of the overall influenza burden (e. g. in 2018 only 765,186 cases and 153 deaths were notified). In Malaysia, beyond WHO basic requirements, the 2018 influenza surveillance protocol sets out the objectives pursued, including: "To provide data that can contribute to the estimation of the burden of severe respiratory disease associated with influenza and other respiratory pathogens", which is yet to be fulfilled  [34]. The novelty of this study is to provide a first crosscountry comparison and evaluation of influenza surveillance system in the Western Pacific Region with prioritized recommendations from the APACI network experts.
Conclusions This study provided an example of how a comparative framework inspired from WHO standard surveillance guidelines can support expert recommendations to drive improvement of influenza surveillance capabilities. Expert recommendations addressed key elements to build stronger surveillance systems such as expanding existing sentinel schemes in primary and secondary care, introducing new tools such as excess-mortality modelling and making surveillance data publicly available on a weekly and annual basis. Such improvements could contribute to better inform national influenza control strategies, enhance public disease awareness, and ultimately improve VCR. Researchers are thus encouraged to use this framework in additional geographies, and further fine-tune it as needed. KS, receives a salary from the APACI which has received funding towards some of its activities from industry sources, including Roche and Seqirus, outside of the submitted work.
Acknowledgments We would like to thank the  APACI  for its enthusiastic and active support to prepare this manuscript and in particular,  Dr. Raja Dhar  from the  Department of Pulmonology, Fortis Hospital in Kolkata, India , member of the APACI for their final review of the manuscript. The manuscript has received an editorial support by  Nicola Truss , inScience Communication, London and was funded by  Sanofi Pasteur.
Study design and treatment JAVELIN Lung 200 (NCT02395172) was an open-label, multicenter, randomized, phase 3 trial. The study design, methodology, and primary analyses have been previously reported in detail  [12]. Briefly, the trial enrolled adult patients with histologically confirmed stage IIIB, IV, or recurrent NSCLC with disease progression after prior platinum-doublet chemotherapy. Patients were excluded from the trial if they had nonsquamous cell NSCLC harboring an EGFR or ALK mutation or prior treatment with an antibody or drug targeting a T-cell coregulatory protein (eg, ICI). The primary analysis population was patients with PD-L1 expression in ≥1% of tumor cells (PD-L1+ population), whereas the secondary analysis population (full analysis set) included patients with PD-L1+ and PD-L1-tumors.
Seventy four (74) samples were also collected before ACT introduction in the Urban-Senegalese capital Dakar, a region that has shifted to malaria elimination plans, and PfKelch13 mutations compared to post ACT samples. Our study provides a map of PfKelch13 distribution in circulating Senegalese P. falciparum clinical isolates from low to high malaria transmission areas. In addition our epidemiology data on the parasitic disease shows an increase of severe malaria cases that could result from the low infection rates and loss of immunity. The prior vs. post ACT Pfkelch13 mutations comparison shows a useful baseline for emerging PfKelch13 polymorphism in parasites under 8 and 9 years ACT drug pressure in Senegal.
Results: Demographic characteristic of the study population, malaria prevalence and mortality. The data of our study were generated from 280 malaria-infected patients, recruited from five regions of variable malaria transmission intensity. From low to high transmission setting hospitals from Louga, Saint-Louis (N = 14), Dakar (N = 25), Kolda (N = 117) and Tambacounda (N = 124) were included respectively. In both the pre-elimination regions Saint-Louis and Louga (referred as Louga in our work) the low number of malaria infections (  14 ) confirms the lowest malaria prevalence. All 280 blood samples were collected between 2014 and 2015 i. e. 8 to 9 years following ACT introduction in Senegal. All included patients were tested and confirmed to be Pf-RDT positive on collection/visit day. Both demographic and clinical characteristics of the study participants are summarized in Table  1.
Sample collection and processing The study was done in accordance to the guidelines of the Institutional Review Board (IRB) of University Cheikh Anta Diop Dakar Senegal and on behalf of the National Research extension at 72°C ; and a final 10 minutes extension at 72°C for the first PCR. The nested PCR was performed using the following settings, 15 minutes initial denaturation at 95°C followed by 40 cycles with 30 seconds denaturation at 95°C, 1 minute of 40 cycles annealing at 60°C, 1 minute of 40 cycles extension at 72°C and a final 10 minute extension at 72°C. PCR products were sequenced (Sanger) and analysed with the Genalys software version 2. 0b  29. Sequencing reactions were performed according to the Dye terminator v3. 1 method using an ABI PRISMs 3730 DNA Analyzer (Applied Biosystems, Foster City, CA, USA).
Mix sequencing contained 2µl PCR product, 0. 5µl BigDye v3. 1, 1. 87µl buffer 5X, 0. 5µl primers (10µm), up to 5. 17µl with water. Conditions were set as follows, 96 °C for 5mn, 25 cycles of 96°C, 10 sec; 60°C for 4mn and 15°C forever. Sequencing products were purified with Sephadex G50 superfine (GE Healthcare). The resulting sequences were next analysed and the corresponding chromatograms closely checked for mutation detections. All nucleotide blasts were done using NCBI blast and Plasmodb 3D7 (PlasmoDB 46 version released Nov 6th 2019) (www. plasmodb. org). One-way ANOVA was performed using GraphPad Prism version 8. 0. 0 (GraphPad Software, San Diego, California USA, www. graphpad. com). Figure Legends.
Spermatogenesis is a complex process regulated by a multitude of genes. The identification and characterization of male-germ-cell-specific genes is crucial to understanding the mechanisms through which the cells develop. The term "TEX gene" was coined by Wang et al. (Nat Genet. 2001; 27: 422-6)  after they used cDNA suppression subtractive hybridization (SSH) to identify new transcripts that were present only in purified mouse spermatogonia. TEX (Testis expressed) orthologues have been found in other vertebrates (mammals, birds, and reptiles), invertebrates, and yeasts. To date, 69 TEX genes have been described in different species and different tissues. To evaluate the expression of each TEX/tex gene, we compiled data from 7 different RNA-Seq mRNA databases in humans, and 4 in the mouse according to the expression atlas database.
The TEX gene family As mentioned above, 69 expressed TEX or Tex genes (61 human genes and 61 mouse genes (Fig. 1 )) are listed in the main databases (https://gtexportal. org/ home/, https://www. ensembl. org/index. html, https:// www. omim. org/, etc. ). These genes are distributed throughout the genome. To evaluate the expression of each TEX/Tex gene, we compiled data from 7 different RNA-Seq mRNA databases in humans, and 4 in the mouse according to the expression atlas database (https://www. ebi. ac. uk/gxa/home). The 7 databases for RNA-Seq mRNA results in humans were: (1) the Genotype- The 4 databases for RNA-Seq mRNA results in the mouse were: (1) the mammalian database from Kaessmann's lab  [11] : 6 tissues (as in humans). The data are reported in Table  1  (for humans), Table  2  (for mice), and Table  3  (for other species).
Tex13 Tex13 is an X-linked gene expressed exclusively in male germ cells. The Tex13 family has 4 members. Wang et al. identified the first two human orthologs (TEX13A and B) in 2001  [7]. The degree of human vs. mouse nucleotide sequence identity for Tex13 varies from one database to another. Lastly, 4 Tex13 genes have been identified: according to Profile Alignment software (https://www. ibi. vu. nl/programs/pralinewww/), the percentage nucleotide sequence identity is 50% for Tex13A, 54% for Tex13B, 30% for Tex13C, and 32% for Tex13D. According to the UniProt database (www. uniprot. org/), the percentage is 23% for TEX13A, 31% for TEX13B, 6% for TEX13C, and 8% for TEX13D. The location of TEX13 proteins within germ cells is nuclear. Using a mouse testicular teratoma cell line (considered to possess the characteristics of male germ cells), Kwon et al.
Tex19 Tex19 is a mammal-specific duplicate gene (since renamed Tex19. 1 and Tex19. 2) found in the mouse and rat. According to the UniProt database, tex19. 1 expression in the embryo decreases after murine embryonic stem and germ cell differentiation. At later stages of development, Tex19 expression is limited to the germ line. tex19. 1 transcripts have also been detected in mouse pluripotent stem cells. It is thought that tex19. 1 encodes a protein expressed solely in germ cells and pluripotent cells. Male Tex19. 1-null mice are infertile, with a defect in meiotic chromosome synapsis, the persistence of DNA DSBs during meiosis, and a loss of post-meiotic germ cells. It was further demonstrated that TEX19. 1  [41]  and its paralog TEX19. 2  [42]  interact with PIWI proteins in mouse adult testis to repress transposable genetic elements and maintain genomic stability through successive generations.
Protein expression Protein expression data remains scarce. For 14 TEX genes, the protein expression pattern is similar to the mRNA expression pattern. A testis-specific protein isoform has been identified for 29 TEX genes, and expression data are missing for 14 other genes. An ovaryspecific protein isoform has only been identified for TEX11. A highly variable testicular location has been reported for 21 TEX genes (Table  1 ), although germinal cell expression (from spermatogonia to spermatids) has been reported in 19 cases. Eight proteins are referenced in the OMIM database (https://omim. org/), and defects in 3 of the coding genes (TEX11, 14 and 15) have been linked to phenotypes.
TEX genes, dysregulation of spermatogenesis, and a predisposition to infertility Thirteen TEX genes are now referenced in the OMIM database, and 3 have been linked to a specific phenotype. Here, we report only the data associated with gene defects (Tables  6  and 7 ). TEX11 (OMIM 300311)  [15-20, 62, 63]  TEX11 (on Xq13. 1) is currently the most frequently reported gene as being associated with azoospermia  [62]. Using an X-chromosome high-resolution microarray, Yatsenko et al. identified the loss of TEX11 exons 9-11 (607del237bp) in two azoospermic patients with homogeneous or mixed meiotic arrest  (47). This in-frame genomic deletion predicted a protein lacking 79 amino acids in the highly conserved sporulation domain SPO22. Additional TEX11 missense and splicing variants were found in 2.
3% versus 1. 7%, respectively; p = 0. 007)  [20]. However, the study did not find any differences between pathologic and benign variants. Since then, additional TEX11 missense variants or deletions have been reported  [47, 4852, 53] ; suggesting that this X-linked gene has a major role on azoospermia. Recently, low TEX11 expression was reported in a man with Sertoli-cell-only (SCO) syndrome  [2]. TEX11 is linked to spermatogenic failure, X-linked, 2 syndrome in the OMIM database (OMIM 309120). In 2015, Zhang et al. explored the possible association between single nucleotide polymorphisms (SNPs) in TEX11 and idiopathic male infertility  [63]. The homozygous rs6525433 polymorphism genotype was significantly associated with general infertility (odds ratio (OR) = 1. 517, 95% confidence interval (CI):1.
Other deleterious variants have been associated with infertility, maturation arrest, and SCO phenotypes  [22, 64]. Taken as a whole, these data suggests that alterations in TEX14 gene has a major impact on the onset of azoospermia. TEX14 is now also listed in the OMIM database as being linked to spermatogenic failure 23 syndrome (OMIM 617707). Furthermore, low TEX14 expression has been reported in a patient with the SCO syndrome  [2]. TEX15 (OMIM 605795)  [2, 26, 37, 63, 65, 66]  The first nonsense mutation (leading to a premature stop codon) in the TEX15 locus was identified by exome sequencing in a consanguineous Turkish family  [26]. The mutation co-segregated with the infertility phenotype; two brothers with nonobstructive azoospermia and an oligozoospermic sibling were homozygous for the mutation.
These males presented a drastically reduced testicular size (by more than 50%) and maturation arrest at the primary spermatocyte stage  [26]. Other nonconsanguineous siblings with nonobstructive azoospermia and a low testicular volume have been found to be compound heterozygotes for deleterious TEX15 variants  [25]. To date, few damaging variants have been identified (Table  4 ). TEX15 has now been linked to spermatogenic failure 25 syndrome in the OMIM database (OMIM 617960). Furthermore, low TEX15 expression has been reported in a man with SCO syndrome  [2].
Aims: Two post-authorisation studies assessed the safety and persistence of patients' use of nalmefene. Methods: The START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and followup data from German, Swedish and UK healthcare databases. Both studies permitted 'all comers' without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities. Results: START study: Overall, the mean duration of nalmefene treatment was 10. 3 ± 7. 3 months (N = 1348), with 49. 0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were 'goal reached' and 'drug cost'.