dataesr/scientific-paragraphs-categorization huggingface dataset:
Murepavadin fulfilled innovation criteria (WHO 2019), including the main criteria for absence of known cross-resistance  (Burrows, 2018) , and reached phase III trials in HAP/VAP caused by P. aeruginosa (NCT03582007, NCT03409679). Unfortunately, murepavadin was prematurely withdrawn from the authorization race on July 2019 due to high incidence of kidney injury 2 , another hard reality of clinical development that can be interrupted even in late phase due to imbalance of benefit/risk ratio for patients. An alternative mode of administration of murepavadin, such as inhalation, is being explored to improve nephrotoxicity. A new phase I has been announced to start in 2022 3. In 2019, RC01 another new antibiotic targeting LPS biogenesis entered in clinical development (Figure  4B ). RC01 inhibits the bacterial enzyme LpxC, a key protein involved in the production of LPS lipid A.
Despite demonstrated efficacy in clinical isolates of P. aeruginosa from CF patients and good safety in preclinical phases, the phase I prematurely stopped for safety concerns (NCT03832517). As illustrated by the two previous antibiotics with new modes of action, murepavadin and RC01, novel targets or chemicals represent an unpredictable toxicity risk, as the transposition of safety signals from preclinical models to human is uncertain  (Theuretzbacher et al. , 2020).
But what's new in the clinical development pipeline since the 2017 WHO alert Evaluation of phases II/III clinical data  (Sims et al. , 2017; Lucasti et al. , 2016; Titov et al. , 2020; Motsch et al. , 2020)  demonstrates that the relebactam/imipenem-cilastatin association is well tolerated and effective in the treatment of cUTIs, cIAIs, HAP/VAP and obtained FDA approval for these therapeutic indications 1,2. Taniborbactam/cefepime association demonstrated in vitro rescue of cefepime activity by taniborbactam against clinical isolates of CRPA  (Hamrick et al. , 2020). Fast Track designated by the FDA, the association skipped phase II and is currently on phase III trial to access the safety and efficacy compared with meropenem in both eradication of bacteria and in symptomatic response as primary endpoint in patients with cUTIs including acute pyelonephritis (NCT03840148).
Another phase III trial in patients with HAP/VAP is scheduled to begin in 2022 3. At least four other new BLI in association with β-lactam are on phase I stage (completed or ongoing) (Figure  4C ): nacubactam, zidebactam, QPX7728 and XNW4107. Whereas nacubactam reported narrow in vitro activity in P. aeruginosa  (Asempa et al. , 2020) , QPX7728 is an ultra-broad-spectrum β-lactamase inhibitor with the broadest spectrum of inhibition in vitro reported to date in a single BLI molecule  (Lomovskaya et al. 2020). Zidebactam in association with cefepime should start a phase III in cUTI or acute pyelonephritis end of 2021 (NCT04979806). Despite this antibiotic-based strategy, other mechanisms can unfortunately confer resistance to β-lactam/BLI new combinations. Beyond βlactamases production, overproduction or extended-spectrum β-lactamases, P.
,2016). APPA02 1 , a new inhaled cocktail of complementary phages, is currently tested for safety and tolerability in a phase I/II trial to treat serious respiratory infections, with an initial emphasis on CF patients (NCT04596319). P. aeruginosa recovery in sputum following multiple doses of treatment will be also explored. In March 2021, a phase I/II trial was initiated for assessment of another targeted inhaled phage therapy YPT01 2 added to standard antimicrobial therapy in the treatment of chronic P. aeruginosa infections in CF (NCT04684641). A multispecies targeting topic phage cocktail TP102 3 was formulated against P. aeruginosa but also Staphylococcus aureus and Acinetobacter baumannii. TP102 started a safety evaluation in subjects with both non-infected and infected diabetic foot ulcers as the primary endpoint and targeted bacteria clearance as secondary endpoint (NCT04803708).
Results of these 3 early phase studies for APPA02, YPT01 and TP102 assessment are expected in 2022. BX004-A, a nebulized bacteriophage therapy entered in a phase Ia/IIb (Figure  4D ). Exploratory objectives include whether this treatment reduces sputum P. aeruginosa bacterial load in CF subjects with chronic P. aeruginosa pulmonary infection (NCT05010577). During the same time, other new topical phage therapies by spray as an adjunct to SOC therapy for the prevention and treatment of P. aeruginosa, S. aureus, or Klebsiella pneumoniae infections will enter in development in pressure ulcers (PL03BM, NCT04815798) and burns (PGX0100, NCT04323475). Despite promising results, both historically and recently, the efficacy of phage therapy has still not been sufficiently examined and documented in high-quality clinical trial in humans to answer the questions raised about how to best use bacteriophages  (Leitner et al.
DEPRIVING BACTERIA FROM A SURVIVAL ESSENTIAL ELEMENT: IRON As an essential nutrient for growth and biofilm establishment, P. aeruginosa has developed different strategies to acquire iron from its environment (haem or siderophores mediated uptake systems and porins)  (Zhang et al. , 2021). Host fights infection reducing iron biodisponibility for its invading bacteria using for example transferrin in serum and lactoferrin in mucosal secretion  (Zhang et al. , 2021). Acting as an iron mimetic, gallium disrupts multiple iron-dependent synthetic and metabolic pathways  (Frei, 2020). Preliminary clinical study raised the possibility that gallium may be a safe and effective treatment for human infections  (Goss et al. , 2018). A phase II study to test IV gallium nitrate to control P. aeruginosa infections in adults with CF started in 2016 (NCT02354859).
But what's new in the clinical development pipeline since the 2017 WHO alert? The phase II clinical trial in adults with CF found no significant difference between the number of responders (defined as a participant having a 5% or greater increase in lung function by day 28) in the IV gallium nitrate and placebo group 1. The primary endpoint was unmet, however a significantly reduction of P. aeruginosa was found in the sputum of gallium treated patients compared to the placebo group for participants who were culture positive for P. aeruginosa at baseline 2. Overall, IV gallium nitrate was well-tolerated compared to placebo. With broad-spectrum anti-infective activity AR501 is being developed in a phase I/IIa (Figure  4D ) to treat chronic bacterial lung infections of CF patients (NCT03669614).
On 2020 positive safety data were reported from the phase I portion of the study, and AR-501 has been granted Fast Track, Qualified Infectious Disease Product, and Orphan Drug Designation by FDA and EMA. The originally planned protocol design was adapted into a phase IIa (dose selection / sample size determination) which results expected in 2022 will be implemented directly in a phase IIb study (efficacy) using the same clinical study protocol 3. This is an encouraging example of simplified and accelerated development supported by Health Authorities in a context of urgent need. Final data collection date for primary outcome measure of ALX009 in healthy volunteers and patients suffering from CF and non-CF bronchiectasis was expected in October 2021 (NCT02598999).
ANTI-BIOFILM STRATEGY Among virulence factors of P. aeruginosa, biofilms increase bacterial adherence, immune system evasion and antibiotic tolerance by blocking the diffusion of positively charged drugs. OligoG is an alginate oligosaccharide with the potential to reduce sputum viscosity of CF patients by chelating calcium  (Ermund et al. , 2017) , easing clearance of mucus from patient airways, reducing microbial burden and inflammation. OligoG was also shown to disrupt biofilm structure of P. aeruginosa mucoid phenotype  (Powell et al. , 2018)  and could in consequence improve host immune system action and the effectiveness of antimicrobial agents. To determine the safety and local tolerability of multiple dose administration of inhaled fragment in healthy volunteers, a phase I study was performed with a particular attention on pulmonary functioning and adverse events (NCT00970346).
But what's new in the clinical development pipeline since the 2017 WHO alert? In a first phase II study in adult CF subjects with P. aeruginosa lung infection, inhalation of OligoG powder over 28 days was shown to be safe, however statistically significant improvement of FEV1 (forced expiratory volume by the patient in one second) was not reached [132]. Lung function is widely used as primary outcome measure in the development of drugs to treat CF but regarding its mode of action could not be adapted to prove an OligoG efficacy, especially when disease is already installed. Post hoc subgroup analyses support mechanism of action for OligoG and warrant further prospective studies  (Van Koningsbruggen-Rietschel et al. , 2020). OligoG has Orphan Drug designation from both the EMA and the FDA and is currently tested in other phase IIb studies in addition to SOC compared to placebo with SOC too (NCT03698448 and NCT03822455).
SNSP113 (SYGN113), a novel large polycationic glycopolymer, poly (acetyl, arginyl) glucosamine was tested in a phase I study in healthy subjects and patients with stable CF (NCT03309358) and is currently evaluated in a phase II study (Figure  4E ). PLG0206 (WLBU2), an engineered cationic antimicrobial peptide with broad-spectrum activity and preventing in vitro P. aeruginosa biofilm growth on airway epithelial cells  (Lashua et al. , 2016) , received Orphan Drug status for prosthetic joint infection and entered in phase 1 trial in healthy subjects in 2018. PLG0206 will enter a phase 1b for treatment of periprosthetic joint infection in 2022 (NCT05137314).
OTHER INNOVATIVE ANTI-VIRULENCE STRATEGIES As T3SS and associated toxins are major virulence factors of P. aeruginosa (Figure  2 ), innovative therapeutic strategies are developed to reduce the infection severity. Despite many hopes based on in vitro or preclinical activities, only one treatment targeting T3SS is currently in clinical development (Figure  4E ). Ftortiazinon, a small molecule with a strong potential as an antibacterial therapy  (Sheremet et al. , 2020) , developed by the Gamaleya Research Institute, entered a phase 2 in combination with cefepime for the treatment of patients with cUTI caused by P. aeruginosa in 2018 (NCT03638830).
aeruginosa infections despite a half century of research effort specifically focused on this challenge  (Sainz-Mejías et al. , 2020; ClinicalTrials. gov. , 2021). Studying pipeline anti-P. aeruginosa since 2017 up to now, shows how development of a new treatment can be a difficult process. Lack of correspondence between in vitro or preclinical study and phase II clinical response questions the choice of pertinent animal models recreating human infection conditions  (Theuretzbacher et al. , 2019; Theuretzbacher et al. , 2020). Methodology used is often a strategic issue, with the crucial definition of the clinically significant primary outcome  (Adlbrecht et al. , 2020; Merakou et al. , 2018)  and the infection-site that could best allow to meet efficacy criteria. The absence of statistically significative evidence is not the evidence of absence of efficacy.
ACKNOWLEDGEMENTS We thank members of  SB  team for support. Work of S. B. team is funded by the  Centre National de la Recherche Scientifique , the  Aix-Marseille Université , and by grant from the  Agence Nationale de la Recherche  ( ANR-21-CE11-0028-01 ). A. L. G. is supported by  "Vaincre la mucoviscidose" (VLM)  and " Association Grégory Lemarchal " (Grant number  RF20190502416  and  RF20210502854 ),  ANR-15-IDEX-02 ,  SATT Linksium and Fondation Université Grenoble Alpes.
In Lebanon, scientists have used a database of species richness across the country to prioritize plant conservation to optimize the management of threatened species  [34]. However, there remains great uncertainty about whether or not designated protected areas will be adequate in the long term  [35, 36]. Furthermore, protecting all potentially suitable areas could be a difficult task if local resources are limited. Today, there is an urgent need to identify both potential refugial areas and populations with high adaptive capacity and to prioritize these areas for effective protection in the long term. In this study, we developed a new conservation index combining mountain topography, genetic diversity of three mountain tree species, and a climate scenario for the Mediterranean region. The objective of this conservation index is to (1) identify potentially suitable microrefugial areas in the mountains, (2) assess the adaptive capacity of populations within or near these areas, and (3) consider the effects of climate change on the populations studied in the areas where they occur.
Objective: To describe and analysed the functional outcome (FO) after spinal meningioma (SM) surgery. Methods: We processed the système national des données de santé (SNDS) i. e. , the French national administrative medical database to retrieve appropriate cases. We analysed the International Classification of Diseases 10 codes to assess the FO. Logistic models were implemented to search for variables associated with a favourable FO i. e. , a patient being independent at home without disabling symptom. Results: A total of 2,844 patients were identified of which 79. 1% were female. Median age at surgery was 66 years, interquartile range (IQR) (56-75). Ninety-five point nine percent of the SMs were removed through a posterior ± lateral approach and 0. 7% need an associated stabilisation. Benign meningioma represented 92.
Neurospine eISSN 2586-6591 pISSN 2586-6583 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons. org/licenses/by-nc/4. 0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. www. e-neurospine. org 97 The 2016 World Health Organization (WHO) classification of tumors affecting the central nervous system (CNS) recognises 3 grades of meningiomas. 6 ] [9]  Management options include regular monitoring especially for incidental tumors, symptom control, surgical excision, radiotherapy (RT) and occasionally chemotherapy but, tailored maximal resection is the treatment of choice for SM. 1] [12]  Administrative medical databases (AMDB) are massive repositories of collected healthcare data for various purposes.
Clinical Material We performed a cross-sectional nationwide descriptive observational and analytic retrospective study using the système national des données de santé (SNDS), the national French medico-administrative database. Incidental SM never operated are not considered in this study; only surgically treated SMs were taken into account. Patients who underwent the surgical resection of a meningioma between the first of January 2008 and to the 31 December 2017 were included. Cases were selected using an algorithm combining 2 variables as described previously: the type of the surgical procedure identified by the Common Classification of Medical Acts and the primary diagnosis according to the International Classification of Diseases (ICD-10). 3, 5, 18, 19 enign meningiomas were considered as corresponding to the D32 ICD-10 codes, atypical to D42 and malignant to C70.
We defined the first recorded date of SM surgery as the index date. Age was classified into elderly ( ≥ 70 years) and non-elderly (18-69 years). Patients below 18 years were excluded (n = 22). The mortality-related morbidity index (MRMI) predictive of all-cause mortality and the expenditure-related morbidity index predictive of health care expenditure were used to assess the global health-state severity. 20 These 2 weighted morbidity indices summarize the association between a set of conditions identified through algorithms using SNDS data and each outcome. They have been validated in the French context against the most used morbidity indices and offer the possibility to choose a morbidity measure adapted to the outcome under study. Further details about the conditions included as predictors, corresponding weights as well as prevalence among the study population are available as Supplementary materials (https://assurance-maladie.
Statistical Methods For the cohort description, continuous variables are reported as medians and interquartile ranges (IQRs); categorical variables are reported as frequencies and proportions. For continuous variables, the Mann-Whitney-Wilcoxon rank-sum test was used for between-group comparisons and for categorical data, the chi-square test was applied. A univariable and stepwise multivariable logistic regression model was employed to identify predictors of a good FO defined above. Variables were included in the multivariable regression if they had a p-value < 0. 15 in the univariable model. In essence, there is no lost to follow-up patient in the SNDS are those who died are automatically registered as such in the database. All tests were 2-sided and statistical significance was defined with an alpha level of 0.
05 (p < 0. 05). Analysis was performed using the SAS Enterprise Guide (ver. 7. 15 HF8, SAS Institute Inc. , Cary, NC, USA) and the R programming language and software environment for statistical computing and graphics (R ver. 4. 1. 2 [2021-11-01]). 21 The statistical programme and workflow were written in R Markdown v2 with RStudio for dynamic and reproducible research. 22.
5 (0. 38-0. 67) < 0. 001* 0. 55 (0. 41-0. 74) < 0. 001* 0. 53 (0. 4-0. 72) < 0. 001* 0. 52 (0. 38-0. 7) < 0. 001* 0. 51 (0. 37-0. 7) < 0. 001* Surgical delay more than 30 days 0. 48 (0. 33-0. 69) < 0. 001* 0. 47 (0. 32-0. 68) < 0. 001* 0. 49 (0. 34-0. of this study was to assess baseline data and long-term FO with its predictors of SM patients. Our study presents a unique modern nationwide populationbased analysis of SM patients. Thanks to the SNDS, we managed to gather the largest ever published series assessing the FO after SM surgery. The strengths of the SNDS reside both in the high number of patients and in the exhaustive data available from every hospital in France, private and public. The SNDS includes many information such as demographic data, medical and surgical procedure with associated diagnoses and date of death.
The database representativeness is nearly perfect, since it includes the whole country's population of nearly 68 million of inhabitants constituting one of the largest AMDB in the world. 13 ompiled from a number of institutions, the SNDS accuracy is nonetheless limited by inconstancies in data collection and recording. The retrospective nature of this study, together with the lack of clarity regarding treatment rationales and nonhomogeneous management strategies without random assignment, needs to be considered when evaluating the results. Moreover, gathering information on the patient status using electronic medical records software, is associated with a risk of imprecision regarding the preoperative clinical state and the outcome. ] [30]  However, they do not report on the FO but mainly on descriptive epidemiology and overall survival.
9-1. 2) (p = 0. 565). 36 If indicated, SM surgery should thus be performed regardless the age and these patients should be referred for surgery as early as possible asserting the concept of "time is spinal cord. "  15  This work highlights the great value of this unique database to evaluate the FO after SM surgery and its predictors. Further inclusion and prolonged follow-up are required to assess other prognostic factors such as the histopathological subtypes, best after SNDS, and the French Brain Tumour DataBase merging. 9.
We reduce and analyse the available JWST ERO and ERS NIRCam imaging (SMACS0723, GLASS, CEERS) in combination with the latest deep ground-based near-infrared imaging in the COSMOS field (provided by UltraVISTA DR5) to produce a new measurement of the evolving galaxy UV luminosity function (LF) o v er the redshift range z = 8 -15. This yields a new estimate of the evolution of UV luminosity density ( ρ UV ), and hence cosmic star formation rate density ( ρ SFR ) out to within < 300 Myr of the Big Bang. Our results confirm that the high-redshift LF is best described by a double power law (rather than a Schechter) function up to z ∼ 10, and that the LF and the resulting derived ρ UV (and thus ρ SFR ), continues to decline gradually and steadily up to z ∼ 15 (as anticipated from previous studies which analysed the pre-existing data in a consistent manner to this study).
2020 ; Adams et al. 2022 ). It is the power of this combined ground-based + space-based approach which we exploit again in this new study of the highredshift galaxy LF, but now for the first time armed with 45 arcmin 2 of deep multiband NIRCam imaging from the JWST Early Release Observations (ERO) and Early Release Science (ERS) programmes, and 1. 8 deg 2 of near-homogeneous near-infrared imaging in the COSMOS field provided by Data Release 5 (DR5) from the UltraV-ISTA surv e y  (McCracken et al. 2012 ). We have used these brand-new datasets to conduct a new search for galaxies at z ≥ 7. 5 in the three early JWST deep fields (SMACS0723, CEERS, and GLASS) and in the COSMOS/UltraVISTA field. The resulting new high-redshift galaxy samples have enabled us to derive a new estimate of the evolution of the galaxy LF, and hence ρ SFR , from z 8 out to z 15, less that 300 Myr after the big bang.
COSMOS/UltraVISTA We utilize near-infrared imaging from the UltraVISTA surv e y  (Mc-Cracken et al. 2012  ) which provides deep YJHK s imaging across 1. 8 deg 2 in the COSMOS field, taken using ESO's VISTA telescope in Chile. The UltraVISTA imaging is split into two regions 'ultradeep' and 'deep' which co v er approximately half the area each. These regions consist of four stripes, each of which alternate between the two depths across the image. In this study we use the fifth data release (DR5) of UltraVISTA which differs primarily from DR4 in providing significant deeper J -band and H -band imaging: 1 mag. deeper in the 'deep' stripes, and 0. 2 mag. deeper in the 'ultradeep' stripes. Within the central 1 deg 2 we complement the new near-infrared UltraVISTA imaging data with optical imaging from the CFHTLS-D2 field from the CFHT Le gac y Surv e y  (Hudelot et al.
2012  ) in u * griz. We also include wider-area optical data co v ering the MNRAS 518,  6011-6040 (2023)  full UltraVISTA field from the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) DR2  (Aihara et al. 2019 )  in the GRIZy filters as well as in two narrow bands, NB 816 and NB 921. All the near-infrared and optical imaging in COSMOS was aligned to the GAIA EDR3 reference frame using SCAMP and re-sampled using SWARP to a common pixel scale of 0. 15-arcsec. Finally, we supplemented our ground-based data sets by adding 3. 6 and 4. 5-μm photometry from Spitzer /IRAC imaging, which experience proves can be invaluable for the refinement of photometric redshifts as well as minimising the level of low-redshift galaxy and dwarf-star contamination in the final high-redshift galaxy sample. The Spitzer /IRAC data in 3.
C A TA L O G U E C R E A T I O N A N D G A L A X Y S E L E C T I O N To create catalogues in the COSMOS fields we utilized inverse variance weighted stacks of the data in the Y , J , H , and K s bands to increase the sensitivity of our detections. of z ∼ 6-10 Lyman-break galaxies. The catalogues were created using SExtractor  (Bertin & Arnouts 1996 )  in dual-image mode with the stacked images as the detection images. A master catalogue was created by combining sources detected in both the detection images, with duplicates remo v ed by retaining the object with the highest signal to noise. For the JWST catalogues we created two rest-frame UV-selected catalogues using SExtractor in dual-image mode with the F 200 W as the detection image. This was to optimise our catalogue to select z ≥ 8 galaxies as this filter will encompass the bright UV flux redward of the Lyman break.