dataesr/scientific-paragraphs-categorization huggingface dataset:
Quantification and Statistical Analysis Data from behavioural and neurochemical experiments were analyzed using Prism 6 software (GraphPad Software, San Diego, CA, USA). The data presented in the graphs are expressed as mean ± S. E. M. Statistical significance was determined using a two-way ANOVA followed by Bonferroni's multiple comparison post hoc tests. The level of significance was set to p < 0. 05. For statistical comparison of changes in the LTP experiments, the steady-state values were computed by averaging 11 consecutive responses obtained over a 5 min period immediately before the theta burst stimulation (baseline value) and at 55-60 min after TB5. Typically, more than one slice was used per mouse and the results of all determinations per genotype and treatment were analyzed to account for the overall variability of LTP responses in the different genotypes.
Microbiome Statistical Analysis In all microbiome analysis except for alpha diversity, taxa with a prevalence of <5% of samples at the genus level were excluded from the analysis as ratios are invariant to the subsetting and this study employs compositional data analysis techniques  [47, 48]. Principal component analysis was performed on centred log-ratio transformed (clr) values using the ALDEx2 library. The number of permutations was set to 1000. Beta diversity was computed in terms of Aitchison distance, or Euclidean distance between CLR-transformed data. Alpha diversity was computed using the iNEXT library  [49]. Piphillin was used for functional inference from 16S rRNA gene sequences in the form of KEGG orthologues  [50]. Gut-Brain Modules (GBMs) and Gut-Metabolic Modules (GMMs) were calculated using the R version of the Gomixer tool  [51].
Stacked bar plots were generated by normalizing counts to 1, generating proportions. Genera that were never detected at a 2% relative abundance or higher were aggregated and defined as rare taxa for the purposes of the stacked bar plots. In cases where more than two factors were considered, the lme4 library in R was used to fit the linear mixed effect models, with animal ID as a random effect if applicable  [52]. Differential abundance of both microbes and functional modules were calculated using implementation of the ALDEx2 library. A p-value of <0. 05 was deemed significant in all cases. To correct for multiple testing in tests involving microbiota or functional modules, the Benjamini-Hochberg (BH) post hoc was performed with a q-value of 0. 1 used as a cut-off. Custom R scripts and functions are available at https://github.
This implies that the enriched diet increases the functional capacity of the microbiome overall. This is reflected by the increase in metabolic potential for amino acid and sugar metabolism. In general, functions that are upregulated in a microbiome are considered to likely be more important for the homeostasis of that microbiome in a given environment  [79]. In this study we used the Piphillin framework, which reflects shotgun sequencing datasets reasonably well for mammalian samples  [80] , to infer microbial function. Indeed, several 16S rRNA gene studies have extended our ability to infer the functional contribution of individual bacterial community members by focusing on groups of genes associated with the synthesis of compounds which have the potential to interact with the human nervous system  [51].
However, the functional inference method used here is limited by the database it employs and given the 16S nature of our data, we have no conclusive evidence of the functional capacities presented here that would require further confirmatory investigation. In summary, the enriched diet did not rescue the negative behavioural effects of stress in Hdc -/-mice, in contrast to Hdc +/+ animals. Due to the substantial effect of histamine absence on the microbiome, even at baseline, we cannot ascertain to what extent the microbiome partakes in preventing the stress-induced alterations in wild type mice fed the enriched diet. Histamine is a ubiquitous molecule and given that lack of histamine causes systemic alterations to the overall physiology of the animal, it is difficult to resolve this issue.
Colours depict effect size, with blue (negative) indicating higher abundances pre-treatment and red (positive) indicating higher abundances post-treatment. * q < 0. 1. Relative abundance of (g) taxa and (h) Gut Brain Modules that displayed an interaction effect in Hdc -/-SCD mice and treatment. Benjamini-Hochberg adjusted q < 0. 1 for all cases. Data were collected from 5 mice per experimental group.
Acknowledgments:  Stéphane Grégoire of Niyazi Acar group , Oeil, nutrition et signalization cellulaire à Dijon for lipid analysis and  MetaToul-Lipidomique Core Facility  ( I2MC, Inserm 1048, Toulouse, France ) for the oxylipins analysis. This research was supported through  European Research Area-Healthy Diet for Healthy Life Project AMBROSIAC  and  Fondazione Ente Cassa Risparmio, Firenze  to  MBP. Sophie Layé  and  Moira Rossito  are supported by the  Fondation pour la Recherche Médicale  (équipe FRM PRINSS  DEQ20170336724 , to SL) and the  Nouvelle Région Aquitaine  ( Engagement 00070700  and  Convention 2017-1R30237-00013179-POST-DOCTORAT ).
The success of event detection relies on data quality (e. g. accuracy, completeness, consistency) as well as on the number of times the event has occurred in the past. To use statistical analysis, it is essential to have significant eruptive and monitoring datasets formatted in a consistent manner. The WOVOdat database of volcanic unrest is one of such standardized resource that allows for the comparison of unrest patterns between eruptions  (Newhall et al. , 2017; Costa et al. , 2019). The identification of the change of a volcano's normal to an unrest state, and the further progression towards eruption is largely based on the availability of time series monitoring data, including geophysical, geodetical, geochemical, and hydrological signals (e. g. Newhall and Dzurisin, 1988; Shroder and Papale, 2015; Loughlin et al.
In general, these earthquakes are shallow and thus preserve most of their high-frequency energy  (Neuberg et al. , 1998). The seismic energy has been used to characterize the size, generation and transport of PFs at Merapi  (Iguchi et al. , 2019)  and other volcanoes (e. g. Yamasato, 1997,; De Angelis et al. , 2007). Brodscholl et al. , 2000  used seismic broadband data to characterize the November 1994 sequential lava dome collapse PF at Merapi, where the seismic signal exhibits a linear relation between source volume and recorded seismic-amplitude envelope area. PF and Rockfall (RF) seismic amplitude-duration data were used as proxies to estimate collapsed lava dome volume of Merapi  (Young, 2007). At the Merapi observatory, hybrid volcanic earthquakes are classified as multiphase (MP) earthquakes  Fig.
Methodology and results In this section we present an approach to calculate the conditional probabilities to detect an on-going eruptive phase given the measured values of the monitoring data of the daily seismic multiphase energy (MPE). First, we explain the use of Monte Carlo simulations to account for the uncertainties in the lava extrusion start and end dates (Table  4 ). Later, we calculate the probability to observe a lava extrusion phase given the range of MPE, and compute how these probabilities have evolved over the years at Merapi. Finally, we evaluate how the MPE thresholds calculated using data from 1993 to 2012 could be used to detect the lava extrusion phases of 2018.
) real time (Fig. 9c ). We also compare the effectiveness of the value of 20 MJ as a threshold by calculating Eqs. (  5 )-(  8 ) for 2018 (Fig. 9b ). The visual camera installed by CVGHM at the crater captured the beginning of the lava dome formation on 11 August 2018. We find that for the 2018 dataset the (past) 7-day moving average of MPE continuously exceeded the 20 MJ threshold 14 days early than the observed onset of lava extrusion; overall for this threshold the test has an accuracy = 79%, precision =67%, sensitivity = 92%, and specificity = 70%, here we don't have associated uncertainties as in Fig. 7  because for 2018 there is an accurate register of the dates when the lava extrusion phase took place.
Discussion Our manuscript aims at contributing to develop methodologies for the correct identification and detection of different eruptive phases and their associated hazards. To achieve this it is essential to have long time series of monitoring data that are self-consistent and standardized (e. g. WOVOdat;  Newhall et al. , 2017) , identify patterns or structures within the data which may be diagnostic of the various types of activities, and have modeling or a statistical tool that can translate the data into useful or applicable results to mitigate the hazards. These three aspects and possible applications of our method to other volcanoes are discussed in turn below.
, 2013)  overshadowing other earthquake types like the MP. Later on 4 November, the PUS and DEL stations were destroyed and subsequently the seismic activity was registered only using the PLA station. Another source of uncertainty in our dataset is the lack of accurate dates when lava extrusion phases occurred, as most observations were via direct visual inspection of the volcano's summit which (due the occurrence of PF currents and explosions) carried major risks. Only recently, the monitoring network acquired thermal high-resolution visual images and movies in stereoscopic configurations  (Kelfoun et al. , 2021). Also, unmanned aerial vehicles (UAV) and satellite remote sensing analysis using Synthetic Aperture Radar (SAR) was used to detect morphological changes as well as to quantify lava-dome extrusion rates during the 2006 and 2010 eruptions  (Pallister et al.
Acknowledgements This research was supported by the  Earth Observatory of Singapore  (grant number  04MNS001816A620OOE01 -WOVOdat ) via its funding from the  National Research Foundation Singapore  and the  Singapore Ministry of Education  under the  Research Centres of Excellence Initiative. This work comprises EOS contribution number  427. We would like to thank  Center for Volcanology and Geological Hazard Mitigation (CVGHM). This work is being part of our on-going  NTU -Geological Agency of Indonesia collaboration under MoU in "Cooperation in Geosciences " and the arrangement between  EOS -CVGHM in "Assessment and Mitigation of Geological Hazards". Kasbani, Hanik Humaida ,  Hendra Gunawan ,  I. G. M. Nandaka  from  CVGHM  are thanked for their support. We also would like to thank  Mr. Nguyen Tien Nhan  and  Mr.
However, most of these candidates  are being clinically evaluated  (33)  as adjuvant therapies in combination with "standard of care" antibiotics. To date, there have been only three nontraditional antibacterial agents approved, all of which are monoclonal antibodies (MAb). Bezlotoxumab (approved by the FDA in 2016) binds and neutralizes Clostridioides difficile toxin B and was approved after the completion of two phase 3 clinical trials (NCT01241552 and NCT01513239)  (34). Raxibacumab was authorized for the treatment of inhalational anthrax in adults and children (approved 2012 by the FDA)  (35). Obiltoxaximab (US FDA, 2016; EMA, 2020)  (36) , like raxibacumab, has been approved to control the symptoms of inhaled anthrax toxins; while the safety profiles of raxibacumab and obiltoxaximab have been investigated in healthy volunteers, fortunately they have not yet been used clinically  (37).
Fixed-dose combinations of potentiators and antibacterial agents are included if they contain an NCE or an NBE. Search strategy. Data from the 2020 WHO antibacterial pipeline report  (10)  were used as a starting point for this updated analysis. Recent antibacterial pipeline reviews  (41) (42) (43) , previous WHO reports  (7, 9) , and The Pew Charitable Trusts' antibiotic development pipeline reviews (6) were also consulted. Additional references were identified using searches of antibacterial compound names and their synonyms from PubMed (https://pubmed. ncbi. nlm. nih. gov/), Google Scholar (https://scholar. google. com. au/), Cross-resistance can be obtained when the levels of the porin OmpK36 are varied. f First systemic formulation of this class, which was previously used in animals and topically in humans.
Gepotidacin is also being evaluated in a phase 3 trial to treat urinary tract infections (UTIs). Updating the 2020 WHO report  (10) , nafithromycin is now being evaluated in a phase 3 trial (CTRI/2019/11/021964) for treatment of community-associated pneumonia (CAP) in India, and the phase 2/3 trial (NCT04505683) of benapenem in China has been completed for complicated urinary tract infections (cUTI), including acute pyelonephritis. Other phase 3 agents of interest: ATM-AVI and tebipenem pivoxil. There are two antibacterial agents in phase 3 development that did not meet this review's inclusion e The DBO-BLIs zidebactam, nacubactam, and ETX0282 also have some antibacterial activity and have been classified as b-lactam enhancers (BLE) (97-99). f Previously used as an antibacterial treatment in animals.
ATM-AVI is being studied by Pfizer in a phase 3 trial (NCT03580044) to treat serious infection due to metallo-b-lactamase (MBL)-producing Gram-negative bacteria (50, 51) with support from the Biomedical Advanced Research and Development Authority (BARDA), Innovative Medicines Initiative (IMI), and AbbVie, through their 2020 acquisition of Allergan. The second is the carbapenem prodrug tebipenem pivoxil  (52, 53) , which was first approved for pediatric use in Japan in 2009 but has not been used elsewhere. Spero Therapeutics recently completed a phase 3 trial (NCT03788967) for tebipenem pivoxil (SPR994) as an oral treatment for Gram-negative cUTI and acute pyelonephritis infections. Clinically, the oral administration of tebipenem pivoxil could provide an alternative to i. v. administered carbapenems.
Traditional antibacterial agents in phase 1 and 2 clinical trials being developed against WHO priority pathogens. We identified 2 compounds in phase 2, 1 in phase 1/2a, and 14 in phase 1 development (Table  4 ). Since the 1 September 2020 cutoff date of the 2020 WHO pipeline report  (10) , two new polymyxin derivatives, MRX-8 (54, 55) (NCT04649541) and QPX-9003 (56, 57) (NCT04808414), started phase 1 trials in November 2020 and June 2021, respectively, as potential treatments for MDR Gram- negative pathogens. XNW-4107 is a BLI being that is developed in combination with imipenem and cilastatin that started a phase 1 in June 2021 (NCT04801043). The developer, Sinovent, has indicated that the XNW-4107 combination will be developed to treat patients with CRE, CRAB, and drug-resistant Pseudomonas aeruginosa  (58).
Thirteen of the traditional antibacterial candidates target M. tuberculosis, and only one, SPR720, is in development for lung infections caused by the NTMs, Mycobacterium avium complex, and Mycobacterium abscessus (Table  5 ). Eight of the 14 traditional antibacterial agents belong to new classes, and 9 have new antibacterial pharmacophores (see below). Since the 2020 WHO report  (10)  was released, two new compounds, TBAJ-587 (NCT04890535) and GSK 2556286 (NCT04472897), have entered phase 1 trials. TBAJ-587 is a bedaquiline analog with enhanced in vitro potency and a projected reduced cardiovascular liability  (61, 62). GSK 2556286 (GSK-286) acts directly on M. tuberculosis, and its mode of action has not been disclosed but has been proposed to involve cholesterol catabolism  (63, 64). In addition, TBI-166 (pyrifazimine) has moved to phase 2 (NCT04670120) and BTZ-043 has started a new phase 1/2 trial (NCT04044001).
Traditional antibacterial agents being developed against C. difficile. There are currently five traditional antibacterial agents (Table  6 ), one in phase 3 (ridinilazole) and four in phase 2 (DNV-3837, MGB-BP-3, ibezapolstat, and CRS3123), being developed to treat C. difficile. Antibacterial drugs used to treat C. difficile infections (CDI) are usually administered orally and absorbed poorly, as the infection is localized in the colon. This has encouraged the development of four new antibacterial classes and modes of action (ridinilazole, MGB-BP-3, ibezapolstat, and CRS3123; Fig. 5 ), while DNV-3837 is differentiated through its administration via i. v. infusion and is being targeted for use in patients who are unable to receive oral administration. Since the 2020 WHO report  (10)  was published, CRS3123 has started a phase 2 trial (NCT04781387).
Nontraditional antibacterial agents in phase 3 clinical trials. We found two nontraditional antibacterial agents in the NDA/MAA phase and four in phase 3 development (Table  7 ). Three are being developed to treat S. aureus infections: tosatoxumab is an MAb  (65) , exebacase is a phage-derived recombinant protein (66), and reltecimod is an immune modulator (CD28 T-lymphocyte receptor mimetic)  (67). Three are being developed to treat C. difficile infections: SER-109 consists of purified Firmicutes spores (68), RBX2660 is a liquid suspension of screened donor fecal microbiota  (69, 70) , and BB128 is a lyophilized donor fecal microbiota product. SER-109 has already successfully completed one phase 3 trial (NCT03183128)  (71). Since the publication of the 2020 WHO pipeline report  (10) , a phase 3 trial (NCT03931941) has started to evaluate RBX2660 as a treatment of C.
CYT107 is a glycosylated recombinant human interleukin (IL-7) that is being tested in a phase 2 trial (NCT04154826) to evaluate its immunotherapeutic response in patients with NTM lung disease. CYT107 has been evaluated in other clinical trials, including a phase 2b trial (NCT02640807) that reported a 3-to 4-fold increase in the absolute lymphocyte count and in circulating CD4 1 and CD8 1 T cells with CYT107 in sepsis patients (predominantly secondary to pneumonia and abdominal infections)  (74). TRL1068 is an MAb that binds to a DNABII epitope conserved across both Gram-positive and Gramnegative bacteria, which leads to bacterial biofilm disintegration, and is being evaluated in a phase 1 trial (NCT04763759) for prosthetic joint infections  (75, 76). BVL-GSK098 recently entered phase 1 (NCT04654143) and works through inactivation of a TetR-like repressor, EthR2, thereby enhancing ethionamide activation  (77).
5 , Fig. S2 ). There are 19 antibacterial agents with 18 new pharmacophores (macozinone and BTZ-043 are both BTZs) with seven inhibiting cell envelope synthesis, two acting at the synthesis level and five affecting DNA synthesis (Fig. 5 , structures in supplemental information Fig. S1 to S3 ). Telacebec inhibits the mycobacterial respiratory system  (82, 83) , which was first targeted by bedaquiline, via inhibition of the respiratory complex bc 1  (84). Half of the 18 new pharmacophores target mycobacteria, and 4 target C. difficile. Four of 19 antibacterial agents have new overarching modes of actions not previously exploited by marketed antibacterial drugs. Two target virulence: fluorothyazinon (phase 2, NCT03638830) and GSK 3882347 (phase 1, NCT04488770). Ftortiazinon inhibits the Gram-negative type III secretion system  (85)  and is being evaluated in a trial in combination with cefepime, and GSK 3882347 functions as an antagonist of the Gramnegative type 1 pilus adhesin (FimH)  (86).
BVL-GSK098 (phase 1, NCT04654143)  (77)  directly inhibits ethionamide-acquired resistance, while GSK 2556286 (phase 1 trial, NCT04472897) is proposed to involve M. tuberculosis cholesterol catabolism  (63, 64). Antibacterial agents that have halted or stopped clinical development. Drug development is inherently risky, and it is not uncommon for clinical development programs to be terminated or halted. The most common reasons for stopping development include lack of efficacy, off-target toxicity, and commercial considerations  (87). While antibacterial agents can drop out of the pipeline due to efficacy and resistance issues, it is more common to be due to toxicity and commercial concerns  (16, 41, 88). A list of antibacterial compounds and nontraditional moieties whose development has been terminated or halted are listed in the supplemental information (Table  S1 ).
ACKNOWLEDGMENTS Funding for the WHO report was kindly provided by the  Governments of Austria and Germany (Ministry of Education and Science). We acknowledge  François Franceschi  ( GARDP, Switzerland), Jennie Hood (Global AMR R&D Hub, Germany ), and  Mike Sharland  (Chair of the  WHO Antibiotic Working Group of the EML/EMLc , and  St George's University London, UK) , who were observers at the November 2020 WHO antibacterial pipeline meeting, as well as  Haileyesus Getahun  ( WHO, Antimicrobial Resistance Division ), for supporting this work. This contribution has been prepared strictly in a personal capacity and reflects the view of the authors. The views expressed must not be attributed to the  WHO , its  Secretariat , or its Member States.
v. / i. v. & oral Qpex Biopharma l l l NA ? --- QPX7728 1 QPX2015 (undisclosed) / boronate-BLI 1 b-lactam (undisclosed) a Pathogen activity: l, active; ?, possibly active; *, not or insufficiently active; NA, activity not assessed, as the antibiotic is focused and developed for only either Grampositive cocci or Gram-negative rods. Agents not active against critical-priority pathogens were assessed for activity against OPP, which includes the high and medium WHO priority pathogens. b Innovation assessment: , criterion fulfilled; ?, inconclusive data; -, criterion not fulfilled. CC, chemical class; MOA, new mode of action; NCR, no cross-resistance; T, new target. c OPP target pathogens: TNP-2198, H. pylori; afabicin, TNP-2092, KBP-7072, TXA-109, and PLG0206, S. aureus. d A phase 3 trial for zidebactam 1 cefepime was registered in July 2021 for cUTI or acute pyelonephritis (NCT04979806).
CC, chemical class; MOA, new mode of action; NCR, no cross-resistance; T, new target. bThis phase 2a trial (NCT04553406) was on FDA clinical hold, but this was lifted in January 2022. cThis is not considered to be a new mode of action, as the GyrB/ParE inhibitor novobiocin was once marketed but is no longer in clinical use. dThe lead drug clofazimine is approved to treat leprosy and has been used off-label for TB treatment.
Data preprocessing The data was preprocessed according to a standard method that we used in several previous studies  (Al Roumi et al. , 2019; Dotan & Dehaene, 2013 , 2016 , 2020; Dotan et al. , 2018; Pinheiro-Chagas et al. , 2017). The finger position was sampled at 60Hz, recorded as a sequence of time-stamped x and y coordinates, and transformed into a fixed sampling rate of 100Hz using cubic spline interpolation. The x,y coordinates were separately smoothed (Gaussian weighting, σ = 20 ms). Per time point, we calculated the direction between the finger coordinates at times t -10 ms and t, and the implied endpoint was defined as the position on the number line that the finger would reach if it kept moving in this direction. Implied endpoints outside the range  [-5, 105]  were considered as -5 or 105.
The required sample size for this t-test was calculated a-priori: assuming a relatively weak and noisy effect (such as the log effect observed in a previous study with this paradigm,  Dotan & Dehaene, 2013 : regression b = 0. 11, σ = 0. 11), setting alpha at 0. 01, aiming at a power of 0. 9, and using one-tailed analysis, yielded a minimum of 16 participants. Accordingly, we included 18 participants in Experiment 1 and 24 participants in Experiment 2. Our Matlab analysis tools, and an experimentation software corresponding to the one we used here, are available on http://trajtracker. com. The raw data is available in http://osf. io/7rvzh.