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Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better efficacy profile without compromising efficacy.

An infection with the tick-borne Rickettsia helvetica has been associated with a broad spectrum of clinical manifestations in humans, but patients are only seldomly reported. Understanding its disease etiology necessitates well-stablished infection models, improving to recognize and diagnose patients with R. helvetica infection and facilitating the development of effective control strategies. In this study, we used C3H/HeN mice as a model to establish R. helvetica infection, achieving a high infection prevalence (89–100 %). While the liver and the spleen DNA consistently tested positive for infection in all challenged mice, additional infected organs included the kidneys, heart, and the lungs. Notably, a low prevalence of infection was observed in I. ricinus nymphs fed on R. helvetica-challenged mice. In addition, larvae were refractory to infection, suggesting that ticks exhibit low susceptibility to the pathogen. To the best of our knowledge, this is the first study of an animal model for R. helvetica infection. It serves as a valuable tool for advancing research on the interactions among the bacterium and its vertebrate host.

Since the beginning of the industrial revolution, atmospheric carbon dioxide (CO2) concentrations have risen steadily and have induced a decrease of the averaged surface ocean pH by 0.1 units, corresponding to an increase in ocean acidity of about 30 %. In addition to ocean warming, ocean acidification poses a tremendous challenge to some marine organisms, especially calcifiers. The need for long-term oceanic observations of pH and temperature is a key element to assess the vulnerability of marine communities and ecosystems to these pressures. Nearshore productive environments, where a large majority of shellfish farming activities are conducted, are known to present pH levels as well as amplitudes of daily and seasonal variations that are much larger than those observed in the open ocean. Yet, to date, there are very few coastal observation sites where these parameters are measured simultaneously and at high frequency. To bridge this gap, an observation network was initiated in 2021 in the framework of the CocoriCO2 project. Six sites were selected along the French Atlantic and Mediterranean coastlines based on their importance in terms of shellfish production and the presence of high- and low-frequency monitoring activities. At each site, autonomous pH sensors were deployed, both inside and outside shellfish production areas, next to high-frequency CTD (conductivity–temperature–depth) probes operated through two operating monitoring networks. pH sensors were set to an acquisition rate of 15 min, and discrete seawater samples were collected biweekly in order to control the quality of pH data (laboratory spectrophotometric measurements) as well as to measure total alkalinity and dissolved inorganic carbon concentrations for full characterization of the carbonate system. While this network has been up and running for more than 2 years, the acquired dataset has already revealed important differences in terms of pH variations between monitored sites related to the influence of diverse processes (freshwater inputs, tides, temperature, biological processes). Data are available at https://doi.org/10.17882/96982 (Petton et al., 2023a).

Abstract Background Muscle aging is associated with a consistent decrease in the ability of muscle tissue to regenerate following intrinsic muscle degradation, injury or overuse. Age‐related imbalance of protein synthesis and degradation, mainly regulated by AKT/mTOR pathway, leads to progressive loss of muscle mass. Maintenance of anabolic and regenerative capacities of skeletal muscles may be regarded as a therapeutic option for sarcopenia and other muscle wasting diseases. Our previous studies have demonstrated that BIO101, a pharmaceutical grade 20‐hydroxyecdysone, increases protein synthesis through the activation of MAS receptor involved in the protective arm of renin‐angiotensin‐aldosterone system. The purpose of the present study was to assess the anabolic and pro‐differentiating properties of BIO101 on C2C12 muscle cells in vitro and to investigate its effects on adult and old mice models in vivo. Methods The effects of BIO101 on C2C12 differentiation were assessed using myogenic transcription factors and protein expression of major kinases of AKT/mTOR pathway by Western blot. The in vivo effects of BIO101 have been investigated in BIO101 orally‐treated (50 mg/kg/day) adult mice (3 months) for 28 days. To demonstrate potential beneficial effect of BIO101 treatment in a sarcopenic mouse model, we use orally treated 22‐month‐old C57Bl6/J mice, for 14 weeks with vehicle or BIO101. Mice body and muscle weight were recorded. Physical performances were assessed using running capacity and muscle contractility tests. Results Anabolic properties of BIO101 were confirmed by the rapid activation of AKT/mTOR, leading to an increase of C2C12 myotubes diameters (+26%, P

Tick paralysis is a potentially fatal condition caused by toxins produced and secreted by tick salivary glands. This survey presents clinical and epidemiological observations of tick paralysis cases in domestic animals in Cyprus. Local veterinarians report typical tick paralysis cases occurring in goats, sheep, dogs, and cats. The animals suffering from paralysis are free from other neurological diseases, have blood and biochemical parameters within normal ranges, and recover fast by simply removing the ticks found predominantly on the head and around the neck. Tick paralysis cases occur in a specific geographic area of Cyprus (Akamas peninsula), from September through March, but not every year. Instead, the phenomenon has 2 periodic cycles of occurrence, a 3- and a 7-year cycle. The 2 cycles are differentiated by severity based on the number of affected animals and the resulting losses. As described for other tick-borne diseases, these cyclic patterns may be attributed to external factors, self-oscillations of the disease system, or the combined action of these mechanisms. Ticks collected from a recent paralysis case in a goat were morphologically and molecularly identified as Ixodes gibbosus. Efforts should be made to characterize the specific toxins involved in tick paralysis and to develop a vaccine, which could prevent significant losses of small ruminants, especially in free-ranging farming systems, a prevalent management approach observed in Cyprus and various regions worldwide.

Despite the significant health risks associated with Dermanyssus gallinae infestations in humans, they are often overlooked. This study investigated a household case of D. gallinae infestation and explored the resulting clinical manifestations and risk of infection in family members. Microfluidic PCR was employed for high-throughput screening of pathogens in collected mites and blood samples from both chickens and family members. Morphological and molecular examinations confirmed the identity of the mites as D. gallinae sensu stricto (s.s.), with evidence indicating recent blood feeding. Results indicated that the mites exclusively harbored various pathogens, including Bartonella spp., Ehrlichia spp., Apicomplexa, and Theileria spp. Blood samples from family members and poultry tested negative for these pathogens, suggesting a potential reservoir role for D. gallinae. The study further identified haplotypes of D. gallinae, classifying them into D. gallinae s.s., cosmopolitan haplogroup A. Serological analysis revealed elevated IgE seroreactivity against mite proteins in the family member with bite lesions. Antibodies against Bartonella spp. were detected in this individual, indicating exposure to the pathogen. In summary, this study sheds light on the clinical manifestations, pathogen detection, and genetic characterization of D. gallinae infestations, underscoring the necessity of adopting comprehensive approaches to manage such infestations effectively.

Abstract Background Ixodid ticks, particularly Rhipicephalus sanguineus s.l., are important vectors of various disease-causing agents in dogs and humans in Cuba. However, our understading of interactions among tick-borne pathogens (TBPs) in infected dogs or the vector R. sanguineus s.l. remains limited. This study integrates microfluidic-based high-throughput real-time PCR data, Yule's Q statistic, and network analysis to elucidate pathogen-pathogen interactions in dogs and ticks in tropical western Cuba. Methods A cross-sectional study involving 46 client-owned dogs was conducted. Blood samples were collected from these dogs, and ticks infesting the same dogs were morphologically and molecularly identified. Nucleic acids were extracted from both canine blood and tick samples. Microfluidic-based high-throughput real-time PCR was employed to detect 25 bacterial species, 10 parasite species, 6 bacterial genera, and 4 parasite taxa, as well as to confirm the identity of the collected ticks. Validation was performed through end-point PCR assays and DNA sequencing analysis. Yule's Q statistic and network analysis were used to analyse the associations between different TBP species based on binary presence-absence data. Results The study revealed a high prevalence of TBPs in both dogs and R. sanguineus s.l., the only tick species found on the dogs. Hepatozoon canis and Ehrlichia canis were among the most common pathogens detected. Co-infections were observed, notably between E. canis and H. canis. Significant correlations were found between the presence of Anaplasma platys and H. canis in both dogs and ticks. A complex co-occurrence network among haemoparasite species was identified, highlighting potential facilitative and inhibitory roles. Notably, H. canis was found as a highly interconnected node, exhibiting significant positive associations with various taxa, including A. platys, and E. canis, suggesting facilitative interactions among these pathogens. Phylogenetic analysis showed genetic diversity in the detected TBPs. Conclusions Overall, this research enhances our understanding of TBPs in Cuba, providing insights into their prevalence, associations, and genetic diversity, with implications for disease surveillance and management. Graphical abstract

Abstract Background Transitional hospital-to-home care programs support safe and timely transition from acute care settings back into the community. Case-mix systems that classify transitional care clients into groups based on their resource utilization can assist with care planning, calculating reimbursement rates in bundled care funding models, and predicting health human resource needs. This study evaluated the fit and relevance of the Resource Utilization Groups version III for Home Care (RUG-III/HC) case-mix classification system in transitional care programs in Ontario, Canada. Methods We conducted a retrospective analysis of clinical assessment data and administrative billing records from a cohort of clients (n = 1,680 care episodes) in transitional home care programs in Ontario. We classified care episodes into established RUG-III/HC groups based on clients’ clinical and functional characteristics and calculated four case-mix indices to describe care relative resource utilization in the study sample. Using these indices in linear regression models, we evaluated the degree to which the RUG-III/HC system can be used to predict care resource utilization. Results A majority of transitional home care clients are classified as being Clinically complex (41.6%) and having Reduced physical functions (37.8%). The RUG-III/HC groups that account for the largest share of clients are those with the lowest hierarchical ranking, indicating low Activities of Daily Living limitations but a range of Instrumental Activities of Daily Living limitations. There is notable heterogeneity in the distribution of clients in RUG-III/HC groups across transitional care programs. The case-mix indices reflect decreasing hierarchical resource use within but not across RUG-III/HC categories. The RUG-III/HC predicts 23.34% of the variance in resource utilization of combined paid and unpaid care time. Conclusions The distribution of clients across RUG-III/HC groups in transitional home care programs is remarkably different from clients in long-stay home care settings. Transitional care programs have a higher proportion of Clinically complex clients and a lower proportion of clients with Reduced physical function. This study contributes to the development of a case-mix system for clients in transitional home care programs which can be used by care managers to inform planning, costing, and resource allocation in these programs.

Abstract Background Dirofilarioses are widespread diseases caused by mosquito-borne nematodes of the family Onchocercidae, genus Dirofilaria. The major etiologic agent of canine dirofilariosis in the American continent is the zoonotic parasite Dirofilaria immitis. Existing reports of filarioid nematodes in Cuba are based solely on morphological and immunological analysis which do not allow unambiguous identification and/or direct detection of causal agents. Results Here we present the molecular characterization of filarioid nematodes found in a dog in Cuba. Based on the molecular and phylogenetic analysis of the 5.8S-ITS2-28S region and cox1 gene fragments, the worms were unambiguously classified as D. immitis. Sequence analysis showed high identity of the gene fragments in this study with others previously obtained from D. immitis found in dogs, wolfs and jackals but also from mosquito vectors of D. immitis. Conclusions Further studies are guarantee to better understand the epidemiological impact of canine dirofilariosis in Cuba as well as the competence of different species of culicid mosquitoes as vectors of Dirofilaria in the country.

Abstract Interactions within the tick microbiome involving symbionts, commensals, and tick‐borne pathogens (TBPs) play a pivotal role in disease ecology. This study explored temporal changes in the microbiome of Rhipicephalus microplus, an important cattle tick vector, focusing on its interaction with Anaplasma marginale. To overcome limitations inherent in sampling methods relying on questing ticks, which may not consistently reflect pathogen presence due to variations in exposure to infected hosts in nature, our study focused on ticks fed on chronically infected cattle. This approach ensures continuous pathogen exposure, providing a more comprehensive understanding of the nesting patterns of A. marginale in the R. microplus microbiome. Using next‐generation sequencing, microbiome dynamics were characterized over 2 years, revealing significant shifts in diversity, composition, and abundance. Anaplasma marginale exhibited varying associations, with its increased abundance correlating with reduced microbial diversity. Co‐occurrence networks demonstrated Anaplasma's evolving role, transitioning from diverse connections to keystone taxa status. An integrative approach involving in silico node removal unveils the impact of Anaplasma on network stability, highlighting its role in conferring robustness to the microbial community. This study provides insights into the intricate interplay between the tick microbiome and A. marginale, shedding light on potential avenues for controlling bovine anaplasmosis through microbiome manipulation.

Summary: Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity.

Abstract Background Ticks can transmit a broad variety of pathogens of medical importance, including Borrelia afzelii, the causative agent of Lyme borreliosis in Europe. Tick microbiota is an important factor modulating, not only vector physiology, but also the vector competence. Anti-microbiota vaccines targeting keystone taxa of tick microbiota can alter tick feeding and modulate the taxonomic and functional profiles of bacterial communities in the vector. However, the impact of anti-microbiota vaccine on tick-borne pathogen development within the vector has not been tested. Results Here, we characterized the Ixodes ricinus microbiota modulation in response to B. afzelii infection and found that the pathogen induces changes in the microbiota composition, its beta diversity and structure of bacterial community assembly. Tick microbiota perturbation by anti-microbiota antibodies or addition of novel commensal bacteria into tick midguts causes departures from the B. afzelii-induced modulation of tick microbiota which resulted in a lower load of the pathogen in I. ricinus. Co-occurrence networks allowed the identification of emergent properties of the bacterial communities which better defined the Borrelia infection-refractory states of the tick microbiota. Conclusions These findings suggest that Borrelia is highly sensitive to tick microbiota perturbations and that departure from the modulation induced by the pathogen in the vector microbiota pose a high cost to the spirochete. Network analysis emerges as a suitable tool to identify emergent properties of the vector microbiota associated with infection-refractory states. Anti-microbiota vaccines can be used as a tool for microbiota perturbation and control of important vector-borne pathogens. Video Abstract

Abstract Ixodes ricinus and Dermacentor reticulatus ticks are important reservoirs and vectors of pathogens. The aim of the present study was to investigate the dynamic of the prevalence and genetic diversity of microorganisms detected in these tick species collected from two ecologically diverse biotopes undergoing disparate long-term climate condition. High-throughput real time PCR confirmed high prevalence of microorganisms detected in sympatrically occurring ticks species. D. reticulatus specimens were the most often infected with Francisella-like endosymbiont (FLE) (up to 100.0%) and Rickettsia spp. (up to 91.7%), while in case of I. ricinus the prevalence of Borreliaceae spirochetes reached up to 25.0%. Moreover, pathogens belonging to genera of Bartonella, Anaplasma, Ehrlichia and Babesia were detected in both tick species regardless the biotope. On the other hand, Neoehrlichia mikurensis was conformed only in I. ricinus in the forest biotope, while genetic material of Theileria spp. was found only in D. reticulatus collected from the meadow. Our study confirmed significant impact of biotope type on prevalence of representatives of Borreliaceae and Rickettsiaceae families. The most common co-infection detected in D. reticulatus was Rickettsia spp. + FLE, while Borreliaceae + R. helvetica was the most common in I. ricinus. Additionally, we found significant genetic diversity of R. raoultii gltA gene across studied years, however such relationship was not observed in ticks from studied biotopes. Our results suggest that ecological type of biotope undergoing disparate long-term climate conditions have an impact on prevalence of tick-borne pathogens in adult D. reticulatus and I. ricinus.

Abstract Background Poor ovarian responders (POR) are women undergoing in-vitro fertilization who respond poorly to ovarian stimulation, resulting in the retrieval of lower number of oocytes, and subsequently lower pregnancy rates. The follicular fluid (FF) provides a crucial microenvironment for the proper development of follicles and oocytes through tightly controlled metabolism and cell signaling. Androgens such as dehydroepiandrosterone (DHEA) have been proposed to alter the POR follicular microenvironment, but the impact DHEA imposes on the FF metabolome and cytokine profiles is unknown. Therefore, the objective of this study is to profile and identify metabolomic changes in the FF with DHEA supplementation in POR patients. Methods FF samples collected from 52 POR patients who underwent IVF with DHEA supplementation (DHEA +) and without (DHEA-; controls) were analyzed using untargeted liquid chromatography-tandem mass spectrometry (LC–MS/MS) metabolomics and a large-scale multiplex suspension immunoassay covering 65 cytokines, chemokines and growth factors. Multivariate statistical modelling by partial least squares-discriminant regression (PLSR) analysis was performed for revealing metabolome-scale differences. Further, differential metabolite analysis between the two groups was performed by PLSR β-coefficient regression analysis and Student’s t-test. Results Untargeted metabolomics identified 118 FF metabolites of diverse chemistries and concentrations which spanned three orders of magnitude. They include metabolic products highly associated with ovarian function – amino acids for regulating pH and osmolarity, lipids such fatty acids and cholesterols for oocyte maturation, and glucocorticoids for ovarian steroidogenesis. Four metabolites, namely, glycerophosphocholine, linoleic acid, progesterone, and valine were significantly lower in DHEA + relative to DHEA- (p

Background: Studies had compared single-embryo transfer to double-embryo transfer with cleavage stage embryos and found that while single-embryo transfer was less costly, it was also associated with a lower live birth rate than double-embryo transfer. A single blastocyst transfer has been shown to improve the live birth rate per cycle compared to single-embryo transfer at cleavage stage. Objectives: To compare live birth rates and real costs of elective single-embryo transfer to double-embryo transfer and to determine the incremental cost-effectiveness ratio of these two strategies in an unselected pool of women in a single center. Design: Retrospective study. Methods: We analyzed data of 4232 women who underwent their first fresh in vitro fertilization/intra-cytoplasmic sperm injection cycles with at least two embryos available for transfer in KK Women’s and Children’s Hospital from 2010 to 2017. Results: Five hundred and sixty-four women underwent elective single-embryo transfer and 3668 women underwent double-embryo transfer. One hundred and fifty-six women who failed to achieve a live birth in their fresh elective single-embryo transfer cycle underwent a sequential thaw single-embryo transfer cycle. Live birth rate of fresh elective single-embryo transfer was significantly higher at 41.3% than that of double-embryo transfer at 32.6%. Cumulative live birth rate for sequential elective single-embryo transfer (fresh elective single-embryo transfer + thaw single-embryo transfer) was 47.9%. After accounting for variables which may affect live birth rates such as age and stage of embryo transfer, the odds of achieving a live birth from double-embryo transfer was 24% lower than that from sequential single-embryo transfer, although not statistically significant. For every live birth gained from an elective single-embryo transfer compared to double-embryo transfer, cost savings were S$20,172 per woman. If a woman had to have a sequential single-embryo transfer after a failed single-embryo transfer in her fresh cycle, cost savings were reduced to S$1476 per woman. Conclusion: Single-embryo transfer is a dominant strategy in an unselected population and adopting it in assisted reproductive treatments (ART) can produce cost savings without compromising on live birth rates.

ABSTRACT Among the most studied mammals in terms of their role in the spread of various pathogens with possible zoonotic effects are bats. These are animals with a very complex lifestyle, diet, and behavior. They are able to fly long distances, thus maintaining and spreading the pathogens they may be carrying. These pathogens also include vector-borne parasites and bacteria that can be spread by ectoparasites such as ticks and bat flies. In the present study, high-throughput screening was performed and we detected three bacterial pathogens: Bartonella spp., Neoehrlichia mikurensis and Mycoplasma spp., and a protozoan parasite: Theileria spp. in paired samples from bats (blood and ectoparasites). In the samples from the bat-arthropod pairs, we were able to detect Bartonella spp. and Mycoplasma spp. which also showed a high phylogenetic diversity, demonstrating the importance of these mammals and the arthropods associated with them in maintaining the spread of pathogens. Previous studies have also reported the presence of these pathogens, with one exception, Neoehrlichia mikurensis, for which phylogenetic analysis revealed less genetic divergence. High-throughput screening can detect more bacteria and parasites at once, reduce screening costs, and improve knowledge of bats as reservoirs of vector-borne pathogens. IMPORTANCE The increasing number of zoonotic pathogens is evident through extensive studies and expanded animal research. Bats, known for their role as reservoirs for various viruses, continue to be significant. However, new findings highlight the emergence of Bartonella spp., such as the human-infecting B. mayotimonensis from bats. Other pathogens like N. mikurensis, Mycoplasma spp., and Theileria spp. found in bat blood and ectoparasites raise concerns, as their impact remains uncertain. These discoveries underscore the urgency for heightened vigilance and proactive measures to understand and monitor zoonotic pathogens. By deepening our knowledge and collaboration, we can mitigate these risks, safeguarding human and animal well-being.

We study the impact of public health messages on intentions to vaccinate and vaccination uptakes, especially among hesitant groups. We performed an experiment comparing the effects of egoistic and altruistic messages on COVID-19 vaccine intentions and behaviour. We administered different messages at random in a survey of 6379 adults in December 2020, following up with participants in the nationally representative survey Citizens’ Attitudes Under COVID-19 Project covering nine high-income countries (Australia, Austria, France, Germany, Italy, New Zealand, Sweden, the UK and the USA). Four alternative interventions were tested, based on narratives of (1) self-protection, (2) protecting others, (3) reducing health risks and (4) economic protection. We measure vaccination intentions in the December 2020 survey and elicit actual vaccination behaviour by respondents in the June/July 2021 survey. Messages conveying self-protection had no effect on vaccine intentions but altruistic messages, emphasising protecting other individuals (0.022, 95% CI −0.004 to 0.048), population health (0.030, 95% CI 0.003 to 0.056) and the economy (0.038, 95% CI 0.013 to 0.064) had substantially stronger effects. These effects were stronger in countries experiencing high COVID-19 mortality (Austria, France, Italy, Sweden, the UK and the USA), where health risks may have been more salient, but weaker and, in several cases, not significant where mortality was low (Australia, Germany and New Zealand). On follow-up at 6 months, these brief communication interventions corresponded to substantially higher vaccination uptake. Our experiments found that commonly employed narratives around self-protection had no effect. However, altruistic messages about protecting individuals, population health and the economy had substantially positive and enduring effects on increasing vaccination intentions. Our results can help structure communication campaigns during pandemics and are likely to generalise to other vaccine-preventable epidemics.

Tuberculosis (TB) continues to disproportionately affect Inuit populations in Canada with some communities having over 300 times higher rate of active TB than Canadian-born, non-Indigenous people. Inuit Tuberculosis Elimination Framework has set the goal of reducing active TB incidence by at least 50% by 2025, aiming to eliminate it by 2030. Whether these goals are achievable with available resources and treatment regimens currently in practice has not been evaluated. We developed an agent-based model of TB transmission to evaluate timelines and milestones attainable in Nunavut, Canada by including case findings, contact-tracing and testing, treatment of latent TB infection (LTBI), and the government investment on housing infrastructure to reduce the average household size. The model was calibrated to ten years of TB incidence data, and simulated for 20 years to project program outcomes. We found that, under a range of plausible scenarios with tracing and testing of 25%–100% of frequent contacts of detected active cases, the goal of 50% reduction in annual incidence by 2025 is not achievable. If active TB cases are identified rapidly within one week of becoming symptomatic, then the annual incidence would reduce below 100 per 100,000 population, with 50% reduction being met between 2025 and 2030. Eliminating TB from Inuit populations would require high rates of contact-tracing and would extend beyond 2030. The findings indicate that time-to-identification of active TB is a critical factor determining program effectiveness, suggesting that investment in resources for rapid case detection is fundamental to controlling TB.

Abstract Rationale Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis. The U.S. food and drug administration approved the use of the anti-VEGF antibody bevacizumab in recurrent GBM. However, resistance to this treatment is frequent and fails to enhance the overall survival of patients. In this study, we aimed to identify novel mechanism(s) responsible for bevacizumab-resistance in CD146-positive glioblastoma. Methods The study was performed using sera from GBM patients and human GBM cell lines in culture or xenografted in nude mice. Results We found that an increase in sCD146 concentration in sera of GBM patients after the first cycle of bevacizumab treatment was significantly associated with poor progression free survival and shorter overall survival. Accordingly, in vitro treatment of CD146-positive glioblastoma cells with bevacizumab led to a high sCD146 secretion, inducing cell invasion. These effects were mediated through integrin αvβ3 and were blocked by mucizumab, a novel humanized anti-sCD146 antibody. In vivo, the combination of bevacizumab with mucizumab impeded CD146 + glioblastoma growth and reduced tumor cell dissemination to an extent significantly higher than that observed with bevacizumab alone. Conclusion We propose sCD146 to be 1/ an early biomarker to predict and 2/ a potential target to prevent bevacizumab resistance in patients with glioblastoma.

The prawn Palaemon serratus exhibits a large distribution (occurring along the Northeastern Atlantic coast to the Mediterranean), and has thus been found suitable as model organism valuable for various ecotoxicological studies. However, little is still known about the potential input of its metabolome and particularly concerning a potential molecular sexual dimorphism observable in the different tissues of this organism. In an ecotoxicological point of view, inter-sex and inter-organ differences of the metabolomes may introduce analytical bias and impact the robustness of the analysis and its interpretation. To explore such possibilities, we obtained qualitative metabolomic data from the analysis of different organs of mature male and female Palaemon serratus. We used ultra-high-performance liquid chromatography-electrospray ionization-high resolution tandem mass spectrometry (UHPLC-ESI-HRMS on positive mode) to characterize the 75%-extracted metabolome of both gills, hepatopancreas, nervous gland, muscle and gonads. The data were dereplicated using specific metabolomic software (MetaboScape 4) and 2,782 features were extracted, 1,720 of them being also analysed on MS/MS mode, supporting molecular networking investigations with Metgem 1.3.6. These metabolites were thus putatively identified using GNPS (Global Natural Product Social) Molecular Networking databases for de-novo annotation followed by manual curation of 84 metabolites. This data provides essential information on the important sexual dimorphism occurring at the molecular level in the different organs and supports further research on physiology and ecotoxicology in common European prawn.

Background and Aims: Early detection and advancement in cancer treatments have drastically improved survivorship. Hence, there is a shift towards long-term quality of life goals such as protecting the oncologic patient’s fertility potential. The study aims to determine the uptake and use of fertility preservation options in women presenting at a tertiary institution in Singapore. This is the first review to outline the uptake rates, methods and fertility outcomes among women undergoing fertility preservation in Singapore. Method: The study is a retrospective review of premenopausal female patients presenting to a single tertiary institution between 2010 and 2019 for fertility preservation. Our primary outcome measures are the uptake rate, type of fertility preservation undertaken and live birth rate. Our secondary outcome are reasons for decline of fertility preservation. Results: Forty-one patients were referred between 2010 and 2019. There were 2 referrals received in 2010 compared to 10 referrals in 2019. Twenty-nine patients underwent fertility preservation procedures, with 27 (93.1%) successful fertility preservation procedures performed. Most of the patients opted for embryo cryopreservation (44.4%) or oocyte cryopreservation (33.3%). Three patients (11.1%) underwent ovarian tissue cryopreservation. Two patients (7.4%) opted for a combination of oocyte and embryo cryopreservation and 1 patient (3.7%) had a combination of ovarian tissue and oocyte cryopreservation. There were 3 successful live births. One patient achieved a live birth from stored embryos achieved from in-vitro maturation subsequent fertilisation. The other two patients achieved live births from stored embryos and oocytes respectively. The most commonly cited reason for declining fertility preservation was financial limitations (41.7%). Conclusion: While the referral rates have been increasing over the years, the rates remain low. Further studies can be done to assess the barriers to fertility preservation referrals. Funding for fertility preservation procedures may increase uptake in this group of women.

Abstract Rickettsia helvetica is an emerging pathogen of the Spotted Fever Group Rickettsia (SFGR) causing spotted fever diseases in various European countries. This tick-borne pathogen replicates in tick tissues such as the midgut and salivary gland, but its potential interactions with the vector microbiota is poorly characterized. The vector microbiome plays a pivotal role in tick-pathogen interactions, and some microbiota members facilitate or impede tick-borne pathogen infection. Manipulations of the tick microbiome have led to reduction in pathogen colonization in the tick vector. However, translating these findings into disease control applications requires a thorough characterization of vector microbiota response to different pathogens. In this study, we analyzed and compared the microbiota of Ixodes ricinus ticks attached on humans and collected in Serbia. Ticks were either infected with R. helvetica, or uninfected with major tick-borne pathogens (referred hereafter as ‘pathogen-free’). We used microbial co-occurrence network analysis to determine keystone taxa of each set of samples, and to study the interaction patterns of the microbial communities in response to pathogen infection. The inferred functional profiles of the tick microbiome in R. helvetica-positive and pathogen-free samples were also compared. Our results show that R. helvetica infection reduces significantly the diversity of the microbiota and the connectivity of the co-occurrence network. In addition, using co-occurrence network we identified bacterial taxa (i.e., Enterobacteriaceae, Comamonadaceae, and Bacillus) that were negatively associated with ‘Rickettsia’ in R. helvetica-infected ticks, suggesting competition between R. helvetica and some members of the tick microbiota. The reconstruction of microbial metabolic pathways shows that the presence of R. helvetica might have a major impact on the metabolic functions of the tick microbiome. These results can inform novel interventions for the prevention of R. helvetica, or other SFGR infections in humans.