bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second messenger c-di-AMP regulates multiple antibiotic sensitivity pathways in Mycobacterium smegmatis by discrete mechanisms
Authors: Pal Aditya Kumar , Ghorai Dipankar , Ge Xueliang , Sarkar Biplab , Sahu Amit Kumar , Chaudhary Vikas , Jhawar Ruchi , Sanyal Suparna , Singh Mahavir , Ghosh Anirban 
Published: October 2024

Abstract
One of the debilitating causes of high mortality in the case of tuberculosis and other bacterial infections is the resistance development against standard drugs. There are limited studies so far to describe how a bacterial second messenger molecule can directly participate in distinctive antibiotic tolerance characteristics of a cell in a mechanism-dependent manner. Here we show that intracellular cyclic di-AMP (c-di-AMP) concentration can modulate drug sensitivity of Mycobacterium smegmatis by interacting with an effector protein or interfering with the 5′-UTR regions in mRNA of the genes and thus causing transcriptional downregulation of important genes in the pathways. We studied four antibiotics with different mechanisms of action: rifampicin, ciprofloxacin, erythromycin, and tobramycin and subsequently found that the level of drug sensitivity of the bacteria is directly proportional to the c-di-AMP concentration inside the cell. Further, we unraveled the underlying molecular mechanisms to delineate the specific genes and pathways regulated by c-di-AMP and hence result in differential drug sensitivity in M. smegmatis.
Unraveling the genomic diversity of the Pseudomonas putida group: exploring taxonomy, core pangenome, and antibiotic resistance mechanisms
Authors: Udaondo Zulema , Ramos Juan Luis , Abram Kaleb 
Published: October 2024

Abstract
The genus Pseudomonas is characterized by its rich genetic diversity, with over 300 species been validly recognized. This reflects significant progress made through sequencing and computational methods. Pseudomonas putida group comprises highly adaptable species that thrive in diverse environments and play various ecological roles, from promoting plant growth to being pathogenic in immunocompromised individuals. By leveraging the GRUMPS computational pipeline, we scrutinized 26 363 genomes labeled as Pseudomonas in the NCBI GenBank, categorizing all Pseudomonas spp. genomes into 435 distinct species-level clusters or cliques. We identified 224 strains deposited under the taxonomic identifier “Pseudomonas putida” distributed within 31 of these species-level clusters, challenging prior classifications. Nine of these 31 cliques contained at least six genomes labeled as “Pseudomonas putida” and were analysed in depth, particularly clique_1 (P. alloputida) and clique_2 (P. putida). Pangenomic analysis of a set of 413 P. putida group strains revealed over 2.2 million proteins and more than 77 000 distinct protein families. The core genome of these 413 strains includes 2226 protein families involved in essential biological processes. Intraspecific genetic homogeneity was observed within each clique, each possessing a distinct genomic identity. These cliques exhibit distinct core genes and diverse subgroups, reflecting adaptation to specific environments. Contrary to traditional views, nosocomial infections by P. alloputida, P. putida, and P. monteilii have been reported, with strains showing varied antibiotic resistance profiles due to diverse mechanisms. This review enhances the taxonomic understanding of key P. putida group species using advanced population genomics approaches and provides a comprehensive understanding of their genetic diversity, ecological roles, interactions, and potential applications.
Internal Flight Anarchy: Points of Divergence from UNHCR Guidelines in Canadian Decision Making
Authors: Zambelli Pia 
Published: October 2024

Abstract
Over the years, Canadian decision makers have come to apply the concept of ‘internal flight alternative’ (IFA) more expansively than recommended by the United Nations High Commissioner for Refugees (UNHCR). Given the significant proportion of refugee claims that are refused on the basis of this concept each year, this divergence of interpretation has a real-life impact. To examine this phenomenon, the article provides a brief overview of the IFA concept, including a review of the scholarly literature and UNHCR guidance. Next, it traces the concept’s development in Canadian law and highlights points of divergence with UNHCR’s position. Finally, the article discusses potential strategies for realignment. The goal is to encourage practitioners and decision makers to think more deeply about the IFA concept, to raise awareness in regard to existing scholarship and applicable norms, and to ensure that these norms are applied in a conscious, humane, and consistent manner.
Methionine supply during mid-gestation modulates the bovine placental mTOR pathway, nutrient transporters, and offspring birth weight in a sex-specific manner
Authors: Gouvêa Vinícius N , Smithyman Mackenzie M , Hentz Fernanda , Bagheri Naghme , Batistel Fernanda 
Published: October 2024

Abstract
The mechanistic target of rapamycin (mTOR) predominantly regulates the expression and activity of placental nutrient transporters. The mTOR pathway can be activated by several nutrients, including the essential amino acid methionine. Additionally, previous research in nonruminant animals suggests that mTOR is influenced in a sexually dimorphic manner. In bovine, there is limited understanding of how maternal nutrition and offspring sexual dimorphism affect the placental transfer of nutrients. Thus, we investigated the effects of increasing the supply of dietary methionine to beef cattle heifers during mid-gestation on mTOR signaling, placental nutrient transporters, and fetal growth in male and female offspring. Forty purebred Angus heifers were used in a randomized complete block design experiment. From days 90 to 180 of gestation, heifers received a basal diet with no added methionine (CON, n = 20), or the basal diet plus 8.3 g of rumen-protected methionine (MET, n = 20) per animal daily. All animals received a basal diet in the first and third trimesters of gestation. Cotyledonary tissue samples were collected at parturition and utilized to examine the mTOR pathway and nutrient transporters through protein and gene expression analysis. The offspring’s body weight was measured at birth. Data were analyzed using a mixed model that included the fixed effect of treatment, offspring sex, their interactions, and the random effect of block. At day 170 of gestation, MET-supplemented heifers showed higher plasma concentrations of methionine and glutamate (P &lt; 0.01) and lower glycine and proline levels (P ≤ 0.01) compared to the CON group. A treatment × sex interaction was observed for calf birth weight (P = 0.03). In heifers that delivered male calves, MET supplementation increased the birth weight of the calves (P &lt; 0.01). However, the dietary treatments had no effect on the birth weight of female calves (P = 0.32). The increase in birth weight of male calves from MET-fed heifers resembles the upregulation of placental mTOR and phosphorylated mTOR (P ≤ 0.03), as well as the amino acid transporters SLC1A5, SLC7A5, SLC38A6, and SLC38A11, and the glucose transporters SLC2A1 and SLC2A8 (P ≤ 0.05). Our findings suggest that increasing the supply of methionine to beef heifers during mid-gestation can modulate placental nutrient transport and fetal growth in a sex-dependent manner and that these effects are mediated, at least in part, by the mTOR pathway.
Osteoclastic ATP6AP2 maintains β-catenin levels to prevent hyper-osteoclastic activation and trabecular bone-loss
Authors: Chen Li , Xiong Lei , Guo Haohan , Feng Xu , Zhu Xiaojuan , Xiong Wen-Cheng 
Published: October 2024

Abstract
Osteoclast (OC) formation and bone resorption are regulated by several factors, including V-ATPase, Wnt/β-catenin, and RANKL/RANK signaling. ATP6AP2, also known as the prorenin receptor (PRR), is an accessory subunit of V-ATPase and a regulator of Wnt/β-catenin signaling. While the V-ATPase subunit ATP6AP1 is essential for OC formation and function, the role of ATP6AP2 in OC-lineage cells is less clear. Here, we provide evidence that ATP6AP2 plays a negative role in osteoclastogenesis and function, contrasting with the positive role of ATP6AP1. Mice with conditional KO (cKO) of ATP6AP2 in OCs (Atp6ap2LysM) exhibit trabecular bone loss, likely due to the increased osteoclastogenesis and activity, since bone formation rates (BFRs) are comparable to control mice. In vitro assays using bone marrow macrophages (BMMs) show that Atp6ap2LysM cultures have more RANKL-induced TRAP+ OC-like cells and increased bone resorptive activity. Further studies reveal that while RANKL signaling and V-ATPase activity are normal, ATP6AP2 KO OCs, but not BMMs, have reduced basal levels of Wnt/β-catenin pathway proteins, such as LRP5/6 and β-catenin, compared to controls. Wnt3A treatment induces β-catenin and suppresses OC formation in both control and ATP6AP2 KO OC-lineage cells, indicating that Wnt/β-catenin signaling negatively regulates OC-formation and operates independently of ATP6AP2. Overall, these results suggest that ATP6AP2 is critical for maintaining basal levels of LRP5/6 receptors and β-catenin in OCs, thus acting as a negative regulator of osteoclastogenesis and activation.
Variation in thermal courtship activity curves across individuals exceeds variation across populations and sexes
Authors: Fowler-Finn Kasey D , Ahuja Shivika , Hercules Jake , Jocson Dowen , Miller Em , Sasson Daniel 
Published: October 2024

Abstract
The dynamics of mating interactions can vary in response to a wide variety of environmental factors. Here, we investigate the potential for individuals to vary consistently in the environmental conditions under which they actively engage in courtship. Specifically, we quantify variation in how courtship activity changes with environmental temperature across levels of biological organization in Enchenopa binotata treehoppers. Male E. binotata produce vibrational courtship signals and receptive females respond with their own sex-specific vibrational courtship signal. We tested each individual twice for the production of courtship signals across a range of ecologically relevant temperatures (18–36 °C). Then, we measured repeatability and variability in the resulting thermal courtship activity curves, including the temperature of peak activity and tolerance to thermal extremes. We also looked at patterns of variation across populations and sexes. We found minimal variation across populations, but significant variation across individuals. Specifically, we found prevalent repeatability in how thermally generalized or specialized individuals are. However, repeatability was limited to females only. We also found higher variability in female traits than in male traits, although patterns of variability did not always predict patterns of repeatability. These results suggest that thermal variation could alter the dynamics of mate competition and that—due to potentially different selective optima for males and females—the sexes may respond to changes in temperature in different ways. Specifically, females show a higher potential to adapt but males show a higher potential to be more robust to changes in temperature due to overall higher courtship activity across temperatures.
Evaluation of transplant drench and foliar insecticide applications for wireworm (Coleoptera: Elateridae) management in sweetpotato
Authors: Schoeppner Emma , Vann Matthew , Ackerman Renee , Cheek Joseph A , Huseth Anders S 
Published: October 2024

Abstract
The revocation of chlorpyrifos tolerances in 2022 left sweetpotato growers without their most important tool to combat a complex of soil-borne root pests that includes wireworms (Coleoptera: Elateridae). Since then, growers have reported increased root damage despite a rapid pivot to pyrethroid-based management systems to replace mechanically incorporated preplant chlorpyrifos broadcast sprays. Our goal was to evaluate the efficacy of alternative insecticide chemistries and application methods to expand the portfolio of management options for wireworms, specifically Conoderus spp. and Melanotus communis (Gyllenhal). We tested (i) insecticidal transplant water drenches and (ii) a foliar spray program targeting adult elaterids. We found that incorporating insecticides into transplant water reduced wireworm damage when compared to untreated transplant water. Our treatments included a recently registered meta-diamide, broflanilide, which represents a promising path to diversify active ingredients and shift away from an overreliance on preplant and post-directed pyrethroid soil sprays. Foliar spray plots had less damage than plots that did not receive foliar sprays. One benefit of adult-focused management is the availability of effective monitoring tools such as sex pheromones and blacklight trapping. Developing a robust adult monitoring program would enable more precise applications of foliar insecticides versus season-long prophylactic soil sprays targeting larvae. Our results demonstrated a significant benefit to both alternative delivery methods. These management alternatives could expand treatment options beyond traditional preplant and post-directed pyrethroid sprays.
Severe myelotoxicities related to Th1, Th2, Th17 and Treg CD4+ T cells subpopulations and their cytokine profiles in Mexican children with acute lymphoblastic leukemia during induction of chemotherapy
Authors: Saavedra-Velez Jacqueline , Ortiz-Lazareno Pablo , Trujillo-Ochoa Luis , Viera-Segura Oliver , Garcia Samuel , Thomas Paul , Friedrich Paola , Caniza Miguela A 
Published: October 2024

Abstract

Background
Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer in the world, and the myelotoxicities due to chemotherapy can lead to severe infections and hemorrhages with high morbidity and mortality. The immune response has implications in the severity of cancer or survival. This immune response is associated with the predominant subpopulations CD4+ T cells and their effector cytokines. However, it is not known if the immune responses are associated with severe myelotoxicities and mortality in children with ALL.

Methods
To evaluate the contributions of immunological factors on ALL severe myelotoxicities, we identified the Th1, Th2, Th9, Th17, Th22 and Tregs subpopulations of CD4+ T cells according to their chemokine receptor expression patterns in peripheral blood mononuclear cells by flow cytometry. We evaluated also their cytokines levels by Milliplex in serum from 10 children with ALL at diagnosis (day 0), during induction (day 19) and at the end of induction (day 30) between April 2022 and July 2023. Clinical characteristics such age, sex, type and risk of ALL, hemoglobin and platelets levels, absolute neutrophil count, grade of severity and type of myelotoxicities, infections, and hemorrhages were collected. Clinical outcomes as hospitalization care requirements, ICU admission, leukemia remission or relapsed and mortality were followed and documented.

Results
The age of children was 8.9 years, (SD,5.6; range 2-16), 60% were male sex, all children had pre- B ALL diagnosis, and 80% were intermediate risk-ALL. Th1 cells were predominant at diagnosis (8.1%) and at the end of induction (7.8%), and Th2 cells at day 19 (7.4%), whereas Th17 were significantly decreased at day 30 (2.6%) (p&lt;0.05). Four patients presented bloodstream infection, two by Gram-positive bacteria (Micrococcus, and Streptococcus), one by Klebsiella pneumoniae antimicrobial resistant, and one by Trichosporum asahii. Severe myelotoxicities were presented in 20% of the patients at day19, and in 30% at day 30. Remission was documented in all patients at day 30 and one was identified with early relapse in the follow-up. Three patients (30%) presented poor outcomes, requiring care in ICU and one died (10%) due to fungal infection. Treg cells were significantly predominant in the children who died by fungal infection (p&lt;0.05), with IL-10 level of 84.6 pg/mL but not detectable IL-35 levels.

Conclusion
Th17 and Treg subpopulations of CD4+ T cells can play an essential role in immune microenvironment during induction related with the severity of the myelotoxicities and infections, and cytokine IL-10 could be used as marker of infection outcome.
Profile Of Infectious Complications in Pediatric Oncology Patients: Experience from Tertiary Referral Hospital in Low and Middle-Income Country
Authors: Adrizain Riyadi , Sari Nur Melani 
Published: October 2024

Abstract

Background
Cancer patients are at higher risk of infections and more likely to have higher morbidity and mortality than the general population, While cancer itself is still the main cause of death in children around the world, in countries with limited health facilities, that might cause delay in seeking treatment, cancer death rate in children could reach 90%; most of them are caused by infectious complications such as typhilitis and mucositis, and febrile neutropenia might contribute to it. The aim of the study was to describe that infectious complications that occur in pediatric oncology patients does correlate with febrile neutropenia and prognosis.

Methods
We collected data using Hospital Information System from October 1, 2022, to October 31, 2023, in pediatric oncology patients aged 1 to 18 years admitted to Hasan Sadikin General Hospital. Data collected included patient characteristics, diagnosis, typhlitis and mucositis, and neutropenia. Mortality data were also collected after auditing by experts from Hasan Sadikin General Hospital.

Results
There were 1982 pediatric oncology patients admitted, 90 (4,5%) were consulted to infectious diseases because of neutropenia; most of these patients (34.4%) were diagnosed with acute myeloblastic leukemia, with acute lymphoblastic leukemia second (24,4%). Most of the patients were &lt;5 years old (42,25%); 77/90 (85,5%) had ANC&lt;500 and most were categorized as high-risk group 62/77 (80,5%). Mucositis and typhlitis occurred more commonly in this group with 17/67 (25,3%) and 2/67 (2,9 %) respectively compared to 3 cases of mucositis and no case of typhlitis in the low-risk group. Mortality rate was 10,4% (7/67) in the high-risk group, and all of them had mucositis and/or typhlitis.

Conclusion
Better quality of care including infection prevention and control is important, especially in high-risk group population with low ANC because infectious complications such as typhlitis and mucositis are much likely to occur and could affect prognosis.
Clinical Epidemiological Characteristics, Diagnosis and Treatment Established in Invasive Fungal Infection in Pediatric Patients: Case Series
Authors: Pérez Ávila Hirad Felipe , Bustamante María Elena Martínez 
Published: October 2024

Abstract

Background
Invasive fungal infection (IFI) represents a public health problem in immunocompromised and critically ill patients, with considerable mortality. Objective is to describe the clinical, epidemiological, diagnostic and treatment characteristics in patients with confirmed invasive fungal infection.

Methods
A case series study was carried out, by reviewing the records of previously healthy pediatric patients, with confirmed invasive fungal infection, from January to December 2022. Information was obtained on sociodemographic, clinical, laboratory variables, cultures, mucormycosis, treatment (antibiotic and antifungal) and complications during the hospital stay. In the statistical analysis, percentages, measures of central tendency and dispersion were obtained according to the Shapiro-Wilk normality test.

Results
Nine patients with invasive fungal infection were analyzed, 55.6% children, mean age 8.6 ± 4.8 years, 91.6% with acute lymphoblastic leukemia type B (50%), 25% with infiltration to the central nervous system, in chemotherapy phase from induction to remission. (88.9%), with jugular central venous catheter (44.4%), mean 29.9 ± 21.6 days-catheter, 88.9% with fever, severe neutropenia and neutropenic colitis, systemic inflammatory response syndrome 55.6%. In blood cultures C. papapsilosis (11.1%) was reported and in mycological culture Aspergillus fumigatus (33.3%), Mucor spp (22.2%) and Fusarium oxysporum (11.1%), 22.2% with fungomas, using amphotericin B (100%), caspofungin (44.4%) and voriconazole (33.3%), with 44.5% mortality.

Conclusion
In immunocompromised or critically ill patients, it is essential to perform strict follow-up to timely identify opportunistic infections and reduce complications.
Dear Malaria: Deer Have Malaria! Prevalence ofPlasmodium odocoilei Infection in White-tailed deer in Pennsylvania
Authors: Reu Kyra , Sundararaman Sesh , Gibison Michelle , John Audrey Odom 
Published: October 2024

Abstract

Background
To combat antimalarial treatment resistance, better understanding of malaria pathogenesis is needed, but existing animal model have various limitations. Notably, prevailing murine models require laboratory infection of non-natural host species. In 2016, the parasite Plasmodium odocoilei was identified in white-tailed deer (Odocoileus virginianus). This was the first non-human mammalian malaria parasite identified in North America, representing a novel naturally occurring model system that allows for integrated examination of host, vector, and systems parasite biology. In addition, sickle hemoglobinopathy is exceptionally common among white-tailed deer, occurring in up to 60% of apparently healthy animals. In humans, the prevalence of sickle hemoglobinopathy in individuals with ancestry from malaria-endemic regions is due to the protective effects of sickle trait against severe malaria. Thus, the white-tailed deer-P. odocoilei system represents the only known naturally occurring model of the association between malaria parasite biology and sickle cell disease. Pennsylvania white-tailed deer have not previously been surveyed for infection. In this study, we determined P. odocoilei prevalence in a sample of 170 Pennsylvania white-tailed deer.

Methods
We amplified the CytB gene of P. odocoilei by nested PCR from DNA extracted from homogenized white-tailed deer tongue tissue obtained from the PennVet Wildlife Futures Program. We confirmed samples screening positive on gel electrophoresis via unprimed sequencing (Plasmidsaurus, USA) and NCBI-BLAST analysis.

Results
We estimate the prevalence of P. odocoilei infection in Pennsylvania white-tailed deer to be 0.6% (1 of 170 samples). Sequencing of the positive sample revealed a 621-bp sequence with close sequence identity to previous North American isolates of P. odocoilei (query cover 91-100%, percent identity 99.34-100.00%). Biobank metadata showed the positive sample originated from a roadkilled yearling male picked up at GPS coordinates (40.8423, -79.0409) on August 15, 2022.

Conclusion
P. odocoilei is endemic to Pennsylvania white-tailed deer. Our future directions include screening of additional samples, determination of host hemoglobin allele frequencies, detailed parasite genetic studies, and entomologic studies to elucidate vector biology. In addition, granular sample metadata collected by the PennVet Wildlife Futures Program will allow us to analyze the effects of geographic, demographic, and temporal variables on epidemiology. In sum, our survey data empowers future Pennsylvania-based studies to take advantage of the only known naturally occurring animal model of sickling and its association with protozoan infection.