bluuebunny/crossref_metadata_2025 huggingface dataset:
Gold nanoparticles activate hydrogenase synthesis and improve heterotrophic growth of Ralstonia eutropha H16
Authors: Manutsyan Tatevik , Blbulyan Syuzanna , Vassilian Anait , Semashko Tatiana , Kirakosyan Gayane , Gabrielyan Lilit , Trchounian Karen , Poladyan Anna
Published: January 2024

Ralstonia eutropha is a facultative chemolithoautotrophic aerobic bacterium that grows using organic substrates or H2 and CO2. Hydrogenases (Hyds) are synthesized under lithoautotrophic, or energy-limited heterotrophic conditions and are used in enzyme fuel cells (EFC) as anodic catalysts. The effects of chemically synthesized gold nanoparticles (Au-NPs) on R. eutropha H16 growth, oxidation-reduction potential (ORP) kinetics, and H2-oxidizing Hyd activity were investigated in this study. Atomic force microscopy showed that thin, plate-shaped Au-NPs were in the nanoscale range with an average size of 5.68 nm. Compared with growth in medium without Au-NPs (control), the presence of Au-NPs stimulated growth, and resulted in a decrease in ORP to negative values. H2-oxidizing activity was not detected in the absence of Au-NPs, but activity was significantly induced (12 U/g CDW) after 24 h of growth with 18 ng/ml, increasing a further 4-fold after 72 h of growth. The results demonstrate that Au-NPs primarily influence the membrane-bound Hyd. In contrast to R. eutropha, Au-NPs had a negligible or negative effect on the growth, Hyd activity, and H2 production of Escherichia coli. The findings of this study offer new perspectives for the production of oxygen-tolerant Hyds and the development of EFCs.
Exploring large-scale gene coexpression networks in peach (Prunus persica L.): a new tool for predicting gene function
Authors: de los Cobos Felipe Pérez , García-Gómez Beatriz E , Orduña-Rubio Luis , Batlle Ignasi , Arús Pere , Matus José Tomás , Eduardo Iban
Published: January 2024

Peach is a model for Prunus genetics and genomics, however, identifying and validating genes associated to peach breeding traits is a complex task. A gene coexpression network (GCN) capable of capturing stable gene–gene relationships would help researchers overcome the intrinsic limitations of peach genetics and genomics approaches and outline future research opportunities. In this study, we created four GCNs from 604 Illumina RNA-Seq libraries. We evaluated the performance of every GCN in predicting functional annotations using an algorithm based on the ‘guilty-by-association’ principle. The GCN with the best performance was COO300, encompassing 21 956 genes. To validate its performance predicting gene function, we performed two case studies. In case study 1, we used two genes involved in fruit flesh softening: the endopolygalacturonases PpPG21 and PpPG22. Genes coexpressing with both genes were extracted and referred to as melting flesh (MF) network. Finally, we performed an enrichment analysis of MF network and compared the results with the current knowledge regarding peach fruit softening. The MF network mostly included genes involved in cell wall expansion and remodeling, and with expressions triggered by ripening-related phytohormones, such as ethylene, auxin, and methyl jasmonate. In case study 2, we explored potential targets of the anthocyanin regulator PpMYB10.1 by comparing its gene-centered coexpression network with that of its grapevine orthologues, identifying a common regulatory network. These results validated COO300 as a powerful tool for peach and Prunus research. This network, renamed as PeachGCN v1.0, and the scripts required to perform a function prediction analysis are available at https://github.com/felipecobos/PeachGCN.
The Ability of a 3-Gene Host Signature in Blood to Distinguish Tuberculous Meningitis From Other Brain Infections
Authors: Huynh Julie , Nhat Le Hoang Thanh , Bao Nguyen Le Hoai , Hai Hoang Thanh , Thu Do Dang Anh , Tram Trinh Thi Bich , Dung Vu Thi Mong , Vinh Do Dinh , Ngoc Nghiem My , Donovan Joseph , Phu Nguyen Hoan , Van Thanh Dang , Thu Nguyen Thi Anh , Bang Nguyen Duc , Ha Dang Thi Minh , Nghia Ho Dang Trung , Van Tan Le , Van Le Hong , Thwaites Guy , Thuong Nguyen Thuy Thuong
Published: January 2024

Background

Tuberculous meningitis (TBM) is difficult to diagnose. We investigated whether a 3-gene host response signature in blood can distinguish TBM from other brain infections.

Methods

The expression of 3 genes (dual specificity phosphatase 3 [DUSP3], guanylate-binding protein [GBP5], krupple-like factor 2 [KLF2]) was analyzed by RNA sequencing of archived whole blood from 4 cohorts of Vietnamese adults: 281 with TBM, 279 with pulmonary tuberculosis, 50 with other brain infections, and 30 healthy controls. Tuberculosis scores (combined 3-gene expression) were calculated following published methodology and discriminatory performance compared using area under a receiver operator characteristic curve (AUC).

Results

GBP5 was upregulated in TBM compared to other brain infections (P < .001), with no difference in DUSP3 and KLF2 expression. The diagnostic performance of GBP5 alone (AUC, 0.74; 95% confidence interval [CI], .67–.81) was slightly better than the 3-gene tuberculosis score (AUC, 0.66; 95% CI, .58–.73) in TBM. Both GBP5 expression and tuberculosis score were higher in participants with human immunodeficiency virus (HIV; P < .001), with good diagnostic performance of GBP5 alone (AUC, 0.86; 95% CI, .80–.93).

Conclusions

The 3-gene host signature in whole blood has the ability to discriminate TBM from other brain infections, including in individuals with HIV. Validation in large prospective diagnostic study is now required.
The role of IFN-γ-mediated host immune responses in monitoring and the elimination of Toxoplasma gondii infection
Authors: Ihara Fumiaki , Yamamoto Masahiro
Published: January 2024

Toxoplasma gondii is a pathogenic protozoan parasite of the Apicomplexa family that affects approximately 30% of the world’s population. Symptoms are usually mild in immunocompetent hosts, but it can pose significant health risks to immunosuppressed patients and pregnant women. Current treatment options are limited, and new therapies and vaccines are needed. The innate immune system is the first to recognize T. gondii infection and activates pro-inflammatory cytokines and chemokines to promote acquired immunity. The IL-12/IFN-γ axis is particularly important, and when this pathway is inhibited, infection becomes uncontrolled and lethal. In mice, receptors such as Toll-like receptor 11 (TLR11), TLR12, and chemokine receptors are involved in T. gondii recognition and the modulation of immune responses. In humans, where TLR11 and TLR12 are absent, other mechanisms have been reported as the innate immune sensing system in T. gondii infection. Immune cells activated in response to infection produce interleukin (IL)-12, which stimulates the proliferation of natural killer cells and T cells and promotes the production of interferon (IFN)-γ. Several IFN-γ-induced anti-T. gondii defense mechanisms inhibit parasite growth. These include nitric oxide (NO) production, indoleamine 2,3-dioxygenase, and the destruction of parasitophorous vacuoles by IFN-γ-inducible immunity related GTPase groups (IRGs and GBPs). Recent studies focusing on the diversity of IRGs in rodents and effector molecules in T. gondii suggest that host immune mechanisms and pathogen immune evasion mechanisms have co-evolved. Furthermore, it has been suggested that cysts are not simply dormant during chronic infection. This review summarizes recent findings on anti-T. gondii innate, adaptive, and cell-autonomous immune responses.
Effective Approaches to Diagnostic Stewardship of Syndromic Molecular Panels
Authors: Hitchcock Matthew M , Gomez Carlos A , Pozdol Joseph , Banaei Niaz
Published: January 2024

Background

Syndromic molecular panels for the diagnosis of gastroenteritis, meningitis/encephalitis, and pneumonia are becoming routinely used for patient care throughout the world.

Content

These rapid, sample-to-answer assays have great potential to improve patient care, infection control, and antimicrobial stewardship. However, diagnostic stewardship is essential for their optimal use and accuracy, and interventions can be applied at all phases of the diagnostic process.

The aim of this review article is to describe effective approaches to diagnostic stewardship for syndromic molecular panels to ensure appropriate test utilization and quality assured results.
Elucidating the Clinical Interpretation and Impact of a Positive Plasma Cell-Free DNA Metagenomics Test Result—A Single Center Retrospective Study
Authors: Vinh Dong Huan , Saleh Tawny , Kaur Ishminder , Yang Shangxin
Published: January 2024

Background

The Karius Test (KT), a cell-free DNA metagenomic next-generation sequencing assay, has potential to improve diagnostic evaluation of infectious diseases. Published data describing clinical impact of positive KT results are limited. We attempt to elucidate the clinical interpretation and impact of positive KT results based on types and patterns of detected pathogens and patient characteristics.

Methods

All positive KT results from a single institution in 2022 were screened. Patients with results that met predefined categories were included for review by a panel of 3 infectious diseases physicians and one clinical microbiologist. Predefined categories included reports with fungal, parasitic, notable bacterial, notable viral pathogens, or polybacterial results (≥3 bacteria). Polybacterial results were further classified into patterns of microbiome detected. Clinical impact and its correlation with result or patient characteristics were explored.

Results

Ninety-two patients met the inclusion criteria, most were immunocompromised (73%). Positive KT results that met predefined categories had the following clinical impact: positive in 30.4%, negative in 2.2%, and none in 65.2%. Polybacterial results, especially interpreted as oral flora had lowest clinical impact (7.1% and 0.0%, respectively), while detection of parasites or notable bacterial pathogens had the highest clinical impact (100% and 77.8%, respectively). There was no correlation between patient characteristics and clinical impact.

Conclusions

Among a cohort of largely immunocompromised patients, we were able to demonstrate clinical impact of specific KT result types and patterns but did not find correlation between patient characteristics and clinical impact. Our results should be confirmed in future larger cohorts.
Evaluation of a New NT-proBNP Immunoassay on an Automated Core Laboratory System
Authors: Logan Samantha , Di Meo Ashley , Shapero Stacey , Fabros Anselmo , Taher Jennifer , Kulasingam Vathany
Published: January 2024

Background

Heart failure remains a major cause of morbidity and mortality despite improvements in treatment. This study aimed to evaluate the Alere N-terminal pro B-type natriuretic peptide (NT-proBNP) immunoassay on the Abbott Alinity i platform.

Methods

The analytical performance including precision, linearity, limit of quantitation (LOQ), carryover, dilution-recovery, and stability was evaluated. A method comparison between the Abbott Alere NT-proBNP assay and Roche Elecsys proBNP II assay was performed using 70 residual plasma samples.

Results

Total imprecision was 4.1%, 3.5%, and 2.3% for low (120.9 ng/L), medium (333.9 ng/L), and high (4767.4 ng/L) QC levels, respectively. The manufacturer’s claimed LOQ of 8.3 ng/L was verified. Method comparison between the Alere NT-proBNP assay and the Elecsys proBNP II assay showed good agreement between assays with an R value of 0.998, a slope of 1.05 (95% CI, 1.03–1.06), and an intercept of 45.81 (95% CI, −46.6.84 to 138.22). The Bland–Altman plot showed an absolute bias of 250 ng/L or 6.02%. Subrange analysis (NT-proBNP <2000 ng/L) showed good agreement with an R value of 0.998, a slope of 1.04 (95% CI, 1.02–1.06), and an intercept of −4.83 (95% CI, −26.95 to 17.28), with a mean bias of 26 ng/L or 3.2%. The stability of NT-proBNP was also verified in lithium heparin plasma samples stored at 4°C over a 7-day period. Hemolysis and lipemia interference thresholds were verified, but icterus impacted NT-proBNP recovery by >20% at low analyte concentrations.

Conclusions

The Alere NT-proBNP assay demonstrated acceptable analytical performance and very good clinical concordance with the Elecsys proBNP II assay.
RNA-based bone histomorphometry: method and its application to explaining postpubertal bone gain in a G610C mouse model of osteogenesis imperfecta
Authors: Makareeva Elena , Sousa Megan , Kent Tristan , de Castro Luis F , Collins Michael T , Leikin Sergey
Published: January 2024

Bone histomorphometry is a well-established approach to assessing skeletal pathology, providing a standard evaluation of the cellular components, architecture, mineralization, and growth of bone tissue. However, it depends in part on the subjective interpretation of cellular morphology by an expert, which introduces bias. In addition, diseases like osteogenesis imperfecta (OI) and fibrous dysplasia are accompanied by changes in the morphology and function of skeletal tissue and cells, hindering consistent evaluation of some morphometric parameters and interpretation of the results. For instance, traditional histomorphometry combined with collagen turnover markers suggested that reduced bone formation in classical OI is accompanied by increased bone resorption. In contrast, the well-documented postpubertal reduction in fractures would be easier to explain by reduced bone resorption after puberty, highlighting the need for less ambiguous measurements. Here we propose an approach to histomorphometry based on in situ mRNA hybridization, which uses Col1a1 as osteoblast and Ctsk as osteoclast markers. This approach can be fully automated and eliminates subjective identification of bone surface cells. We validate these markers based on the expression of Bglap, Ibsp, and Acp5. Comparison with traditional histological and tartrate-resistant acid phosphatase staining of the same sections suggests that mRNA-based analysis is more reliable. Unlike inconclusive traditional histomorphometry of mice with α2(I)-Gly610 to Cys substitution in the collagen triple helix, mRNA-based measurements reveal reduced osteoclastogenesis in 11-wk-old animals consistent with the postpubertal catch-up osteogenesis observed by microCT. We optimize the technique for cryosections of mineralized bone and sections of paraffin-embedded decalcified tissue, simplifying and broadening its applications. We illustrate the application of the mRNA-based approach to human samples using the example of a McCune-Albright syndrome patient. By eliminating confounding effects of altered cellular morphology and the need for subjective morphological evaluation, this approach may provide a more reproducible and accessible evaluation of bone pathology.
Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men
Authors: Svensson Johan , Ohlsson Claes , Karlsson Magnus K , Herlitz Hans , Lorentzon Mattias , Lewerin Catharina , Mellström Dan
Published: January 2024

Overt and subclinical hyperthyroidism are associated with an increased fracture risk, but whether thyroid hormones are associated with fracture risk in individuals with normal thyroid-stimulating hormone (TSH) has mostly been investigated in women. Therefore, we investigated if serum levels of free thyroxine (FT4) or TSH are associated with fracture risk in Swedish men. We followed (median 12.2 yr) elderly men (n = 1825; mean age 75, range 69–81 yr) participating in the Gothenburg and Malmö subcohorts of the prospective, population-based MrOS-Sweden study. The statistical analyses included Cox proportional hazards regression. Men receiving levothyroxine treatment were excluded. In our total cohort, serum FT4 (per SD increase) was associated with increased risk of major osteoporotic fractures (MOFs; n = 479; fully adjusted hazard ratio [HR] 1.14, 95% CI, 1.05–1.24) and hip fractures (n = 207; HR 1.18, 95% CI, 1.04–1.33). Also, in men with normal TSH (n = 1658), FT4 (per SD increase) was significantly associated with increased risk of MOF and hip fractures. Furthermore, men in the highest FT4 quartile had a 1.5-fold increase in hip fracture risk compared with men in the three lower FT4 quartiles, both in the total population and in men with normal TSH (fully adjusted: HR 1.45, 95% CI, 1.04–2.02 and HR 1.51, 95% CI, 1.07–2.12, respectively). In contrast, the risk of MOF was not statistically different in the highest FT4 quartile compared with the three lower FT4 quartiles. Finally, serum TSH was not associated with fracture risk after full adjustment for covariates. In conclusion, serum FT4, but not serum TSH, is a predictor of hip fracture risk in elderly Swedish men. Additionally, there was an association between FT4 (per SD increase) and the risk of MOF.
Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study
Authors: Brown Janet , Paggiosi Margaret A , Rathbone Emma , Gregory Walter , Bertelli Gian , Din Omar , McCloskey Eugene , Dodwell David , Cameron David , Eastell Richard , Coleman Robert
Published: January 2024

Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites. One hundred twenty had previously been randomized to zoledronate (19 doses of 4 mg over 5 yr) and 104 to the control arm. BMD and BTMs were assessed at sub-study entry, 6 (BTMs only), 12, 24, and 60 mo following the completion of AZURE. As expected, mean BMD, T-scores, and Z-scores at sub-study entry were higher in the zoledronate vs the control arm. At the lumbar spine, the mean (SD) standardized BMD (sBMD) was 1123 (201) and 985 (182) mg/cm2 in the zoledronate and control arms, respectively (P < .0001). The baseline differences in sBMD persisted at all assessed skeletal sites and throughout the 5-yr follow-up period. In patients completing zoledronate treatment, BTMs were significantly lower than those in the control arm (α- and β-urinary C-telopeptide of type-I collagen, both P < .00001; serum intact pro-collagen I N-propeptide, P < .00001 and serum tartrate-resistant acid phosphatase 5b, P = .0001). Some offset of bone turnover inhibition occurred in the 12 mo following the completion of zoledronate treatment. Thereafter, during the 60 mo of follow-up, all BTMs remained suppressed in the zoledronate arm relative to the control arm. In conclusion, in addition to the known anti-cancer benefits of adjuvant zoledronate, there are likely to be positive, lasting benefits in BMD and bone turnover.
Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice
Authors: Hofstee Marloes I , Siverino Claudia , Saito Motoo , Meghwani Himanshu , Tapia-Dean James , Arveladze Samson , Hildebrand Maria , Rangel-Moreno Javier , Riool Martijn , Zeiter Stephan , Zaat Sebastian A J , Moriarty T Fintan , Muthukrishnan Gowrishankar
Published: January 2024

Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections. The involvement of PVL in S. aureus pathogenesis during bone infections has not been studied extensively yet. To investigate this, humanized BALB/c Rag2−/−Il2rg−/−SirpaNODFlk2−/− (huBRGSF) mice were subjected to transtibial implant-associated osteomyelitis with community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 wild type strain (WT), an isogenic mutant lacking lukF/S-PV (Δpvl), or complemented mutant (Δpvl+pvl). Three days post-surgery, Δpvl-infected huBRGSF mice had a less severe infection compared to WT-infected animals as characterized by 1) improved clinical outcomes, 2) lower ex vivo bacterial bone burden, 3) absence of staphylococcal abscess communities (SACs) in their bone marrow, and 4) compromised MRSA dissemination to internal organs (liver, kidney, spleen, heart). Interestingly, Δpvl-infected huBRGSF mice had fewer human myeloid cells, neutrophils, and HLA-DR+ monocytes in the bone niche compared to WT-infected animals. Expectedly, a smaller fraction of human myeloid cells were apoptotic in the Δpvl-infected huBRGSF animals. Taken together, our study highlights the pivotal role of PVL during acute implant-associated osteomyelitis in humanized mice.
A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss
Authors: de la Bastide Christopher , Soares Lissa , Lui Li-Yung , Harrington James , Cawthon Peggy , Orwoll Eric , Kado Deborah , Meliker Jaymie
Published: January 2024

Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long–term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross–sectional studies, this will be the first well–powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long–term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.
Insect frass composition and potential use as an organic fertilizer in circular economies
Authors: Amorim Helen C S , Ashworth Amanda J , Arsi Komala , Rojas M Guadalupe , Morales-Ramos Juan A , Donoghue Annie , Robinson Kelsy
Published: January 2024

Insect manure or “frass” has emerged as an alternative nutrient source for alleviating the dependence on fossil fuel-based fertilizers, reducing food waste, and promoting food security. Yet, research on insect frass chemical composition is in its infancy. Here, we assessed the chemical properties of yellow mealworm (Tenebrio molitor L.) frass compared with poultry litter (PL). Insect frass was obtained from the National Biological Control Laboratory (NBCL; IF-L) and an insect-rearing company (IF-C). PL was collected from facilities in Arkansas (PL-AR) and North Carolina (PL-NC). Samples were analyzed for pH, electrical conductivity, macro- and micronutrients, heavy metals, pathogens, and indicator microorganisms. On average, insect frass had 43% and 47% higher C and N than PL, respectively (P < 0.05). Considering a 5 mg/ha application rate, IF-C can supply 159 kg N/ha, twice the N supply of PL-AR (78 kg/ha). IF-L had a 53% higher P supply than PL-NC. Mean K, Ca, S, and micronutrient contents were higher in PL than in frass (P < 0.05), whereas As, Cd, Cr, and Pb were nearly absent in frass. Chemical composition and pathogens in fertilizer sources were largely affected by insect-rearing substrate and supplements used in poultry and insect production. Insect frass utilized in this study had optimum C and N rates relative to PL, suggesting a promising soil amendment for improving soil health and C sequestration, thus contributing to sustainable agricultural intensification and reuse of food waste in circular economies.
Transmission Patterns of Norovirus From Infected Children to Household Members in León, Nicaragua
Authors: Vielot Nadja A , Zepeda Omar , Reyes Yaoska , González Fredman , Toval-Ruíz Christian , Munguia Nancy , Picado Yorling , Becker-Dreps Sylvia , Bucardo Filemon
Published: January 2024

Norovirus is a common and highly transmissible gastrointestinal pathogen. Among 34 Nicaraguan households with a norovirus-infected child, 48% experienced norovirus transmission within 1 week, infecting 18% of household members; GII norovirus was more commonly transmitted than GI. Pediatric norovirus vaccines could prevent both index cases and transmission to close contacts.
A Holy Vine and Scattered Bread: Realized Eschatology in Didache 9.2, 4
Authors: Brewer J Brittain
Published: January 2024

Several recent studies on the eschatology of the Didache have concluded that the Didache maintains an entirely futurist eschatology. Following David Aune’s work, this article argues that the Didache’s eschatology, when understood in terms of the eucharistic prayers, is better described in realized or inaugurated terms. The two particular prayers in question concern the holy vine of David and the bread scattered upon the mountain. Both of these images, when understood against the backdrop of Old Testament and Second Temple theology, carry significant eschatological motifs, suggesting that the Didache is not restricted by futurist or strictly millenarian concerns. Instead, the Didache shows evidence of being a document whose community maintained both a participatory and anticipatory relationship to the kingdom of God.
Country-Specific Screening, Prevalence, and Immunity Rates for Hepatitis B Infection in a Large US Safety-Net System
Authors: Zhou Kali , Sumethasorn Matt , Wong Christopher , Terrault Norah A
Published: January 2024

Country- and region-specific estimates of hepatitis B virus (HBV) screening, prevalence, and immunity rates are provided for 202 868 adults from 174 unique countries in a large urban safety-net system. Of these, 41.8% (95% confidence interval, 41.5%–42.0%) were screened, with age-adjusted HBV prevalence of 0.9% (.9%–1.0%); 55.3% (54.9%–55.7%) had immunity testing, and 32.4% (31.9%–33.0%) were immune.
Outbreak of Diarrhea Caused by a Novel Cryptosporidium hominis Subtype During British Military Training in Kenya
Authors: Toriro Romeo , Pallett Scott , Woolley Stephen , Bennett Charlie , Hale Isra , Heylings Jennifer , Wilkins Daniel , Connelly Thomas , Muia Kennedy , Avery Patrick , Stuart Andrew , Morgan Laura , Davies Mark , Nevin William , Quantick Oliver , Robinson Guy , Elwin Kristin , Chalmers Rachel , Burns Daniel , Beeching Nicholas , Fletcher Thomas , O’Shea Matthew
Published: January 2024

Background

We report clinical, epidemiological, and laboratory features of a large diarrhea outbreak caused by a novel Cryptosporidium hominis subtype during British military training in Kenya between February and April 2022.

Methods

Data were collated from diarrhea cases, and fecal samples were analyzed on site using the multiplex polymerase chain reaction (PCR) BioFire FilmArray. Water was tested using Colilert kits (IDEXX, UK). DNA was extracted from feces for molecular characterization of Cryptosporidium A135, Lib13, ssu rRNA, and gp60 genes.

Results

One hundred seventy-two of 1200 (14.3%) personnel at risk developed diarrhea over 69 days. One hundred six primary fecal samples were tested, and 63/106 (59.4%; 95% CI, 0.49%–0.69%) were positive for Cryptosporidium spp. Thirty-eight had Cryptosporidium spp. alone, and 25 had Cryptosporidium spp. with ≥1 other pathogen. A further 27/106 (25.5%; 95% CI, 0.18%–0.35%) had non-Cryptosporidium pathogens only, and 16/106 (15.1%; 95% CI, 0.09%–0.23%) were negative. C. hominis was detected in 58/63 (92.1%) Cryptosporidium spp.–positive primary samples, but the others were not genotypable. Twenty-seven C. hominis specimens were subtypable; 1 was gp60 subtype IeA11G3T3, and 26 were an unusual subtype, ImA13G1 (GenBank accession OP699729), supporting epidemiological evidence suggesting a point source outbreak from contaminated swimming water. Diarrhea persisted for a mean (SD) of 7.6 (4.6) days in Cryptosporidium spp. cases compared with 2.3 (0.9) days in non-Cryptosporidium cases (P = .001).

Conclusions

Real-time multiplex PCR fecal testing was vital in managing this large cryptosporidiosis outbreak. The etiology of a rare C. hominis gp60 subtype emphasizes the need for more genotypic surveillance to identify widening host and geographic ranges of novel C. hominis subtypes.
The death of ‘traditional’ charivari and the invention of pot-banging in Spain,
c
.1960–2020
Authors: Kerry Matthew
Published: January 2024

Banging together pots and pans has become established as a common protest technique in Spain and across the world. Pot-banging can be linked to charivari: a centuries-old, Europe-wide, nuptial practice that subjected a marrying couple to mocking moral critique, which was also adapted for political ends. This article, however, distinguishes between nuptial charivari (the cencerrada) and recent political pot-banging (the cacerolada). The former suffered a process decline and disappearance while the latter, separately, was imported into Spain from Latin America in the late 1980s. The lack of connection between the two is reflected in different terms, but can be further established through close attention to their respective staging, gendered nature, meaning and sound. The case of Spanish pot-banging sheds light on the fate of ‘traditions’ during the Transition from the Francoist dictatorship to democracy, particularly in terms of changing notions of individual rights, civility and gender relations, and has implications for how historians approach the history of collective action. Historians should pay greater attention to how techniques are transmitted and learned within and across borders. The history of modern protest is perhaps more disjointed than modernizing approaches suggest.
Mitigating modal noise in multimode circular fibres by optical agitation using a galvanometer
Authors: Ghosh Supriyo , Boonsri Chantira , Martin William , Jones Hugh R A , Choochalerm Piyamas , Usher Sarah , Yerolatsitis Stephanos , Wocial Thomas , Wright Thomas
Published: January 2024

Modal noise appears due to the non-uniform and unstable distribution of light intensity among the finite number of modes in multimode fibres. It is an important limiting factor in measuring radial velocity precisely by fibre-fed high-resolution spectrographs. The problem can become particularly severe as the fibre’s core become smaller and the number of modes that can propagate reduces. Thus, mitigating modal noise in relatively small core fibres still remains a challenge. We present here a novel technique to suppress modal noise. Two movable mirrors in the form of a galvanometer re-image the mode-pattern of an input fibre to an output fibre. The mixing of modes coupled to the output fibre can be controlled by the movement of mirrors applying two sinusoidal signals through a voltage generator. We test the technique for four multimode circular fibres: 10 and 50 $\mu$m step-index, 50 $\mu$m graded-index, and a combination of 50 $\mu$m graded-index and 5:1 tapered fibres (GI50t). We present the results of mode suppression both in terms of the direct image of the output fibre and spectrum of white light obtained with the high-resolution spectrograph. We found that the galvanometer mitigated modal noise in all the tested fibres, but was most useful for smaller core fibres. However, there is a trade-off between the modal noise reduction and light-loss. The GI50t provides the best result with about 60 per cent mitigation of modal noise at a cost of about 5 per cent output light-loss. Our solution is easy to use and can be implemented in fibre-fed spectrographs.
Removing Barriers to Entry in Medicine: Evidence from Pakistan
Authors: Aqeel Fatima
Published: January 2024

In 1992, Pakistan equalized admissions criteria for women and men applying to medical schools, causing a rapid increase in the female share of medical graduates. Using birth cohort variation, I find that equalizing admissions criteria increased employment among female doctors by 21 percentage points and among doctors overall by 9 percentage points, even though female doctors are less likely to be employed than male doctors. Earnings for male medical graduates increased as lower ability males were crowded out. The 1992 reform led to increased gender diversification in a wide range of medical specialties, but it also concentrated doctors in urban districts where women prefer to practice.
Variation in Pathogenicity and Subsequent Production of Sclerotia ofSclerotinia sclerotiorumIsolates in Different Cover Crops, Flower Strips, and Weeds
Authors: Zamani-Noor Nazanin , Brand Sinja , Noshin Faria , Söchting Hans-Peter
Published: January 2024

Cover crops and flower strips are used in agricultural fields as part of integrated pest management strategies. However, their potential as secondary hosts of soilborne pathogens such as Sclerotinia sclerotiorum in oilseed rape cultivation is not fully comprehended. In the current study, we evaluated the effect of pathogen virulence on the development of Sclerotinia stem/leaf rot and sclerotia production in 33 plant species from 11 botanical families using two S. sclerotiorum isolates. Furthermore, the effect of sclerotial size on carpogenic germination was studied. Results showed that the pathogen’s virulence significantly affected the occurrence and development of Sclerotinia stem/leaf rot and the subsequent production of sclerotia. Among all plant species tested, 26 were more susceptible to the highly aggressive S. sclerotiorum isolate, which produced more and bigger sclerotia in 17 species than the less aggressive isolate. Moreover, a stronger positive correlation was found between the relative lesion length of plants inoculated with the highly aggressive isolate and the number of sclerotia produced by this isolate (Spearman’s rank correlation coefficient [rs] = 0.572; P = 0.004). Additionally, we found that larger and heavier sclerotia produced stipes and apothecia earlier and at a greater rate than smaller ones. The heavyweight class had the highest carpogenic germination rate (82.4%), followed by the average (67.2%) and lightweight classes (59.5%). Our findings highlight the need for further investigation into the potential risks associated with cover crops, weeds, and flower strips as secondary hosts of soilborne pathogens in agricultural fields.
Lost in Translation: Failure of Preclinical Studies to Accurately Predict the Effect of Regional Analgesia on Cancer Recurrence
Authors: Cata Juan P. , Sessler Daniel I.
Published: January 2024

The major goal of translational research is to evaluate the efficacy and effectiveness of treatments and interventions that have emerged from exhaustive preclinical evidence. In 2007, a major clinical trial was started to investigate the impact of paravertebral analgesia on breast cancer recurrence. The trial was based on preclinical evidence demonstrating that spinal anesthesia suppressed metastatic dissemination by inhibiting surgical stress, boosting the immunological response, avoiding volatile anesthetics, and reducing opioid use. However, that trial and three more recent randomized trials with a total of 4,770 patients demonstrate that regional analgesia does not improve survival outcomes after breast, lung, and abdominal cancers. An obvious question is why there was an almost complete disconnect between the copious preclinical investigations suggesting benefit and robust clinical trials showing no benefit? The answer is complex but may result from preclinical research being mechanistically driven and based on reductionist models. Both basic scientists and clinical investigators underestimated the limitations of various preclinical models, leading to the apparently incorrect hypothesis that regional anesthesia reduces cancer recurrence. This article reviews factors that contributed to the discordance between the laboratory science, suggesting that regional analgesia might reduce cancer recurrence and clinical trials showing that it does not—and what can be learned from the disconnect.
CDH1 hypermethylation: a potential molecular pathway for invasiveness in glioblastoma
Authors: Belut Daniel R. , Lima Estela de O. , Zanini Marco A. , Galvani Aline F. , Furtado Fabiana B. , Ferrasi Adriana C.
Published: January 2024

Glioblastoma is the most aggressive central nervous system primary tumor. Prognosis is poor, mainly due to the malignant characteristics of the tumor, such as high cell proliferation and invasiveness. CDH1 hypermethylation is linked to the invasive potential in various cancer types, but its importance is still unknown in glioblastoma. In this context, the methylation status of CDH1 was analyzed using MSP-PCR (Methylation-specific Polymerase Chain Reaction) in glioblastoma (n = 34) and normal glial tissue samples (n = 11). CDH1 hypermethylation was found in 39.4% (13/34) of the tumor samples and none of the normal glial tissue, suggesting a relation between CDH1 hypermethylation and glioblastoma (P = 0.0195). Finally, this study showed unprecedented information that could contribute to clarifying the molecular pathways involved in the invasiveness and aggressiveness of this type of cancer.
Autoimmune gastritis serological biomarkers in gastric cancer patients
Authors: Kriķe Petra , Appel Meret Sophia , Shums Zakera , Poļaka Inese , Kojalo Ilona , Rudzīte Dace , Tolmanis Ivars , Kiršners Arnis , Bogdanova Inga , Aleksandravica Ilona , Norman Gary L. , Leja Mārcis
Published: January 2024

The role of autoimmunity in the pathogenesis of gastric cancer remains controversial. We studied antiparietal cell antibody (anti-PCA) and anti-intrinsic factor antibody (anti-IFA) levels and their associations with pepsinogen I/pepsinogen II levels in patients with gastric adenocarcinoma compared to a control group with mild or no atrophy of the stomach mucosa. Plasma levels of anti-PCA and anti-IFA were measured by ELISA (Inova Diagnostics Inc, San Diego, California, USA). The cutoff value for anti-PCA and anti-IFA positivity was ≥25 units. Altogether 214 patients (126 men, 88 women, median age 64.46, range: 35–86) with confirmed gastric adenocarcinoma and 214 control cases paired for age and sex were included in the study. Positive anti-PCA was present in 22 (10.3%) gastric cancer patients and controls (P ≥ 0.999); positive anti-IFA in 6 (2.8%) and 4 (1.9.%), P < 0.232, respectively.

We did not find significant differences in anti-PCA and anti-IFA positivity between gastric cancer patients and the control group; further investigation is required to better understand the potential involvement of autoimmune gastritis in the development of gastric cancer.
HIV-1 subtypes and latent reservoirs
Authors: Ranga Udaykumar , Panchapakesan Arun , Saini Chhavi
Published: January 2024

Purpose of review

We explore the current status of research on HIV-1 subtype-specific variations and their impact on HIV-1 latency. We also briefly address the controversy surrounding the decision-making process governing the ON/OFF states of HIV-1 transcription, specifically focusing on the regulatory elements, the long terminal repeat (LTR), and Tat. Understanding the decision-making process is crucial for developing effective intervention strategies, such as the 'shock-and-kill’ approach, to reactivate latent HIV-1.

Recent findings

Attention has been drawn to subtype-specific transcription factor binding site (TFBS) variations and the possible impact of these variations on viral latency. Further, diverse subtype-specific assays have been developed to quantify the latent viral reservoirs. One interesting observation is the relatively larger latent reservoirs in HIV-1B infection than those of other viral subtypes, which needs rigorous validation. The emergence of LTR-variant viral strains in HIV-1C demonstrating significantly higher levels of latency reversal has been reported.

Despite persistent and substantial efforts, latent HIV-1 remains a formidable challenge to a functional cure. Determined and continued commitment is needed to understand the ON/OFF decision-making process of HIV-1 latency, develop rigorous assays for accurately quantifying the latent reservoirs, and identify potent latency-reversing agents and cocktails targeting multiple latency stages. The review emphasizes the importance of including diverse viral subtypes in future latency research.
Pharmacological approaches to promote cell death of latent HIV reservoirs
Authors: Pinzone Marilia Rita , Shan Liang
Published: January 2024

Purpose of review

HIV requires lifelong antiviral treatment due to the persistence of a reservoir of latently infected cells. Multiple strategies have been pursued to promote the death of infected cells.

Recent findings

Several groups have focused on multipronged approaches to induce apoptosis of infected cells. One approach is to combine latency reversal agents with proapoptotic compounds and cytotoxic T cells to first reactivate and then clear infected cells. Other strategies include using natural killer cells or chimeric antigen receptor cells to decrease the size of the reservoir.

A novel strategy is to promote cell death by pyroptosis. This mechanism relies on the activation of the caspase recruitment domain-containing protein 8 (CARD8) inflammasome by the HIV protease and can be potentiated by nonnucleoside reverse transcriptase inhibitors.

The achievement of a clinically significant reduction in the size of the reservoir will likely require a combination strategy since none of the approaches pursued so far has been successful on its own in clinical trials. This discrepancy between promising in vitro findings and modest in vivo results highlights the hurdles of identifying a universally effective strategy given the wide heterogeneity of the HIV reservoirs in terms of tissue location, capability to undergo latency reversal and susceptibility to cell death.
Targeting noncoding RNAs to reactivate or eliminate latent HIV reservoirs
Authors: Beliakova-Bethell Nadejda
Published: January 2024

Purpose of review

Expression of noncoding RNAs (ncRNAs) is more tissue and cell type-specific than expression of protein-coding genes. Understanding the mechanisms of action of ncRNAs and their roles in HIV replication and latency may inform targets for the latent HIV reservoir reactivation or elimination with high specificity to CD4+ T cells latently infected with HIV.

Recent findings

While the number of studies in the field of ncRNAs and HIV is limited, evidence points to complex interactions between different ncRNAs, protein-coding RNAs, and proteins. Latency-reversing agents modulate the expression of ncRNAs, with some effects being inhibitory for HIV reactivation. An important limitation of basic research on the ncRNA mechanisms of action is the reliance on cell lines. Because of cell type specificity, it is uncertain whether the ncRNAs function similarly in primary cells.

Comprehensive functional screens to uncover all ncRNAs that regulate HIV expression and the detailed exploration of their mechanisms of action in relevant cell types are needed to identify promising targets for HIV reservoir clearance. Classes of ncRNAs as a whole rather than individual ncRNAs might represent an attractive target for reservoir elimination. Compound screens for latency reversal should factor in the complexity of their effects on ncRNAs.
Harnessing immune cells to eliminate HIV reservoirs
Authors: Grasberger Paula , Sondrini Abigail R. , Clayton Kiera L.
Published: January 2024

Purpose of review

Despite decades of insights about how CD8+ T cells and natural killer (NK) cells contribute to natural control of infection, additional hurdles (mutational escape from cellular immunity, sequence diversity, and hard-to-access tissue reservoirs) will need to be overcome to develop a cure. In this review, we highlight recent findings of novel mechanisms of antiviral cellular immunity and discuss current strategies for therapeutic deisgn.

Recent findings

Of note are the apparent converging roles of viral antigen-specific MHC-E-restricted CD8+ T cells and NK cells, interleukin (IL)-15 biologics to boost cytotoxicity, and broadly neutralizing antibodies in their native form or as anitbody fragments to neutralize virus and engage cellular immunity, respectively. Finally, renewed interest in myeloid cells as relevant viral reservoirs is an encouraging sign for designing inclusive therapeutic strategies.

Several studies have shown promise in many preclinical models of disease, including simian immunodeficiency virus (SIV)/SHIV infection in nonhuman primates and HIV infection in humanized mice. However, each model comes with its own limitations and may not fully predict human responses. We eagerly await the results of clinical trails assessing the efficacy of these strategies to achieve reductions in viral reservoirs, delay viral rebound, or ultimately elicit immune based control of infection without combination antiretroviral therapy (cART).
The Role of Palliative Care in Cardiovascular Disease
Authors: McClung John Arthur , Frishman William H. , Aronow Wilbert S.
Published: January 2024

The American Heart Association has recommended that palliative care be integrated into the care of all patients with advanced cardiac illnesses. Notwithstanding, the number of patients receiving specialist palliative intervention worldwide remains extremely small. This review examines the nature of palliative care and what is known about its delivery to patients with cardiac illness. Most of the published literature on the subject concern advanced heart failure; however, some data also exist regarding patients with heart transplantation, pulmonary hypertension, valvular disease, congenital heart disease, indwelling devices, mechanical circulatory support, and advanced coronary disease. In addition, outcome data, certification requirements, workforce challenges, barriers to implementation, and a potential caveat about palliative care will also be examined. Further work is required regarding appropriate means of implementation, quality control, and timing of intervention.
A review of racial disparities in ovarian cancer and clinical trials
Authors: Ali Maryam , Tewari Krishnansu S.
Published: January 2024

Purpose of review

Ovarian cancer ranks fifth in mortality among women with cancer and accounts for more death compared to any other gynecological cancers. This review summarizes the most recent literature on disparities in ovarian cancer as well as within recent clinical trials.

Recent findings

Recent studies have identified a notable disparity in genetic testing utilization, disease stage at the time of diagnosis, and adherence to treatment guidelines between Black women and their White counterparts, ultimately leading to increased mortality rates among Black women from ovarian cancer. Additionally, there is an underreporting of race in clinical trials and those that do report race demonstrate significant racial disparities within trial participants with the majority of participants being White.

It is imperative that we address the significant racial disparities within ovarian cancer and clinical trials to establish a framework of equitable healthcare provision. Multiple determinants, such as implicit bias, provider mistrust, accessibility hurdles, and socioeconomic influences, appear to contribute to the current disparities faced by women of color. Further investigation is warranted, encompassing a deeper understanding of diverse patient perspectives and identifying barriers to receiving optimal care and participating in clinical trials.