bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin receptor (+) stromal cells respond to periodontitis and attenuate alveolar bone repair via CCRL2-mediated Wnt inhibition
Authors: Chen Yongliang , Weng Yuteng , Huang Jie , Li Qin , Sun Bin , Wang Haicheng , Wang Zuolin
Published: March 2024

The impaired bone healing in tooth extraction sockets due to periodontitis presents a major obstacle to restoring oral health. The mechanisms regulating the osteogenic capacity of jawbone-derived stromal cells in the periodontitis microenvironment remain elusive. Leptin receptor (LepR) expressing stromal cells, which largely overlap with Cxcl12-abundant reticular (CAR) cells in bone tissue, rapidly proliferate and differentiate into bone-forming cells during extraction socket healing to support alveolar bone repair. In this study, we identify that CCRL2 is significantly expressed and inhibits osteogenesis in LepR+/CAR cells of alveolar bones with periodontitis. The Ccrl2-KO mice exhibit significant improvements in bone healing in extraction sockets with periodontitis. Specifically, the binding of CCRL2 to SFRP1 on the surface of LepR+/CAR cells can amplify the suppressive effect of SFRP1 on Wnt signaling under inflammation, thus hindering the osteogenic differentiation of LepR+/CAR cells and resulting in poor bone healing in extraction sockets with periodontitis. Together, we clarify that the CCRL2 receptor of LepR+/CAR cells can respond to periodontitis and crosstalk with Wnt signaling to deteriorate extraction socket healing.
The chromatin remodeling factor Arid1a cooperates with Jun/Fos to promote osteoclastogenesis by epigenetically upregulating Siglec15 expression
Authors: Zhang Yongxing , Sun Hangxiang , Huang Fei , Chen Yang , Ding Xiying , Zhou Chenhe , Wu Yan , Zhang Qing , Ma Xiao , Wang Jun , Yue Rui , Shen Li , Sun Xuxu , Ye Zhaoming
Published: March 2024

Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow–derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell–cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid–binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.
The systematics of the amphidromous shrimp Macrobrachium tenellum (Smith, 1871) (Decapoda: Caridea: Palaemonidae) from the Mexican Pacific slope
Authors: Meza-Sánchez Iris Gabriela , Maeda-Martínez Alejandro M , Obregón-Barboza Hortencia , García-Velazco Humberto , Rodríguez-Almaraz Gabino A , Ruiz-Campos Gorgonio , Murugan Gopal
Published: March 2024

We had previously revised the systematics of four species of MacrobrachiumSpence Bate, 1868 from the Pacific coast of Mexico, including the Baja California Peninsula (BCP): M. americanumSpence Bate, 1868, M. digueti (Bouvier, 1895), M. hobbsi Nates & Villalobos in Villalobos Hiriart & Nates Rodríguez, 1990, and M. occidentale Holthuis, 1950. Genetic analyses of the mitochondrial markers 16S ribosomal RNA (16S) and cytochrome oxidase I (COI) of individuals of these morphological species from BCP have shown that, even facing the Gulf of California (Sea of Cortés) as an apparent marine ecological barrier, they are conspecific to their respective genetic lineages (species) found from the Pacific slope of mainland Mexico. We discuss the systematics of the fifth species of Macrobrachium from the Mexican Pacific slope, M. tenellum (Smith, 1871) to test the hypothesis that individuals of the putative M. tenellum from BCP belong to the same species from the Pacific slope of mainland Mexico. We revised the morphological characters of taxonomic importance using material obtained in the field and voucher material deposited in Mexican scientific collections, and performed molecular genetic analyses with newly generated fragments of the mitochondrial markers 16S and COI. We conclude, as in our previous studies on Macrobrachium species of the region, that the examined specimens of the putative M. tenellum from BCP belong to the same species found on the Pacific slope of mainland Mexico, and that oceanic dispersal is responsible for the distribution of the species of Macrobrachium in the peninsula rather than by vicariant events.
A randomized comparison of online mindfulness-based group sex therapy vs supportive group sex education to address sexual dysfunction in breast cancer survivors
Authors: Brotto Lori A , Walker Lauren , Sears Carly , Woo Shannon , Millman Roanne , Zdaniuk Bozena
Published: March 2024

Background

Sexual difficulties and vaginal pain are common following treatment for breast cancer.

Aim

The goal of this study was to evaluate an online mindfulness-based group sex therapy vs an online supportive sex education group therapy to address these sexual difficulties.

Methods

Breast cancer survivors (n = 118) were randomized to 1 of the 2 arms; 116 provided informed consent and completed the time 1 assessment. Treatment included 8 weekly 2-hour online group sessions. Those randomized to the mindfulness group completed daily mindfulness exercises, and those in the comparison arm read and completed exercises pertaining to sex education.

Outcomes

Assessments were repeated at posttreatment and 6 months after the completion of the group.

Results

There was a main effect of treatment on primary endpoints of sexual desire, sexual distress, and vaginal pain, with all outcomes showing significant improvements, with no differential impact by treatment arm. Secondary endpoints of interoceptive awareness, mindfulness, and rumination about sex also significantly improved with both treatments, with no group-by-time interaction.

Conclusion

Both mindfulness-based sex therapy and supportive sex education delivered in group format online are effective for improving many facets of sexual function, vaginal pain, rumination, mindfulness, and interoceptive awareness in breast cancer survivors.

Strengths and Limitations

We used a randomized methodology. Future studies should seek to diversify participants.

Clinical Implications

These findings highlight the need to offer similar treatments to more breast cancer survivors immediately after and in the years following cancer treatment as a means of improving survivorship quality of life.
Predicting Functional Consequences of Recent Natural Selection in Britain
Authors: Poyraz Lin , Colbran Laura L , Mathieson Iain
Published: March 2024

Ancient DNA can directly reveal the contribution of natural selection to human genomic variation. However, while the analysis of ancient DNA has been successful at identifying genomic signals of selection, inferring the phenotypic consequences of that selection has been more difficult. Most trait-associated variants are noncoding, so we expect that a large proportion of the phenotypic effects of selection will also act through noncoding variation. Since we cannot measure gene expression directly in ancient individuals, we used an approach (Joint-Tissue Imputation [JTI]) developed to predict gene expression from genotype data. We tested for changes in the predicted expression of 17,384 protein coding genes over a time transect of 4,500 years using 91 present-day and 616 ancient individuals from Britain. We identified 28 genes at seven genomic loci with significant (false discovery rate [FDR] < 0.05) changes in predicted expression levels in this time period. We compared the results from our transcriptome-wide scan to a genome-wide scan based on estimating per-single nucleotide polymorphism (SNP) selection coefficients from time series data. At five previously identified loci, our approach allowed us to highlight small numbers of genes with evidence for significant shifts in expression from peaks that in some cases span tens of genes. At two novel loci (SLC44A5 and NUP85), we identify selection on gene expression not captured by scans based on genomic signatures of selection. Finally, we show how classical selection statistics (iHS and SDS) can be combined with JTI models to incorporate functional information into scans that use present-day data alone. These results demonstrate the potential of this type of information to explore both the causes and consequences of natural selection.
Very long-term outcomes of pediatric patients treated for optic pathway gliomas: A longitudinal cohort study
Authors: Morin Alice , Allodji Rodrigue , Kariyawasam Dulanjalee , Touraine Philippe , Puget Stéphanie , Beccaria Kevin , De Carli Emilie , Kieffer Virginie , Rivollet Sophie , Abbou Samuel , Fayech Chiraz , Souchard Vincent , Dufour Christelle , De Vathaire Florent , Bolle Stéphanie , Grill Jacques , Fresneau Brice
Published: March 2024

Background

Optic pathway gliomas (OPGs) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications.

Methods

We included patients treated at Gustave Roussy (GR) between January 1980 and December 2015 for OPG, before 18 years old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and updated, thanks to the GR long-term follow-up program and French national mortality registry for patients included in the French Childhood Cancer Survivor Study.

Results

We included 182 5-year OPG-childhood survivors in the analysis (sex ratio M/F 0.8, 35% with neurofibromatosis type 1 [NF1]). With a median follow-up of 17.2 years (range = 5–41), we registered 82 relapses, 9 second malignancies, and 15 deaths as first events after 5 years, resulting in 20-year conditional overall survival (C-OS) and late events-free survival of 79.9% (95% confidence interval [CI] = 71–86) and 43.5% (95% CI = 36–51), respectively. Radiotherapy exposure in NF1 patients (hazard ratio [HR] = 6, 95% CI = 1.7–21.2) and hypothalamic involvement (HR = 3.2, 95% CI = 1.4–7.3) were significantly associated with C-OS in multivariable analyses. Ninety-five percent of 5-year OPG survivors suffered from any health condition, especially visual acuity “<1/10” (n = 109), pituitary deficiency (n = 106), and neurocognitive impairment (n = 89). NF1 (HR 2.1) was associated with precocious puberty. With a median time post-diagnosis of 4.2 years, 33 cerebrovascular events were observed in 21 patients.

Conclusions

Late relapses, second malignancies, and cerebrovascular diseases are severe late events resulting in premature mortality. Morbidity is high and needs after-cancer care to improve quality of life. Risk factors could be considered to better stratify long-term follow-up.
MicroRNA1432 regulates rice drought stress tolerance by targeting the CALMODULIN-LIKE2 gene
Authors: Luo Guangyu , Li Lin , Yang Xiaoyu , Yu Yu , Gao Lei , Mo Beixin , Chen Xuemei , Liu Lin
Published: March 2024

Due to climate change, drought has become a major threat to rice (Oryza sativa L.) growth and yield worldwide. Understanding the genetic basis of drought tolerance in rice is therefore of great importance. Here, we identified a microRNA, miR1432, which regulates rice drought tolerance by targeting the CALMODULIN-LIKE2 (OsCaML2) gene. Mutation of MIR1432 or suppression of miR1432 expression significantly impaired seed germination and seedling growth under drought-stress conditions. Molecular analysis demonstrated that miR1432 affected rice drought tolerance by directly targeting OsCaML2, which encodes an EF-hand chiral calcium-binding protein. Overexpression of a miR1432-resistant form of OsCaML2 (OEmCaML2) phenocopied the mir1432 mutant and miR1432 suppression plants. Furthermore, the suppression of miR1432 severely affected the expression of genes involved in responses to stimulation, metabolism and signal transduction, especially the mitogen-activated protein kinase (MAPK) pathway and hormone transduction pathway in rice under drought stress. Thus, our findings show that the miR1432-OsCaML2 module plays an important role in the regulation of rice drought tolerance, suggesting its potential utilization in developing molecular breeding strategies that improve crop drought tolerance.
Woolly mutation with the Get02 locus overcomes the polygenic nature of trichome-based pest resistance in tomato
Authors: Vendemiatti Eloisa , Hernández-De Lira Inty Omar , Snijders Roxane , Torne-Srivastava Tanmayee , Therezan Rodrigo , Simioni Prants Gabriela , Lopez-Ortiz Carlos , Reddy Umesh K , Bleeker Petra , Schenck Craig A , Peres Lázaro Eustáquio Pereira , Benedito Vagner Augusto
Published: March 2024

Type-IV glandular trichomes, which only occur in the juvenile developmental phase of the cultivated tomato (Solanum lycopersicum), produce acylsugars that broadly protect against arthropod herbivory. Previously, we introgressed the capacity to retain type-IV trichomes in the adult phase from the wild tomato, Solanum galapagense, into the cultivated species cv. Micro-Tom (MT). The resulting MT-Galapagos enhanced trichome (MT-Get) introgression line contained 5 loci associated with enhancing the density of type-IV trichomes in adult plants. We genetically dissected MT-Get and obtained a subline containing only the locus on Chromosome 2 (MT-Get02). This genotype displayed about half the density of type-IV trichomes compared to the wild progenitor. However, when we stacked the gain-of-function allele of WOOLLY, which encodes a homeodomain leucine zipper IV transcription factor, Get02/Wo exhibited double the number of type-IV trichomes compared to S. galapagense. This discovery corroborates previous reports positioning WOOLLY as a master regulator of trichome development. Acylsugar levels in Get02/Wo were comparable to the wild progenitor, although the composition of acylsugar types differed, especially regarding fewer types with medium-length acyl chains. Agronomical parameters of Get02/Wo, including yield, were comparable to MT. Pest resistance assays showed enhanced protection against silverleaf whitefly (Bemisia tabaci), tobacco hornworm (Manduca sexta), and the fungus Septoria lycopersici. However, resistance levels did not reach those of the wild progenitor, suggesting the specificity of acylsugar types in the pest resistance mechanism. Our findings in trichome-mediated resistance advance the development of robust, naturally resistant tomato varieties, harnessing the potential of natural genetic variation. Moreover, by manipulating only 2 loci, we achieved exceptional results for a highly complex, polygenic trait, such as herbivory resistance in tomato.
ROP GTPases with a geranylgeranylation motif modulate alkaloid biosynthesis in Catharanthus roseus
Authors: Pedenla Bomzan Dikki , Sharma Anuj , Lemos Cruz Pamela , Carqueijeiro Ines , Bellenger Léo , Rai Avanish , Thippesh Akshay Kumar , Chinnegowda Venkatesha S , Parihar Durgesh , Ducos Eric , Courdavault Vincent , Nagegowda Dinesh A
Published: March 2024

Rho of Plant (ROP) GTPases function as molecular switches that control signaling processes essential for growth, development, and defense. However, their role in specialized metabolism is poorly understood. Previously, we demonstrated that inhibition of protein geranylgeranyl transferase (PGGT-I) negatively impacts the biosynthesis of monoterpene indole alkaloids (MIA) in Madagascar periwinkle (Catharanthus roseus), indicating the involvement of prenylated proteins in signaling. Here, we show through biochemical, molecular, and in planta approaches that specific geranylgeranylated ROPs modulate C. roseus MIA biosynthesis. Among the six C. roseus ROP GTPases (CrROPs), only CrROP3 and CrROP5, having a C-terminal CSIL motif, were specifically prenylated by PGGT-I. Additionally, their transcripts showed higher expression in most parts than other CrROPs. Protein–protein interaction studies revealed that CrROP3 and CrROP5, but not ΔCrROP3, ΔCrROP5, and CrROP2 lacking the CSIL motif, interacted with CrPGGT-I. Further, CrROP3 and CrROP5 exhibited nuclear localization, whereas CrROP2 was localized to the plasma membrane. In planta functional studies revealed that silencing of CrROP3 and CrROP5 negatively affected MIA biosynthesis, while their overexpression upregulated MIA formation. In contrast, silencing and overexpression of CrROP2 had no effect on MIA biosynthesis. Moreover, overexpression of ΔCrROP3 and ΔCrROP5 mutants devoid of sequence coding for the CSIL motif failed to enhance MIA biosynthesis. These results implicate that CrROP3 and CrROP5 have a positive regulatory role on MIA biosynthesis and thus shed light on how geranylgeranylated ROP GTPases mediate the modulation of specialized metabolism in C. roseus.
Unveiling silenced narratives: a scoping review on sexual function challenges in migrant and refugee women
Authors: Mirzaei Damabi Negin , Begum Mumtaz , Avery Jodie C , Padhani Zahra Ali , Lassi Zohra S
Published: March 2024

Introduction

Of the approximately 281 million international migrants and 35.3 million refugees around the world, almost half are women. These individuals experience significant stress due to language barriers, financial difficulties, poor living and working conditions, and discrimination. Consequently, concerns related to sexuality may receive lower priority despite their significant impact on overall well-being.

Objectives

This scoping review aims to review the sexual function of migrant and refugee women and identify any knowledge gaps in the field.

Methods

We conducted a scoping review following the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews). We searched online databases—Medline, Embase, Emcare, PsycINFO, CINAHL, Scopus, Web of Science, and Cochrane—and gray literature, with no restrictions on year of publication, language, or study design. Utilizing Covidence software, 2 authors screened and extracted data from studies based on predetermined eligibility criteria. A thematic analysis was executed, and findings were reported descriptively.

Results

Initially, we identified 5615 studies; after screening titles, abstracts, and full texts, we ultimately included 12 studies. The review identified a limited body of research with various unvalidated tools. Moreover, these studies yielded heterogeneous results: migrant women reported less sexual knowledge, experience, and liberal attitudes, resulting in lower rates of desire and arousal as compared with nonmigrants. Some studies showed lower sexual function in migrants, while others found no significant differences between migrants and nonmigrants. The assimilation into Western cultures may influence migrants’ sexual attitudes and behaviors. Factors such as education and gender role ideology can also significantly affect sexual function among migrant populations.

Conclusion

This review underscores the limitations in previous sexual function research, emphasizing the need for a more inclusive approach. It also offers valuable insights for codesigning programs to address sexual dysfunction among migrant and refugee women, improving their well-being. Future research should prioritize neglected populations and create culturally sensitive interventions to reduce sexual health disparities in migrants.
Factors Associated With the Maintenance of Cost-effectiveness at Five Years in Adult Spinal Deformity Corrective Surgery
Authors: Passias Peter G. , Mir Jamshaid M. , Dave Pooja , Smith Justin S. , Lafage Renaud , Gum Jeffrey , Line Breton G. , Diebo Bassel , Daniels Alan H. , Hamilton David Kojo , Buell Thomas J. , Scheer Justin K. , Eastlack Robert K. , Mullin Jeffrey P. , Mundis Gregory M. , Hosogane Naobumi , Yagi Mitsuru , Schoenfeld Andrew J. , Uribe Juan S. , Anand Neel , Mummaneni Praveen V. , Chou Dean , Klineberg Eric O. , Kebaish Khaled M. , Lewis Stephen J. , Gupta Munish C. , Kim Han Jo , Hart Robert A. , Lenke Lawrence G. , Ames Christopher P. , Shaffrey Christopher I. , Schwab Frank J. , Lafage Virginie , Hostin Richard A. , Bess Shay , Burton Douglas C. ,   on behalf of the International Spine Study Group
Published: March 2024

Study Design.

Retrospective cohort.

Objective.

To evaluate factors associated with the long-term durability of cost-effectiveness (CE) in ASD patients.

Background.

A substantial increase in costs associated with the surgical treatment for adult spinal deformity (ASD) has given precedence to scrutinize the value and utility it provides.

Methods.

We included 327 operative ASD patients with five-year (5 yr) follow-up. Published methods were used to determine costs based on CMS.gov definitions and were based on the average DRG reimbursement rates. The utility was calculated using quality-adjusted life-years (QALY) utilizing the Oswestry Disability Index (ODI) converted to Short-Form Six-Dimension (SF-6D), with a 3% discount applied for its decline in life expectancy. The CE threshold of $150,000 was used for primary analysis.

Results.

Major and minor complication rates were 11% and 47%, respectively, with 26% undergoing reoperation by five years. The mean cost associated with surgery was $91,095±$47,003, with a utility gain of 0.091±0.086 at one years, QALY gained at 2 years of 0.171±0.183, and at five years of 0.42±0.43. The cost per QALY at two years was $414,885, which decreased to $142,058 at five years.

With the threshold of $150,000 for CE, 19% met CE at two years and 56% at five years. In those in which revision was avoided, 87% met cumulative CE till life expectancy. Controlling analysis depicted higher baseline CCI and pelvic tilt (PT) to be the strongest predictors for not maintaining durable CE to five years [CCI OR: 1.821 (1.159–2.862), P=0.009] [PT OR: 1.079 (1.007–1.155), P=0.030].

Conclusions.

Most patients achieved cost-effectiveness after four years postoperatively, with 56% meeting at five years postoperatively. When revision was avoided, 87% of patients met cumulative cost-effectiveness till life expectancy. Mechanical complications were predictive of failure to achieve cost-effectiveness at two years, while comorbidity burden and medical complications were at five years.
N-Acetylcysteine to Reduce Mortality for Patients Requiring Cardiac Catheterization or Cardiac Surgery: A Systematic Review and Meta-analysis
Authors: Gakuba Clement , Dumitrascu Alexandru-Daniel , Marsan Pierre-Emmanuel , Legallois Damien , Hanouz Jean-Luc , Vivien Denis , Martinez de Lizarrondo Sara , Gauberti Maxime , Cerasuolo Damiano
Published: March 2024

Multimers of von Willebrand factor play a critical role in various processes inducing morbidity and mortality in cardiovascular-risk patients. With the ability to reduce von Willebrand factor multimers, N-acetylcysteine (NAC) could reduce mortality in patients undergoing coronary catheterization or cardiac surgery. However, its impact in perioperative period has never been studied so far in regard of its potential cardiovascular benefits. Then, 4 databases were searched for randomized controlled trials that compared in-hospital mortality between an experimental group, with NAC, and a control group without NAC, in patients undergoing coronary catheterization or cardiac surgery. The primary efficacy outcome was in-hospital mortality. Secondary outcomes were the occurrence of thrombotic events, major cardiovascular events, myocardial infarction, and contrast-induced nephropathy. The safety outcome was occurrence of hemorrhagic events. Nineteen studies totaling 3718 patients were included. Pooled analysis demonstrated a reduction of in-hospital mortality associated with NAC: odds ratio, 0.60; 95% confidence interval, 0.39–0.92; P = 0.02. The occurrence of secondary outcomes was not significantly reduced with NAC except for contrast-induced nephropathy. No difference was reported for hemorrhagic events. Subgroup analyses revealed a life-saving effect of NAC in a dose-dependent manner with reduction of in-hospital mortality for the NAC high-dose group, but not for the NAC standard-dose (<3500-mg) group. In conclusion, without being able to conclude on the nature of the mechanism involved, our review suggests a benefit of NAC in cardiovascular-risk patients in perioperative period in terms of mortality and supports prospective confirmatory studies.
Berberine alleviates concanavalin A–induced autoimmune hepatitis in mice by modulating the gut microbiota
Authors: Yang Hao , Liu Qingqing , Liu Haixia , Kang Xing , Tian Haixia , Kang Yongbo , Li Lin , Yang Xiaodan , Ren Peng , Kuang Xiaoyu , Wang Xiaohui , Guo Linzhi , Tong Mingwei , Ma Jieqiong , Fan Weiping
Published: March 2024

Background:

Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology accompanied by intestinal dysbiosis and a damaged intestinal barrier. Berberine (BBR) is a traditional antibacterial medicine that has a variety of pharmacological properties. It has been reported that BBR alleviates AIH, but relevant mechanisms remain to be fully explored.

Methods:

BBR was orally administered at doses of 100 mg⋅kg−1⋅d−1 for 7 days to mice before concanavalin A–induced AIH model establishment. Histopathological, immunohistochemical, immunofluorescence, western blotting, ELISA, 16S rRNA analysis, flow cytometry, real-time quantitative PCR, and fecal microbiota transplantation studies were performed to ascertain BBR effects and mechanisms in AIH mice.

Results:

We found that liver necrosis and apoptosis were decreased upon BBR administration; the levels of serum transaminase, serum lipopolysaccharide, liver proinflammatory factors TNF-α, interferon-γ, IL-1β, and IL-17A, and the proportion of Th17 cells in spleen cells were all reduced, while the anti-inflammatory factor IL-10 and regulatory T cell proportions were increased. Moreover, BBR treatment increased beneficial and reduced harmful bacteria in the gut. BBR also strengthened ileal barrier function by increasing the expression of the tight junction proteins zonula occludens-1 and occludin, thereby blocking lipopolysaccharide translocation, preventing lipopolysaccharide/toll-like receptor 4 (TLR4)/ NF-κB pathway activation, and inhibiting inflammatory factor production in the liver. Fecal microbiota transplantation from BBR to model mice also showed that BBR potentially alleviated AIH by altering the gut microbiota.

Conclusions:

BBR alleviated concanavalin A–induced AIH by modulating the gut microbiota and related immune regulation. These results shed more light on potential BBR therapeutic strategies for AIH.
Clinical Evaluation of the Alinity m STI Multiplex PCR Assay
Authors: Lima Amorce , Uy Dominic , Kostera Joshua , Silbert Suzane
Published: March 2024

Background

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are routinely tested and reported; however, Trichomonas vaginalis (TV) is the most common sexually transmitted infection (STI) in the United States and the prevalence of Mycoplasma genitalium (MG) infections is likely higher than estimated. We examined the clinical performance of the Alinity m STI assay for detection and surveillance of CT/NG/TV/MG in urine specimens from patients at a large academic medical center.

Methods

Urine specimen from 198 patients was tested in this evaluation. Alinity m STI and Aptima Combo 2 CT/NG and TV assay (Panther System) results were compared, with discrepant results run on the cobas 6800 CT/NG, TV/MG assays. Analyzer turnaround times, time from loading the specimen on the analyzer to results reporting, were determined for Alinity m and Panther systems.

Results

Overall percent agreements of the Alinity m in comparison with the Aptima and cobas assays for CT, NG, TV, and MG were 99.5% (97.2%, 99.9%), 99.5% (97.2%, 99.9%), 98.4% (95.5%, 99.5%), and 86.4% (66.7%, 95.3), respectively. There were 5 discrepant samples (CT, 1; NG, 1; TV, 3) between the Alinity m and the Aptima assays, and 3 MG discrepant samples between the Alinity m STI and cobas 6800. Two of the 5 Aptima and Alinity m discrepant samples were resolved as they yielded similar results on both Alinity m and cobas 6800. TV and MG infections comprised 54% of the positive samples and were more often asymptomatic than CT and NG infections. Analyzer turnaround time was 3 hours 25 minutes for the Aptima CT/NG, 3 hours 25 minutes for Aptima TV, and 1 hour 55 minutes for Alinity m STI assay.

Conclusions

The Alinity m STI assay allows for fast and simultaneous detection of the 4 major STI pathogens, which can facilitate surveillance and provide accurate results to help clinicians diagnose for initiation of appropriate treatment.
Changing Stimulation Frequency Improves Implanted Peripheral Nerve Stimulator Effects Following Post-Traumatic Total Hip Arthroplasty: A Case Report
Authors: Pierson Chris J. , Velez Natalie , Jain Nitin B. , Konda Chaitanya
Published: March 2024

Total hip arthroplasty (THA) is an effective procedure to improve pain, range of motion, and function for a variety of conditions, including osteoarthritis and post-traumatic arthritis. Up to 28% of patients had persistent pain at the surgical site 12 to 18 months following THA, even in the absence of surgical complications. Currently, there are no widely accepted non-pharmacological treatments for persistent postoperative pain for THA. This case report details the successful management of a 53-year-old man with chronic pain and weakness following post-traumatic THA. He was initially treated with a single-lead percutaneous peripheral nerve stimulator near the right femoral nerve for four weeks with 100 Hz frequency sensory-level parameters. Four weeks after implantation, the frequency was changed to 12 Hz with a goal of motor-level stimulation. During the following three-week time period, his hip flexion strength improved from 10.36 kg to 23.04 kg. His Lower Extremity Functional Scale improved from 35/80 (43.75%) to 54/80 (67.5%) within a five-week time period. This case’s success demonstrates how PNS may help improve post-operative persistent pain and weakness in many patients, including those with post-traumatic arthroplasty.
Inflammatory markers in pregnancy are associated with postpartum weight in South African women living with HIV on antiretroviral therapy
Authors: Madlala Hlengiwe P. , Myer Landon , Geffen Hayli , Rusch Jody , Shey Muki S. , Meyer Demi , Goedecke Julia H. , Malaba Thokozile R. , Gray Clive M. , Newell Marie-Louise , Jao Jennifer
Published: March 2024

Background:

Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH.

Setting:

A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included.

Methods:

Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks.

Results:

Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain.

Conclusion:

These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.
18F-Florbetapir PET/CT and 68Ga-FAPI PET/CT in a Case of Light Chain Amyloidosis With Predominant Multiple Tumor-Like Deposits
Authors: Zhang Yuke , Wang Xuezhu , Ren Chao , Shen Kaini , Huo Li
Published: March 2024

A 66-year-old man presented with multiple masses in different regions, including the left groin, back subcutaneous area, and lungs. Pathological examination confirmed localized amyloid deposits after 3 surgeries. Serum-free λ light chains were elevated. To evaluate systemic involvement, the patient underwent 18F-Florbetapir PET/CT and 68Ga-FAPI-04 PET/CT. Both scans showed increased uptake in multiple masses and nodules throughout the body. This report presents a rare case of light chain (AL) amyloidosis, primarily characterized by multiple localized tumor-like deposits with high activity on 18F-Florbetapir PET/CT and 68Ga-FAPI-04 PET/CT.
Making Moral Decisions With Artificial Agents As Advisors. AnfNIRS Study
Authors: Fabre Eve Florianne , Mouratille Damien , Bonnemains Vincent , Palmiotti Grazia Pia , Causse Mickael
Published: March 2024

Artificial Intelligence (AI) is on the verge of impacting every domain of our lives. It is increasingly being used as an advisor to assist in making decisions. The present study aimed at investigating the influence of moral arguments provided by AI-advisors (i.e., decision aid tool) on human moral decision-making and the associated neural correlates. Participants were presented with sacrificial moral dilemmas and had to make moral decisions either by themselves (i.e., baseline run) or with AI-advisors that provided utilitarian or deontological arguments (i.e., AI-advised run), while their brain activity was measured using anfNIRS device. Overall, AI-advisors significantly influenced participants. Longer response times and a decrease in right dorsolateral prefrontal cortex activity were observed in response to deontological arguments than to utilitarian arguments. Being provided with deontological arguments by machines appears to have led to a decreased appraisal of the affective response to the dilemmas. This resulted in a reduced level of utilitarianism, supposedly in an attempt to avoid behaving in a less cold-blooded way than machines and preserve their (self-)image. Taken together, these results suggest that motivational power can led to a voluntary up- and down- regulation of affective processes along moral decision-making.
Optimal Placement of High-Channel Visual Prostheses in Human Retinotopic Visual Cortex
Authors: van Hoof Rick , Lozano Antonio , Wang Feng , Klink P. Christiaan , Roelfsema Pieter R. , Goebel Rainer
Published: March 2024

Abstract

Objective

Recent strides in neurotechnology show potential to restore vision in individuals afflicted with blindness due to early visual pathway damage. As neuroprostheses mature and become available to a larger population, manual placement and evaluation of electrode designs becomes costly and impractical. An automatic method to optimize the implantation process of electrode arrays at large-scale is currently lacking.

Approach

Here, we present a comprehensive method to automatically optimize electrode placement for visual prostheses, with the objective of matching pre-defined phosphene distributions. Our approach makes use of retinotopic predictions combined with individual anatomy data to minimize discrepancies between simulated and target phosphene patterns. While demonstrated with a 1000-channel 3D electrode array in V1, our pipeline is versatile, potentially accommodating any electrode design and allowing for design evaluation.

Main results

Notably, our results show that individually optimized placements in 362 brain hemi-spheres outperform average brain solutions, underscoring the significance of anatomical specificity. We further show how virtual implantation of multiple individual brains highlights the challenges of achieving full visual field coverage owing to single electrode constraints, which may be overcome by introducing multiple arrays of electrodes. Including additional surgical considerations, such as intracranial vasculature, in future iterations could refine the optimization process.

Significance

Our open-source software streamlines the refinement of surgical procedures and facilitates simulation studies, offering a realistic exploration of electrode configuration possibilities.
DeST-OT: Alignment of Spatiotemporal Transcriptomics Data
Authors: Halmos Peter , Liu Xinhao , Gold Julian , Chen Feng , Ding Li , Raphael Benjamin J.
Published: March 2024

Spatially resolved transcriptomics (SRT) measures mRNA transcripts at thousands of locations within a tissue slice, revealing spatial variations in gene expression and distribution of cell types. In recent studies, SRT has been applied to tissue slices from multiple timepoints during the development of an organism. Alignment of thisspatiotemporaltranscriptomics data can provide insights into the gene expression programs governing the growth and differentiation of cells over space and time. We introduceDeST-OT(DevelopmentalSpatioTemporalOptimalTransport), a method to align SRT slices from pairs of developmental timepoints using the framework of optimal transport (OT).DeST-OTusessemi-relaxedoptimal transport to precisely model cellular growth, death, and differentiation processes that are not well-modeled by existing alignment methods. We demonstrate the advantage ofDeST-OTon simulated slices. We further introduce two metrics to quantify the plausibility of a spatiotemporal alignment: agrowth distortion metricwhich quantifies the discrepancy between the inferred and the true cell type growth rates, and amigration metricwhich quantifies the distance traveled between ancestor and descendant cells.DeST-OToutperforms existing methods on these metrics in the alignment of spatiotemporal transcriptomics data from the development of axolotl brain.

Code availability

Software is available athttps://github.com/raphael-group/DeST_OT
Two new qPCR assays for detecting and quantifying theAspergillus flavusandAspergillus parasiticusclades in maize kernels
Authors: Leharanger A. , Paumier D. , Orlando B. , Bailly S. , Valade R.
Published: March 2024

The fungi ofAspergillussectionFlavimostly produce carcinogenic mycotoxins — aflatoxins (AFs) — of two types: types B and G (AFBs and AFGs). AF are highly hazardous for human and animal health. Their levels in food and feed are therefore highly regulated, with a low acceptable limit for AF content. In France, global warming has led to the detection of AFs in maize harvests since 2015. Mycoflora analyses have identified two species,A. flavus(producing AFBs) andA. parasiticus(producing both AFBs and AFGs), as responsible for this AF contamination. However, mycoflora analysis is a time-consuming method that cannot readily be applied to large numbers of samples. We propose here an alternative clade-specific functional TaqMan® qPCR method based on the calmodulin gene for distinguishing between theA. flavusclade (AfC) and theA. parasiticusclade (ApC). We applied this method to 553 maize samples collected in three different harvest years (2018 to 2020). Both clades were detected in about 40% of the samples tested. As expected, we observed significant positive correlations between AFBs and AfC DNA (R² =0.708), and between AFGs and ApC DNA (R² =0.885). This method will be useful for the rapid, simple and cheap characterisation of maize grain contamination withAspergillussectionFlavi. This method will make it possible to study the relationship between agroclimatic conditions, AF content and species prevalence, to facilitate the anticipation of AF risks due to global warming in France.
OligoY pipeline for full Y chromosome painting
Authors: Almeida Isabela , Bonilla Bruno Henry Angel , Lisboa Santana Pinheiro Mara Maria , Bernardo Carvalho Antonio , Vibranovski Maria Dulcetti
Published: March 2024

Motivation

The standard protocol for designing probes used in full chromosome fluorescent labeling experiments does not include repetitive sequences to avoid off-target hybridization. Due to the Y chromosome’s highly repetitive nature, most assembly nowadays still have heavily fragmented and incomplete Y sequences. Among these, the remaining non-repetitive sequences are insufficient to design probes and efficiently perform FISH Oligopaint assays, since they do not cover most regions of the chromosome. Ergo, cytogenetic studies with the Y are sparse, and analysis such as its function throughout the cell cycle and insights into its evolutionary history and relationships with other regions of the genome remain poorly studied.

Results

In this work, we introduce a new pipeline for designing FISH Oligopaint probes for the Y chromosome of any species of interest. OligoY pipeline uses open-source tools, enriches the amount of contigs assigned to the Y chromosome from the draft assembly, and effectively uses repetitive sequences unique to the target chromosome to design probes. Throughout all of its steps, the pipeline guarantees the user the autonomy to choose parameters, thus maximizing overall efficiency of cytogenetic experiments. After extensive in silico andin situtests and validations withDrosophila melanogaster, we showed for the first time a pipeline for probe design that significantly increases previous Y chromosome staining with no off-target signal.

Availability

The pipeline is available athttps://github.com/isabela42/OligoY.
Genetics-driven Risk Predictions with Differentiable Mendelian Randomization
Authors: Sens Daniel , Gräf Ludwig , Shilova Liubov , Casale Francesco Paolo
Published: March 2024

Accurate predictive models of future disease onset are crucial for effective preventive healthcare, yet longitudinal datasets linking early risk factors to subsequent health outcomes are scarce. To address this challenge, we introduce Differentiable Mendelian Randomization (DMR), an extension of the classical Mendelian Randomization framework to learn risk predictors without longitudinal data. To do so, DMR leverages risk factors and genetic data from a healthy cohort, along with results from genome-wide association studies (GWAS) of diseases of interest. After training, the learned predictor can be used to assess risk for new patients solely based on risk factors. We validated DMR through comprehensive simulations and in future type 2 diabetes predictions in UK Biobank participants without diabetes, using follow-up onset labels for validation. Finally, we apply DMR to predict future Alzheimer’s onset from brain imaging biomarkers. Overall, with DMR we offer a new perspective in predictive modeling, showing it is possible to learn risk predictors leveraging genetics rather than longitudinal data.
Acute, chronic and conditioned effects of intranasal oxytocin in the mu opioid receptor knockout mouse model of autism: social context matters
Authors: Pantouli Fani , Pujol Camille , Derieux Cécile , Fonteneau Mathieu , Pellissier Lucie P , Marsol Claire , Karpenko Julie , Bonnet Dominique , Hibert Marcel , Bailey Alexis , Merrer Julie Le , Becker Jerome AJ
Published: March 2024

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behaviours. Multiple studies have highlighted the potential of oxytocin (OT) to ameliorate behavioural abnormalities in animal models and subjects with ASD. Clinical trials, however, yielded disappointing results. Our study aimed at challenging hypotheses accounting for such negative results by assessing the behavioural effects of different regimens of OT administration in theOprm1null mouse model of ASD. We assessed the effects of intranasal OT injected once at different doses and time points following administration, or chronically, on ASD-related behaviours inOprm1+/+and Oprm1-/-mice. We then tested whether pairing intranasal OT injection with social experience would influence its outcome on ASD-like core symptoms, and measured gene expression in several regions of the reward/social circuit. Acute intranasal OT improved social behaviour inOprm1-/-mice at a moderate dose (0.3 IU) shortly after administration (5 min). Effects on non-social behaviours were limited. Chronic OT at this dose maintained beneficial effects inOprm1null mice but was deleterious in wild-type mice. Finally, improvements in the social behaviour ofOprm1-/-mice were greater and longer lasting when OT was administered in a social context, while the expression of OT and vasopressin receptor genes, as well as marker genes of striatal projection neurons, was suppressed. Our results highlight the importance of considering dosage and social context when evaluating the effects of OT treatment in ASD.

Highlights

Acute intranasal oxytocin improved social behaviour shortly after administration

Effects of oxytocin on non-social behaviours were limited

Chronic oxytocin maintained beneficial effects in mutant mice but was deleterious in wild-type mice

Oxytocin triggers greater and longer-lasting improvements in social behaviour when administered within a social context

Chronic oxytocin suppresses the expression of its own receptor gene and key striatal neuron gene markers
metaRange: A framework to build mechanistic range models
Authors: Fallert Stefan , Li Lea , Sarmento Cabral Juliano
Published: March 2024

1

Mechanistic or process-based models offer great insights into the range dynamics of species facing non-equilibrium conditions, such as climate and land-use changes or invasive species. Their consideration of underlying mechanisms relaxes the species-environment equilibrium assumed by correlative approaches, while also generating conservation-relevant indicators, such as range-wide abundance time-series and migration rates if demographically explicit. However, the computational complexity of mechanistic models limits their development and applicability to large spatiotemporal extents.

We developed the R package ‘metaRange’ that is a modular framework to build population-based and metabolically constrained range models. It provides a function catalogue for users to calculate niche-based suitability, metabolic scaling, population dynamics, biotic interactions, and kernel-based dispersal, which may include directed movement. The framework’s modularity enables the user to combine, extend, or replace these functions, making it possible to customize the model to the ecology of the study system. The package supports an unlimited number of static or dynamic environmental factors as input, including climate and land use.

As an example, we simulated 100 virtual species in Germany on a 1 km2resolution over 110 years under realistic environmental fluctuations in three scenarios: without competition, with competition, and with competition and a generalist-specialist trade-off. The results are in accordance with theoretical expectations. Due to the population-level, the package can execute such extensive simulation experiments on regular enduser hardware in a short amount of time. We provide detailed technical documentation, both for the individual functions in the package as well as instructions on how to set up different types of model structures and experimental designs.

The metaRange framework enables process-based simulations of range dynamic of multiple interacting species on a high resolution and low computational demand. We believe that it allows for theoretical insights and hypotheses testing about future range dynamics of real-world species, which may better support conservation policies targeting biodiversity loss mitigation.