bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utero-placental expression and functional implications of HSD11B1 and HSD11B2 in canine pregnancy
Authors: Tavares Pereira Miguel , Schuler Gerhard , Aslan Selim , Payan-Carreira Rita , Reichler Iris M , Reynaud Karine , Kowalewski Mariusz P 
Published: February 2023

AbstractGlucocorticoids modulate the feto-maternal interface during the induction of parturition. In the dog, the prepartum rise of cortisol in the maternal circulation appears to be erratic, and information about its contribution to the prepartum luteolytic cascade is scarce. However, the local placental upregulation of glucocorticoid receptor (GR/NR3C1) at term led to the hypothesis that species-specific regulatory mechanisms might apply to the involvement of cortisol in canine parturition. Therefore, here, we assessed the canine uterine/utero-placental spatio-temporal expression of hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1; reduces cortisone to cortisol), and -2 (HSD11B2; oxidizes cortisol to the inactive cortisone). Both enzymes were detectable throughout pregnancy. Their transcriptional levels were elevated following implantation, with a strong increase in HSD11B2 post-implantation (days 18–25 of pregnancy), and in HSD11B1 at mid-gestation (days 35–40) (P &lt; 0.05). Interestingly, when compared pairwise, HSD11B2 transcripts were higher during post-implantation, whereas HSD11B1 dominated during mid-gestation and luteolysis (P &lt; 0.05). A custom-made species-specific antibody generated against HSD11B2 confirmed its decreased expression at prepartum luteolysis. Moreover, in mid-pregnant dogs treated with aglepristone, HSD11B1 was significantly higher than −2 (P &lt; 0.05). HSD11B2 (protein and transcript) was localized mostly in the syncytiotrophoblast, whereas HSD11B1 mRNA was mainly localized in cytotrophoblast cells. Finally, in a functional approach using placental microsomes, a reduced conversion capacity to deactivate cortisol into cortisone was observed during prepartum luteolysis, fitting well with the diminished HSD11B2 levels. In particular, the latter findings support the presence of local increased cortisol availability at term in the dog, contrasting with an enhanced inactivation of cortisol during early pregnancy.
iCre recombinase expressed in the anti-Müllerian hormone receptor 2 gene causes global genetic modification in the mouse
Authors: Dickson Mackenzie J , Gruzdev Artiom , DeMayo Francesco J 
Published: February 2023

AbstractGenetically engineered mice are widely used to study the impact of altered gene expression in vivo. Within the reproductive tract, the Amhr2-IRES-Cre(Bhr) mouse model is used to ablate genes in ovarian granulosa and uterine stromal cells. There are reports of Amhr2-IRES-Cre(Bhr) inducing recombination in non-target tissues. We hypothesized the inefficiency or off-target Cre action in Amhr2-IRES-Cre(Bhr) mice is due to lack of recombination in every cell that expresses Amhr2. To investigate, we created a new targeted knock-in mouse model, Amhr2-iCre(Fjd), by inserting a codon-optimized improved Cre (iCre) into exon 1 of the Amhr2 gene. Amhr2-iCre(Fjd)/+ males were mated with females that contain a lox-stop-lox cassette in the Sun1 gene so when DNA recombination occurs, SUN1-sfGFP fusion protein is expressed in a peri-nuclear pattern. In adult Amhr2-iCre(Fjd)/+ Sun1LsL/+ mice, Amhr2-iCre(Fjd)-mediated genetic recombination was apparent in uterine epithelial, stromal, and myometrial cells, while Amhr2-IRES-Cre(Bhr)/+ Sun1LsL/+ females demonstrated inter-mouse variability of Amhr2-IRES-Cre(Bhr) activity in uterine cells. Fluorescence was observed in Amhr2-iCre(Fjd)-positive mice at post-natal Day 1, indicating global genetic recombination, while fluorescence of individual Amhr2-IRES-Cre(Bhr)-positive pups varied. To determine the developmental stage that genetic recombination first occurs, Sun1LsL/LsL females were super-ovulated and mated with Amhr2-IRES-Cre(Bhr)/+ or Amhr2(iCre/+)Fjd males, then putative zygotes were collected and cultured. In the four-cell embryo, Amhr2-iCre(Fjd) and Amhr2-IRES-Cre(Bhr) activities were apparent in 100% and 25–100% of cells, respectively. In conclusion, Amhr2-IRES-Cre(Bhr) or Amhr2-iCre(Fjd) driven by the Amhr2 promoter is active in the early embryo and can lead to global genetic modification, rendering this transgenic mouse model ineffective.
Karyotypic diversity: a neglected trait to explain angiosperm diversification?
Authors: Carta Angelino , Escudero Marcial 
Published: February 2023

AbstractEvolutionary changes in karyotype provide genetic support to organisms’ differentiation and adaptation; however, the association between karyotype diversity and species diversification in flowering plants (angiosperms) remains to be fully elucidated. We sought evidence for this association within a phylogenetic framework using a dataset comprising &gt; 413,000 worldwide chromosome counts of 66,000 angiosperms species. Karyotypic diversity (e.g., number of distinct chromosome numbers) explains species richness and diversification rates at both family and genus levels highlighting that chromosome evolution has probably played, at least, an important role in reinforcing speciation that was already initiated or completed by other geographical or ecological drivers. Thus, research programs investigating chromosome variation as a direct or indirect driver of diversification should be encouraged.
Transcriptomic analysis provides insight into the mechanism of IKKβ-mediated suppression of HPV18E6-induced cellular abnormalities
Authors: Collins Quincy P , Grunsted Michael J , Arcila Dahiana , Xiong Yi , Padash Barmchi Mojgan 
Published: February 2023

Abstract
High-risk human papillomaviruses (HPVs) 16 and 18 are responsible for more than 70% of cervical cancers and majority of other HPV-associated cancers world-wide. Current treatments for these cancers have limited efficacy, which in turn has resulted in disease recurrence and poor survival rates in advanced disease stages. Hence, there is a significant need for development of novel molecularly-targeted therapeutics. This can only be achieved through improved understanding of disease mechanism. Recently, we developed a Drosophila model of HPV18E6 plus human E3 ubiquitin ligase (hUBE3A) and demonstrated that the E6-induced cellular abnormalities are conserved between humans and flies. Subsequently, we demonstrated that reduced level and activity of IKKβ, a regulator of NF-κB, suppresses the cellular abnormalities induced by E6 oncoprotein and that the interaction of IKKβ and E6 is conserved in human cells. In this study, we performed transcriptomic analysis to identify differentially expressed genes that play a role in IKKβ-mediated suppression of E6-induced defects. Transcriptome analysis identified 215 genes whose expression was altered due to reduced levels of IKKβ. Of these 215 genes, 151 genes showed annotations. These analyses were followed by functional genetic interaction screen using RNAi, overexpression, and mutant fly strains for identified genes. The screen identified several genes including genes involved in Hippo and Toll pathways as well as junctional complexes whose downregulation or upregulation resulted in alterations of E6-induced defects. Subsequently, RT-PCR analysis was performed for validation of altered gene expression level for a few representative genes. Our results indicate an involvement for Hippo and Toll pathways in IKKβ-mediated suppression of E6 + hUBE3A-induced cellular abnormalities. Therefore, this study enhances our understanding of the mechanisms underlying HPV-induced cancer and can potentially lead to identification of novel drug targets for cancers associated with HPV.
Application of Dried Urine Spots for Non-Targeted Quadrupole Time-of-Flight Drug Screening
Authors: Stöth Frederike , Martin Fabritius Marie , Weinmann Wolfgang , Luginbühl Marc , Gaugler Stefan , König Stefan 
Published: February 2023

Abstract
The use of dried urine spots (DUS) can simplify sample handling, shipment and storage when compared to liquid urine samples. To prepare DUS, a small amount of urine is pipetted on a filter paper card. The subsequent drying of the specimen can prevent the post-sampling formation or degradation of substances (e.g., caused by bacteria). To evaluate the potential of DUS screening, 17 authentic urine samples, containing a broad range of substances, were extracted and analyzed on a Sciex TripleTOF® 5600+ System using a non-targeted screening and library searching approach. The screening results were compared to the analysis of the same urine sample in liquid form, using the same high-resolution liquid chromatography--quadrupole time-of-flight mass spectrometry method. More than 65 different legal and illegal drugs were successfully identified within the investigated 17 urine samples using the DUS screening approach. When compared to the analysis of liquid urine, the following compounds could not be identified: 1x ecgonine methyl ester, 1x nicotine, 1x promazine and 1x 11-nor-9-carboxy-∆9-tetrahydrocannabinol. Overall, 95.2% of the target substances that have been detected in liquid urine were identified correctly using the DUS approach. In conclusion, DUS screening offers a simple, cost-effective and easier sample handling alternative to the traditional use of liquid urine and provides the detection of the most important substances for forensic requirements. Furthermore, the DUS sample preparation can be fully automated (sample documentation, internal standard application and extraction).
Benign osteonecrosis of the external ear canal: case series
Authors: Chandler Kiyoshi , Hawthorne McKenna , Georgolios Alexandros 
Published: February 2023

Abstract
Benign osteonecrosis of the external ear canal is a rare pathology that commonly gets misdiagnosed as cholesteatoma of the external ear canal, keratosis obturans and malignant otitis externa. Each pathology has characteristics that allow for differentiation between them. Careful analysis is required to diagnose properly and determine the best modality of management. This case series presents two patients that were diagnosed with benign osteonecrosis of the external ear canal and is being managed conservatively with serial debridement. Response to conservative treatment has resulted in adequate control of symptoms in both patients.
Single-port laparoscopic surgery for parasitic cystic teratoma of the greater omentum and bilateral ovarian teratomas: a case report
Authors: Misawa Akihiko , Kimura Eizo , Oka Aiko , Osanai Kiyono , Suzuki Atsushi 
Published: February 2023

Abstract
Teratomas of extragonadal origin are extremely rare. The most common extragonadal site is the greater omentum. A 36-year-old woman was referred to our department for treatment of bilateral ovarian tumors. A 3- to 4-cm mass was observed in each ovary; bilateral ovarian mature cystic teratoma was diagnosed through imaging studies. The patient underwent single-port laparoscopic surgery, during which we found not only bilateral ovarian mature cystic teratomas but also an omental tumor macroscopically similar to the ovarian teratomas. The ovarian and omental teratomas were successfully removed through single-port laparoscopic surgery. The histopathological diagnosis of the omental tumor was parasitic mature cystic teratoma.
Efficacy of Conservative Interventions for Musculoskeletal Conditions on Pain and Disability in Active Serving Military Personnel—A Systematic Review
Authors: Bounds Courtney L , Coppieters Michel W , Thomson Hayley W , Larsen Brianna , Evans Kerrie 
Published: February 2023

ABSTRACT

Introduction
Musculoskeletal (MSK) injuries and associated pain disorders are one of the leading causes for soldiers not being medically fit for deployment, impacting force capability and readiness. Musculoskeletal pain continues to be a leading cause of disability within military services and is associated with a substantial financial burden. A better understanding of the effectiveness of MSK pain management strategies is required. This review was designed to determine the efficacy of nonsurgical interventions, such as physiotherapy, exercise, pharmacology, and multidisciplinary programs, to manage MSK conditions in active serving military populations.

Materials and Methods
MEDLINE, Embase, CINAHL, and SPORTDiscus were searched to identify relevant randomized clinical trials. Recommended methods were used for article identification, selection, and data extraction. The Cochrane Risk of Bias tool and the Grade of Recommendation, Assessment, Development, and Evaluation were used to appraise the studies. Where possible, meta-analyses were performed. The review was conducted according to the PRISMA guidelines.

Results
Nineteen articles (1,408 participants) met the eligibility criteria. Low back pain (LBP) was the most frequently investigated condition, followed by knee pain, neck pain, and shoulder pain. Early physiotherapy, exercise and adjunct chiropractic manipulation (for LBP), and multidisciplinary pain programs (physiotherapy, occupational therapy, and psychology) (for chronic MSK pain) improved pain (standardized mean difference ranged from −0.39 to −1.34; low strength of evidence). Participation in multidisciplinary pain programs, adjunct chiropractic manipulation, and early physiotherapy improved disability (for LBP) (standardized mean difference ranged from −0.45 to −0.86; low to very low strength of evidence). No studies evaluated pain medication. Dietary supplements (glucosamine, chondroitin sulfate, and manganese ascorbate), electrotherapy, isolated lumbar muscle exercises, home cervical traction, or training in virtual reality showed no benefit. The studies had a high risk of bias, were typically underpowered, and demonstrated high clinical heterogeneity.

Conclusions
Currently available randomized clinical trials do not provide sufficient evidence to guide military organizations or health care professionals in making appropriate treatment decisions to manage MSK pain in active serving military personnel. Future research is essential to enable evidence-based recommendations for the effective management of MSK pain conditions in this unique population.
Perspectives on Health With Spinal Cord Injury Now and in the Future: A Qualitative Descriptive Study
Authors: Baehr Laura A , Fisher Kathleen , Finley Margaret 
Published: February 2023

Abstract

Objective
Over the past half century, the landscape of life and aging with spinal cord injury (SCI) has changed drastically, in part due to medical advancements and the rapidly increasing aging population. With these changes comes a critical need for rehabilitation professionals to understand aging with SCI in relation to strategies that support health maintenance over time. The purpose of this study was to identify and describe the meaning of health maintenance and aging outlook from the perspectives of individuals living with SCI.

Methods
A qualitative descriptive approach using focus group interviews and thematic analysis was used to generate a rich understanding of shared experiences with SCI by allowing for discussion among participants.

Results
Participants were 24 individuals ranging in age from 22 to 76 years who were living with chronic SCI (&gt;12 months), with injury duration ranging from 3 to 47 years. Health maintenance was connected to 3 themes: self-management routine to prevent secondary health conditions; importance of injury acceptance over time; and engagement with disability networks. Aging outlook was linked to fear of functional dependence and lack of evidence-based education on aging with SCI.

Conclusion
These findings suggest that individuals living with SCI would benefit from clinical support that acknowledges psychological and social aspects of health beyond physical routines.

Impact
These findings inform the development and implementation of SCI-related interventions to maximize healthy aging. It is crucial for clinicians and researchers to investigate issues beyond routine self-management and functional independence to support the emotional adjustment of life with SCI. Unique personal considerations based on life stage when injured warrant investigation. Education and advocacy for peer support is imperative at all life stages given its positive impact on health.
Small-molecule screening in aged Drosophila identifies mGluR as a regulator of age-related sleep impairment
Authors: Hou Xue , Hayashi Reina , Itoh Motoyuki , Tonoki Ayako 
Published: February 2023

Abstract
As a normal physiological phenomenon, aging has a significant impact on sleep. Aging leads to sleep impairment, including sleep loss, fragmented sleep, and a lower arousal threshold, leading to various diseases. Because sleep regulates memory consolidation, age-dependent sleep impairment also affects memory. However, the mechanisms underlying age-related sleep dysregulation and its impact on memory remain unclear. Using male and female Drosophila as a model, which possesses sleep characteristics similar to those of mammals and exhibits age-dependent sleep impairment, we performed small-molecule screening to identify novel regulators of age-dependent decline in sleep. The screening identified 3,3ʹ-difluorobenzaldazine (DFB), a positive allosteric modulator of the metabotropic glutamate receptor (mGluR) 5, as a novel sleep-promoting compound in aged flies. We found that mutant flies of mGluR, a single mGluR gene in Drosophila, and decreased mGluR expression had significant impairment in sleep and memory due to olfactory conditioning. The decreased sleep phenotype in the mGluR mutants was not promoted by DFB, suggesting that the effects of DFB on age-dependent sleep impairment are dependent on mGluR. Although aging decreases the expression of mGluR and the binding scaffold proteins Homer and Shank, the transient overexpression of mGluR in neurons improves sleep in both young and aged flies. Overall, these findings indicate that age-dependent decreased expression or function of mGluR impairs sleep and memory in flies, which could lead to age-related sleep and memory impairment.
Taurine protects against perfluorooctanoic acid-induced hepatotoxicity via inhibition of oxidative stress, inflammatory, and apoptotic pathways
Authors: Naderi Maloos , Seyedabadi Mohammad , Amiri Fereshteh Talebpour , Mohammadi Ebrahim , Akbari Sholeh , Shaki Fatemeh 
Published: February 2023

AbstractWe are constantly encountering with low doses of chemicals in everyday life rather than toxic doses at a time. So, ongoing low-dose exposures of environmental chemicals commonly encountered are very likely to cause an adverse health effects. Perfluorooctanoic acid (PFOA) is frequently used for production of an array of consumer products and industrial processes. The present study evaluated the underlying mechanisms of PFOA-induced liver damage and also potential protection by taurine. Male Wistar rats were exposed to PFOA alone and in combination with taurine (25, 50, and 100 mg/kg/day) by gavage for 4 weeks. Liver function tests as well as histopathological examinations were studied. Also, oxidative stress markers, mitochondrial function, and nitric oxide (NO) production in liver tissues were measured. In addition, the expression of apoptosis-related genes (caspase-3, Bax, and Bcl-2), inflammation-associated genes (TNF-α, IL-6, NF-B), and c-Jun-N-terminal kinase (JNK) were evaluated. Taurine significantly reversed serum biochemical and histopathological alterations in the liver tissue following exposure to PFOA (10 mg/kg/day). Similarly, taurine alleviated mitochondrial oxidative damage-induced by PFOA in the liver tissue. An increased Bcl2: Bax ratio with decrees in the expression level of caspase-3, and decreased expression of inflammatory markers (TNF-α and IL-6), NF-B, and JNK were also observed following the administration of taurine. These findings suggest a protective role of taurine against PFOA-induced hepatotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis.
Launching telemedicine in a tertiary ambulatory pediatric orthopedic clinic during the coronavirus disease-19 pandemic: a retrospective study
Authors: Wong Cynthis , Bent Melissa A , Omar Hanna , Abousamra Oussama 
Published: February 2023

Objective
Telemedicine services increased dramaticallyduring the coronavirus disease (COVID-19) pandemic, with limited studies on its implementation within pediatric orthopedics. The goal of this study was to examine patient satisfaction and the efficacy of pediatric orthopedic telemedicine visits.

Methods
Two hundred and sixty-nine qualifying telehealth visits took place at a metropolitan area pediatric institute between 1 March and 30 May 2020. Patients were invited to complete an anonymous satisfaction survey on their telemedicine experience. Sixty-seven patients responded to the survey. A chart review was completed for all 269 telemedicine visits.

Results
Ninety-two percent (249/269) of telemedicine visits were with established patients, and 95% (256/269) of visits were satisfactorily completed without further evaluation, with one visit requiring urgent in-person evaluation. Overall, patients were satisfied with initiating the telemedicine visit (mean score of 4.56/5), as they felt comfortable discussing needs with the provider (4.68/5), and the visit saved time (4.61/5). However, patients were less enthused when deciding if telemedicine was of comparable quality to an in-person visit (3.68/5).

Conclusion
Our analysis showed that telemedicine is a viable alternative to in-person visits for various pediatric orthopedic visits, with minimal urgent complications. Patients benefited primarily from the time savings when using a telemedicine visit. However, our study also demonstrates certain limitations of telemedicine, likely due to patients’ perceived value of an in-person evaluation. Our study’s findings should encourage the continued implementation of pediatric orthopedic telemedicine as an adjunct to in-person clinical practice.
HIV and comorbidities – the importance of gut inflammation and the kynurenine pathway
Authors: MacCann Rachel , Landay Alan L. , Mallon Patrick W.G. 
Published: February 2023

Purpose of review
The purpose of this article is to review alterations in microbiota composition, diversity, and functional features in the context of chronic inflammation and comorbidities associated with HIV infection.

Recent findings
The gut microbiome is an important mediator of host immunity, and disruption of gut homeostasis can contribute to both systemic inflammation and immune activation. Ageing and HIV share features of intestinal damage, microbial translocation and alterations in bacterial composition that contribute to a proinflammatory state and development of age-related comorbidities. One such inflammatory pathway reviewed is the nicotinamide adenine dinucleotide (NAD+) producing kynurenine pathway (KP). Kynurenine metabolites regulate many biological processes including host-microbiome communication, immunity and oxidative stress and the KP in turn is influenced by the microbiome environment. Age-associated decline in NAD+ is implicated as a driving factor in many age-associated diseases, including those seen in people with HIV (PWH). Recent studies have shown that KP can influence metabolic changes in PWH, including increased abdominal adiposity and cardiovascular disease. Furthermore, KP activity increases with age in the general population, but it is elevated in PWH at all ages compared to age-matched controls. Host or microbiome-mediated targeting of this pathway has merits to increase healthy longevity and has potential therapeutic applications in PWH.

Summary
As a growing proportion of PWH age, many face increased risks of developing age-related comorbidities. Chronic inflammation, a pillar of geroscience, the science of ageing and of age-related disease, is influenced by the gut microbiome and its metabolites. Combined, these contribute to a systemic inflammatory signature. Advances in geroscience-based approaches and therapeutics offer a novel paradigm for addressing age-related diseases and chronic inflammation in HIV infection. Whether targeted inhibition of KP activity alleviates pathological conditions or promotes successful ageing in PWH remains to be determined.