bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Buprenorphine/Naloxone Low-dose Induction in Pregnancy: A Case Report
Authors: Coish Rebecca , Hardial Janine 
Published: August 2022

Background
Medication for opioid use disorder (OUD) with methadone or buprenorphine/naloxone is recommended for pregnant women with OUD. Traditional buprenorphine/naloxone induction requires patients to be in moderate withdrawal before the first dose of medication to minimize the chances of precipitated withdrawal. The low-dose buprenorphine “microinduction” (Bernese) method was described in 2016 and involves giving small doses of buprenorphine to patients for whom opioid withdrawal was not desirable. This method is being used widely in Vancouver in the context of high rates of overdose due to fentanyl poisoning.

Case Presentation
A 24-year-old woman, in her first pregnancy, with severe opioid and stimulant use disorder successfully started on buprenorphine/naloxone through a low-dose-induction protocol. The dose was started at 0.5 mg sublingual daily and slowly increased to 18 mg over 17 days. She continued to use fentanyl/heroin during the induction. She did not experience precipitated withdrawal and was able to stop using nonprescribed opioids once at a therapeutic dose of buprenorphine/naloxone.

Discussion
This represents the first documented case of successful buprenorphine/naloxone low-dose induction in pregnancy. First-line recommendations still remain to use traditional buprenorphine/naloxone induction when patients present in withdrawal. Obtaining informed consent regarding the lack of research on low-dose induction in pregnancy as well as discussion of risks and benefits is essential.

Conclusion
Low-dose induction with buprenorphine/naloxone was successfully done in an outpatient setting. This represents a novel way of initiation of medication for OUD, which may enhance choice and collaboration between health care providers and women impacted by substance use in pregnancy.
Salivary metabolome indicates a shift in tyrosine metabolism in patients with burning mouth syndrome: a prospective case–control study
Authors: Moreau Charlotte , El Habnouni Chakib , Lecron Jean-Claude , Morel Franck , Delwail Adriana , Le Gall-Ianotto Christelle , Le Garrec Raphaele , Misery Laurent , Piver Eric , Vaillant Loïc , Lefevre Antoine , Emond Patrick , Blasco Hélène , Samimi Mahtab 
Published: August 2022

Abstract
The pathophysiology of primary burning mouth syndrome (BMS) remains controversial. Targeted analyses or “omics” approach of saliva provide diagnostic or pathophysiological biomarkers. This pilot study's primary objective was to explore the pathophysiology of BMS through a comparative analysis of the salivary metabolome among 26 BMS female cases and 25 age- and sex-matched control subjects. Secondary objectives included comparative analyses of inflammatory cytokines, neuroinflammatory markers, and steroid hormones among cases and control subjects, and among BMS patients according to their clinical characteristics. Salivary metabolome, neuroinflammatory markers, cytokines, and steroids were, respectively, analysed by liquid chromatography coupled with mass spectrometry, ELISA and protease activity assay, and multiparametric Luminex method. Among the 166 detected metabolites, univariate analysis did not find any discriminant metabolite between groups. Supervised multivariate analysis divided patients into 2 groups with an accuracy of 60% but did not allow significant discrimination (permutation test, P = 0.35). Among the metabolites contributing to the model, 3 belonging to the tyrosine pathway (l-dopa, l-tyrosine, and tyramine) were involved in the discrimination between cases and control subjects, and among BMS patients according to their levels of pain. Among the detectable molecules, levels of cytokines, steroid hormones, and neuroinflammatory markers did not differ between cases and control subjects and were not associated with characteristics of BMS patients. These results do not support the involvement of steroid hormones, inflammatory cytokines, or inflammatory neurogenic mediators in the pathophysiology of pain in BMS, whereas the observed shift in tyrosine metabolism may indicate an adaptative response to chronic pain or an impaired dopaminergic transmission.
ARMS/Kidins220 regulates nociception by controlling brain-derived neurotrophic factor secretion
Authors: Sánchez-Sánchez Julia , Vicente-García Cristina , Cañada-García Daniel , Martín-Zanca Dionisio , Arévalo Juan C. 
Published: August 2022

AbstractPain is an alarm mechanism to prevent body damage in response to noxious stimuli. The nerve growth factor (NGF)/TrkA axis plays an essential role as pain mediator, and several clinical trials using antibodies against NGF have yielded promising results, but side effects have precluded their clinical approval. A better understanding of the mechanism of NGF/TrkA–mediated nociception is needed. Here, we find that ARMS/Kidins220, a scaffold protein for Trk receptors, is a modulator of nociception. Male mice, with ARMS/Kidins220 reduction exclusively in TrkA-expressing cells, displayed hyperalgesia to heat, inflammatory, and capsaicin stimuli, but not to cold or mechanical stimuli. Simultaneous deletion of brain-derived neurotrophic factor (BDNF) reversed the effects of ARMS/Kidins220 knock down alone. Mechanistically, ARMS/Kidins220 levels are reduced in vitro and in vivo in response to capsaicin through calpains, and this reduction leads to enhanced regulated BDNF secretion from dorsal root ganglion. Altogether, these data indicate that ARMS/Kidins220 protein levels have a role as a pain modulator in the NGF/TrkA axis regulating BDNF secretion.
Physician Assistant Students’ Perspective on Ultrasound as an Educational Technology
Authors: Breunig Michael , Plooster Corbin , Huckabee Michael 
Published: August 2022

Introduction
The use of ultrasound as an educational technology in medical education to teach basic sciences, including anatomy and physical examination techniques, has become common. Multiple studies have demonstrated the benefits of using ultrasound to teach anatomy and physical examination skills; however, this has not been studied in physician assistant (PA) students.

Methods
This qualitative phenomenological research used 5 semi-structured interviews of first semester PA students to obtain a deeper understanding of students’ perspectives. Dominant coding categories were identified through open coding, and thematic analysis was completed to identify emerging themes of participants’ perspectives.

Results
Overall, the students positively perceived this use of ultrasound. Four themes emerged regarding PA students’ perspectives of ultrasound as an educational technology within their Clinical Anatomy and History and Physical Examination classes: solidifying the curriculum, desiring more, looking ahead, and burden of curriculum.

Discussion
This study supports the use of ultrasound as an educational technology to solidify prior learning; however, steps to ensure student commitment to the technology should be taken. Careful consideration for curricular sequencing and allocation of time should be utilized by programs attempting to integrate ultrasound in this manner. Hands-on experiences, rather than faculty demonstrations, and clinical correlation should be utilized whenever possible.
Conservative Treatment for Cervical Adenocarcinoma In Situ: Long Term Results
Authors: Monti Ermelinda , Somigliana Edgardo , Alberico Daniela , Boero Veronica , Iorio Maria , Di Loreto Eugenia , Dell'acqua Andrea , Liverani Carlo Antonio 
Published: August 2022

Objective
This study aimed to evaluate the effectiveness of conservative treatment for cervical adenocarcinoma in situ (AIS).

Materials and Methods
This is a retrospective study on women with histologically confirmed AIS on cervical loop electrosurgical excision procedure specimen, treated conservatively between 2008 and 2020 in our center, Ospedale Maggiore Policlinico, Milan. The main outcome investigated was the risk of recurrence defined as a subsequent finding of recurrent AIS or invasive adenocarcinoma in a long-term follow-up. The disease-free survival curve was computed using the Kaplan-Meyer method. All patients underwent colposcopy with endocervical curettage and cytology every 6 months for the first 2 years after initial surgery and then annual cytology.

Results
Thirty women, aged 26 to 51 years, with histologically proven AIS on excisional specimen with negative margins, negative apex, and negative endocervical curettage were included. The median follow-up was 5.4 years. One woman had a recurrence of AIS after 8 years of follow-up and underwent total hysterectomy. No invasive cervical disease was detected during surveillance.

Conclusions
Women with cervical AIS can be managed conservatively by an excisional procedure, provided that the margins are free and a close and long-term follow-up is guaranteed.
Hyperviscosity syndromes; hemorheology for physicians and the use of microfluidic devices
Authors: Musick Jamie O. , Fibben Kirby S. , Lam Wilbur A. 
Published: August 2022

Purpose of review
Hyperviscosity syndromes can lead to significant morbidity and mortality. Existing methods to measure microcirculatory rheology are not readily available and limited in relevance and accuracy at this level. In this review, we review selected hyperviscosity syndromes and the advancement of their knowledge using microfluidic platforms.

Recent findings
Viscosity changes drastically at the microvascular level as the physical properties of the cells themselves become the major determinants of resistance to blood flow. Current, outdated viscosity measurements only quantify whole blood or serum. Changes in blood composition, cell number, or the physical properties themselves lead to increased blood viscosity. Given the significant morbidity and mortality from hyperviscosity syndromes, new biophysical tools are needed and being developed to study microvascular biophysical and hemodynamic conditions at this microvascular level to help predict those at risk and guide therapeutic treatment.

Summary
The use of ‘lab-on-a-chip’ technology continues to rise to relevance with point of care, personalized testing and medicine as customizable microfluidic platforms enable independent control of many in vivo factors and are a powerful tool to study microcirculatory hemorheology.
The New 2021 CKD-EPI Equation Without Race in a European Cohort of Renal Transplanted Patients
Authors: Delanaye Pierre , Masson Ingrid , Maillard Nicolas , Pottel Hans , Mariat Christophe 
Published: August 2022

Background.
Whether the new chronic kidney disease-epidemiology (CKD-EPI) equation without the race variable remains accurate enough for glomerular filtration rate (GFR) estimation in non-US kidney transplant recipients (KTRs) is unclear. We sought to compare the predictive performance between this equation and the classical CKD-EPI equation in a French cohort of KTRs. We also evaluated the performance of the European Kidney Function Consortium (EKFC) equation, an estimate that has proved very accurate in nontransplant patients and that does not include race variable.

Methods.
We retrospectively selected 489 KTRs for whom GFR was measured by inulin clearance. Performances of GFR equations were compared according to median bias, imprecision, and accuracy within 30% (P30) and 20% (P20). Differences in P20/P30 were tested using the exact McNemar test.

Results.
Although the 4 equations exhibited a similar level of imprecision, the bias of the new CKD-EPI equation was +5.5 (4.0; 6.6) mL/min/1.73 m², much higher than the bias of the classical CKD-EPI, EKFC, and Modified Diet in Renal Diseases (MDRD) equation (2.4 [1.7;3.5], 2.2 [1.1;3.1], and −0.5 [−1.5; 1.0] mL/min/1.73 m², respectively). The new CKD-EPI equation was significantly less accurate with a P30 of 68.3% as compared with 74.2%, 75.3%, and 77.1% for the classical CKD-EPI, EKFC, and MDRD equation, respectively. The EKFC equation outperformed both versions of the CKD-EPI equation in terms of P20.

Conclusions.
The new CKD-EPI equation is suboptimal for the care and follow-up of European transplanted patients. The EKFC equation shows at least a similar performance to the MDRD and the classical CKD-EPI equation. Further validation of the EKFC equation in KTRs from a diverse ethnic background is needed.
Preliminary Clinical Experience of Molnupiravir to Prevent Progression of COVID-19 in Kidney Transplant Recipients
Authors: Villamarín Miguel , Márquez-Algaba Ester , Esperalba Juliana , Perelló Manuel , Los Arcos Ibai , Campany David , Moreso Francisco , Len Oscar 
Published: August 2022

Background.
Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs).

Methods.
ingle-center prospective cohort study‚ all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included.

Results.
Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin–based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines‚ and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir‚ and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity.

Conclusions.
Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.
Inflammatory responses is induced in pulmonary embolic lung: evaluation by a reproducible pulmonary embolism model in mice
Authors: Okabe Honoka , Kato Haruka , Yoshida Momoka , Kotake Mayu , Tanabe Ruriko , Matano Yasuki , Yoshida Masaki , Nomura Shintaro , Yamashita Atsushi , Nagai Nobuo 
Published: August 2022

AbstractBackgroundSince previously established models of pulmonary embolism showed a large variability in the degree of ischemia, it is difficult to assess the pathophysiological response in the lung after embolization. Here, we established a model of pulmonary embolism by certain amount of relatively small thrombi, in which the degree of ischemia was reproducible.MethodsThrombi with a maximum diameter of 100 μm or 500 μm were administered intravenously under anesthesia, and the survival ratio at 4 hours was evaluated. The location of thrombi in the lung was visualized by administration of fluorescent-labeled thrombus, and the hemodynamics of the lung after administration of thrombi was evaluated. CT angiography was also performed to evaluate the ratio of the embolized vessels. In addition, cytokine mRNAs was quantified 4 hours in embolized lung. Immunohistochemical analysis for interleukin (IL)-6 and CD68 as a marker of macrophages were also performed.ResultsIt was found that mice with 100 μm clots, but not with 500 μm clots, showed a dose-dependence of survival between 2.3 μL/g and 3.0 μL/g at 4 hours from embolization induction. In mice treated with 2.5 μL/g of 100 μm thrombus, thrombi were located in the peripheral region of the lung, which was consistent with the disruption of blood circulation the peripheral region. In addition, about 60% of the vessels with a diameter of less than 100 μm were occluded in these mice. In the lungs after 4 hours of embolization, IL-6 mRNA and tumor necrosis factor (TNF)-α mRNA were significantly higher and lower than control lungs. IL-6 was expressed in CD68-positive macrophages in both embolized and control lungs after 4 hours of embolization, and the number of each positive cells were comparable in both embolized and control lungs.ConclusionsThese results show that the pulmonary embolization model induced by a certain amount of small thrombus is useful for evaluating the pathological responses in the embolized lung. Furthermore, it was found that IL-6 expression was increased in macrophages in the embolized lung, indicating that inflammatory responses may contribute to the pathogenesis of pulmonary embolism.
Local production of reactive oxygen species drives vincristine-induced axon degeneration
Authors: Gómez-Deza Jorge , Slavutsky Anastasia L. , Nebiyou Matthew , Le Pichon Claire E. 
Published: August 2022

AbstractNeurological side effects arising from chemotherapy, such as severe pain and cognitive impairment, are a major concern for cancer patients. These major side effects can lead to reduction or termination of chemotherapy medication in patients, negatively impacting their prognoses. With cancer survival rates improving dramatically, addressing side effects of cancer treatment has become pressing. Here, we use iPSC-derived human neurons to investigate the molecular mechanisms that lead to neurotoxicity induced by vincristine, a common chemotherapeutic used to treat solid tumors. Our results uncover a novel mechanism by which vincristine causes a local increase in mitochondrial proteins that produce reactive oxygen species (ROS) in the axon. Vincristine triggers a cascade of axon pathology, causing mitochondrial dysfunction that leads to elevated axonal ROS levels and SARM1-dependent axon degeneration. Importantly, we show that the neurotoxic effect of increased axonal ROS can be mitigated by the small molecule mdivi-1 and antioxidants glutathione and mitoquinone, identifying a novel therapeutic avenue to treat the neurological effects of chemotherapy.
Sucrose-stimulated Salivary pH as an Adjunct to Caries Risk Assessment
Authors: Okuji David , Odusanwo Olutayo , Wu Yinxiang , Yeh Susanna , Dhar Sohini 
Published: August 2022

AbstractBackgroundChild and maternal sucrose-stimulated salivary pH (SSS pH) levels have the potential to be associated with childhood caries.AimThis study investigated the relationships among child and maternal SSS pH and child caries diagnosis, severity, and risk.DesignSSS pH levels were measured from 202 pediatric subjects and 175 mothers. Early childhood caries (ECC) and severe ECC (SECC) diagnoses, caries risk assessment (CRA) results, and caries severity scores were recorded. The associations between child and maternal SSS pH and children’s caries risk, diagnosis, and severity were respectively assessed using regression models.ResultsChildren with SSS pH ≤5.6 had higher odds to be diagnosed with ECC or SECC (aOR=7.27), and higher odds to present with moderate to extensive caries severity (aOR=5.63). Child SSS pH was associated with multiple risk factors on a CRA. When child SSS pH was adjusted for age, gender, and race/ethnicity as a predictor for SECC and ECC, the sensitivity and specificity estimates increased. Maternal and child SSS pH were positively associated.ConclusionsDentists should consider the use of children’s SSS pH as an inexpensive adjunct to the CRA and know that maternal and child SSS pH are significantly associated.
CRISPR/Cas9 screens implicate RARA and SPNS1 in doxorubicin cardiotoxicity
Authors: Lv Wenjian , Shao Yeng , Hoshino Atsushi , Arany Zoltan , Musunuru Kiran , McDermott-Roe Chris 
Published: August 2022

AbstractDoxorubicin (DOX) is an efficacious chemotherapy compound used to treat various cancers which elicits severe side effects, including heart failure. Uptake of DOX by cardiomyocytes causes metabolic dysfunction and cell death but causal mechanisms remain largely undefined. We applied genome-wide CRISPR/Cas9 knockout screens to discover genetic modifiers of DOX-induced cardiomyocyte cell death, and independently, DOX uptake and clearance. Both screens discovered known and novel factors. In cell death screens and validation studies, loss of retinoic acid receptor-α (RARA) predisposed cardiomyocytes to DOX-mediated cell death. Conversely, RARA activation reduced DOX cytotoxicity in wild type cardiomyocytes. RNA-Seq analysis revealed that whilst DOX caused large-scale suppression of metabolic and mitochondrial gene expression, RARA activation mitigated this effect. In DOX accumulation screens, an essential role for lysosomes in DOX clearance was observed. Loss of Sphingolipid Transporter 1 (SPNS1) led to DOX hyperaccumulation, suppression of autophagy, increased DNA damage, and increased cell death. Hence, SPNS1 plays a key role in buffering against DOX accumulation and toxicity. Collectively, our study nominated hundreds of drug-gene interactions, providing a springboard for exploration of causal mechanisms, and a technical framework for future screening campaigns.
Impact of OEI requirement on parallel hybrid electric turboprop regional aircraft optimization
Authors: Quillet Dominik , Boulanger Vincent , Rancourt David , Freer Richard , Bertrand Pierre 
Published: August 2022

Purpose
Parallel hybrid electric (HE) propulsion retrofit is a promising alternative to reduce fuel burn of aircraft operating on short regional flights. However, if the batteries are depleted at the end of the mission, the hybrid powertrain designs with downsized gas turbines (GTs) and additional electric motors might not meet the one-engine inoperative (OEI) missed approach climb performance required by the certification. Alternatively, hybrid designs using the original full-size GT can perform one engine climb without electric assistance. This paper aims to evaluate the impact of overshoot climb requirements on powertrain design and performance comparing the two design approaches.

Design/methodology/approach
An aircraft-level parametric mission analysis model is used to evaluate aircraft performance combined with an optimization framework including multiple constraints. An indirect approach using metamodels is used to optimize powertrain sizing and operation strategy.

Findings
Considering OEI climb requirements, no benefits were found using a design with downsized GTs. Equivalent fuel burns were found for hybrid designs that keep the original size GTs, but do not require electric energy for the OEI overshoot at the end of the mission. Then, it is recommended to size the GT to maintain the emergency climb capabilities with no electric assistance to ensure power availability regardless of remaining battery energy.

Originality/value
This work introduces a new perspective on parallel HE sizing with consideration for the dependency of power capability at aircraft level on the electric energy availability in case of critical mission scenarios such as overshoot climb at the end of the mission.