bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital financial inclusion, Financial Mismatch and Small and medium-sized enterprises Financing Constraints
Authors: Hu Guohui , Wang Sisi
Published: May 2023

Digital financial inclusion through the use of big data, artificial intelligence and other emerging technologies is becoming increasingly sophisticated in China. Using a sample of 843 SMEs in Shenzhen Stock Exchange from 2012-2021, this paper investigates the impact of digital financial inclusion on SMEs’ financing constraints and its mechanism of action using a fixed effects model. It is found that digital financial inclusion can significantly alleviate the financing constraints of SMEs. Further analysis of the mechanism of action reveals that digital financial inclusion can indeed reduce the level of financing constraints by alleviating the financial mismatch of enterprises. The heterogeneity analysis finds that this mitigating effect is greater among non-state versus eastern SMEs. This study sheds new light on alleviating the financing constraints of SMEs and improving financial mismatch.
A literature review of stock price crash risk: Evidence from its influencing factors
Authors: Xiao Di
Published: May 2023

Since the last century, stock price crash risk has always been a hot issue for researchers, capital market investors, corporate managements, and regulators. Therefore, it’s important to investigate what factors may affect stock price crash risk which may be helpful for stakeholders to effectively cope with and prevent the financial risk. In this paper, I investigate the existing literature of the influencing factors of stock price crash risk. Further, I did the distribution analysis of stock price crash risk by year and industry based on China’s A-share listed companies from 2011-2020. The result shows that, finance industry was exposed to slightest crash risk, whereas education industry was exposed to the highest. The summary and findings in this study may provide some implications to researchers, regulators, and investors.
Elastografie von Schilddrüsenknoten
Authors: Petersen Manuela , Klemenz Burkhard , Schenke Simone A.
Published: May 2023

Hintergrund Die Elastografie ist eine bildgebende Methode, um die Elastizität von Gewebe zu untersuchen. Inzwischen wurden verschiedene Elastografie-Verfahren entwickelt, die nach der Art des angewandten Stimulus unterteilt werden. Prinzipiell ist zwischen der Strain-Elastografie (SE) und Scherwellen-Elastografie (SWE) zu unterscheiden. Beide Methoden bieten neben der konventionellen B-Mode-Sonografie eine weitere Möglichkeit zur Beurteilung von Schilddrüsenerkrankungen.

Ziel der Arbeit Es soll ein Überblick über die
Elastografie-Verfahren einschließlich der physikalischen Grundlagen vermittelt werden sowie
ihre Bedeutung im Abklärungsalgorithmus von Schilddrüsenknoten.

Material und Methoden Internationale Leitlinien sowie aktuelle Arbeiten zur Elastografie wurden selektiv recherchiert.

Ergebnisse Die Elastografie liefert zusätzliche Informationen gegenüber der konventionellen B-Mode-Sonografie. Der wesentliche physikalische Mechanismus, dem der Gewebekontrast in allen Elastogrammen zugrunde liegt, ist die Änderung der Schersteifigkeit. Neben der qualitativen Erfassung der Elastizität in der SE ist mit der SWE eine Quantifizierung möglich. In der internationalen Literatur wurde die Elastografie als einzelne Methode oder im Vergleich bzw. in Kombination zur konventionellen B-Mode-Sonografie und insbesondere mit der Standardisierung mittels eines Risikostratifizierungssystems (RSS, TIRADS) analysiert. Die Ergebnisse zeigten sich durchaus kontrovers. Bei Knoten mit unklaren Befunden der Feinnadelbiopsie (Bethesda III/IV) führte die Kombination aus morphologischen Kriterien und Elastografie zu einer Verbesserung der diagnostischen Genauigkeit. Insbesondere der hohe negative prädiktive Wert weicher Knoten stellt einen relevanten Mehrwert dar. Diese Stärke der Methode kann bei der Abklärung von Knoten mit mittlerem Malignomrisiko oder von unklaren FNB-Ergebnissen eine wichtige Rolle spielen. Die Elastografie wurde bisher nur in das (überwiegend durch das EU-TIRADS abgelöste) French-TIRADS integriert. Obwohl das Verfahren im EU-TIRADS als Komplementärmethode Erwähnung findet, wurde eine Integration nicht beschrieben. Limitationen des Verfahrens sind idealisierte Grundannahmen, Hersteller- und Untersucherabhängigkeit sowie Artefakte.

Schlussfolgerung Die Elastografie kann bei der Beurteilung von Schilddrüsenknoten die standardisierten Diagnostikverfahren sinnvoll ergänzen, insbesondere bei Knoten mit mittlerem Malignomrisiko und unklaren Ergebnissen in der Feinnadelpunktion.
Fahrt ins Ungewisse
Authors: Trux Marc-Justin
Published: May 2023

Um eine angemessene Personalsituation in vollstationären Pflegeeinrichtungen zu gewährleisten, soll zum 1.7.2023 das bundeseinheitliche Personalbemessungsverfahren (PeBeM) implementiert werden. Die Zeit drängt, gleichzeitig sind noch viele Fragen zu klären – zum Zeitplan, zur Finanzierung und zur einheitlichen Umsetzung.
Free Tissue Transfer in Sickle Cell Disease: A Case Report and Systematic Review
Authors: Huang Anne , Patel Ronak A. , Gottlieb Lawrence J.
Published: May 2023

Hemoglobinopathies such as sickle cell disease (SCD) are traditionally considered a relative contraindication to free tissue transfer, due to concerns that erythrocyte sickling will increase the risk of microvascular thrombosis and flap failure. This article describes a case report with the successful use of free tissue transfer in a patient with SCD and provides a systematic literature review on free tissue transfer in SCD. A retrospective chart review was performed of a patient with SCD who underwent free tissue transfer at the authors' institution. A systematic literature review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed using the keywords “free tissue transfer,” “free flap,” or “microsurgery” and “sickle cell” on PubMed, Ovid/Medline, and Scopus. A 29-year-old male with delayed presentation of an electrical burn to the face and scalp underwent wound closure with a free anterolateral thigh flap. Key management principles included red blood cell transfusion to keep hemoglobin S under 30% and hemoglobin greater than 10 g/dL, maintenance of hydration, normothermia, adequate analgesia, and postoperative anticoagulation. Systematic literature review identified 7 articles describing 13 cases of free tissue transfer in 10 patients with SCD, with combined complete free flap success in 10 of the 13 flaps. Free tissue transfer can be successfully performed in patients with SCD. However, evidence on the optimal management of this unique patient population in the perioperative period after free tissue transfer is limited to case reports in the literature.
Trends and Innovations in Autologous Breast Reconstruction
Authors: Speck Nicole E. , Grufman Vendela , Farhadi Jian
Published: May 2023

More than 40 years have passed since the description of the first “free abdominoplasty flap” for breast reconstruction by Holmström. In the meantime, surgical advances and technological innovations have resulted in the widespread adoption of autologous breast reconstruction to recreate the female breast after mastectomy. While concepts and techniques are continuing to evolve, maintaining an overview is challenging. This article provides a review of current trends and recent innovations in autologous breast reconstruction.
Androgen Receptor Expression in ER and PR Negative Breast Cancer—A Study from a Tertiary Hospital in Northern India
Authors: Sidhu Sumeet , Kwatra Kanwardeep Singh , Kinsley Pamela Alice
Published: May 2023

Objectives Breast cancer is the leading cause of cancer-related deaths in women. Estrogen (ER) and progesterone receptor (PR) status and Her2 overexpression are major determinants in therapeutic decision making. Triple-negative breast cancers (TNBCs) have limited treatment options. Androgen receptor (AR) expression opens up therapeutic avenues for these patients. The aim of this article was to study the immunohistochemical expression of ARs in ER and PR Negative breast carcinomas and to correlate AR expression with various clinical, histopathological, and other immunohistochemical parameters.

Materials and Methods It is a cross-sectional study including 105 ER and PR Negative cases of breast carcinoma. Clinical parameters, histopathology, and immunohistochemical expression of AR, Her2, and Ki67 were analyzed in all cases.

Results AR expression was observed in 63.8% of ER and PR Negative breast cancers. In this group, AR expression was strongly associated with Her2 co-expression (89.2%) as compared to TNBCs (45.8%); p-value = 0.0002. Significant correlation was also observed between AR expression and tumor necrosis (p-value = 0.034) and postmenopausal status (p = 0.007).

Conclusion Our study shows that significant proportion of ER and PR Negative breast carcinomas (ER- PR- Her2+ and TNBCs) show AR expression. We strongly recommend routine evaluation of all hormone receptor-negative breast carcinomas for AR status by immunohistochemistry.
Bilateral Minithoracotomy for Mitral Valve Repair and Coronary Bypass Grafting
Authors: Fagu Albi , Pingpoh Clarence , Berger Tim , Siepe Matthias
Published: May 2023

Background Combined mitral valve and coronary artery surgery is usually accomplished via a median sternotomy and is associated with increased mortality and morbidity.

Case Description We report on a 67-year-old patient with mitral valve regurgitation and concomitant coronary artery disease (CAD). The mitral valve was repaired using the loops and ring technique, and the left anterior descending artery was revascularized using the left internal mammary artery through a bilateral minithoracotomy approach. The postoperative course was uneventful.

Conclusion Patients with mitral valve pathologies and concomitant CAD can be successfully operated via a bilateral minithoracotomy approach.
Quality of plant-based diet and the risk of dementia and depression among middle-aged and older population
Authors: Wu Hanzhang , Gu Yeqing , Meng Ge , Wu Hongmei , Zhang Shunming , Wang Xuena , Zhang Juanjuan , Huang Tao , Niu Kaijun
Published: May 2023

Background

several previous studies have shown the importance of the plant-based diets. However, not all plant-based foods are necessarily beneficial for dementia or depression. This study aimed to prospectively investigate the association between an overall plant-based diet and the incidence of dementia or depression.

Methods

we included 180,532 participants from the UK Biobank cohort study, free of a history of cardiovascular disease, cancer, dementia and depression at baseline. We calculated an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) based on 17 major food groups from Oxford WebQ. Dementia and depression were evaluated using hospital inpatient records in UK Biobank. Cox proportional hazards regression models were used to estimate the association between PDIs and the incidence of dementia or depression.

Results

during the follow-up, 1,428 dementia cases and 6,781 depression cases were documented. After adjusting for several potential confounders and comparing the highest with the lowest quintile of three plant-based diet indices, the multivariable hazard ratios (95% confidence intervals (CIs)) for dementia were 1.03 (0.87, 1.23) for PDI, 0.82 (0.68, 0.98) for hPDI and 1.29 (1.08, 1.53) for uPDI. The hazard ratios (95% CI) for depression were 1.06 (0.98, 1.14) for PDI, 0.92 (0.85, 0.99) for hPDI and 1.15 (1.07, 1.24) for uPDI.

Conclusion

a plant-based diet rich in healthier plant foods was associated with a lower risk of dementia and depression, whereas a plant-based diet that emphasises less-healthy plant foods was associated with a higher risk of dementia and depression.
A Kazakhstani English Language teacher’s perspective on multilingual practices
Authors: Klyshbekova Maira
Published: May 2023

Kazakhstan is now embracing a trilingual education policy through the use of Kazakh, Russian, and English as mediums of instruction. The policy expects multilingual practices from the teachers of content disciplines; however, the same cannot be said for English language teachers. English language teachers are still trapped in English-only practices, making them rely on only the target language when teaching. I, as a Kazakhstani teacher who worked in a trilingual school, decided to challenge this monolingual perspective and try to incorporate multilingual practices into my teaching. In this article, I present my reflections on my past and current teaching beliefs and propose that multilingual practices in the form of pedagogical translanguaging can be seen as legitimate teaching strategies that can be part of ELT classrooms.
Phylogenomic Testing of Root Hypotheses
Authors: Tria Fernando D K , Landan Giddy , Picazo Devani Romero , Dagan Tal
Published: May 2023

The determination of the last common ancestor (LCA) of a group of species plays a vital role in evolutionary theory. Traditionally, an LCA is inferred by the rooting of a fully resolved species tree. From a theoretical perspective, however, inference of the LCA amounts to the reconstruction of just one branch—the root branch—of the true species tree and should therefore be a much easier task than the full resolution of the species tree. Discarding the reliance on a hypothesized species tree and its rooting leads us to reevaluate what phylogenetic signal is directly relevant to LCA inference and to recast the task as that of sampling the total evidence from all gene families at the genomic scope. Here, we reformulate LCA and root inference in the framework of statistical hypothesis testing and outline an analytical procedure to formally test competing a priori LCA hypotheses and to infer confidence sets for the earliest speciation events in the history of a group of species. Applying our methods to two demonstrative data sets, we show that our inference of the opisthokonta LCA is well in agreement with the common knowledge. Inference of the proteobacteria LCA shows that it is most closely related to modern Epsilonproteobacteria, raising the possibility that it may have been characterized by a chemolithoautotrophic and anaerobic life style. Our inference is based on data comprising between 43% (opisthokonta) and 86% (proteobacteria) of all gene families. Approaching LCA inference within a statistical framework renders the phylogenomic inference powerful and robust.
Streptococcus pyogenes Colonization in Children Aged 24–59 Months in the Gambia: Impact of Live Attenuated Influenza Vaccine and Associated Serological Responses
Authors: Keeley Alexander J , Groves Danielle , Armitage Edwin P , Senghore Elina , Jagne Ya Jankey , Sallah Hadijatou J , Drammeh Sainabou , Angyal Adri , Hornsby Hailey , de Crombrugghe Gabrielle , Smeesters Pierre R , Rossi Omar , Carducci Martina , Peno Chikondi , Bogaert Debby , Kampmann Beate , Marks Michael , Shaw Helen A , Turner Claire R , de Silva Thushan I
Published: May 2023

Background

Immunity to Streptococcus pyogenes in high burden settings is poorly understood. We explored S. pyogenes nasopharyngeal colonization after intranasal live attenuated influenza vaccine (LAIV) among Gambian children aged 24–59 months, and resulting serological response to 7 antigens.

Methods

A post hoc analysis was performed in 320 children randomized to receive LAIV at baseline (LAIV group) or not (control). S. pyogenes colonization was determined by quantitative polymerase chain reaction (qPCR) on nasopharyngeal swabs from baseline (day 0), day 7, and day 21. Anti-streptococcal IgG was quantified, including a subset with paired serum before/after S. pyogenes acquisition.

Results

The point prevalence of S. pyogenes colonization was 7%–13%. In children negative at day 0, S. pyogenes was detected at day 7 or 21 in 18% of LAIV group and 11% of control group participants (P = .12). The odds ratio (OR) for colonization over time was significantly increased in the LAIV group (day 21 vs day 0 OR, 3.18; P = .003) but not in the control group (OR, 0.86; P = .79). The highest IgG increases following asymptomatic colonization were seen for M1 and SpyCEP proteins.

Conclusions

Asymptomatic S. pyogenes colonization appears modestly increased by LAIV, and may be immunologically significant. LAIV could be used to study influenza-S. pyogenes interactions.

Clinical Trials Registration. NCT02972957.
The Role of Introgression During the Radiation of Endemic Fishes Adapted to Living at Extreme Altitudes in the Tibetan Plateau
Authors: Qian Yuting , Meng Minghui , Zhou Chaowei , Liu Haiping , Jiang Haifeng , Xu Youwei , Chen Wenjun , Ding Zufa , Liu Yang , Gong Xiong , Wang Cheng , Lei Yi , Wang Tai , Wang Ying , Gan Xiaoni , Meyer Axel , He Shunping , Yang Liandong
Published: May 2023

Recent genomic analyses of evolutionary radiations suggest that ancient introgression may facilitate rapid diversification and adaptive radiation. The loach genus Triplophysa, a genus with most species endemic to Tibetan Plateau, shows ecological diversity and rapid evolution and represents a potential example of adaptive radiation linked to the uplift of the Tibetan Plateau. Here, we interrogate the complex evolutionary history of Triplophysa fishes through the analysis of whole-genome sequences. By reconstructing the phylogeny of Triplophysa, quantifying introgression across this clade, and simulating speciation and migration processes, we confirm that extensive gene flow events occurred across disparate Triplophysa species. Our results suggest that introgression plays a more substantial role than incomplete lineage sorting in underpinning phylogenetic discordance in Triplophysa. The results also indicate that genomic regions affected by ancient gene flow exhibit characteristics of lower recombination rates and nucleotide diversity and may associate with selection. Simulation analysis of Triplophysa tibetana suggests that the species may have been affected by the Gonghe Movement in the third uplift of the Tibetan Plateau, resulting in founder effects and a subsequent reduction in Ne.
Fluoroquinolone Use Among Hospitalized Children: Diagnosis-Based Stratification to Identify Stewardship Targets
Authors: Parzen-Johnson Simon , Sun Shan , Scardina Tonya , Patel Sameer J
Published: May 2023

Background

As FQ (fluoroquinolone) use has shifted in pediatric populations, better metrics are needed to guide targeted antibiotic stewardship interventions and limit development of adverse events and resistance, particularly in medically complex children. In this study, we identify high-utilization groups based on underlying medical conditions and describe their relative FQ use over time.

Methods

This study is a retrospective analysis of data from the Pediatric Health Information System database from 2016 to 2020. We identify high-utilization groups based on underlying medical conditions using International Classification of Diseases, Ninth or Tenth Revision codes. We delineate overall trends in the use of FQs in the inpatient setting, including rate and proportional use by each patient group.

Results

Patients with an oncology diagnosis represent a large (25%–44%) and rising proportion (+4.8%/year, P = .001) of national FQ use over the study period. Patients with intra-abdominal infections, including appendicitis, have had a significant increase in both their relative proportional use of FQs (+0.6%/year, P = .037) and proportion of FQ use per admission encounter over the study period (+0.6%/year, P = .008). Patients with cystic fibrosis represent a decreasing proportion of overall use (−2.1%/year, P = .011) and have decreasing FQ use per inpatient encounter (−0.8%/year, P = .001).

Conclusions

Patients with an oncology diagnosis and patients with an intra-abdominal infection appear to be targets for FQ stewardship. Patients with cystic fibrosis have decreasing inpatient FQ use.

Key Points: This study describes fluoroquinolone use among hospitalized children from 2016 to 2020, stratified by underlying diagnoses. These trends are used to identify high-yield antibiotic stewardship targets.
Coupling of light and nutrients affects Microcystis gas vesicle content at different depths
Authors: Wu Tianhao , Wang Cai , Cao Jing , Hou Zeying , Chu Zhaosheng
Published: May 2023

Lakes are important water resources for human beings, but Microcystis blooms pose a serious threat to drinking water security and aquatic ecosystems. Gas vesicles (GVs) are an important trigger for the occurrence of Microcystis blooms. To understand the effects of light and nutrients on GV content, the phytoplankton in Lake Erhai were investigated. The results showed that the average GV content in the surface water was higher than that in the deep water. The total nitrogen in water affected the GV content by limiting the protein content, and the content of GVs increased by 9.2 μm3/cell for each 1.0 pg/cell increase in the intracellular nitrogen content. Moreover, light and total phosphorus affected the GV content in deep water by limiting the energy supply, and the content of GVs increased by 52.4 μm3/cell for each 1.0 pg/cell increase in the intracellular phosphorus content. These results indicate that for lakes with low transparency, decreasing the total phosphorus concentration can reduce the GV content. Reducing the total nitrogen concentration can reduce the GV content and decrease the dominance of Microcystis in all lakes. This study provides useful information for the control of Microcystis.
What happened when medical staff in Beijing, China wore over-apron dosemeters?
Authors: Cui Limeng , Tian Qingxiang , Feng Zechen , Ma Yongzhong
Published: May 2023

The wearing method of personal dosemeters for medical staff changed from under to outside the operator’s protective apron in April 2020. We measured the radiation dose Hp(10) for medical staff in Beijing from September 2020 to October 2021. The study population consisted of 3291 medical staff. All participants were divided into three groups. After excluding unusually low doses, the collected data higher than the detection limit involved 811 (7.8%) of 10 395 readings from 479 (14.6%) of 3291 staff. The mean equivalent dose was 1.4 mSv/3 months, with an SD of 2.3 mSv. The calculated average annual effective doses of radiation workers in the three groups after the interventional procedures from September 2020 to October 2021 ranged from 0.47 to 0.63 mSv/year, with median values of 0.32, 0.23 and 0.26 mSv/year, respectively.
0238 Neighborhood Determinants of Sleep and the Moderating Role of Cultural Factors Among American Indian and Alaska Native Adolescents
Authors: Mousavi Zahra Avah , Troxel Wendy , Dickerson Daniel , Dong Lu , Brown Ryan , Palimaru Alina , Klein David , Johnson Carrie , D’Amico Elizabeth
Published: May 2023

Introduction

Increasing evidence suggests the neighborhood social environment may be an important predictor of sleep, yet this has not been explored among urban American Indian and Alaska Native (AI/AN) adolescents, a population that faces significant health disparities due to exposure to historic and contemporary stressors. This study aimed to examine the association between neighborhood social environment and sleep among Native adolescents as well as the moderating role of cultural factors in this association.

Methods

The sample included 133 AI/AN adolescents (age 12 to 16) residing in urban settings in California (57.1% female, Mage=14.03, SDage=1.35). Perceived neighborhood social environment included safety and cohesion. Perceived cultural factors included identification with Native culture (e.g., I feel a strong attachment towards my tribal group) and historical loss (e.g., Losing our culture). Sleep duration, efficiency, and wake after sleep onset (WASO) were measured via actigraphy. Subjective sleep disturbance was measured via questionnaire. Age, sex, mother’s education, depression, anxiety, and body mass index (BMI) were included as covariates.

Results

Greater neighborhood safety was significantly associated with lower sleep disturbance (b = -2.17, SE = .8, p = .008), higher sleep efficiency (b = -2.17, SE = .8, p = .008), and lower WASO (b = -2.17, SE = .8, p = .008), even after covariate adjustment. Neighborhood cohesion was not associated with any sleep outcomes. Cultural factors moderated the association between neighborhood social environment and sleep outcomes (p’s<.05 for moderation). Specifically, both neighborhood safety and cohesion predicted lower sleep disturbance only among individuals with greater cultural identity. Further, neighborhood safety predicted greater sleep efficiency and lower WASO only among individuals with greater historical loss.

Conclusion

Findings from this study move the field forward in understanding sleep health among AI/AN adolescents and address the moderating role of culture between neighborhood environment and sleep. The association between neighborhood social environment and sleep outcomes was more robust for urban AI/AN adolescents who more strongly identified with their Native culture and who reported thinking about historical loss more frequently. Research should consider intersecting aspects of social context in predicting sleep outcomes, particularly among groups that face sleep and other health disparities.

Support (if any)
0587 Demographic Characteristics and Comorbidities of Patients With Narcolepsy: A Propensity Score–Matched Cohort Study
Authors: Lipford Melissa , Ip Wui , Awasthi Samir , Moore J Layne , Tippmann-Peikert Maja , Asfahan Shahir , Singh Gajinder Pal , Gudeman Jennifer
Published: May 2023

Introduction

Narcolepsy is a rare, chronic sleep disorder whose symptoms detrimentally impact quality of life. Narcolepsy has a complex phenotype associated with multiple comorbid conditions. This is the first study to use aggregate electronic health record (EHR) data to characterize the demographics and comorbidities of patients with narcolepsy.

Methods

An EHR-based search identified first-time Mayo Clinic patients between 2000–2020. Included patients had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 disease-supportive statement in the clinical notes (identified using a natural language processing algorithm). A control cohort was propensity-matched for birth year, age at first institutional encounter, sex, race, ethnicity, number of diagnosis codes, and mortality. Common comorbidities were compared and ranked between cohorts by odds ratio (OR); P values were adjusted and calculated based on Bonferroni correction.

Results

In the EHR database (N=6,389,186 patients), 2057 patients with narcolepsy were identified (median age at first presentation to Mayo clinic, 32 y [range, 17–48]; 59.6% female; 92.6% white; 89.2% non-Hispanic) and propensity-matched with a control cohort of 2057 patients (median age at first presentation to Mayo clinic, 35 y [range, 12–52]; 58.9% female; 94.6% white; 84.5% non-Hispanic). Among the top comorbidities that occurred more frequently in the narcolepsy cohort compared to the control cohort (OR [95% CI]; P< 0.001]) were sleep disorders (restless leg syndrome, 3.94 [3.09–5.02]; obstructive sleep apnea, 3.27 [2.83–3.79]; insomnia, 1.84 [1.57–2.17]); mood disorders (depression, 2.11 [1.86-2.40]; dysthymia, 1.86 [1.54–2.25]; anxiety, 1.67 [1.46–1.89]); and pain disorders (chronic pain syndrome, 2.20 [1.76–2.76]; migraine, 1.96 [1.66–2.31]; fibromyalgia, 1.90 [1.61–2.25]; carpal tunnel syndrome, 1.80 [1.46–2.22]; myalgia, 1.69 [1.45–1.97]). Other comorbidities statistically significantly associated with narcolepsy were (OR range, 1.33–1.95) irritable bowel syndrome (P< 0.001), asthma (P< 0.001), cervical spondylosis (P< 0.01), syncope (P< 0.01), and hypothyroidism (P< 0.05).

Conclusion

This propensity-matched cohort study affirmed prior studies of increased psychiatric and sleep disorders in patients with narcolepsy. Narcolepsy patients were twice as likely to experience chronic pain syndrome compared to the matched control group. Understanding common narcolepsy comorbidities may help optimize treatment efficacy and increase understanding of the medical/psychiatric challenges of narcolepsy patients.

Support (if any)

Avadel Pharmaceuticals
0634 An RCT of Brief CBT for Insomnia among Primary Care Patients with Suicidal Ideation
Authors: Pigeon Wilfred , Crean Hugh , Bishop Todd , Cross Wendi , Youngren Westely , Funderburk Jennifer
Published: May 2023

Introduction

There is an established association between insomnia and suicide. As with many conditions, the preponderance of patients with either insomnia or with suicidal ideation (SI) are seen in primary care settings. Brief forms of cognitive behavioral therapy for insomnia (bCBTi) have been delivered in primary care including to patients with mental health conditions. We sought to test the efficacy of bCBTi among primary care insomnia patients endorsing SI.

Methods

A sample of 194 participants endorsing SI and meeting criteria for insomnia disorder along with depression and/or posttraumatic stress disorder (PTSD) were randomly assigned to receive either four weekly sessions of bCBTi (n=98) or Sleep Hygiene (n=96). Participants engaged in suicide safety planning or a review of their existing safety plan. To be consistent with the primary care milieu, intervention sessions averaged < 30 minutes in duration with all intervention sessions audio-recorded and subjected to fidelity ratings. Outcome measures include the: Insomnia Severity Index (ISI; primary endpoint): Scale for Suicidal Ideation (SSI); Patient Health Questionnaire-Depression (PHQ-9); and PTSD Symptom Checklist-DSM 5 (PCL-5) administered at baseline and 6, 12, 18, 24, and 30-week follow-ups. Mixed effect analyses will test for linear change in each outcome over time, as well as examining intervention effects on these trajectories. The study also gathers initial data on barriers and facilitators to aid future implementation efforts.

Results

The study sample consists of 194 U.S. Military Veterans with a mean (sd) age of 51.5 (13.7) years, 23% of whom are female, 17% racial minorities and 9% ethnic minorities. Mean baseline values for the outcome measures are: ISI 19.1 (4.1); SSI 3.5 (5.3); PHQ-9 15.2 (5.1); and PCL-5 43.4 (14.3). Data collection will be completed in Spring 2023. In addition to complete enrollment and retention data, we will present results of analyses on primary (ISI) and secondary (SSI, PHQ-9, PCL-5) outcomes across all time points.

Conclusion

This randomized trial was designed to establish the feasibility and effectiveness of treating insomnia in primary care environments as a suicide prevention strategy while gathering data to facilitate implementation if the findings warrant.

Support (if any)

U.S. Department of Veterans Affairs Office of Research & Develpment (I01 HX002183)
Wnt-β-catenin in hepatobiliary homeostasis, injury, and repair
Authors: Nejak-Bowen Kari , Monga Satdarshan P.
Published: May 2023

Wnt-β-catenin signaling has emerged as an important regulatory pathway in the liver, playing key roles in zonation and mediating contextual hepatobiliary repair after injuries. In this review, we will address the major advances in understanding the role of Wnt signaling in hepatic zonation, regeneration, and cholestasis-induced injury. We will also touch on some important unanswered questions and discuss the relevance of modulating the pathway to provide therapies for complex liver pathologies that remain a continued unmet clinical need.
Spectrum of Liver Pathology in Dyskeratosis Congenita
Authors: Putra Juan , Agarwal Suneet , Al-Ibraheemi Alyaa , Alomari Ahmad I. , Perez-Atayde Antonio R.
Published: May 2023

Dyskeratosis congenita (DC) is a rare multisystemic disorder associated with defective telomere maintenance. Frequent clinical manifestations of DC include reticular skin pigmentation, dystrophic nails, oral leukoplakia, and bone marrow failure. Hepatic disturbances are reported to occur in 7% of DC patients. This study aimed to evaluate the histopathologic spectrum of hepatic involvement in this disorder. DC patients with liver tissue in the pathology database at Boston Children’s Hospital from 1995 to 2022 were identified. Clinical and pathologic information was documented. Thirteen specimens from 11 DC patients were included (M:F = 7:4; median age at the time of liver tissue evaluation: 18 y). DC-associated gene mutations were identified in 9 patients; TERF1-interacting nuclear factor 2 (TINF2) was the most frequently represented gene mutation, seen in 4 patients. All patients had bone marrow failure, whereas dystrophic nails, cutaneous abnormal pigmentation, and oral leukoplakia were noted in 73%, 64%, and 55% of patients, respectively. Seven patients underwent bone marrow transplants before biopsy/autopsy (median interval of 45 mo). Histologically, 3 of 4 patients who presented with portal hypertension showed noncirrhotic changes (nodular regenerative hyperplasia and/or obliterative portal venopathy), whereas prominent central and sinusoidal fibrosis was noted in patients with intrahepatic shunting and those showing features of chronic passive congestion. All cases showed hepatocyte anisonucleosis. One patient developed hepatic angiosarcoma, and another 1 had colorectal adenocarcinoma metastatic to the liver. DC patients show heterogeneous histologic findings in their liver. The findings of noncirrhotic portal hypertension, intrahepatic shunting, and angiosarcoma suggest vascular functional/structural pathology as a possible unifying etiology of hepatic manifestations of DC.
Visits to Alberta Emergency Departments for Child Mental Health Concerns During the COVID-19 Pandemic
Authors: Newton Amanda S. , Xie Jianling , Wright Bruce , Lategan Conné , Winston Kathleen , Freedman Stephen B.
Published: May 2023

Objective

We examined emergency department (ED) mental health visit trends by children in relation to periods of school closure and reopening during the COVID-19 pandemic in Alberta, Canada.

Methods

Mental health visits by school-aged children (5 to <18 years) were extracted from the Emergency Department Information System, a province-wide database, from March 11, 2020, to November 30, 2021 (pandemic period; n = 18,997) and March 1, 2019, to March 10, 2020 (1-year, prepandemic comparator period; n = 11,540). We calculated age-specific visit rates and compared rate differences between periods of school closure (March 15–June 30, 2020; November 30, 2020–January 10, 2021; April 22–June 30, 2021) and reopening (September 4–November 29, 2020; January 11–April 21, 2021; September 3–November 30, 2021) to matched prepandemic periods. We used a ratio of relative risk to examine the risk of a visit during closures versus reopenings.

Results

The cohort included 11,540 prepandemic visits and 18,997 pandemic visits. Compared with prepandemic periods, ED visit rates increased across all ages during the first (+85.53%; 95% confidence interval [CI], 73.68% to 100.41%) and third (+19.92%; 95% CI, 13.28% to 26.95%) school closures, and decreased during the second closure (−15.37%; 95% CI, −22.22% to −7.92%). During school reopenings, visit rates decreased across all ages during the first reopening (−9.30%; 95% CI, −13.94% to −4.41%) and increased during the third reopening (+13.59%; 95% CI, 8.13% to 19.34%); rates did not change significantly during the second reopening (2.54%; 95% CI, −3.45% to 8.90%). The risk of a visit during school closure versus reopening was only higher for the first closure with 2.06 times the risk (95% CI, 1.88 to 2.25).

Conclusions

Emergency department mental health visit rates were highest during the first school closure of the COVID-19 pandemic, and the risk of a visit during this closure period was twice compared with when schools first reopened.
Epidemiology of cranial infections in battlefield-related penetrating and open cranial injuries
Authors: Meister Melissa R. , Boulter Jason H. , Yabes Joseph M. , Sercy Erica , Shaikh Faraz , Yokoi Hana , Stewart Laveta , Scanlon Michaela M. , Shields Margaret M. , Kim Alexander , Tribble David R. , Bartanusz Viktor , Dengler Bradley A.
Published: May 2023

BACKGROUND

Penetrating brain injuries are a potentially lethal injury associated with substantial morbidity and mortality. We examined characteristics and outcomes among military personnel who sustained battlefield-related open and penetrating cranial injuries during military conflicts in Iraq and Afghanistan.

METHODS

Military personnel wounded during deployment (2009–2014) were included if they sustained an open or penetrating cranial injury and were admitted to participating hospitals in the United States. Injury characteristics, treatment course, neurosurgical interventions, antibiotic use, and infection profiles were examined.

RESULTS

The study population included 106 wounded personnel, of whom 12 (11.3%) had an intracranial infection. Posttrauma prophylactic antibiotics were prescribed in more than 98% of patients. Patients who developed central nervous system (CNS) infections were more likely to have undergone a ventriculostomy (p = 0.003), had a ventriculostomy in place for a longer period (17 vs. 11 days; p = 0.007), had more neurosurgical procedures (p < 0.001), and have lower presenting Glasgow Coma Scale (p = 0.01) and higher Sequential Organ Failure Assessment scores (p = 0.018). Time to diagnosis of CNS infection was a median of 12 days postinjury (interquartile range, 7–22 days) with differences in timing by injury severity (critical head injury had median of 6 days, while maximal [currently untreatable] head injury had a median of 13.5 days), presence of other injury profiles in addition to head/face/neck (median, 22 days), and the presence of other infections in addition to CNS infections (median, 13.5 days). The overall length of hospitalization was a median of 50 days, and two patients died.

CONCLUSION

Approximately 11% of wounded military personnel with open and penetrating cranial injuries developed CNS infections. These patients were more critically injured (e.g., lower Glasgow Coma Scale and higher Sequential Organ Failure Assessment scores) and required more invasive neurosurgical procedures.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
The impact of delivery by a fixed-wing, sling-launched unmanned aerial vehicle on the hematologic function of whole blood
Authors: Peltier Grantham C. , Meledeo Michael A.
Published: May 2023

BACKGROUND

Unmanned aerial vehicles (UAVs) have been shown to shorten delivery times of medical products in health care, providing a potential answer to the question of prehospital resuscitation where blood and blood products are not readily available. While the capabilities and efficiencies of delivery via UAVs are already well established, the postdelivery viability and hemostatic function of whole blood has not been examined.

METHODS

Whole blood units were sampled for a preflight control and loaded onto a fixed wing UAV. The UAVs flew in predetermined flight paths to either deliver via parachute drop or direct recovery after UAV capture by arresting gear. Postflight and preflight samples were assayed for coagulation function with thromboelastography, blood chemistry, and free hemoglobin to observe hemolysis.

RESULTS

No significant differences in any metric were observed between the blood samples assayed preflight versus those flown and parachute dropped or those flown and recovered from the UAV.

CONCLUSION

The use of UAVs for delivery of whole blood offers significant benefits for prehospital care. Further innovations in UAV and transportation technologies will expand on an already strong foundation.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Detecting and attributing the causes of biodiversity change: needs, gaps and solutions
Authors: Tekwa Eden , Gonzalez Andrew , Zurell Damaris , O'Connor Mary
Published: May 2023

This issue addresses the multifaceted problems of understanding biodiversity change to meet emerging international development and conservation goals, national economic accounting and diverse community needs. Recent international agreements highlight the need to establish monitoring and assessment programmes at national and regional levels. We identify an opportunity for the research community to develop the methods for robust detection and attribution of biodiversity change that will contribute to national assessments and guide conservation action. The 16 contributions of this issue address six major aspects of biodiversity assessment: connecting policy to science, establishing observation, improving statistical estimation, detecting change, attributing causes and projecting the future. These studies are led by experts in Indigenous studies, economics, ecology, conservation, statistics, and computer science, with representations from Asia, Africa, South America, North America and Europe. The results place biodiversity science in the context of policy needs and provide an updated roadmap for how to observe biodiversity change in a way that supports conservation action via robust detection and attribution science.

This article is part of the theme issue ‘Detecting and attributing the causes of biodiversity change: needs, gaps and solutions’
Disrupting and diversifying the values, voices and governance principles that shape biodiversity science and management
Authors: Salomon Anne K. , Okamoto Daniel K. , Wilson Ḵii'iljuus Barbara J. , Tommy Happynook hiininaasim , Wickaninnish  , Mack wiicuckum Anne , Allan Davidson Skil Hiilans , Guujaaw Gidansda , L. Humchitt Wigvilhba Wakas Harvey , Happynook Tom Mexsis , Cox weiwimtaeek Christina , Gillette Hyuuštulth Francis , Christiansen n'yasim Samantha , Dragon Dianna , Kobluk Hannah M. , Lee Lynn C. , Tinker M. Tim , Silver Jennifer J. , Armitage Derek , McKechnie Iain , MacNeil Aaron , Hillis Dylan , Muhl Ella-Kari , Gregr Edward J. , Commander Christian J. C. , Augustine Arianna
Published: May 2023

With climate, biodiversity and inequity crises squarely upon us, never has there been a more pressing time to rethink how we conceptualize, understand and manage our relationship with Earth's biodiversity. Here, we describe governance principles of 17 Indigenous Nations from the Northwest Coast of North America used to understand and steward relationships among all components of nature, including humans. We then chart the colonial origins of biodiversity science and use the complex case of sea otter recovery to illuminate how ancestral governance principles can be mobilized to characterize, manage and restore biodiversity in more inclusive, integrative and equitable ways. To enhance environmental sustainability, resilience and social justice amid today's crises, we need to broaden who benefits from and participates in the sciences of biodiversity by expanding the values and methodologies that shape such initiatives. In practice, biodiversity conservation and natural resource management need to shift from centralized, siloed approaches to those that can accommodate plurality in values, objectives, governance systems, legal traditions and ways of knowing. In doing so, developing solutions to our planetary crises becomes a shared responsibility.

This article is part of the theme issue ‘Detecting and attributing the causes of biodiversity change: needs, gaps and solutions’.
Attempts to limit sporulation in the probiotic strain Bacillus subtilis BG01-4TM through mutation accumulation and selection
Authors: Bosnar Luke M. , Shindler Anya E. , Wood Jennifer , Patch Craig , Franks Ashley E.
Published: May 2023

The use of bacterial spores in probiotics over viable loads of bacteria has many advantages, including the durability of spores, which allows spore-based probiotics to effectively traverse the various biochemical barriers present in the gastrointestinal tract. However, the majority of spore-based probiotics developed currently aim to treat adults, and there is a litany of differences between the adult and infant intestinal systems, including the immaturity and low microbial species diversity observed within the intestines of infants. These differences are only further exacerbated in premature infants with necrotizing enterocolitis (NEC) and indicates that what may be appropriate for an adult or even a healthy full-term infant may not be suited for an unhealthy premature infant. Complications from using spore-based probiotics for premature infants with NEC may involve the spores remaining dormant and adhering to the intestinal epithelia, the out-competing of commensal bacteria by spores, and most importantly the innate antibiotic resistance of spores. Also, the ability of

Bacillus subtilis

to produce spores under duress may result in less

B. subtilis

perishing within the intestines and releasing membrane branched-chain fatty acids. The isolate

B. subtilis

BG01-4TM is a proprietary strain developed by Vernx Biotechnology through accumulating mutations within the BG01-4TM genome in a serial batch culture. Strain BG01-4TM was provided as a non-spore-forming

B. subtilis

, but a positive sporulation status for BG01-4TM was confirmed through in vitro testing and suggested that selection for the sporulation defective genes could occur within an environment that would select against sporulation. The durability of key sporulation genes was ratified in this study, as the ability of BG01-4TM to produce spores was not eliminated by the attempts to select against sporulation genes in BG01-4TM by the epigenetic factors of high glucose and low pH. However, a variation in the genes in isolate BG01-4-8 involved in the regulation of sporulation is believed to have occurred during the mutation selection from the parent strain BG01-4TM. An alteration in selected sporulation regulation genes is expected to have occurred from BG01-4TM to BG01-4-8, with BG01-4-8 producing spores within 24 h, ~48 h quicker than BG01-4TM.
Acute intermittent hypoxia-induced increases maximal motor unit discharge rates in people with chronic incomplete spinal cord injury
Authors: Pearcey Gregory E P , Afsharipour Babak , Holobar Aleš , Sandhu Milap S , Rymer W Zev
Published: May 2023

Acute intermittent hypoxia (AIH) is an emerging technique for enhancing neuroplasticity and function in respiratory and limb musculature. Thus far, AIH-induced improvements in strength have been reported for upper and lower limb muscles after chronic incomplete cervical spinal cord injury (iSCI) but the underlying mechanisms have been elusive. We used high-density surface electromyography (HDsEMG) to determine if motor unit discharge behaviour is altered after 15 × 60 s exposures to 9% inspired oxygen interspersed with 21% inspired oxygen (AIH), compared to breathing only 21% air (SHAM). We recorded HDsEMG from the biceps and triceps brachii of seven individuals with iSCI during maximal elbow flexion and extension contractions, and motor unit spike trains were identified using convolutive blind source separation. After AIH, elbow flexion and extension torque increased by 54% and 59% from baseline (p = 0.003), respectively, whereas there was no change after SHAM. Across muscles, motor unit discharge rates increased by ∼4 pulses per second (p = 0.002) during maximal efforts, from pre to post AIH. These results suggest that excitability and/or activation of spinal motoneurons are augmented after AIH, providing a mechanism to explain AIH-induced increases in voluntary strength. Pending validation, AIH may be helpful in conjunction with other therapies to enhance rehabilitation outcomes due to these enhancements in motor unit function and strength.