bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective multi-night sleep monitoring at home: variability of sleep parameters between nights and implications for the reliability of sleep assessment in clinical trials
Authors: Chouraki Alexandre , Tournant Julia , Arnal Pierrick , Pépin Jean-Louis , Bailly Sébastien
Published: December 2022

Study Objectives

In-laboratory polysomnography is the current gold standard for objective sleep measurements in clinical trials, but this does not capture night-to-night variability in sleep parameters. This study analyzed variability in sleep parameters recorded over multiple nights of sleep in an ecological setting using a portable sleep monitor and then estimated the minimum sample sizes required to reliably account for inter- and intra-individual variability in sleep parameters.

Methods

Participants were males who self-reported the absence of sleep disorders, and used a sleep monitoring device (Dreem Headband, Dreem, France) over multiple nights of sleep. Night-to-night variability of sleep parameters was determined over five consecutive weeknights using coefficients of variation (CV), and the minimal number of individuals and nights needed to reliably determine each sleep parameter was assessed.

Results

Night-to-night variability for the whole group (n = 94; 470 nights) was high (CV 0.44–0.58) for N2, N3, sleep onset and persistent sleep latencies, and wake after sleep onset (WASO), medium (CV 0.22–0.28) for N1 and N3 percentage, awakenings and REM latency, and low (CV 0.04–0.19) for sleep efficiency, N2 and REM percentages, total sleep time (TST) and micro-arousal index. Minimum sample sizes for reliable assessment of TST and WASO were 2 nights with 10 participants and 4 nights with 50 participants, respectively.

Conclusions

Night-to-night variability of sleep parameters is underestimated and under-recognized. These data on variability in commonly used sleep parameters will facilitate better estimation of sample sizes and number of nights required in clinical trials based on the outcomes of interest.
An Exploration of the Transition of Clinical Nurses to an Academic Nurse Lecturer Role
Authors: Axiak Sally , Axiak Marija
Published: December 2022

This qualitative study was conducted with eight professional nurses who transitioned from clinical practice to full-time lecturing in higher education. The study aimed to establish how nurse lecturers experience this major transition. Qualitative questionnaires were analyzed thematically. Four themes that collectively encapsulate the transitioning journey emerged: embarking on a career change, the transitioning period, supporting each other, and communication. Interwoven within the data was evidence that an informal community of practice developed and was the primary means of initial support and ongoing guidance, positively influencing the lecturers’ engagement and progression in their new career.
Growth Modulation by Tension Band Plate in Achondroplasia With Varus Knee Deformity: Comparison of Gait Analysis Measurements
Authors: Ulusaloglu Armagan C. , Asma Ali , Silva Luiz C. , Miller Freeman , Mackenzie William G. , Mackenzie W.G. Stuart
Published: December 2022

Background:

Limited evidence exists concerning growth modulation by tension band plate (TBP) to correct varus deformity in patients with achondroplasia with limited growth due to FGFR3 gene mutation. We evaluated the efficacy of TBP in children with achondroplasia with genu varum and reported the static radiographic and dynamic motion data to determine parameters that impact the rate of deformity correction.

Methods:

Patients with achondroplasia with genu varum who underwent TBP surgery for growth modulation were studied. Those with at least 1 year of follow-up with TBP were included. Radiographic parameters were measured. Growth velocity of femoral/tibial length was calculated separately. Patients were deemed successful or unsuccessful. Spearman correlation analysis and Student t test were used to describe statistical results.

Results:

Twenty-two patients (41 limbs; 12 girls) fulfilled our criteria. Mean age at TBP surgery was 7.6±2.4 years. Thirty-six femoral TBP and 41 tibial TBP were in place for 24.5±9.7 months. Mean mechanical axis deviation, mechanical lateral distal femoral angle, and medial proximal tibial angle preoperatively were 30.1±7.6 mm, 97.2±6.4, and 80.3±4.3 degrees, and 11±15.6 mm, 87.4±5.9, and 84.7±5.3 degrees at last follow-up (P<0.001). Fifteen limbs were successfully straightened; 4 limbs were in more varus than the initial deformity. Twenty-four limbs with TBP were still undergoing correction. In successful limbs, mean age at surgery was 6.5±1.7 years and duration of TBP was 29.9±7.8 months. In 4 unsuccessful limbs, mean age at surgery was 11.7±1.2 years. Analysis in the gait laboratory included physical examination with the measurement of knee varus and kinematic varus based on a posterior view static standing photograph. Photographic measurement of varus was higher than the radiographic measurement.

Conclusions:

Growth modulation by TBP surgery is a reliable and simple technique to correct genu varum in achondroplasia. An early age at TBP implementation (mean: 6.5 y) is crucial to successfully correct the varus knee deformity. Furthermore, we recommend early and regular surveillance of achondroplasia for progressive varus knee deformity.

Level of Evidence:

Level IV—cohort study.
Effects of Body Mass Index on Presentation and Outcomes of COVID-19 among Heart Transplant and Left Ventricular Assist Device Patients: A Multi-Institutional Study
Authors: Iyengar Amit , Cohen William , Han Jason , Helmers Mark , Kelly John J. , Patrick William , Moss Noah , Molina Ezequiel J. , Sheikh Farooq H. , Houston Brian A. , Tedford Ryan J. , Shore Supriya , Vorovich Esther E. , Hsich Eileen M. , Bensitel Albatoul , Alexander Kevin M. , Chaudhry Sunit-Preet , Vidula Himabindu , Kilic Arman , Genuardi Michael V. , Birati Edo Y. , Atluri Pavan
Published: December 2022

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted.
Sequestration of Antimicrobial Agents in Xcoating and Heparin-Coated Extracorporeal Membrane Oxygenation Circuits: An In Vitro Study
Authors: Kato Takafumi , Enokiya Tomoyuki , Morikawa Yoshihiko , Okuda Masahiro , Imai Hiroshi
Published: December 2022

Limited data exist to guide antimicrobial therapy commonly prescribed to patients undergoing extracorporeal membrane oxygenation (ECMO). This study aimed to describe the kinetics of the cefazolin, doripenem, daptomycin, and levofloxacin in heparin-coated and Xcoating ECMO circuits. Circuits were primed with bovine whole blood and maintained at a physiological pH and temperature for 24 h. Each antimicrobial agent was added to the whole blood before priming. Equivalent doses of these drugs were added to glass jars containing fresh bovine whole blood as a control. Serial blood samples were collected from the ECMO circuits and controls over 24 h, and drug concentrations were quantified using validated assays. The concentrations of cefazolin, doripenem, daptomycin, and levofloxacin did not decrease significantly over 24 h. Collectively, these antimicrobial agents can be administered without the need to consider sequestration when using either heparin-coated or Xcoating circuits.
Traditional Chinese Medicine and COVID-19: Experiences, Lessons, and Suggestions
Authors: Yuan Zuo-Biao , Amieux Paul S.
Published: December 2022

Coronavirus disease-2019 (COVID-19) has now entered its third year as a worldwide pandemic. Unlike the Unites States, over 90% of patients have used traditional Chinese medicine (TCM) in China combined with conventional western medicine. The present minireview/commentary summarizes the experiences of TCM in the treatment of COVID-19 combined with conventional western medicine, lessons from the United States and some additional insights. COVID-19 falls into the category of “dampness−toxin plague” and is divided into five stages: mild stage, moderate stage, severe stage, critical stage, and recovery stage. Clinical trials conducted in China have suggested that TCM treatment plays a significant role in alleviating clinical symptoms, decreasing the time of hospitalization, reducing the overall fatality rate, and providing other beneficial outcomes when combined with conventional western medicine. To date, TCM is not widely used in the American hospital system. Only one TCM clinical trial to treat mild to moderate COVID-19 has been registered with ClinicalTrials.gov. A suggestion of dialogues among associated parties is proposed. TCM has been used as part of an integrative medicine treatment paradigm combined with conventional western medicine for COVID-19 in China. As registered clinical trials combining conventional western medicine with TCM continue to be produced and show positive benefits, the possibilities for TCM integration into treatment protocols for COVID-19 will become more of a possibility in the United States.
Total knee arthroplasty in patients with Parkinson’s disease: A systematic review and meta-analysis protocol
Authors: Sun Guangchen , Yu Hui , Cui Jun , Li Ming , Ru Yuefang
Published: December 2022

Background:

Parkinson’s disease (PD) patients have been shown to have various musculoskeletal problems, the postoperative outcomes of total knee arthroplasty procedure might be less predictable if performed on a patient who has PD. We conducted a protocol for systematic review and meta-analysis to evaluate the functional outcomes, activity levels, mortalities, implant survival rates, and complications of total knee arthroplasty in patients with PD.

Methods:

This study follows the guideline of the preferred reporting items for systematic reviews and meta-analyses protocols and has been registered on the International Prospective Register of Systematic Reviews with CRD42022375885. Two independent reviewers will search for databases including PubMed, Embase, Cochrane Library website, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database using the search strategies recommended by the Cochrane Back Review Group. The RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) will be used to conduct the meta-analyses.

Results:

The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:

This study may provide evidence for the clinical application of total knee arthroplasty in patients with PD.
Risk factors for 90-day all-cause mortality in post-operative central nervous system infections (PCNSIs): A retrospective study of 99 patients in China
Authors: Zhao Yanan , Deng Wenjing , Teng Junfang , Xu Yafei , Pan Pengwei , Jin Di
Published: December 2022

Post-operative central nervous system infections (PCNSIs) are serious complications of craniotomy. Many factors, including patient-related, surgical, and postoperative factors, affect the survival of patients with PCNSIs. Timely and effective implementation of antibiotics targeting pathogenic bacteria is crucial to reduce mortality. Metagenomic next-generation sequencing (mNGS) has been used successfully to detect pathogens associated with infectious diseases. This study was designed to evaluate the factors influencing mortality and to explore the application value of mNGS in patients with PCNSIs. We conducted a retrospective study of patients with PCNSIs in our unit from 1/12/2019 to 28/2/2021. Clinical data, cerebrospinal fluid (CSF) parameters, surgical information, and mNGS results were collected. Follow-up telephone calls were made in June 2021 for 90 days survival after discharge. 99 patients were enrolled, and the overall mortality rate was 36.4% (36/99). Kaplan–Meier survival analysis suggested that the risk factors for poor prognosis included age ≥ 53 years, Glasgow Coma scale (GCS) score ≤ 8, CSF/blood glucose ratio (C/B-Glu) ≤ 0.23, 2 or more operations, mechanical ventilation (MV), and non-mNGS test. MV and poor wound healing were independent risk factors for 90 day mortality according to the multivariate Cox proportional hazards model (OR = 6.136, P = .017, OR = 2.260, P = .035, respectively). Among the enrolled patients, causative pathogens were identified in 37. Gram-negative pathogens were found in 22 (59.5%) patients, and the remaining 15 (40.5%) were Gram-positive pathogens. Univariate analysis showed that white cell count and protein and lactate levels in the CSF of the Gram-negative group were higher than those of the Gram-positive group (P < .05). mNGS and conventional microbiological culture were tested in 34 patients, and the positive detection rate of mNGS was 52.9%, which was significantly higher than that of microbiological culture (52.9% vs 26.5%, χ
2 = 4.54, P = .033). The mortality rate of PCNSIs is high, and patients with MV and poor wound healing have a higher mortality risk. Gram-negative pathogens were the predominant pathogens in the patients with PCNSIs. mNGS testing has higher sensitivity and has the potential to reduce the risk of mortality in patients with PCNSIs.
Comparison of hysterectomy and uterine artery embolization in the treatment of symptomatic uterine fibroids: A protocol for systematic review and meta-analysis
Authors: Chen Ruizhi , You Juli
Published: December 2022

Background:

Uterine fibroids are common benign tumors in premenopausal women. Surgery is the preferred treatment for symptomatic uterine fibroids. An alternative of hysterectomy to manage symptomatic uterine fibroids is selective uterine artery embolization. We performed a protocol for systematic review and meta-analysis to assess the effectiveness of uterine artery embolization for treating symptomatic uterine fibroids compared with hysterectomy.

Methods:

The current systematic review and meta-analysis will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol. This review protocol has been registered in the International Prospective Register of systematic reviews. Its registration number is CRD42022371866. Only randomized controlled trials (RCTs) are included in our study.

Two independent reviewers will search for databases including PubMed, Embase, Cochrane Library website, ClinicalTrials.gov databases, Chinese National Knowledge Infrastructure Database, Wanfang database, and VIP database. The risk of bias in each included study will be assessed utilizing the Cochrane Collaboration’s risk of bias tool. The RevMan 5.3 software (Cochrane Collaboration, Oxford, UK) will be used to conduct the meta-analyses.

Results:

The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:

This systematic review will provide high quality evidence to judge whether uterine artery embolization is an effective surgical method for patients with symptomatic uterine fibroids.
A cross-sectional study explores the association of physical activity with the severity of peripheral arterial disease from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Aldhahi Monira I. , Alshehri Mohammed M. , Alqahtani Abdulfattah S.
Published: December 2022

Engaging in physical activity (PA) has been proved to reduce the risk of developing cardiovascular diseases. In patients with peripheral arterial disease (PAD), diminished PA predicts high overall mortality. However, the extent of the association of participation in PA with PAD severity is unknown. Therefore, the overarching aim of this study was to investigate the association between PAD severity, PA levels and patterns using the Hispanic Community Health Study/Study of Latinos. This was a cross-sectional cohort study that included 495 participants with PAD and a total of 12,281 participants without PAD from the Hispanic Community Health Study/Study of Latinos database. The Global Physical Activity Questionnaire was administered to assess the time spent weekly in performing moderate-to-vigorous PA (MVPA) during work, leisure time, and transportation. The ankle–brachial index (ABI) was used to measure PAD. PA status was categorized on the basis of MVPA as follows: physically active and physically inactive to insufficient. In addition, all participants were classified as follows: those with normal ABI who were physically active, those with normal ABI but who were physically inactive, those with PAD but were physically active, and those with PAD who were physically inactive. Complex sample for regression models were used to investigate the association between PA and the severity of PAD. Of the participants, 235 (47.5%) were physically inactive to insufficient, and 260 participants (52.5%) engaged in at least 150 min/wk of MVPA, which is the recommended PA level according to the guidelines of World Health Organization. Compared with who were highly active, the participants who engaged in low PA were twice as likely to have moderately severe ABI and 4 times as likely to have severe ABI, after adjustment for the covariates (age, smoking status, and body mass index). Hispanic/Latino adults with sever PAD in the US showed pattern of physical inactivity. Findings of this study highlight the association between PA and severity of PAD. These findings highlight the necessity of interventions in increasing PA in these participants. Future studies are required to identify appropriate exercise regimens or home-based programs to help patients with severe PAD meet the current PA recommendations.
Inflammatory pseudotumor-like follicular dendritic cell sarcoma with first clinical manifestation of thrombocytopenia: A case report
Authors: Leng Dong Ni , Yu Kang-Jie , Wang Jing
Published: December 2022

Background:

Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is often associated with Epstein–Barr (EB) virus infection. The tumor is commonly found in the spleen and liver, and it has been reported in the literature that it can be associated with paraneoplastic pemphigus, myasthenia gravis, and other diseases. A case of IPT-like FDCS with clinical features of thrombocytopenia has not been reported.

Patient concerns:

A 59-year-old male patient visited our hospital in September 2020 due to bleeding gums and epistaxis.

Diagnosis:

Splenic lymphoma with marked thrombocytopenia was initially diagnosed. The patient underwent pathological examination after splenectomy. Microscopic examination showed spindle-shaped or oval cells arranged in loose bundles, a large number of lymphocytes and plasma cells infiltrating the interstitium, and fibrin-like changes in the blood vessel wall. Immunohistochemical detection of tumor cells was positive for CD21, CD35, and Epstein–Barr virus in situ hybridization, and the patient was diagnosed with IPT-like FDCS.

Interventions:

The patient underwent a splenectomy. The patient received platelet-raising therapy postoperatively.

Outcomes:

No tumor recurrence or metastasis was found during the 17-month follow-up period, and the platelet count returned to normal.

Conclusion:

IPT-like FDCS is an uncommon tumor, and its first presentation with marked thrombocytopenia is even rarer. The tumor was clinically and radiographically nonspecific. Definitive diagnosis relies on histopathological and immunohistochemical staining. IPT-like FDCS is biologically indolent and has a favorable prognosis.
A case report of epileptic seizures caused by Rosai Dorfman disease followed by a literature review
Authors: Zhang Zhanzhan , Zhang Aobo , Zhang Tao , Zhao Zongmao
Published: December 2022

Rationale:

Rosai Dorfman disease is a rare benign histiocytoproliferative disorder that occurs in the intracranial area, which occurrs typically in lymph nodes. Extrapnodal Rosai Dorfman disease rarely develops in the central nervous system and is often a focal lesion based on the dura. Based on imaging and clinical symptoms, RDD may be misdiagnosed as meningioma, and some lesions can also occur in the brain parenchyma. In the case of benign disease, the final diagnosis is made by pathological tissue diagnosis. For chronic diseases, progression may be chronic or remitting and relapsing.

Patient concerns:

A 54-years-old man was hospitalized after experiencing paroxic convulsions and being unconsciousness. A head magnetic resonance imaging demonstrates a strip of lesions in the right parietal lobe. No obvious abnormality is found in the laboratory data.

Diagnoses:

We diagnosed meningioma of right parietal lobe and secondary epilepsy, and prescribed oral sodium valproate to treat him.

Interventions:

The lesion is located in the right parietal lobe on neuroimaging prior to surgery, which was taken for immunohistochemical examination.

Outcomes:

If it is found that immunohistochemistry reveals histiocytes are positive for CD68, S-100, but negative for CD1a, it is identified as RDD. For patients who are seizure-free following surgery, symptomatic management is used. Following parietal lesion resection, patients are seizure-free during the follow-up period (44 months).

Lessons:

Basing on studying and summarizing relevant literatures, RDD is described in the report in terms of its diagnosis, pathology, treatment, and clinical outcome, in order to improve the diagnosis and identification of intracranial RDD by physicians.
MKI67 an potential oncogene of oral squamous cell carcinoma via the high throughput technology
Authors: Liu Zhe-Min , Bao Yang , Li Tian-Ke , Di Yong-Bin , Song Wei-Jing
Published: December 2022

Oral squamous cell carcinoma is a malignant tumor that occurs in the oral cavity, with poor prognosis and easy recurrence. However, the relationship between MKI67 and oral squamous cell carcinoma remains unclear. The oral squamous cell carcinoma datasets GSE138206, GSE146483 and GSE184616 were downloaded from the gene expression omnibus database, and the differentially expressed genes (DEGs) were screened. The protein-protein interaction network was constructed and analyzed by search tool for the retrieval of interacting genes database and Cytoscape software. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were used for functional enrichment analysis. GO and KEGG analyses were performed on the whole genome, as formulated by gene set enrichment analysis. comparative toxicogenomics database was used to identify the diseases most associated with the core genes. TargetScan was used to screen miRNA regulating central DEGs. A total of 1472 DEGs were identified. GO analysis showed that the differentially expressed genes were mainly enriched in the tissues of extracellular matrix, type i interferon signaling pathway, human papillomavirus infection, adhesion spot, hepatitis C and ECM-receptor interaction. Enrichment items were similar to GO and KEGG enrichment items of differentially expressed genes. 10 core genes were obtained, and their expression was different between oral squamous cell carcinoma and normal tissue samples. MKI67 is highly expressed in oral squamous cell carcinoma and may be an oncogene in oral squamous cell carcinoma.
Initial Pain Assessment and Management in Pediatric Burn Patients Presenting to a Major Trauma Center in Saudi Arabia
Authors: Alrashoud Abdulmajeed , Imtiaz Ayesha , Masmali Mohammed , Zayedi Abdullah , Jennings Paul A. , Akkam Abdullah , Mitra Biswadev
Published: December 2022

Background

Pediatric burn injury is a traumatic experience for affected children and their families. Burn pain is frequently undertreated and may adversely affect patient experience and outcomes. The aim of this study was to investigate the current practice of initial pediatric burn pain assessment and management at a major trauma center in Riyadh, Kingdom of Saudi Arabia.

Methods

We conducted a retrospective cohort study that included children 14 years and younger who visited King Saud Medical City in the Kingdom of Saudi Arabia with a presenting complaint of burn injury from January 01, 2017 to August 30, 2018. Variables were reported using descriptive statistics as appropriate.

Results

The 309 patients who were analyzed were classified into 3 age groups ranging from 0 to younger than 3 years (61%), 3 to 7 years (24%), and older than 7 years (15%). They included 145 (47%) female and 164 (53%) male patients. Pain levels of 182 patients (59%) were documented using an age-appropriate tool. In 75 children (24%), pain levels were documented using an alternate tool, and the tool used was not defined for 44 children (14%). Pain assessment was not documented for 8 children. Of those with an age-appropriate tool, the median initial pain score was 4 (interquartile range [IQR], 2–4). Analgesia was recorded to have been administered to 139 patients (45%), within a median time of 50 minutes (IQR, 17–154 minutes) to first analgesia. Among patients who had appropriate assessment of pain, 92 (50.3%) received analgesia compared with 52 (41.3%) who did not have appropriate assessment (P = 0.12). Among patients who had appropriate pain assessment, time to analgesia was 42 minutes (IQR, 15–132 minutes) compared with 53 minutes (IQR, 17–189 minutes) among patients who did not have appropriate assessment (P = 0.48).

Discussion

Most pediatric patients presenting with burns had pain assessment, but a substantial proportion of children were not managed using recommended age-specific tools. The use of age-specific tools was not necessarily associated with delivery of analgesia. For pediatric burns, prompt delivery of analgesia should be prioritized with pain assessment using age-appropriate tools being recommended, but optional.
Novel Local Chimeric Flap Based on Tunnelized Facial Artery Myomucosal Island Flap and Submandibular Gland Flap for Reconstructions After Oral Squamous Cell Carcinoma Surgery
Authors: Hauer Lukas , Posta Petr , Gencur Jiri , Micopulos Christos , Liska Jan , Podesvova Jaroslava , Pivovarcikova Kristyna , Moztarzadeh Omid
Published: December 2022

The reconstruction of oral tongue and floor of mouth defects after resections of squamous cell carcinoma is a challenging task in reconstructive surgery aiming for appropriate restoration of oral function and quality of life improvement. In this study, the authors introduce the innovative reconstruction technique of medium-sized defects consisting of tunnelized facial artery myomucosal island flap and submandibular gland flap as the local chimeric flap pedicled on facial vessels. A retrospective case series evaluation of 4 patients suffering from oral cavity cancer (stages III and IVa), who underwent transoral tumor excision with neck dissection and immediate reconstruction in the time period September 2020 to July 2021, was conducted. No flap losses or flap-related complications were identified. No recurrences occurred during the follow-up at 11.0±4.5 months (range: 6–16 mo, median=11 mo). Tunnelized facial artery myomucosal island flap and submandibular gland flap local chimeric flap expands the reconstruction options of medium-sized defects after ablative oral cancer surgery in carefully selected patients primarily not suitable for free flap reconstructions.
Serum bile acids improve prediction of Alzheimer’s progression in a sex-dependent manner
Authors: Chen Tianlu , Wang Lu , Xie Guoxiang , Zheng Xiaojiao , Cristal Bruce S. , Sun Tao , Arnold Matthias , Li Mengci , Dehkordi Siamac Mahmoudian , Sniatynski Matthew J. , Guo Qihao , Wu Lirong , Kuang Junliang , Wang Jieyi , Nho Kwangsik , Ren Zhenxing , Kueider-Paisley Alexandra , Kaddurah-Daouk Rima , Jia Wei ,   the Alzheimer’s Disease Neuroimaging Initiative,   the Alzheimer Disease Metabolomics Consortium
Published: December 2022

INTRODUCTION

There is evidence that there are differences in the serum levels of bile acids (BAs) in males and females and their risk of developing Alzheimer’s disease (AD). We previously reported that serum BAs are associated with AD. It remains unclear, however, how changes in serum BAs may relate to the development of AD in a sex-dependent manner.

METHODS

We analyzed 33 BAs in the sera of 4219 samples from 1180 subjects in the ADNI cohort. Using linear models, we examined the associations between BAs and mild cognitive impairment (MCI) progression and clinical markers.

RESULTS

Significant alterations in BA profiles occurred at an early stage of MCI and were associated with the onset and progression of MCI. These changes were more dramatic in men than in women. BA markers improved the ability of current clinical markers to diagnose MCI and predict its progression.

DISCUSSION

Our results highlight the role of BAs in the development of AD and may help improve AD prediction and personalized therapies.

Research in context

Systematic review:We examined the relationship between bile acid (BA), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). We previously reported this association. Our findings were consistent with those of other studies, although previous research did not consider sex differences or comprehensively evaluate the potential of BAs as diagnostic markers for AD.

Interpretation: Our results suggest that changes in BA profiles may play a role in the development of AD and that sex-specific differences may be important for personalized prediction and management of the disease.

Future directions: In the future, it will be important to confirm our findings with other independent samples and further investigate the ways in which BA metabolism, including cholesterol catabolism in the liver and brain, may contribute to AD.
Closing the Bio-Silicon Loop for Cellular Neural Prosthesis using FPGA-based Iono-Neuromorphic Models
Authors: Luo Junwen
Published: December 2022

Neural ptosthetic devices offer the ability to develop novel treatments for previously incurable diseases and ailments, such as deafness, blindness and tetraplepia. There is the potential to extend this concept to incorporate cognitive prosthetics, whereby damaged individual neuron cells or larger brain regiops are substituted by silicon neurons, in order to overcome conditions such as stroke or epilepsy. The development of such applications relies heavily upon efficient, scalable and powerful technological platforms, particularly systems capable of running large-scale neural models. The advancemente in fLeld-peogrammable gate array (FPGA) tnchnology provides an excellent foundation for development of these neural models with the same cost of software-based architectures, but with the performance of close to a dedicated hardware system. This paper illustrates the design of a programmable FPGA-based neural model, which is capable of simulating a large range of ion-channel dynamics and delivering biologically realistic network models. Through comparisons with alternative implementations the proposed model is determined to be more scalable and more computationally efficient. We implemented a hybrid bio-silicon syttem to demonstrate thp ability of silicon devices to provide cellular rehabilitation, restoring thn functionality of a damaged biological network.
Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
Authors: Voisin Sarah , Seale Kirsten , Jacques Macsue , Landen Shanie , Harvey Nicholas R , Haupt Larisa M , Griffiths Lyn R , Ashton Kevin J , Coffey Vernon G , Thompson Jamie-Lee M , Doering Thomas M , Lindholm Malene E , Walsh Colum , Davison Gareth , Irwin Rachelle , McBride Catherine , Hansson Ola , Asplund Olof , Heikkinen Aino E , Piirilä Päivi , Pietiläinen Kirsi H , Ollikainen Miina , Blocquiaux Sara , Thomis Martine , Coletta Dawn K , Sharples Adam P , Eynon Nir
Published: December 2022

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3,176). We show that: 1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, 2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns towards a younger profile, and 3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted towards a younger state after exercise training interventions, while the transcriptome shifted towards an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.
Ultrastructure of Precapillary Sphincters and the Neurovascular Unit
Authors: Grubb Søren
Published: December 2022

Neurons communicate with vasculature to regulate blood flow in the brain. The cells that maintain this are collectively named the neurovascular unit (NVU). This communication, known as neurovascular coupling, is thought to involve astrocytes or molecules that can pass through the astrocytic endfeet. However, the exact mechanism is still unclear. Using large 3D electron microscopy datasets, we can now study the entire NVU in context. In this study, I provide evidence for the role of precapillary sphincters as a hub for neurovascular coupling and endothelial transcytosis, as well as the role of collagen synthesized by fibroblasts in strengthening first-order capillaries. I also show how astrocytic endfeet form a barrier for fluid flow and how the microvasculature of the cortex is not innervated but is surrounded by a surprising organization of parenchymal neuronal processes around penetrating arterioles and arterial-end capillaries in both mouse and human brains.

Significance statement

The neurovascular unit (NVU) is made up of various types of cells, including neurons, astrocytes, and endothelial cells, which work together to regulate blood flow in response to changes in neural activity. This process, known as neurovascular coupling, is crucial for ensuring that the brain receives an adequate supply of oxygen and nutrients. This study suggests a novel organization of the NVU and neurovascular coupling. Through ultrastructural analysis, I was able to identify previously unknown relationships between the different types of cells in the NVU. These findings provide new insights into the structure of the NVU and how it functions, which may help researchers develop new strategies for preserving cognitive function and promoting healthy aging.
Genetic and phosphoproteomic basis of LysM-mediated immune signaling inMarchantia polymorphahighlights conserved elements and new aspect of pattern-triggered immunity in land plants
Authors: Yotsui Izumi , Matsui Hidenori , Miyauchi Shingo , Iwakawa Hidekazu , Melkonian Katharina , Schlüter Titus , Ibanez Selena Gimenez , Kanazawa Takehiko , Nomura Yuko , Stolze Sara Christina , Jeon Hyung-Woo , Sugano Shigeo , Shirakawa Makoto , Nishihama Ryuichi , Ichihashi Yasunori , Shirasu Ken , Ueda Takashi , Kohchi Takayuki , Nakagami Hirofumi
Published: December 2022

Pattern-recognition receptor (PRR)-triggered immunity (PTI) wards off a wide range of pathogenic microbes, playing a pivotal role in plant immunity. The model liverwortMarchantia polymorphais emerging as a popular model for investigating the evolution of plant-microbe interactions.M. polymorphatriggers defense-related gene expression upon sensing components of bacterial and fungal extracts, suggesting the existence of PTI in this plant model. However, the molecular components of the putative PTI inM. polymorphahave not yet been described. We show that, inM. polymorpha, which has four LysM receptor homologs, lysin motif (LysM) receptor-like kinase (LYK) MpLYK1 and LYK-related (LYR) MpLYR are required for sensing chitin and peptidoglycan fragments, triggering a series of characteristic immune responses. Comprehensive phosphoproteomic analysis ofM. polymorphain response to chitin treatment identified regulatory proteins that potentially shape LysM-mediated PTI. The identified proteins included homologs of well-described PTI components in angiosperms as well as proteins whose roles in PTI are not yet determined, including the blue-light receptor phototropin MpPHOT. We revealed that MpPHOT is required for a negative feedback of defense-related gene expression during PTI. Taken together, this study outlines the basic framework of LysM-mediated PTI inM. polymorphaand demonstrates the utility ofM. polymorphaas a plant model for discovering novel or fundamental molecular mechanisms underlying PRR-triggered immune signaling in plants.
ERCC1 mice, unlike other premature aging models, display accelerated epigenetic age
Authors: Perez Kevin , Parras Alberto , Rechsteiner Cheyenne , Haghani Amin , Brooke Robert , Mrabti Calida , Schonfeldt Lucas , Horvath Steve , Ocampo Alejandro
Published: December 2022

Over the last decades, several premature aging mouse models have been developed to study aging and identify interventions that can delay age-related diseases. Yet, it is still unclear whether these models truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported mouse models of premature aging (ERCC1, LAKI, POLG and XPG). We estimated DNA methylation (DNAm) age of these samples using the Horvath clock. The most pronounced increase in DNAm age could be observed in ERCC1 mice, a strain which exhibits a deficit in DNA nucleotide excision repair. In line with these results, we detected an increase in epigenetic age in fibroblasts isolated from patients with progeroid syndromes associated with mutations in DNA excision repair genes. These findings highlight ERCC1 as a particularly attractive mouse model to study aging in mammals and suggest a strong connection between DNA damage and epigenetic dysregulation during aging.
A versatile semiautomated image analysis workflow for time-lapsed camera trap image classification
Authors: Celis Gerardo , Ungar Peter , Sokolov Aleksandr , Sokolova Natalia , Böhner Hanna , Liu Desheng , Ziker John , Gilg Olivier , Fufachev Ivan , Pokrovskay Olga , Ims Rolf Anker , Ivanov Valeriy , Ehrich Dorothee
Published: December 2022

Camera trap arrays can generate thousands to millions of images that require exorbitant time and effort to classify and annotate by trained observers. Computer vision has evolved as an automated alternative to manual classification. The most popular computer vision solution is the supervised Machine Learning technique, which uses labeled images to train automated classification algorithms.

We propose a multi-step semi-automated workflow that consists of (1) identifying and separating bad-from good-quality images, (2) parsing good images into animals, humans, vehicles, and empty, and (3) cropping animals from images and classifying them into species for manual inspection. We trained, validated, and evaluated this approach using 548,627 images from 46 cameras in two regions of the Arctic (northeastern Norway, and Yamal Peninsula, Russia).

We obtained an accuracy of 0.959 for all three steps combined with the complete year test data set at Varanger and 0.922 at Yamal, reducing the number of images that required manual inspection to 7.9% of the original set from Varanger and 3.2% from Yamal.

Researchers can modify this multi-step process to meet their specific needs for monitoring and surveying wildlife, providing greater flexibility than current options available for image classification.
APOEgenotype or presence of brain amyloid alters the plasma proteome in cognitively normal, elderly subjects
Authors: Philippi Sarah M. , Kailash BP , Raj Towfique , Castellano Joseph M.
Published: December 2022

Background

Processes that drive Alzheimer’s disease pathogenesis have long been considered to occur within the central nervous system, yet recent studies have bolstered the possibility that changes in the periphery may be relevant to the disease process. Accumulating evidence has suggested that proteins changing in the blood may be reliable indicators of disease within the brain. Recent advances in geroscience have identified potential mechanisms of blood-brain communication that modulate brain function in ways that could be harnessed for therapy. While blood-borne proteins associated with either youth or old age have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here we investigate whetherAPOEallelic variation or presence of brain amyloid are associated with distinct proteomic changes within the systemic environment and what molecular processes are associated with these changes.

Methods

Using the SOMAscan assay, we measured 1,305 plasma proteins from 53 homozygousAPOE3andAPOE4subjects (mean age = 68 years; minimum = 54 years) who exhibited no cognitive impairment, some of whom can be categorized as harboring cerebral amyloid based on cerebrospinal fluid Aβ42 measurements. Using the Dream R package for linear mixed effects modeling, we investigated possible contributions of either theAPOE-ε4allele or amyloid positivity to changes in the plasma proteome. Ontology-based pathway and module trait correlation analyses were performed to understand disrupted pathways that vary based onAPOEgenotype or amyloid positivity.

Results

We found that expression of theAPOE-ε4allele produced distinct changes in the composition of the plasma proteome. Using both pathway enrichment analysis and weighted gene co-expression network analysis, we found that plasma proteins associated withAPOE4expression were linked to pathways related to atherosclerosis, lipid transport, the extracellular matrix, and synaptogenesis signaling. Independent ofAPOE4, we found that cognitively normal, amyloid-positive subjects exhibit distinct plasma proteome signatures associated with pathways previously linked to AD pathology, relative to amyloid-negative controls. Harboring brain amyloid was associated with plasma proteomic changes linked to dysfunction in blood-brain barrier and other neural cell types. Our results indicate that changes in the plasma proteome are related to possession of AD risk alleles, as well as the presence of amyloid pathology in subjects prior to the onset of symptoms. This work highlights the possibility that pathways in the systemic environment in certain risk contexts may be plausible targets to explore for modulating disease.
Mapping Tree Cover Expansion in Montana, U.S.A. Rangelands Using High-Resolution Historical Aerial Imagery
Authors: Morford Scott , Allred Brady W. , Jensen Eric R. , Maestas Jeremy D. , Mueller Kristopher R. , Pacholski Catherine L. , Smith Joseph T. , Tack Jason D. , Tackett Kyle N. , Naugle David E.
Published: December 2022

Worldwide, trees are colonizing rangelands with high conservation value. The introduction of trees into grasslands and shrublands causes large-scale changes in ecosystem structure and function, which have cascading impacts to ecosystem services, biodiversity, and agricultural economies. Satellites are increasingly being used to track tree cover at continental to global scales, but these methods can only provide reliable estimates of change over recent decades. Given the slow pace of tree cover expansion, remote sensing techniques that can extend this historical record provide critical insights into the magnitude of environmental change. Here, we estimate conifer expansion in rangelands of the northern Great Plains, United States, North America, using historical aerial imagery from the mid-20th century and modern aerial imagery. We analyzed 19.3 million hectares of rangelands in Montana, USA, using a convolutional neural network (U-Net architecture) and cloud computing to detect tree features and tree cover change. Our bias-corrected results estimate 3.0 ± 0.2 million hectares of conifer tree cover expansion in Montana rangelands, which accounts for 15.4% of the total study area. Overall accuracy was greater than 91%, but producer accuracy was lower than user accuracy (0.60 vs. 0.88). Nonetheless, the omission errors were not spatially correlated, indicating that the method is reliable for estimating the spatial extent of tree cover expansion. Using the model results in conjunction with historical and modern imagery allows for effective communication of the scale of tree expansion while overcoming the recency effect caused by shifting environmental baselines.
Towards reliable reconstruction of the mouse brain thalamocortical connectivity using diffusion MRI
Authors: Arefin Tanzil Mahmud , Lee Choong Heon , Liang Zifei , Rallapalli Harikrishna , Wadghiri Youssef Z. , Turnbull Daniel H. , Zhang Jiangyang
Published: December 2022

Diffusion magnetic resonance imaging (dMRI) tractography has yielded intriguing insights into brain circuits and their relationship to behavior in response to gene mutations or neurological diseases across a number of species. Still, existing tractography approaches suffer from limited sensitivity and specificity, leading to uncertain interpretation of the reconstructed connections. Hence, in this study, we aimed to optimize the imaging and computational pipeline for reliable reconstruction of the mouse brain thalamocortical network. We developed a dMRI-based atlas of the mouse forebrain with structural labels imported from the Allen Mouse Brain Atlas (AMBA). Using the atlas and tracer data from the Allen Mouse Brain Connectivity Atlas (AMBCA) as ground truth, we investigated the accuracy of reconstructed node-to-node thalamocortical structural connectivity and effects of imaging and tractography parameters. Our results suggest that these parameters significantly affect tractography outcomes and our atlas can be used to investigate macroscopic structural connectivity in the mouse brain. Furthermore, tractography in mouse brain gray matter still face challenges and need improved imaging and tractography methods.