bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of cognitive behavioral active engagement training on test item construction skills among primary school teachers in Nigeria
Authors: Ede Moses Onyemaechi , Agah John J. , Okeke Chinedu Ifedi , Chuks Zudonu Onisoman , Oguguo Basil C.E. , Agu Patricia Uzoamaka , Ene Catherine U. , Ekesionye Ngozi E. , Nji Ifeyinwa Awele , Eze Chikodili , Manafa Ifeyinwa F.
Published: September 2021

Background:

Most classroom teachers are weak in constructing test items for assessment of students. This study examined the effects of cognitive behavioral active engagement training on test items construction skills among primary school teachers in Nigeria.

Methods:

We adopted a randomized pretest–posttest control group design. A total of 148 participants served as the study sample. One instrument was used for data collection. The participants were administered the instrument at 4 different times. Test construction guide was employed to implement the training. Data analysis was completed using analysis of covariance.

Results

The researchers found that cognitive behavioral active engagement training had a significant effect on participants’ test items construction scores as measured by test construction skills inventory at posttest, first and second follow-up stages.

Conclusion

The researchers concluded that cognitive behavioral active engagement training is efficacious in the improvement of test items construction skills among primary school teachers in Nigeria.
Two years outcomes of treating full-thickness macula hole associated with idiopathic macular telangiectasia type 2 by internal limiting membrane inverted flap technique
Authors: Nishiyama Shungo , Iwase Takeshi
Published: September 2021

Rational:

Macular telangiectasia (MacTel) is an uncommon ocular disorder that can lead to legal blindness. MacTel type 2 is characterized by a bilateral loss of macular transparency, the presence of white crystals on the retina, aberrant blood vessel growth, and neurodegeneration of the macula. Full-thickness macular holes (FTMHs) are a prominent cause of vision reduction in MacTel type 2, and the standard care for an FTMH is pars plana vitrectomy (PPV) to restore the FTMH and best-corrected visual acuity (BCVA). However, surgical outcomes in previous reports were not good, with a lack of closure or a reopening of the FTMH, compared with those with an idiopathic FTMH. Thus, this study aimed to determine the surgical outcomes of PPV with the inverted ILM flap technique for the treatment of FTMHs with a 2-year postoperative follow-up in three patients with MacTel type 2.

Patient concerns:

This study involved 3 patients who had been diagnosed with MacTel type 2 at a local eye clinic and who was subsequently referred to our department for a more detailed examination.

Diagnoses:

Three patients were diagnosed with MacTel type 2 using dilated ophthalmoscopy, fluorescein angiography, and optical coherence tomography (OCT) in both eyes. A FTMH was developed and visual acuity decreased during follow-up period in all of the patients.

Interventions:

Each patient underwent PPV in 1 eye using the inverted ILM-flap technique, gas tamponade, and prone positioning.

Outcomes:

The FTMH was successfully closed in the 3 cases after the surgery. OCT showed that the FTMH remained closed at the last follow-up examination in 2 patients and vision improved to 20/20 and 20/25. In the other patient, the hole was closed temporarily after surgery, but was reopened at 6 months. The vision had improved to 20/60 until the hole was reopened, and it was 20/100 at the final follow-up examination.

Lessons:

Although only 3 patients were examined, the inverted ILM-flap technique may be an effective and safe method to close an FTMH in patients with MacTel type 2. However, the surgery cannot prevent the reopening of the hole when the retinal atrophy progresses.
Removal of a catheter mount and heat-and-moisture exchanger improves hypercapnia in patients with acute respiratory distress syndrome
Authors: Shimoda Takaya , Sekino Motohiro , Higashijima Ushio , Matsumoto Sojiro , Sato Shuntaro , Yano Rintaro , Egashira Takashi , Araki Hiroshi , Naoya Iwasaki , Miki Suzumura , Koyanagi Ryo , Hayashi Makoto , Kurihara Shintaro , Hara Tetsuya
Published: September 2021

To avoid ventilator-associated lung injury in acute respiratory distress syndrome (ARDS) treatment, respiratory management should be performed at a low tidal volume of 6 to 8 mL/kg and plateau pressure of ≤30 cmH2O. However, such lung-protective ventilation often results in hypercapnia, which is a risk factor for poor outcomes. The purpose of this study was to retrospectively evaluate the effectiveness and safety of the removal of a catheter mount (CM) and using heated humidifiers (HH) instead of a heat-and-moisture exchanger (HME) for reducing the mechanical dead space created by the CM and HME, which may improve hypercapnia in patients with ARDS.

This retrospective observational study included adult patients with ARDS, who developed hypercapnia (PaCO2 > 45 mm Hg) during mechanical ventilation, with target tidal volumes between 6 and 8 mL/kg and a plateau pressure of ≤30 cmH2O, and underwent stepwise removal of CM and HME (replaced with HH). The PaCO2 values were measured at 3 points: ventilator circuit with CM and HME (CM + HME) use, with HME (HME), and with HH (HH), and the overall number of accidental extubations was evaluated. Ventilator values (tidal volume, respiratory rate, minutes volume) were evaluated at the same points.

A total of 21 patients with mild-to-moderate ARDS who were treated under deep sedation were included. The values of PaCO2 at HME (52.7 ± 7.4 mm Hg, P < .0001) and HH (46.3 ± 6.8 mm Hg, P < .0001) were significantly lower than those at CM + HME (55.9 ± 7.9 mm Hg). Measured ventilator values were similar at CM + HME, HME, and HH. There were no cases of reintubation due to accidental extubation after the removal of CM.

The removal of CM and HME reduced PaCO2 values without changing the ventilator settings in deeply sedated patients with mild-to-moderate ARDS on lung-protective ventilation. Caution should be exercised, as the removal of a CM may result in circuit disconnection or accidental extubation. Nevertheless, this intervention may improve hypercapnia and promote lung-protective ventilation.
Drugs in Focus
Authors: Mas Emmanuel , Borrelli Osvaldo , Broekaert Ilse , de‐Carpi J. Martin , Dolinsek Jernej , Miele Erasmo , Pienar Corina , Koninckx C. Ribes , Thomassen Ruth‐Anne , Thomson Mike , Tzivinikos Christo , Benninga Marc A.
Published: September 2021

Octreotide, a somatostatin analogue, has been used for more than 20 years in children with gastrointestinal bleeding, chylothorax or chylous ascites, intestinal lymphangiectasia, pancreatitis, intestinal dysmotility, and severe diarrhoea; however, until now, there is a lack of randomised clinical trials evaluating the efficacy of this compound in childhood. Hence, we aimed to review the literature in order to determine the evidence of its use and safety in children, using PubMed from 2000 to 2021 with the search terms “octreotide” and “children” and “bleeding or chylous ascites or chylothorax or acute pancreatitis or lymphangiectasia or diarrhoea or intestinal dysmotility”.
Health Promotion and Wellness in Neurologic Physical Therapy: Strategies to Advance Practice
Authors: Rafferty Miriam R. , Held Bradford Elissa C. , Fritz Stacy , Hutchinson Karen J. , Miczak Kimberly , Resnick Arielle , Billinger Sandra A.
Published: September 2021

Background and Purpose:

Neurologic physical therapy (PT) can assist people with neurologic conditions and injuries to optimize their health and well-being by addressing barriers at the individual, relationship, community, and societal levels. The purpose of this special interest article is to provide consensus-driven strategies to address barriers to implementing health promotion and wellness (HPW)-related neurologic PT practice.

Summary of Key Points:

Environmental scan, literature review, and expert input were used to determine barriers and develop strategies. Barriers include lack of time; low knowledge, self-efficacy, and awareness; client complexity; and lack of HPW resources; as well as concerns regarding payment and scope of practice. Four key strategies emerged: (1) develop and disseminate a consensus-based scope of practice for HPW in neurologic PT; (2) increase knowledge of resources related to HPW; (3) promote delivery models for HPW-related neurologic PT; and (4) encourage advocacy, community building and partnership along the continuum of care.

Recommendations for Clinical Practice:

Clinicians should practice to their full scope of HPW-related PT practice. This includes optimizing movement, including physical activity and fitness, as well as reinforcing the importance of healthy sleep, nutrition, stress, and smoking cessation. These activities address primary, secondary, and tertiary prevention. Clinicians are encouraged to report their experiences with HPW-focused delivery models and outcomes. Additional research is needed to understand the full impact of HPW on PT practice (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A364).
HMB45/PRAME, a Novel Double Staining for the Diagnosis of Melanocytic Neoplasms: Technical Aspects, Results, and Comparison With Other Commercially Available Staining (PRAME and Melan A/PRAME)
Authors: Grillini Marco , Ricci Costantino , Pino Vincenzo , Pedrini Silvia , Fiorentino Michelangelo , Corti Barbara
Published: September 2021

PRAME (PReferentially expressed Antigen in MElanoma) is a tumor-associated antigen that was recently found to be expressed by malignant melanocytic lesions but not by benign ones, thus resulting useful in this diagnostic field. PRAME could also be expressed by some normal tissues and nonmelanocytic tumors, suggesting as caution should be adopted to use PRAME as a “pan-melanoma” marker for the differential diagnosis with other malignant tumors. Until now, PRAME expression was exclusively investigated through single staining with a monoclonal antibody targeting PRAME and with double staining for Melan A/PRAME found to be useful in specific diagnostic sets. Herein, we studied the expression of PRAME in 40 melanocytic lesions and 23 nonmelanocytic ones using PRAME, Melan A/PRAME, and novel double staining for HMB45/PRAME. Although our results need to be validated, they support the adoption of HMB45/PRAME, alone or in combination with PRAME and Melan A/PRAME, as a helpful marker in the diagnosis of melanocytic neoplasms with a high concordance rate between primary melanoma and corresponding metastases.
Feasibility of Point-of-Care Ultrasound for Diagnosing Hypertrophic Pyloric Stenosis in the Emergency Department
Authors: Park Jun Sung , Byun Young-Hoon , Choi Seung Jun , Lee Jong Seung , Ryu Jeong-Min , Lee Jeong-Yong
Published: September 2021

Objectives

This study aimed to investigate the feasibility of point-of-care ultrasound (POCUS) for diagnosing hypertrophic pyloric stenosis (HPS) in the emergency department (ED).

Methods

A retrospective study was conducted in infants aged younger than 90 days who were brought to the ED due to vomiting between January 2015 and December 2019. Of these, infants who were clinically suspected of having HPS and underwent ultrasound were included and categorized into 3 groups: POCUS only, POCUS followed by radiologist-performed ultrasound (RADUS), and RADUS only. All confirmative diagnoses of HPS were made by RADUS. The diagnostic performance of POCUS was analyzed, and the ED patient flow was compared between the POCUS-performed (POCUS only or POCUS followed by RADUS) and RADUS-only groups.

Results

Overall, 171 patients with a median age of 34 days were included. Of these, 79 patients (46.2%) underwent POCUS only, and none had HPS; 50 patients (29.2%) underwent POCUS followed by RADUS; and 42 patients (24.5%) underwent RADUS only. Overall, 41 patients (24.0%) were diagnosed with HPS, and POCUS showed a sensitivity of 96.6% and specificity of 94.0%. In the total cohort, length of stay in the ED (EDLOS) was shorter in the POCUS-performed group than in the RADUS-only group (2.6 vs 3.8 hours,P= 0.015). Among non-HPS patients, time to disposition (1.8 vs 2.7 hours,P= 0.005) and EDLOS (2.0 vs 3.0 hours,P= 0.004) were shorter in the POCUS-performed group than in the RADUS-only group. Performing POCUS followed by RADUS did not significantly delay the treatment among HPS patients.

Conclusions

Point-of-care ultrasound is accurate and useful for diagnosing HPS and improved the ED patient flow by reducing EDLOS and door-to-disposition time in non-HPS patients.
Lessons Learned From Implementing Rehabilitation at a COVID-19 Field Hospital
Authors: McLaughlin Kevin H. , Simon Lauren , Friedman Michael , Siddiqui Zishan K. , Ficke James R. , Kantsiper Melinda E. ,   CONQUER COVID Consortium
Published: September 2021

Rehabilitation experts play an important role in preventing hospital-acquired debility, increasing patients’ abilities to safely perform activities of daily living, and facilitating discharge to the home setting for patients with COVID-19. Surges in COVID-19 hospitalization rates combined with increases in length of hospital stay and decreases in postacute care placements have necessitated the opening of COVID-19 field hospitals around the country. Most field hospitals lack the resources to offer a full suite of rehabilitation services, but there are opportunities for small teams of rehabilitation experts to increase their reach by using innovative strategies. This article describes the implementation of a small team of rehabilitation experts in a COVID-19 field hospital and strategies used by this team to maximize patient activity and mobility, facilitate timely discharge, and maximize the number of patients discharged to the home setting. Strategies include training nonclinical staff to assist with activity and mobility promotion and using a rehabilitation triage system to determine needs of individual patients and facilitate efficient resource utilization. The authors reflect on successful aspects of these strategies, as well as barriers to rehabilitation implementation, and make recommendations for other field hospitals seeking to implement rehabilitation during the COVID-19 pandemic or future health crises.
Psychobiological Mechanisms in Somatic Symptom Disorder and Depressive Disorders: An Ecological Momentary Assessment Approach
Authors: Mewes Ricarda , Feneberg Anja C. , Doerr Johanna M. , Nater Urs M.
Published: September 2021

Objective

Persistent somatic symptoms cause strong impairment in persons with somatic symptom disorder (SSD) and depressive disorders (DDs). Specific negative psychological factors (NPFs), such as catastrophizing, negative affectivity, and behavioral avoidance, are assumed to contribute to this impairment and may maintain symptoms via dysregulations of biological stress systems. We examined the associations between NPF and somatic symptoms in the daily life of women with SSD or DD and investigated the mediating role of psychobiological stress responses.

Methods

Twenty-nine women with SSD and 29 women with DD participated in an ecological momentary assessment study. For 14 days, intensity of and impairment by somatic symptoms, NPF, and stress-related biological measures (cortisol, alpha-amylase) were assessed five times per day using an electronic device and saliva samples. Multilevel models were conducted.

Results

The greater the number of NPF, the higher the concurrent and time-lagged intensity of and impairment by somatic symptoms in both groups (12.0%–38.6% of variance explained; χ2(12) p < .001 for all models). NPFs were associated with higher cortisol levels in women with DD and with lower levels in women with SSD (interaction NPF by group: B = −0.04, p = .042 for concurrent; B = −0.06, p = .019 for time-lagged). In women with SSD, lower cortisol levels were associated with higher intensity at the next measurement time point (group by cortisol: B = −1.71, p = .020). No mediation effects were found.

Conclusions

NPFs may be considered as transdiagnostic factors in the development and treatment of impairing somatic symptoms. Our findings will allow the development of new treatment strategies that use ecological momentary intervention approaches focusing on NPF.
Brief Report: Efficacy and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Females Living With HIV: An Integrated Analysis of 5 Trials
Authors: Orkin Chloe , Ajana Faiza , Kityo Cissy , Koenig Ellen , Natukunda Eva , Gandhi-Patel Bhumi , Wang Hui , Liu Yapei , Wei Xuelian , White Kirsten , Makadzange Tariro , Pikora Cheryl , McNicholl Ian , Collins Sean E. , Brainard Diana , Chuck Susan K.
Published: September 2021

Background:

We characterized the efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in a broad population of pediatric/adolescent/adult/elderly females living with HIV (FWH).

Setting:

Integrated analysis.

Methods:

Available data from 5 trials were integrated. Week 48 virologic suppression (HIV-1 RNA <50 copies/mL), resistance, adverse events (AEs), and laboratory parameters were assessed.

Results:

Three hundred and seventy-three FWH [304 virologically suppressed; 69 antiretroviral therapy (ART)-naive] received B/F/TAF [data from comparator regimens available for 306 individuals (236 virologically suppressed and 70 ART-naive participants)]. Virologic suppression rates with B/F/TAF at week 48 were high regardless of age in participants virologically suppressed at baseline (≥95%) and in ART-naive participants (≥87%). Virologic suppression rates were similar in B/F/TAF and comparator regimens (both virologically suppressed and ART-naive groups). Treatment-emergent resistance was not detected in the B/F/TAF group. AEs considered related to study drugs were experienced by 9.2% (B/F/TAF) and 5.5% (comparator regimen) of virologically suppressed participants and 15.9% (B/F/TAF) and 31.4% (comparator regimen) of ART-naive participants. For virologically suppressed and ART-naive FWH combined, only 1 of the 373 B/F/TAF–treated and 2 of the 306 comparator-regimen participants discontinued because of AEs (none were bone/renal/hepatic AEs); grade 3/4 AEs were experienced by 5.1% (B/F/TAF) and 7.8% (comparator regimen); and grade 3/4 elevation of low-density lipoprotein/total cholesterol occurred in 2.7%/0.3% (B/F/TAF) and 5.9%/2.0% (comparator regimen). At week 48, median changes from baseline estimated glomerular filtration rate in adults were <5 mL/min; results were similar in B/F/TAF and comparator-regimen groups.

Conclusion:

B/F/TAF treatment was effective and well tolerated over 48 weeks, confirming B/F/TAF as an option for a broad population of FWH.
Diagnostic Performance of Proton Magnetic Resonance Spectroscopy and 18F-Fluorocholine PET to Differentiate Benign From Malignant Breast Lesions
Authors: Wu Li-An , Yen Ruoh-Fang , Shih Tiffany Ting-Fang , Chen Kuan-Lin , Wang Jane
Published: September 2021

Purpose

The aim of this study was to evaluate the diagnostic performance of the proton magnetic resonance spectroscopy (MRS) and 18F-fluorocholine (FCH) PET for suspicious breast findings on conventional imaging (mammography and breast ultrasound).

Methods

From September 2012 to December 2015, 37 women with 39 breast lesions on conventional imaging were enrolled and underwent proton MRS and FCH PET. The MRS parameters of choline signal-to-noise ratio (SNR), choline integral (I(cho)), and the PET parameters including SUVmax in the prone (SUV1) and supine (SUV2) positions were analyzed. Receiver operating characteristic curves with the area under the curve, sensitivity, and specificity under the optimal cutoff points for the different parameters were determined.

Results

Twenty-three lesions (59%) were malignant, and 16 (41.0%) were benign. The malignant lesions tended to show significantly higher MRS and PET parameters than benign lesions (choline SNR, P = 0.007; I(cho), P = 0.003; SUV1 and SUV2, P < 0.0001). Fair to moderate correlations were noted between the choline SNR and PET parameters (SUV1, Spearman rank correlation coefficient, ρ = 0.477; SUV2, ρ = 0.483), as well as I(cho) and PET parameters (SUV1, ρ = 0.493; SUV2, ρ = 0.549). The SUV2 showed the highest diagnostic performance (area under the curve, 0.918). Using 2.5 as the optimal cutoff point, the SUV2 yields 89.5% sensitivity and 87.5% specificity for differentiating malignant from benign lesions.

Conclusion

The MRS parameters were fairly to moderately correlated with FCH PET parameters, and both could differentiate malignant from benign breast lesions with SUV2 showing best diagnostic performance.
Acute Disseminated Encephalomyelitis in FET PET/MR
Authors: Lohaus Niklas , Mader Cäcilia , Jelcic Ilijas , Reimann Regina , Huellner Martin W.
Published: September 2021

After 3 weeks of daily headache, a 28-year-old, otherwise healthy woman was admitted to the emergency department with a first-time generalized seizure. CT showed a left frontal mass with perifocal edema. Brain MRI raised the suspicion of cerebral lymphoma. Cerebrospinal fluid analysis revealed mononuclear pleocytosis of 14 cells/μL without malignant cells, normal protein levels, and absence of oligoclonal bands. FET PET/MRI of the lesion showed FET characteristics of inflammatory disease, and acute disseminated encephalomyelitis was suggested as diagnosis. Final histopathological results from brain biopsy confirmed acute disseminated encephalomyelitis.
An Incidental Uptake of 18F-Choline in Paraganglioma
Authors: Castello Angelo , Zuccotti Giulia , Bonatto Elena , Florimonte Luigia , Castellani Massimo
Published: September 2021

We present a case of carotid glomus paraganglioma incidentally detected using 18F-choline PET/CT in a 63-year-old man with prostate cancer. 18F-choline PET/CT scan demonstrated a small area of 18F-choline uptake (SUVmax, 2.3) in the right parapharyngeal space of the neck, later diagnosed as paraganglioma with low proliferation index. 18F-choline PET/CT may represent a valid alternative for studying paraganglioma when either 18F-DOPA or 68Ga-SSA are not available.
FDG PET/CT of Primary Ewing Sarcoma of the Peritoneum
Authors: Jiang Chengzhi , Peng Xiang , Ye Hui , Zhang Yanyin , Zheng Kai
Published: September 2021

Ewing sarcoma (ES), which is described as diffuse endothelioma of the bone, is divided into osseous and extraosseous ES mostly affecting children and adolescents. In addition, ES of the peritoneum is rare. We present a case of a 46-year-old man with ES of the peritoneum in whom FDG PET/CT showed high radiotracer activity in the primary tumor.
Subclinical Hypothyroidism After 225Ac-DOTATATE Therapy in a Case of Metastatic Neuroendocrine Tumor
Authors: Kavanal Anwin Joseph , Satapathy Swayamjeet , Sood Ashwani , Khosla Divya , Mittal Bhagwant Rai
Published: September 2021

Radiation-induced thyroid dysfunction is very rarely associated with peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors using β-emitting radionuclides. With the emergence of α radionuclide such as 225Ac, PRRT using these radionuclides has shown better results; however, data on the toxicity profile are limited. This is a case report describing the thyroid dysfunction developed in a patient with inoperable metastatic neuroendocrine tumor with unknown primary after PRRT using 225Ac-DOTATATE, which has never been reported previously.
68Ga-Exendin-4 PET/CT Differentiates Insulinoma From Accessory Spleen in a Patient Presenting Indeterminate MRI and 68Ga-DOTATATE PET/CT Findings
Authors: Pang Yizhen , Meng Tinghua , Shang Qihang , Chen Zheng , Chen Haojun
Published: September 2021

A 55-year-old woman with endogenous hyperinsulinemia hypoglycemia was clinically diagnosed with insulinoma. Contrast-enhanced MRI revealed an inconclusive hypointense lesion in the pancreatic tail, and the enhancement pattern does not support the diagnosis of insulinoma. 68Ga-DOTATATE PET/CT showed intense radioactivity in this nodule, similar to the radioactivity of the adjacent spleen. Therefore, the diagnosis of accessory spleen cannot be excluded. Follow-up with 68Ga-exendin-4 PET/CT also showed intense uptake in this nodule, but no significant uptake in the spleen was observed at this time. Therefore, the insulinoma was unmasked from the spleen, excluding the diagnosis of accessory spleen, and allowing curative surgery.
Pyruvate-Driven Oxidative Phosphorylation is Downregulated in Sepsis-Induced Cardiomyopathy: A Study of Mitochondrial Proteome
Authors: Shimada Briana K. , Boyman Liron , Huang Weiliang , Zhu Jing , Yang Yang , Chen Fengqian , Kane Maureen A. , Yadava Nagendra , Zou Lin , Lederer W. Jonathan , Polster Brian M. , Chao Wei
Published: September 2021

Background:

Sepsis-induced cardiomyopathy (SIC) is a major contributing factor for morbidity and mortality in sepsis. Accumulative evidence has suggested that cardiac mitochondrial oxidative phosphorylation is attenuated in sepsis, but the underlying molecular mechanisms remain incompletely understood.

Methods:

Adult male mice of 9 to 12 weeks old were subjected to sham or cecal ligation and puncture procedure. Echocardiography in vivo and Langendorff-perfused hearts were used to assess cardiac function 24 h after the procedures. Unbiased proteomics analysis was performed to profile mitochondrial proteins in the hearts of both sham and SIC mice. Seahorse respirator technology was used to evaluate oxygen consumption in purified mitochondria.

Results:

Of the 665 mitochondrial proteins identified in the proteomics assay, 35 were altered in septic mice. The mitochondrial remodeling involved various energy metabolism pathways including subunits of the electron transport chain, fatty acid catabolism, and carbohydrate oxidative metabolism. We also identified a significant increase of pyruvate dehydrogenase (PDH) kinase 4 (PDK4) and inhibition of PDH activity in septic hearts. Furthermore, compared to sham mice, mitochondrial oxygen consumption of septic mice was significantly reduced when pyruvate was provided as a substrate. However, it was unchanged when PDH was bypassed by directly supplying the Complex I substrate NADH, or by using the Complex II substrate succinate, or using Complex IV substrate, or by providing the beta-oxidation substrate palmitoylcarnitine, neither of which require PDH for mitochondrial oxygen consumption.

Conclusions:

These data demonstrate a broad mitochondrial protein remodeling, PDH inactivation and impaired pyruvate-fueled oxidative phosphorylation during SIC, and provide a molecular framework for further exploration.
Cell graph neural networks enable the digital staging of tumor microenvironment and precise prediction of patient survival in gastric cancer
Authors: Wang Yanan , Wang Yu Guang , Hu Changyuan , Li Ming , Fan Yanan , Otter Nina , Sam Ikuan , Gou Hongquan , Hu Yiqun , Kwok Terry , Zalcberg John , Boussioutas Alex , Daly Roger J. , Montúfar Guido , Liò Pietro , Xu Dakang , Webb Geoffrey I. , Song Jiangning
Published: September 2021

Gastric cancer is one of the deadliest cancers worldwide. Accurate prognosis is essential for effective clinical assessment and treatment. Spatial patterns in the tumor microenvironment (TME) are conceptually indicative of the staging and progression of gastric cancer patients. Using spatial patterns of the TME by integrating and transforming the multiplexed immunohistochemistry (mIHC) images as Cell-Graphs, we propose a novel graph neural network-based approach, termed Cell-Graph Signature or CGSignature, powered by artificial intelligence, for digital staging of TME and precise prediction of patient survival in gastric cancer. In this study, patient survival prediction is formulated as either a binary (short-term and long-term) or ternary (short-term, medium-term, and long-term) classification task. Extensive benchmarking experiments demonstrate that the CGSignature achieves outstanding model performance, with Area Under the Receiver-Operating Characteristic curve (AUROC) of 0.960±0.01, and 0.771±0.024 to 0.904±0.012 for the binary- and ternary-classification, respectively. Moreover, Kaplan-Meier survival analysis indicates that the ‘digital-grade’ cancer staging produced by CGSignature provides a remarkable capability in discriminating both binary and ternary classes with statistical significance (p-value < 0.0001), significantly outperforming the AJCC 8th edition Tumor-Node-Metastasis staging system. Using Cell-Graphs extracted from mIHC images, CGSignature improves the assessment of the link between the TME spatial patterns and patient prognosis. Our study suggests the feasibility and benefits of such artificial intelligence-powered digital staging system in diagnostic pathology and precision oncology.
Abnormal Functional Network Topology and its Dynamics during Sustained Attention Processing Significantly Implicate Post-TBI Attention Deficits in Children
Authors: Cao Meng , Halperin Jeffrey M. , Li Xiaobo
Published: September 2021

Traumatic brain injury (TBI) is highly prevalent in children. Attention deficits are among the most common and persistent post-TBI cognitive and behavioral sequalae that can contribute to adverse outcomes. This study investigated the topological properties of the functional brain network for sustained attention processing and their dynamics in 42 children with severe post-TBI attention deficits (TBI-A) and 47 matched healthy controls. Functional MRI (fMRI) data during a block-designed sustained attention task was collected for each subject, with each full task block further divided into the pre-, early-, late-, and post-stimulation stages. The task-related functional brain network was constructed using the graph theoretic technique. Then the sliding-window-based method was utilized to assess the dynamics of the topological properties in each stimulation stage. The results showed that relative to the matched controls, children with TBI-A had significantly reduced nodal efficiency and/or degree of left postcentral, inferior parietal, inferior temporal, and fusiform gyri and their decreased stability during the early- and late-stimulation stages. The left postcentral inferior parietal network anomalies were found to be significantly associated with elevated inattentive symptoms in children with TBI-A. These results suggest that abnormal functional network characteristics and their dynamics associated with left parietal lobe may significantly link to the onset of the severe post-TBI attention deficits in children.
Unstable periodic orbits are faithful biomarker for the onset of epileptic seizure
Authors: Pal Mayukha , Bhattacherjee Sree , Panigrahi Prasanta K.
Published: September 2021

EEG signals of healthy individuals and epileptic patients, when treated as time series of evolving dynamical systems, are found to display characteristic differences in the behavior of the unstable periodic orbits (UPO), marking the transition from regular periodic variations to self-similar dynamics. The UPO, manifesting as broad resonances in the Fourier power spectra, are quite prominent in their presence in the normal signals and are either absent or considerably weakened with a shift towards lower frequency in the epileptic condition. The weighted average and visibility power computed for the UPO region are found to distinguish epileptic seizure from healthy individuals’ EEG. Remarkably, the unstable periodic motion for healthy ones is well described by damped harmonic motion, the orbits displaying smooth dynamics. In contrast, the epileptic cases show bi-stability and piecewise linear motion for the larger orbits, exhibiting large sudden jumps in the ‘velocity’ (referred to the rate of change of the EEG potentials), characteristically different from the healthy cases, highlighting the efficacy of the UPO as biomarkers. For both the regions, 8-14Hz UPO and 40-45Hz resonance, we used data driven analysis to derive the system dynamics in terms of sinusoidal functions, which reveal the presence of higher harmonics, confirming nonlinearity of the underlying system and leading to quantification of the discernible differences between the healthy and epileptic patients. The gamma wave region in the 40-45Hz range, connecting the conscious and the unconscious states of the brain, reveals well-structured coherence phenomena, in addition to the prominent resonance, which potentially can be used as a biomarker for the epileptic seizure. The wavelet scalogram analysis for both UPO and 40-45Hz region also clearly differentiates the healthy condition from epileptic seizure, confirming the above dynamical picture, depicting the higher harmonic generation, and intermixing of different modes in these two regions of interest.

Significance

Unstable periodic orbits are demonstrated as faithful biomarkers for detecting seizure, being prominently present in the Fourier power spectra of the EEG signals of the healthy individuals and either being absent or significantly suppressed for the epileptic cases, showing distinctly different behavior for the unstable orbits, in the two cases. A phase space study, with EEG potential and its rate of change as coordinate and corresponding velocity, clearly delineates the dynamics in healthy and diseased individuals, demonstrating the absence or weakening of UPO, that can be a reliable bio-signature for the epileptic seizure. The phase-space analysis in the gamma region also shows specific signatures in the form of coherent oscillations and higher harmonic generation, further confirmed through wavelet analysis.
Fission stories: Using PomBase to understand Schizosaccharomyces pombe biology
Authors: Harris Midori A. , Rutherford Kim M. , Hayles Jacqueline , Lock Antonia , Bähler Jürg , Oliver Stephen G. , Mata Juan , Wood Valerie
Published: September 2021

PomBase (www.pombase.org), the model organism database (MOD) for the fission yeast Schizosaccharomyces pombe, supports research within and beyond the S. pombe community by integrating and presenting genetic, molecular, and cell biological knowledge into intuitive displays and comprehensive data collections. With new content, novel query capabilities, and biologist-friendly data summaries and visualisation, PomBase also drives innovation in the MOD community.
ACE-Neuro: A Tailored Exercise Oncology Program for Neuro-Oncology Patients – Study Protocol
Authors: Daun Julia T. , Capozzi Lauren C. , Urgoiti Gloria Roldan , McDonough Meghan H. , Easaw Jacob C. , McNeely Margaret , Francis George J. , Williamson Tanya , Danyluk Jessica , McLaughlin Emma , Ospina Paula A. , de Guzman Wilding Marie , Radke Lori , Driga Amy , Lesiuk Christine , Culos-Reed S. Nicole
Published: September 2021

Background

Patients with primary brain tumours lack access to exercise oncology and wellness resources. The purpose of the Alberta Cancer Exercise – Neuro-Oncology (ACE-Neuro) study is to assess the feasibility of a tailored neuro-oncology exercise program for patients across Alberta, Canada. The primary outcome is to assess the feasibility of ACE-Neuro. The secondary outcome is to examine preliminary effectiveness of ACE-Neuro on patient-reported outcomes and functional fitness.

Methods

Neuro-oncology patients with a malignant or benign primary brain tumour that are pre, on, or completed treatment, are >18 years, and able to consent in English are eligible to participate in the study. Following referral from the clinical team to cancer rehabilitation and the study team, participants are triaged to determine their appropriateness for ACE-Neuro or other cancer rehabilitation or physiatry resources. In ACE-Neuro, participants complete a tailored 12-week exercise program with pre-post assessments of patient-reported outcomes, functional fitness, and physical activity. ACE-Neuro includes individual and group-based exercise sessions, as well as health coaching.

Conclusion

We are supporting ACE-Neuro implementation into clinical cancer care, with assessment of needs enabling a tailored exercise prescription.
Remotely detected plant function in two midwestern prairie grassland experiments reveals belowground processes
Authors: Cavender-Bares Jeannine M. , Schweiger Anna K. , Gamon John A. , Gholizadeh Hamed , Helzer Kimberly , Lapadat Cathleen , Madritch Michael D. , Townsend Philip A. , Wang Zhihui , Hobbie Sarah E.
Published: September 2021

Imaging spectroscopy provides the opportunity to incorporate leaf and canopy optical data into ecological studies, but the extent to which remote sensing of vegetation can enhance the study of belowground processes is not well understood. In grassland systems, aboveground and belowground vegetation quantity and quality are coupled, and both influence belowground microbial processes and nutrient cycling, providing a potential link between remote sensing and belowground processes. We hypothesized that ecosystem productivity, and the chemical, structural and phylogenetic-functional composition of plant communities would be detectable with remote sensing and could be used to characterize belowground plant and soil processes in two grassland biodiversity experiments—the BioDIV experiment at Cedar Creek Ecosystem Science Reserve in Minnesota and the Wood River Nature Conservancy experiment in Nebraska. Specifically, we tested whether aboveground vegetation chemistry and productivity, as detected from airborne sensors, predict soil properties microbial processes and community composition. Imaging spectroscopy data were used to map aboveground biomass and green vegetation cover, functional traits and phylogenetic-functional community composition of vegetation. We examined the relationships between the image-derived variables and soil carbon and nitrogen concentration, microbial community composition, biomass and extracellular enzyme activity, and soil processes, including net nitrogen mineralization. In the BioDIV experiment—which has low overall diversity and productivity despite high variation in each—belowground processes were driven mainly by variation in the amount of organic matter inputs to soils. As a consequence, soil respiration, microbial biomass and enzyme activity, and fungal and bacterial composition and diversity were significantly predicted by remotely sensed vegetation cover. In contrast, at Wood River, where plant diversity and productivity were consistently higher, remotely sensed functional, chemical and phylogenetic composition of vegetation predicted belowground extracellular enzyme activity, microbial biomass, and net nitrogen mineralization rates, while aboveground biomass did not. The strong, contrasting associations between the quantity and chemistry of aboveground inputs with belowground soil processes and properties provide a basis for using imaging spectroscopy to understand belowground processes across productivity gradients in grassland systems. However, a mechanistic understanding of how above and belowground components interact among different ecosystems remains critical to extending these results broadly.
Biparental age effects in the burying beetle Nicrophorus vespilloides
Authors: Cope Hilary , Ivimey-Cook Edward , Moorad Jacob
Published: September 2021

Parental age at reproduction influences offspring size and survival by affecting prenatal and postnatal conditions in a wide variety of species, including humans. However, most investigations into this manifestation of ageing focus upon maternal age effects; the effects of paternal age and interactions between maternal and paternal age are often neglected. Furthermore, even when maternal age effects are studied, pre- and postnatal effects are confounded. Using a cross-fostered experimental design, we investigated the joint effects of paternal and pre- and postnatal maternal ages on numerous offspring outcomes in a laboratory population of a species of burying beetle, Nicrophorus vespilloides. When we correct our tests for significance for multiple comparisons, we found no clear evidence for any parental effect senescence acting on egg size, larval weight, or larval survival. Nor did we find a statistical effect of paternal or egg producer age on the outcomes of foster mothers as measured by weight change experienced during caregiving. These findings are consistent with recent negative results reported in a similar study of N. vespilloides maternal age effects while also expanding these to other offspring traits and to paternal age effects. We discuss how the peculiar life history of this species may promote selection to resist the evolution of parental age effects, and how this might have influenced our ability to detect senescence.
Functional characterization of the biogenic amine transporter system on human macrophages
Authors: Mackie Phillip M , Gopinath Adithya , Montas Dominic M , Nielsen Alyssa , Nolan Rachel , Runner Kaitlyn , Matt Stephanie , McNamee John , Riklan Joshua , Adachi Kengo , Doty Andria , Ramirez-Zamora Adolfo , Yan Long , Gaskill Peter J , Streit Wolfgang J , Okun Michael S , Khoshbouei Habibeh
Published: September 2021

Monocyte-derived macrophages are key players in tissue homeostasis and disease regulated by a variety of signaling molecules. Recent literature has highlighted the ability for biogenic amines to regulate macrophage functions, but the mechanisms governing biogenic amine signaling on and around immune cells remains nebulous. In the central nervous system, biogenic amine transporters are regarded as the master regulators of neurotransmitter signaling. While we and others have shown macrophages express these transporters, relatively little is known of their function on these cells. To address these knowledge gaps, we interrogated the function of norepinephrine (NET) and dopamine (DAT) transporters on human monocyte-derived macrophages. We found that both NET and DAT are present and can uptake substrate from the extracellular space at baseline. Not only was DAT expressed in cultured macrophages, but it was also detected in a subset of intestinal macrophages in situ. Surprisingly, we discovered a NET-independent, DAT-mediated immuno-modulatory mechanism in response to lipopolysaccharide (LPS). LPS induced reverse transport of dopamine through DAT, engaging autocrine/paracrine signaling loop that regulated the macrophage response. Removing this signaling loop enhanced the pro-inflammatory response to LPS. Finally, we found that this DAT-immune axis was disrupted in disease. Collectively, our data introduce a novel role for DAT in the regulation of innate immunity during health and disease.
(Un)common space in infant neuroimaging studies: a systematic review of infant templates
Authors: Dufford Alexander J. , Hahn C. Alice , Peterson Hannah , Gini Silvia , Mehta Saloni , Alfano Alexis , Scheinost Dustin
Published: September 2021

In neuroimaging, spatial normalization is an important step that maps an individual’s brain onto a template brain permitting downstream statistical analyses. Yet, in infant neuroimaging, there remain several technical challenges that have prevented the establishment of a standardized template for spatial normalization. Thus, many different approaches are used in the literature. To quantify the popularity and variability of these approaches in infant neuroimaging studies, we performed a systematic review of infant MRI studies from 2000 to 2020. Here, we present results from 833 studies meeting inclusion criteria. Studies were classified into 1) processing data in single subject space, 2) using a predefined, or “off the shelf”, template, 3) creating a study specific template or 4) using a hybrid of these methods. We found that across the studies in the systematic review, single subject space was the most used (no common space). This was the most used common space for DWI and structural MRI studies while fMRI studies preferred off the shelf atlases. We found a pattern such that more recently published studies are more commonly using off the shelf atlases. When considering special populations, preterm studies most used single subject space while, when no special populations were being analyzed, an off the shelf template was most common. The most used off the shelf templates were the UNC Infant Atlases (26.1%). Using a systematic review of infant neuroimaging studies, we highlight a lack of an established “standard” template brain in these studies.
Benchmarking of a Bayesian single cell RNAseq differential gene expression test for dose-response study designs
Authors: Nault Rance , Saha Satabdi , Bhattacharya Sudin , Dodson Jack , Sinha Samiran , Maiti Tapabrata , Zacharewski Tim
Published: September 2021

The application of single-cell RNA sequencing (scRNAseq) for the evaluation of chemicals, drugs, and food contaminants presents the opportunity to consider cellular heterogeneity in pharmacological and toxicological responses. Current differential gene expression analysis (DGEA) methods focus primarily on two group comparisons, not multi-group dose-response study designs used in safety assessments. To benchmark DGEA methods for dose-response scRNAseq experiments, we proposed a multiplicity corrected Bayesian testing approach and compare it against 8 other methods including two frequentist fit-for-purpose tests using simulated and experimental data. Our Bayesian test method outperformed all other tests for a broad range of accuracy metrics including control of false positive error rates. Most notable, the fit-for-purpose and standard multiple group DGEA methods were superior to the two group scRNAseq methods for dose-response study designs. Collectively, our benchmarking of DGEA methods demonstrates the importance in considering study design when determining the most appropriate test methods.
Parallel evolution of urban-rural clines in melanism in a widespread mammal
Authors: Cosentino Bradley J. , Gibbs James P.
Published: September 2021

Urbanization is the dominant trend of global land use change. The replicated nature of environmental change associated with urbanization should drive parallel evolution, yet insight into the repeatability of evolutionary processes in urban areas has been limited by a lack of multi-city studies. Here we leverage community science data on coat color in >60,000 eastern gray squirrels (Sciurus carolinensis) across 43 North American cities to test for parallel clines in melanism, a genetically based trait associated with thermoregulation and crypsis. We show the prevalence of melanism was positively associated with urbanization as measured by impervious cover. Urban-rural clines in melanism were strongest in the largest cities with extensive forest cover and weakest or absent in cities with warmer winter temperatures, where thermal selection likely limits the prevalence of melanism. Our results suggest that novel traits can evolve in a highly repeatable manner among urban areas, modified by factors intrinsic to individual cities, including their size, land cover, and climate.