bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary CNS myeloma with remission after systemic CNS-penetrating agents
Authors: Fernandez Luis G , Oyon Daniel Eduardo , Gondi Vinai , Grimm Sean , Khan Osaama H
Published: July 2022

Background

CNS myeloma is a rare manifestation of multiple myeloma and is often associated with a dismal prognosis; however, cases are increasing in frequency as overall survival improves for MM. There is currently no standardized treatment for CNS myeloma; however, different chemotherapy and radiotherapy regimens have been described.

Methods

We had previously reported on the efficacy of proton-based craniospinal irradiation in a patient with CNS myeloma; here we present a patient with a history of extramedullary plasmacytoma, 10 years in remission status post standard systemic chemotherapy, with biopsy-proven CNS myeloma successfully treated with systemic chemotherapy as a first-line treatment.

Results

The patient achieved clinical and radiographic remission on 2 separate occasions with systemic chemotherapy alone.

Conclusions

This case demonstrates that systemically administered agents may have activity in CNS myeloma. Further investigations are necessary to establish the optimal combination of agents and treatment schedules.
Evaluation of the association between plasma glucose-dependent insulinotropic polypeptide, respiratory quotient, and intramuscular fat deposition in feedlot cattle fed different levels of dry matter intake
Authors: Ortiz-Fraguada M Y , Relling A E
Published: July 2022

The objectives of this trial were to evaluate the association between different levels of dry matter intake (DMI) on gas exchange, plasma glucose-dependent insulinotropic polypeptide (GIP) concentration, and intramuscular (IM) fat deposition. We used 60 individually fed backgrounded Angus × SimAngus-crossbred steers (n = 30) in a randomized complete block design. Steers (paired by body weight [BW] and gain to feed ratio [G:F]) were randomly allocated to one of the following treatments: ad libitum intake (AI) or restricted intake (RI; the same diet fed at 85% of the AI) of a finishing diet. The diet contained 61% cracked corn, 9% corn silage, 15% distillers’ dried grains with solubles, 5% soyhulls, and 10% of a protein-mineral-vitamin premix. Measurements of CO2 emission and consumption of O2, and respiratory quotient (RQ) were taken using the GreenFeed system (n = 15/treatment). Plasma and gas samples were collected 10 d before slaughter, 1 h before and 2 h after feeding. Plasma glucose, non-esterified fatty acids, GIP, and insulin concentration and gasses (O2, CO2, and RQ) were analyzed using the MIXED procedure of SAS evaluating the fixed effect of treatment, time (repeated measurement) and their interaction, and the random effect of the block. Final BW and carcass characteristics were analyzed with a similar model, without the time statement and its interaction. Compared with RI, AI steers had greater (P < 0.01) DMI and average daily gain (ADG). Steers on AI had greater final BW (P = 0.02), tended to have a greater ribeye area (P = 0.09), and had lower plasma GIP concentration (P = 0.04). There was no treatment effect (P ≥ 0.11) on G:F, subcutaneous backfat (BF), and IM fat, O2 consumption, CO2 emission, and RQ. Plasma glucose concentration of AI steers was greater before and after feeding than RI (P < 0.05). In conclusion, feeding steers ad libitum increased DMI, ADG, and plasma glucose and GIP concentration but does not affect G:F, BF, IM fat, CO2 emission, and O2 consumption. Plasma GIP concentration and RQ are not associated with IM fat deposition.
Leadership engagement creates a powerful team
Authors: Olmstead John , Wellington W. Zeh
Published: July 2022

A surgical department uses four strategies to attract and retain workers
Defining Objective Measures of Physician Stress in Simulated Critical Communication Encounters
Authors: Wolfe Amy H. J. , Hinds Pamela S. , du Plessis Adre J. , Gordish-Dressman Heather , Arnold Robert M. , Soghier Lamia
Published: July 2022

OBJECTIVES:

This study had three aims: 1) quantify the difference in stress levels between low and high stress roles during simulated critical communication encounters using objective physiologic data (heart rate variability [HRV]) and subjective measures (State-Trait Anxiety Inventory [STAI]), 2) define the relationship between subjective and objective measures of stress, and 3) define the impact of trainee preparedness and reported self-efficacy on stress levels.

DESIGN:

Mixed methods simulation-based study.

SETTING:

Single center.

PATIENTS:

Pediatric critical care fellows and faculty (n = 12).

INTERVENTIONS:

Subjects participated in six simulated scenarios in both high stress “hot seat” and low stress “observer” roles.

MEASUREMENTS AND MAIN RESULTS:

Subjective stress was measured using the STAI at baseline and after each scenario. Objective stress was measured continuously using a wearable biometric device measuring HRV. Previous residency communication training and self-confidence surrounding various communication topics were collected via questionnaire. Significant changes in subjective (STAI) and objective stress (HRV) measurements in the low- versus high-stress roles were observed. STAI scores increased 8 points during low stress and 12 points during high stress role (p = 0.021) compared with baseline. Two specific HRV markers, root mean square of successive differences between normal heartbeats, a marker of parasympathetic tone, and the low frequency/high frequency (LF/HF) ratio, a marker of sympathetic activation, were significantly correlated with STAI levels (–0.032, p = 0.001; 1.030, p = 0.002, respectively). Participants who reported increased confidence in discussing code status had a significant decrease in stress response (measured via LF/HF ratio) during both the observer (p = 0.033) and hot seat roles (p = <0.001).

CONCLUSIONS:

Communicating life-altering news in a simulated environment is a stressful experience. This stress results in physiologic changes that can be measured continuously using HRV. HRV measurement may serve as a novel method in evaluating the effectiveness of communication training programs and measuring future stress-reduction interventions.
Postintensive Care Syndrome-Family Associated With COVID-19 Infection
Authors: Shirasaki Kasumi , Hifumi Toru , Isokawa Shutaro , Hashiuchi Shinsuke , Tanaka Shinobu , Yanagisawa Yaeko , Takahashi Osamu , Otani Norio
Published: July 2022

OBJECTIVES:

To assess the prevalence of and risk factors for postintensive care syndrome in family (PICS-F) in the COVID-19 era.

DESIGN:

A single-center retrospective study using questionnaires and telephone calls.

SETTING:

An ICU at St. Luke’s International Hospital.

PATIENTS:

Patients who were treated for COVID-19–related acute respiratory distress syndrome between March 23, 2020, and September 30, 2021, and their family members participated.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

PICS-F refers to the psychologic distress such as anxiety, depression, and posttraumatic stress disorder (PTSD) experienced by the patient’s family. The primary outcome was PICS-F occurrence. Furthermore, factors related to PICS-F development were identified using statistical analysis. Of 85 patients with COVID-19 who were admitted to the ICU, 57 family members consented to the study and completed the survey, and 54 family members’ data were analyzed. The median age of family members was 53.5 years, 68.5% were female, and 46.3% were spouses. The median age of patients was 55.5 years, and 83.3% were male. During their ICU stay, 68.5% received invasive mechanical ventilation, 11.1% received venovenous extracorporeal membrane oxygenation, and 11.1% underwent tracheostomy. The median ICU and hospital stays were 7 and 22 days, respectively. Overall PICS-F occurred in 33%. Anxiety, depression, and PTSD occurred in 24%, 26%, and 4% of family members, respectively. The prevalence of all three components of PICS-F was 4%. Multivariable analysis showed that Family Satisfaction with the ICU Survey (FS-ICU) scores were independently associated with PICS-F development (odds ratio, 0.941; 95% CI, 0.891–0.983; p = 0.005).

CONCLUSIONS:

One-third of family members of COVID-19 patients admitted to the ICU had symptoms of PICS-F. These results suggest that measurement of FS-ICU may be helpful as a predictor of PICS-F development. In addition, increasing the level of ICU care satisfaction of the family members may prevent PICS-F.
A Review of Pathologic Myopia
Authors: Raval Nilesh , Kang Joann J. , Kim Yu Hyon
Published: July 2022

Pathologic myopia is a leading cause of vision loss worldwide and is most prevalent in developed nations in East and Southeast Asia. Although the pathophysiologic mechanisms behind pathologic myopia have yet to be elucidated, the process is thought to stem from excessive axial elongation of the globe and subsequent degeneration of vital structures within the posterior segment. The array of complications that arise from this condition can lead to significant visual impairment. The purpose of this article is to review the classification, pathophysiology, complications, and management of pathologic myopia.
Course Prerequisites: Here, There, and Everywhere. Time to Standardize?
Authors: Snyder Jennifer , Brown Darwin , Quincy Brenda
Published: July 2022

Introduction

This study’s aim was to examine prerequisite course requirements and compare them to previous studies with a secondary aim to examine potential differences relative to program characteristics.

Methods

Data were extracted from the websites of 265 entry-level physician assistant (PA) programs from October 2020 until December 2020. Course prerequisites as well as number of courses and semester hours required were described and examined according to program location, phase, Carnegie Classification, association with a medical school, and the public/private status of the sponsoring institution.

Results

Of 264 PA programs, more than 50% of programs required 6 common prerequisites: anatomy, physiology, microbiology, statistics, general chemistry, and psychology. The total number of unique prerequisite courses was 28 for all programs with a reduction in humanities and social sciences semester hours compared to previous studies and a slight increase in credit hours required for the common 6 courses. Total prerequisite hours and courses required were higher for master’s programs; private, not-for-profit programs; newly established programs; and those not associated with a medical school. Newer programs are generally located in private, not-for-profit educational institutions that are not associated with a medical school. Programs in the Mountain Division required a lower number of prerequisites, and the South Region required the greatest number of prerequisite courses and semester hours.

Discussion

The present study demonstrates a difference in prerequisite requirements across the country. This could translate to increased cost and a potential barrier to those considering a career as a PA.
COVID Collaborations: A Physician Assistant Program and Health Department Partnership
Authors: Jones Quinnette , Blazar Melinda , Blackley Tara , Lyn Michelle J. , Johnson Frederick S.
Published: July 2022

The onset of the COVID-19 pandemic resulted in the displacement of clinical-phase medical learners across the country. Physician assistant (PA) and other health professions programs were challenged to innovate and offer alternate learning experiences that would meet students’ needs as future health care professionals. At the same time, local and state health departments were faced with quickly increasing their capacity for contact tracing and case investigation in response to the growing number of COVID-19 infections. Through a collaborative partnership based on the needs of the local health department and clinical-phase PA students, the Duke PA program developed an elective in which students served as contact tracers and case investigators. PA students provided over 1500 hours of contact tracing and case investigation support to the local health department. Qualitative review showed students gained a greater appreciation of the impact of social determinants of health, saw first-hand how the pandemic disproportionately affected communities of color, and increased their knowledge about the role of public health. The partnership between the PA program and the health department was mutually beneficial and established a foundation for future collaborative experiences that support both the community and the needs of health professions’ learners.
Bone marrow adiposity in diabetes and clinical interventions
Authors: Shu Jessica B. , Kim Tiffany Y.
Published: July 2022

Purpose of review

This study aims to review bone marrow adipose tissue (BMAT) changes in people with diabetes, contributing factors, and interventions.

Recent findings

In type 1 diabetes (T1D), BMAT levels are similar to healthy controls, although few studies have been performed. In type 2 diabetes (T2D), both BMAT content and composition appear altered, and recent bone histomorphometry data suggests increased BMAT is both through adipocyte hyperplasia and hypertrophy. Position emission tomography scanning suggests BMAT is a major source of basal glucose uptake. BMAT is responsive to metabolic interventions.

BMAT is a unique fat depot that is influenced by metabolic factors and proposed to negatively affect the skeleton. BMAT alterations are more consistently seen in T2D compared to T1D. Interventions such as thiazolidinedione treatment may increase BMAT, whereas metformin treatment, weight loss, and exercise may decrease BMAT. Further understanding of the role of BMAT will provide insight into the pathogenesis of diabetic bone disease and could lead to targeted preventive and therapeutic strategies.
Understanding and Optimizing Family Caregiver Participation in Dyadic Research
Authors: Irani Elliane , Mogle Jacqueline , Durante Ángela , Juárez-Vela Raúl , Vellone Ercole , Buck Harleah G.
Published: July 2022

Background

Research to understand self-care behaviors increasingly engages patient–caregiver dyads. However, collecting data on dyads requires both members to complete the research protocol, potentially resulting in biased information if caregivers who do not participate differ from caregivers who do.

Objectives

The aim of the study was to examine how recruitment conditions and patients’ appraisal of dyadic engagement in heart failure management are related to caregiver participation across two research studies.

Methods

We used logistic regression to examine whether recruitment strategy and patients’ responses on the dyadic symptom management-type instrument were associated with caregivers’ participation.

Results

Caregivers not present at the initial recruitment were less likely to participate in the study. Regardless of recruitment strategy, caregivers were less likely to participate if the patient indicated primary responsibility for heart failure management. In the restricted recruitment study (recruiting both dyad members simultaneously), caregiver participation was significantly higher when patients selected a collaborative-oriented care type relative to patient- or caregiver-oriented type.

Discussion

Instruments assessing dyad-level information could aid researchers in deploying resources at recruitment, as well as in adjusting results for data that could bias results and conclusions. Our findings support the importance of considering the recruitment strategy as well as dyadic care type as part of the recruitment process.
Comparison of thicknesses of talar cartilage, tibialis anterior, and gastrocnemius muscles between high-activity patients with unilateral traumatic transtibial amputation and nonamputated individuals: A clinical and sonographic study
Authors: Örücü Atar Merve , Bilgin Esra , Demir Yasin , Korkmaz Nurdan , Gürçay Eda
Published: July 2022

Background:

The aim of this study was to compare the thicknesses of intact talar cartilage, tibialis anterior (TA), gastrocnemius medialis (GCM), and gastrocnemius lateralis (GCL) muscles of traumatic unilateral transtibial amputees with that of nonamputated individuals by ultrasound and to investigate the relationship between cartilage and muscle thickness measurements with clinical parameters.

Methods:

Thirty-six patients with unilateral traumatic transtibial amputation, and 36 age-matched, sex-matched, and body mass index–matched nonamputated controls were included in this cross-sectional study. Subjects’ talar cartilage, TA, GCM, and GCL muscle thickness measurements were performed using musculoskeletal ultrasound. Other outcome measures were 6-minute walking test, the Foot and Ankle Outcome Score, and Short Form-36.

Results:

TA and GCM muscles were thicker on the intact limbs of the patients than those of the controls (p = 0.015 and p = 0.014, respectively). There was no statistically significant difference in talar cartilage and GCL muscle thicknesses when patients were compared with control subjects. Talar cartilage thickness was positively correlated with body mass index, 6-minute walking test, and sport and recreation subscale score of the Foot and Ankle Outcome Score. TA and GCM muscle thicknesses were positively correlated with the duration of prosthesis use and role limitations because of the physical health subscale score of Short Form-36.

Conclusions:

TA and GCM muscles were found to be thickened on the intact sides of traumatic unilateral transtibial amputees. The correlations between lower leg muscle thicknesses and clinical parameters suggest that the observed thickness change is not necessarily pathological and has potential impact on function at least in our young cohort.
68Ga-FAPI-46 PET/CT in a Metastatic Castration-Resistant Prostate Cancer Patient With Low PSMA Expression
Authors: Aryana Kamran , Manafi-Farid Reyhaneh , Amini Hamidreza , Divband Ghasemali , Moghadam Soroush Zarehparvar
Published: July 2022

A 70-year-old man with mCRPC (metastatic castration-resistant prostate cancer) was referred for 68Ga-PSMA PET/CT for restaging and the possibility of targeted molecular radioligand therapy with 177Lu-PSMA. Numerous 68Ga-PSMA–avid skeletal metastases with low SUVs were noted. Because of low PSMA expression, a 68Ga-FAPI-46 PET/CT was performed to evaluate the eligibility for FAPI-based radioligand therapy. There were some discordant findings between 68Ga-PSMA and 68Ga-FAPI PET/CT scans regarding the detectability of lesions and SUVs. Our case signifies that 68Ga-FAPI theragnostic may have a potential role in the treatment of mCRPC patients with insignificant PSMA expression or in cases after the failure of 177Lu-PSMA therapy.
Diagnostic Test Accuracy of 18F-FDG PET or PET/CT in Merkel Cell Carcinoma
Authors: Shim Sung Ryul , Kim Seong-Jang
Published: July 2022

Objective

The purpose of the current study was to evaluate the diagnostic accuracies of 18F-FDG PET or PET/CT for diagnosis of Merkel cell carcinoma (MCC) through a systematic review and meta-analysis.

Methods

The PubMed, Cochrane database, and EMBASE database, from January 1990 to January 31, 2022, were searched for studies evaluating diagnostic performance of 18F-FDG PET or PET/CT for MCC. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR−), and constructed summary receiver operating characteristic curves.

Results

Across 9 studies (259 patients), the pooled sensitivity of 18F-FDG PET or PET/CT was 0.91 (95% confidence interval [CI], 0.85–0.95) and a pooled specificity of 0.93 (95% CI, 0.86–0.97). Likelihood ratio syntheses gave an overall LR+ of 14.0 (95% CI, 6.6–29.6) and LR− of 0.09 (95% CI, 0.05–0.17). The pooled diagnostic odds ratio was 153 (95% CI, 57–416).

Conclusion

18F-FDG PET/CT showed an excellent performance for diagnosis of MCC. The likelihood ratio scattergram indicated that 18F-FDG PET or PET/CT is useful for exclusion and confirmation of MCC. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of 18F-FDG PET or PET/CT for MCC patients.
Neurophysiology of Juvenile and Progressive Myoclonic Epilepsy
Authors: Acharya Jayant N. , Acharya Vinita J.
Published: July 2022

Myoclonus can be epileptic or nonepileptic. Epileptic myoclonus has been defined in clinical, neurophysiological, and neuroanatomical terms. Juvenile myoclonic epilepsy (JME) is typically considered to be an adolescent-onset idiopathic generalized epilepsy with a combination of myoclonic, generalized tonic–clonic, and absence seizures and normal cognitive status that responds well to anti-seizure medications but requires lifelong treatment. EEG shows generalized epileptiform discharges and photosensitivity. Recent observations indicate that the clinical picture of JME is heterogeneous and a number of neuropsychological and imaging studies have shown structural and functional abnormalities in the frontal lobes and thalamus. Advances in neurophysiology and imaging suggest that JME may not be a truly generalized epilepsy, in that restricted cortical and subcortical networks appear to be involved rather than the entire brain. Some patients with JME may be refractory to anti-seizure medications and attempts have been made to identify neurophysiological biomarkers predicting resistance. Progressive myoclonic epilepsy is a syndrome with multiple specific causes. It is distinct from JME because of the occurrence of progressive neurologic dysfunction in addition to myoclonus and generalized tonic–clonic seizures but may sometimes be difficult to distinguish from JME or misdiagnosed as drug-resistant JME. This article provides an overview of progressive myoclonic epilepsy and focuses on the clinical and neurophysiological findings in the two most commonly recognized forms of progressive myoclonic epilepsy—Unverricht–Lundborg disease (EPM1) and Lafora disease (EPM2). A variety of neurophysiological tests can be used to distinguish between JME and progressive myoclonic epilepsy and between EPM1 and EPM2.
Erysipelothrix anatis sp. nov., Erysipelothrix aquatica sp. nov. and Erysipelothrix urinaevulpis sp. nov., three novel species of the genus, and emended description of Erysipelothrix
Authors: Eisenberg Tobias , Mühldorfer Kristin , Erhard Marcel , Fawzy Ahmad , Kehm Sabine , Ewers Christa , Semmler Torsten , Blom Jochen , Lipski André , Rau Jörg , Kämpfer Peter , Glaeser Stefanie P.
Published: July 2022

Seven genotypically distinct strains assigned to the genus

Erysipelothrix

were isolated in different laboratories from several animal sources. Strain D17_0559-3-2-1T and three further strains were isolated from samples of duck, pig and goose. The strains had >99 % 16S rRNA gene sequence similarity to each other and to strain VA92-K48T and two further strains isolated from samples of medical leech and a turtle. The closest related type strains to the seven strains were those of

Erysipelothrix inopinata

(96.74 %) and

Erysipelothrix rhusiopathiae

(95.93 %). Average nucleotide identity, amino acid identity and in silico DNA–DNA hybridization results showed that the strains represented two separate novel species. One further phylogenetically distinct strain (165301687T) was isolated from fox urine. The strain had highest 16S rRNA gene sequence similarity to the type strains of

Erysipelothrix tonsillarum

(95.67 %), followed by

Erysipelothrix piscisicarius

(95.58 %) and

Erysipelothrix larvae

(94.22 %) and represented a further novel species. Chemotaxonomic and physiological data of the novel strains were assessed, but failed to unequivocally differentiate the novel species from existing members of the genus. MALDI-TOF MS data proved the discrimination of at least strain 165301687T from all currently described species. Based on the presented phylogenomic and physiological data, we propose three novel species, Erysipelothrix anatis sp. nov. with strain D17_0559-3-2-1T (=DSM 111258T= CIP 111884T=CCM 9044T) as type strain, Erysipelothrix aquatica sp. nov. with strain VA92-K48T (=DSM 106012T=LMG 30351T=CIP 111492T) as type strain and Erysipelothrix urinaevulpis sp. nov. with strain 165301687T (=DSM 106013T= LMG 30352T= CIP 111494T) as type strain.
Hexokinase 1b is a novel target for Non–small-cell lung cancer
Authors: Yozgat Yasemin , Karakoc Emre , Sahin Ozgur , Cimen Seyma , Rabeh Wael M. , Aydin Mehmet Serif , Mardinoglu Adil , Gursel Ihsan , Cakir Asli , Sensoy Ozge , Ozdemir Ekrem M. , Bayrak Yusuf , Gunluoglu Mehmet Z. , Saatci Ozge , Jabbar Javaid , Ferreira Juliana C. , Aslan Melike Dinccelik , Yildirim Muzaffer , Mansoor Samman , Kerman Bilal E. , Aladag Zeynep , Kim Woonghee , Arif Muhammad , Vatandaslar Emre , Tok Olgu E. , Dogru Zeynep , Demir Aslı G. O. , Yildirim Tugce Canavar , Yozgat İhsan , Senturk Serif , Ozturk Gurkan , Cevher Murat Alper
Published: July 2022

Deregulation of glycolysis is common in non-small cell lung cancer (NSCLC). Hexokinase (HK) enzymes catalyze the phosphoryl-group-transfer in glucose metabolism. There are a very few studies that have begun to reveal the connections between glucose metabolism and splicing programs. Unlike HK2 gene, which is expressed as a single transcript, there are several transcripts of the HK1 gene due to alternative splicing. However, the functional differential roles of HK1 isoforms in glucose metabolism and tumor progression are still elusive. Here, we show that primary NSCLC patient tumor cells metabolically differ from the normal lung epithelium where they display predominant expression of one of the HK1 transcripts, hexokinase1b (HK1b). We utilized CRISPR-Cas9 system to selectively target specific HK1b isoform in NSCLC and show that silencing HK1b in NSCLC cells inhibits tumorigenesis through diminishing glycolysis and proliferation. Our findings constitute the first demonstration of the first biochemical distinction between the HK1 splice variants. Finally, HK1b deletion sensitizes NSCLC cells to standard-of-care, cisplatin treatment, and the combination therapy synergistically increases both apoptotic cell death by cisplatin and autophagic cell death by increased formation of LC3-II associated autophagic vesicles and myelinoid bodies. Notably, loss of HK1b leads to cellular DNA damage, further combination with cisplatin therapy showed significantly increased levels of DNA damage. Importantly, we showed that glycolysis and cisplatin resistance can be restored by adding-back HK1b in HK1b knock-out cells. Our findings reveal that targeting HK1b isoform alone or in combination with cisplatin may represent a novel strategy for NSCLC patients.
High Variability Periods in the EEG: A New Temporal Metric that Reflects Brain States
Authors: Parameshwaran Dhanya , Thiagarajan Tara
Published: July 2022

Here we define a new metric to characterize temporal patterns of amplitude variability in the EEG signal and demonstrate that this feature of the signal varies significantly with brain state. The metric uses the standard deviation of waveform amplitude in a short moving time window of 3-20 seconds with 50% overlap. We define “High Variability Periods” or “HVPs” as segments when the moving standard deviation of the waveform amplitude is continuously higher than a cutoff defined as the 25th percentile of variability. HVPs typically last on the order of tens of seconds and are punctuated by low variability periods or “LVPs” of shorter duration. We further show that the HVP characteristics differ between various conditions. HVPs in the resting state eyes closed condition are substantially and significantly shorter in duration and smaller in area relative to eyes open. In addition, in recordings from monkeys, HVPs disappear under anesthesia and do not reappear in early periods of recovery from anesthesia suggesting long term changes to the signal. Altogether this demonstrates that HVP metrics have discriminatory power and may therefore be important in predicting brain states and outcomes. Finally, they are fast to estimate and can be tracked in time, and therefore suited for near real-time monitoring in low-electrode configuration systems.
PTEN and BRCA1 tumor suppressor loss associated tumor immune microenvironment exhibits differential response to therapeutic STING pathway activation in a murine model of ovarian cancer
Authors: Shakfa Noor , Li Deyang , Conseil Gwenaëlle , Lightbody Elizabeth , Wilson-Sanchez Juliette , Hamade Ali , Chenard Stephen , Laight Brian , Afriyie-Asante Afrakoma , Tyryshkin Kathrin , Köbel Martin , Koti Madhuri
Published: July 2022

Background

High grade serous ovarian carcinoma (HGSC) is the most lethal gynecologic malignancy characterized by chemoresistance and high rates of recurrence. HGSC tumors display a high prevalence of tumor suppressor gene loss. Loss of BRCA1 and PTEN function due to mutations or epigenetic influence have been widely associated with variable clinical outcomes, where tumors with BRCA1 mutations exhibit increased chemosensitivity and those with PTEN mutations have been reported to exhibit chemoresistance. Given the established type 1 interferon regulatory function of BRCA1 and PTEN genes and associated contrasting T cell infiltrated and non-infiltrated tumor immune microenvironment (TIME) states, in this study we investigated the potential of Stimulator of Interferon Genes (STING) pathway activation in improving overall survival via enhancing chemotherapy response, specifically in tumors with PTEN deficiency.

Methods

Expression of PTEN protein was evaluated in tissue microarrays generated using pre-treatment tumors collected from a cohort of 110 patients with HGSC. Multiplex immunofluorescence staining was performed to determine spatial profiles and density of selected lymphoid and myeloid cells. In vivo studies using the syngeneic murine HGSC cell lines, ID8-Trp53-/-; Pten-/-and ID8-Trp53-/-; Brca1-/-, were conducted to characterize the TIME and response to carboplatin chemotherapy in combination with exogenous STING activation therapy.

Results

Tumors with absence of PTEN protein exhibited a significantly decreased disease specific survival and intra-epithelial CD68+ macrophage infiltration as compared to intact PTEN expression. In vivo studies demonstrated that Pten deficient ovarian cancer cells establish an immunosuppressed TIME characterized by increased proportions of M2-like macrophages, GR1+ MDSCs in the ascites, and reduced effector CD8+ cytotoxic T cell function compared to Brca1 deficient cells; further, tumors from mice injected with Pten deficient ID8 cells exhibited an aggressive behavior due to suppressive macrophage dominance in the malignant ascites. In combination with chemotherapy, exogenous STING activation resulted in longer overall survival in mice injected with Pten deficient ID8 cells, reprogrammed intraperitoneal M2-like macrophages derived from Pten deficient ascites to a M1-like phenotype and rescued CD8+ cytotoxic T cell activation.

Conclusions

This study reveals the importance of considering the influence of cancer cell intrinsic genetic alterations on the TIME for therapeutic selection. We establish the rationale for the optimal incorporation of interferon activating therapies as a novel combination strategy in PTEN deficient HGSC.
The role of wingbeat frequency and amplitude in flight power
Authors: Krishnan Krishnamoorthy , Garde Baptiste , Bennison Ashley , Cole Nik C. , Cole Emma-L. , Darby Jamie , Elliott Kyle H. , Fell Adam , Gómez-Laich Agustina , de Grissac Sophie , Jessopp Mark , Lempidakis Emmanouil , Mizutani Yuichi , Prudor Aurélien , Quetting Michael , Quintana Flavio , Robotka Hermina , Roulin Alexandre , Ryan Peter G. , Schalcher Kim , Schoombie Stefan , Tatayah Vikash , Tremblay Fred , Weimerskirch Henri , Whelan Shannon , Wikelski Martin , Yoda Ken , Hedenström Anders , Shepard Emily L.C.
Published: July 2022

Body-mounted accelerometers provide a new prospect for estimating power use in flying birds, as the signal varies with the two major kinematic determinants of aerodynamic power: wingbeat frequency and amplitude. Yet wingbeat frequency is sometimes used as a proxy for power output in isolation. There is therefore a need to understand which kinematic parameter birds vary and whether this is predicted by flight mode (e.g., accelerating, ascending/descending flight), speed or morphology. We investigate this using high-frequency acceleration data from (i) 14 species flying in the wild, (ii) two species flying in controlled conditions in a wind tunnel and (iii) a review of experimental and field studies. While wingbeat frequency and amplitude were positively correlated, R2 values were generally low, supporting the idea that parameters can vary independently. Indeed, birds were more likely to modulate wingbeat amplitude for more energy-demanding flight modes, including climbing and take-off. Nonetheless, the striking variability even within species and flight types, highlights the complexity of describing the kinematic relationships, which appear sensitive to both the biological and physical context. Notwithstanding this acceleration metrics that incorporate both kinematic parameters should be more robust proxies for power than wingbeat frequency alone.
Genome assembly and association tests identify interacting loci associated with vigor, precocity, and sex in interspecific pistachio rootstocks
Authors: Palmer William , Jacygrad Ewelina , Sagayaradj Sagayamary , Cavanaugh Keri , Han Rongkui , Bertier Lien , Beede Bob , Kafkas Salih , Golino Deborah , Preece John , Michelmore Richard
Published: July 2022

Understanding the basis of hybrid vigor remains a key question in crop breeding and improvement, especially for rootstock development where F1hybrids are extensively utilized. Full-sibling UCB-1 F1seedling rootstocks are widely planted in commercial pistachio orchards that are generated by crossing two highly heterozygous outbreeding parental trees ofPistacia atlantica(female) andP. integerrima(male). This results in extensive phenotypic variability, prompting costly removal of low-yielding small trees. To identify the genetic basis of this variability, we assembled chromosome-scale genome assemblies of the parental trees of UCB-1. We genotyped 960 UCB-1 trees in an experimental orchard for which we also collected multi-year phenotypes. We genotyped an additional 1,358 rootstocks in six commercial pistachio orchards and collected single-year tree size data. Genome-wide single marker association tests identified loci associated with tree size and shape, sex, and precocity. In the experimental orchard, we identified multiple trait-associated loci and a strong candidate for ZZ/ZW sex chromosomes. We found significant marker associations unique to different traits and to early vs. late phenotypic measures of the same trait. We detected two loci strongly associated with rootstock size in commercial orchards. Pseudo-testcross classification of markers demonstrated that the trait-associated alleles for each locus were segregating in the gametes of opposite parents. These two loci interact epistatically to generate the bimodal distribution of tree size with undesirable small trees observed by growers. We identified candidate genes within these regions. These findings provide a foundational resource for marker development and genetic selection of vigorous pistachio UCB-1 rootstock.
Nuclear architecture protein Distal antenna balances genome-binding and phase-separation properties to regulate neuroblast competence
Authors: Benchorin Gillie , Li Maggie Jiaqi , Cho Richard Jangwon , Hu Yuxin , Kohwi Minoree
Published: July 2022

Neural progenitors transit through multiple competence states that restrict production of each neural cell type. In Drosophila neuroblasts, a timed genome reorganization relocates the cell fate gene, hunchback, to the nuclear periphery, terminating competence to produce early-born neurons. Distal antenna (Dan), a pipsqueak (Psq) superfamily protein, is transiently downregulated at mid-embryogenesis, which is required for this relocation. Here we find that Dan is a highly intrinsically disordered protein, and when its Psq DNA-binding domain is increasingly disrupted, Dan coalesces into steadily larger, interconnected hubs of rapid protein exchange. Consistent with these phase-separation properties, Dan has a predicted LARKS domain, a structural motif that forms reversible interactions associated with phase-separation. In the embryo, loss of either the Psq motif or the LARKS domain abrogates Dan’s ability to maintain neuroblast early competence upon misexpression, suggesting that Dan requires both DNA-binding and phase-separation to regulate neuroblast competence. Finally, we found that Dan strongly interacts with proteins of the nuclear pore complex (NPC), and Elys, a core NPC scaffold protein known to regulate genome architecture, binds the hb intron and is required for competence termination. Together, the results support a model for how Dan’s phase-separation properties can mediate dynamic restructuring by balancing genome-binding, self-association, and interaction among nuclear architecture regulators.
Implicit prices of attributes of fine German Riesling: magnitude and heterogeneity
Authors: Fedoseev Vladimir , Fedoseeva Svetlana , Herrmann Roland
Published: July 2022

Purpose

This study aims to analyse how wine attributes affect prices of fine German Riesling wines, provide estimates of the magnitude and heterogeneity of the attributes' implicit prices and draw conclusions on the pricing of fine wine and the research methodology.

Design/methodology/approach

Implicit prices of attributes of fine German Rieslings are estimated with fixed-effects regressions and their heterogeneity across quantiles of the conditional price distribution is tested with quantile-regression techniques. The analysis is based on a unique online data set for prices and characteristics of collectible wines.

Findings

Quality levels according to the German Prädikat system, additional quality awards for exceptional quality, the wine region, age or vintage as well as ullage and the bottle condition are relevant when explaining the price of cellarable wine. Additionally, the influence of the firm's individual reputation is very strong. Relative price premiums for some major attributes of fine German Riesling change significantly across quantiles of the conditional price distribution. Other attributes are characterised by a rather stable relative (but not absolute) price premium.

Originality/value

This is, to the best of our knowledge, the first hedonic price analysis which concentrates exclusively on fine German Riesling wine. By applying both classical and quantile regressions, the authors are able to derive new insights on quality-price linkages in this growing segment of collectible wine and on the research methodology.
Resilience assessment of health-care facilities within urban context: learning from a non-profit hospital in Tehran, Iran
Authors: Rahmani Mehrdad , Lotfata Aynaz , Khoshnevis Sarasadat , Javanmardi Komar , Akdogan Mehmet Emin
Published: July 2022

Purpose

Tehran’s health-care system is growing, yet it lacks emergency planning procedures. The premise of this study is that the urban environment around a hospital is just as robust as the hospital itself. This study aims to look at hospital resilience in an urban setting to see where it may be improved to keep the hospital operational during a disaster.

Design/methodology/approach

The urban resilience (UR) of Amir-Alam Hospital was analyzed in this study using a customized version of the United Nations Office for Disaster Risk Reduction’s City Resilience Profiling Tool. The 34 indications were broken down into five categories.

Findings

The result revealed that the hospital’s UR score was 51.75 out of 100, indicating medium resilience. The results of this study enable the decision-makers to determine what measures they may take to improve the hospital’s resilience in terms of its surrounding urban context.

Originality/value

The originality of this research is based on the surrounding urban environment’s resilience as an integral part of hospital resilience.
The impact of advanced manufacturing technology (AMT) application on product innovation performance: a model of mediated moderated effect
Authors: Wang Guilian , Zhang Liyan , Guo Jing
Published: July 2022

Purpose

Drawing on the integration of the knowledge-based theory and the resource orchestration theory, this study aims to develop a moderated mediation model on how design/manufacturing/administrative advanced manufacturing technology (AMT) influences product innovation performance. The authors hypothesized that the absorption capacity could mediate the AMT-innovation performance link and that design–manufacturing integration (DMI) could positively moderate the mediating effect of the absorption capacity.

Design/methodology/approach

To test the hypothesis, the authors conducted a mail survey of equipment manufacturing firms and obtained 302 valid responses for data analysis. Both hierarchical regression and bootstrapping analysis were conducted to empirically test the research model.

Findings

It is revealed that the absorption capacity partially mediated the effect of AMT on innovation and that DMI enhanced the mediated effect. Specifically, the mediating effect of the absorption capacity was more substantial and significant when DMI was high. However, the mediating effect of the absorption capacity was weaker and insignificant when DMI was low.

Originality/value

Overall, this study contributes to the AMT theory on innovation by identifying the absorption capacity and DMI as two key factors that elucidate why and under what conditions AMT affects innovation. Moreover, this study advises managers that besides developing AMT, firms should cultivate a strong DMI, which directs the absorption capacity toward converting the valuable knowledge in firms’ capital equipment into increased innovation performance.
Family firm competitiveness and owner involvement
Authors: Buchanan Bonnie , Martikainen Minna , Nikkinen Jussi
Published: July 2022

Purpose

In many countries, small and medium-sizes enterprises (SMEs) are primarily responsible for wealth, economic growth, innovation and research and development. In this paper, the authors examine the impact of family ownership and owner involvement on the financial performance of unlisted Finnish SMEs.

Design/methodology/approach

This is an empirical paper using a random sample of 1,137 non-listed Finnish SMEs. Through regression analyses and robustness tests, the authors examine the effects of family management, family and employee ownership and involvement.

Findings

Using profitability measures, the authors find family-owned and controlled SMEs perform significantly better than non-family firms. The number of family members actively involved in daily business operations bears a significant negative relation to firm performance. In contrast, non-family firms in which owners are actively involved, provide comparable returns to family firms, suggesting that in non-family firms active involvement contributes to performance. The authors find that employee ownership in SMEs does not provide an efficient way to compensate employees since more dispersed ownership does not lead to higher performance.

Research limitations/implications

SME employee ownership does not provide an efficient way to compensate employees since more dispersed ownership does not lead to higher performance.

Practical implications

In the case of Finland, family ownership is an effective organisational structure. As the depth of the COVID pandemic remains uncertain, firms with committed ownership are key to the economic recovery.

Originality/value

The authors approach the family ownership and involvement issue from a different angle. Unlike earlier studies, the authors examine the impact of both family ownership and involvement on the financial performance of privately owned SMEs. This paper helps shed light on the role of family ownership and involvement as a possible explanatory factor of overall economic performance.
Integrating circular economy strategies and business models: a systematic literature review
Authors: Foroozanfar Mohammad Hossein , Imanipour Narges , Sajadi Seyed Mojtaba
Published: July 2022

Purpose

This study aims to undertake a review of the circular economy (CE) and business model (BM) literature by conducting a thematic analysis and developing a framework.

Design/methodology/approach

To address the research questions, a systematic literature review was conducted. Finally, 106 publications were chosen based on two main criteria.

Findings

The authors performed an athematic analysis of CE drivers. This analysis identifies five key areas: environmental, economic, social, regulatory and institutional factors, as well as emerging approaches for addressing CE drivers. A framework for the circular economy business model (CEBM) has been developed by integrating BM value dimensions and three primary CE strategies, including closing, slowing and narrowing resource loops. Additionally, the authors’ framework considers the CEBM’s sustainability impact in emerging economies.

Research limitations/implications

This study is limited in two ways: one is inherent in the concept of CE, particularly CEBM, and the other is methodological.

Originality/value

This study contributes to the body of knowledge about CE and BM in three ways. First, this research includes a thematic analysis of CE drivers, as well as themes and subthemes. Additionally, the authors discuss an emerging approach for CE drivers. Second, the authors make a contribution by proposing a framework for CEBM that takes value dimensions and CE strategies into account for the emerging economy context. Third, the authors shed light on potential avenues for further research.
Hybrid manufacturing-remanufacturing system of essential commodity in the context of COVID-19
Authors: Bhide Amol Vasant , Akarte Milind M.
Published: July 2022

Purpose

This paper aims to assess the feasibility of a hybrid manufacturing and remanufacturing system (HMRS) for essential commodities in the context of COVID-19. Specifically, it emphasises using HMRS based on costs associated with various manufacturing activities.

Design/methodology/approach

The combination of mathematical model and system dynamics is used to model the HMRS system. The model was tried on sanitiser bottle manufacturing to generalise the result.

Findings

The remanufacturing cost is higher because of reverse logistics, inspection and holding costs. Ultimately remanufacturing costs turn out to be lesser than the original manufacturing the moment system attains stability.

Practical implications

The study put forth the reason to encourage remanufacturing towards sustainability through government incentives.

Originality/value

The study put forth the feasibility of the HMRS system for an essential commodity in the context of a covid pandemic. The research implemented system dynamics for modelling and validation.