bluuebunny/crossref_metadata_2025 huggingface dataset:
SYST-26 INVESTIGATING THE FUNCTIONAL ROLE OF GPNMB IN GLIOBLASTOMA AND THE TUMOR IMMUNE MICROENVIRONMENT AND ITS TARGETED ELIMINATION USING CAR-T CELLS
Authors: Savage Neil , Zemp Franz , Mikolajewicz Nicholas , Han Hong , Venugopal Chitra , Tatari Nazanin , Chokshi Chirayu , Kislinger Thomas , Mahoney Douglas , Moffat Jason , Singh Sheila
Published: August 2023

INTRODUCTION

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is active in the extracellular matrix of glioblastoma and presents a promising immunotherapy target for both tumor cells and immunosuppressive macrophages.

METHODS

Immunohistochemistry was performed on patient derived xenograft (PDX) brains and tissue samples of 16 patient-matched primary/recurrent GBMs and 23 normal organ tissues. Whole cell proteomics was performed on 43 matched primary/recurrent GBM samples. CRISPR/Cas9 was used to eliminate expression in GBM lines and proliferation and mouse survival times measured. GPNMB knockout clones generated in GL261 were engrafted in immunocompetent mice to examine single cell transcriptomes using sciRNA sequencing at endpoint. A second-generation CAR-T was developed to target GPNMB-expressing populations, and efficacy was interrogated using in vitro assays and GBM PDX models.

RESULTS

GPNMB was absent in most normal tissues but detected in residual PDX tumors treated orthotopically with CD133 CAR-Ts. Tissue microarrays and whole cell proteomics showed GPNMB upregulation in recurrent GBMs compared to primary (p=0.0349 vs. p=0.0033) while absent in normal tissues. Single cell sequencing data of patient GBMs revealed GPNMB was also highly expressed in tumor-associated macrophages. Eliminating GPNMB in GBM cell lines decreased proliferation (P<0.001) and prolonged survival times in all mouse models (P<0.01). GPNMB knockout clones displayed downregulation of hallmark signaling pathways of GBM such as PDGFR, TGF-beta, Integrins and Stats, and decreased innate/adaptive immune activation. CAR-T cytotoxicity and activation was observed in vitro and in vivo resulting in decreased tumor burden (P<0.001) and increased survival times (P<0.001).

CONCLUSIONS

We show GPNMB influences tumor-intrinsic biology of GBM and is also active in macrophages in the recurrent GBM immune microenvironment. By targeting GPNMB alongside CD133, combinatorial therapeutic regimens could target both the cancer stem cell hierarchy and its supportive niche. Administration of both CAR-T cell therapies to humanized mice engrafted with patient-derived GBMs is underway.
SYST-33 GENERATION OF ALLOGENEIC CAR-T CIRCUMVENTS FUNCTIONAL DEFICITS IN PATIENT-DERIVED AUTOLOGOUS PRODUCT FOR GLIOBLASTOMA
Authors: Shaikh Muhammad Vaseem , Salim Sabra K , Maich William T , Anand Alisha , Wei Jeffrey , Subapanditha Minomi K , Suk Yujin , Singh Manoj , Tabunshchyk Zoya , Chen Katie , Vora Parvez , Venugopal Chitra , Moffat Jason , Singh Sheila K
Published: August 2023

Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a poor prognosis despite aggressive standard of care. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in liquid malignancies, but clinical trials in GBM targeting various tumor antigens have not shown durable clinical benefit. While this may be attributable to various tumor-intrinsic immune evasion strategies characteristic of GBM, little work has assessed whether the issue is due to the quality of the CAR-T treatment itself. Currently, CAR-Ts for clinical studies are manufactured in an autologous setting wherein T-cells are extracted from patients, engineered ex-vivo, and subsequently re-infused back. However, peripheral T-cells taken from untreated GBM patients have demonstrated qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to establish whether CAR-Ts generated from GBM patients would show reduced efficacy in comparison to healthy donors using our previously validated CD133 CAR-T. In this work, we show pre-treatment exhaustion and reduced survival advantage in autologous, patient-derived CD133-targeting CAR-T cell products using an orthotopic xenograft model of human GBM. To overcome the functional and logistical considerations of autologous therapy, we additionally aimed to generate an “off-the-shelf” allogeneic CD133 CAR-T. Using CRISPR gene editing technology, we generated TCR-knockout CAR-T cells with comparable pre-clinical efficacy to our autologous models. Ultimately, this work highlights the need to reassess autologous CAR-T therapy for GBM, and consider allogeneic approaches as biologically-informed therapeutic alternatives.
TIPS-03 A PHASE 1 STUDY OF GALLIUM MALTOLATE (GAM) IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM)
Authors: Connelly Jennifer , Schmainda Kathleen , Al-Gizawiy Mona , Santos-Pinhero Fernando , Chitambar Christopher
Published: August 2023

Glioblastoma remains the most aggressive malignant brain tumor with universally poor prognosis. New treatments are needed which target novelpathways. GBM cells have significantly greater requirements for iron and display markedly higher levels of transferrin receptors for iron uptake and ferritin for iron storage than surrounding normal astrocytes. The increased intracellular iron pool drives GBM activity. Previously, we showed that since gallium shares certain chemical properties with iron, it can inhibit malignant cell growth by disrupting tumor iron homeostasis. Recently, we reported that GaM is cytotoxic to GBM cell lines and stem cells but not to microvascular endothelial cells. In rodent orthotopically implanted human GBM xenografts, orally administered GaM reduced tumor volume and prolonged animal survival. These preclinical studies form the basis for our Phase 1 study which evaluates GaM in patients with recurrent GBM. The trial will follow a 3 + 3 phase 1 dose escalation design. Three to six patients at each dose level will receive GaM 500 mg/d, 1000 mg/d, or 1500 mg/day for a minimum of two 28-day cycles. Patients age >= 18 years with histologically confirmed GBM or molecular GBM with recurrent measurable disease are eligible. In the absence of measurable disease, pathologic confirmation of recurrence is required. Primary objectives are to determine a maximum-tolerated dose and recommended Phase 2 dose. Safety/tolerability will be assessed. Secondary objectives include disease assessments and evaluation of PFS and OS. Correlative studies planned are sequential blood levels of gallium, iron, Tf, ferritin, and hepcidin. Available tumor tissues will be examined for the expression iron biomarkers by immunochemistry. The study is currently enrolling. Patients will receive study drug until disease progression, unacceptable adverse events, patient withdrawal, or death. To date, 5 patients received GaM 500 mg/d without DLT and 4 patients started GaM 1000 mg/d.
TIPS-07 LONGITUDINAL CSF PROTEOMICS FOR MONITORING AND PHARMACODYNAMIC BIOMARKER DISCOVERY
Authors: Riviere-Cazaux Cecile , Ikram Samar , Andersen Katherine , Warrington Arthur , Burns Terry
Published: August 2023

Rapid feedback is needed to understand the individualized biological impacts of novel glioma therapies. We are performing glioma biomarker discovery by serial cerebrospinal fluid (CSF) sampling from Ommaya reservoirs or lumbar punctures to determine how the CSF proteome can reveal early longitudinal intelligence regarding glioma status, biology, and therapeutic response. We aimed to leverage access to each patient’s glioma via CSF to identify candidate biomarkers of tumor burden, biology, and therapeutic challenge. Global proteomic CSF analysis was performed via Somalogic– an aptamer-based technology for highly sensitive and specific analysis of over 7,000 proteins. Discovery analysis comprised of the top 500 ranked proteins in the CSF from seven patients with high-grade gliomas versus non-glioma (normal pressure hydrocephalus) controls. The top HGG proteins were then filtered to include only proteins that met two additional criteria of 1) decrease with resection, and 2) increase with recurrence in individual paired patient samples. Additionally, in individual patients for whom serial CSF samples were available, protein fold change lists were created and ranked to determine the most or least differentially abundant proteins between various time points. Proteomic enrichment analysis revealed a conserved HGG CSF proteomic signature defined by 79 proteins, including ones known to be over-expressed in solid tumor malignancies, such as retinoblastoma binding protein 4, heat shock protein 90, and sorcin. The HGG proteomic signature was consistently enriched in an independent validation cohort consisting of 13 gliomas diverse in primary versus recurrent status, subtype, and grade, when compared to independent control CSF samples. Encouragingly, proteins in the HGG signature decreased in two patients following decreased tumor burden from surgical resection. Our preliminary data demonstrate the ability to gain detailed, individualized insights regarding glioma biology, tumor burden, and evolution through global CSF proteomics acquired from longitudinal neurosurgical access to each patient’s unique glioma.
TIPS-12 PHASE I CLINICAL STUDY OF TG02 CAPSULE IN THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMAS WITH FAILED TMZ TREATMENT
Authors: Guo Chengcheng , Yang Qunying , Cao Xi , Liao Yixiang , Li Xiaoyi , Dai Xiangrong , Chen Zhongping
Published: August 2023

BACKGROUND

This study(NCT 03904628) is a dose-escalation, open-label phase I study which enrolled high grade glioma patients who failed with temozolomide(TMZ) treatment. The study purpose is to investigate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of an multi-kinase inhibitor (TG02 capsule, with primary inhibitory effects on cyclin-dependent kinases), as a new therapy for patients with recurrent high-grade glioma patients.

METHODS

The key inclusion criteria were 18-75 years old, glioblastoma or anaplastic astrocytoma confirmed by histology; when disease progression after receiving temozolomide; according to RANO criteria had evaluable lesions; ECOG performance status of 0-2. Eligible patients were enrolled sequentially into different dose groups and received TG02 capsule every 4 weeks .The dose was increased in a traditional 3 + 3 design. Primary endpoints were the dose-limited toxicity (DLT) and the maximum tolerated dose(MTD). Second endpoints were pharmacokinetic characteristics and preliminary efficacy.

RESULTS

Between May 2019 and November 2021, twelve patients were enrolled. No DLT was occurred and MTD was not defined in study. The plasma concentration of TG02 reached the maximum at 2 h after administration, and the elimination half-life was about 7 h. Eleven patients(91.7%) had one or more treatment-related adverse events (TRAEs) assessed using CTCAE 5.0. Most frequent TRAEs were vomiting (91.7%), diarrhea (75.0%), and 50% of the patients had grade 3 or 4 AEs. There were no treatment-related deaths. The median progression-free survival (PFS) was 1.77 months (95%CI:0.82 ~ 4.24). The median OS was 9.63 months (95%CI:2.66 ~ NE).

CONCLUSION

TG02 capsule is safe and tolerable in patients with recurrent high-grade gliomas. Switching to using TG02 capsule showed some patients had intracranial tumor reduction who failed to treat with TMZ. TG02 can be further explored with combined therapy in the treatment of gliomas.
Creatinine to Cystatin-C Ratio in Renal Cell Carcinoma: A Clinically Pragmatic Prognostic Factor and Sarcopenia Biomarker
Authors: Schmeusser Benjamin N , Biermann Henry , Nicaise Edouard H , Ali Adil A , Patil Dattatraya H , Midenberg Eric , Helman Talia , Armas-Phan Manuel , Nabavizadeh Reza , Joshi Shreyas S , Narayan Vikram M , Bilen Mehmet A , Psutka Sarah P , Ogan Kenneth , Master Viraj A
Published: August 2023

Introduction

Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy.

Methods

We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression.

Results

A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia.

Conclusions

Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy.
Effectiveness of Cognitive Functional Therapy Versus Core Exercises and Manual Therapy in Patients With Chronic Low Back Pain After Spinal Surgery: Randomized Controlled Trial
Authors: Avila Leonardo , da Silva Morgana Duarte , Neves Marcos Lisboa , Abreu Andre Rogerio , Fiuza Cibelle Ramos , Fukusawa Leandro , de Sá Ferreira Arthur , Meziat-Filho Ney
Published: August 2023

Objective

Our aim was to investigate whether cognitive functional therapy (CFT) was more effective than core exercises and manual therapy (CORE-MT) in improving pain and function for patients with chronic low back pain after spinal surgery.

Methods

This study was a randomized controlled superiority trial in a university hospital and a private physical therapist clinic in Santa Catarina, Brazil. Eighty participants who were 18 to 75 years old and had chronic low back pain after spinal surgery received 4 to 12 treatment sessions of CFT or CORE-MT once per week for a maximum period of 12 weeks. Primary outcomes were pain intensity (numeric pain rating scale, scored from 0 to 10) and function (Patient-Specific Functional Scale, scored from 0 to 10) after intervention.

Results

We obtained primary outcome data for 75 participants (93.7%). CFT was more effective, with a large effect size, than CORE-MT in reducing pain intensity (mean difference [MD] = 2.42; 95% CI = 1.69–3.14; effect size [d] = 0.85) and improving function (MD = −2.47; 95% CI = −3.08 to −1.87; effect size = 0.95) after intervention (mean = 10.4 weeks [standard deviation = 2.17] after the beginning of treatment). The differences were maintained at 22 weeks for pain intensity (MD = 1.64; 95% CI = 0.98–2.3; effect size = 0.68) and function (MD = −2.01; 95% CI = −2.6 to −1.41; effect size = 0.81).

Conclusion

CFT was more effective than CORE-MT, with large effect sizes, and may be an option for patients with chronic low back pain after spinal surgery.

Impact

CFT reduces pain and improves function, with large effect sizes, compared with CORE-MT. The difference between CFT and CORE-MT was sustained at the midterm follow-up. Treatment with CFT may be an option for patients with chronic low back pain after spinal surgery.
Influence of Co-occurring Weakly Pathogenic Bacterial Species on Bacterial Spot Disease Dynamics on Tomato
Authors: Sadhukhan Shreya , Jacques Marie-Agnes , Potnis Neha
Published: August 2023

Mixed infections caused by multiple pathogenic and weakly pathogenic strains inhabiting the same host plants are common in nature and may modify pathogen dynamics. However, traditional plant pathogen studies have mostly focused on the binary interaction between a single host and a single pathogen. In this study, we have looked beyond this binary interaction and evaluated the impact of coinfection on disease dynamics on tomato using the bacterial spot pathogen Xanthomonas perforans (Xp), the co-occurring weakly pathogenic strain of X. arboricola (Xa), and the co-occurring potential weak pathogenic strain of Pseudomonas capsici (Pc). Time-series coinfection experiments monitoring disease severity and within-host population dynamics revealed higher disease severity in coinfection by three species compared with infection by Xp alone. However, coinfection by dual species, Xp and Pc, or Xa resulted in lower disease severity compared with Xp alone. Thus, coinfection outcomes depend on interacting species. Weak pathogens could exploit Xp to colonize the host plant as indicated by their higher populations in coinfection. However, Xp population dynamics were dependent on the coinfecting partner. While resource competition might be a possible explanation for lower Xp population in dual coinfection, interaction of Pc with the host was found to influence Xp population. Interestingly, Xp population was higher in the presence of three-species interaction compared with Xp and Xa coinfection, suggesting potential modulation of cooperative interactions among Xp and Xa in three-species coinfection rather than competitive interactions. Humidity played a significant role in population dynamics of the three species. Overall, this study highlighted the importance of coinfection dynamics in studying plant disease outbreaks.
Utility of Negative Pressure Wound Therapy: Raising the Bar in Chest Masculinization Surgery
Authors: Abu El Hawa Areeg A. , Dekker Paige K. , Mizher Rami , Orra Susan , Fan Kenneth L. , Del Corral Gabriel
Published: August 2023

Background:

Prophylactic use of negative pressure wound therapy (NPWT) has been shown to decrease the incidence of postoperative complications. This study aimed to evaluate the utility of NPWT in chest masculinization with free nipple graft (FNG).

Methods:

All consecutive male patients undergoing chest masculinization with FNG by a single provider at a single center were reviewed. Postoperative treatment with either NPWT or standard wound care (SWC) defined this study’s cohorts. Patient characteristics and postoperative complications were compared between patients receiving NPWT versus SWC.

Results:

One hundred thirty-one patients with 262 closed breast incisions (NPWT=72, SWC=190) met inclusion criteria. Overall complications were higher in the SWC cohort (n=80/190, 42%) compared to the NPWT cohort (n = 13/72, 18%, p < 0.001). The NPWT group had significantly lower rates of partial nipple graft loss (9/72, 12.5% versus 47/190, 24.7%, p = 0.031), seroma formation (1/72, 1.4% versus 15/190, 7.9%, p = 0.037), and nipple hypopigmentation (6/72, 8.3% versus 36/190, 18.9%, p = 0.024) when compared to the SWC cohort. Time to drain removal was significantly faster in the NPWT group (NPWT 7 days versus SWC 9 days, p ≤ 0.001).

Conclusions:

Patients receiving NPWT over their closed incisions following chest masculinization with FNG were found to have significantly lower rates of partial nipple graft necrosis, seroma formation, and time to drain removal compared to those receiving SWC. Future prospective, randomized studies to further elucidate the role of NPWT in top surgery are warranted.
Immediate Skin Replacement Allows for Nipple-sparing, Direct-to-implant Reconstruction in Patients with Advanced Breast Cancers
Authors: Schwartz Jean-Claude D. , Binstock Michael
Published: August 2023

Mastectomy has evolved from approaches that involved extensive skin resection to nipple-sparing mastectomy (NSM). However, patients with advanced breast cancers who require extensive skin resection usually also have their nipple areola complexes (NACs) removed, even if they are distant from the cancer. Implant reconstruction in these patients is challenging as they require tissue expansion and, typically, radiotherapy with additional surgeries to complete their reconstruction. The aesthetic results of this approach are inferior to NSM and direct-to-implant reconstruction. In patients who require significant skin resection but whose NACs are free of tumor, we have found that immediate skin replacement using a muscle-sparing latissimus dorsi flap allows for NSM and direct-to-implant reconstruction, obviating the need for tissue expansion, delayed implant placement, and NAC reconstruction. Here, we report on 12 patients in whom this approach is utilized.
Prepectoral Conversion of Subpectoral Implants for Animation Deformity after Breast Reconstruction: Technique and Experience
Authors: Shikhman Alexander , Erz Logan , Brown Meghan , Wagner Douglas
Published: August 2023

Background:

Implant-based breast reconstruction in postmastectomy patients is commonly performed in a submuscular plane. Following reconstruction, animation deformity can be a displeasing aesthetic result for patients. In addition, patients may experience more postoperative pain with a submuscular reconstruction. Prepectoral conversion of submuscular implant position is an option for addressing these concerns. We describe a detailed technique and review our results.

Methods:

A retrospective review was conducted of all prepectoral conversions performed by the senior author (DSW) from 2017 to 2019 after IRB approval. All patients presented with animation deformity and another symptom such as asymmetry, pain, and/or capsular contracture. Patients underwent prepectoral conversion with smooth silicone gel implants. Demographic data, outcomes, and patient satisfaction were reviewed.

Results:

Prepectoral conversion was performed in 33 consecutive patients (57 breasts) with animation deformity. Twelve patients had capsular contracture, seven complained of pain, and five had ruptured implants. Postoperative complications included three infections requiring implant removal in two breasts, one implant exposure and one hematoma requiring implant replacement, five seromas requiring aspiration, and one capsular contracture. Seven patients had contour abnormalities addressed with secondary autologous fat grafting. Ultimately, all patients had elimination of animation deformity and were satisfied with the results of the conversion.

Conclusions:

Unsatisfactory results of subpectoral implant reconstruction such as animation deformity and chronic pain have led the reconstructive surgeon to consider various techniques to address these issues. The conversion to a prepectoral plane will effectively eliminate animation deformity, resolve pain, and yield satisfactory results in these patients.
Plastic Surgery Diversity through the Decade: Where We Stand and How We Can Improve
Authors: Hernandez J. Andres , Kloer Carmen I. , Porras Fimbres Denisse , Phillips Brett T. , Cendales Linda C.
Published: August 2023

Background:

Several studies over the past decade have investigated diversity within the field of plastic surgery, yet it remains unclear if an increase has resulted. This study sought to review the status of diversity within plastic surgery over the last decade and form strategies for residency programs to increase diversity recruitment.

Methods:

Data analysis of racial demographics from the Association of American Medical Colleges databases was completed for all medical students, integrated plastic surgery residency applicants, integrated plastic surgery residents, and academic faculty from 2010 to 2020. Proportional averages were analyzed comparing 5 year durations with heteroscedastic t-tests. Interviews were then conducted with medical school diversity and inclusion officers across the country and subsequent thematic analysis was completed. Finally, diversity recruitment recommendations were synthesized from interview data.

Results:

There was no significant change in demographics of integrated plastic surgery applicants between 2010–2014 and 2015–2020. The only significant finding among integrated plastic surgery residents yielded a reduction in the “Hispanic/ Latino” group (4% -3%, P = 0.01). Faculty data showed an increase in “Hispanic/ Latino” (4% -5%, P < 0.01) and “other” (4% -5%, P = 0.02) groups with a reduction in “White” faculty members (74% -70%, P < 0.01). Final recommendations for diversity recruitment were then formed from diversity and inclusion officer interviews.

Conclusions:

Continuous and sustainable work with respect to diversity and inclusion within plastic surgery has an opportunity for growth. Implementation of key recommendations by residency programs can change the face of our specialty going forward.
Cross-sectional Vascularization Pattern of the Adipofascial Anterolateral Thigh Flap for Application in Tissue-engineered Bone Grafts
Authors: Buergin Joel , Werth Lucas , Largo René , Scherberich Arnaud , Schaefer Dirk J. , Kaempfen Alexandre
Published: August 2023

Background:

As part of the engineering of bone grafts, wrapping constructs in well-vascularized tissue, such as fascial flaps, improves bone formation. Our aim was to understand the cross-sectional vascularization pattern of human adipofascial flaps for this application.

Methods:

Seven adipofascial anterolateral thigh (ALT) flaps were harvested from five human cadaveric specimens. Axial vessel density was analyzed by immunohistochemistry and quantitative histology.

Results:

We found a high density of blood vessels directly superficial to and close to the fascia. A secondary plexus in between this first suprafascial plexus and the subdermal plexus was also identified. In all specimens, this second plexus showed less vascular density, and appeared to be at a constant level within the suprafascial fat throughout the flaps. The peak measurements for this secondary plexus varied between 1.2 and 2 mm above the deep fascia, depending on the donor’s body mass index.

Conclusions:

Quantitative immunohistochemistry is a reliable method to quantify and locate vessel density in an adipofascial flap. This is vital information before wrapping nonvascularized material into such a flap to estimate the inosculation potential of these vessels and likelihood of survival of the tissue. To profit from both suprafascial vascular plexuses, a correlation between subcutaneous tissue thickness and distance of the second plexus to the fascia should be further investigated. For the moment, we recommend maintaining at least 2–3 mm of subcutaneous fatty tissue on the fascia, to profit from both plexuses. Engineered constructs should be wrapped on the superficial medial side of the fascial flap to enhance vascularization.
The Scratch Collapse Test for Diagnosis and Treatment of Trigger Sites for Migraine Surgery
Authors: Chim Harvey
Published: August 2023

Diagnosis of trigger sites for migraine surgery relies on history to detect a constellation of symptoms and secondarily, nerve blocks, imaging studies, and Doppler probe examination. The scratch collapse test (SCT) has been described for localization of compressive neuropathies in the upper and lower extremities. In this study, we hypothesized that the SCT could also be used to diagnose trigger sites for surgical planning in migraine surgery. Eleven consecutive patients presenting for migraine surgery, and four patients presenting with recurrent headaches and secondary trigger sites after initial successful migraine surgery were examined with the SCT using a standard protocol to assess involvement of bilateral sites I, II, IV, V, and VI, with the carpal tunnel as a negative control. The SCT was positive bilaterally at sites I, II, IV, V, and VI for all patients presenting primarily for migraine surgery, regardless of trigger sites localized by history and other secondary modalities. The SCT, however, correlated with secondary trigger sites localized through history and examination for patients presenting with recurrent migraine headaches after previous primary surgery. The SCT is not reliable for localization of trigger sites in patients presenting primarily for migraine surgery. This likely relates to central sensitization of migraine headaches, leading to global cutaneous allodynia in the head and neck. In patients with recurrent migraine headaches, abrogation of central sensitization following the initial surgery allows diagnosis of secondary trigger sites through the SCT.
Brachybacterium atlanticum sp. nov., a novel marine bacterium isolated from the Atlantic Ocean
Authors: de Castro Inês , Ribeiro Susana , Oliveira Vanessa , Coelho Francisco J. R. C. , de Lurdes Dapkevicius Maria , de Azevedo Eduardo Brito , Barcelos e Ramos Joana
Published: August 2023

A bacterial strain, PhyBa_CO2_2T, was isolated from the North Atlantic Gyre, offshore Terceira Island in the Azores. Initially, the NCBI nucleotide blast analysis based on 16S rRNA gene sequences revealed that the strain belongs to the genus

Brachybacterium

, with a 100 % identity with

Brachybacterium paraconglomeratum

LMG 19861T. However, further genomic characterization through average nucleotide identity (ANI) and digital DNA–DNA hybridization analyses showed values of 96.06 and 64.80 %, respectively. Comparative genomics also highlighted differences in gene content. The genome size of PhyBa_CO2_2T is 3.6 Mbp and the DNA G+C content is 72.1 mol%. Chemotaxonomic analysis demonstrated that the composition of the fatty acids was mainly composed of anteiso-C15 : 0 (46.04 %), iso-C16 : 0 (13.70 %) and anteiso-C17 : 0 (9.48 %), and the polar lipids were mainly diphosphatidylglycerol, phosphatidylglycerol and two unidentified glycolipids. Furthermore, the diagnostic amino acid of the cell wall was meso-diaminopimelic acid and the predominant menaquinone was MK7. Finally, phenotypic analysis revealed differences in biochemical profiles between PhyBa_CO2_2T and its closely related strains in terms of indole production, urease and β-glucuronidase activity. Therefore, based on the genomic, chemotaxonomic and phenotypic data obtained, we concluded that strain PhyBa_CO2_2T represents a new species, for which the name Brachybacterium atlanticum sp. nov. is proposed in reference to its isolation site. The type strain is PhyBa_CO2_2T (=DSM 114113T= CECT 30695T).
Vibrio aestuarianus clade A and clade B isolates are associated with Pacific oyster (Magallana gigas) disease outbreaks across Ireland
Authors: Coyle Nicola M. , O'Toole Ciar , Thomas Jennifer C. L. , Ryder David , Feil Edward J. , Geary Michelle , Bean Timothy P. , Joseph Andrew Wokorac , Waine Ava , Cheslett Deborah , Verner-Jeffreys David W.
Published: August 2023

Bacteria from the family

Vibrionaceae

have been implicated in mass mortalities of farmed Pacific oysters (Magallana gigas) in multiple countries, leading to substantial impairment of growth in the sector. In Ireland there has been concern that

Vibrio

have been involved in serious summer outbreaks. There is evidence that

Vibrio aestuarianus

is increasingly becoming the main pathogen of concern for the Pacific oyster industry in Ireland. While bacteria belonging to the

Vibrio splendidus

clade are also detected frequently in mortality episodes, their role in the outbreaks of summer mortality is not well understood. To identify and characterize strains involved in these outbreaks, 43

Vibrio

isolates were recovered from Pacific oyster summer mass mortality episodes in Ireland from 2008 to 2015 and these were whole-genome sequenced. Among these, 25 were found to be

V. aestuarianus

(implicated in disease) and 18 were members of the

V. splendidus

species complex (role in disease undetermined). Two distinct clades of

V. aestuarianus

– clade A and clade B – were found that had previously been described as circulating within French oyster culture. The high degree of similarity between the Irish and French

V. aestuarianus

isolates points to translocation of the pathogen between Europe’s two major oyster-producing countries, probably via trade in spat and other age classes.

V. splendidus

isolates were more diverse, but the data reveal a single clone of this species that has spread across oyster farms in Ireland. This underscores that

Vibrio

could be transmitted readily across oyster farms. The presence of

V. aestuarianus

clades A and B in not only France but also Ireland adds weight to growing concern that this pathogen is spreading and impacting Pacific oyster production within Europe.
Tailored Photoacoustic Apertures with Superimposed Optical Holograms
Authors: Howe Glenn A. , Tang Meng-Xing , Rowlands Christopher J.
Published: August 2023

A new method of generating potentially arbitrary photoacoustic wavefronts with optical holograms is presented. This method uses nanosecond laser pulses at 1064 nm that are split into four time-delayed components by means of a configurable multipass optical delay apparatus which serves to map the pulses onto phase-delayed regions of a given acoustic wavefront. A single spatial light modulator generates separate holograms for each component which are imaged onto a photoacoustic transducer comprised of a thermoelastic polymer. The spatially- and temporally-modulated holograms facilitate a phased array effect which enables beam steering of the resulting acoustic pulse. For a first experimental demonstration of the method, as verified by simulation, an acoustic beam is steered in four directions by around 5 degrees.
The effect of transcranial direct current stimulation over the dorsolateral prefrontal cortex on behavioral and brain activity indices of visuospatial attention in intrinsic reward contexts
Authors: Akil Atakan M. , Cserjési Renáta , Németh Dezső , Nagy Tamás , Demetrovics Zsolt , Logemann H. N. Alexander
Published: August 2023

Research indicates a connection between frontal brain activity asymmetry and self-regulation, particularly, approach and inhibitory tendencies. However, the underlying brain mechanism remains unclear. Our preregistered study used transcranial direct current stimulation (tDCS) to overcome limitations in prior correlational studies, investigating the link between frontal alpha asymmetry (FAA), a potential neuromarker and a treatment target for relevant psychiatric disorders, and the behavioral and brain activity components related to approach and avoidance tendencies, as observed in a visuospatial cueing (VSC) paradigm. We utilized a randomized sham-controlled design with 65 healthy participants. Participants’ resting-state EEG was recorded to calculate FAA scores before and after 2 mA anodal tDCS to the right frontal site. They also completed a VSC task with neutral and intrinsic reward-associated (food) conditions. Results indicated no impact of tDCS on FAA or behavioral attentional bias/disengagement. Surprisingly, secondary analyses revealed tDCS enhancing attentional bias for rewards, as seen in enhanced Late Directing Attention Positivity and P1 effect. However, these effects did not translate into observable behavioral changes. The observed effects are consistent with a noradrenergic mechanism rather than asymmetry of brain activity.
Robust spatial self-organization in crowds of asynchronous pedestrians
Authors: Tomaru Takenori , Nishiyama Yuta , Feliciani Claudio , Murakami Hisashi
Published: August 2023

Similar to other animal groups, human crowds exhibit a variety of self-organized collective behaviors. Spontaneous formation of unidirectional lanes in bidirectional pedestrian flows is one of the most striking examples of self-organization in human crowds. In addition, previous experimental studies have suggested that stepping among pedestrians is spontaneously synchronized over time. However, those studies have primarily focused on one-dimensional, single-file crowds, limiting our understanding of temporal stepping patterns in crowds with more freedom of movement and their relationship to spatial patterns of organization. Here, we conducted experiments of bidirectional pedestrian flows (24 pedestrians in each group) and investigated the relationship between collective footsteps and self-organized lane formation by tracking each individual trajectory as well as foot-stepping kinematics. We found that, unlike previous studies, pedestrians did not spontaneously align their steps unless there was an external auditory cue to follow. Moreover, we found that footstep synchronization generated by external cues disturbed the flexibility of pedestrians’ lateral movements, increased potential collision risks, and narrowed the formed lanes, suggesting structural instability in the spatial organization. These results imply that, without external cues, pedestrians marching out of step with each other can efficiently self-organize into robust structures. Understanding how asynchronous individuals contribute to ordered collective behavior has potential applications for promoting efficient crowd management and will inform theoretical models for human and other animal collective behavior with asynchronous positional updates.
Evaluation of ownership structure and audit-quality in the wake of the Covid-19 crisis: empirical evidence from Jordan
Authors: Alharasis Esraa Esam
Published: August 2023

Purpose

This study aims to collect new empirical evidence to determine how different forms of ownership structure responded to the recent COVID-19 crisis. In light of this tragedy, it explores the relationship between ownership structure forms (i.e. block-holders, foreign, institutional and family ownerships) and audit quality (proxied by audit fees).

Design/methodology/approach

In total, 3,200 firm-year observations for Jordanian enterprises covering the years 2005 through 2020 are used in an ordinary least squares regression with firm-clustered standard error to assess the hypotheses.

Findings

The regression results showed that COVID-19 strengthens the association between each type of ownership (i.e. block-holders, foreign, institutional ownership forms) and audit quality. This result reflects the need for high-quality audit services during the pandemic by such owners to improve their business decisions and limit agency-conflict issues. However, the analysis failed to find any effect of COVID-19 when it comes to family ownership. Family-controlled firms may react faster in crisis situations, and correspondingly, they do not bear high audit costs. The extended analysis covering the years 2005–2022 came to the same results.

Practical implications

The results aid authorities in their control and management of the auditing business. The findings have important consequences for policymakers, lawmakers, regulators and the audit profession as they assess the growing issues in an uncertain economic environment. Evidence is provided that may be used to reassure investors and aid authorities as they devise appropriate remedies to the pandemic-triggered economic crisis. The findings may aid in the improvement of legislation that governs Jordan’s auditing industry. Furthermore, the results can be generalized to other Middle Eastern countries.

Originality/value

To the best of the authors’ knowledge, this is the first study to empirically evaluate how different types of ownership affect audit quality in response to a dramatic shift in auditors’ working conditions brought on by the global health calamity. In emerging economies like Jordan, this type of analysis allows for preliminary assumptions to be established about ownership status during the COVID-19 outbreak. It adds to the body of auditing knowledge by shedding light on how various kinds of ownership affect responses to adverse events. This assessment is intended to serve as the definitive testimony in the field of accounting regarding the effects of the coronavirus across various corporations’ portfolios.
Supply network resilience capabilities: a social–ecological perspective
Authors: Statsenko Larissa , Jayasinghe Ruchini Senarath , Soosay Claudine
Published: August 2023

Purpose

This study aims to investigate supply network (SN) resilience capabilities across the organizational, supply chain (SC) and industry levels by drawing on the complex adaptive systems (CASs) theory and the social–ecological perspective of resilience. An empirically grounded framework operationalizes the concept of social–ecological resilience by expounding resilience capabilities across phases of the CAS adaptive cycle.

Design/methodology/approach

This research uses a qualitative multiple case study approach. It draws on the case of the Australian Defence Manufacturing SN (ADM SN) during COVID-19 disruptions. A total of 28 interviews with senior decision makers from 17 companies, complemented by 5 interviews with the Australian Defence SC organizations and secondary data analysis, support the findings.

Findings

Individual organizations’ SC visibility and flexibility enabled by effective risk management and collaboration enhance the ability of the SN to anticipate and prepare for disruption. At the same time, the strength of SC relationships reduces resilience. SN disruption response velocity is enabled by inventory redundancy, process flexibility at the organizational level and visibility and collaboration at the SC level. Institutional support at the national industry level, development of value-adding capabilities and manufacturing process flexibility at the organizational level enhances the SN’s ability to re-organize. The transition from hierarchical to decentralized collaborative governance enhances SN resilience.

Practical implications

From a practitioner’s perspective, the findings highlight the need to embrace a broader view of SC beyond immediate tiers. Decision-makers in multinational companies must recognize the long-term impact of their procurement decisions on the supplier ecosystem. Developing local supplier capabilities rather than relying on established global SCs will pay off with future resilience. It, however, demands substantial investment and radical changes across all SC tiers. The lesson for smaller firms is not to over-rely on the existing relationships with supply partners. Although trust-based relationships and collaboration are essential, over-commitment can be counterproductive during global disruptions. With a lack of visibility and control over the SC, operational flexibility is critical for small firms to adapt to shifts in supply and demand.

Originality/value

To the best of the authors’ knowledge, this empirical research is one of the first attempts to operationalize the social–ecological perspective of SN resilience. Evidence-based theoretical propositions contribute to the emerging conversation about the CAS nature of resilience by demonstrating the multi-level effects of resilience capabilities.
The impact of migrant workers’ inclusion on subjective well-being, organizational identification, and organizational citizenship behavior
Authors: Agyeiwaah Elizabeth , Bangwayo-Skeete Prosper , Opoku Emmanuel Kwame
Published: August 2023

Purpose

Building on the social exchange theory, this study aims to investigate the impact of perceived workgroup inclusion on migrant subjective well-being, organization identification and organizational citizenship behavior (OCB).

Design/methodology/approach

Structural equation modeling was applied to 440 surveyed migrant workers in Macau’s tourism and hospitality industry.

Findings

Perceived workgroup inclusion has a positive influence on migrant workers’ subjective well-being and organizational identification, which both in turn positively affect their OCBs.

Originality/value

Based on the social exchange theory, this study formulates a model that explains how migrant workers' inclusion impacts their well-being, identification and organizational behaviors. It provides theoretical and practical insights into how migrant workers’ inclusion could serve as a talent management strategy that promotes OCBs.
Alterations of SIRT1/SIRT3 subcellular distribution in aging undermine cardiometabolic homeostasis during ischemia and reperfusion
Authors: Zhang Jingwen , Wang Hao , Slotabec Lily , Cheng Feng , Tan Yi , Li Ji
Published: August 2023

Age‐related sensors Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) play an essential role in the protective response upon myocardial ischemia and/or reperfusion (I/R). However, the subcellular localization and co‐regulatory network between cardiac SIRT1 and SIRT3 remain unknown, especially their effects on age‐related metabolic regulation during acute ischemia and I/R. Here, we found that defects of cardiac SIRT1 or SIRT3 with aging result in an exacerbated cardiac physiological structural and functional deterioration after acute ischemic stress and failed recovery through reperfusion operation. In aged hearts, SIRT1 translocated into mitochondria and recruited more mitochondria SIRT3 to enhance their interaction during acute ischemia, acting as adaptive protection for the aging hearts from further mitochondria dysfunction. Subsequently, SIRT3‐targeted proteomics revealed that SIRT1 plays a crucial role in maintaining mitochondrial integrity through SIRT3‐mediated substrate metabolism during acute ischemic and I/R stress. Although the loss of SIRT1/SIRT3 led to a compromised PGC‐1α/PPARα‐mediated transcriptional control of fatty acid oxidation in response to acute ischemia and I/R, their crosstalk in mitochondria plays a more important role in the aging heart during acute ischemia. However, the increased mitochondria SIRT1‐SIRT3 interaction promoted adaptive protection to aging‐related fatty acid metabolic disorder via deacetylation of long‐chain acyl CoA dehydrogenase (LCAD) during ischemic insults. Therefore, the dynamic network of SIRT1/SIRT3 acts as a mediator that regulates adaptive metabolic response to improve the tolerance of aged hearts to ischemic insults, which will facilitate investigation into the role of SIRT1/SIRT3 in age‐related ischemic heart disease.
Drawing African Diasporic women anthropologists in dialogue: Decolonizing the canon
Authors: Johnson Amanda Walker
Published: August 2023

Inspired by the use of naming and portraiture together in the Black artivism–such as that protesting the murders of George Floyd and Breonna Taylor–this paper reflects on the use of portrait drawing as a practice of genealogy. While working on a project to raise the visibility of scholars and their works in the African Diaspora, specifically Francophone women anthropologists, I felt compelled to draw their portraits. Drawing African Diasporic women into dialogue from the archive attends to temporality, vision, and listening, elements centered within anthropological practice, but also implicated in the attachment of the discipline to colonial logics, particularly of allochronism, objectification and silencing. The multisensory, embodied and slow practice of drawing alongside reading scholars' works allows for diasporic time‐travel, shifting the gaze, and constructing a decolonizing “listening genre”.
Unambiguous identification ofAncylostoma caninumandUncinaria stenocephalain Australian and New Zealand dogs from faecal samples
Authors: Stocker T , Scott I , Šlapeta J
Published: August 2023

Hookworms (Ancylostomatidae) are well‐known parasites in dogs due to their health impacts and zoonotic potential. While faecal analysis is the traditional method for detection, improvements in husbandry and deworming have decreased their prevalence in urban owned dogs. Drug resistance inAncylostoma caninumis becoming a discussion point in small animal practices across the region. This study aimed to identify hookworm species present in Australian and New Zealand dogs using molecular techniques. The ITS‐2 and isotype‐1 β‐tubulin assays were used to identify and quantify hookworm species. Results showed absence of coinfection in Australian samples from Greater Sydney region belonging either toA. caninumorUncinaria stenocephala, while New Zealand samples were a mixture ofA. caninumandU. stenocephala. The amplified isotype‐1 β‐tubulin sequences exhibited susceptibility to benzimidazole drugs. Rare mutations were identified inA. caninumandU. stenocephalasequences, representing a small percentage of reads. This study highlights the importance of molecular techniques in accurately identifying and quantifying hookworm species in dog populations.