bluuebunny/crossref_metadata_2025 huggingface dataset:
The international trade in human vaccines before COVID‐19
Authors: Segarra‐Blasco Agustí , Teruel Mercedes , Cattaruzzo Sebastiano
Published: October 2023

The recent COVID‐19 pandemic has highlighted the importance of global access to human vaccines. There is, however, no empirical work on either the unequal distribution of international trade or on its determinants. Applying a gravity model to the UN Comtrade database between 2000 and 2019, we explain the patterns of bilateral trade across 116 countries. Using the Poisson Pseudo‐Maximum Likelihood methodology, our results show that inequalities in international vaccine trade have steadily increased. In general, supply and demand drivers play a role in explaining the flow of human vaccines. The impact of these drivers varies depending on the income level of the importing country. High‐income countries intensify their flows with demand factors such as GDP per capita, or supply factors such as the location of big pharmaceutical companies. Conversely, low‐income countries receive more vaccines according to their population. Our results show that a poor country that houses a big pharmaceutical company acts as an exporting platform to developing and poor countries. Middle‐income countries present features similar to rich countries both by producing more and also by exporting more. The imbalance endangers the global fight against the current COVID‐19 pandemic.
Intrinsic Diophantine approximation on circles and spheres
Authors: Cha Byungchul , Kim Dong Han
Published: October 2023

We study Lagrange spectra arising from intrinsic Diophantine approximation of circles and spheres. More precisely, we consider three circles embedded in or and three spheres embedded in or . We present a unified framework to connect the Lagrange spectra of these six spaces with the spectra of and . Thanks to prior work of Asmus L. Schmidt on the spectra of and , we obtain as a corollary, for each of the six spectra, the smallest accumulation point and the initial discrete part leading up to it completely.
Deposition and optical properties investigation of components for multilayer electrochromic system
Authors: Rybak Janusz , Marszalek Konstanty W.
Published: October 2023

Electrochromic materials are materials that change their optical properties under the influence of an applied electrical potential. They can be based on different types of electrochromes, ranging from metal oxides (e.g., WO3, MO3, TiO, or NiO) to organic materials (such as SmPc2, EuPc2, or YbPc2). The choice of electrochromic material determines the subsequent choice of components, such as the electrolyte, also called the fast ion conductor, and the ion storage layer. In this paper, the authors present methods for the deposition of the individual functional layers of the electrochromic system, together with the parameters of the deposition processes. The construction of the high-vacuum apparatus on which the layers were deposited is presented. The results of structural and optical measurements of the deposited layers are also presented.
In Science Journals
Authors: Osborne Ian S. , Seale Madeleine , Foley John F. , Stajic Jelena , Funk Michael A. , Hurtley Stella M. , Fogg Christiana N. , Malo Courtney , Lempriere Sarah A. , Vignieri Sacha , Stern Peter , Yeston Jake S. , Isles Hannah M.
Published: October 2023

Highlights from the
Science
family of journals
Mountain mice break altitude record for mammalian life
Authors: Pennisi Elizabeth
Published: October 2023

How rodents survive on summits is a mystery
In Kenya, rising lakes prompt novel climate change lawsuit
Authors: Baraka Carey
Published: October 2023

Residents around Lake Baringo say the government has failed to address flooding caused by a warming climate
Increased iron utilization and oxidative stress tolerance in a
Vibrio cholerae flrA
mutant confers resistance to amoeba predation
Authors: Hoque M. Mozammel , Noorian Parisa , Espinoza-Vergara Gustavo , Adhikary Srijon , To Joyce , Rice Scott A. , McDougald Diane
Published: October 2023

The flagellar transcriptional regulator
flrA
initiates the regulatory cascade of flagellum synthesis in
Vibrio cholerae
. Previously, we observed an increase in sub-populations of
V. cholerae
carrying mutations in the
flrA
gene during long-term co-adaptation with the amoeba host
Acanthamoeba castellanii
. The
flrA
mutants exhibit increased growth and intracellular survival in the amoeba host but the molecular mechanisms were unknown. Using an in-frame deletion of
flrA,
here we show that the absence of
flrA
increases pathogen growth and induces a distinct
V. cholerae
transcriptomic signature during amoeba predation. Transcriptome analysis of a
flrA
mutant in
A. castellanii
revealed that several genes involved in iron acquisition and amino acid biosynthesis are highly up-regulated compared to the wild-type strain. Furthermore, we show that iron availability is crucial for the survival of
V. cholerae
in amoeba. We also report that
V. cholerae
KatB and KatG catalases confer an increased tolerance to oxidative stress. We conclude that the increased survival of the
flrA
mutant in amoeba is due to a combination of factors, including resistance to oxidative stress and an increased capacity to utilize essential nutrients such as iron and amino acids. Together, the results presented here detail how a bacterial pathogen increases resistance to protozoan predation, thereby allowing for increased survival in the environment.

IMPORTANCE

Persistence of
V. cholerae
in the aquatic environment contributes to the fatal diarrheal disease cholera, which remains a global health burden. In the environment, bacteria face predation pressure by heterotrophic protists such as the free-living amoeba
A. castellanii
. This study explores how a mutant of
V. cholerae
adapts to acquire essential nutrients and survive predation. Here, we observed that up-regulation of iron acquisition genes and genes regulating resistance to oxidative stress enhances pathogen fitness. Our data show that
V. cholerae
can defend predation to overcome nutrient limitation and oxidative stress, resulting in an enhanced survival inside the protozoan hosts.
Genomic epidemiology reveals the dominance of Hennepin County in the transmission of SARS-CoV-2 in Minnesota from 2020 to 2022
Authors: Scotch Matthew , Lauer Kimberly , Wieben Eric D. , Cherukuri Yesesri , Cunningham Julie M. , Klee Eric W. , Harrington Jonathan J. , Lau Julie S. , McDonough Samantha J. , Mutawe Mark , O'Horo John C. , Rentmeester Chad E. , Schlicher Nicole R. , White Valerie T. , Schneider Susan K. , Vedell Peter T. , Wang Xiong , Yao Joseph D. , Pritt Bobbi S. , Norgan Andrew P.
Published: October 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had an unprecedented impact on human health and highlights the need for genomic epidemiology studies to increase our understanding of virus evolution and spread and to inform policy decisions. We sequenced viral genomes from over 22,000 patient samples tested at Mayo Clinic Laboratories between 2020 and 2022 and used Bayesian phylodynamics to describe county and regional spread in Minnesota. The earliest calculated introduction into Minnesota was to Hennepin County from a domestic source around 22 January 2020; 6 weeks before the first confirmed case in the state. This led to the virus spreading to Northern Minnesota and, eventually, the rest of the state. International introductions were most abundant in Hennepin (home to the Minneapolis/St. Paul International Airport) totaling 45 (out of 107) over the 2-year period. Southern Minnesota counties were most common for domestic introductions, with 19 (out of 64), potentially driven by bordering states such as Iowa and Wisconsin as well as Illinois, which is nearby. Hennepin also was, by far, the most dominant source of in-state transmissions to other Minnesota locations (
n
= 772) over the 2-year period. We also analyzed the diversity of the location source of SARS-CoV-2 viruses in each county and noted the timing of state-wide policies as well as trends in clinical cases. Neither the number of clinical cases nor the major policy decisions, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, appeared to have an impact on virus diversity across each individual county.

IMPORTANCE

We analyzed over 22,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes of patient samples tested at Mayo Clinic Laboratories during a 2-year period in the COVID-19 pandemic, which included Alpha, Delta, and Omicron variants of concern to examine the roles and relationships of Minnesota virus transmission. We found that Hennepin County, the most populous county, drove the transmission of SARS-CoV-2 viruses in the state after including the formation of earlier clades including 20A, 20C, and 20G, as well as variants of concern Alpha and Delta. We also found that Hennepin County was the source for most of the county-to-county introductions after an initial predicted introduction with the virus in early 2020 from an international source, while other counties acted as transmission “sinks.” In addition, major policies, such as the end of the lockdown period in 2020 or the end of all restrictions in 2021, did not appear to have an impact on virus diversity across individual counties.
Channelrhodopsins: From Phototaxis to Optogenetics
Authors: Govorunova Elena G. , Sineshchekov Oleg A.
Published: October 2023

Channelrhodopsins stand out among other retinal proteins because of their capacity to generate passive ionic currents following photoactivation. Owing to that, channelrhodopsins are widely used in neuroscience and cardiology as instruments for optogenetic manipulation of the activity of excitable cells. Photocurrents generated by channelrhodopsins were first discovered in the cells of green algae in the 1970s. In this review we describe this discovery and discuss the current state of research in the field.
Biomarkers of the End-Stage Renal Disease Progression: Beyond the GFR
Authors: Yakupova Elmira I. , Abramicheva Polina A. , Bocharnikov Alexey D. , Andrianova Nadezda V. , Plotnikov Egor Y.
Published: October 2023

Chronic kidney disease can progress to the end-stage renal disease (ESRD) characterized by a high risk of morbidity and mortality. ESRD requires immediate therapy or even dialysis or kidney transplantation, therefore, its timely diagnostics is critical for many patients. ESRD is associated with pathological changes, such as inflammation, fibrosis, endocrine disorders, and epigenetic changes in various cells, which could serve as ESRD markers. The review summarizes information on conventional and new ESRD biomarkers that can be assessed in kidney tissue, blood, and urine. Some biomarkers are specific to a particular pathology, while others are more universal. Here, we suggest several universal inflammatory, fibrotic, hormonal, and epigenetic markers indicative of severe deterioration of renal function and ESRD progression for improvement of ESRD diagnostics.
Modification of Lugano criteria by pre-infusion tumor kinetics improves early survival prediction for patients with lymphoma under chimeric antigen receptor T-cell therapy
Authors: Winkelmann Michael , Blumenberg Viktoria , Rejeski Kai , Quell Christina , Bücklein Veit , Ingenerf Maria , Unterrainer Marcus , Schmidt Christian , Dekorsy Franziska J , Bartenstein Peter , Ricke Jens , von Bergwelt-Baildon Michael , Subklewe Marion , Kunz Wolfgang G
Published: October 2023

Background

Chimeric antigen receptor T-cell therapy (CART) is effective for patients with refractory or relapsed lymphoma with prolongation of survival. We aimed to improve the prediction of Lugano criteria for overall survival (OS) at 30-day follow-up (FU1) by including the pre-infusion tumor growth rate (TGRpre-BL) and its early change to 30-day FU1 imaging (TGRpost-BL).

Methods

Consecutive patients with pre-baseline (pre-BL), baseline (BL) and FU1 imaging with CT or positron emission tomography/CT before CART were included. TGR was defined as change of Lugano criteria-based tumor burden between pre-BL, BL and FU1 examinations in relation to days between imaging examinations. Overall response and progression-free survival were determined based on Lugano criteria. Proportional Cox regression analysis studied association of TGR with OS. For survival analysis, OS was analyzed using Kaplan-Meier survival curves.

Results

Fifty-nine out of 81 patients met the inclusion criteria. At 30-day FU1 8 patients (13.6%) had a complete response (CR), 25 patients (42.4%) a partial response (PR), 15 patients (25.4%) a stable disease (SD), and 11 patients (18.6%) a progressive disease (PD) according to CT-based Lugano criteria. The median TGRpre-BLwas −0.6 mm2/day, 24.4 mm2/day, −5.1 mm2/day, and 18.6 mm2/day and the median TGRpost-BLwas −16.7 mm2/day, −102.0 mm2/day, −19.8 mm2/day and 8.5 mm2/day in CR, PR, SD, and PD patients, respectively. PD patients could be subclassified into a cohort with an increase in TGR (7 of 11 patients (64%), PD TGRpre-to-post-BL INCR) and a cohort with a decrease in TGR (4 of 11 patients (36%), PD TGRpre-to-post-BL DECR) from pre-BL to post-BL. PD TGRpre-to-post-BL DECRpatients exhibited similar OS to patients classified as SD, while PD TGRpre-to-post-BL INCRpatients had significantly shorter OS (65 days vs 471 days, p<0.001).

Conclusion

In the context of CART, the additional use of TGRpre-BLand its change to TGRpost-BLdetermined at 30-day FU1 showed better OS prognostication for patients with overall PD according to Lugano criteria. Therefore, this modification of the Lugano classification should be explored as a potential novel imaging biomarker of early response and should be validated prospectively in future studies.
Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) neutralization counteracts T cell immune evasion in breast cancer
Authors: Travelli Cristina , Colombo Giorgia , Aliotta Martina , Fagiani Francesca , Fava Natalia , De Sanctis Rita , Grolla Ambra A , Garcia Joe G N , Clemente Nausicaa , Portararo Paola , Costanza Massimo , Condorelli Fabrizio , Colombo Mario Paolo , Sangaletti Sabina , Genazzani Armando A
Published: October 2023

Background

Nicotinamide phosphoribosyltransferase (NAMPT) is a key intracellular enzyme that participates in nicotinamide adenine dinucleotide (NAD) homeostasis as well as a released cytokine (eNAMPT) that is elevated in inflammatory conditions and in cancer. In patients with breast cancer, circulating eNAMPT is elevated and its plasma levels correlate with prognosis and staging. In light of this, we investigated the contribution of eNAMPT in triple negative mammary carcinoma progression by investigating the effect of its neutralization via a specific neutralizing monoclonal antibody (C269).

Methods

We used female BALB/c mice injected with 4T1 clone 5 cells and female C57BL6 injected with EO771 cells, evaluating tumoral size, spleen weight and number of metastases. We injected two times a week the anti-eNAMPT neutralizing antibody and we sacrificed the mice after 28 days. Harvested tumors were analyzed by histopathology, flow cytometry, western blot, immunohistochemistry, immunofluorescence and RNA sequencing to define tumor characteristics (isolating tumor infiltrating lymphocytes and tumoral cells) and to investigate the molecular mechanisms behind the observed phenotype. Moreover, we dissected the functional relationship between T cells and tumoral cells using three-dimensional (3D) co-cultures.

Results

The neutralization of eNAMPT with C269 led to decreased tumor size and reduced number of lung metastases. RNA sequencing and functional assays showed that eNAMPT controlled T-cell response via the programmed death-ligand 1/programmed cell death protein 1 (PD-L1/PD-1) axis and its neutralization led to a restoration of antitumoral immune responses. In particular, eNAMPT neutralization was able to activate CD8+IFNγ+GrzB+T cells, reducing the immunosuppressive phenotype of T regulatory cells.

Conclusions

These studies indicate for the first time eNAMPT as a novel immunotherapeutic target for triple negative breast cancer.
A dedicated application of evolutionary algorithms: synchrotron X-ray radiation optimization based on an in-vacuum undulator
Authors: Ketenoglu Bora , Bostanci Erkan , Ketenoglu Didem , Canbay Ali Can , Harder Manuel , Karaca Adnan Sahin , Eren Engin , Aydin Ayhan , Yin Zhong , Guzel Mehmet Serdar , Martins Michael
Published: October 2023

Following the rapid growth in accelerator-based light sources research since the mid of 20th century, miscellaneous third generation synchrotron radiation (SR) facilities such as SSRL, APS, ESRF, PETRA-III, and SPring-8 have come into existence. These SR source facilities provide 1020–1025 photons/s/mrad2/mm2/0.1%BW peak brightness within the photon energy range of 10–105 eV. Since different measurement techniques are utilized at X-ray beamlines of SR facilities, many kinds of insertion devices (i.e., undulators and wigglers) and optical components (e.g., high-resolution monochromators, double-crystal monochromators, lenses, mirrors, etc.) are employed for each experimental setup as a matter of course. Under the circumstances, optimization of a synchrotron beamline is a big concern for many scientists to ensure required radiation characteristics (i.e., photon flux, spot size, photon energy, etc.) for dedicated user experiments. In this respect, an in-vacuum hybrid undulator driven by a 6 GeV synchrotron electron beam is optimized using evolutionary algorithms (EA). Finally, it is shown that EA results are well consistent with both the literature and the analytical calculations, resulting in a promising design estimation for beamline scientists.
Implementing and improving designated care partner programs in three Ontario long-term care homes
Authors: Conklin James , Dehcheshmeh Maryam Mohammadi , Archibald Douglas , Elliott Jacobi , Hsu Amy , Kothari Anita , Stolee Paul , Sveistrup Heidi
Published: October 2023

Long-term care (LTC) residents have an increased risk of social isolation and loneliness, and these risks were exacerbated by pandemic policies that restricted visitors. The designated care partner (DCP) program was introduced in some LTC homes to allow designated family members to safely enter the homes and provide support for residents. We undertook a developmental evaluation (DE) to support the development and implementation of the DCP program in three Ontario LTC homes during the COVID-19 pandemic. Data were collected from 65 staff and DCPs through seven iterations of a DE process. Analysis used directed and inductive coding and theming procedures to create a description of the DCP experience. Themes illustrated the barriers and facilitators to the DCP program and revealed a pervasive deficit of care due to inadequate funding, staff shortages, and an acrimonious relationship between staff and family members. Our project demonstrated a need for additional resources and stronger partnerships between staff and family caregivers.
Revision of Motec Total Wrist Replacement in the Second Metacarpal
Authors: MAHER Mark , ESTFAN Rami , STOREY Philip , PACKER Greg
Published: October 2023

Wrist arthroplasty is becoming more commonplace, with various implant choices available. The Motec (Swemac Orthopaedics AB, Linköping, Sweden) cementless ball-and-socket system is being increasingly utilised and is designed for the distal component to be implanted into the third metacarpal. However, distal component failure is a recognised complication. We outline our experience with the revision of this component into the second metacarpal. This technical note is presented through our experience of two patients who underwent revision arthroplasty for the management of peri-prosthetic fracture of the third metacarpal. This technique has demonstrated a safe and viable solution to this complication, achieving good anatomical centre of rotation, function, range of movement and patient satisfaction.

Level of Evidence: Level V (Therapeutic)
Angioleiomyoma – A Case Report
Authors: AMRUTIYA Pratik Arvind , BROWN Oliver Scott , PAPANIKOS Efstratios , MALLINA Ravi
Published: October 2023

Angioleiomyoma is a rare benign soft tissue tumour arising from smooth muscle, representing <1% of upper limb soft tissue tumours. We report a 54-year-old male presenting with a progressively enlarging atraumatic lesion along the palmar side of the base of the ring and little finger. A biopsy was done to determine the diagnosis. Intraoperatively, the lump was found to be intimately related to the radial digital artery, it could not be excised en-bloc without transecting the radial digital artery of the little finger. Following excision, the ends of the digital artery were anastomosed. At 10-months follow-up, the hand was fully functional without any evidence of cold-intolerance or neurological deficit along the distribution of the digital nerve. We review the literature on angioleiomyoma and report careful resection of the tumour with digital artery transection and repair as a treatment option for angioleiomyoma of the digital artery.

Level of Evidence: Level V (Therapeutic)
Carer Peer Workers in Borderline Personality Services: Providing Reciprocal Understanding and Personal Strategies to Family Members
Authors: Barr Karlen R. , Townsend Michelle L. , Grenyer Brin F. S.
Published: October 2023

The value that carer peer workers may offer family members with lived experience of BPD has not been investigated thoroughly to date. This study aims to investigate the unique contributions of carer peer workers in supporting family members who care for consumers with BPD. Mixed method questionnaires were completed by family members, consumers, carer peer workers, and clinicians (N = 24) at five mental health services. Qualitative responses were analysed using thematic analysis. Family members felt understood due to the personable, reciprocal approach of carer peer workers, which differentiated carer peer workers from clinicians. Carer peer workers benefitted from their role by finding purpose and found hearing about similar experiences of family members challenging. Through interactions with carer peer workers, clinicians gained insight to the carer role. This study provided evidence that carer peer workers may play a unique role in supporting family members with lived experience of BPD.
Analysis of Inherent Characteristics of Two‐Speed Planetary Gear Transmission System
Authors: Tan Wuzhong , Zheng Zhibin , Wu Xueshen , Xiang Enming , Yan Yixiong
Published: October 2023

In the helicopter transmission system, because the two‐speed gear planetary transmission system without power interruption adopts the design of a double planetary gear system, the complexity of the structure leads to the time‐varying meshing stiffness, tooth surface friction and the interaction between components and other nonlinear factors are uncontrollable, and causes the helicopter transmission system vibration noise, unstable operation, and other problems. To solve the above problems, the inherent characteristics of the two‐speed planetary gear transmission system without power interruption were studied and analyzed to find out the influence law of its inherent characteristics. The inherent characteristics of a planetary gear drive system are mainly related to the integrated stiffness such as component mass, support stiffness, and meshing stiffness in the system. Based on the centralized mass method, the translation‐torsional coupling dynamics model of the double planetary gear drive system was established. According to the displacement coordination relationship between the components of the system, the dynamics equation of the double planetary gear drive system was constructed. The mass matrix and stiffness matrix were obtained using MATLAB, and the system’s natural frequency was obtained by solving the dynamics equation. The results show that the low‐order natural frequency is mainly the torsional vibration mode of the center component and the torsional vibration mode of the center component. The influence of the mass of the component on the natural frequency is more complex and has a certain influence on both the high‐ and low‐order natural frequency. The support stiffness in the system mainly affects the low‐order natural frequency and the meshing stiffness in the system mainly affects the high‐order natural frequency.
Consumer and Provider Perspectives on Hospital in the Home: A Qualitative Study
Authors: Roberts Natalie , Carrigan Ann , Hibbert Peter , Williams Robyn-Clay , Austin Elizabeth , Fajardo Pulido Diana , Meulenbroeks Isabelle , Nguyen Hao Mi , Hatem Sarah , Maka Katherine , Loy Graeme , Braithwaite Jeffrey
Published: October 2023

The delivery of acute health care has changed with the adoption of new technologies to meet changing community needs. In response to this, hospital systems and governments have invested in alternative models of care, including hospital in the home (HITH), where acute care that would typically require inpatient treatment is provided in the patient’s home. The academic literature presents evidence for comparable or improved patient outcomes associated with HITH interventions. However, it is currently unknown how consumers and providers view the model in the context of a new healthcare facility. This study aimed to elicit consumer and provider views about HITH and how the implementation of a HITH model of care in a new hospital could meet their healthcare needs. We adopted a qualitative approach for this research. Semistructured workshops and interviews were conducted via Zoom, where we presented patient vignettes of different models of care to consumers and providers and recorded their responses using scribes. Qualitative data were independently coded by pairs of researchers to identify themes and subthemes, and demographic data were aggregated. A total of 51 consumers and 35 providers attended the workshops. Consumers and providers frequently described similar themes, particularly accessibility, patient factors, and the health system consequences of HITH. However, the importance and focus of these topics varied across participants. Participants endorsed HITH as a flexible, patient-centred model with potential for wellbeing benefits. However, they noted the potential need for additional resources and increased anxiety among patients with lower health literacy. To address this, participants described the need for clear escalation protocols, communication channels, and expectations around HITH care. In conclusion, HITH is an established model that brings acute care into the homes of patients. The findings of this study support the provision of flexible acute care delivery to meet consumer needs and address the challenges encountered during the COVID-19 pandemic.
An Improved Direct Torque Control with an Advanced Broken-Bar Fault Diagnosis for Induction Motor Drives
Authors: Aissa Oualid , Reffas Abderrahim , Talhaoui Hicham , Ziane Djamel , Saim Abdelhakim
Published: October 2023

This paper presents an advanced strategy combining fuzzy logic and artificial neural networks (ANNs) for direct torque control (DTC) and broken-bar fault diagnosis in induction motors. More specifically, a fuzzy-based controller is used to simultaneously minimize the stator flux and the electromagnetic torque ripples. A neural switching table is then proposed to achieve the interface inverter control. Besides, a closed-loop broken-bar fault detection strategy based on the Hilbert technique (HT) with the discrete wavelet transform (DWT) and ANNs is proposed. The fault detection is performed by analyzing the induction motor’s stator current by using the combined techniques HT-DWT. The effect of a broken-bar fault on the machine varies according to the number and position of the broken bars. The neural detector was used in order to identify the number of broken bars through only one current measurement. The effectiveness of the developed control has been verified using MATLAB/Simulink and real-time simulation in OPAL-RT 4510. Obtained results show improved performances in terms of torque ripple minimization and stator current quality, evaluated, respectively, at 43.75% and 41.26% as well as a rigorous motor health monitoring.
A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART SWOG 1609 Cohort 47) in Patients with Gestational Trophoblastic Neoplasia
Authors: Patel Sandip P. , Othus Megan , Chae Young Kwang , Dennis Michael J. , Gordon Sarah , Mutch David , Samlowski Wolfram , Robinson William R. “Rusty” , Sharon Elad , Ryan Christopher , Lopez Gabby , Plets Melissa , Blanke Charles , Kurzrock Razelle
Published: October 2023

Purpose:

The efficacy of immune checkpoint blockade in gestational trophoblastic neoplasia (GTN) remains uncertain. We report the results of the GTN cohort of SWOG S1609 dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART).

Patients and Methods:

This prospective, open-label phase II trial evaluated ipilimumab plus nivolumab across multiple rare tumor cohorts, including GTN. Eligible patients received nivolumab 240 mg, i.v. every 2 weeks and ipilimumab 1 mg/kg i.v. every 6 weeks. The primary endpoint was overall response rate [ORR; complete response (CR) + partial response (PR)] by quantitative serum beta human chorionic gonadotropin (β-hCG); secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.

Results:

Four patients with refractory GTN enrolled and received therapy. At 11 months of ongoing follow-up, 3 of 4 patients responded [ORR = 75% (CR, 25%, n = 1, tumor mutation burden = 1 mutation/megabase; PD-L1 tumor proportion score = 50%); PR, 50%, n = 2)]. Responders included malignant gestational trophoblastic neoplasm (n = 1, CR, PFS 11+ months) and choriocarcinoma (n = 2, both PRs, PFS 10+ and 6+ months). One patient with epithelioid trophoblastic tumor experienced disease progression. The 6-month PFS was 75% [95% confidence interval (CI), 43%–100%], and the median PFS was not reached (range, 35–339+ days); all 4 patients were alive at last follow-up. Two patients experienced grade 3 immune-related toxicity (arthralgia and colitis); there were no grade ≥4 events.

Conclusions:

Ipilimumab plus nivolumab demonstrated efficacy in chemotherapy-refractory GTN, an ultra-rare cancer affecting young women. Three of 4 patients achieved ongoing objective responses with a reasonable safety profile at 6–11+ months.
Metastatic Melanoma Treatment with Pembrolizumab after Hypersensitivity Reaction to Nivolumab: A Case Report
Authors: Cruse Alyssa R. , Basilio Alexa J. , Lawson David H.
Published: October 2023

Programmed death protein-1 (PD-1) checkpoint inhibitors such as pembrolizumab and nivolumab are cornerstones to metastatic melanoma treatment, and they are often considered to be pharmacologically similar and interchangeable when it comes to designing chemotherapy regimens. In this case report, we describe a patient who had consistent immune reactions to nivolumab infusion but was able to tolerate pembrolizumab, without any reactions, when given hydrocortisone premedication. This case demonstrates a successful transition from one PD-1 checkpoint inhibitor to another with resolution of infusion-related reactions in a patient undergoing treatment for metastatic melanoma.
Late-Onset Melorheostosis: A Case Report
Authors: Vo Thanh Toan , To Kha , Dang Thanh Nghia , Vo Toan Phuc , Nguyen Duc Thien , Nguyen Duc Cong , Nguyen Manh Khanh , Nguyen Van Thai
Published: October 2023

Melorheostosis is a rare benign bone pathology involving bone dysplasia and hyperostosis. The disease can be recognized with a characteristic radiographic feature of radiopaque lesions dripping along a long bone’s diaphysis. The aberrant bone formation and development manifests mainly as pain, edema, and paresthesia of the affected limb. Severe cases may report limb deformity as well as limited range of motion. Until now, there have been approximately 300 cases reported about melorheostosis worldwide and its diverse clinical picture and age distribution. In Vietnam, there is only one known case of melorheostosis discovered incidentally via radiography. The scarcity of cases presents a challenge within the medical community in recognizing and diagnosing the condition, and a delayed diagnosis can lead to severe contracture and compromised limb motility. In this article, we reported an 82-year-old case of polyostotic melorheostosis with late onset and predominant edema, affecting the sternum, the ribs, and multiple bones of the right extremities and presented our clinical approach for a geriatric patient with chronic limb edema. Our case is distinctive in terms of anatomical location as well as the predominant 20-year non-pitting edema. A prompt diagnosis was made upon the classic dripping candle wax radiographic features emphasizing the role of plain X-ray in establishing the diagnosis without extraneous utilization of other modalities and invasive procedures. Exclusion of other causes of chronic edema such as lymphadenopathy, malignancy as well as parasitic infection is of clinical importance.
Salt-Taste Polymorphism TRPV1-rs8065080 Is Associated with Increased Likelihood of Depression in an Elderly Cohort
Authors: Ferraris Celeste , Scarlett Christopher J. , Veysey Martin , Lucock Mark , Bucher Tamara , Beckett Emma L.
Published: October 2023

Introduction: Despite the prevalence of depression and anxiety worldwide, their aetiologies remain unclear, and they can be difficult to diagnose and treat. Changes in salt-taste perception have been found in both conditions. Single-nucleotide polymorphisms (SNPs) in the salt-taste-related gene, TRPV1, have been associated with alterations to salt-taste perception, preference, and sodium consumption. Diet quality is a known modifier of depression and anxiety and recently, sodium intake has been studied in mental health. However, the relationships between salt-taste genetics, depression, anxiety, and these dietary factors are yet to be elucidated. Methods: Data from the well-characterized cross-sectional Retirement Health and Lifestyle Study (n = 536, ≥65 y) were used to explore the relationships between the salt-taste SNP TRPV1-rs8065080, levels of depression and anxiety (Hospital Anxiety and Depression Scale, HADS), estimated sodium intake, and diet quality in this secondary analysis. Standard least-squares regression and nominal logistic regression modelling were used to compare continuous and categorical variables, respectively, with analyses stratified by sex. Results: Presence of the TRPV1-rs8065080 variant allele (C) was found to increase the likelihood of having depression (HADS) in the total population and in males. The associations remained significant after adjusting for sodium intake, three diet quality indices, and demographic variables, suggesting that TRPV1-rs8065080 genotype is driving the association with depression. Discussion/Conclusion: Future studies should explore extra-oral functions of the SNP and salt-taste receptors in the brain and the roles of neurotransmitters common to both depression and salt taste to improve the management of this increasingly prevalent and difficult-to-treat condition.
NSCLC: Tumorzellen in den Luftwegen jenseits vom Tumorrand haben prognostische Bedeutung
Authors: Lesser Thomas
Published: October 2023

Background: The current accuracy of frozen section diagnosis of tumor spread through air spaces (STAS) in non-small cell lung cancer (NSCLC) is poor. However, the accuracy and prognostic value of STAS assessment on frozen sections in small-sized NSCLC (diameter ≤2 cm) is unknown. Methods: Three hundred fifty-two patients with clinical stage I NSCLC (≤2 cm) were included, of which the parafin sections and frozen sections were reviewed. The accuracy of STAS diagnosis in frozen sections was assessed using parafin sections as the gold standard. The relationship between STAS on frozen sections and prognosis was assessed by the Kaplan–Meier method and log-rank tests. Results: STAS on frozen sections in 58 of 352 patients could not be evaluated. In the other 294 patients, 36.39% (107/294) was STAS-positive on parafin sections and 29.59% (87/294) on frozen sections. The accuracy of frozen section diagnosis of STAS was 74.14% (218/294), sensitivity was 55.14% (59/107), specifcity was 85.02% (159/187) and agreement was moderate (K = 0.418). In subgroup analysis, the Kappa values for frozen section diagnosis of STAS in the consolidation-to-tumor ratio (CTR) ≤0.5 group and CTR > 0.5 group were 0.368, 0.415, respectively. In survival analysis, STAS-positive frozen sections were associated with worse recurrence-free survival in the CTR >0.5 group (P > 0.5) suggests that frozen section assessment of STAS can be applied to the treatment strategy of small-sized NSCLC with CTR > 0.5.
Gut Microbe-Metabolite Profiles Are Associated with Microbial Pathways of Longevity in Women: A Cross-Sectional Study Conducted in China
Authors: Zhang Qinren , Meng Ning , Li Ruiding , He Qianzu , Liang Xiaolin , Zhou Fan , Zheng Wenxuan , Ma Jinke , Yu Xiaohan , Tan Kaiyan , Li Quanyang
Published: October 2023

Introduction: Recent research on the gut deepens people’s understanding of the role of gut microbe-metabolites in longevity. However, most of the longevity population is female, and the gut microbe-metabolites associated with longevity in women remain unknown. Here, we hypothesize that the gut microbe-metabolite levels differed between the longevity women (LW, age ≥90) and the elderly women (EW, 60 < age <90). Methods: We performed a cross-sectional study of 22 women in Guangxi longevity areas. 16S rRNA full-length sequencing, bioinformatic analysis, and nuclear magnetic resonance hydrogen spectra were determined to analyze the gut microbiota, microbial pathways, and fecal metabolites. We evaluated significant differences and relationships in gut microbe-metabolites and microbial pathways using the Mann-Whitney test and Spearman correlation, respectively. Results: The EW experienced gut dysbiosis characterized by a higher Firmicutes/Bacteroidetes (F/B) value. The LW showed a higher abundance of Bacteroides and Alistipes, which might support health maintenance. Moreover, LW enriched alanine, aspartate, and glutamate metabolism, histidine metabolism, and pyruvate metabolism, leading to major changes in histidine, fumaric acid, acetate, valine, and aspartate. Interestingly, the most valuable metabolic pathway based on differential fecal metabolites confirmed the KEGG microbial pathway “alanine, aspartate, and glutamate metabolism” enriched in LW. Impressively, Bacteroides and Alistipes were positively correlated with alanine, aspartate, and glutamate metabolism, thus improving the level of aspartate, which could be a particular pathway related to longevity. Conclusion: The enriched gut genus and microbial pathways in LW showed a significant correlation, which might mediate the production of metabolites related to longevity.
Cerebral Microbleeds Are Associated with Widespread Blood-Brain Barrier Leakage
Authors: Li Yue , Li Man , Zuo Long , Li Xuanting , Hou Yutong , Hu Wenli
Published: October 2023

Introduction: The pathogenesis of cerebral microbleeds (CMBs) is incompletely understood, but blood-brain barrier (BBB) leakage may play a key role. This study aimed to investigate the relationship between compromised BBB integrity and CMBs as well as cognitive function. Methods: Ninety-seven participants were enrolled in this cross-sectional study, involving 24 CMB patients. Dynamic contrast-enhanced-magnetic resonance imaging was used to measure BBB permeability, and cognitive function was assessed by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Results: Compared with participants without CMBs, CMB patients had higher volume transfer constant (Ktrans, all p < 0.01) and area under the concentration curve (AUC, all p < 0.05) in normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter (DGM). Multivariable linear regression analyses revealed that CMB patients had significantly higher Ktrans in NAWM and AUC in NAWM, WMH, and CGM after adjustment for age, sex, vascular risk factors, and cognitive scores. MMSE and MoCA scores decreased with increasing Ktrans in WMH and DGM as well as AUC in WMH after adjustment for age, sex, CMB group, and education length. Conclusion: This study demonstrated that widespread BBB leakage was prevalent in CMB patients, suggesting that compromised BBB integrity may play a key role in the pathogenesis of CMBs and could lead to cognitive impairment.
Screening for Inflammatory Markers Identifies IL-18Rα as a Potential Link between Exenatide and Its Anti-Inflammatory Effect: New Results from the Combat-JUDO Randomized Controlled Trial
Authors: Stenlid Rasmus , Cerenius Sara Y. , Manell Hannes , Küçükemre Aydin Banu , Mörwald Katharina , Gomahr Julian , Höghammar Mitkas Marina , Eriksson Ida , Ciba Iris , Geiersberger Sabine , Thivel David , Weghuber Daniel , Bergsten Peter , Forslund Anders
Published: October 2023

Introduction: Obesity is associated with chronic inflammation. Chronic inflammation has also been linked to insulin resistance and type 2 diabetes, metabolic associated fatty liver disease, and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor analogs (GLP-1RA) are clinically used to treat obesity, with known anti-inflammatory properties. How the GLP-1RA exenatide effects inflammation in adolescents with obesity is not fully investigated. Methods: Forty-four patients were randomized to receive weekly subcutaneous injections with either 2 mg exenatide or placebo for 6 months. Plasma samples were collected at baseline and at the end of the study, and 92 inflammatory proteins were measured. Results: Following treatment with exenatide, 15 out of the 92 proteins were decreased, and one was increased. However, after adjustment for multiple testing, only IL-18Rα was significantly lowered following treatment. Conclusions: Weekly injections with 2 mg of exenatide lowers circulating IL-18Rα in adolescents with obesity, which may be a potential link between exenatide and its anti-inflammatory effect in vivo. This contributes to exenatide’s pharmaceutical potential as a treatment for obesity beyond weight control and glucose tolerance, and should be further studied mechanistically.
Cure Glomerulonephropathy Pathology Classification and Core Scoring Criteria, Reproducibility, and Clinicopathologic Correlations
Authors: Palmer Matthew B , Royal Virginie , Jennette J. Charles , Smith Abigail R. , Liu Qian , Ambruzs Josephine M. , Andeen Nicole K. , D’Agati Vivette D. , Fogo Agnes B. , Gaut Joseph , Gbadegesin Rasheed A. , Greenbaum Larry A. , Hou Jean , Helmuth Margaret E , Lafayette Richard A. , Liapis Helen , Robinson Bruce , Stokes Michael B. , Twombley Katherine , Yin Hong , Nast Cynthia C. ,   for the CureGN Consortium
Published: October 2023

Introduction: Cure Glomerulonephropathy (CureGN) is an observational cohort study of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), or IgA nephropathy. We developed a conventional, consensus-based scoring system to document pathologic features for application across multiple pathologists and herein describe the protocol, reproducibility, and correlation with clinical parameters at biopsy. Methods: Definitions were established for glomerular, tubular, interstitial, and vascular lesions evaluated semiquantitatively using digitized light microscopy slides and electron micrographs, and reported immunofluorescence. Cases with curated pathology materials as of April 2019 were scored by a randomly assigned pathologist, with at least 10% of cases scored by a second pathologist. Scoring reproducibility was assessed using Gwet’s agreement coefficient (AC)1 statistic and correlations with clinical variables were performed. Results: Of 800 scored biopsies (134 MCD, 194 FSGS, 206 MN, 266 IgA), 94 were scored twice (11.8%). Of 60 pathology features, 46 (76.7%) demonstrated excellent (AC1>0.8), and 12 (20.0%) had good (AC1 0.6–0.8) reproducibility. Mesangial hypercellularity scored as absent, focal, or diffuse had moderate reproducibility (AC1 = 0.58), but good reproducibility (AC1 = 0.71) when scored as absent or focal versus diffuse. The percent glomeruli scored as no lesions had fair reproducibility (AC1 = 0.34). Strongest correlations between pathologic features and clinical characteristics at biopsy included interstitial inflammation, interstitial fibrosis, and tubular atrophy with estimated glomerular filtration rate, foot process effacement with urine protein/creatinine ratio, and active crescents with hematuria. Conclusions: Most scored pathology features showed excellent reproducibility, demonstrating consistency for these features across multiple pathologists. Correlations between certain pathologic features and expected clinical characteristics show the value of this approach for future studies on clinicopathologic correlations and biomarker discovery.
A Hermenêutica como um dos Processos de Análise e Estruturação da Performance Musical
Authors: Lima Sonia Regina Albano de
Published: October 2023

O texto que se segue tem como objetivo central discorrer e avaliar de que maneira a hermenêutica pode ser empregada nas questões envolvendo a performance musical, tomando como fundamentação teórica, entre outros, os textos de Morais (2014), Albano de Lima (2005- 2022) e Bartz (2022). Os procedimentos interpretativos circunscritos a criação musical não serão objeto desta investigação, ainda que seja possível adotar a mesma metodologia de análise.
Uma canção que ninguém escreveu: quatro reflexões sobre intertextualidade em Uma Canção de Marcelo Segreto
Authors: Brandão Paulo de Tarso
Published: October 2023

Partindo dos conceitos de intertextualidade e dialogismo, o presente artigo faz uma breve análise da música “Uma Canção” composta por Marcelo Segreto, que abre o disco Rádio Lixão da banda paulista Filarmônica de Pasárgada. Analisando o procedimento composicional utilizado por Marcelo Segreto surgem quatro reflexões que são desenvolvidas: 1º - O conceito de intertextualidade e seu uso enquanto recurso composicional; 2º - O conceito de autoria e sua problemática no campo da arte pós-moderna; 3º - O uso da paródia e da apropriação em Uma Canção como fator de ambivalência com relação à tradição da canção; 4º- A influência tropicalista no processo composicional de Uma Canção.  Estas quatro reflexões, autônomas entre si, confluem para uma reflexão maior que subjaz ao texto: Como as ferramentas intertextuais podem servir ao processo de composição de canções.
Chronology of Violas according to Researchers
Authors: Ferreira João de Araújo
Published: October 2023

This work aims to reinvestigate, organize and centralize translations of terms cited by researchers as related to the ancestry of “VIOLAS”: belted box chordophones, better known for being part of orchestras - the so-called “family of violins”, where they are “bowed” instruments, that is, played primarily by bow - but also chordophones of similar shape, “fingered” (played directly by the fingers or some objects popularly called plectrum, as guitar picks).

It was observed that most scholars would have assumed that “viola” and its variations in different languages would have been just names of bowed instruments, among other inaccuracies repeated in a chain for centuries, so it would be necessary to point out these situations in order to subsidize new studies in several areas of Science. The developments were based on the Dialectical Methodology and the historical-social contexts were estimated from the oldest records found for each variation of names, in the main European languages, since Latin used at 2nd century BC. The database was created through extensive research of sources pointed out by different types of researches at different times.

Among the main reasons for carrying out this kind of reinvestigation is to include in previous investigative equations new factors such as the possibility of the existence of fingered instruments in the records. The main processes carried out were: reanalyze translations most used in publications; observe changes and variations of names among the different languages and identify possible patterns over the period.