bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series
Authors: Hoarau Cyrille , Maleki Alireza , Bouillet Laurence , Boccon-Gibod Isabelle
Published: July 2024

Background

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that manifests clinically as recurrent episodes of swelling affecting multiple anatomical locations. Long-term prophylaxis (LTP) aims to control the disease by preventing HAE attacks. Previously, treatments such as attenuated androgens have been used for LTP, but they have an unfavorable adverse effect profile. Today, these limitations may be overcome by patients transitioning to newer, targeted therapies including oral berotralstat and subcutaneous lanadelumab. This case series reports the transition process between different prophylactic therapies in a family with HAE in a real-world setting.

Results

Four adult patient cases from the same family who underwent transitions in HAE prophylaxis are presented. Three were female and one male. Two patients who transitioned to berotralstat were initially prescribed attenuated androgens. Two patients were not taking LTP at the time of initiating targeted treatment but had previously been prescribed tranexamic acid. The length of transition varied between the patients, with the longest time taken to stabilize on new therapy being 26 months. All patients received regular follow-up in person or by telephone and all four required an adjustment from their initial treatment plan.

Conclusions

Transitioning between LTP in HAE may help improve control of attacks, avoid unwanted adverse effects, or better cater to individual patient preferences. Newer targeted therapies have been shown to be effective and should be discussed with patients. Shared decision-making is a tool that can aid these discussions. The transition journey between LTP therapies in HAE may not be straightforward and is specific to each patient. Physicians should consider complicating factors such as patient anxieties around changing treatment, adverse effects, preferred routes of administration, and speed of transition. Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary.
Short and long-term acceptability and efficacy of extended-release cornstarch in the hepatic glycogen storage diseases: results from the Glyde study
Authors: Weinstein DA , Jackson RJ , Brennan EA , Williams M , Davison JE , Boer F de , Derks TGJ , Ellerton C , Faragher B , Gribben J , Labrune P , McKittrick KM , Murphy E , Ross KM , Steuerwald U , Voillot C , Woodward AJM , Mundy HR
Published: July 2024

Background

Hypoglycaemia is the primary manifestation of all the hepatic types of glycogen storage disease (GSD). In 2008, Glycosade®, an extended-release waxy maize cornstarch, was reported as an alternative to uncooked cornstarch (UCCS) which could prolong the duration of fasting in the GSD population. To date, there has been minimal published experience in (a) young children, (b) the ketotic forms of GSD, and (c) with daytime dosing. The Glyde study was created as a prospective, global initiative to test the efficacy and tolerance of Glycosade use across a broader and more diverse population.

Methods

A randomised double-blind cross-over fasting study assessing the tolerance and efficacy of Glycosade compared with cornstarch was performed across disease types and ages. Participants and clinicians chose the product deemed superior, whilst still blinded. Participants were followed for 2 years to assess long-term metabolic control, growth, and quality of life.

Results

Sixty-one participants (age 2–62 years; 59% female) were enrolled, and 58 participants completed the fasting studies (28 GSD I; 30 GSD III, VI, IX). Glycosade improved duration of fasting in GSD I and duration of fasting without ketosis in the ketotic forms. Chronic Glycosade use was chosen by 69% of participants. Those treated with Glycosade for the 2-year chronic phase used fewer doses of therapy while markers of metabolic control remained stable.

Conclusion

The Glyde study is the first multi-centre international trial demonstrating the efficacy and tolerance of Glycosade in a large cohort of hepatic GSD patients across a diverse international population. The ability to use fewer doses of therapy per day and avoidance of overnight therapy may improve compliance, safety, and quality of life without sacrificing metabolic control.
Exome sequencing in undiagnosed congenital myopathy reveals new genes and refines genes–phenotypes correlations
Authors: de Feraudy Yvan , Vandroux Marie , Romero Norma Beatriz , Schneider Raphaël , Saker Safaa , Boland Anne , Deleuze Jean-François , Biancalana Valérie , Böhm Johann , Laporte Jocelyn
Published: July 2024

Background

Congenital myopathies are severe genetic diseases with a strong impact on patient autonomy and often on survival. A large number of patients do not have a genetic diagnosis, precluding genetic counseling and appropriate clinical management. Our objective was to find novel pathogenic variants and genes associated with congenital myopathies and to decrease diagnostic odysseys and dead-end.

Methods

To identify pathogenic variants and genes implicated in congenital myopathies, we established and conducted the MYOCAPTURE project from 2009 to 2018 to perform exome sequencing in a large cohort of 310 families partially excluded for the main known genes.

Results

Pathogenic variants were identified in 156 families (50%), among which 123 families (40%) had a conclusive diagnosis. Only 44 (36%) of the resolved cases were linked to a known myopathy gene with the corresponding phenotype, while 55 (44%) were linked to pathogenic variants in a known myopathy gene with atypical signs, highlighting that most genetic diagnosis could not be anticipated based on clinical–histological assessments in this cohort. An important phenotypic and genetic heterogeneity was observed for the different genes and for the different congenital myopathy subtypes, respectively. In addition, we identified 14 new myopathy genes not previously associated with muscle diseases (20% of all diagnosed cases) that we previously reported in the literature, revealing novel pathomechanisms and potential therapeutic targets.

Conclusions

Overall, this approach illustrates the importance of massive parallel gene sequencing as a comprehensive tool for establishing a molecular diagnosis for families with congenital myopathies. It also emphasizes the contribution of clinical data, histological findings on muscle biopsies, and the availability of DNA samples from additional family members to the diagnostic success rate. This study facilitated and accelerated the genetic diagnosis of congenital myopathies, improved health care for several patients, and opened novel perspectives for either repurposing of existing molecules or the development of novel treatments.
Applications of extraembryonic tissue-derived cells in vascular tissue regeneration
Authors: Goushki Mehdi Amiri , Kharat Zahra , Kehtari Mousa , Sohi Alireza Naderi , Ahvaz Hana Hanaee , Rad Iman , HosseinZadeh Simzar , Kouhkan Fatemeh , Kabiri Mahboubeh
Published: July 2024

Vascular tissue engineering is a promising approach for regenerating damaged blood vessels and developing new therapeutic approaches for heart disease treatment. To date, different sources of cells have been recognized that offer assistance within the recovery of heart supply routes and veins with distinctive capacities and are compelling for heart regeneration. However, some challenges still remain that need to be overcome to establish the full potential application of these cells. In this paper, we review the different cell sources used for vascular tissue engineering, focusing on extraembryonic tissue-derived cells (ESCs), and elucidate their roles in cardiovascular disease. In addition, we highlight the intricate interplay between mechanical and biochemical factors in regulating mesenchymal stem cell (MSC) differentiation, offering insights into optimizing their application in vascular tissues.
Performance comparison of quantum-safe multivariate polynomial public key encapsulation algorithm
Authors: Kuang Randy , Perepechaenko Maria , Toth Ryan , Barbeau Michel
Published: July 2024

A novel quantum-safe key encapsulation algorithm, called Multivariate Polynomial Public Key (MPPK), was recently proposed by Kuang, Perepechaenko, and Barbeau. Security of the MPPK key encapsulation mechanism does not rely on the prime factorization or discrete logarithm problems. It builds upon the NP-completeness of the modular Diophantine equation problem, for which there are no known efficient classical or quantum algorithms. Hence, it is resistant to known quantum computing attacks. The private key of MPPK comprises a pair of multivariate polynomials. In a companion paper, we analyzed the performance of MPPK when these polynomials are quadratic. The analysis highlighted the MPPK high decapsulation time. We found that, while maintaining the security strength, the polynomials can be linear. Considerable performance gains are obtained for the decapsulation process. In this article, we benchmark the linear case and compare the results with the previous quadratic case.
Adaptive pulse shaping for OFDM RadCom systems in highly dynamic scenarios
Authors: He Haonan , Liang Tianhao , Zhang Tingting
Published: July 2024

Due to the spectrum and complexity efficiency, the integrated radar and communications (RadCom) systems have been widely favored, in which orthogonal frequency division multiplexing (OFDM) is the most popular signal to conduct the two functions simultaneously. However, an unoptimized pulse could suffer from severe inter-carrier interference (ICI) and high out-of-band emission (OOBE), which greatly degrades the system performance. In this paper, we introduce the pulse shaping scheme dedicated to RadCom systems, in which both transmitter and receiver can adaptively design pulses with the assistance of radar estimation. We first optimize the transmitting pulse with the weighted sum of signal-to-interference-plus-noise ratio (SINR) and OOBE by employing the popular genetic algorithm. Then, we design an improved-matched pulse at the receiver for maximizing the SINR with the fmincon solver. In this way, they both utilize the readily available radar information and keep the pulse optimal even in highly dynamic scenarios, which makes the most of RadCom systems while avoiding the overhead of channel estimation and feedback. Simulations prove the feasibility of proposed scheme and reveal that the radar image and communications SINR stay close to their optimum in most cases with much lower OOBE. An improved-matched pulse can further improve the communications performance when severe ICI occurs compared with a matched pulse.
Teacher support, grit and L2 willingness to communicate: the mediating effect of foreign language enjoyment
Authors: Yang Yanyu , Cui Yongze , Yao Suhua
Published: July 2024

Informed by some relevant theories of positive psychology, the current study examined the interrelations among teacher support, grit, and L2 willingness to communicate (WTC), focusing mainly on the mediating role of foreign language enjoyment (FLE). A sample of 619 university students in China participated in this cross-sectional survey. Structural equation modeling (SEM) was used to analyze the gathered data. The results showed that grit could directly and positively predict L2 WTC. Furthermore, teacher support and grit could affect L2 WTC via the mediating role of FLE. These findings served as empirical evidence from the second language acquisition (SLA) domain for positive psychology, revealing the influential mechanism shaping the interconnectedness among all the constructs. The study concluded with a discussion of pedagogical implications and suggestions for future research.
Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication)
Authors: Azuma Takayasu , Sato Yoshihiro , Chiba Hiroto , Haga Junichiro
Published: July 2024

Background

Appendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm.

Case presentation

An 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy.

Conclusion

We experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103–1108, 2022)
Refugee voices vs. humanitarian choices: how much can refugee-led organizations redefine power and agency in post-2019 Lebanon?
Authors: Diab Jasmin Lilian , Jasiukaitis Simona , El-Zakka Yara
Published: July 2024

In the humanitarian landscape, especially post-COVID-19, there has been a notable pivot towards inclusivity and participatory methodologies, emphasizing the pivotal role of refugee-led organizations (RLOs). In Lebanon, amidst persistent economic and political turmoil, RLOs serve as crucial support systems for Syrian and Palestinian refugees within an environment plagued by inconsistent refugee policies and heightened vulnerabilities. Academic discourse underscores the increasing significance of RLOs in humanitarian assistance, yet systemic hurdles such as power differentials and tokenistic inclusion have emerged, constraining their effectiveness and integration within the humanitarian sphere. This study critically examines the application of inclusivity within humanitarian operations, aligned with the principles outlined in the Agenda for Humanity, specifically scrutinizing how prevailing narratives and operational dynamics may marginalize RLOs in Lebanon, thereby impeding their efficacy. It endeavors to evaluate how RLOs can assert themselves as principal stakeholders in humanitarian endeavors, striving for a more equitable and pragmatic approach to power dynamics and strategic planning for refugee communities. Utilizing a qualitative and participatory methodology, this research engages with diverse RLOs in Lebanon, conducting interviews to realistically and practically frame their experiences, obstacles, and contributions within the humanitarian landscape across entrenched and often rigid hierarchies, power dynamics, and tokenism within Lebanon’s broader humanitarian landscape.
IgA nephropathy recurrence after living donor kidney transplantation: a retrospective analysis of postoperative outcomes at a single high-volume transplant center
Authors: Schmidt Jacob , Liefeldt Lutz , Baysal Emre , Töpfer Stella , Dagnæs-Hansen Julia , Lerchbaumer Markus , Schlomm Thorsten , Ralla Bernhard , Friedersdorff Frank , Peters Robert
Published: July 2024

Background

IgA nephropathy (IgAN) is a common primary glomerulonephritis leading to end-stage renal disease. Living donor kidney transplantation (LDKT) is considered a favorable treatment option, but IgAN recurrence rates and the impact on outcome is unclear. In the present study, we retrospectively analyzed the rate of IgAN recurrence, risk factors and clinical outcomes in LDKT recipients.

Methods

We analyzed 193 adult patients who received a LDKT between 2011 and 2017 of which 32 (16.7%) had IgAN as underlying disease. Demographic data and clinical outcomes, especially regarding IgAN recurrence, were evaluated. Mean follow-up period was 102.13 months in the IgAN group vs. 97.27 months in the control group.

Results

Among the IgAN cohort, five (15.63%) experienced IgAN recurrence. Patients with IgAN underwent LDKT at a significantly younger age (p < 0.001). No significant differences were observed in demographic factors, HLA-mismatches, or AB0-compatibility. Patients receiving an immunosuppressive regimen including Cyclosporine A (60% vs. 7.4%) instead of Tacrolimus (40% vs. 92.6%) were significantly more likely to develop IgAN recurrences (p < 0.001). Moreover, early post-surgery serum creatinine levels were higher in the recurrence group at one week (4.25 vs. 1.65 mg/dl; p < 0.001), one month (2.13 vs. 1.53 mg/dl; p = 0.027) and two years (2.65 vs. 1.34 mg/dl; p = 0.008). Although graft survival displayed a tendency towards inferior outcomes after recurrence, significance was not reached (p = 0.14, log-rank test).

Conclusion

Living donor kidney transplantation continues to be recommended as the preferred treatment option for IgAN patients, despite the potential risk of recurrence and graft loss.
Mitochondrial neurogastrointestinal encephalopathy: a case report
Authors: Jamalipour Soufi Ghazaleh , Hekmatnia Ali , Hekmatnia Farzaneh , Zarei Andrew Parviz , Riahi Farshad , Shafieyoon Shamim , Azizollahi Sara
Published: July 2024

Background

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an autosomal recessive disease associated with alterations in mitochondrial DNA (mtDNA). The typical age of onset of MNGIE is between the first and second decade of life. Diagnosis requires the presence of several key clinical features: sensorimotor neuropathy, external ophthalmoplegia, ocular ptosis, leukoencephalopathy, and gastrointestinal (GI) dysmotility. Unfortunately, MNGIE diagnosis is very challenging, and patients often undergo multiple diagnostic and surgical operations that are unnecessary.

Case presentation

This case is of a 51-year-old male presenting with a 2-year history of limb weakness, GI problems and cachexia. There was also a 1-year history of progressive ptosis and ophthalmoplegia. The patient’s uncle and brother had both died from GI-related issues prior to the age of 40. On physical examination, ocular motility was impaired in all directions and there was atrophy and reduction in power in both lower and upper extremities. FLAIR and T2-weighted sequences of brain MRI demonstrated diffuse cerebral white matter hyperintensity (leukoencephalopathy). On discharge, the patient was referred for genetic consultation for bone marrow transplantation and had regular follow-up with a gastroenterology specialist.

Conclusion

In patients presenting with chronic progressive ophthalmoplegia, severe gastrointestinal complications, sensorimotor neuropathy and white matter lesions on MRI, it is important to consider investigating for MNGIE.
Revolutionizing consumer insights: the impact of fMRI in neuromarketing research
Authors: Alsharif Ahmed H. , Mohd Isa Salmi
Published: July 2024

This study performs a comprehensive bibliometric (performance analysis) and thematic content analysis of global research in "neuromarketing or consumer neuroscience" and "functional magnetic resonance imaging or fMRI." Utilizing the PRISMA framework and R package software, we analyzed thirty-six Scopus-indexed articles. The USA and California Institute of Technology emerged as leading contributors, with Rangel, A., and Reimann, M., as notable authors. Prominent themes include 'advertising,' 'product,' 'price,' and 'brand', with the “Journal of Consumer Psychology” and “Journal of Neuroscience” being key publications. The most cited article is "Marketing actions can modulate neural representations of experienced pleasantness," with 620 citations. In addition, fMRI has been used to study consumer behavior (impulsiveness, reward, emotion, decision-making, and memory) toward marketing stimuli such as price (WTP), advertising (celebrity endorsement, MSV), product (packaging design), and brand (Halal logo, label, and personality). This study provides an invaluable literature review matrix and detailed insights into the current trends in global neuromarketing research utilizing fMRI. This study highlights the significant impact of fMRI in both academic and commercial realms, offering new insights for targeted marketing and consumer behavior research. It provides valuable guidance for developing more effective advertising strategies, understanding consumer decision-making processes, enhancing business performance, and collaborating academically.
The Ungrading Learning Theory We Have Is Not the Ungrading Learning Theory We Need
Authors: Sorensen-Unruh Clarissa
Published: July 2024

Ungrading is an emancipatory pedagogy that focuses on evaluative assessment of learning. Self-regulated learning (SRL) is deficit framed in the literature and in practice and is insufficient as a learning theory for ungrading. I propose an asset-framed learning theory that combines funds of knowledge and community cultural wealth as an alternative.
I-SPY2 Endocrine Optimization Pilot (EOP): Neoadjuvant amcenestrant +/- abemaciclib +/- letrozole in molecularly selected patients (pts) with HR+ HER2- stage 2/3 breast cancer (BC).
Authors: Chien Amy Jo , Mukhtar Rita A. , Giridhar Karthik , Olopade Olufunmilayo I. , Kalinsky Kevin , Vaklavas Christos , Elias Anthony D. , Wei Mei , Goetz Matthew P. , van 't Veer Laura , Alkhafaji Silver , Rugo Hope S. , Chen Nan , Symmans W. Fraser Fraser , Borowsky Alexander D. , Brown Swigart Lamorna , Onishi Natsuko , Yee Douglas , Hylton Nola , Esserman Laura
Published: July 2024

601

Background: EOP is an I-SPY2 neoadjuvant sub-study designed to test the tolerability and impact of novel endocrine-based strategies in stage 2/3 BC pts predicted to have lower benefit from chemotherapy. Amcenestrant (A) is an oral selective estrogen receptor degrader (SERD) with activity in hormone receptor positive (HR+) HER2- metastatic BC. Methods: EOP eligibility included pts screened for the main I-SPY2 trial with HR+ HER2-, MammaPrint (MP) low risk Stage 2/3 BC. Pts with MP High risk tumor signatures were eligible if clinically node-negative (cN-). Pts were stratified by SET index and menopausal status. Pts were randomized to 3 arms: A 200 mg qd (A), A + abemaciclib 150 mg bid (AA), A + letrozole 2.5 mg qd (AL). Premenopausal pts received concurrent ovarian function suppression. Treatment was for 6 mos followed by surgery. Baseline (BL) and 3-wk biopsies were performed. Breast MRIs were conducted at BL (T0), 3 wks (T1), 12 wks (T2), 6 mos (T3). The primary endpoint was feasibility, defined as >75% of pts completing >75% study therapy. Results: Between May 2021 and Aug 2022, 74 pts were randomized: 31 A, 21 AA, 22 AL. Median age 50 years, 54% premenopausal, 38% clinically node-positive (cN+). 41% pts had ductal, 38% lobular, 11% mixed ductal/lobular histology. Mean BL tumor Ki67 (central testing) was 16.9%, 88% MP low, 76% SET index Hi. Pt and tumor characteristics were balanced across the 3 arms. Treatment in all 3 arms was feasible with 95% of pts completing >75% study therapy. Most common AEs include grade 1-2 hot flashes (69%) and fatigue (66%). Grade 3 AEs include neutropenia (2 pts) and diarrhea (1 pt) in AA. Table summarizes key response endpoints, which were similar between pre- and postmenopausal pts. Of 28 cN+ pts, 2 (7%) were pathologically node-negative (pN-). Mean MRI Functional Tumor Volume (cc) change between T0->T1, T1->T2, T2->T3, T0->T3 was -6.06 (-34.2%), -3.55 (-29.2%), -0.829 (-20.1%), -11.3 (-68.4%), respectively, similar across arms (p=0.396).ctDNA was detected in 10/59 (17%) pts at T0. ctDNA became undetectable in 6 pts, decreased in 4 pts, and went from ctDNA undetectable at baseline to detectable at T3 in 2 pts. Conclusions: Six months of neoadjuvant endocrine therapy (NET) with the oral SERD amcenestrant is feasible, well-tolerated, and demonstrates anti-proliferative and anti-tumor activity in pre- and postmenopausal pts. NET provides a rich platform for biomarker discovery and investigating response to endocrine therapy. Clinical trial information: NCT01042379 . [Table: see text]
The impact of neighborhood socioeconomic deprivation on overall survival for patients with metastatic pancreatic cancer: An incidence-based retrospective cohort study.
Authors: Pattnaik Aishwarya , Powers Benjamin Daniel
Published: July 2024

e16340

Background: Studies have demonstrated that metastatic pancreatic cancer patients are undertreated in the United States, which leads to worse overall survival (OS). However, these studies have typically used large geographic areas (zip codes or counties) for assessment of socioeconomic deprivation (SED). Using a statewide cancer registry, SED at the neighborhood level was used to assess receipt of treatment and OS for metastatic pancreatic cancer patients. Methods: Using the incidence-based Florida Cancer Data System, pancreatic adenocarcinoma patients diagnosed from 2007-2015were identified. The predictor variable was the Area Deprivation Index (ADI), a composite measure of SED and validated dataset that ranks neighborhoods (census block groups) from 1-100 (higher scores = higher deprivation) at the national level. Demographic, tumor, and treatment variables were assessed. Descriptive statistics and survival analysis with Kaplan-Meier curves and the log-rank test were used. Results: Overall, 9,747 patients met inclusion criteria; 53.9% were male and the median age was 70 (range 19-102). When assessed by SED quartile, there were significant differences by age, gender, race, ethnicity, insurance, and receipt of chemotherapy (p < 0.05). For the cohort, 46.5% of patients received chemotherapy. However, 54% of the lowest SED cohort received chemotherapy compared to 39.4% of the highest SED cohort (p < 0.001). The 30- and 90-day mortality was 21.7% and 50.1%, respectively. For the lowest SED quartile, 30- and 90-day mortality were 18.5% and 43.4%, respectively, compared to the highest SED quartile rate of 25.1% and 56.2%, respectively (p < 0.001 for both). Median OS was 2.9 months. The median OS for the lowest and highest SED quartiles was 3.8 and 2.4 months, respectively (p < 0.001). For patients who received chemotherapy, median OS was 6.3 months. The median OS of the lowest and highest SED quartiles for those who received chemotherapy was 7.2 and 5.9 months, respectively (p < 0.001). Conclusions: In an incidence-based, statewide cancer registry, the median OS for metastatic pancreatic cancer patients remains poor (2.9 months) and most patients do not receive chemotherapy. Additionally, higher SED patients had worse survival than lower SED patients at several time points. These data suggest that SED impacts OS and future studies are needed to understand the multilevel factors, including cancer care coordination, that lead to survival disparities in metastatic pancreatic cancer. [Table: see text]
A first-in-human phase 1 trial of dose escalating intrathecal (IT) dendritic cells (cDC1s) primed against HER2/HER3 in patients (pts) with leptomeningeal disease (LMD) from triple-negative (TNBC) or HER2+ breast cancer (BC).
Authors: Forsyth Peter A. J. , Gandhi Shipra , Wilcox Jessica , Law Vincent , Mo Qianxing , Chen Zhihua , Ahmed Kamran A. , Piteo Cecily , Evernden Brittany , Pina Yolanda , Boire Adrienne Ann , Kalinski Pawel , Czerniecki Brian J.
Published: July 2024

TPS2090

Background: Leptomeningeal disease (LMD) is a devastating complication of BC where it occurs in approximately 5% of pts and has a dismal prognosis. The CSF of pts with LMD have an innate (PMID:34035069), but not adaptive, immune response (bioRxiv 2023.03.17.533041; doi: https://doi.org/10.1101/2023.03.17.533041) that is insufficient to combat LMD. We used IT cDC1 to elicit an adaptive response in murine LMD and found that IT cDC1s were safe, induced a Th1 response, cured most HER2+ LMD, and prevented LMD recurrence (PMCID: 9354231). This Th1 response was CD4+ > CD8+ T cell dependent and produced marked B cell infiltration in the CSF. Mechanistic studies are in progress. These cDC1s have been shown to induce Th1 responses to HER2 and HER3 tumors and prolong survival in preclinical models (PMID: 35710296; PMID: 34785506). And there are several trials of cDC1s in BC patients that are ongoing (NCT03384914, NCT03387553, NCT05504707, NCT05325632, NCT04348747, NCT05378464). On the basis of our murine studies we hypothesized testing cDC1 therapy in pts that a RP2D would be found and the CSF following cDC1 therapy would be remodeled to have a Th1 adaptive immunological profile. Methods: This is a phase I single-arm, non-randomized dose escalation multicenter study to establish 1) the safety of IT cDC1s in pts with LMD, and 2) associations between clinical outcomes & translational CSF studies such as scRNAseq and cytokine/chemokine arrays. Eligibility includes TNBC or HER+ LMD pts, prior pCSpRT/WBRT, ECOG PS ≤2, cytologic or MRI diagnosis of LMD, normal marrow and organ function, life expectancy of ≥ 8 weeks, and an Ommaya reservoir in place. Exclusions included other treatments to treat LMD ≤ 2 wks or < five ½ lives, > 8mg of DXM/D or equivalent, pregnancy or immunodeficiency syndromes were excluded. IT cDC1s were administered once a week x 12 wks at one of 4 dose levels (1 X 106 – 5 X 107 cDC1s) until PD, DLT or withdrawal during those 12 wks. Primary Endpoints was to 1) determine the safety and DLTs, and 2) association between various clinical endpoints and immune profiles in the CSF. We used the Bayesian Optimal Interval (BOIN) design to find the MTD. Response was measured using RANO-LM (PMID: 30715514). DLTs were defined as ≥ gr. 3 not due to LMD & didn’t respond to medical intervention/CSF removal ≤ 96 hrs. Final pre & post cDC1 treatment cyto-, chemokine profiles and cellular/tumor profiles (scRNAseq) will be determined and associations between these and clinical endpoints will be determined. As of 01 30 2024 the 1st cohort closed with three pts (1 TNBC, 2 HER2+ pts)at the dose of 1 X 106 cDC1s. Clinical trial information: NCT05809752 .
Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function
Authors: Vella Max , Mohan Sneha , Christie Hannah , Bailey Kent R , Cobelli Claudio , Dalla Man Chiara , Matveyenko Aleksey , Egan Aoife M , Vella Adrian
Published: July 2024

Context

Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes.

Objective

To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes.

Design

The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model.

Setting

The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN.

Participants

Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank.

Intervention

Two-hour, 7-sample OGTT.

Main Outcome Measures

Fasting, nadir, and integrated glucagon concentrations.

Results

One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype.

Conclusion

The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.
Ο ρόλος της συλλογικής μνήμης και της συμμετοχής της κοινότητας στην παραγωγή του κοινού χώρου
Authors: Στριγκλόγιαννης Σέργιος
Published: July 2024

Ποιός θα έχει την τελική απόφαση για το πως θα παραχθούν και θα κατοικηθούν οι χώροι της πόλης; Πως οι διαδικασίες συλλογικής μνήμης επηρεάζουν τις συλλογικές πρακτικές οικειοποίησης, διεκδίκησης και νοηματοδότησης, γράφοντας με τον τρόπο αυτό αμφισβητούμενες χωρικότητες στο σώμα της πόλης; Πως η συλλογική μνήμη και η συμμετοχή της κοινότητας επηρεάζουν την παραγωγή του κοινού χώρου; Η παρούσα έρευνα εστιάζει στις έννοιες της συμμετοχής και της συλλογικής μνήμης με στόχο τη διερεύνηση του ρόλου τους στην διεκδίκηση, παραγωγή και νοηματοδότηση ενός χώρου ως κοινό (common space). Σε θεωρητικό επίπεδο δημιουργείται ένα τριαδικό ερευνητικό σχήμα στο οποίο οι πολυεπίπεδες έννοιες της συμμετοχής στην παραγωγή χώρου και της συλλογικής μνήμης συναντούν το θεωρητικό υπόβαθρο των κοινών και του κοινού χώρου, και εξετάζονται υπό ένα νέο πρίσμα με σκοπό να δώσουν απάντηση στα βασικά ερευνητικά ερωτήματα, ενώ στην πράξη η σχέση μεταξύ τους αναζητείται μέσω τριών περιπτώσεων μελέτης: Αρχικά, στην εναλλακτική πρόταση της καθηγήτριας Α. Βρυχέα για την ανάπλαση του παλιού προσφυγικού συνοικισμού της Θήβας με την συμμετοχή των κατοίκων. Στη συνέχεια στους συλλογικούς αγώνες των κατοίκων για την διεκδίκηση και υπεράσπισης του λόφου Φιλοπάππου, και στις επίσημες στρατηγικές συμμετοχικής παραγωγής χώρου του Δήμου Αθηναίων. Τέλος, η παρούσα έρευνα πρόβληματοποιεί όχι μόνο τον χώρο ως κοινό αγαθό αλλά και τη μνήμη, καθώς επισημαίνει το δικαίωμα στην κοινή μνήμη στο χώρο - μίας μνήμης των κοινών.
Refinancing of trade loans - technologies and financial models
Authors: Pokamestov Il'ya , Gamilovskaya Anna , Lednev Mihal , Frolova Viktoriya , Chvanov Grigoriy
Published: July 2024

The monographs outline the theoretical and methodological foundations of refinancing trade loans, researching technologies and financial models of such transactions in the innovative economy of various sectors. The features of trade loans, methods of assessing and managing risks in operations of this kind and combating fraud in the trade finance system are highlighted. Rating models and risk management algorithms are used in this area, in particular in factor transactions and functionality.
The effectiveness of ketamine in medication of treatment-resistant depression - review
Authors: Brzozowska Patrycja , Bulska Klaudia , Sławek Konrad , Piela Andrzej , Piotrowski Jan , Hądzlik Izabela , Biały-Karbowniczek Julia , Nowińska Bianka , Łuczak Blanka , Słychan Katarzyna
Published: July 2024

In spite of the variety of antidepressant drugs available for treating depressive disorder, treatment  resistant depression (TRD) is still prevalent among the population. 
Despite being used mainly in anesthesia, and mostly phased out by more modern anesthetics, ketamine shows potential when it comes to depressive disorder treatment.
We've set out to investigate the the relevant body of work to determine the efficacy of ketamine usage in patients with TRD.
 
Research shows that usage of ketamine used in patients with TRD leads to mood elevation, better cognitive functions, sleep and appetite. Moreover, ketamine is shown to decrease suicidal thoughts and shows potential in acute actions in emergency situations, especially with its faster effects when compared to traditional antidepressants. Some research show significant reduction in suicidal thoughts after just one infusion of ketamine.
Clinicians have developed intranasal, subcutaneous, intramuscular and oral ways of administering ketamine, which, though less bioavailable, when compered to intravenous use, are much more convenient and less expensive for the patients. All those ways of administering the drug have their upsides and downsides, and theres still debate on which is best.
Ketamine shows promise in patients with TRD. Some studies show that up to 70% of people with TRD response to ketamine, which might show efficacy of ketamine usage in those patients
 
State of knowledge:
Despite extensive research in the field of depression treatment, there's considerable lack of comprehensive reviews of efficacy of ketamine usage in cases where traditional ways of treating depression have failed. In the face of increasing number cases of treatment resistant depression worldwide, this paper aims to gather research papers regarding this topic and synthesize it into comprehensive review.
Gut microbiota and thyroid diseases – summary of current knowledge
Authors: Daniluk Aleksander , Iwaniuk Kaja , Wojda Martyna , Świstowska Magdalena , Wielgosz Aleksandra
Published: July 2024

Introduction and purpose: The gut microbiota is a diverse collection of microorganisms that coexist in the human intestine. Disorders in its structure leads to dysregulation of huge number of organs, including the thyroid. This review summarizes the latest findings regarding the links between gut microbiota and common thyroid diseases: Hashimoto's thyroiditis, Graves' disease and thyroid cancer.
Materials and methods: This review was based on the PubMed and Google Scholar databases, using keywords: „gut microbiota AND thyroid/Hashimoto/Graves/thyroid cancer”, „Graves’ disease”, ,,Hashimoto thyroiditis”.
Description of knowledge: Gut dysbiosis can contribute to autoimmune thyroid diseases by influencing micronutrient availability and immune regulation. Specific bacterial species may impact Hashimoto's development by regulating neurotransmitters and hormone secretion. In Graves' disease, significant changes in gut microbiota suggest their potential role in autoimmune processes. Research on gut microbiota in thyroid cancer suggests potential diagnostic tools and implicates gut microbiota alterations in tumor development.
Conclusions: Significant gut microbiota changes are observed in Hashimoto's thyroiditis, Graves' disease, and thyroid cancer compared to healthy individuals, indicating a possible association. However, the exact mechanisms remain unclear, necessitating further research to understand how microbiota alterations contribute to these diseases.
Rockafellian Relaxation and Stochastic Optimization Under Perturbations
Authors: Royset Johannes O. , Chen Louis L. , Eckstrand Eric
Published: July 2024

In practice, optimization models are often prone to unavoidable inaccuracies because of dubious assumptions and corrupted data. Traditionally, this placed special emphasis on risk-based and robust formulations, and their focus on “conservative” decisions. We develop, in contrast, an “optimistic” framework based on Rockafellian relaxations in which optimization is conducted not only over the original decision space but also jointly with a choice of model perturbation. The framework enables us to address challenging problems with ambiguous probability distributions from the areas of two-stage stochastic optimization without relatively complete recourse, probability functions lacking continuity properties, expectation constraints, and outlier analysis. We are also able to circumvent the fundamental difficulty in stochastic optimization that convergence of distributions fails to guarantee convergence of expectations. The framework centers on the novel concepts of exact and limit-exact Rockafellians, with interpretations of “negative” regularization emerging in certain settings. We illustrate the role of Phi-divergence, examine rates of convergence under changing distributions, and explore extensions to first-order optimality conditions. The main development is free of assumptions about convexity, smoothness, and even continuity of objective functions. Numerical results in the setting of computer vision and text analytics with label noise illustrate the framework.

Funding: This work was supported by the Air Force Office of Scientific Research (Mathematical Optimization Program) under the grant: “Optimal Decision Making under Tight Performance Requirements in Adversarial and Uncertain Environments: Insight from Rockafellian Functions.”
Noteworthy record of melanism in Leopardus tigrinus from El Cocuy National Natural Park, Colombia
Authors: Cáceres-Martínez Carlos H. , Zamora-Abrego Joan Gastón , González-Maya José F.
Published: July 2024

El melanismo es el exceso de la pigmentación oscura que cubre parcial o totalmente el cuerpo de un animal.  La presencia de individuos melánicos es relativamente común en varias de las especies de felinos.  El objetivo de esta nota es reportar el segundo caso de melanismo en Leopardus tigrinus en vida libre para Colombia.  Para el país solo existe un registro publicado para el departamento de Caldas.  Entre junio de 2012 y marzo de 2020 se colocaron 158 estaciones simples de fototrampeo, en 5 áreas protegidas en la Cordillera Oriental de Colombia.  Después de casi 8 años de monitoreo y con un esfuerzo de muestreo de 60,704 noches/trampa, registramos un individuo melánico de L. tigrinus, en el Parque Nacional Natural El Cocuy.  Hasta ahora, la presencia de individuos de L. tigrinus melánicos se ha registrado principalmente en Brasil (aunque una vez se aclare su taxonomía pueda corresponder a una especie diferente).  Para Colombia se cuenta con un registro documentado a más de 350 km de distancia del nuestro (departamento de Boyacá).  Se considera que este fenómeno puede ser una respuesta adaptativa de las especies a presiones evolutivas del ambiente, y ha sido propuesta como una estrategia de segregación de nicho; sin embargo, dada la rareza de este fenotipo en el área de estudio, y en general a lo largo de su distribución, es necesario recabar mayor evidencia que pueda potencialmente explicar las fuerzas selectivas que favorecen o limitan este tipo de expresión fenotípica.
Predation of Sumichrast's vesper rat Nyctomys sumichrasti by the lizard Basiliscus plumifrons
Authors: Alvarado Randy , Mora José Manuel
Published: July 2024

En Costa Rica hay 33 especies de Cricetidae, incluida Nyctomys sumichrasti, una rata relativamente poco común.  En Costa Rica, habita principalmente en el dosel y rara vez se le ve debido a sus hábitos nocturnos y arbóreos.  En México, se le ha observado tanto en las copas de los árboles como en el suelo en medio de vegetación densa y árboles.  Durante una caminata en Selva Verde Lodge en el norte de Costa Rica, observamos un evento de depredación.  Tomamos fotos desde aproximadamente 5 m para no perturbar al depredador.  Identificamos al depredador en el lugar y luego confirmamos la identificación de la presa al comparar nuestras fotos con otras imágenes, guías de campo y claves taxonómicas.  El 19 de marzo de 2023 a las 17:28 hr, observamos a una hembra adulta de basilisco verde (Basiliscus plumifrons) que depredó y consumió una Nyctomys sumichrasti.  El basilisco persiguió a la rata por el suelo, la agarró con sus mandíbulas, la mató y luego la engulló.  Todo el proceso duró aproximadamente 40 minutos.  Nyctomys sumichrasti visita edificios en Selva Verde lodge donde siempre hay basiliscos. Estos son diurnos, mientras que N. sumichrasti es nocturna, pero pueden coincidir en actividad y ubicación. Recientemente, un basilisco verde hembra capturó una lagartija nocturna, y semanas antes, un macho de la misma especie consumió una cría de iguana verde en la misma área.
New records of small mammals in the diet of the buff-fronted owl, Aegolius harrisii and the black-and-white owl, Strix nigrolineata, along with a review of mammal prey of owls in Colombia
Authors: Marín-Giraldo Valentina , Chaves-Castaño Sarah , Mejía-Fontecha Ingrith Y. , Velásquez-Guarín Daniela , Mejía-Egas Ofelia , López-Ordoñez Juan Pablo , Ramírez-Chaves Héctor E.
Published: July 2024

La dieta de los búhos y lechuzas de Colombia ha sido escasamente estudiada.  El consumo de murciélagos y otros pequeños mamíferos ha sido registrado para Aegolius harrisii y Strix nigrolineata en otros países de Centro y Sudamérica; sin embargo, no había información sobre el tema para Colombia.  Presentamos nuevas observaciones de la depredación de mamíferos por búhos en Colombia y una breve revisión de registros históricos.  Reportamos el intento de consumo de un murciélago del género Platyrrhinus por parte del búho bicolor (Aegolius harrisii) y la presencia de murciélagos (Dermanura y Rhogeessa) y musarañas (Cryptotis) en una egagrópila del búho carinegro (Strix nigrolineata), en los Andes de Colombia.  La revisión de la literatura y datos de colecciones biológicas arrojó un total de al menos 30 especies de mamíferos que han sido registradas en la dieta de 8 especies adicionales de búhos en el país.  Los roedores son las presas con mayor número de reportes, que incluyen taxa de bosques, áreas urbanas y periurbanas.  Esta información puede ser útil para estudios posteriores sobre los posibles efectos de la pérdida del hábitat en el consumo de mamíferos por búhos y su papel como controladores de hospederos de agentes zoonóticos.
Scavenging insects found on a carcass of the endangered Galápagos sea lion Zalophus wollebaeki
Authors: Román Andrea C. , Chicaiza-Herrera Janna , Betancourt-Cargua Lenyn , Pinto C. Miguel
Published: July 2024

El lobo marino (Zalophus wollebaeki) es una especie endémica de las Galápagos.  Cadáveres de lobos marinos de las Galápagos se encuentran con frecuencia en las playas, pero poco se conoce sobre sus descomponedores.  El objetivo del presente trabajo es reportar una muestra de insectos encontrados sobre un cadáver de lobo marino.  En noviembre de 2022 se halló un cuerpo de Z. wollebaeki en el islote Caamaño del que se recolectaron e identificaron pupas y adultos de insectos carroñeros.  Se encontraron 2 especies de escarabajos y 1 de mosca.  Los especímenes fueron identificados como: Phaleria manicata (Coleoptera: Tenebrionidae), Dermestes ater (Coleoptera: Dermestidae) y Galopagomyia inoa (Diptera: Sarcophagidae).  Phaleria manicata y G. inoa se reportan por primera vez en el cuerpo de un lobo marino.  En las Galápagos, los insectos carroñeros y el papel que desempeñan en el proceso de descomposición son poco conocidos.  Por lo tanto, más estudios se deben focalizar en comprender el papel ecológico de las comunidades de descomponedores en los distintos ecosistemas de las Islas Galápagos.
Felis catus preying on a Megasorex gigas, an endemic and threatened shrew from México
Authors: Ortega-Álvarez Rubén , Guevara Lázaro
Published: July 2024

Los gatos (Felis catus) han proliferado de forma dramática, generando un serio problema de conservación mundial.  En regiones tropicales y megadiversas, su impacto sobre la vida silvestre ha sido pobremente documentado.  El objetivo de esta nota fue reportar la captura de una musaraña presuntamente cazada por un gato en Colima, México.  En enero 30, 2022, le quitamos una musaraña a un gato en el Centro Universitario de Gestión Ambiental (CEUGEA).  Detectamos inicialmente al gato a 25 m mientras jugaba con una presa.  Nos aproximamos y lo espantamos para examinar la musaraña, la cual estaba fresca y presentaba una herida en uno de sus flancos.  Tras una revisión minuciosa del espécimen, se identificó como musaraña gigante mexicana, Megasorex gigas, con base en características externas y craneales.  Megasorex es un género monotípico endémico del oeste de México.  Está considerada como Amenazada por el gobierno mexicano y se le considera rara.  Los gatos han sido observados cazando la fauna de CEUGEA, mientras que los reportes de gatos depredando musarañas han sido históricamente típicos en países de zonas templadas.  En regiones tropicales, las anécdotas de gatos llevando musarañas a casas no son desconocidas.  Sin embargo, no existe un registro preciso ni formal de estos eventos que permita documentar el impacto de estos depredadores sobre las musarañas.  Esperamos que esta nota contribuya a iniciar la sistematización de los registros asociados a la depredación de musarañas por gatos para mejorar la comprensión del efecto de especies exóticas invasoras sobre la fauna nativa de países megadiversos.