bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Genomic Identification of Predictors of Sensitivity and Mechanisms of Resistance to Multivalent Second-Generation TRAIL-R2 Agonists
Authors: Grinkevitch Vera , Wappett Mark , Crawford Nyree , Price Stacey , Lees Andrea , McCann Christopher , McAllister Katherine , Prehn Jochen , Young Jamie , Bateson Jess , Gallagher Lewis , Michaut Magali , Iyer Vivek , Chatzipli Aikaterini , Barthorpe Syd , Ciznadija Daniel , Sloma Ido , Wesa Amy , Tice David A. , Wessels Lodewyk , Garnett Mathew , Longley Daniel B. , McDermott Ultan , McDade Simon S.
Published: January 2022

Multivalent second-generation TRAIL-R2 agonists are currently in late preclinical development and early clinical trials. Herein, we use a representative second-generation agent, MEDI3039, to address two major clinical challenges facing these agents: lack of predictive biomarkers to enable patient selection and emergence of resistance. Genome-wide CRISPR knockout screens were notable for the lack of resistance mechanisms beyond the canonical TRAIL-R2 pathway (caspase-8, FADD, BID) as well as p53 and BAX in TP53 wild-type models, whereas a CRISPR activatory screen identified cell death inhibitors MCL-1 and BCL-XL as mechanisms to suppress MEDI3039-induced cell death. High-throughput drug screening failed to identify genomic alterations associated with response to MEDI3039; however, transcriptomics analysis revealed striking association between MEDI3039 sensitivity and expression of core components of the extrinsic apoptotic pathway, most notably its main apoptotic effector caspase-8 in solid tumor cell lines. Further analyses of colorectal cell lines and patient-derived xenografts identified caspase-8 expression ratio to its endogenous regulator FLIP(L) as predictive of sensitivity to MEDI3039 in several major solid tumor types and a further subset indicated by caspase-8:MCL-1 ratio. Subsequent MEDI3039 combination screening of TRAIL-R2, caspase-8, FADD, and BID knockout models with 60 compounds with varying mechanisms of action identified two inhibitor of apoptosis proteins (IAP) that exhibited strong synergy with MEDI3039 that could reverse resistance only in BID-deleted models. In summary, we identify the ratios of caspase-8:FLIP(L) and caspase-8:MCL-1 as potential predictive biomarkers for second-generation TRAIL-R2 agonists and loss of key effectors such as FADD and caspase-8 as likely drivers of clinical resistance in solid tumors.
Olaparib-Induced Senescence Is Bypassed through G2–M Checkpoint Override in Olaparib-Resistant Prostate Cancer
Authors: Lombard Alan P. , Armstrong Cameron M. , D'Abronzo Leandro S. , Ning Shu , Leslie Amy R. , Sharifi Masuda , Lou Wei , Evans Christopher P. , Dall'Era Marc , Chen Hong-Wu , Chen Xinbin , Gao Allen C.
Published: January 2022

PARP inhibition represents the dawn of precision medicine for treating prostate cancer. Despite this advance, questions remain regarding the use of PARP inhibitors (PARPi) for the treatment of this disease, including (i) how specifically do PARPi-sensitive tumor cells respond to treatment, and (ii) how does PARPi resistance develop? To address these questions, we characterized response to olaparib in sensitive LNCaP and C4-2B cells and developed two olaparib-resistant derivative cell line models from each, termed LN-OlapR and 2B-OlapR, respectively. OlapR cells possess distinct morphology from parental cells and display robust resistance to olaparib and other clinically relevant PARPis, including rucaparib, niraparib, and talazoparib. In LNCaP and C4-2B cells, we found that olaparib induces massive DNA damage, leading to activation of the G2–M checkpoint, activation of p53, and cell-cycle arrest. Furthermore, our data suggest that G2–M checkpoint activation leads to both cell death and senescence associated with p21 activity. In contrast, both LN-OlapR and 2B-OlapR cells do not arrest at G2–M and display a markedly blunted response to olaparib treatment. Interestingly, both OlapR cell lines harbor increased DNA damage relative to parental cells, suggesting that OlapR cells accumulate and manage persistent DNA damage during acquisition of resistance, likely through augmenting DNA repair capacity. Further impairing DNA repair through CDK1 inhibition enhances DNA damage, induces cell death, and sensitizes OlapR cells to olaparib treatment. Our data together further our understanding of PARPi treatment and provide a cellular platform system for the study of response and resistance to PARP inhibition.
Preclinical Development of ADCT-601, a Novel Pyrrolobenzodiazepine Dimer-based Antibody–drug Conjugate Targeting AXL-expressing Cancers
Authors: Zammarchi Francesca , Havenith Karin EG. , Chivers Simon , Hogg Paul , Bertelli Francois , Tyrer Peter , Janghra Narinder , Reinert Halla W. , Hartley John A. , van Berkel Patrick H.
Published: January 2022

AXL, a tyrosine kinase receptor that is overexpressed in many solid and hematologic malignancies, facilitates cancer progression and is associated with poor clinical outcomes. Importantly, drug-induced expression of AXL results in resistance to conventional chemotherapy and targeted therapies. Together with its presence on multiple cell types in the tumor immune microenvironment, these features make it an attractive therapeutic target for AXL-expressing malignancies.

ADCT-601 (mipasetamab uzoptirine) is an AXL-targeted antibody–drug conjugate (ADC) comprising a humanized anti-AXL antibody site specifically conjugated using GlycoConnect technology to PL1601, which contains HydraSpace, a Val-Ala cleavable linker and the potent pyrrolobenzodiazepine (PBD) dimer cytotoxin SG3199. This study aimed to validate the ADCT-601 mode of action and evaluate its efficacy in vitro and in vivo, as well as its tolerability and pharmacokinetics.

ADCT-601 bound to both soluble and membranous AXL, and was rapidly internalized by AXL-expressing tumor cells, allowing release of PBD dimer, DNA interstrand cross-linking, and subsequent cell killing. In vivo, ADCT-601 had potent and durable antitumor activity in a wide variety of human cancer xenograft mouse models, including patient-derived xenograft models with heterogeneous AXL expression where ADCT-601 antitumor activity was markedly superior to an auristatin-based comparator ADC. Notably, ADCT-601 had antitumor activity in a monomethyl auristatin E–resistant lung-cancer model and synergized with the PARP inhibitor olaparib in a BRCA1-mutated ovarian cancer model. ADCT-601 was well tolerated at doses of up to 6 mg/kg and showed excellent stability in vivo.

These preclinical results warrant further evaluation of ADCT-601 in the clinic.
89Zr-ImmunoPET Shows Therapeutic Efficacy of Anti-CD20-IFNα Fusion Protein in a Murine B-cell Lymphoma Model
Authors: Zettlitz Kirstin A. , Salazar Felix B. , Yamada Reiko E. , Trinh K. Ryan , Vasuthasawat Alex , Timmerman John M. , Morrison Sherie L. , Wu Anna M.
Published: January 2022

Antibody-mediated tumor delivery of cytokines can overcome limitations of systemic administration (toxicity, short half-lives). Previous work showed improved antitumor potency of anti-CD20-IFNα fusion proteins in preclinical mouse models of B-cell lymphoma. Although tumor targeting is mediated by the antibody part of the fusion protein, the cytokine component might strongly influence biodistribution and pharmacokinetics, as a result of its affinity, size, valency, and receptor distribution.

Here, we used immunoPET to study the in vivo biodistribution and tumor targeting of the anti-CD20 rituximab-murine IFNα1 fusion protein (Rit-mIFNα) and compared it with the parental mAb (rituximab, Rit). Rit-mIFNα and Rit were radiolabeled with zirconium-89 (89Zr, t1/2 78.4 hours) and injected into C3H mice bearing syngeneic B-cell lymphomas (38C13-hCD20). Dynamic [(2 hours post injection (p.i.)] and static (4, 24, and 72 hours) PET scans were acquired. Ex vivo biodistribution was performed after the final scan.

Both 89Zr-Rit-mIFNα and 89Zr-Rit specifically target hCD20-expressing B-cell lymphoma in vivo. 89Zr-Rit-mIFNα showed specific uptake in tumors (7.6 ± 1.0 %ID/g at 75 hours p.i.), which was significantly lower than 89Zr-Rit (38.4 ± 9.9 %ID/g, P < 0.0001). ImmunoPET studies also revealed differences in the biodistribution, 89Zr-Rit-mIFNα showed rapid blood clearance and high accumulation in the liver compared with 89Zr-Rit. Importantly, immunoPET clearly revealed a therapeutic effect of the single 89Zr-Rit-mIFNα dose, resulting in smaller tumors and fewer lymph node metastases compared with mice receiving 89Zr-Rit. Mice receiving 89Zr-Rit-mIFNα had enlarged spleens, suggesting that systemic immune activation contributes to therapeutic efficacy in addition to the direct antitumoral activity of IFNα.

In conclusion, immunoPET allows the noninvasive tracking and quantification of the antibody-cytokine fusion protein and helps understand the in vivo behavior and therapeutic efficacy.
Metabolic Control of Germline Formation and Differentiation in Mammals
Authors: Hayashi Yohei , Matsui Yasuhisa
Published: January 2022

Background: The germ cell lineage involves dynamic epigenetic changes during its formation and differentiation that are completely different from those of the somatic cell lineage. Metabolites and metabolic pathways have been reported as key factors related to the regulation of epigenetics as cofactors and substrates. However, our knowledge about the metabolic characteristics of germ cells, especially during the fetal stage, and their transition during differentiation is quite limited due to the rarity of the cells. Nevertheless, recent developments in omics technologies have made it possible to extract comprehensive metabolomic features of germ cells. Summary: In this review, we present the latest researches on the metabolic properties of germ cells in 4 stages: primordial germ cell specification, fetal germ cell differentiation, spermatogenesis, and oogenesis. At every stage, extensive published data has been accumulated on energy metabolism, and it is possible to describe its changes during germ cell differentiation in detail. As pluripotent stem cells differentiate into germ cells, energy metabolism shifts from glycolysis to oxidative phosphorylation; however, in spermatogenesis, glycolytic pathways are also temporarily dominant in spermatogonial stem cells. Although the significance of metabolic pathways other than energy metabolism in germ cell differentiation is largely unknown, the relation of the pentose phosphate pathway and Ser-Gly-one-carbon metabolism with germ cell properties has been suggested at various stages. We further discuss the relationship between these characteristic metabolic pathways and epigenetic regulation during germ cell specification and differentiation. Finally, the relevance of dietary and supplemental interventions on germ cell function and epigenomic regulation is also discussed. Key Messages: Comprehensive elucidation of metabolic features and metabolism-epigenome crosstalk in germ cells is important to reveal how the characteristic metabolic pathways are involved in the germ cell regulation. The accumulation of such insights would lead to suggestions for optimal diets and supplements to maintain reproductive health through modulating metabolic and epigenetic status of germ cells.
Anxiolytic Effects of Chronic Intranasal Oxytocin on Neural Responses to Threat Are Dose-Frequency Dependent
Authors: Kou Juan , Zhang Yingying , Zhou Feng , Gao Zhao , Yao Shuxia , Zhao Weihua , Li Hong , Lei Yi , Gao Shan , Kendrick Keith M. , Becker Benjamin
Published: January 2022

Introduction: Anxiety disorders are prevalent mental conditions characterized by exaggerated anxious arousal and threat reactivity. Animal and human studies suggest an anxiolytic potential of the neuropeptide oxytocin (OT), yet, while a clinical application will require chronic administration protocols, previous human studies have exclusively focused on single-dose (acute) intranasal OT effects. Objective: To facilitate the translation of the potential anxiolytic mechanism of OT into clinical application, we determined whether the anxiolytic effects of OT are maintained with repeated (chronic) administration or are influenced by dose frequency and trait anxiety. Methods: In a pre-registered double-blind randomized placebo-controlled pharmaco-fMRI trial the acute (single dose) as well as chronic effects of two different dose frequencies of OT (OT administered daily for 5 days or every other day) on emotional reactivity were assessed in n = 147 individuals with high versus low trait anxiety (ClinicalTrials.gov ID: NCT03085654). Results: OT produced valence, dose frequency, and trait anxiety-specific effects, such that the low-frequency (intermittent) chronic dosage specifically attenuated a neural reactivity increase in amygdala-insula-prefrontal circuits observed in the high anxious placebo-treated subjects in response to threatening but not positive stimuli. Conclusions: The present trial provides the first evidence that low-dose frequency chronic intranasal OT has the potential to alleviate exaggerated neural threat reactivity in subjects with elevated anxiety levels, suggesting a treatment potential for anxiety disorders.
Outcome Comparison of Different Reconstructive Approaches for Axillary Defects Secondary to Radical Excision of Hidradenitis Suppurativa
Authors: Tereshenko Vlad , Schweizer Riccardo , Waldner Matthias , Kim Bong-Sung , Giovanoli Pietro , Klein Holger Jan
Published: January 2022

Background: Radical excision of debilitating hidradenitis suppurativa lesions is the only curative approach in the advanced stages of the disease. Different concepts for axillary reconstruction do exist, but data on their clinical outcome are scarce. Methods: This is a retrospective cohort study of two reconstructive methods (posterior arm flap vs. vacuum-assisted closure [VAC] + split-thickness skin graft [STSG]) for axillary defects in patients with severe axillary hidradenitis suppurativa treated at the University Hospital Zurich between 2005 and 2020. Results: A total of 35 patients (mean age 36 ± 10 years, mean BMI 29 ± 5 kg/m2, Hurley stage II–III) with 67 operated axillae were stratified according to their type of reconstruction. Median operation time in the flap group was 144 min (IQR 114–207) (cumulative 181 min [IQR 124–300]) and 50 min (IQR 40–81) in the VAC + STSG group (cumulative 151 min [IQR 94–194], p < 0.01; p = 0.20 [cumulative time]). The cumulative length of stay was 6 ± 3 days in the flap group and 14 ± 7 days in the VAC + STSG group (p < 0.01). Time to complete wound healing was 27 days (IQR 20–49) in the flap group and 62 days (IQR 41–75) in the VAC + STSG group (p < 0.01). Vancouver Scar Scale score was 6 (IQR 4–9) in the flap group and 11 (IQR 9–12) in the VAC + STSG group (p < 0.01). Protective sensory recovery was most satisfactory in the flap group (p < 0.01). Forty-four percent of patients of the VAC + STSG group demonstrated functional impairment of arm abduction. Time to return to work was less in group A with 42 days (IQR 27–57) needed as compared to group B with 48 days (IQR 34–55) needed (p = 0.32). The average cost saving was 25% higher for the flap group than for the VAC + STSG group. Conclusion: Despite an increased operation time, axillary reconstruction by the posterior arm flap yields a reduced length of stay, less time to complete wound healing along with restoration of a protective sensibility, and less axillary scarring avoiding functional deficits – eventually allowing earlier return to work.
Diet and Lifestyle Habits in Early-Onset Colorectal Cancer: A Pilot Case-Control Study
Authors: Puzzono Marta , Mannucci Alessandro , Di Leo Milena , Zuppardo Raffaella A. , Russo Michele , Ditonno Ilaria , Goni Elisabetta , Notaristefano Chiara , Azzolini Francesco , Fanti Lorella , Viale Edi , Elmore Ugo , Pantaleo Giuseppe , Cascinu Stefano , Rosati Riccardo , Cavestro Giulia Martina
Published: January 2022

Background: Early-onset colorectal cancer (eoCRC), defined as a colorectal cancer (CRC) in patients younger than 50 years old, shows an increasing incidence worldwide in the latest years. The role of exogenous factors associated with CRC has been largely overlooked in eoCRC. Here, we conducted a case-control study to evaluate the diet and the lifestyle habits in an Italian population of patients with eoCRC, compared to age-matched healthy controls (HCs). Methods: We enrolled 118 subjects (47 cases, 71 controls) in a third-level academic hospital. We analyzed epidemiological features (age, sex, body mass index), lifestyle behaviors (smoking habits, physical activity, type of diet, use of dietary supplements), and eating habits (semiquantitative food-frequency questionnaire) in eoCRCs and HCs, covering the previous 5 years. Results: In our cohort, positive family history of CRC was significantly associated with the development of eoCRC (p = 0.004). Fresh meat (p = 0.003), processed meat (p < 0.001), dairy products (p = 0.013), and smoking (p = 0.0001) were significantly associated with eoCRC compared to controls. Other variables did not differ significantly between the two groups. Conclusion: Fresh and processed meat, dairy products, and smoking could be considered significant risk factors for eoCRC, although further confirmation by international multicenter studies is desirable. Diet and smoking could be the main areas of future interventions for eoCRC primary prevention.
The Role of Faecalibacterium, Roseburia, and Butyrate in Inflammatory Bowel Disease
Authors: Faden Howard
Published: January 2022

Faecalibacterium and Roseburia are major producers of butyrate in the intestine. A reduced abundance of the organisms and a concurrent reduction in butyrate levels are associated with inflammatory bowel disease.
Current and Novel Treatment Strategies in Children with Congenital Adrenal Hyperplasia
Authors: Nordenström Anna , Falhammar Henrik , Lajic Svetlana
Published: January 2022

Background: The standard treatment for congenital adrenal hyperplasia (CAH) in children is still hydrocortisone. Improved strategies for timing of the dose during the day and the dose per square meter body surface area used in children of different ages and developmental phases have improved the situation and outcome for the patients. Neonatal screening enables an earlier diagnosis and initiation of treatment, prevents from adrenal crisis, and improves growth and development also for children with the less severe forms of CAH. Summary: This review describes the current treatment strategies for children with CAH and discusses some potential treatment options that have been developed with the primary aim to decrease the adrenal androgen production. Novel modified release glucocorticoid therapies are also discussed. Key Messages: The long-term effects of the new adjunct therapies are unknown, and some are not suitable for use in children and adolescents. The effects of the new therapies on bone mineral density, gonadal functions, and long-term cognitive development are yet to be assessed. It is not known what levels of adrenal androgens are optimal for normal growth, puberty, and bone health. The basis of using glucocorticoids and mineralocorticoids in the treatment of CAH remains, and in some individuals, it may be beneficial to add therapies to reduce the androgen load during certain life stages.
Modelo de governança interfederativa
Authors: Pontes Denio Igor Silva de , Carvalho Hermano José Batista de
Published: January 2022

Por meio das Leis complementares nº 14/1973 e nº 20/1974, a União estabeleceu as primeiras regiões metropolitanas (RMs) no Brasil, nos termos da Constituição de 1967. A Constituição de 1988 estadualizou a prerrogativa para o reconhecimento das RMs, mas deixou uma lacuna (§ 3º do art. 25) sobre a governança metropolitana. Para preencher essa lacuna, foi instituído o Estatuto da Metrópole (Lei nº 13.089/2015). Assim, as RMs passaram a ser criadas por lei complementar estadual, visando integrar a organização, o planejamento e a execução de funções públicas de interesse comum (FPICs). Nesse sentido, consubstancia-se como interesse da pesquisa a dimensão gestionária das RMs, ou seja, conhecer e analisar os modelos de governança interfederativa no Brasil. Em outras palavras, empreendeu-se um estudo em quatro RMs (Belo Horizonte, Vitória, Fortaleza e Cariri) para compreender se os modelos de governança interfederativa executados são, suficientemente, calibrados para desenvolver proximidades não geográficas. Considerou-se que não existe um modelo “perfeito”, embora existam modelos que foram testados e funcionam bem dentro das suas realidades. Portanto, cada RM possui características singulares que devem ser consideradas antes de implantar um modelo de governança. Inferiu-se que a governança territorial é uma ferramenta capaz de configurar e reconfigurar RMs, por meio de compromissos, acordos e convenções. Além disso, para que a proximidade geográfica se torne uma vantagem competitiva para as RMs, os gestores devem empreender esforços para desenvolver proximidades não geográficas.
A participação comunitária em projetos de soluções baseadas na natureza na cidade de São Paulo: estudo das hortas urbanas, Horta da Dona Sebastiana, Agrofavela-Refazenda e Horta Popular Criando Esperança
Authors: Costa Babette Martins da , Sakurai Tatiana
Published: January 2022

As hortas urbanas integram a categoria de Soluções Baseadas na Natureza (SbN) capazes de proporcionar benefícios tanto ambientais quanto sociais; entre estas, podemos citar a regulação de microclimas urbanos, o suporte à diversidade e segurança alimentar, o incentivo à educação ambiental e a resiliência de comunidades. O artigo tem como objetivo investigar se projetos dessa natureza, quando criados e geridos sob a iniciativa de comunidades, organizações de bairro e outros grupos sociais possuem maior eficiência, engajamento e continuidade em comparação a projetos de iniciativa privada e/ou pública, sem participação social em sua criação e desenvolvimento. Por meio de estudos de casos múltiplo, ao lado de entrevistas semi-estruturadas com lideranças, visitas de campo e pesquisa bibliográfica, foram selecionadas três hortas urbanas em contextos periféricos na cidade de São Paulo: a Horta da Dona Sebastiana, membro da Associação de Agricultores da Zona Leste e auxiliada por uma Organização Não Governamental; a AgroFavela-Refazenda, localizada em Paraisópolis, patrocinada por uma empresa multinacional; e a Horta Popular Criando Esperança, na Vila Nova Esperança, autônoma.
O trabalho também discute o conceito de Justiça Ambiental como um interessante instrumento de análise, em uma cidade socialmente e ambientalmente desigual como São Paulo - na qual os riscos ambientais e a falta de investimento atingem desproporcionalmente populações mais pobres e vulneráveis. Como resultado, concluiu-se que projetos como as hortas urbanas podem ser ferramentas potenciais de redução de desigualdades ambientais e, quando com a participação de comunidades, também transformadores sociais. Ressalta-se a importância da implementação de SbNs em áreas periféricas, as quais sofrem mais injustiças ambientais e necessitam mais destas infraestruturas do que nas áreas nobres de São Paulo - onde muitas SBNs são atualmente construídas e amplamente divulgadas.
Benchmarking functional connectivity by the structure and geometry of the human brain
Authors: Liu Zhen-Qi , Betzel Richard F. , Misic Bratislav
Published: January 2022

The brain’s structural connectivity supports the propagation of electrical impulses, manifesting as patterns of coactivation, termed functional connectivity. Functional connectivity emerges from the underlying sparse structural connections, particularly through polysynaptic communication. As a result, functional connections between brain regions without direct structural links are numerous, but their organization is not completely understood. Here we investigate the organization of functional connections without direct structural links. We develop a simple, data-driven method to benchmark functional connections with respect to their underlying structural and geometric embedding. We then use this method to reweigh and reexpress functional connectivity. We find evidence of unexpectedly strong functional connectivity among distal brain regions and within the default mode network. We also find unexpectedly strong functional connectivity at the apex of the unimodal-transmodal hierarchy. Our results suggest that both phenomena—functional modules and functional hierarchies—emerge from functional interactions that transcend the underlying structure and geometry. These findings also potentially explain recent reports that structural and functional connectivity gradually diverge in transmodal cortex. Collectively, we show how structural connectivity and geometry can be used as a natural frame of reference with which to study functional connectivity patterns in the brain.
Elective incisional hernia repair: lower risk of postoperative wound infection with laparoscopic versus open repair
Authors: Goh Serene Si Ning , Sanghvi Kaushal Amitbhai , Koura Aaryan Nath , Rao Jaideepraj Krishnaraj , Oo Aung Myint
Published: January 2022

Introduction:

The superiority of laparoscopic repair over open repair of incisional hernias (IHs) in the elective setting is still controversial. Our study aimed to compare the postoperative outcomes of laparoscopic and open elective IH repair in an Asian population.

Methods:

This retrospective study was conducted in an acute general hospital in Singapore between 2010 and 2015. Inclusion criteria were IH repair in an elective setting, IHs with diameter of 3–15 cm, and location at the ventral abdominal wall. We excluded patients who underwent emergency repair, had recurrent hernias or had loss of abdominal wall domain (i.e. hernia sac containing more than 30% of abdominal contents or any solid organs). Postoperative outcomes within a year such as recurrence, pain, infection, haematoma and seroma formation were compared between the two groups.

Results:

There were 174 eligible patients. The majority were elderly Chinese women who were overweight. Open repair was performed in 49.4% of patients, while 50.6% underwent laparoscopic repair. The mean operation time for open repair was 116 minutes (116 ± 60.6 minutes) and 139 minutes (136 ± 64.1 minutes) for laparoscopic repair (P = 0.079). Within a year after open repair, postoperative wound infection occurred in 15.1% of the patients in the open repair group compared to 1.1% in the laparoscopic group (P = 0.0007). Postoperative pain, recurrence and haematoma/seroma formation were comparable.

Conclusion:

Elective laparoscopic IH repair has comparable outcomes with open repair and may offer the advantage of reduced postoperative wound infection rates.
The Philosophical Background of Yoḥanan Alemanno: Remarks on Logic and Psychology
Authors: Gentili Hanna
Published: January 2022

The convergence of philosophical and kabbalistic sources in the works of Yoḥanan Alemanno (ca. 1435–ca. 1504) attests to the richness of fifteenth-century scholarship in Italy, specifically its reception of sources that had characterized cultural debates across the Mediterranean for centuries. Beginning with a discussion of his personal notebook (Oxford, Bodleian Library, Ms Reggio 23), and focusing on his treatment of logic and psychology, this study demonstrates the extent to which Alemanno relied on the Jewish Aristotelian tradition based on the translations of Averroes’ Arabic commentaries. Moreover, it shows the relationship between this tradition and the kabbalistic themes addressed by the author in his works.
Pulp: My Reply to Ryszard Śmietanka-Kruszelnicki
Authors: Tokarska-Bakir Joanna
Published: January 2022

The article is the author’s response to Dr. Ryszard Śmietanka-Kruszelnicki’s review of Pod klątwą: Społeczny portret pogrom kieleckiego [Under Curse: A Social Portrait of the Kielce Pogrom] (2018), which appeared in the journal Polish-Jewish Studies in January 2021.
Beyond Conceptions of Fascism and Fascist Conceptions: On the Category of Fascization
Authors: Stoll Katrin
Published: January 2022

In discussing conceptions and definitions of fascism, this text offers a new and broader perspective on the phenomenon by introducing the concept of fascization as an analytical tool. Given the fact that the conditions that fascism produced have not been destroyed, its elements have not been delegitimized and that the fascist imagination still exists in European and non-European societies, the author argues that we need a new category connecting the past and present without historicizing fascism. The author identifies practices and forms of fascization in evidence such as the EU anti-migrant and anti-refugee policy as well as racist violence in Germany after reunification. The author critically examines various definitions of fascism and analyses its key characteristics including the fascist community from a psychoanalytical perspective. The author also looks at the historiographical debate concerning the question of whether or not fascism could be considered revolutionary or counter-revolutionary. Making a clear-cut distinction between fascism and National Socialism, the author re-visits the case of Ernst Nolte whose interpretation of the origins of National Socialism  resurrected the Nazi Weltanschauung by normalizing and justifying the Nazi campaign against the European Jews.
Birth of the Beta-knife Thyroidectomy: The Radiance of Saul Hertz
Authors: Ehrhardt John D. , Gulec Seza A.
Published: January 2022

This is the story of how one man’s life’s work allowed for Iodine-131 (I-131) to become a therapy for hyperthyroidism and thyroid cancer. What is now a standard in our times arose from Saul Hertz’s rather challenging and humble beginnings. Thyroid lobectomy and total thyroidectomy were therapeutic mainstays for thyroid disease until Hertz treated his first patient with radioactive iodine (RAI) ablation therapy at Massachusetts General Hospital (MGH) on March 31, 1941. His concepts for using beta particle emission from RAI to ablate thyroid tissue were revolutionary. Hertz’s RAI therapy translated to research with thyroid cancer by the mid-1940s. The high-energy beta particles produced cytolethal effects on remnant thyroid tissue left behind by total thyroidectomy, thereby accomplishing completion thyroidectomy in some patients. Progressive surgeons from the Hertz era incorporated RAI into their practice. MGH surgery resident Francis Moore took sabbatical from clinical training to do translational research with RAI and other radioisotopes. Irving Ariel of New York became known as a nuclear surgeon in the wake of Hertz’s work. George Crile Jr of Cleveland became an RAI advocate for the surgical community, implementing several paradigm-changing concepts in thyroid disease along the way. Hertz was a visionary who sparked this movement, predicting many of the molecular dilemmas with RAI-tumor avidity that clinical researchers continue to navigate today. This timely history for surgical oncologists and endocrine surgeons traces the development of RAI therapy through the life of Saul Hertz, a biographical window influenced by social stigma, political controversy, and mainstream media.
Did More Otolaryngology Residency Applicants Match at Their Home Institutions in 2021? Investigating the Impact of the COVID-19 Pandemic
Authors: Mulcahy Collin F. , Terhaar Samantha J. , Boulos Sameh , Lee Esther , Zapanta Philip E.
Published: January 2022

Objective:

To compare the proportion of applicants who matched to their home otolaryngology program during the COVID-19 pandemic compared to the previous 5 years.

Methods:

A “home program match” status was identified for residents in each PGY level and in incoming interns. The “home match proportion” (HMP) was then calculated for each program for each year from 2016 to 2021. The difference in the distribution of home matches between PGY0 and PGY 1, 2, 3, 4, and 5 were analyzed using the chi-square independence test and Fisher’s exact test. Statistical significance was declared at P < .05.

Results:

A total of 1885 residents were identified from 101 otolaryngology residency programs. The distribution of PGY0s who home matched was statistically higher when separately compared to PGY1-5s. (PGY0 vs PGY 1, 2, 3, 4, 5: 96 [30.1%] vs 63 [19.3%] P = .002, 73 [22.9%] P = .048, 50 [16.3%] P < 0.0005, 59 [19.2%] P = .002, 52 [16.9%] P < .0005). There was no statistical difference in any binary combination within PGY1 through PGY5.

Conclusion:

Nearly a third of applicants matched to their home institution for otolaryngology during the 2021 application cycle, a statistically significant increase compared to an average of the previous 5 years. While there are likely many reasons for this increase, we believe that the severely limited nature of away rotations due to the COVID-19 pandemic played a significant role in this outcome.
Pushing the Limits of Surface-Enhanced Raman Spectroscopy (SERS) with Deep Learning: Identification of Multiple Species with Closely Related Molecular Structures
Authors: Lebrun Alexis , Fortin Hubert , Fontaine Nicolas , Fillion Daniel , Barbier Olivier , Boudreau Denis
Published: January 2022

Raman spectroscopy is a non-destructive and label-free molecular identification technique capable of producing highly specific spectra with various bands correlated to molecular structure. Moreover, the enhanced detection sensitivity offered by surface-enhanced Raman spectroscopy (SERS) allows analyzing mixtures of related chemical species in a relatively short measurement time. Combining SERS with deep learning algorithms allows in some cases to increase detection and classification capabilities even further. The present study evaluates the potential of applying deep learning algorithms to SERS spectroscopy to differentiate and classify different species of bile acids, a large family of molecules with low Raman cross sections and molecular structures that often differ by a single hydroxyl group. Moreover, the study of these molecules is of interest for the medical community since they have distinct pathological roles and are currently viewed as potential markers of gut microbiome imbalances. A convolutional neural network model was developed and used to classify SERS spectra from five bile acid species. The model succeeded in identifying the five analytes despite very similar molecular structures and was found to be reliable even at low analyte concentrations.
Structural Analysis of Injection-Molded Polyoxymethylene Treated Below a Melting Point Using Field-Emission Scanning Electron Microscopy and Infrared Spectroscopy
Authors: Amaki Yuko , Okada Hideki , Nagai Naoto
Published: January 2022

The heat treatment of an injection-molded polyoxymethylene slightly below the melting point and subsequent isothermal treatment at 130 °C were performed. The polyoxymethylene structure was examined using field-emission scanning electron microscopy and polarization infrared reflection measurements. After the heat treatment, a significant change in the surface morphology was observed, and the reflection spectrum derived from the polariton in the injection direction also changed dramatically. Since the reflection spectrum in the injection direction contains the reflection component of the perpendicular direction and vice versa, the polarization spectra of both directions can be calculated consistently. The mixing ratio of each crossed component and the pure relative permittivity both parallel and perpendicular to the main-chain direction were determined using the oscillator model. The heat treatment reduced the ratio of the perpendicular component and increased the order structure until just before melting. The structural changes characterized by the two techniques, along with Raman spectroscopy and differential scanning calorimetry, are discussed.
Black Bodies in America as the Metaphors for Oppression, Poverty, Violence, and Hate: Searching for Sustainable Solutions Beyond the Black-letter Law
Authors: Iheme Williams
Published: January 2022

Black people in America have often been labeled outlaws, deviants, and nonconformists who are disinterested in complying with the laid down rules. However, from a long range experience dating back to slavery, they recognize that rules in the American context whether the Slave Codes, Black Codes, Jim Crows, or the contemporary law, are machinations of the legal system to perpetuate oppression and violence against Blackness. Toward self-preservation, they have learned to radically resist acts of oppression such as wrongful arrests by the police and the functional denial of their rights to be presumed innocent, protest and bear arms, even if such resistance necessitates a stark disobedience to the law enforcement. The Stono Rebellion of 1739 and other slave uprisings used resistance to achieve the abolition of chattel slavery. In the contemporary times, the Black radical tradition pursues the eradication of criminal enslavement by promoting Black protests and resistance against wrongful arrests: wrongful arrests have been identified as the preliminary steps toward mass Black incarceration. In opposition to the mainstream perspective in American literature, this paper uses a functional-analytical approach to legal reasoning to analyze key legal, historical, and sociological issues surrounding the existence of Black people in America in order to show that slavery is still functionally alive: it argues positively for the legitimacy and appropriateness of the Black radical tradition as a reliable means of effectuating the myriad black-letter rights that started in 1865 under the Thirteenth Amendment.
Electrochemical impedance spectroscopy characteristic of degradation process for carbon fiber/vinyl ester composites in salt water
Authors: Tang Yuming , Dun Yuchao , Chen Xueping , Zhou Yong , Zhao Xuhui , Zuo Yu
Published: January 2022

The Electrochemical impedance spectroscopy of the T700/VE (vinyl ester) carbon fiber composite in 3.5% NaCl solution under open circuit potential (OCP) and cathodic polarization (−0.6 VSCE and −1.2 VSCE) conditions were studied, the moisture absorption was evaluated by weight gain test, and the degradation process was analyzed combined with scanning electron microscope. The T700/VE composite has very good resistance to degradation under OCP condition for long time (205 days) immersion, with about 0.38% moisture uptake and a slight decrease of low-frequency impedance (| Z|0.01 Hz). Cathodic polarization remarkably promotes the diffusion of moisture and ions in the resin matrix, the de-bonding between resin and carbon fibers, and characteristic of a porous electrode occurrence with a very quick decrease in | Z|0.01 Hz value. The variation of | Z|0.01 Hz is negatively correlated with the moisture absorption under OCP and −0.6 VSCE polarization conditions. So, | Z|0.01Hz may be used to monitor the water absorption and degradation process of the composite.
Graphene oxide and reduced graphene oxide nanocomposites grafted with hollow gold nanoshells as photothermal agents
Authors: Rodriguez-Montelongo Sayma A , Gonzalez-Maldonado Mario A , Silva-Ramirez Ana S , Castillo Martin del Campo Claudia G , Ruiz Facundo , Gonzalez-Ortega Omar
Published: January 2022

Nanocomposites based on graphene oxide (GO) or reduced graphene oxide (rGO) grafted with hollow gold nanoshells (HGNs) were developed as enhanced photothermal agents with improved biocompatibility. Infrared and Raman spectroscopy allowed determining that graphene was highly oxidized due to the presence of oxygenated groups that allowed further functionalization and provided anchor points for the grafting of HGNs. Using HRTEM and STEM, good dispersion of the HGN on the surface of the graphitic materials was observed. Meanwhile, using UV–Vis spectroscopy, an increase of absorbance in the near-infrared region was appreciated, resulting in an enhancement of the photothermal properties of the nanocomposites in contrast to the materials separately. Remarkable temperature increases were obtained in short periods of irradiation using a low-power laser. Moreover, a decrease in the cytotoxicity of GO and rGO was observed in the human neuronal line hNS1 under the presence of the plasmonic nanoparticles on the surface.
Consoling the Bereaved: Exploring How Sympathy Cards Influence What People Say
Authors: Calderwood Kimberly A. , Alberton Amy M.
Published: January 2022

In a sequential mixed methods study, interview data showed that bereaved parents consistently reported “stupid” or “insensitive” things people said that were not helpful when their child died. Subsequently, a discourse analysis of 170 sympathy cards was conducted to assess societal messaging that may influence people’s insensitive words. The findings reflected two distinct time periods in the bereavement process: a time of sadness followed by a time of peace. Possible links to insensitive things people said included: suggestions that the sad time should only last a few days, suggestions of “healing,” religious statements such as the deceased being with God or advice to pray to God, and notions of celebration in some contexts. Very few excerpts were similar to the advice-giving quotes that interviewees considered to be insensitive. Many cards reflected the love and memories inherent in creating a continuing bond with the deceased and achieving peace.
A Neuro-Integrative Assessment of Perceptual-Motor Performance and Wellness in ROTC Cadets
Authors: Wilkerson Gary B. , Colston Marisa A. , Grillo Ashley N. , Rogers Abigail J. , Perry Tyler , Acocello Shellie N.
Published: January 2022

Resting heart rate variability (HRV) may be a useful index of both brain-based executive function and general health. Our purpose in this study was to quantify relationships among HRV, perceptual-motor performance metrics, and wellness survey responses. A cohort of 32 male Reserve Officer Training Corp (ROTC) cadets completed a dual-task upper extremity reaction time (UERT) test, two tests of whole-body reactive agility, and a 10-item wellness survey that produced a 0–100 Overall Wellness Index (OWI). We averaged participants’ resting HRV measurements twice per week over 10 weeks to derive an intra-individual grand mean (HRV-IIGM) and over a series of days we calculated an intra-individual coefficient of variation (HRV-IICV). We used median values for the two HRV metrics (HRV-IIGM and HRV-IICV) to separate the cadets into equal-sized high and low HRV groups to form the dependent variable for logistic regression analyses. We found a significant inverse relationship between HRV-IIGM and HRV-IICV ( r = –0.723, p < .001). Differences in UERT in the left versus right visual hemifields (L–R Diff) and OWI scores were strongly related to both HRV-IIGM ≤ 4.49 and HRV-IICV ≥ 6.95%. Logistic regression models that included L–R Diff and OWI showed 71% classification accuracy for HRV-IIGM (Model χ2 [2] = 12.47, p = .002, Nagelkerke R2 = 0.430) and 81% classification accuracy for HRV-IICV (Model χ2 [2] = 14.88, p = .001, Nagelkerke R2 = 0.496). These findings suggest that resting HRV, perceptual-motor efficiency, and overall wellness are highly interrelated, supporting a multi-factor biopsychosocial assessment to guide the design and implementation of interventions to maximize operational effectiveness for ROTC cadets and other military personnel.
Impact of COVID-19 Pandemic on HOME Advantage in Different European Professional Basketball Leagues
Authors: Alonso Enrique , Lorenzo Alberto , Ribas Carlos , Gómez Miguel Ángel
Published: January 2022

Our purpose in this study was to examine the impact of the COVID-19 pandemic on home advantage (HA) in sports by comparing European professional basketball games in which spectators were present (pre-pandemic) with “ghost” games in which spectators were absent (during the pandemic). A secondary objective was to analyze how team ability interacted with HA by comparing HA affects pre-pandemic and during the pandemic in the context of differing team ability levels. We used Wilcoxon and Mann–Whitney U tests to identify HA through differences in home win percentages (HW%) between pre-pandemic and pandemic games. Additionally, we ran the Kruskal–Wallis test to identify HA and HW% differences between different team ability levels (high to low). Teams had higher HA and HW% pre-pandemic than during the pandemic. In turn, low level teams presented a higher HA compared to teams at other team ability levels. Thus, low level teams benefited more from playing at their home-court. However, low level teams showed lower HW% than medium and high team ability levels, showing that team ability is more important than HA in determining game outcomes.
Self-Control Measurement Methodologies: An Integrative Approach
Authors: Pilcher June J. , Morris Drew M. , Erikson Dylan N.
Published: January 2022

The study of self-control occurs in many different types of experimental settings using a wide range of methodologies. In addition, measures of self-control vary in their procedures and operational definitions from simple questionnaires to complex scenarios where individuals must choose to act or not. The present summary draws on trends within the literature using widely accepted measures of self-control. The measures are organized based on established paradigms in the literature and focus on three categories: executive functioning tasks, delay of gratification tasks, and subjective-report surveys. We also include an “additional measures” category to capture measures that do not readily fit in these three categories. Finally, we discuss recent approaches to the scientific exploration of self-control and integrate the categories of measures used here within these approaches. This integration incorporates a wide range of research paradigms and provides direction for future studies.
Psychological Issues Among Spanish Adolescents and Young People when Coming out of the Closet to Their Families
Authors: Dueñas Jorge-Manuel , Morales-Vives Fabia , Galea Natalie
Published: January 2022

Some social settings may make the process of “coming out” more difficult for gay males and lesbian females, and the decision to do so may be even more problematic for adolescents and young people. As a result, some may choose to hide their sexual orientation, leading to emotional suffering. This study aims to analyze the differences in perceived stress, life satisfaction, happiness, and psychological distress experienced by both coming out and closeted young people and teens. The sample included a total of 228 Spanish young people aged 16–23 years old ( M = 19.69, SD = 1.81) who identified themselves as gay or lesbian (73.2% women). The results of this study show that people in the closet show greater psychological distress (anxiety and depressive symptomatology) and perceived stress. Although perceived stress is positively related to psychological distress in both groups, the correlation is higher in the closeted group. This suggests that perceived stress has more serious consequences on the mental health of the closeted group than of the “coming out” group. To sum up, the results show the importance of family support for gay and lesbian young people.