bluuebunny/crossref_metadata_2025 huggingface dataset:
Aeschylus' Prometheus
Authors: Manousakis Nikos
Published: November 2023

Prometheus Bound (Prometheus Vinctus) is a tragedy of disputed authorship in the Aeschylean corpus, and the only extant Greek drama populated almost entirely by divine beings. The play was popular in Late Antiquity, the Middle Ages, and subsequent centuries. It puts on stage the feud between the Titan Prometheus, a member of the older generation of gods, and Zeus, the leader of the new divine order, the Olympians. The plot consists of a series of encounters between the immobile Titan, Zeus’ vassals/accomplices/emissaries, and a supernaturally afflicted mortal—a victim of Zeus’ passion. Prometheus opens with an interlocutory prologue of two speaking (Hephaestus, Power) and two nonspeaking (Prometheus, Violence) characters. It is set far in uninhibited Scythia, where, by Zeus’ order, Hephaestus, Power, and Violence take Prometheus to be bound: paying the penalty for stealing fire, a divine possession, and offering it to the mortals. Reluctant at first, Hephaestus eventually yields and binds his kindred god. After the three deities leave, the Titan is left alone on stage, speaking a soliloquy about his sorrows, when, suddenly, a Chorus of Oceanids arrives. The divine maidens show pity for the sufferer, and he recounts the story of how he (along with his mother Themis–Gaia) benefited Zeus, helping him to become ruler of the gods, and how the Olympian is repaying him. Then the maidens’ father, Oceanus, another Titan, who is, however, on very good terms with the currently prevailing order, visits Prometheus’ remote exile. He attempts to change the bound Titan’s mind and bring reconciliation with Zeus. However, Prometheus sends him away, refusing to comply and to be politic. Subsequently, the only human character in the play enters. Daughter of Inachus, king of Argos, Io has now grown horns (the actor is shown onstage wearing a horned mask) as part of her transformation into a cow, and is pursued by a gadfly due to Hera’s jealousy of her husband’s lust for the mortal girl. She is driven to Prometheus’ rock of torture, where the two have a long conversation, and the Titan foretells the end of her wanderings: Zeus will release her from her pains in Egypt. Yet Prometheus also reveals, to a certain extent, how Zeus’ reign will come to an end: the Olympian ruler will father a son superior to him, and this son will remove him from power. Io leaves, and Hermes is sent to the bound Prometheus to draw out the secret about Zeus’ future fall. The Titan refuses to cooperate and Zeus causes an earthquake, throwing him into Tartarus. The Chorus, contrary to Hermes’ advice, stays with Prometheus. This drama is a technically demanding spectacle: it involves a Chorus airborne in some kind of car, an airborne Oceanus riding a mythic bird, and, most likely, a somehow visibly perceivable earthquake. By Aeschylean standards, there are not many textual difficulties in this play, and its Greek is comparatively easy.
Asconius
Authors: Ramsey John T.
Published: November 2023

Quintus Asconius Pedianus was born c. 4 ce, most likely at Patavium (Padua), the hometown of Livy. At the age of seventy-two, he went blind and lived for another twelve years. As a young man, Asconius moved in the highest echelons of society, for instance, attending a banquet in 28 as the guest of a consul. In the age of Nero, in the years c. 53 ce to 57, Asconius composed commentaries on perhaps as many as thirty of Cicero’s speeches, five of which survive thanks to having been preserved in a heavily damaged, 9th-century manuscript that is no longer extant. Asconius conducted meticulous research and is noted for his reliability. He consulted primary sources such as the official state archives (Acta) and other writings produced in the age of Cicero. He often cites his sources and occasionally even confesses that his research proved fruitless on a particular topic. The historian on whom Asconius appears to have relied most heavily is the 1st-century annalist Fenestella. Asconius’s comments on the speeches are highly selective and are confined mostly to historical and proposographical matters. By comparison, later scholia on Cicero’s speeches tend to comment on mundane matters of grammar, vocabulary, and rhetoric. Each of Asconius’s commentaries begins with a statement of the year in which the speech was delivered. Background information is presented under the heading Argumentum and ranges from several paragraphs to as many as twelve pages. There follow lemmata from the Ciceronian speeches themselves to which Asconius appends his comments. Frequent cross references, all backward looking, show that the collection was arranged chronologically, by the delivery dates of the speeches, and there is no evidence that the extant commentaries have been abridged. The work is written in a plain, transparent style and appears to have been dedicated to Asconius’s sons. Given the painstaking nature of Asconius’s research and the broad range of speeches included in his collection—not just the “popular” ones read in schools teaching rhetoric—his aim was to produce an enduring work of scholarship. His accomplishment earned him a place, alongside Livy and Sallust, in Suetonius’s De historicis, a collection of biographies commemorating Rome’s leading historians. The only other work, no longer extant, that can be securely attributed to Asconius is a treatise refuting Virgil’s critics. Very uncertain is evidence that Asconius may have written a biography of the historian Sallust and an essay on longevity.
Vicarious Trauma and Resilience in Social Work Practice with Refugees and Forcibly Displaced Populations
Authors: Ciro Dianne , Engstrom David
Published: November 2023

Helping professionals, such as social workers, who work with refugees and asylum seekers are exposed to their clients’ trauma on a regular basis; in some cases, they are exposed every day. As noted in: (1) Secondary Traumatic Stress and Burnout among Refugee Resettlement Workers: The Role of Coping and Emotional Intelligence and (2) Second-Hand Emotion? Exploring the Contagion and Impact of Trauma and Distress in the Asylum Law Context, observing and caring for the scars of torture, persecution, violence, harassment, and family separation, among other catastrophic events that refugees and asylum seekers experience can impact social work providers and other helping professionals who bear witness to these traumatic experiences. Articles, such as (1) Compassion Fatigue: Coping with Secondary Traumatic Stress Disorder in Those Who Treat the Traumatized, (2) Vicarious Traumatization: A Framework for Understanding the Psychological Effects of Working with Victims, and (3) Job Burnout highlight some of the short-term and long-term effects of working with trauma- related client material, including experiencing Compassion Fatigue (CF), Vicarious Trauma (VT), and Burnout (BO). In Vicarious Resilience: A New Concept in Work with Those Who Survive Trauma we also learn that in some cases, providers who work with refugees and asylees report experiencing Vicarious Resilience (VR) and growth. While working with highly traumatized populations creates some universal challenges for all helping professionals, the complex effects of extreme violence, traumatic loss, and adversity associated with the refugee and asylee experience have long lasting effects on survivors and unique challenges for social work providers that require a different set of skills than solely appreciating a person’s inner suffering. Social workers who work with refugees and asylum seekers often find themselves wearing multiple hats, including the role of healer, advocate, helper, and confidant, leaving them highly susceptible to experiences of CF, VT, and BO. However, social workers and agencies can take steps to foster the VR and growth of staff working with these communities.
Anti-Natalism
Authors: Singh Asheel
Published: November 2023

While most people would agree that there is sometimes an element of moral wrongness to procreation, anti-natalism, a burgeoning field in contemporary ethics, holds that procreation itself is (almost) always morally wrong. Anti-natal intuitions have been expressed in various forms throughout history, but this entry is primarily concerned with the systematic explorations of anti-natalism that have emerged in the current century. Notably, the explosion of critical interest in anti-natalism can be traced to the seminal work of a single contemporary analytic philosopher, David Benatar. The primary focus of this entry is thus on how the view has developed in analytic philosophy, and not on how “anti-natalism” is generally employed in public policy (i.e., as population reduction efforts). A novel taxonomy of anti-natalist rationales is offered, and notable pro-natal views are discussed, along with some salient historical antecedents to the current systematic debate.
Jewish Women in Renaissance and Reformation Europe
Authors: Baskin Judith R.
Published: November 2023

This bibliography focuses on primary documents, monographs, and articles highlighting Jewish women and their activities in Renaissance Italy and in German-speaking regions between approximately 1400 and 1750. The research gathered here affirms that while gender constituted the primary determinant in an individual’s life, social class was also of significant importance. The larger a family’s resources, the more likely a woman was to be educated and to have access to powerful kinship and community networks. In the bibliographical discussions that follow, Italy and German-speaking areas are addressed separately.
Feminist Perspectives on International Law
Authors: Barrow Amy
Published: November 2023

Feminist perspectives provide a critical lens through which to examine international law’s rules, systems, and structures. In the early twentieth century, women’s activism and organizing during World War I was instrumental in drawing attention to the absence of women in peacemaking processes, leading to the creation of feminist peace organizations whose advocacy was highly influential in generating debate regarding the role of international bodies and women’s equal participation in international lawmaking. Second-wave feminist scholarship during the sixties and seventies drew attention to women’s legal and political status, including issues such as reproductive rights and nondiscrimination, influencing legal reforms in domestic law systems. Significant societal debate on these questions of gender equality did not always directly translate to international law settings. However, the global women’s conferences that occurred at regular intervals during the UN Decade for Women (1975–1985) provided the political opportunity structure for women’s groups to organize transnationally. While evident political differences emerged between feminist activists from the Global North and Global South, these tensions nevertheless heightened awareness of international law’s limited engagement with women’s myriad lived experiences. The adoption of the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) in 1979 provided a foundation for feminist critique centering on the marginalization of women’s rights in international law. The application of a feminist lens to the entire ambit and breadth of international law occurred at a later period during the early nineties. This seminal scholarship coincided with the post–Cold War period, which saw significant social and political change globally. Witnessing a surge in regional ethnic-based conflicts and their gendered impacts, feminist scholars engaged in critique of the law of armed conflict, international criminal law, and transitional justice processes. While the successes of feminist interventions in international law, particularly in relation to the women, peace and security agenda at the UN Security Council, have been cautiously acknowledged, some areas of international law have proved to be particularly resistant to feminist analysis. Although theoretical perspectives, including postcolonial and Third World Approaches to International Law (TWAIL), are yet to move from the periphery to the center of feminist analyses, they provide an important lens through which to understand the tensions that emerge from feminist interventions in international law, as does theoretical engagement with queer and nonbinary perspectives. Scholars have also increasingly engaged in feminist introspection, scrutinizing whether feminist methodologies provide an effective analytical tool to examine international law.
Ethnic, Linguistic, Religious, and Regional Minority Participation and Representation in Africa
Authors: MacLean Lauren , Harris Kirk
Published: November 2023

Understanding ethnic, linguistic, religious, and regional minority participation and representation in Africa is both empirically and normatively fraught. Who counts as a minority? Which minority identities are politically salient? Answering these questions is essential to the study of minority political participation, yet doing so requires making challenging decisions about how to describe the identities of individuals and groups, as well as how to regard the claims of leaders seeking to speak on behalf of group interests. It is also critical to explore whose interests are served by “minority” discourses. Given the centrality of identity politics on the continent the answers to these questions are pertinent to political scientists studying a range of phenomena, from conflict, to voting, to public goods provision or legislator behavior. Historically speaking, ethnic identities, most often defined on the basis of linguistic difference (with other cultural differences serving as secondary identity markers) have received the most scholarly attention. Scholars have understood minority participation in terms of citizens’ relation to state power. However, regional and religious identities that either cut across or reinforce ethnic boundaries have also been salient in certain contexts. For example, ethno-regional identities have been the basis for political party competition, civil conflict, and even secession movements. Of course, the salience of broader regional identities that cross national borders has been somewhat mitigated by the persistence of the borders imposed on African states during colonialism. While religion is essential to the identities of many Africans, its political role varies across the continent. While in some areas, religious identities may diffuse political differences and contribute to democratic peacebuilding, in others, they may be deployed to mobilize collective action from voter turnout to social protest or even civil war. Often, in these latter contexts, religious identities overlap with significant ethnic divisions or subnational inequalities between regions. Finally, the policies of African states toward the treatment of minority identities is as varied as the issues that they face, with states adopting a range of policies, including the conscious affirmation of minority identities; the suppression of identities in the name of liberal, inclusive citizenship norms; and the active persecution of certain identities. Transnational actors such as international donors, multinational corporations, intergovernmental organizations, and international non-governmental organizations (NGOs) also play an increasingly significant role in responding to minority group issues or putting pressure on states to modify their policies toward certain groups.
Multicultural Families
Authors: Soliz Jordan , Minniear Mackensie
Published: November 2023

Many have heralded the rise of multiculturalism as a sign of the changing times, and a signal of a new, more accepting era. While there have been major demographic shifts in immigration patterns, ethnicity and race, and acceptance of different family types, most of the research and pedagogy concerning family communication still centers on family roles and processes that assume a singular cultural, racial, or ethnic identity in the family. Defining a “multicultural” family is difficult, as our definitions of what constitutes culture, nationality, identity, and difference are always changing globally, and largely context specific. For example, a multicultural family in the United States may conjure an image of a family made up of multiple different races, while a multicultural family in Thailand, may conjure an image of a family made up of different religious or ethnic practices. Evident in the scholarship of these is families is the complexity of defining and distinguishing ethnicity, race, and culture. Race and ethnicity both share the assumption that said group has a common culture and is from a certain geographical region. However, race tends to reflect socially constructed physical or visible difference, while ethnic groups tend to have some type of cultural marker of social boundaries rather than a visible boundary. These definitions are clearly not fixed, with many scholars arguing that it is not always possible to neatly divide these facets of identity. Nonetheless, when reviewing the literature, we do notice that studies on “multicultural” families—whether framed as cultural, ethnic, or racial diversity in the family—tend to focus on communication, identity, and difference. In this way “multicultural” families contend with some facet of differentness that they discuss and negotiate within their family. This bibliography presents literature overviewing several approaches to studying multicultural families. After reviewing core texts, it overviews general family relationships that are marked by cultural and/or ethnic-racial differences, including multiracial-ethnic families and immigrant families. It then presents work specifically on marital relationships, parent-child relationships, and sibling relationships. Given the growing literature on transracial and international adoption, the next section is dedicated to research exploring how adaptive families negotiate differences. Lastly, when examining multicultural families, it is equally important to look at how these families are represented outside of the immediate family system. To do this, it reviews media representations of multicultural families.
Institutional Pragmatics
Authors: Nguyen Hanh thi , Nguyen Minh Thi Thuy
Published: November 2023

Pragmatics of institutional interaction is concerned with how utterances acquire their meanings in professional or organizational contexts. Most of the insights on institutional interaction or “talk at work” come from ethnomethodological and conversation analytic studies. A majority of research in this area focuses on the interaction between the providers of institutional services (institutional agents such as doctors, psychiatrists, therapists, store clerks, teachers) and the receivers of those services (laypersons such as patients, clients, customers, students). Less research has been on “backstage” interaction among members of the institutions themselves. The sections below will first introduce publications on overall theoretical and methodological approaches, then summarize selected studies in two main domains of institutional discourses, professional-layperson interaction and professional-professional interaction.
Current and future advances in practice: a practical approach to the diagnosis and management of primary central nervous system vasculitis
Authors: Junek Mats , Perera Kanjana S , Kiczek Matthew , Hajj-Ali Rula A
Published: November 2023

Primary CNS vasculitis (CNSV) is a rare, idiopathic autoimmune disease that, if untreated, can cause significant morbidity and mortality. It is a challenging diagnosis due to multiple mimics that can be difficult to differentiate, given that the CNS is an immunologically privileged and structurally isolated space. As such, diagnosis requires comprehensive multimodal investigations. Usually, a brain biopsy is required to confirm the diagnosis. Treatment of CNSV involves aggressive immunosuppression, but relapses and morbidity remain common. This expert review provides the reader with a deeper understanding of presentations of CNSV and the multiple parallel diagnostic pathways that are required to diagnose CNSV (and recognize its mimics), highlights the important knowledge gaps that exist in the disease and also highlights how we might be able to care for these patients better in the future.
How Credit Constraints Impact Job Finding Rates, Sorting, and Aggregate Output
Authors: Herkenhoff Kyle , Phillips Gordon , Cohen-Cole Ethan
Published: November 2023

How do consumer credit markets affect the allocation of workers to firms, output, and labour productivity? We address this question in two steps. First, we use new micro-data to estimate empirical elasticities of job search patterns to credit. Second, we estimate our novel theory of sorting under risk aversion to match these elasticities, and then we conduct aggregate counterfactuals. Empirically, we show that an increase in credit limits worth 10% of prior annual earnings allows individuals to take 0.33 weeks longer to find a job. Conditional on finding a job, they earn 1.85% more and work at higher paying firms. We also find that young and high-utilization individuals are more responsive to credit. Theoretically, we integrate risk aversion and borrowing into a model with worker and firm heterogeneity. We estimate the model to match our new empirical elasticities, and we then measure how the credit expansion from 1964 to 2004 affected sorting and output. Sorting improves as credit expands since constrained workers—in particular constrained, young, high human capital workers—find more capital-intensive jobs.
Cytotoxic activity of isoquinoline alkaloids and herbal extracts from selected plants against human cancer cell lines: harnessing the research potential in cancer drug discovery with modern scientific trends and technology
Authors: Bhandare Saurabh Dilip , Malode Sarika Shivaji
Published: November 2023

The increasing prevalence of cancer has led to a growing interest in alternative medicine methods and treatments. This study aimed to assess the cytotoxicity of isoquinoline alkaloids and herbal extracts from selected plants against human cancer cell lines, including melanoma and squamous cell carcinoma. The investigation involved in vitro cell viability assays using various cancer cell lines and normal skin fibroblasts as control cells. Additionally, a zebrafish model was employed for in vivo evaluation of cytotoxic activity. The results indicated that the tested alkaloids and extracts exhibited promising cytotoxic effects, showing higher potency than standard chemotherapeutic drugs. In comparison, these findings support the exploration of isoquinoline alkaloids and herbal extracts as potential candidates for developing novel anti-melanoma and anti-squamous cell carcinoma drugs. The primary inclusion criterion that was taken into consideration in this study effort was the therapeutic application of the cytotoxic effects of specific plant-based pharmacological components or chemicals produced from herbal extracts that are ordinarily cytotoxic.
Conserved and species‐specific transcriptional responses to daily programmed resistance exercise in rat and mouse
Authors: Viggars Mark R. , Sutherland Hazel , Cardozo Christopher P. , Jarvis Jonathan C.
Published: November 2023

Mice are often used in gain or loss of function studies to understand how genes regulate metabolism and adaptation to exercise in skeletal muscle. Once‐daily resistance training with electrical nerve stimulation produces hypertrophy of the dorsiflexors in rat, but not in mouse. Using implantable pulse generators, we assessed the acute transcriptional response (1‐h post‐exercise) after 2, 10, and 20 days of training in free‐living mice and rats using identical nerve stimulation paradigms. RNA sequencing revealed strong concordance in the timecourse of many transcriptional responses in the tibialis anterior muscles of both species including responses related to “stress responses/immediate‐early genes, and “collagen homeostasis,” “ribosomal subunits,” “autophagy,” and “focal adhesion.” However, pathways associated with energy metabolism including “carbon metabolism,” “oxidative phosphorylation,” “mitochondrial translation,” “propanoate metabolism,” and “valine, leucine, and isoleucine degradation” were oppositely regulated between species. These pathways were suppressed in the rat but upregulated in the mouse. Our transcriptional analysis suggests that although many pathways associated with growth show remarkable similarities between species, the absence of an actual growth response in the mouse may be because the mouse prioritizes energy metabolism, specifically the replenishment of fuel stores and intermediate metabolites.
Great Toe Interphalangeal Fusion for Hallux Valgus Interphalangeus Deformity in Young Patients
Authors: Westberry David E. , Shull Emily R. , Layton Branum
Published: November 2023

Objectives:

The purposes of this study were to examine indications, radiographic outcomes, and clinical complications for primary arthrodesis of the great toe interphalangeal (IP) joint in young patients.

Background:

Hallux valgus interphalangeus deformity of the great toe is uncommon in the pediatric population and often requires fusion of the IP joint.

Methods:

A retrospective review of patients, ages 8 to 19 years, who underwent operative fusion of the great toe IP joint, and had >1 year radiographic follow-up was performed. Medical records and radiographs were reviewed to determine indications for surgery, concomitant procedures, success of fusion, complications, and need for revision procedures or elective hardware removal. Differences between pre and postradiographic outcomes for the hallux valgus angle, IP angle, and intermetatarsal angle were analyzed.

Results:

Twenty-seven patients (31 feet) were included in the analyses. The average age at fusion surgery was 14.9 years (SD ± 2.3) with a mean follow-up visit of 35.2 months. The most common indications for fusion of the great toe IP joint were pain and deformity. Kirschner wire fixation was utilized in 7 cases, with the remaining 24 cases fixed with a single retrograde cannulated screw. Fifty-five concomitant toe and foot procedures were performed in 21 feet (68%) to address additional foot and toe deformity. Successful fusion occurred in 30 of 31 toes after the primary fusion. Patient satisfaction with the toe position and diminished pain were high (94.1%). Significant improvement was noted in the measure of the IP angle (P < 0.001), with minimal clinical change in the hallux valgus angle (P = 0.24) or the intermetatarsal angle (P = 0.03).

Conclusions:

Hallux valgus interphalangeus of the great toe was successfully managed with the fusion of the IP joint. Single screw fixation or the use of Kirschner wires led to similar outcomes. Hardware-related issues with the use of screws were the most common adverse outcome. Patients should be made aware of the possible need for hardware removal after fusion utilizing screw fixation.

Level of Evidence:

Level IV—a retrospective case series.
Temporal trends in incidence and mortality of cervical cancer in China from 1990 to 2019 and predictions for 2034
Authors: Li Shuang , Huang Min , Zhu Yan , Zeng Hai , Zhang Fan
Published: November 2023

Objective

This study aimed to analyze long-term trends of cervical cancer (CC) burden in China based on the GBD 2019 data and provide information and data support for formulating corresponding policies to control CC.

Methods

Incidence and mortality rate data of CC in China were described using GBD 2019 data. The Joinpoint regression analysis and age-period-cohort model were implemented to describe temporal trends of CC in China over the past 30 years. ARIMA model was used to predict trends of disease burden of CC in China for the next 15 years.

Results

From 1990 to 2019, the relative percentage change in age-standardized incidence rate (ASIR) of CC in Chinese women was 30.91 (95% UI: −50.13 to 96.78), and the relative percentage change in age-standardized mortality rate (ASMR) was −12.37 (95% UI: −63.54 to 28.52). The age-period-cohort model had different impacts on incidence and mortality rates. Overall annual percentage change (APC) (net drift) in incidence risk was 1.22 (95% CI: 0.87–1.57), and the overall APC (net drift) in mortality risk was −0.143 (95% CI: −0.38 to 0.09). The ARIMA model predicted ASIR and ASMR trends of CC for the next 15 years.

Conclusion

From 1990 to 2019, the overall incidence risk of CC in Chinese has shown an upward trend, with an earlier occurrence in the high-incidence age groups, while mortality risk showed a downward trend. It is anticipated that over the next 15 years, the incidence rate will decrease, while the mortality rate will initially rise before decreasing.
Cancer mortality patterns in selected Northern and Southern African countries
Authors: Pizzato Margherita , Santucci Claudia , Parazzini Fabio , Negri Eva , La Vecchia Carlo
Published: November 2023

Background

Non-communicable diseases have been rapidly increasing in African countries. We provided updated cancer death patterns in selected African countries over the last two decades.

Methods

We extracted official death certifications and population data from the WHO and the United Nations Population Division databases. We computed country- and sex-specific age-standardized mortality rates per 100 000 person-years for all cancers combined and ten major cancer sites for the periods 2005–2007 and 2015–2017.

Results

Lung cancer ranked first for male cancer mortality in all selected countries in the last available period (with the highest rates in Réunion 24/100 000), except for South Africa where prostate cancer was the leading cause of death (23/100 000). Prostate cancer ranked second in Morocco and Tunisia and third in Mauritius and Réunion. Among Egyptian men, leukemia ranked second (with a stable rate of 4.2/100 000) and bladder cancer third (3.5/100 000). Among women, the leading cancer-related cause of death was breast cancer in all selected countries (with the highest rates in Mauritius 19.6/100 000 in 2015–2017), except for South Africa where uterus cancer ranked first (17/100 000). In the second rank there were colorectal cancer in Tunisia (2/100 000), Réunion (9/100 000) and Mauritius (8/100 000), and leukemia in Egypt (3.2/100 000). Colorectal and pancreas cancer mortality rates increased, while stomach cancer mortality rates declined.

Conclusion

Certified cancer mortality rates are low on a global scale. However, mortality rates from selected screening detectable cancers, as well as from infection-related cancers, are comparatively high, calling for improvements in prevention strategies.
The multicenter experience in the multidisciplinary Italian breast units: a review and update
Authors: Magnoni Francesca , Tinterri Corrado , Corso Giovanni , Curigliano Giuseppe , Leonardi Maria Cristina , Toesca Antonio , Rocco Nicola , Catalano Francesca , Bianchi Beatrice , Lauria Federica , Caldarella Pietro , Pagani Gianmatteo , Galimberti Viviana , Veronesi Paolo
Published: November 2023

A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS.
Minocycline as a potential anxiolytic drug: systematic review and meta-analysis of evidence in murine models
Authors: Iglesias Lia P. , Soares Nicia , Asth Laila , Moreira Fabricio A. , Aguiar Daniele C.
Published: November 2023

Minocycline is a tetracycline antibiotic with off-label use as an anti-inflammatory drug. Because it can cross the blood-brain barrier, minocycline has been proposed as an alternative treatment for psychiatric disorders, in which inflammation plays an important role. However, its beneficial effects on anxiety disorders are unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy of minocycline as an anxiolytic drug in preclinical models. We performed a PubMed search according to the PRISMA guidelines and PICOS strategy. The risk of bias was evaluated using the SYRCLE tool. We included studies that determined the efficacy of minocycline in animal models of anxiety that may involve exposures (e.g. stressors, immunomodulators, injury). Data extracted included treatment effect, dose range, route of administration, and potential mechanisms for the anxiolytic effect. Meta-analysis of twenty studies showed that minocycline reduced anxiety-like behavior in rodents previously exposed to stress or immunostimulants but not in exposure-naïve animals. This effect was not associated with the dose administered or treatment duration. The mechanism for the anxiolytic activity of minocycline may depend on its anti-inflammatory effects in the brain regions involving anxiety. These suggest that minocycline could be repurposed as a treatment for anxiety and related disorders and warrants further evaluation.
Reproducibility and predictive value of three grading systems for intraoperative adverse events in a cohort of abdominal surgery
Authors: Gawria L. , Krielen P. , Stommel M.W.J. , van Goor H. , ten Broek R.P.G.
Published: November 2023

Introduction:

Intraoperative adverse events (iAEs) are increasingly recognized for their impact on patient outcomes. The Kaafarani classification and Surgical Apgar Score (SAS) were developed to assess the intraoperative course; however, both have their drawbacks. ClassIntra was validated for iAEs of any origin. This study compares the Kaafarani and SAS to ClassIntra considering predictive value and interrater reliability in a cohort of abdominal surgery to support implementation of a classification in clinical practice.

Methods:

The authors made use of the LAParotomy or LAParoscopy and ADhesiolysis (LAPAD) study database of elective abdominal surgery. Detailed descriptions on iAEs were collected in real-time by a researcher. For the current research aim, all iAEs were graded according ClassIntra, Kaafarani, and SAS (score ≤4). The predictive value was assessed using univariable and multivariable linear regression and the area under the receiver operating curve (AUROC). Two teams graded ClassIntra and Kaafarani to assess the interrater reliability using Cohen’s Kappa.

Results:

A total of 755 surgeries were included, in which 335 (44%) iAEs were graded according to ClassIntra, 228 (30%) to Kaafarani, and 130 (20%) to SAS. All classifications were significantly correlated to postoperative complications, with an AUROC of 0.67 (95% CI: 0.62–0.72), 0.64 (0.59–0.70), and 0.71 (0.56–0.76), respectively. For the secondary endpoint, the interrater reliability of ClassIntra with κ 0.87 (95% CI: 0.84–0.90) and Kaafarani 0.90 (95% CI: 0.87–0.93) was both strong.

Conclusion:

ClassIntra, Kaafarani, and SAS can be used for reporting of iAEs in abdominal surgery with good predictive value for postoperative complications, with strong reliability. ClassIntra, compared with Kaafarani and SAS, included the most iAEs and has the most comprehensive definition suitable for uniform reporting of iAEs in clinical practice and research.
Normalization weighted combination scores re-evaluate TNM staging of gastric cancer: a retrospective cohort study based on a multicenter database
Authors: Wu Junpeng , Wang Hao , Yin Xin , Wang Yufei , Lu Zhanfei , Zhang Jiaqi , Zhang Yao , Xue Yingwei
Published: November 2023

Background:

The pathological depth of tumor invasion (pT) and lymph node metastasis (pN) are critical independent prognostic factors for patients with gastric cancer, representing effective methods for evaluating prognosis. In this study, we employed a normalization weight combination score to calculate the weight ratio of the pT stage and pN stage. Subsequently, we established a novel wTN staging model based on these T and N weights, evaluating its prognostic capacity.

Methods:

This study utilized a training cohort from A Medical University Cancer Hospital and a validation cohort from the SEER database. LASSO and Cox regression were employed to screen clinical characteristics. Multivariate linear regression and cluster analysis calculated the weight ratio of T stage and N stage in the training and validation cohorts, respectively, followed by re-staging. Prognostic value was evaluated using C-index, likelihood ratio, Wald, and Score tests for wTN stage and TNM stage. A nomogram model was developed, and accuracy was assessed using ROC, DCA, and RCS analyses.

Results:

LASSO was used for initial screening, selecting 8 potential features for Cox analysis. Age, tumor size, MLNs, and tumor location were confirmed as independent prognostic factors. wTN was calculated in the training and validation cohorts, and nomograms were established with the independent factors. N stage had a higher weight proportion than T stage in both cohorts (0.625/0.375 in training cohort, 0.556/0.444 in validation cohort). wTN outperformed the 8th TNM stage in C-index, likelihood ratio, Wald, and Score tests in the training cohort, with successful validation in the validation cohort. Stratified analysis of distinct pathological types further demonstrates that wTN staging exhibits superior prognostic performance.

Conclusion:

The wTN staging model based on T stage and N stage weights has a good prognostic value for gastric cancer patients. The same conclusion was obtained in different pathological stratification.
Six steps for a successful aesthetic free flap reconstruction shaping after minimally invasive mastectomy – a retrospective case-control study
Authors: Wong Allen Wei-Jiat , Kuo Wen-Ling , Cheong David Chon-Fok , Tsai Hsiu-Pei , Kao Shu-Wei , Chen Chia-Fang , Huang Jung-Ju
Published: November 2023

Objective:

Breast cancer treatment has evolved to the modern skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM). To better perform these surgeries, minimally invasive techniques using the endoscope, or Da Vinci Robotic Surgery platform have been developed. The deep inferior epigastric perforator (DIEP) flap is the gold standard in breast reconstruction, but it is still not commonly performed after minimally invasive mastectomy due technical difficulty. Here we introduced six key steps to a successful aesthetic autologous free flap reconstruction in in minimally invasive mastectomies.

Methods:

There are six main steps to our technique: placement of mastectomy incision, precise flap design after angiography studies, trial of shaping, transcutaneous medial suture, footprint recreation and post-operative shaping with bra. Between November 2018 and July 2022, a total of 67 immediate breast reconstructions using free perforator flaps were performed in 63 patients after minimally invasive NSM.

Results:

The results from the minimally invasive mastectomy group were compared with a group of conventional mastectomy patients (n=41) performed during the same period. There were no significant differences in flap exploration rates. 100% of the flaps survived. In the minimally invasive group, the final scar was placed in the lateral region, where it would be hidden from the anterior view. Only 70.7% of the conventional mastectomy group could achieve a hidden lateral scar (P<0.001). The aesthetic revision rates were similar between two groups.

Conclusion:

With attention to the six steps above, autologous free flap reconstruction can be offered reliably in the setting of minimally invasive mastectomy.
Benefit of perioperative radiotherapy for hepatocellular carcinoma: a quality-based systematic review and meta-analysis
Authors: Rim Chai Hong , Park Sunmin , Yoon Won Sup
Published: November 2023

Introduction:

Although surgery is the standard curative modality for hepatocellular carcinoma, more than two-thirds experience intrahepatic recurrence. Since no standard perioperative treatment has been established, the authors performed a meta-analysis to evaluate the benefits of perioperative radiotherapy (RT).

Methods:

The PubMed, MEDLINE, EMBASE, and Cochrane Library were searched until May 2023. Randomized or propensity-matched studies evaluating at least five major clinical factors investigating benefit of perioperative RT, were included. The main effect measure were the pooled odds ratios (OR) regarding the benefit of perioperative RT using 2-year overall survival (OS) and 1-year disease-free survival (DFS) data.

Results:

Seven studies (five randomized and two propensity-matched studies) involving 815 patients were included. The pooled ORs for 1-year DFS and 2-year OS were 0.359 (95% CI: 0.246–0.523) and 0.371 (95% CI: 0.293–0.576), respectively, favoring perioperative RT, with very low heterogeneity. In the subgroup analyses, the benefits of OS and DFS were consistent between the two subgroups [portal vein thrombosis (PVT) and narrow resection margin (RM) groups]. In the PVT subgroup, the pooled OS rates at both 1-year and 2-year (75.6 vs. 36.9%, P<0.001; 25.6 vs. 9.9%, P=0.004) and DFS rates at both 1-year and 2-year (25.2 vs. 10.3%, P=0.194; 11.9 vs. 3.0%, P=0.022) were higher in the perioperative RT group. In the narrow RM subgroup, the surgery and RT groups showed higher pooled OS rates for both 1-year and 2-year (97.3 vs. 91.9%, P=0.042; 90.4 vs. 78.7%, P=0.051) and DFS (88.1 vs. 72.6%, P<0.001; 70.1 vs. 51.7%, P<0.001). Grade 5 toxicity was not reported, and three studies reported grade ≥3 or higher liver function test abnormalities, ranging from 4.8–19.2%.

Conclusion:

The present study supports the oncological benefits of perioperative RT, for cases with high-risk of recurrence. Oncologic outcomes between subgroups differed according to clinical indications.
Amino acid kinetics in the critically ill
Authors: Deutz Nicolaas E.P. , Haines Krista L. , Wischmeier Paul E. , Engelen Mariëlle P.K.J.
Published: November 2023

Purpose of review

Stable isotope methods have been used for many years to assess whole body protein and amino acid kinetics in critically ill patients. In recent years, new isotope approaches and tracer insights have been developed. The tracer pulse approach has some advantages above the established primed-continuous tracer infusion approach because of the high amount of metabolic information obtained, easy applicability, and low tracer costs. Effects of disease severity and sex on amino acid kinetics in ICU patients will also be addressed.

Recent findings

Current knowledge was synthesized on specific perturbations in amino acid metabolism in critically ill patients, employing novel methodologies such as the pulse tracer approach and computational modeling. Variations were evaluated in amino acid production and linked to severity of critical illness, as measured by SOFA score, and sex. Production of the branched-chain amino acids (BCAAs), glutamine, tau-methylhistidine and hydroxyproline were elevated in critical illness, likely related to increased transamination of the individual BCAAs or increased breakdown of proteins. Citrulline production was reduced, indicative of impaired gut mucosa function. Sex and disease severity independently influenced amino acid kinetics in ICU patients.

Novel tracer and computational approaches have been developed to simultaneously measure postabsorptive kinetics of multiple amino acids that can be used in critical illness. The collective findings lay the groundwork for targeted individualized nutritional strategies in ICU settings aimed at enhancing patient outcomes taking into account disease severity and sex.
The future of HOXA-expressing leukemias: Menin inhibitor response and resistance
Authors: Wenge Daniela V. , Armstrong Scott A.
Published: November 2023

Purpose of review

We provide an update on the successes and ongoing challenges of Menin inhibition as a novel approach for the treatment of patients with acute leukemias that express HOXA cluster genes including leukemias with KMT2A-rearrangements, NPM1 mutations or NUP98-rearrangements. Initial clinical trials show promising response rates in heavily pretreated patients suggesting these inhibitors may have a significant impact on patient outcome. Furthermore, the development of resistance mutations that decrease drug binding affinity, validates Menin as a therapeutic target in human cancers. Therapeutic strategies aiming at overcoming and preventing resistance, are of high clinical relevance.

Recent findings

Several Menin inhibitor chemotypes have entered clinical trials. Acquired point mutations have recently been described as a mechanism of resistance towards Menin inhibitors. However, resistance can develop in absence of these mutations. Combination therapies are currently being investigated in preclinical models and in early phase clinical trials.

Given the remarkable overall response rates, shedding light on treatment options for patients whose leukemias develop resistance to Menin inhibitors is an imminent clinical need. Studying the underlying mechanisms to inform clinical decision making, and to potentially prevent the development of resistance is of outmost importance.
Obstructive sleep apnea for the rhinologist
Authors: Nogues Juan C. , Jain Nikhita , Chou Courtney T. , Lin Fred Y.
Published: November 2023

Purpose

Obstructive sleep apnea (OSA) is a ubiquitous disease defined by repetitive partial or complete cessation of airflow during sleep caused by upper airway collapse. Otolaryngologists play a crucial role in the management of OSA, which is rapidly evolving with the advent of new surgical techniques and medical devices. Here we review the medical and surgical treatment options for OSA with a focus on unique considerations for patients with OSA who undergo nasal, sinus, and skull base surgery.

Recent findings

Treatment of OSA includes both nonsurgical and surgical options. Positive airway pressure (PAP) therapy remains the first-line medical treatment for OSA, but alternatives such as oral appliance and positional therapy are viable alternatives. Surgical treatments include pharyngeal and tongue base surgery, hypoglossal nerve stimulation therapy, and skeletal surgery. Nasal surgery has been shown to improve sleep quality and continuous positive airway pressure (CPAP) tolerance and usage. Sinus and skull base patients with comorbid OSA have special perioperative considerations for the rhinologist to consider such as the need for overnight observation and timing of CPAP therapy resumption.

OSA patients present with special considerations for the rhinologist. Patients with moderate to severe OSA may benefit from overnight observation after ambulatory surgery, especially those with an elevated BMI, cardiopulmonary comorbidities, and those who are not using CPAP regularly at home. Though CPAP may be safely resumed in the perioperative setting of nasal, sinus, and skull base surgery, the exact timing depends on patient, surgeon, and systemic factors such as severity of OSA, CPAP pressures required, extent of surgery, and the postoperative monitoring setting. Lastly, nasal and sinus surgery can improve sleep quality and CPAP tolerance and compliance in patients with OSA.