bluuebunny/crossref_metadata_2025 huggingface dataset:
Zay
Authors: Meyer Ronny
Published: May 2023

This chapter describes the linguistic features of the Zay language, which is endangered and exclusively used for oral communication. Zay uses nonlinear morphology with verbs but usually fully vocalized stems with nominals. Open word classes refer to verbs and nominals, while closed word classes are pronouns, relators and modifiers, and interjections. Zay syntax is characterized by an obligatory system of focus and clausal status marking that, in this form, is not found in other Ethiosemitic languages.
Linguistic diversity in Ethiopian languages
Authors: Meyer Ronny , Yigezu Moges
Published: May 2023

This chapter emphasizes that Ethiopia is a linguistically and culturally diverse country whose area and ethnolinguistic composition has varied over time. It describes Ethiopia’s historical ethnolinguistic composition and communication patterns, noting that many Ethiopian languages were first discovered in the period lasting from the end of the 19th to the middle of the 20th centuries. The chapter also highlights the first comprehensive investigation of ethnolinguistic diversity in Ethiopia including aspects of societal language use: the Survey of Language Use and Language Teaching in Eastern Africa in 1968–1971. Ultimately, this chapter examines how a language can function as either a native, second, or foreign language. It also studies the linguistic variation due to differences regarding social prestige or status, gender, age, occupation, etc. as well as the enduring and widespread bilingualism in Ethiopia.
Language endangerment in Ethiopia
Authors: Amha Azeb , Leyew Zelealem
Published: May 2023

This chapter discusses language vitality and language loss and speakers’ attitude towards their language. It analyzes how the loss of little-known and under-studied languages creates gaps in our understanding of human language and cognition. The chapter examines social and scholarly efforts to curb language loss or at least keep proper documentation of the languages and cultures of minority groups for future generations. It engages with literature that deal with various types of extinct and endangered languages, and with criteria for assessing the status of endangered languages, and diverse risk-assessment factors. The chapter addresses language diversity and endangerment as reflected in Ethiopian national censuses. It recounts the inconsistencies in census results, with focus on the two most recent censuses (conducted in 1994 and 2007) because of their impact on current educational and language development efforts. The chapter illustrates how official language and educational policies affect language vitality, and it emphasizes on the need for curbing language endangerment.
Kafa
Authors: Theil Rolf
Published: May 2023

This chapter expounds on Kafa and its dialects: E-Dialects and A-Dialects. The segmental phonology of Kafa is referenced on Theil (2007), while the tonology is based on Taddese (2001). However, the description of morphology, syntax, and pragmatics is based on A-Dialects. Additionally, the orthography of Kafa is based on Roman writings or Fidel script. However, tones and gemination are not marked. Kafa’s major morphophonological processes range between gemination, tonal bridge effect, and absorption, while verbal derivations are determined through causative and medio-passive means. The chapter also notes invariable copula, inflective verb equative, and inflected locative verb as the three Kafa expressions of the term ‘be’.
Sheko
Authors: Hellenthal Anne-Christie
Published: May 2023

This chapter focuses on the grammar of Sheko. Its phonology stands out through a series of retroflex sibilants and four levels of tone. After discussing word classes, derivation is treated, showing among others how the combination of causative and middle morphemes codes reciprocity. The discussion of the verb system comprises stem formation, aspectual and modal distinctions as well as stance marking. Sheko has a rich array of complex verb constructions, such as medial clause chains and different types of subordinate clauses. In relative clauses, a resumptive pronoun may occur before the antecedent. In interrogatives, elision occurs of grammatical morphemes which are required in declaratives, thus making subtractive morphology one of the ways in which questions are formed. The discussion of nominal morphology shows close relationships between gender, definiteness, and number. Some nominal marking also occur on verbal forms. Furthermore, several types of information structure and focus are distinguished based on the presence and absence of subject clitics and their exact position in main and medial clauses.
Language in the media
Authors: Wakjira Bedilu , Shiferaw Teshager
Published: May 2023

This chapter describes how the social foundation of literacy in Ethiopia is entrenched in religion. It underlines that the requirement for education emanated from the institutional interests of churches and mosques. Being literate was synonymous with being clerical, as books and other written materials were almost exclusively on religious matters. The chapter also outlines the start of the production of books and reading materials in Ethiopian languages in the 19th century. It discusses the introduction of newspapers in the late 19th century by Europeans who started to print brief newsletters with a focus mainly on religion but also on Amharic and Tigrinya grammar. Ultimately, this chapter peeks at how journalism and the readership of print media started to grow as a result of improvements in literacy. The chapter also analyzes the expansion of printing presses in Ethiopia and a major change in language policy.
Scripts and writing in Ethiopia
Authors: Meyer Ronny , Wakjira Bedilu
Published: May 2023

This chapter presents a concise overview of scripts and writing practices in Ethiopia. It starts with an account of the evolution and modification of the Fidel script used for writing Geez and Amharic, then introduces major principles used for its adaption to write other Ethiopian languages. The chapter also highlights the earliest extant written testimonies in Ethiopia and Eritrea: Pseudo-Sabaic inscriptions from the 8th or 7th century bc written in a South Arabian script. It also mentions the first indigenous Ethiopic script—an abjad whose earliest remnants date to a period between the 1st and 3rd centuries ad. Ultimately, this chapter gives a very brief summary of other scripts in Ethiopia, and displays the current script choice for writing Ethiopian languages used in education.
Transcranial Stimulation and the Pain Experience
Authors: Fitzgibbon Bernadette , Schabrun Siobhan
Published: May 2023

Transcranial stimulation describes non-invasive approaches to modulate activity within the underlying cortex, providing methods to probe and treat pain. These approaches have informed the pathophysiological underpinnings of acute and chronic pain and have been used to modulate the perception of pain in healthy individuals and clinical populations. However, the therapeutic application of transcranial stimulation for pain remains largely investigational. This chapter provides an overview of the current state of the evidence for transcranial stimulation in pain, focusing on transcranial magnetic and transcranial electrical stimulation, as well as newer approaches such as transcutaneous vagus nerve stimulation and transcranial focused ultrasound. Adjunctive treatment approaches, where transcranial stimulation is combined with other forms of therapy, are also discussed. Throughout the chapter, limitations and future directions for the field are presented.
Ethiopia and the Spanish Civil War Before and During World War II
Authors: Garretson Peter , McVeigh Stephen
Published: May 2023

This chapter assesses the impact of two “small wars,” in Ethiopia and Spain, that preceded World War II during the 1930s. Most importantly, they foreshadowed what was to come in the much more destructive total war of World War II. In both wars, the Italians and Germans used airplanes to bomb and strafe in a manner unseen in World War I. The role of the dictators—Mussolini, Hitler, and Franco—highlighted the weakness of the democratic leadership of the United Kingdom, France, and the United States, whose use of diplomacy, collective security, and the League of Nations was rendered ineffective. Interestingly, the weapons of mass destruction that Mussolini used in Ethiopia were not used in World War II, although the fear of their use was widespread. Both Mussolini and Hitler used these wars to train and prepare for wars to come.
Medicine and Disability
Authors: Kinder John M.
Published: May 2023

Medicine played a contradictory role in World War II and its aftermath. The development of new drugs and casualty evacuation techniques allowed military physicians to save the lives of millions of combatants. During the war, doctors introduced novel techniques for combating the effects of altitude sickness, malaria, and psychological trauma; at war’s end, they participated in government-sponsored efforts to rehabilitate millions of disabled veterans. However, physicians were by no means innocent bystanders. In the United States, doctors used their professional expertise to reinforce exclusionary doctrines of race and sexuality, while German and Japanese physicians carried out ghastly medical experiments on prisoners in the name of science. Ultimately, military medicine was deeply implicated in both the war’s immense violence and in the efforts to grapple with World War II’s postwar legacies of disability and trauma.
Eastern Europe in World War II
Authors: Cornelius Deborah S. , Grant Jonathan A.
Published: May 2023

As Europe headed for war it became almost inevitable that the Eastern European countries of Poland, Romania, and Hungary would be drawn into the conflict. Germany had plans to harness the region economically and make it subservient to the Reich. Given that each of the Eastern European countries viewed the spread of communism from the Soviet Union as the most immediate threat, the central question became whether they would enter the German orbit as occupied countries, client states, or allies. Poland would first bear the brunt of Nazi and Soviet attack and occupation, whereas Romania and Hungary would gradually move into the German sphere of influence. This chapter addresses the respective roles of Poland, Romania, and Hungary in the war and their contributions to the war effort.
Ideological Origins of World War II
Authors: Tismaneanu Vladimir , Iacob Bogdan C.
Published: May 2023

The chapter explores the role played by the most influential revolutionary movements of the past century, Communism and Fascism, alongside Japanese ultra-nationalism in fueling the tumult of the interwar period that led to World War II. It highlights the conflict among colonialisms, as Britain and France tried to keep the world unchanged under the pressure from post-1933 Germany, Mussolini’s dreams of Mediterranean empire, and Japan’s anti-Western push for imperial and racial hegemony across East Asia. The analysis explains the historical, divine mission intrinsic to images of the upcoming war among revisionist powers—Germany, Italy, Japan, and the Soviet Union. These challengers of the status-quo mobilized contestation throughout the world that subverted domestic orders and international hierarchies. The war brought unprecedented radicalization—achieving the right form of modernity became a matter of life or death. Such realignment of the globe was, until 1989–1991, the legacy of World War II and of its ideological origins.
The Eastern Front, 1943–1945
Authors: Stone David R.
Published: May 2023

After the summer 1943 failure of Nazi Germany’s Kursk offensive, the dynamic of the war on the Eastern Front changed fundamentally. Germany was no longer able to mount major offensives, but only minor and reactive attacks in response to Soviet overextension. The Soviet military, by contrast, enjoyed increasing advantages in manpower and material. In addition, the Red Army’s officer corps was increasingly professional, and Soviet ruler Joseph Stalin had come to trust their judgment. Although Soviet casualties always remained higher than German, the Soviet economy and population base sustained losses that Germany could ill-afford, particular as German allies were driven out of the war. In a series of major offensives—the pursuit after Kursk, the destruction of Germany’s Army Group Center in Belorussia, the winter 1944–1945 drive through Poland into Germany, and the final conquest of Berlin—the Red Army systematically annihilated Adolf Hitler’s army and finally his regime.
The Environmental Impact
Authors: Closmann Charles
Published: May 2023

This chapter considers the environmental legacy of World War II and how scholars have approached this topic. Emphasizing the tangible consequences of this war, most scholars agree that World War II decisively transformed global ecosystems in complex ways. In particular, historians have identified the enormous devastation of rural landscapes and cities that occurred during the war. They have also generally agreed that the effects of marshalling natural resources for war, such as forests, have had more enduring effects on global environments than combat. Finally, this chapter points out some areas, such as the research on “militarized landscapes,” where less agreement exists. In the case of “militarized landscapes,” scholars have debated, among other things, the discourse surrounding habitat protection and species loss at former military training grounds, firing ranges, and other sites.
North Africa and Italy
Authors: Porch Douglas
Published: May 2023

From a global war perspective, the notion, current into the twentieth-first century, that the Mediterranean was an opportunistic and incremental theater of marginal strategic impact, that competed for resources with more strategically lucrative fronts, can no longer stand close scrutiny. Far from being lured into the Mediterranean to salvage Britain’s sputtering war effort there and reinforce Churchill’s imperial ambitions, the U.S. commitment reinforced Roosevelt’s “Europe first” strategy. It offered a place where the Western Allies could learn to fight at diminished risk and at a strategic advantage against overextended Axis forces. It seriously attrited Axis resources, and even provided the theater that unhinged the Axis. It became the venue for France’s return to the war on the Allied side. It bought time for Roosevelt to build up U.S. military might, and hence increase American influence in the postwar reconfiguration of Europe. For better or worse, the Mediterranean campaign initiated the political transformation of the region. The Mediterranean commitment was central to Roosevelt’s vision of building a stable, liberal, democratic postwar European order, one that avoided the risks and dangers of a premature engagement in Northern Europe. For their part, Axis leaders proved unable to formulate a similar comprehensive strategic vision for the Mediterranean.
The Battle of Britain
Authors: Stewart Andrew
Published: May 2023

The summer of 1940 represents one of key moments of World War II. While it specifically centered on military operations in Europe, the ramifications of the German failure to defeat Britain would impact upon the eventual outcome of the global conflict. Having been ignominiously defeated during the May battles and with its military forced to flee from the Continent, the British people waited for an invading force to arrive. With a refusal to accept any political compromise, assembled alongside the remnants of the professional army that had been rescued from the beaches of France, was a vast citizen militia supported by an expeditionary force which had travelled from across the British Empire. The most visible element of the battle was fought in the skies but, on the ground, frantic preparations were made to defend the country. Ultimately, neither these plans nor the often poorly equipped forces that stood ready to fight were tested. Despite the narrative that was quick to emerge and has endured ever since, the outcome of any attempted invasion would actually have been very difficult to determine.
The Middle East during World War II
Authors: Güngör Hakan , Garretson Peter
Published: May 2023

This chapter assesses the impact of World War II on the four key countries of the Middle East (Egypt, Iraq, Iran, and Turkey), arguing that the roles of political, economic, and social change were just as important as the military. The war helped centralize and strengthen all four states. Politically, Britain intervened in Egypt and Iraq, while both the United States and Britain intervened in Iran. Britain also put great pressure on Turkey to declare war on Germany while the United States played a more subtle role that would eventually help lead to Turkey’s becoming a key ally during the Cold War. Economically, the Middle East Center played a key role in strengthening the economies of most all the countries in the Middle East, while raw materials were a key factor in Turkey and oil in Iran. The role of the military and of the Palestinian question are not extensively dealt with.
Western Religious Leaders, Communities, and Organizations Before and During World War II
Authors: Barnett Victoria J.
Published: May 2023

“Religion”—in the form of tradition, religious communities and institutions, religious leadership, and international organizations—became a global force during the twentieth century and was a multifaceted and profound aspect of World War II. Colonialism, the rise of fascism and other ethno-nationalist movements in interwar Europe, church–state issues, and refugee issues were areas in which religious figures played a powerful role. By the 1920s, there was an international network of religious leaders and organizations, and a growing sense among European and North American religious leaders that they had a larger global and political responsibility. This chapter will examine the influences on western religious leaders, communities, and organizations in the early twentieth century and offer an analysis of how these historical factors shaped their responses in the era of “total war.”
The Axis Invasion of the Soviet Union, 1941–1943
Authors: Grant Jonathan A.
Published: May 2023

`When Germany invaded the Soviet Union on June 22, 1941, a German victory was not impossible but the German expectation of defeating the USSR within six weeks was highly unrealistic and it grossly overestimated their logistical capabilities while underestimating Soviet capabilities. The scale of Soviet prisoners taken by the Germans in the pockets at Bialystok-Minsk and Smolensk made those battles seem like crushing victories, but the Germans had failed to strike the decisive blow. Although German mistakes played a role when accounting for the final victory of the Red Army, other factors cannot be ignored in understanding the resiliency of the USSR. From the very start, the Soviets mobilized for a long war. After recovering from surprise and suffering horrendous losses early in the war, the Soviets eventually held their own and earned their victory. Motivations of Stalinism and nationalism, combined with the German Army’s participation in war crimes, stiffened Soviet resistance.
The Air War
Authors: Johnson M. Houston
Published: May 2023

This chapter examines the air war in Germany and Italy, including background conditions, the 1939 and 1940 battles on the Continent and the Battle of Britain, the Eastern Front, the Mediterranean theater, and strategic bombing and moral considerations thereof. It summarizes the technological, operational, and strategic considerations influencing all the major combatant air forces and describes how those factors shaped the air war in Europe. The chapter then examines major phases of the air war, from early German Blitzkrieg attacks to the combined bombing offensive’s role in establishing Allied air superiority over the continent. The chapter pays particular attention to strategic doctrine, focusing on the origins and effects of Allied strategic bombing efforts and ethical questions emerging from those actions. It also comments on how the air war shaped the larger conflict.
The “No Reasons” View
Authors: Smuts Aaron
Published: May 2023

Although we can try to explain why we love, we can never justify our love. Love is neither based on reasons, nor is it responsive to reasons, nor can it be assessed for normative reasons. Love can be odd, unfortunate, fortuitous, or even sadly lacking, but it can never be appropriate or inappropriate. We may have a variety of reasons to act on our love, but we cannot justify our loving feelings. Shakespeare’s Bottom was right: “Reason and love keep little company together now-a-days.” Indeed, they keep none and they never kept any: there are no justifying reasons for love.
RETICULON-LIKE PROTEIN B2 is a proviral factor co-opted for the biogenesis of viral replication organelles in plants
Authors: Zhang Qianshen , Wen Zhiyan , Zhang Xin , She Jiajie , Wang Xiaoling , Gao Zongyu , Wang Ruiqi , Zhao Xiaofei , Su Zhen , Li Zhen , Li Dawei , Wang Xiaofeng , Zhang Yongliang
Published: May 2023

Endomembrane remodeling to form a viral replication complex (VRC) is crucial for a virus to establish infection in a host. Although the composition and function of VRCs have been intensively studied, host factors involved in the assembly of VRCs for plant RNA viruses have not been fully explored. TurboID-based proximity labeling (PL) has emerged as a robust tool for probing molecular interactions in planta. However, few studies have employed the TurboID-based PL technique for investigating plant virus replication. Here, we used Beet black scorch virus (BBSV), an endoplasmic reticulum (ER)–replicating virus, as a model and systematically investigated the composition of BBSV VRCs in Nicotiana benthamiana by fusing the TurboID enzyme to viral replication protein p23. Among the 185 identified p23-proximal proteins, the reticulon family of proteins showed high reproducibility in the mass spectrometry data sets. We focused on RETICULON-LIKE PROTEIN B2 (RTNLB2) and demonstrated its proviral functions in BBSV replication. We showed that RTNLB2 binds to p23, induces ER membrane curvature, and constricts ER tubules to facilitate the assembly of BBSV VRCs. Our comprehensive proximal interactome analysis of BBSV VRCs provides a resource for understanding plant viral replication and offers additional insights into the formation of membrane scaffolds for viral RNA synthesis.
Cucumber NUCLEAR FACTOR-YC2/-YC9 target translocon component CsTIC21 in chloroplast photomorphogenesis
Authors: Ke Xubo , Shen Junjun , Niu Yuqian , Zhao Hongjiao , Guo Yalu , Sun Piaoyun , Yang Tongwen , Jiang Yanxin , Zhao Bosi , Wang Zheng , Wu Tao , Wang Huasen , Li Zheng
Published: May 2023

Light signals promote photomorphogenesis and photosynthesis, allowing plants to establish photoautotrophic growth. Chloroplasts are organelles responsible for photosynthesis in which light energy is converted into chemical energy and stored as organic matter. However, how light regulates chloroplast photomorphogenesis remains unclear. Here, we isolated a cucumber (Cucumis sativus L.) mutant albino seedling (as) from an ethyl methane sulfonate mutagenesis library with an albino phenotype. Map-based cloning revealed that the mutation occurred in a component of cucumber translocon at the inner membrane of chloroplasts (CsTIC21). Subsequently, virus-induced gene silencing and CRISPR/Cas9 analyses confirmed the association between the mutant gene and the as phenotype. Loss-of-function of CsTIC21 induces malformation of chloroplast formation, leading to albinism and death in cucumber. Notably, CsTIC21 transcription was very low in etiolated seedlings grown in the dark and was upregulated by light, with expression patterns similar to those of Nuclear factor-YC (NF-YC) genes. Here, 7 cucumber NF-YC family genes (CsNF-YC) were identified, among which the expression of 4 genes (CsNF-YC1, -YC2, -YC9, and -YC13) responded to light. Gene silencing of all CsNF-YC genes in cucumber indicated that CsNF-YC2, -YC9, -YC11-1, and -YC11-2 induced distinct etiolated growth and decreased chlorophyll content. Interaction studies verified that CsNF-YC2 and CsNF-YC9 target the CsTIC21 promoter directly and promote gene transcription. These findings provide mechanistic insights on the role of the NF-YCs–TIC21 module in chloroplast photomorphogenesis promoted by light in cucumber.
Inflation and Individual Investors’ Behavior: Evidence from the German Hyperinflation
Authors: Braggion Fabio , von Meyerinck Felix , Schaub Nic
Published: May 2023

We analyze how individual investors respond to inflation. We introduce a unique data set containing information on local inflation and security portfolios of more than 2,000 clients of a German bank between 1920 and 1924, covering the German hyperinflation. We find that individual investors buy fewer (sell more) stocks when facing higher local inflation. This effect is more pronounced for less sophisticated investors. Moreover, we document a positive relation between local inflation and forgone returns following stock sales. Our findings are consistent with individual investors suffering from money illusion. Alternative explanations, such as consumption needs, are unlikely to drive our results.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis
Authors: Bredemeier Markus , Duarte Ângela L , Pinheiro Marcelo M , Kahlow Bárbara S , Macieira José C , Ranza Roberto , Miranda José R , Valim Valéria , de Castro Gláucio R , Bértolo Manoel B , Sauma Maria F , Fernandes Vander , Ribeiro Ana C , Teodoro Reginaldo B , Brenol Claiton V , Carvalho Hellen M , Studart Sâmia A , Pinheiro Geraldo R , da Rocha Laurindo F , de Lima Hugo D , Pereira Ivânio A , Gazzeta Morgana O , Kakehasi Adriana M , Louzada Paulo , Hayata André L , Lupo Cristiano M , da Silveira Inês G , Kowalski Sergio C , Titton David C , Chakr Rafael M , Ranzolin Aline , Xavier Ricardo M , Laurindo Ieda M
Published: May 2023

Objectives

To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi).

Methods

BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses.

Results

The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs.

Conclusion

Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.
Steady decrease in systemic sclerosis mortality rates at younger ages over the past five decades
Authors: Yen Eric Y , Singh Devanshu R , Singh Ram Raj
Published: May 2023

Objective

We aimed to assess SSc mortality by age in the general population over the past five decades.

Methods

This is a population-based study using a national mortality database and the census data for all US residents. We calculated the proportions of deaths for SSc and for all other causes (non-SSc) by age, and calculated age-standardized mortality rates (ASMRs) for SSc and non-SSc, and the ratio of SSc-ASMR to non-SSc-ASMR by age groups for each year from 1968 through 2015. We performed joinpoint regression to estimate the average annual percent change (AAPC) for each of these parameters.

Results

SSc was recorded as the underlying cause of death in 5457 decedents aged ≤44 years, 18 395 aged 45–64, and 22 946 aged ≥65 from 1968 through 2015. At ages ≤44, the proportion of annual deaths decreased more for SSc than for non-SSc: AAPC, –2.2% (95% CI, –2.4% to –2.0%) for SSc vs –1.5% (–1.9% to –1.1%) for non-SSc. Consistently, SSc-ASMR decreased from 1.0 (95% CI, 0.8–1.2) in 1968 to 0.4 (0.3–0.5) per million persons in 2015, a cumulative decrease of 60% at an AAPC of –1.9% (95% CI, –2.5% to –1.2%) at ages ≤44. The SSc-ASMR:non-SSc-ASMR ratio also decreased [cumulative –20%; AAPC –0.3% (95% CI, –1.15% to 0.55%)] in the ≤44-years group. In contrast, those aged ≥65 experienced a steep increase in the SSc-ASMR [cumulative 187.0%; AAPC 2.0% (95% CI, 1.8–2.2)] and the SSc-ASMR:non-SSc-ASMR ratio [cumulative 395.4%; AAPC 3.3% (95% CI, 2.9–3.7)].

Conclusion

Mortality for SSc has steadily decreased at younger ages over the past five decades.
Variation within major internal repeats of KSHV in vivo
Authors: Santiago Jan Clement , Westfall Dylan H , Adams Scott V , Okuku Fred , Phipps Warren , Mullins James I
Published: May 2023

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma (KS), yet the viral genetic factors that lead to the development of KS in KSHV-infected individuals have not been fully elucidated. Nearly, all previous analyses of KSHV genomic evolution and diversity have excluded the three major internal repeat regions: the two origins of lytic replication, internal repeats 1 and 2 (IR1 and IR2), and the latency-associated nuclear antigen (LANA) repeat domain (LANAr). These regions encode protein domains that are essential to the KSHV infection cycle but have been rarely sequenced due to their extended repetitive nature and high guanine and cytosine (GC) content. The limited data available suggest that their sequences and repeat lengths are more heterogeneous across individuals than in the remainder of the KSHV genome. To assess their diversity, the full-length IR1, IR2, and LANAr sequences, tagged with unique molecular identifiers (UMIs), were obtained by Pacific Biosciences’ single-molecule real-time sequencing (SMRT-UMI) from twenty-four tumors and six matching oral swabs from sixteen adults in Uganda with advanced KS. Intra-host single-nucleotide variation involved an average of 0.16 per cent of base positions in the repeat regions compared to a nearly identical average of 0.17 per cent of base positions in the remainder of the genome. Tandem repeat unit (TRU) counts varied by only one from the intra-host consensus in a majority of individuals. Including the TRU indels, the average intra-host pairwise identity was 98.3 per cent for IR1, 99.6 per cent for IR2 and 98.9 per cent for LANAr. More individuals had mismatches and variable TRU counts in IR1 (twelve/sixteen) than in IR2 (two/sixteen). There were no open reading frames in the Kaposin coding sequence inside IR2 in at least fifty-five of ninety-six sequences. In summary, the KSHV major internal repeats, like the rest of the genome in individuals with KS, have low diversity. IR1 was the most variable among the repeats, and no intact Kaposin reading frames were present in IR2 of the majority of genomes sampled.
Heart failure
Authors: Vuckovic Karen M. , Ryan Catherine , Gomez Yorman , Bierle Rebecca
Published: May 2023

Heart failure (HF) is a chronic syndrome that requires patients to manage signs and symptoms and adhere to a complex medication regimen. This article discusses updates in HF care related to a universal definition and new therapies, focusing on the four pillars of therapy for HF with reduced ejection fraction.
Autoregulatory Cerebral Perfusion Pressure Insults in Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: The Role of Insult Intensity and Duration on Clinical Outcome
Authors: Svedung Wettervik Teodor , Hånell Anders , Howells Timothy , Engström Elisabeth R. , Lewén Anders , Enblad Per
Published: May 2023

Background:

This single-center, retrospective study investigated the outcome effect of the combined intensity and duration of differences between actual cerebral perfusion pressure (CPP) and optimal cerebral perfusion pressure (CPPopt), and also for absolute CPP, in patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH).

Methods:

A total of 378 TBI and 432 aSAH patients treated in a neurointensive care unit between 2008 and 2018 with at least 24 hours of CPPopt data during the first 10 days following injury, and with 6-month (TBI) or 12-month (aSAH) extended Glasgow Outcome Scale (GOS-E) scores, were included in the study. ∆CPPopt-insults (∆CPPopt=actual CPP−CPPopt) and CPP-insults were visualized as 2-dimensional plots to highlight the combined effect of insult intensity (mm Hg) and duration (min) on patient outcome.

Results:

In TBI patients, a zone of ∆CPPopt ± 10 mm Hg was associated with more favorable outcome, with transitions towards unfavorable outcome above and below this zone. CPP in the range of 60 to 80 mm Hg was associated with higher GOS-E, whereas CPP outside this range was associated with lower GOS-E. In aSAH patients, there was no clear transition from higher to lower GOS-E for ∆CPPopt-insults; however, there was a transition from favorable to unfavorable outcome when CPP was <80 mm Hg.

Conclusions:

TBI patients with CPP close to CPPopt exhibited better clinical outcomes, and absolute CPP within the 60 to 80 mm Hg range was also associated with favorable outcome. In aSAH patients, there was no clear transition for ∆CPPopt-insults in relation to outcome, whereas generally high absolute CPP values were associated overall with favorable recovery.
Efficacy and Safety of Bruton Tyrosine Kinase Inhibitor Plus Anti-CD20 Antibody Therapy Compared With Chemoimmunotherapy as Front-line Treatment for Chronic Lymphocytic Leukemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Nguyen Thi Thuy , Thanh Nhu Nguyen , Tran Van Khoi , Van Cau Nguyen , Lin Chiou-Feng
Published: May 2023

Treatment with chemoimmunotherapy (CIT) is considered an appropriate front-line treatment option for chronic lymphocytic leukemia (CLL). However, outcomes remain suboptimal. Bruton tyrosine kinase inhibitor (BTKi) combined with anti-CD20 antibody is an effective treatment for treatment-naïve, relapsed/refractory CLL patients. A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of CIT versus BTKi + anti-CD20 antibody as front-line treatment for CLL patients. The endpoints of interest included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response (CR) rate, and safety. Four trials (including 1479 patients) were available as of December 2022 and fulfilled the eligibility criteria. BTKi + anti-CD20 antibody treatment significantly prolonged PFS [hazard ratio (HR), 0.25; 95% confidence interval (CI), 0.15–0.42] compared with CIT, while the combination therapy did not significantly improve OS compared with CIT (HR, 0.73; 95% CI, 0.50–1.06). We observed consistent benefits for PFS among patients with unfavorable features. Although pooled analysis indicated that the addition of BTKi to anti-CD20 antibody led to a higher ORR than CIT [risk ratio (RR), 1.16; 95% CI, 1.13–1.20], there was no difference in CR between the two arms (RR, 1.10; 95% CI, 0.27–4.55). The risk of grade ≥3 adverse effects (AE) was comparable between the two groups (RR, 1.04; 95% CI, 0.92–1.17). The BTKi + anti-CD20 antibody therapy has superior outcomes compared with CIT among patients with treatment-naïve CLL, without excess of toxicity. Future studies should compare next-generation targeted agent combinations versus CIT to determine the optimal management of CLL patients.
Ambient PM2.5 and acute incidence of myocardial infarction in China: a case-crossover study and health impact assessment
Authors: Ban Jie , Ma Runmei , Liu An , Wang Qing , Chen Chen , Sun Qinghua , Wang Yanwen , Hu Jianlin , Li Tiantian
Published: May 2023

Background and purpose:

Evidence investigating the association between ambient fine particulate matters (PM2.5) and acute incidence of myocardial infarction in developing countries is limited. This study aims to investigate linear and nonlinear patterns for the association between PM2.5 and acute incidence of myocardial infarction based on multicounty registry dataset and evaluate the reduction of premature myocardial infarction incidence under different pollution control objectives in China.

Methods:

Thirty-six thousand six hundred and seventy-nine registered myocardial infarction incidence cases from 15 Chinese counties from January 1, 2013, to December 31, 2017, were obtained. We adopted a time-stratified case-crossover design with conditional logistic regression models.

Results:

With a 10 μg/m3 increase in PM2.5 exposure, there was an increase of 0.98% (95% CI: 0.40%–1.57%) in acute incidence risk of myocardial infarction. The corresponding values for males and individuals aged over 74 years were 1.58% (95% CI: 0.82%–2.35%) and 1.19% (95% CI: 0.35%–2.05%) respectively, indicating higher risks than other groups. The nonlinear concentration–response curve indicated a steeper slope under daily exposure below 50 μg/m3 and the marginal avoided premature morbidity became larger under the current air quality standard.

Conclusions:

The robust findings from this study may suggest the necessity for a continuous reduction of PM2.5 exposure concentration from the perspectives of public health.
Fluorescence In Situ Hybridization as Diagnostic Tool for Implant-associated Infections: A Pilot Study on Added Value
Authors: Scheuermann-Poley Catharina , Wiessner Alexandra , Kikhney Judith , Gatzer Renate , Müller Martin , Stichling Marcus , Moter Annette , Willy Christian
Published: May 2023

Background:

Implant-associated infections are a devastating complication in surgery. Especially in infections with biofilm-forming microorganisms, the identification of the causing microorganism remains a challenge. However, the classification as biofilm is not possible with conventional polymerase chain reaction or culture-based diagnostics. The aim of this study was to evaluate the additional value of fluorescence in situ hybridization (FISH) and nucleic acid amplification technique (FISHseq) to discuss a diagnostic benefit of the culture-independent methods and to map spatial organization of pathogens and microbial biofilms in wounds.

Methods:

In total, 118 tissue samples from 60 patients with clinically suspected implant-associated infections (n = 32 joint replacements, n = 24 open reduction and internal fixation, n = 4 projectiles) were analyzed using classic microbiological culture and culture-independent FISH in combination with polymerase chain reaction and sequencing (FISHseq).

Results:

In 56 of 60 wounds, FISHseq achieved an added value. FISHseq confirmed the result of cultural microbiological examinations in 41 of the 60 wounds. In 12 wounds, one or more additional pathogens were detected by FISHseq. FISHseq could show that the bacteria initially detected by culture corresponded to a contamination in three wounds and could exclude that the identified commensal pathogens were a contamination in four other wounds. In five wounds, a nonplanktonic bacterial life form was detected.

Conclusions:

The study revealed that FISHseq gives additional diagnostic information, including therapy-relevant findings that were missed by culture. In addition, nonplanktonic bacterial life forms could also be detected with FISHseq, albeit less frequently than previously indicated.
Lateral Canthotomy Revisited: A Refined Surgical Approach for Orbital Access
Authors: Soliman Luke , Rhee Ben , Lerner Julia L. , Sobti Nikhil , Rao Vinay , Woo Albert S.
Published: May 2023

The transconjunctival incision is a common and effective approach for establishing surgical exposure to the orbital floor. When access to the lateral orbit is also required, this incision may be extended by an accompanying lateral canthotomy, which releases the tarsal plates from the conjunctiva. Although this approach broadens surgical access through a simple extension, it is often remarked for unpredictable healing patterns and negative aesthetic sequelae, such as rounding of the lateral canthal angle. Traditionally, lateral canthotomy is performed by a transverse incision through a natural skin crease of the lateral palpebral fissure. Herein, we discuss our experience with a less common approach to lateral canthotomy, in which only the inferior crus of the lateral canthal tendon is divided. This approach limits manipulation of delicate orbital anatomy and aims to minimize unsightly scarring while still affording excellent visualization of the lateral orbit and orbital floor.
The Impact of Prior Breast Augmentation on Breast Reconstruction after Mastectomy
Authors: Clegg Devin J. , Salomon Brett J. , Porter Christopher G. , Mazonas Thomas W. , Heidel Robert E. , Stephenson Stacy M. , Herbig Kathleen S. , Chun Joseph T. , Lloyd Jillian M. , Boukovalas Stefanos
Published: May 2023

Background:

The risk of women developing breast cancer after augmentation mammaplasty may be lower than the general population, with minimal current literature on breast reconstruction in this population. We sought to evaluate the impact of previous augmentation on postmastectomy breast reconstruction.

Methods:

Retrospective review of patients who underwent mastectomies from 2017 to 2021 at our institution was performed. Analysis included frequencies and percentages, descriptive statistics, chi-square analysis, and Fisher exact test.

Results:

Four hundred seventy patients were included, with average body mass index of 29.1 kg/m2, 96% identifying as White, and an average age at diagnosis of 59.3 years. Twenty (4.2%) patients had a prior breast augmentation. Reconstruction was performed in 80% of the previously augmented patients compared to 49.9% of nonaugmented patients (P = 0.01). Reconstruction was alloplastic in 100% of augmented and 88.7% of nonaugmented patients (P = 0.15). All reconstructed augmented patients underwent immediate reconstruction compared with 90.5% of nonaugmented patients (P = 0.37), and two-stage reconstruction was most common (75.0% versus 63.5%; P = 0.42). Of the previously augmented patients, 87.5% increased implant volume, 75% underwent same implant plane reconstruction, and 68.75% underwent same implant-type reconstruction as their augmentation.

Conclusions:

Previously augmented patients were more likely to undergo reconstruction after mastectomy at our institution. All reconstructed augmented patients underwent alloplastic reconstruction, with most performed immediately in staged fashion. Most patients favored silicone implants and maintained the same implant type and plane of reconstruction, with increased implant volume. Larger studies are required to further investigate these trends.
Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?
Authors: Yonkers Kimberly A. , Altemus Margaret , Gilstad-Hayden Kathryn , Kornstein Susan G. , Gueorguieva Ralitza
Published: May 2023

Purpose/Background

Daily treatment with sertraline improves functional impairment among individuals with premenstrual dysphoric disorder (PMDD). We do not know whether treatment initiated at symptom onset also improves functional impairment.

Methods/Procedures

This 3-site, double blind, randomized, clinical trial compared sertraline (25–100 mg) to similar appearing placebo, both administered at symptom onset, for reduction of PMDD symptoms. Ninety participants were allocated to sertraline and 94 participants to placebo. Functional outcomes from the Daily Ratings of the Severity of Problems included (1) reduced productivity or efficiency at work, school, home, or daily routine; (2) interference with hobbies or social activities; and (3) interference with relationships. Items were measured from 1 (no interference) to 6 (extreme interference) and averaged for the final 5 luteal phase days. This secondary analysis examined whether improvement in functional domains was greater for those allocated to sertraline compared with placebo. Second, we used causal mediation analyses to explore whether specific PMDD symptoms mediated functional improvement.

Results/Findings

Only relationship functioning improved significantly with active treatment between baseline and the end of the second cycle (active group mean [SD] change, −1.39 [1.38]; placebo group mean change, −0.76 [1.20]; β = −0.40; SE, 0.15; P = 0.009). The total effect of treatment on interference was −0.37 (95% confidence interval [CI], −0.66 to −0.09; P = 0.011). Given the nonsignificant direct effect (0.11; 95% CI, −0.07 to 0.29; P = 0.24) and significant indirect effect (−0.48; 95% CI, −0.71 to −0.24; P < 0.001), amelioration of anger/irritability likely mediated reductions in relationship interference.

Implications/Conclusions

That anger/irritability mediates impairments in relationship functioning has face validity but should be replicated in other data sets.

Trial Registration

ClinicalTrials.gov identifier NCT00536198.
Drain fluid biomarkers for the diagnosis of clinically relevant postoperative pancreatic fistula - a diagnostic accuracy systematic review and meta-analysis
Authors: Rykina-Tameeva Nadya , MacCulloch Daniel , Hipperson Luke , Ulyannikova Yulia , Samra Jaswinder S , Mittal Anubhav , Sahni Sumit
Published: May 2023

Background:

Pancreatectomy is the only curative treatment available for pancreatic cancer and a necessity for patients with challenging pancreatic pathology. To optimise outcomes, postsurgical complications such as clinically relevant postoperative pancreatic fistula (CR-POPF) should be minimised. Central to this is the ability to predict and diagnose CR-POPF, potentially through drain fluid biomarkers. This study aimed to assess the utility of drain fluid biomarkers for predicting CR-POPF by conducting a diagnostic test accuracy systematic review and meta-analysis.

Methods:

Five databases were searched for relevant and original papers published from January 2000 – December 2021, with citation chaining capturing additional studies. The QUADAS-2 tool was used to assess the risk of bias and concerns regarding applicability of the selected studies.

Results:

Seventy-eight papers were included in the meta-analysis, encompassing six drain biomarkers and 30758 patients with a CR-POPF prevalence of 17.42%. The pooled sensitivity and specificity for 15 cut-offs was determined. Potential triage tests (Negative Predictive Value>90%) were identified for the ruling-out of CR-POPF and included post-operative day 1 (POD1) drain amylase in pancreatoduodenectomy (PD) patients (300 U/L) and in mixed surgical cohorts (2500 U/L), POD3 drain amylase in PD patients (1000-1010 U/L) and drain lipase in mixed surgery groups (180 U/L). Notably, drain POD3 lipase had a higher sensitivity than POD3 amylase, while POD3 amylase had a higher specificity than POD1.

Conclusions:

The current findings using the pooled cut-offs will offer options for clinicians seeking to identify patients for quicker recovery. Improving the reporting of future diagnostic test studies will further clarify the diagnostic utility of drain fluid biomarkers, facilitating their inclusion in multi-variable risk-stratification models and the improvement of pancreatectomy outcomes.