bluuebunny/crossref_metadata_2025 huggingface dataset:
PSII-B-21 Development of an industry relevant graduate certificate for regulatory affairs in animal health
Authors: Larson Haley E , Adams Alison P , Stuteville Rebekkah
Published: October 2021

Seven years of data collection and industry collaboration identified a longstanding need from the animal health corridor for educational offerings focused on regulatory affairs for animal health products. The animal health corridor, anchored by Manhattan, Kansas and Columbia, Missouri, is home to more than 300 animal health companies, representing the largest concentration in the world. When surveying industry needs, Kansas State University received 446 responses from individuals in this area and found 40% indicated interest in “policy and regulations,” with 64% of interested respondents showing strong interest with programming at the graduate level. Meetings with industry representatives further confirmed results of the survey by highlighting a need for educational programming focused on animal health product license requirements with USDA, FDA, and EPA. At a roundtable with 22 Animal Health organizations, 64% of attendees had strong interest in a program focused on “regulatory aspects of drug and vaccine development in animal health.” In response to these findings, a graduate certificate was launched in 2019 encompassing regulatory development and management of animal health products. Curriculum was crafted in close collaboration with an industry advisory panel, because comparable academic models were not available. Interests to maintain industry contacts within the courses have led to integration of notable engagement techniques as the course format moves toward asynchronous delivery. Curriculum encompasses regulatory development of animal pharmaceuticals, pesticides, biologics, and diagnostics from pre- to post- licensure. The presentation will explain objectives of the certificate, data gathered regarding industry need, process of certificate design and curriculum co-creation with industry partners, and resulting curriculum. Additionally, since the new courses in the regulatory affairs certificate have been offered since spring 2020, the presentation will examine strategies for working with subject matter experts in the online classroom, plans for assessment of student learning, and educational background of enrolled students.
War and order: rethinking criminal accountability for the Iraq War
Authors: Grady Kate
Published: October 2021

Public calls for the criminal accountability of UK and US politicians for the 2003 Iraq war are part of the war’s legal legacies. This article questions whether criminal sanction can be a corrective to war by considering whether the relationship between the two might be understood as symbiotic.
The Union Occupation of Coastal North Carolina
Authors: Silkenat David
Published: October 2021

In 1861 and 1862, Union forces invaded and occupied eastern North Carolina. This chapter explores the origins, execution, and consequences of this invasion, looking at its military, social, and political significance. It highlights the weakness of Confederate fortifications along the North Carolina coast and the Union military leadership of Cmdr. Silas Stringham, Maj. Gen. Benjamin Butler, Brig. Gen. Ambrose Burnside, and Capt. Louis Goldsborough. As one of the first sites in the South occupied by the Union Army, coastal North Carolina created an early venue for wartime Reconstruction. The chapter emphasizes how African Americans responded to the Union invasion, escaping from slavery, forming refugee camps in Union enclaves, and working for the Union war effort. In 1862, Military Governor Edward Stanly tried to reinstitute slavery.
The Civil War in Arkansas, 1862
Authors: Cutrer Thomas W.
Published: October 2021

The Civil War in Arkansas in 1862 saw only two major battles, at Pea Pidge (or Elkhorn Tavern) and Prairie Grove, both of which were substantial Union victories. But of at least equal importance, the war in this sparsely populated, largely rural and impoverished region was characterized by deep and bitter divisions in loyalties of the states’ citizens, the marked indifference of the administration of Confederate Pres. Jefferson Davis in Richmond, and a notable lack of effective leadership and cooperation among the various Confederate generals. The result was the loss of the state to the Southern cause and the onset of brutal partisan warfare behind the lines between secessionist and Unionist neighbors.
Vicksburg and Port Hudson
Authors: Hess Earl J.
Published: October 2021

Two sieges of Confederate bastions on the Mississippi River resulted in the Union conquest of the Mississippi Valley in July 1863. The fall of Vicksburg deeply wounded Confederate Mississippi, fractured White support for the Southern cause, and cracked open slavery in the west central part of the state. Tens of thousands of Black refugees fled plantations for the Union Army, many joining newly created Black regiments that would occupy Union posts in the valley. The fall of Vicksburg eliminated the most powerful Confederate blockade to Northern commercial use of the Mississippi River and played a pivotal role in boosting Northern and depressing Southern war morale. Problems associated with Confederate repatriation of thirty thousand paroled soldiers contributed to the breakdown of the prisoner exchange system. The fall of Port Hudson, overshadowed by Vicksburg, nevertheless completed Union conquest of the valley and allowed Northern merchant vessels to steam to New Orleans once again. The emotional benefit of these twin victories was worth the physical effort in reducing both strongholds, emboldening the North and dispiriting the South.
The Battle of Helena, the Little Rock Campaign, and the Capture of Fort Smith, 1863
Authors: Moneyhon Carl H.
Published: October 2021

The Battle of Helena, the Little Rock Campaign, and the capture of Fort Smith led to Union control over the Arkansas River Valley and most of Arkansas to the north of the river. Militarily this resulted in impeding Confederate operations in Missouri, the establishment of a potential base of operations for Union campaigns in Texas, and easier logistical support for Union forces in Indian Territory. A major result of these movements was the emancipation of thousands of slaves. Politically they brought a restoration of a pro-Union government in Arkansas. The occupation of Little Rock produced renewed economic prosperity and, under the benevolent policies of Union Maj. Gen. Frederick Steele, a return of normal social activity among the civilian population, though producing privation and disruption of gender and age roles in the surrounding countryside.
The Tullahoma and Chickamauga Campaigns
Authors: Bledsoe Andrew S.
Published: October 2021

This chapter explores the origins, conduct, and consequences of the 1863 Tullahoma and Chickamauga campaigns, part of the Union strategy to capture the critical Confederate transportation hub at Chattanooga. These campaigns turned on the politics of command, with discord on both sides shaping events and the personalities of commanders Maj. Gen. William S. Rosecrans and Gen. Braxton Bragg playing important roles in the outcome of these conflicts. The campaigns also resulted in widespread disruption in Georgia, Alabama, and middle and east Tennessee as widespread foraging, food shortages, and a growing number of refugees and displaced persons felt its effects. Guerrillas ranged through the Tennessee River Valley, preying upon soldiers and civilians alike. Unionists in the region found themselves in complicated and painful situations as they negotiated the difficult environment of invasion and military occupation. Both sides also experienced significant defeats in these campaigns; the Confederates, who lost most of Tennessee during the Tullahoma Campaign, and the Union, losing at the Battle of Chickamauga. These issues of discord, disruption, and defeat also played out against the backdrops of emancipation and national political consequences bearing on the coming 1864 U.S. presidential election. As the chapter demonstrates, the consequences of these campaigns were important for the Union’s continuing effort to secure Chattanooga and carry the war deep into the Confederate heartland in 1864.
The Fall of Petersburg and Appomattox
Authors: Varon Elizabeth R.
Published: October 2021

Americans experienced the last months of the Civil War as uncertain and full of dramatic events that together finally spelled the Confederacy’s doom. The Union capitalized on its advantages in manpower and materiel, on the command harmony of Lt. Gen. Ulysses S. Grant and his team, and on the political momentum of President Abraham Lincoln’s emancipation policy to seize the prizes of Richmond and Petersburg and send the Confederate government and Gen. Robert E. Lee’s Army of Northern Virginia into flight. Confederates, confronting shortages of manpower and materiel, debated how to prolong the fight and clung to the hope that Lee’s army would win victories that breathed new life into the Confederate project. President Lincoln framed this last season of war as a moral reckoning with slavery and the moment to advance the work of reunion. The final campaigns were a watershed in the process of emancipation, as Lee’s surrender brought many slaves their de facto freedom.
Occupation, 1865–1877
Authors: Lang Andrew F.
Published: October 2021

Restoring the Union and securing emancipation after the Civil War depended on the U.S. Army. But the symbolism of standing military forces operating at the domestic vanguard of social and political change hampered the army’s ability to conduct a widespread occupation. The success of Reconstruction (1865–1877) depended on the army integrating itself in unprecedented ways in political affairs, social conditions, and economic markets to forge a new South stable enough never again to threaten the Union’s survival, but not too centralized to appear coercive. Ultimately, the very institution that reintegrated the formerly rebellious states into their proper federal orbit was also regarded by White Northerners and Southerners as an unstable threat to democratic self-determination. Hampered by a consistent and rapid demobilization, the army could not wield the tools necessary to prevent former Confederates from regaining political power and “redeeming” the South into an eerie image of its prewar self.
Globalizing the Americas Through Twentieth-Century Youth Organizations
Authors: Albarrán Elena Jackson
Published: October 2021

The twentieth century saw an unprecedented rise in youth culture in the Americas through the proliferation of organizations that channeled their energy into politically, culturally, and socially constructive activities. Many political leaders saw such organizations as strategic vehicles for nation-building, and official sponsorship of youth organizations burgeoned alongside the emergence of populist-style politics in the region that spanned the ideological spectrum. The relationship between national political projects and organized youth cultures can be traced in a rough chronological sweep through the region in four sections. These include nationalism and race expressed in cultures of the Boy Scouts and Girl Guides; neocolonial desires behind the pan-American youth exchanges of the Good Neighbor period; the ideological poles of populism in Peronist Argentina and Castro’s Cuba; and contestatory youth cultures in South American dictatorships during the late Cold War period. Over time and across countries, the intended state-sponsored political and social goals of organizing children and youth were often nuanced—if not completely undermined—by young people’s own plans as active members with goals of their own.
Airport Luxury Retail
Authors: Pinder Debbie , Roberts Joanne
Published: October 2021

The evolution of luxury retailing in the airport has followed the growth in air travel resulting from globalisation, the privatisation, and the deregulation of air transport and the rise of low-cost airlines. Airport luxury retailing serves a resilient global market and it is an important source of sales for luxury-brand companies. Moreover, luxury brands have recognised the commercial significance and public relations value of an international airport location where they deploy a sophisticated visual language to promote their global brand identity. The distribution of luxury goods in international airports through luxury-brand stores and multibrand duty-free outlets is investigated and consideration is given to the future of luxury in the airport.
Luxury Business
Authors: Donzé Pierre-Yves , Pouillard Véronique , Roberts Joanne
Published: October 2021

The high growth experienced by luxury companies during the last three decades has attracted the attention of a broad range of scholars from various academic disciplines, from history to management and critical studies. This chapter discusses their respective contributions for a better understanding of contemporary luxury business. Additionally, it offers new perspectives on the major global issues faced by this industry in the post-COVID pandemic era, namely, the globalisation of markets and dependency on China; income inequality, the democratisation of luxury, and authenticity; questions concerning production; sustainability; and the challenges to European dominance of the luxury industry.
Musical Informance
Authors: Headlam Dave
Published: October 2021

The information age has pushed music performance into the era of music informance, in which information and performance are combined in an integrated way. The types of presentation formats and analytical information found in public music theory are ideal for music informance, and present-day explorations of informance on the Internet have a history of noted musical informants including Leonard Bernstein and Glenn Gould. In order to continue to be relevant and to thrive in our connected world, live and recorded music scenarios need to develop ever more innovative ways to enhance music performance with information effectively presented in music informance.
The Panathenaia and Local Festivals
Authors: Shear Julia L.
Published: October 2021

Unlike the four Panhellenic festivals with their focus on what it meant to be Greek, regional and city celebrations and their competitions concentrated on more local concerns. At the Panathenaia at Athens, the Eretrian Artemisia at Amarynthos, and the Delia on Delos, how one participated in the competitions and other spectacles was crucial to the dynamics of the festival and the construction of its politics. In the case of the Panathenaia, the restrictions on participation kept the focus on Athenians and those closely associated with the city. The Artemisia concentrated on local issues, particularly in the years after 340 bce on recovering from civil strife, while the Delia functioned at the level of the region. Both the Artemisia and the Delia show how the politics of a celebration may change over time. These local festivals existed in tension between the needs of the sponsoring community and its relationships to other cities and region(s).
The Decline and Fall of Spectacle
Authors: Milliman Paul
Published: October 2021

This article analyses the decline and fall of most forms of Roman spectacle in Late Antiquity, as the empire contracted in some places and collapsed in others. It explores the evolution and development of various other spectacles—especially equestrian games like tournaments, hunting, and palii—in Rome’s medieval and early modern Latin, Byzantine, and Islamic successor societies, which shared many of the characteristics of ancient spectacle in terms of function if not necessarily form. It also examines the privatization of public spectacle and sites of spectacle in the Middle Ages, as well as the enduring impact of the images of Roman spectacle—especially those associated with the hippodrome in Constantinople—as expressions of political power in medieval and early modern Europe.
Naval Events and Aquacades
Authors: Taylor Rabun
Published: October 2021

Roman water spectacle took several forms. The literary sources favour bloody spectacles featuring condemned criminals and prisoners of war. In theatres or amphitheatres, the orchestra or arena might be flooded and convicts forced to play the parts of well-known mythic heroes facing mortal danger in some Greek tale with a ‘watery’ theme. Larger naval battle shows, called naumachiae, took place rarely, and almost exclusively at Rome, in specially designed basins. These pitted two teams in mortal naval combat, complete with custom-built ships and real weapons. Less commonly described, but frequently staged, was the hydromime—water pageantry taking numerous forms, such as synchronized swimming, mimed sketches of popular myths, and other kinds of light entertainment. There is little evidence that any form of Roman water spectacle had precursors in the Greek world, but the naumachia may bear a distant relationship to Athenian ephebic boating competitions first attested in the fourth century bce.
Coins
Authors: Elkins Nathan T.
Published: October 2021

The evidence provided by coins has not been systematically incorporated in studies of ancient sport and spectacle. Coins are a source material as important as other documentary and visual sources; arguably, they are potentially of even greater importance, since coins constitute a more complete visual record than any other surviving form of ancient art. Students of sport and spectacle that will benefit most from numismatics are those who grapple with questions about identity, perception, and political expediency in the ancient games. This contribution explores the different ways in which sport and spectacle were referred to on Greek and Roman coins. In the Greek world, city-states referred to festivals and athletics on their coins to announce their identities, whether through the depiction of Panhellenic festivals, local competitions, or the renowned athletes to which they were home. Even under Roman rule, coins of the Greek cities made reference to games in this way. In the Roman republic and empire, coin designs dealt more with the ideological agenda of the authority behind the production of coins (e.g., republican moneyer, late republican triumvir, or the emperor). As a result, depictions of games tended to reflect political expediency. For instance, some republican moneyers promised to hold games if elected to the aedileship and some emperors commemorated their sponsorship of and provisioning for games. Many coins that celebrated certain festivals or construction work on entertainment buildings may have been produced for special distributions, perhaps at the festivals or dedicatory games in question.
Pompeii and Games
Authors: Jacobelli Luciana
Published: October 2021

Pompeii represents a special lens for understanding urban games during the Roman period, with its preservation of the daily surroundings, monuments, and artefacts of performers, organizers, and fans, as well as the notices (edicta), graffiti, paintings, and objects that attest to the arrangements for and engagement with spectacles. Particularly important is the evidence for how Pompeii (and likely other small towns) differed from Rome: as to scale, the financial resources of local magistrates, obviously, could not compare to those of the emperor. Pompeiian graffiti indicate that deaths were few during fights and the architectural details of the amphitheatre point not to the participation of ferocious wild beasts, but rather local animals. The painted edicta suggest that the occasion and dates for spectacle did not coordinate with the most important festivals celebrated in Rome or in the main towns of Campania. Nevertheless, games held great importance even in a ‘minor’ urban context such as Pompeii, as evident in the popularity achieved by some magistrates for having organized munificent games, and in the spreading celebrity of performers, so deeply rooted in society today.
Too Much of a Good Thing
Authors: Dean-Jones Lesley
Published: October 2021

In classical Greece physicians were not in direct competition with gymnastics trainers. Both professions had expertise in the effects of exercise on the body, but their expertise dealt with different kinds of bodies and had different aims. Doctors used exercise to keep or return bodies to health; trainers developed bodies to perform certain types of exercise. In maintaining and inducing health, doctors were usually concerned simply to balance bodily constituents, but some advice on more vigorous exercise for individuals diagnosed with incipient illness illuminates ancient concepts on how the body could be improved by training for specific athletic events. Pursuing these techniques for too long, however, could lead to disease.
The Titer of Citrus Yellow Vein Clearing Virus Is Positively Associated with the Severity of Symptoms in Infected Citrus Seedlings
Authors: Bin Yu , Xu Jianjian , Duan Yu , Ma Zhimin , Zhang Qi , Wang Chunqing , Su Yue , Jiang Qiqi , Song Zhen , Zhou Changyong
Published: October 2021

Citrus yellow vein clearing virus (CYVCV), a new member of the genus Mandarivirus in the family Alphaflexiviridae, is the causal agent of citrus yellow vein clearing disease. CYVCV is transmitted to citrus by Dialeurodes citri, grafting, and contaminated knife blades, threatening citrus production. In this study, four infectious full-length complementary DNA clones of CYVCV (namely AY112, AY132, AY212, and AY221) derived from CYVCV isolate AY were obtained through yeast homologous recombination and inoculated to ‘Eureka’ lemon (Citrus limon Burm. f.) by Agrobacterium-mediated vacuum infiltration. Pathogenicity analysis indicated that the clones AY212 and AY221 caused more severe symptoms than AY112 and AY132. Northern blot and quantitative reverse transcription PCR analyses showed that the titers of virulent clones (AY212 and AY221) were significantly higher than those of attenuated clones (AY112 and AY132) in the infected ‘Eureka’ lemon seedlings. Subsequent comparative studies of viral infectivity, accumulation, and symptoms induced by AY221 in nine citrus cultivars indicated that the infectivity of AY221 varied from 25 to 100% between cultivars; ‘Oota’ ponkan (C. reticulata L.) showed the lowest infection rate, with mild symptoms, which might be a useful resource for CYVCY-resistance genes; and CYVCV titer was positively associated with the symptom development in infected citrus seedlings. In general, this report revealed the biological properties of CYVCV, thus laying a foundation for further investigation of pathogenic mechanisms in this virus.
Identification and Pathogenicity of Fungi Associated with Leaf Spot of Muskmelon in Eastern Shandong Province, China
Authors: Yu Xiaoyan , Zhang Jing , Zhang Xue , Yang Xilang , Xu Xi , Lin Jiaying , Bing Hui , Wang Xiangjing , Zhao Junwei , Xiang Wensheng
Published: October 2021

Leaf spot is a serious disease in the growth and development of muskmelon, which can affect its quality and yield. Over the past years, Malianzhuang Muskmelon Base, the main muskmelon producing area in Shandong Province, China, has been seriously affected by leaf spot. Since 2018, symptomatic leaves were collected from 11 production areas of this base to determine the pathogens of muskmelon foliar diseases. Two-hundred fungal strains were isolated and 10 genera and 17 species were identified based on morphological characteristics and multilocus phylogenetic analysis (ITS, GADPH, RPB2, HIS3, EF-1α, and LSU). The most frequently isolated species from each sampling area was Alternaria tenuissima with 77 strains, followed by A. alternata. Pathogenicity experiments showed that A. alternata, A. tenuissima, Fusarium neocosmosporiellum (formerly Neocosmospora vasinfecta), F. acuminatum, Exserohilum rostratum, Bipolaris sorokiniana, and Stagonosporopsis cucurbitacearum (formerly Didymella bryoniae) could cause symptoms highly similar to those of infected leaves observed under natural conditions in the field. Therefore, these fungal isolates are considered to be the primary pathogens causing muskmelon leaf spot, and A. tenuissima and A. alternata were the most common and virulent pathogens in this study. In addition, this is the first study of F. neocosmosporiellum, F. acuminatum, E. rostratum, and B. sorokiniana as pathogens associated to muskmelon leaf spot in China as well as the world.
Doctoral education for the nurse educator
Authors: Langevin Kerri M.
Published: October 2021

Which degree is for me?
Identifying the Factors that Affect Consistent Hearing Aid Use in Young Children With Early Identified Hearing Loss: A Scoping Review
Authors: Nailand Lisa , Munro Natalie , Purcell Alison
Published: October 2021

Objectives:

This study is a scoping review examining factors that affect consistent hearing aid use in young children with early identified hearing loss (HL).

Design:

Online databases were used to identify journal articles published between 2009 and 2019, yielding over 1800 citations. The citations were uploaded into an online software product called Covidence that enables scoping/systematic review management. After duplicates were removed, 857 articles were screened by abstract and title name, 93 of which were put through for full-text screening. Twenty-five articles met predetermined inclusion and exclusion criteria. Appraisal tools were utilized to establish the quality of the studies included. Numerical summaries were used to synthesize and describe the data set. Thematic analysis was utilized to identify global and subthemes within the data set.

Results:

Numerical summaries revealed that over half of the studies in the data set used a quantitative design. Thematic analysis of the data identified four global themes namely, “each child is an individual,” “parents are key,” “parents require support,” and “professionals make a difference.” Each global theme was further divided into subthemes, most of which centered around the parents of children with HL. Each subtheme was categorized as a malleable or a fixed factor that impacts on hearing aid use in young children with HL.

Conclusions:

This scoping review identified malleable and fixed factors that impact on hearing aid use in young children with HL. These factors centered around the individual characteristics of children with HL, the key responsibility their parents have, and the important contribution that professionals can make. Irrespective of whether factors are malleable or fixed, parents and professionals working with children with HL can have a positive impact on hearing aid use. This is likely to have a flow on, positive impact on their overall communication and learning outcomes.
The risk of stroke after acute myocardial infarction in patients with and without atrial fibrillation: A nationwide cohort study
Authors: Chiang Cheng-Hung , Hung Wan-Ting , Huang Wei-Chun , Jheng Ying-Chun , Lai Wei-Yi , Lin Yi-Ying , Lin Tzu-Wei , Lin Kun-Chang , Cheng Chin-Chang , Kuo Feng-Yu
Published: October 2021

Background:

Acute myocardial infarction (AMI) and atrial fibrillation (AF) are risk factors for stroke. The risk of stroke after AMI may differ between patients with and without AF. The aim of this study was to evaluate the impact of AF on stroke in patients after the first AMI.

Methods:

This was a retrospective, nationwide cohort study. Patients with a primary diagnosis of a first AMI between 2000 and 2012 were included. All patients were followed up until ischemic stroke or transient ischemic attack (TIA), or December 31, 2012, whichever occurred first. Kaplan–Meier cumulative survival curves were constructed to compare ischemic stroke or TIA between AMI patients with and without AF.

Results:

A total of 170 472 patients were enrolled in this study. Among them, 8530 patients with AF were identified. The propensity score matching technique was used to match 8530 patients without AF of similar ages and sexes. Overall, the 12-year stroke rate was significantly higher in patients with AF than in those without AF (log-rank p < 0.001), including different sexes, ages, and interventional therapy subgroups. Patients with pre-existing AF had higher stroke rates than those with newly diagnosed AF in male sex, age below 65 years, and those receiving interventional therapy subgroups. In Cox proportional-hazard regression analysis, AF was an independent risk factor for stroke after the first AMI (hazard ratio, 1.67; 95% CI: 1.5-1.87).

Conclusion:

AF significantly increases stroke risk after the first AMI. In patients with AF, those with pre-existing AF have higher stroke risks in male sex, age below 65 years, and those with interventional therapy than those with newly diagnosed AF.
Single pulley double-strand anchor suture fixation of the coronoid process in terrible triad of the elbow injury
Authors: Lin Kai-Cheng , Lai Wei-Yi , Yang Yi-Ping , Lin Yi-Yin , Lin Tzu-Wei , Wang Chia-Lin , Tai Hsiao-Yun , Tsai Fu-Ting , Tsai Yi-Ching , Tarng Yih-Wen
Published: October 2021

Background:

Terrible triad of the elbow injury is difficult to manage, and the role of the coronoid process in instability is very important. We describe a simple, modified suture technique to fix a coronoid process fragment using suture anchor fixation.

Methods:

Eight patients (three female and five male) with coronoid process injuries with the fragment involving <50% of the total height (Regan-Morrey type I/II) in terrible triad of elbow injury were included. Patients were treated operatively via a lateral Kocher’s approach, and coronoid process fractures were repaired with a single pulley double-strand suture technique. Structures were addressed in a sequential fashion—the coronoid process, radial head, lateral ulnar collateral ligament.

Results:

All patients were treated with the single pulley double-strand anchor suture technique and the coronoid process fragment was found to be in good contact with the original avulsion site using the method. The final Mayo Elbow Performance Score was excellent (> 90) in six patients and good (between 85 and 89) in two patients after operation 6 months.

Conclusion:

The single pulley double-strand suture tie method using a suture anchor is a less invasive and simpler fixation method for the repair of coronoid process fractures in patients with terrible triad of the elbow injuries and results in good outcomes.
Metastasis Suppressor Genes in Pancreatic Cancer
Authors: Bhattacharya Arnav , Santhoshkumar Anirudh , Kurahara Hiroshi , Harihar Sitaram
Published: October 2021

Pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC), has for long remained a deadly form of cancer characterized by high mortality rates resulting from metastasis to multiple organs. Several factors, including the late manifestation of the disease, partly amplified by lack of efficient screening methods, have hampered the drive to design an effective therapeutic strategy to treat this deadly cancer. Understanding the biology of PDAC progression and identifying critical genes regulating these processes are essential to overcome the barriers toward effective treatment. Metastasis suppressor genes have been shown to inhibit multiple steps in the metastatic cascade without affecting primary tumor formation and are considered to hold promise for treating metastatic cancers. In this review, we catalog the bona fide metastasis suppressor genes reported in PDAC and discuss their known mechanism of action.
Decellularized Matrix Bioscaffolds
Authors: Hashemi Javad , Barati Ghasem , Bibak Bahram
Published: October 2021

Type 1 diabetes is an autoimmune disease, and its incidence is usually estimated in the range of 5% to 10%. Currently, the administration of exogenous insulin is the standard of care therapy. However, this therapy is not effective in some patients who may develop some chronic complications. Islet transplantation into the liver is another therapy with promising outcomes; however, the long-term efficacy of this therapeutic option is limited to a small number of patients. Because native extracellular matrix (ECM) components provide a suitable microenvironment for islet functions, engineering a 3-dimensional construct that recapitulates the native pancreatic environment could address these obstacles. Many attempts have been conducted to mimic an in vivo microenvironment to increase the survival of islets or islet-like clusters. With the advent of decellularization technology, it is possible to use a native ECM in organ engineering. Pancreatic decellularized bioscaffold provides proper cell-cell and cell-ECM interactions and retains growth factors that are critical in the determination of cell fate within a native organ. This review summarizes the current knowledge of decellularized matrix technology and addresses its possible limitations before use in the clinic.
Xanthogranulomatous Pancreatitis Accompanied by Xanthogranulomatous Cholecystitis
Authors: Imokawa Tomoki , Ito Kyoji , Takemura Nobuyuki , Inagaki Fuyuki , Mihara Fuminori , Kokudo Norihiro
Published: October 2021

Xanthogranulomatous pancreatitis (XGP) is extremely rare, with only 31 cases reported in the English literature to date. We reviewed previously reported 17 articles about XGP and report an additional case of XGP. This is the first case of XGP with xanthogranulomatous cholecystitis accompanied by intraductal papillary mucinous carcinoma (IPMC) in an 80-year-old woman. She was referred to our hospital with jaundice and general malaise and was found to have a cystic mass at the pancreatic head and a solid mass at the pancreatic tail, with dilation of both the main pancreatic duct and biliary tract noted on computed tomography. Diagnosis of IPMC at the pancreatic head with neuroendocrine tumor at the pancreatic tail was made, and the patient underwent subtotal stomach-preserving pancreatoduodenectomy with enucleation of the mass at the tail. Pathological examination revealed IPMC with xanthogranulomatous changes around the IPMC and at the pancreatic tail and gallbladder. Xanthogranulomatous pancreatitis could be induced by inflammatory reaction due to obstruction of the pancreatic duct and biliary tract by mucin produced in the IPMC. It is sometimes difficult to preoperatively differentiate XGP from malignant pancreatic tumors, such as pancreatic carcinoma or neuroendocrine tumor, using imaging studies.
Female Genital Mutilation: Treatment Updates and the Need for Education
Authors: Easwaran Lavanya , Eidelson Sarah A. , Jain Anika , Akaniru Obianuju , Rattan Rishi , Thaller Seth
Published: October 2021

Introduction:

Female genital mutilation/cutting (FGM/C) refers to ritual surgical procedures performed that intentionally alter genitalia for nonmedical purposes. Female genital mutilation/ cutting is a lifelong problem for women that can have detrimental effects on menstruation, pregnancy, sexual health, and self-esteem. In 2016 the Centers for Disease Control and Prevention estimated 513,000 women and children in the United States were victims of or at risk for FGM/C. Currently, few studies discuss potential management options for FGM/C and their associated complications. Aims of this study are to review contemporary research on FGM/C, discuss current surgical therapies in the pediatric and adult populations, and draw attention to the urgent need for further education.

Methods:

The authors conducted a literature review using PubMed, and identified 731 articles in the adult and pediatric populations. The articles were cross-referenced with 2 systematic reviews, and duplicates were discarded. Based on our criteria, 9 articles were included.

Results:

Based on our findings, defibulation offers patients a better quality of life with a low rate of complication. Similarly, clitoral reconstruction has shown favorable results for treatment of FGM/C. Using the Female Sexual Function Index can better help standardize measurements of sexual health outcomes. Currently, established clinical guidelines are lacking and there is limited training on the recognition and treatment of FGM/C.

Conclusions:

This study supports clitoral reconstruction and defibulation as effective therapies for FGM/C. Reconstructive surgeons are at the forefront of developing and providing these surgical treatments. Further research including randomized controlled studies and long-term follow-up are needed to better elucidate the best therapeutic options.
Subglossopalatal Membrane With Associated Cleft Palate, Cardiovascular, and Neurologic Anomalies
Authors: Engel Ricardo , Greenberg Yitzchok , Rozzelle Arlene
Published: October 2021

Subglossopalatal membrane (or subglossopalatal synechia) is a rare clinical entity that can lead to respiratory distress and feeding difficulty due to oral obstruction. Here, the authors present a case of subglossopalatal membrane with associated cleft palate and cardiovascular and neurologic anomalies that was treated with surgical excision and lip-tongue adhesion. Etiology of these membranes is believed to be intrauterine fetal insult. Membranes should be treated with excision, whereas taking care to ensure patency of the airway. Presence of a subglossopalatal membrane should prompt thorough examination for additional congenital anomalies.
Sevoflurane modulation of tetrodotoxin-resistant Na+ channels in small-sized dorsal root ganglion neurons of rats
Authors: Kim Gimin , Nakamura Michiko , Cho Jin-Hwa , Nam Soonhyeun , Jang Il-Sung
Published: October 2021

Objective

Volatile anesthetics are widely used for general anesthesia during surgical operations. Voltage-gated Na+ channels expressed in central neurons are major targets for volatile anesthetics; but it is unclear whether these drugs modulate native tetrodotoxin-resistant (TTX-R) Na+ channels, which are involved in the development and maintenance of inflammatory pain.

Methods

In this study, we examined the effects of sevoflurane on TTX-R Na+ currents (INa) in acutely isolated rat dorsal root ganglion neurons, using a whole-cell patch-clamp technique.

Results

Sevoflurane slightly potentiated the peak amplitude of transient TTX-R INa but more potently inhibited slow voltage-ramp-induced persistent INa in a concentration-dependent manner. Sevoflurane (0.86 ± 0.02 mM) (1) slightly shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) reduced the extent of use-dependent inhibition of Na+ channels, (3) accelerated the onset of inactivation and (4) delayed the recovery from inactivation of TTX-R Na+ channels. Thus, sevoflurane has diverse effects on TTX-R Na+ channels expressed in nociceptive neurons.

Conclusions

The present results suggest that the inhibition of persistent INa and the modulation of the voltage dependence and inactivation might be, at least in part, responsible for the analgesic effects elicited by sevoflurane.
Anticipatory regulation of cardiovascular system on emergence of auditory-motor interaction in young infants
Authors: Shinya Yuta , Oku Kensuke , Watanabe Hama , Taga Gentaro , Fujii Shinya
Published: October 2021

Humans develop auditory-motor interaction to produce a variety of rhythmic sounds using body movements, which are often produced and amplified with tools, such as drumming. The extended production of sounds allows us to express a wide range of emotions, accompanied by physiological changes. According to previous studies, even young infants enhance movements in response to auditory feedback. However, their exhibition of physiological adaptation on emergence of auditory-motor interaction is unclear. We investigated the movement and cardiac changes associated with auditory feedback to spontaneous limb movements in 3-month-old infants. The results showed that infants increased the frequency of limb movements inducing auditory feedback, while they exhibited the more regular rhythm of the limb movements. Furthermore, heart rate increase associated with the limb movement was first inhibited immediately after the timing of the auditory feedback, which may reflect sustained attention to the auditory stimuli. Then, through auditory-motor experience, the heart rate increase was inhibited even prior to the auditory feedback, leading to suppression on the peak intensity of the heart rate increase. These findings suggest that young infants regulate the cardiovascular system as well as limb movements in anticipation of the auditory feedback. The anticipatory regulation associated with movement and attentional changes may contribute to reduced cardiovascular stress in auditory-motor interaction, and provide a developmental basis for more sophisticated goal-directed behavior of producing rhythmic sounds.
Role of the reaction-structure coupling in temperature compensation of the KaiABC circadian rhythm
Authors: Sasai Masaki
Published: October 2021

When the mixture solution of cyanobacterial proteins, KaiA, KaiB, and KaiC, is incubated with ATP in vitro, the phosphorylation level of KaiC shows stable oscillations with the temperature-compensated circadian period. Elucidating this temperature compensation is essential for understanding the KaiABC circadian clock, but its mechanism has remained a mystery. We analyzed the KaiABC temperature compensation by developing a theoretical model describing the feedback relations among reactions and structural transitions in the KaiC molecule. The model showed that the reduced structural cooperativity should weaken the negative feedback coupling among reactions and structural transitions, which enlarges the oscillation amplitude and period, explaining the observed significant period extension upon single amino-acid residue substitution. We propose that an increase in thermal fluctuations similarly attenuates the reaction-structure feedback, explaining the temperature compensation in the KaiABC clock. The model explained the experimentally observed responses of the oscillation phase to the temperature shift or the ADP-concentration change and suggested that the ATPase reactions in the CI domain of KaiC affect the period depending on how the reaction rates are modulated. The KaiABC clock provides a unique opportunity to analyze how the reaction-structure coupling regulates the system-level synchronized oscillations of molecules.

Author summary

The reconstituted KaiABC circadian clock provides a unique opportunity to analyze how the effects of chemical and structural features of individual molecules determine the system-level oscillations of many molecules. By modeling the coupling of chemical reactions and structural transitions in the KaiC molecule, we showed that reducing the coupling strength enlarges the oscillation amplitude and period, explaining the observed striking change of the period length upon single-residue substitution in KaiC. We propose that thermal fluctuations attenuate the reaction-structure coupling similarly to the residue substitution, explaining the stable temperature compensation observed in the KaiABC clock. The combined experimental and theoretical analyses should open a way to develop techniques to design the system-level molecular oscillations, further providing a basis for understanding circadian clocks in vivo.
Intermanual transfer of visuomotor learning is facilitated by a cognitive strategy
Authors: De Havas Jack , Haggard Patrick , Gomi Hiroaki , Bestmann Sven , Ikegaya Yuji , Hagura Nobuhiro
Published: October 2021

Humans continuously adapt their movement to a novel environment by recalibrating their sensorimotor system. Recent evidence, however, shows that explicit planning to compensate for external changes, i.e. a cognitive strategy, can also aid performance. If such a strategy is indeed planned in external space, it should improve performance in an effector independent manner. We tested this hypothesis by examining whether promoting a cognitive strategy during a visual-force adaptation task performed in one hand can facilitate learning for the opposite hand. Participants rapidly adjusted the height of visual bar on screen to a target level by isometrically exerting force on a handle using their right hand. Visuomotor gain increased during the task and participants learned the increased gain. Visual feedback was continuously provided for one group, while for another group only the endpoint of the force trajectory was presented. The latter has been reported to promote cognitive strategy use. We found that endpoint feedback produced stronger intermanual transfer of learning and slower response times than continuous feedback. In a separate experiment, we confirmed that the aftereffect is indeed reduced when only endpoint feedback is provided, a finding that has been consistently observed when cognitive strategies are used. The results suggest that intermanual transfer can be facilitated by a cognitive strategy. This indicates that the behavioral observation of intermanual transfer can be achieved either by forming an effector-independent motor representation, or by sharing an effector-independent cognitive strategy between the hands.

New and noteworthy

The causes and consequences of cognitive strategy use for motor learning are poorly understood. We tested whether a visuomotor task learned using a strategy generalizes across effectors. Visual feedback was manipulated to enhance the use of a cognitive strategy. Learning using a cognitive strategy for one hand transferred to the task performed by the un-learned hand. Our result suggests that intermanual transfer can also result from a common cognitive strategy used to control both hands.
Functional single cell selection and annotated profiling of dynamically changing cancer cells
Authors: You Li , Su Pin-Rui , Betjes Max , Rad Reza Ghadiri , Beerens Cecile , van Oosten Eva , Leufkens Felix , Gasecka Paulina , Muraro Mauro , van Tol Ruud , Chou Ting-Chun , van Steenderen Debby , Farooq Shazia , Hardillo Jose Angelito U. , de Jong Robert Baatenburg , Brinks Daan , Chien Miao-Ping
Published: October 2021

A method connecting single cell genomic or transcriptomic profiles to functional cellular characteristics, in particular time-varying phenotypic changes, would be transformative for single cell and cancer biology. Here, we present fSCS: functional single cell selection. This technology combines a custom-built ultrawide field-of-view optical screening microscope, fast automated image analysis and a new photolabeling method, phototagging, using a newly synthesized visible-light-photoactivatable dye. Using fSCS, we screen, selectively photolabel and isolate cells of interest from large heterogeneous populations based on functional dynamics like fast migration, morphological variation, small molecule uptake or cell division. We combined fSCS with single cell RNA sequencing for functionally annotated transcriptomic profiling of fast migrating and spindle-shaped MCF10A cells with or without TGFβ induction. We identified critical genes and pathways driving aggressive migration as well as mesenchymal-like morphology that could not be detected with state-of-the-art single cell transcriptomic analysis. fSCS provides a crucial upstream selection paradigm for single cell sequencing independent of biomarkers, allows enrichment of rare cells and can facilitate the identification and understanding of molecular mechanisms underlying functional phenotypes.