bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial
Authors: Cao Junning , Guo Hongqian , Ji Dongmei , Shen Weina , Zhang Shun , Hsieh Chih-Yi , Xiong Cai Sui , Edward Tian Ye , Xu Cong , Zhang Pin , Xu Binghe
Published: June 2023

Background

Senaparib, a novel poly(ADP-ribose) polymerase 1/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors.

Patients and Methods

Adults with advanced solid tumors who had failed ³1 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with ≥1 objective response and one dose higher, as well as those at the MTD/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and/or RP2D of senaparib.

Results

Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10/44) overall (all partial responses) and 26.9% (n=7/26) for patients harboring BRCA1/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively.

Conclusions

Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD.

ClinicalTrials.gov Identifier

NCT03508011
Bluegrass as Folk Music in the Czech Republic
Authors: Bidgood Lee
Published: June 2023

Since the mid-1950s Czech Americanists have sought out the country music subgenre of bluegrass, reformulating and performing it as a part of “folk-spectrum music,” a constellation of sounds and practices that does not always fit within the boundaries of folkloric or popular music. Attending to Czech bluegrass sheds light on the evolving post-socialist landscape and provides new perspectives on folk-related music making in Czech and central-eastern European contexts. As in the United States and elsewhere, bluegrass has become a means for mediating tensions and paradoxes that arise between ideas of “folk,” “traditional,” and “popular” music. This chapter presents ways that Czechs have adapted the practices and repertories of bluegrass-related music in dialogue with folk and folkloric music so that they all have appeal and functionality as a part of local and regional contexts.
Marriage and Wedding Traditions among the Cortorar Roma in Romania
Authors: Tesăr Cătălina
Published: June 2023

This chapter gives an ethnographic account of marital practices and their ceremonial manifestations among the Romani population of Cortorari living in central Romania, Transylvania. Marriage-making is central both to the fulfillment of gendered personhood and to the definition of Cortorari as a collective. The public enactment of marriages in agreements, contracts, and weddings communicates the moral and social order of the community. (Grand)Parents arrange the marriages of their offspring, the process of which unfolds as follows: the bride is removed from her parental house; is relocated into the groom’s parents’ house; produces offspring, compulsorily a boy; and is incorporated into the marital family, who should receive a dowry. Yet such an achievement is fraught with difficulties, and marital ties are fragile and continuously under threat of unraveling. To offset the tendency toward dissolution, Cortorari place at the center of their marriages ancient chalices inherited from their forebears and passed along male lines.
India’s Approach to Nuclear Security
Authors: Rajagopalan Rajeswari Pillai
Published: June 2023

The chapter provides an analytical overview of India’s approach to nuclear security. It details the legal and institutional steps India has taken to strengthen its nuclear security credentials, while capturing some of the internal political debates that provide an Indian perspective on nuclear security. The chapter also focuses on the logic for India’s nuclear security policy by examining the country’s growing atomic energy sector as well as the changing threat environment. While this chapter does not provide a fully comprehensive narrative of India’s nuclear security approach, it does discuss some of the challenging aspects, such as nuclear and radiological material control and accounting systems, security culture, the insider threat, and nuclear regulation. The chapter’s concluding section identifies areas that India needs to strengthen further in order to improve nuclear security measures as well as external perceptions of India’s nuclear security policy.
Conversion of a Research Reactor from HEU to LEU in Nigeria
Authors: Adamu Hamisu A. , Jonah Sunday A.
Published: June 2023

The Nigeria Research Reactor-1 (NIRR-1) is the first nuclear research reactor in the country. It was acquired as a training and educational tool for the development of a future nuclear energy programme in Nigeria. The project to build the reactor was initiated in 1996 under a tripartite agreement between China, Nigeria, and the International Atomic Energy Agency (IAEA) via a project and supply agreement (PSA). NIRR-1, a miniature neutron source reactor (MNSR) developed in China, was commissioned in 2004 with a highly enriched uranium (HEU) core. However, due to increased global security concerns over the threat of nuclear terrorism and increased insecurity in Nigeria, steps were subsequently taken to convert from the reactor to run on low enriched uranium (LEU), through a partnership with the IAEA and other countries. The conversion of NIRR-1 has denied non-state actors potential access to weapons-grade uranium, enhancing nuclear security in Nigeria and globally through permanent threat reduction.
State Sponsorship of Nuclear Terrorism
Authors: Ackerman Gary A. , Early Bryan R.
Published: June 2023

What constitutes state-sponsored nuclear terrorism and what security threat does it pose? There are two very different categories of nuclear terrorism: that involving the detonation of nuclear weapons, and that involving attacks against nuclear facilities. The first type of nuclear terrorism has received the greatest amount of attention, involving governments providing terrorists with military-grade nuclear weapons or the fissile material for use in improvised nuclear devices (INDs). The second category of state-sponsored nuclear terrorism involves providing aid for physical or cyber-attacks against nuclear infrastructure. The chapter compares the characteristics of these four different types of state-sponsored nuclear terrorism and reveals that aiding terrorist cyber-attacks against nuclear facilities is the most likely form of state-sponsored nuclear terrorism to occur. The chapter’s conclusion discusses the implications for nuclear security policy.
The Right to Health
Authors: Yamin Alicia Ely , Boghosian Tara
Published: June 2023

This chapter underscores the inextricable connections between democratic governance and population health, which is often treated as a purely technical matter to be determined by clinical expertise and health economists. First, the chapter sets out some of the implications of conceptualizing health as a right, arguing that defining the progressive realization of the right to health requires putting into place choice situations, which evolve and necessitate trade-offs. Second, the chapter outlines the actions that governments and other actors are obligated to undertake to respect, protect, and fulfill the right to health in terms of laws, policies, and institutional practices. The chapter focuses in particular on health systems, as institutional arrangements are too often neglected in discussions of health rights. The chapter argues that a right to health requires (1) sufficient pooled funding, (2) democratically justified priority-setting to define the contours of legal entitlements, (3) an organization of the health system that does not lead to inadvertent discrimination, and (4) the imperative of adequate information not just relating specifically to health procedures but to health-related decision-making more broadly. The last part of the chapter addresses the need to go beyond the nation-state in today’s globalized world, where both people and determinants of health are clearly not contained within borders.
AI Governance
Authors: Dafoe Allan
Published: June 2023

Artificial intelligence (AI) will be a transformative technology, with extreme potential risks and benefits. AI governance refers to the norms and institutions shaping how AI is built and deployed, as well as the policy and research efforts to make it go well. This chapter argues that the field of AI governance should have an expansive and ambitious scope, commensurate to the challenges, with robust internal collaboration given transferable lessons and shared policy opportunities. To make sense of the impacts of AI, the chapter offers three theoretical lenses, focusing on distinct mechanisms, impacts, and challenges. These lenses regard AI as a general purpose technology, an information technology, and an intelligence technology. The chapter then provides a lens on governance focusing on institutional fit and adaptation to the externalities produced by AI. Institutional adaptation will be especially difficult when a governance issue touches on deep social conflicts. Great power security competition poses a particular challenge because it can induce extreme—even existential—risks and is among the hardest dynamics to govern. Building strong competent global institutions to govern powerful AI would be a historically unparalleled challenge, but ultimately may be required to steer away from the greatest risks inherent to great power competition.
Electoral Malfeasance in Historical Political Economy
Authors: Mares Isabela
Published: June 2023

During the period between 1870 and 1914, many electoral democracies adopted reforms that reduced various forms of electoral malfeasance. Some reforms imposed harsher punishment for bribery or the politicization of state resources during campaigns. Others improved electoral secrecy, providing better protection of voters’ autonomy. This chapter draws on recent research in historical political economy (HPE) that has examined the adoption of these electoral reforms. The chapter discusses the limitations of modernization and redistributivist approaches to democratization in explaining the adoption of these reforms. By highlighting the consequences of elite splits, one can account for the formation of encompassing majorities that support the reduction of electoral malfeasance.
Land in Violent Conflict Studies
Authors: Grajales Jacobo , Chauveau Jean-Pierre
Published: June 2023

Numerous civil wars are linked to land conflicts and grievances, even if this link cannot be reduced to a simple causal relationship. This chapter outlines some connections between land and violent conflicts, highlighting three forms of interconnection. First, it describes how land tensions play a role in the emergence and escalation of violent conflict. Second, it examines how land property relations are fashioned and transformed by the effects of violence. Third, it presents some of the conflict-resolution techniques that have been elaborated in response to land-related violence. The chapter takes a decisive step away from the dominant approaches embraced by development practitioners and aid agencies, which tend to think in terms of transitional sequences that shift directly away from war toward “postconflict.” It argues instead for a better appreciation of the connections between lengthy transformations in the political economy of land and shorter-term variations in the intensity of violence.
Brain Stimulation and the NUMERICAL Brain
Authors: Cappelletti Marinella , Saccani Maria Silvia
Published: June 2023

Here we review the contribution of brain stimulation studies to the understanding of number and arithmetic processes. We show that these studies have significantly contributed to detail the architecture of numerical processing and its critical relation with brain regions such as the parietal and the frontal areas. We also present studies that aimed to boost number and arithmetic learning combining brain stimulation and training in healthy adults. These indicate that stimulation of suitable brain areas may induce long-term changes when coupled with an appropriate training regime. We claim that despite this progress, some of the findings thus far are still relatively heterogeneous, and that studies focusing on atypical and developing populations, such as people with dyscalculia, are currently scarce. Ultimately therefore, this promising progress indicates the need of future detailed and well-controlled investigations to fully benefit from the use of brain stimulation, also combined with training.
NATO
Authors: Grant Thomas D.
Published: June 2023

Since its founding in 1949, the North Atlantic Treaty Organization (NATO) has served as the principal security organization of the Euro-Atlantic world. A well-remarked difference between the post-World War I settlement and that which followed World War II was that the latter involved the US in a lasting commitment to European security; the former had not. NATO became the legal framework in which that commitment was formalized and implemented. NATO’s role in Europe long has occasioned assessment of its military-political aspect. NATO’s contributions to international law in Europe also merit assessment. NATO, by its very presence in Europe, has facilitated the settlement of legal disputes. Though less remarked upon than the European Union’s role in this regard, NATO also has served as a guarantor of shared democratic values and rule of law.
Cultural Evolution and Diet
Authors: Walker Catherine , Thomas Mark G.
Published: June 2023

Diet and culture are probably the two most central and entangled sub-plots in the story of human evolution. Most if not all of the major cultural transitions over the last 3 million years had large impacts on diet, and even today, some of the strongest signatures of natural selection in our genomes are linked to dietary change. Failure to adapt to shifts in diet over the past 10,000 years has been implicated in a number of chronic and complex diseases, the so-called ‘diseases of modernity’ including coronary heart disease, type II diabetes, obesity, and some cancers. The complex relationships between diet, biology, and culture originate from the earliest stone tool use, if not earlier, and have played key roles in the evolution of many human characteristics, including large brains, reduced gut size, high aerobic capacity, and tool use. Today, food ways and cuisines have strong cultural, ethnic, and geographic associations, and, in some populations, correlate with known biological adaptations. In this chapter we discuss the relationship between diet, culture, and biology through the major Palaeolithic and Neolithic transitions, and how culture and diet—and sometimes our biology—have remained entwined over the past 3 million years and into the present day.
Experimental expansion of relative telencephalon size improves the main executive function abilities in guppy
Authors: Triki Zegni , Fong Stephanie , Amcoff Mirjam , Vàsquez-Nilsson Sebastian , Kolm Niclas
Published: June 2023

Executive functions are a set of cognitive control processes required for optimizing goal-directed behavior. Despite more than two centuries of research on executive functions, mostly in humans and nonhuman primates, there is still a knowledge gap in what constitutes the mechanistic basis of evolutionary variation in executive function abilities. Here, we show experimentally that size changes in a forebrain structure (i.e. telencephalon) underlie individual variation in executive function capacities in a fish. For this, we used male guppies (Poecilia reticulata) issued from artificial selection lines with substantial differences in telencephalon size relative to the rest of the brain. We tested fish from the up- and down-selected lines not only in three tasks for the main core executive functions: cognitive flexibility, inhibitory control, and working memory, but also in a basic conditioning test that does not require executive functions. Individuals with relatively larger telencephalons outperformed individuals with smaller telencephalons in all three executive function assays but not in the conditioning assay. Based on our findings, we propose that the telencephalon is the executive brain in teleost fish. Together, it suggests that selective enlargement of key brain structures with distinct functions, like the fish telencephalon, is a potent evolutionary pathway toward evolutionary enhancement of advanced cognitive abilities in vertebrates.
Hazardous air pollutant emissions estimates from wildfires in the wildland urban interface
Authors: Holder Amara L , Ahmed Aranya , Vukovich Jeffrey M , Rao Venkatesh
Published: June 2023

Fires that occur in the wildland urban interface (WUI) often burn structures, vehicles, and their contents in addition to biomass in the natural landscape. Because these fires burn near population centers, their emissions may have a sizeable impact on public health, necessitating a better understanding of criteria and hazardous air pollutants emitted from these fires and how they differ from wildland fires. Previous studies on the toxicity of emissions from the combustion of building materials and vehicles have shown that urban fires may emit numerous toxic species such as hydrogen cyanide, hydrogen fluoride, hydrogen chloride, isocyanates, polycyclic aromatic hydrocarbons (PAHs), dioxins and furans, and a range of toxic organic compounds (e.g. benzene toluene, xylenes, styrene, and formaldehyde) and metals (e.g. lead, chromium, cadmium, and arsenic). We surveyed the literature to create a compendium of emission factors for species emitted from the combustion of building and vehicle materials and compared them with those from wildland fires. Emission factors for some toxic species like PAH and some organic compounds were several orders of magnitude greater than those from wildfires. We used this emission factor compendium to calculate a bounding estimate of the emissions from several notable WUI fires in the western United States to show that urban fuels may contribute a sizeable portion of the toxic emissions into the atmosphere. However, large gaps remain in our understanding of the fuel composition, fuel consumption, and combustion conditions in WUI fires that constrain our ability to estimate the impact of WUI fires.
MiraBest: a data set of morphologically classified radio galaxies for machine learning
Authors: Porter Fiona A M , Scaife Anna M M
Published: June 2023

The volume of data from current and future observatories has motivated the increased development and application of automated machine learning methodologies for astronomy. However, less attention has been given to the production of standardized data sets for assessing the performance of different machine learning algorithms within astronomy and astrophysics. Here we describe in detail the MiraBest data set, a publicly available batched data set of 1256 radio-loud AGN from NVSS and FIRST, filtered to 0.03 < z < 0.1, manually labelled by Miraghaei and Best according to the Fanaroff–Riley morphological classification, created for machine learning applications and compatible for use with standard deep learning libraries. We outline the principles underlying the construction of the data set, the sample selection and pre-processing methodology, data set structure and composition, as well as a comparison of MiraBest to other data sets used in the literature. Existing applications that utilize the MiraBest data set are reviewed, and an extended data set of 2100 sources is created by cross-matching MiraBest with other catalogues of radio-loud AGN that have been used more widely in the literature for machine learning applications.
The transformation of foundation law in Hungary, with particular regard to private foundations
Authors: Sándor István
Published: June 2023

The article provides an overview of the system of regulation of Hungarian foundations, the individual types of foundations and their characteristics. It provides an overview of the features of public foundations and political foundations operating in the public sector, as well as the general rules applicable to private foundations and family foundations. The author pays special attention to the asset management foundations, analysing in detail the peculiarities of the public interest and private interest versions, with particular regard to their outstanding advantages in the international context.
Intrareliability and Interreliability of Low-Cost Devices to Measure Skin Tone, Moisture, and Oiliness
Authors: Girasol Carlos Eduardo , Rangon Flávia Belavenuto , Borsari Guilherme Castro , de Jesus Guirro Rinaldo Roberto , de Oliveira Guirro Elaine Caldeira
Published: June 2023

OBJECTIVE

To evaluate the intraexaminer and interexaminer reliability of low-cost commercial devices to measure skin tone, moisture, and oiliness; determine associations with the Fitzpatrick Scale; and compare results with those of widely used commercial equipment.

METHODS

Researchers bilaterally collected a total of 36 samples from 18 participants. For data acquisition, two experienced raters were considered for skin index assessment. Evaluations were conducted independently, with measurements taken at two different times with an interval between them, thus enabling intrarater and interrater reliability measures. The measurements were made with two low-cost devices and compared with those acquired using standard equipment for such analyses.

RESULTS

For the intraexaminer reliability results, the authors observed intraclass correlation coefficient ranging from moderate to high reliability between these tools (0.747-0.971). Regarding interexaminer reliability, intraclass correlation coefficient ranging from moderate to high (0.541-0.939) were observed. For the results of the correlations, a moderate to a large association was observed for skin tone. However, a small association for moisture was observed among the tools.

CONCLUSIONS

Evaluations of skin tonality, oiliness, and moisture showed moderate to excellent intrareliability and interreliability. These methods can be applied in different environments, especially clinics, because of their low cost and ease of use.
Introducing palliative care into the treatment of a critically ill patient
Authors: Robinson Charles C. , Evans Michael M. , Riley Kiernan , Kowalchik Kaléi , Adams Lucy , DeSanto Logan , Lucey Megan
Published: June 2023

Although it often carries a negative stigma, palliative care can greatly improve the quality of life of patients with critical illnesses.
The Other Infodemic: Media Misinformation about Involuntary Commitment for Substance Use
Authors: Kang Sunyou , McCreedy Katie , Messinger John , Bhargava Rahul , Beletsky Leo
Published: June 2023

Background

As drug-related deaths have surged, the number and scope of legal mechanisms authorizing involuntary commitment for substance use have expanded. Media coverage of involuntary commitment routinely ignores documented health and ethical concerns. Prevalence and dynamics of misinformation about involuntary commitment for substance use have not been assessed.

Methods

Media content mentioning involuntary commitment for substance use published between January 2015 and October 2020 was aggregated using MediaCloud. Articles were redundantly coded for viewpoints presented, substances mentioned, discussion of incarceration, and mentions of specific drugs. In addition, we tracked Facebook shares of coded content.

Results

Nearly half (48%) of articles unequivocally endorsed involuntary commitment, 30% presented a mixed viewpoint, and 22% endorsed a health-based or rights-based critique. Only 7% of articles included perspectives of people with lived experience of involuntary commitment. Critical articles received nearly twice as many Facebook shares (199,909 shares) as supportive and mixed narratives combined (112,429 shares combined).

Discussion

Empirical and ethical concerns about involuntary commitment for substance use are largely absent from coverage in mainstream media, as are voices of those with lived experience. Better alignment between news coverage and science is vital to inform effective policy responses to emerging public health challenges.
Efficacy and safety of intravenous Zolidronic acid in the treatment of pediatric osteogenesis imperfecta: a systematic review
Authors: Mahmoud Ines , Bouden Selma , Sahli Mariem , Rouached Leila , Ben Tekaya Aicha , Tekaya Rawdha , Saidane Olfa , Abdelmoula Leila
Published: June 2023

Osteogenesis imperfecta is an inherited clinically heterogeneous disorder of bone metabolism characterized by bone and skeletal fragility and an increased risk of fractures. Pamidronate infusion was the standard treatment, but zoledronic acid is increasingly used to treat children with osteogenesis imperfecta. We conducted a systematic literature review to evaluate the efficacy and safety of intravenous zoledronic acid in the treatment of osteogenesis imperfecta in pediatric patients. A systematic review of the published literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were clinical trials and observational studies including pediatric patients (<16 years) with osteogenesis imperfecta treated with zoledronic acid. We selected articles published during the 20 past years. The selected languages were English and French. We included articles with a minimum sample size of five patients. Six articles fulfilled the selection criteria. The majority of patients were Chinese (58%). The predominant sex was male (65%), and the age of included patients ranged from 2.5 weeks to 16.8 years. For all patients, zoledronic infusions were administrated intravenously. The zoledronic treatment duration ranged from 1 to 3 years. Densitometry parameters before and after zoledronic treatment were evaluated and showed significant improvement both in lumbar spine-bone mineral density Z-score and femoral neck-bone mineral density Z-scores. A significant decrease in fracture rate has also been noted both in vertebral and nonvertebral fracture incidence. The two most common side effects were fever and flu-like reactions. None of the patients presented severe adverse events. Zoledronic acid appeared to be well-tolerated and effective in the treatment of pediatric osteogenesis imperfecta.
Feasibility of C2 Pedicle Screw Fixation With the “in-out-in” Technique for Patients With Basilar Invagination
Authors: Xu Panjie , Lin Junyu , Xiao Hang , Zheng Jianying , Ji Wei
Published: June 2023

Study Design.

Retrospective study.

Objective.

To evaluate the feasibility of C2 pedicle screw fixation with the “in-out-in” technique in patients with basilar invagination (BI).

Summary of Background Data.

The “in-out-in” technique is a fixation technique in which the screw enters the vertebrae through the parapedicle. The technique has been used in upper cervical spine fixation. However, anatomic parameters associated with the application of this technique in patients with BI are unclear.

Materials and Methods.

We measured the C2 pedicle width (PW), the distance between the vertebral artery (VA) and the transverse foramen (VATF), the safe zone, and the limit zone. The lateral safe zone is the distance from the medial/lateral cortex of the C2 pedicle to the VA (LPVA/MPVA), and the medial safe zone is the distance from the medial/lateral cortex of the C2 pedicle to the dura (MPD/LPD). The lateral limit zone is the sum of LPVA/MPVA and VATF (LPTF/MPTF), and the medial limit zone is the distance from the medial/lateral cortex of the C2 pedicle to the spinal cord (MPSC/LPSC). PW, LPVA, MPVA, and VATF were measured on the reconstructed CT angiography. PW, MPD, LPD, MPSC, and LPSC were measured on MRI. We define a width greater than 4 mm as safe for screw. The t-test was used to compare the parameters between male and female, left and right sides in all patients, and PW in CTA and MRI data in the same patient. For intrarater reliabilities, interclass correlation coefficients were calculated.

Results.

A total of 154 patients (49 CTA, 143 MRI) were included. The average PW, LPVA, MPVA, LPTF, MPTF, MPD, LPD, MPSC, and LPSC were 5.30 mm, 1.28 mm, 6.60 mm, 2.45 mm, 8.94 mm, 2.09 mm, 7.07 mm, 5.51 mm, and 10.48 mm, respectively. Furthermore, in patients with PW <4 mm, 53.6% of MPVA, 86.2% of LPTF, and all limit zones were larger than 4 mm.

Conclusions.

In patients with BI, there is sufficient space medially and laterally to the C2 pedicle for partial screw encroachment to achieve “in-out-in” fixation, even if the pedicle is small.

Level of Evidence.

Level—4
PRAME Immunohistochemical Expression and TERT Promoter Mutational Analysis as Ancillary Diagnostic Tools for Differentiating Proliferative Nodules From Melanoma Arising in Congenital Nevi
Authors: Boutko Anastasiya , Hagstrom Michael , Lampley Nathaniel , Roth Andrew , Olivares Shantel , Dhillon Soneet , Fumero-Velázquez Mónica , Benton Sarah , Zhao Jeffrey , Zhang Bin , Dittmann David , Asadbeigi Sepideh , Busam Klaus J. , Gerami Pedram
Published: June 2023

Proliferative nodules (PNs) are benign melanocytic proliferations that typically develop within congenital melanocytic nevi. These tumors have overlapping histological features with melanoma. Ancillary immunohistochemistry and genomic sequencing are often used in diagnostically challenging cases. To assess the utility of preferentially expressed antigen in melanoma (PRAME) immunoreactivity and telomerase reverse transcriptase (TERT) promoter mutation analysis in distinguishing PNs from melanoma arising in congenital nevi cases. Twenty-one PNs and 2 melanomas arising in congenital nevi were immunohistochemically stained with PRAME. Cases with adequate tissue were also assessed for TERT promoter mutations through sequencing studies. The positivity rates in the PN cases were compared with those of the melanomas. Two of 21 PN cases were diffusely positive for PRAME (≥75% of the tumor cells positive). Two of 2 melanomas arising in congenital nevus cases were also diffusely PRAME positive. The difference was statistically significant using a Fisher exact test. None of the tumors harbored TERT promoter mutations. PRAME immunohistochemical marker may have diagnostic value in distinguishing diagnostically challenging PNs from melanoma, but diffuse expression is not specific for melanoma.
Use of the Intercostal Artery-based Latissimus Dorsi Muscle for Intrathoracic Reconstruction after Division of the Thoracodorsal Vessels and Latissimus Dorsi Muscle
Authors: Cherukuri Sai , Blackmon Shanda , Bakri Karim , Mardini Samir , Moran Steven L. , Gibreel Waleed
Published: June 2023

The latissimus dorsi muscle is the workhorse flap for intrathoracic reconstruction. Prior thoracotomy, which divides the latissimus dorsi muscle, limits the muscle’s intrathoracic reach. We present our experience using the distal portion of the muscle for intrathoracic reconstruction based off an intercostal vessel. We also demonstrate the ability of this intercostal perforator to allow for chimeric flap elevation with a separate skin paddle, depending on the branching pattern of the intercostal vessels. This study provides a case series of three consecutive patients, treated between September 2021 and June 2022. The intrathoracic pathology addressed in these patients are bronchopleural fistula, aortoesophageal fistula, and bronchoesophageal fistula. All patients had the resolution of symptoms related to intrathoracic fistulae and did not experience recurrence. This novel pedicled muscle flap can be an additional option for patients with prior thoracotomy and avoids the morbidity which can be seen with the serratus or rectus abdominis muscle flaps.
Serologic Evaluations in the Distinction Between Sinusitis-Related Orbital Cellulitis and Periorbital Necrotizing Fasciitis
Authors: Wladis Edward J. , Tomlinson Lauren A. , Moorjani Smriti , Rothschild Michael I.
Published: June 2023

Purpose:

While sinusitis-related orbital cellulitis (SROC) and periorbital necrotizing fasciitis (PNF) share similar clinical presentations, they are managed differently, making rapid recognition of the appropriate clinical entity critical to optimal outcomes. This study was performed to assess whether serologic testing might help clinicians to distinguish between SROC and PNF.

Methods:

A retrospective review analysis was used to compare initial complete blood counts and comprehensive metabolic panels among adult patients with SROC and PNF. Statistical evaluations were used to determine the significance of differences between the groups.

Results:

Thirteen patients with PNF and 14 patients with SROC were identified. The 2 groups were similar in age, gender, and likelihood of immunosuppression (p > 0.05 for each metric). Mean leukocyte counts were 18.52 (standard deviation = 7.02) and 10.31 (standard deviation = 5.77) for PNF and SROC, respectively (p = 0.0057). White blood cell levels were above normal limits for 12 patients with PNF (92.3%) and 7 patients with SROC (50%) (p = 0.017). No other laboratory test was significantly different between the 2 groups.

Conclusions:

While the majority of serologic testing was quite similar in patients with either SROC or PNF, leukocyte levels may represent an important clue to distinguish between the two diseases. Clinical evaluation remains the gold standard to make the proper diagnosis, but markedly elevated white blood cell counts should prompt clinicians to at least consider a diagnosis of PNF.
Experiences of nurse practitioners with telehealth during the COVID-19 pandemic
Authors: Reilly Janet , Liphart Rhoads Jenna , Bettin Tina , Dennik-Champion Gina , Bansal Gaurav
Published: June 2023

Background:

The COVID-19 pandemic brought many changes to the way nurse practitioners (NPs) provided care for patients, including the explosive and instantaneous use of telehealth in lieu of face-to-face services to maintain safe health care access and provision for patients and providers.

Purpose:

Although the literature abounds with patient perspectives and benefits of telehealth, little is found about the perceptions and experiences of NPs providing telehealth services during this time when telehealth was the primary care mode of providing nonacute care.

Methodology:

This mixed-methods, descriptive, exploratory study describes demographic and quantitative data about telehealth experiences collected from NPs across the nation early in the pandemic during fall 2020, and similar quantitative data collected later in spring 2021 from NPs in one state.

Results:

Significant findings between the 2020 national and 2021 state NP data include years of NP experience and the NP perceived barriers in the provision of telehealth services.

Conclusions:

Major patient-centric telehealth barriers were patient comfort with and accessibility to telehealth software. Major NP perceived telehealth barriers were regulatory laws, difficulty including telehealth visits into workflow when seeing patients in person, and comfort using telehealth software.

Implications:

Specific strategies can help to overcome identified telehealth barriers.
The Prognostic Value of TTF-1/NKX2-1 in Lung Squamous Cell Carcinoma
Authors: Liao Yida , Yang Fan , Li Xiao , Chen Kezhong , Wang Jun
Published: June 2023

Background:

TTF-1/NKX2-1 is a lineage-specific transcription factor that is expressed in the thyroid gland, lung, and forehead. It functions as a key component in regulating lung morphogenesis and differentiation. It is mainly expressed in lung adenocarcinoma, while its prognostic value in non-small-cell lung cancer remains controversial. This study evaluates the prognostic value of TTF-1 in different cellular locations in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC).

Materials and Methods:

The expression of TTF-1 was analyzed by immunohistochemistry in 492 patients (ADC 340 and SCC 152) who had undergone surgery between June 2004 and June 2012. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

Results:

Positive TTF-1 expression was 68.2% in ADC (located in the nucleus) and 29.6% in SCC (cytoplasm staining). The presence of TTF-1 was associated with better OS in SCC and ADC (P=0.000 and P=0.003, respectively). In SCC, an increased level of TTF-1 was associated with a longer disease-free survival (DFS). Positive TTF-1 expression was an independent favorable prognostic factor in SCC (P=0.020, HR: 2.789, 95%CI: 1.172–6.637) and ADC (P=0.025, HR: 1.680, 95%CI: 1.069–2.641).

Conclusions:

TTF-1 was largely located in the nucleus of ADC, while it always accumulated in the cytoplasm of SCC. The higher level of TTF-1 in the different subcellular locations of ADC and SCC was an independent, favorable prognostic factor, respectively. Increased TTF-1 in the cytoplasm of SCC was associated with a longer OS and DFS.
Online information on chronic pain in 3 countries: an assessment of readability, credibility, and accuracy
Authors: Basnet Ritu , Mendez David Ruiz , Lugo-González Isaías , O'Hagan Edel , O'Keeffe Mary , Sharma Saurab , Pate Joshua W. , Kennedy David S.
Published: June 2023

Objectives:

To assess the readability, credibility, and accuracy of online information on chronic pain in Australia, Mexico, and Nepal.

Methods:

We assessed Google-based websites and government health websites about chronic pain for readability (using the Flesch Kincaid Readability Ease tool), credibility (using the Journal of American Medical Association [JAMA] benchmark criteria and Health on the Net Code [HONcode]), and accuracy (using 3 core concepts of pain science education: (1) pain does not mean my body is damaged; (2) thoughts, emotions, and experiences affect pain; and (3) I can retrain my overactive pain system).

Results:

We assessed 71 Google-based websites and 15 government websites. There were no significant between-country differences in chronic pain information retrieved through Google for readability, credibility, or accuracy. Based on readability scores, the websites were “fairly difficult to read,” suitable for ages 15 to 17 years or grades 10 to 12 years. For credibility, less than 30% of all websites met the full JAMA criteria, and more than 60% were not HONcode certified. For accuracy, all 3 core concepts were present in less than 30% of websites. Moreover, we found that the Australian government websites have low readability but are credible, and the majority provided all 3 core concepts in pain science education. A single Mexican government website had low readability without any core concepts but was credible.

Conclusion:

The readability, credibility, and accuracy of online information on chronic pain should be improved internationally to support facilitating better management of chronic pain.
Therapeutic Options for Migraines in the Microsurgical Patient: A Scoping Review
Authors: Stearns Stephen A. , Xun Helen , Haddad Anthony , Rinkinen Jacob , Bustos Valeria P. , Lee Bernard T.
Published: June 2023

Background:

There exists an increasing array of treatments proposed to prevent, alleviate, and abort symptoms of a migraine; however, for patients who undergo reconstructive microsurgery, caution must be taken to preserve vascular integrity. This study is the first-to-date scoping review of vascular and bleeding risk of current migraine therapies, with the purpose of identifying potential therapeutic agents for postoperative migraine management appropriate for microsurgical patients.

Methods:

Currently available migraine therapeutics were compiled from UpToDate and the American Academy of Family Physicians. A PubMed literature review was performed for each therapeutic’s effect on bleeding or vascular involvement. Data were compiled into tables of abortive, symptom-controlling and prophylactic, and non-pharmacologic treatments. Expert microsurgeons reviewed the data to provide recommendations for optimized patient care.

Results:

Triptans and other ergot derivatives demonstrated strong evidence of vasoconstriction and were greatly advised against for immediate post-microsurgical use. Novel pharmaceutical therapies like Lasmiditan and CGRP antagonists have no literature indicating potential for vasoconstriction or hematoma and remain an investigational option for abortive medical treatment. For symptom control, acetaminophen appears the safest option, with clinical judgment and further research needed for use of NSAIDs. Alternative treatment techniques may include migraine prophylaxis with botulinum toxin injection or nutraceutical treatment via magnesium supplementation or Coenzyme Q10 administration, minimizing the need for additional medication in the postoperative setting.

Conclusions:

Patients undergoing reconstructive microsurgery have a unique medical profile limiting the therapeutic options available to treat migraines. This review provides preliminary evidence to be considered as a guide for prescribing therapeutics for migraine in the postoperative setting.
Comparing Combination Triamcinolone Acetonide and 5-Fluorouracil with Monotherapy Triamcinolone Acetonide or 5-Fluorouracil in the Treatment of Hypertrophic Scars: A Systematic Review and Meta-Analysis
Authors: Mavilakandy Akash K. , Vayalapra Sushanth , Minty Iona , Parekh Jvalant N. , Charles Walton N. , Khajuria Ankur
Published: June 2023

Background:

Keloids and hypertrophic scars cause physical and psychosocial problems. A combination of 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC) may enhance the treatment of pathologic scars, although the evidence base is limited. The authors compared the efficacy and complication rates of combination intralesional TAC and 5-FU with those of monotherapy intralesional TAC or 5-FU for the treatment of keloids and hypertrophic scars.

Methods:

Embase, MEDLINE, and CENTRAL were searched by two independent reviewers. The primary outcome was treatment efficacy (51% to 100% improvement). Study quality and risk of bias were assessed using the Cochrane risk of bias tool.

Results:

Of 277 articles screened, 13 studies were included, comprising 12 randomized control trials and one nonrandomized study. Six studies compared combination intralesional therapy versus monotherapy 5-FU, and nine studies compared combination intralesional therapy versus monotherapy TAC. The combined group demonstrated superior objective treatment efficacy compared with the monotherapy TAC group (OR, 3.45; 95% CI, 2.22 to 5.35; I2 = 0%; P < 0.00001) and monotherapy 5-FU group (OR, 4.17; 95% CI, 2.21 to 7.87; I2 = 0%; P < 0.0001). Telangiectasia was less frequent in combination therapy (OR, 0.24; 95% CI, 0.11 to 0.52; I2 = 0%; P = 0.0003) compared with monotherapy TAC.

Conclusions:

Combined intralesional TAC and 5-FU administration demonstrated superior treatment efficacy outcomes compared with monotherapy TAC or 5-FU. Patient-reported outcome measures should be incorporated in the design of future research to justify clinical recommendations.

Clinical Relevance Statement:

Combined TAC and 5-FU has demonstrated superior treatment efficacy outcomes compared to monotherapy TAC or 5-FU in the treatment of hypertrophic scars and keloids.
“Postoperative Outcomes Following Buried Penis Reconstruction: A Single-Institution Experience Using the Wisconsin Classification System”
Authors: Seitz Allison J. , Edalatpour Armin , Israel Jacqueline S. , Grimes Matthew D. , Williams Daniel H. , Poore Samuel O.
Published: June 2023

Background:

Adult acquired buried penis (AABP) is a complex condition often necessitating surgical intervention. This study seeks to examine the validity of the Wisconsin Classification System (WCS) in guiding the surgical management of AABP. Additionally, we aimed to identify which factors contribute to postoperative complications and persistent symptoms following AABP repair.

Methods:

We retrospectively reviewed all patients who underwent surgical repair of AABP from 2015-2021 by the senior author at our institution. Patients were categorized according to anatomic characteristics using the WCS. Preoperative symptoms, postoperative symptoms, and postoperative complications were evaluated.

Results:

Fifty-two patients underwent AABP repair. The mean age was 56.5±14.8 years, and the mean duration of follow-up was 350.0±517.4 days. The assigned preoperative WCS score was congruent with operative management in most patients (86.0%). Morbid obesity (BMI>40.0kg/m2) and postoperative complications were associated with persistent symptoms following AABP repair (p=0.026 and p=0.021, respectively). Increased WCS score was not associated with persistent postoperative symptoms (p=0.314). Morbid obesity (p=0.003), diabetes (p=0.029) and having a panniculectomy during AABP repair (p=0.046) increased the odds for developing postoperative complications. Patients with Type I AABP had significantly fewer complications than those with Type II, III, or IV (p=0.032).

Conclusions:

The Wisconsin Classification System serves as a preoperative guide, an educational tool for patients, and provides a framework for the discussion of intraoperative maneuvers and the likelihood of complications. It is imperative to counsel patients on the surgical management of AABP and the postoperative course, as this may permit realistic patient expectations and optimize outcomes.
Optimizing Facial Esthetic Outcomes: Adding Distraction Osteogenesis to Your Classic Orthognathic Surgery Armamentarium
Authors: Vinzenz Kurt , Patel Pravin K. , Cohen Mimis
Published: June 2023

Classical orthognathic procedures have long been known to improve the facial esthetic contours and proportions of face by restoring the skeletal foundation, on which the soft-tissue drapes. Distraction osteogenesis was introduced to solve complex skeletal abnormalities in patients with craniofacial conditions that could not be solved by classical orthognathic surgery techniques. The gradual expansion in this group of patients showed not only greater skeletal stability, but the expansion at various tissue planes improved the facial appearance. In this report we review our experience in 22 cases with dentofacial skeletal abnormities for whom we believe achieved aesthetic outcomes could not habe been with classical orthognathic techniques alone. In addition, distraction at the interdental regions allowed for “tailoring” of the osteotomies and for simultaneous expansion at the occlusal level.