bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualization of oxidized guanine nucleotides accumulation in living cells with split MutT
Authors: Fujikawa Yoshihiro , Kawai Hidehiko , Suzuki Tetsuya , Kamiya Hiroyuki
Published: May 2024

Cancer cells produce vast quantities of reactive oxygen species, leading to the accumulation of toxic nucleotides as 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate (8-oxo-dGTP). The human MTH1 protein catalyzes the hydrolysis of 8-oxo-dGTP, and cancer cells are dependent on MTH1 for their survival. MTH1 inhibitors are possible candidates for a class of anticancer drugs; however, a reliable screening system using live cells has not been developed. Here we report a visualization method for 8-oxo-dGTP and its related nucleotides in living cells. Escherichia coli MutT, a functional homologue of MTH1, is divided into the N-terminal (1–95) and C-terminal (96–129) parts (Mu95 and 96tT, respectively). Mu95 and 96tT were fused to Ash (assembly helper tag) and hAG (Azami Green), respectively, to visualize the nucleotides as fluorescent foci formed upon the Ash-hAG association. The foci were highly increased when human cells expressing Ash-Mu95 and hAG-96tT were treated with 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and 8-oxo-dGTP. The foci formation by 8-oxo-dG(TP) was strikingly enhanced by the MTH1 knockdown. Moreover, known MTH1 inhibitors and oxidizing reagents also increased foci. This is the first system that visualizes damaged nucleotides in living cells, provides an excellent detection method for the oxidized nucleotides and oxidative stress, and enables high throughput screening for MTH1 inhibitors.
GPSFun: geometry-aware protein sequence function predictions with language models
Authors: Yuan Qianmu , Tian Chong , Song Yidong , Ou Peihua , Zhu Mingming , Zhao Huiying , Yang Yuedong
Published: May 2024

Knowledge of protein function is essential for elucidating disease mechanisms and discovering new drug targets. However, there is a widening gap between the exponential growth of protein sequences and their limited function annotations. In our prior studies, we have developed a series of methods including GraphPPIS, GraphSite, LMetalSite and SPROF-GO for protein function annotations at residue or protein level. To further enhance their applicability and performance, we now present GPSFun, a versatile web server for Geometry-aware Protein Sequence Function annotations, which equips our previous tools with language models and geometric deep learning. Specifically, GPSFun employs large language models to efficiently predict 3D conformations of the input protein sequences and extract informative sequence embeddings. Subsequently, geometric graph neural networks are utilized to capture the sequence and structure patterns in the protein graphs, facilitating various downstream predictions including protein–ligand binding sites, gene ontologies, subcellular locations and protein solubility. Notably, GPSFun achieves superior performance to state-of-the-art methods across diverse tasks without requiring multiple sequence alignments or experimental protein structures. GPSFun is freely available to all users at https://bio-web1.nscc-gz.cn/app/GPSFun with user-friendly interfaces and rich visualizations.
Aggrescan4D: structure-informed analysis of pH-dependent protein aggregation
Authors: Bárcenas Oriol , Kuriata Aleksander , Zalewski Mateusz , Iglesias Valentín , Pintado-Grima Carlos , Firlik Grzegorz , Burdukiewicz Michał , Kmiecik Sebastian , Ventura Salvador
Published: May 2024

Protein aggregation is behind the genesis of incurable diseases and imposes constraints on drug discovery and the industrial production and formulation of proteins. Over the years, we have been advancing the Aggresscan3D (A3D) method, aiming to deepen our comprehension of protein aggregation and assist the engineering of protein solubility. Since its inception, A3D has become one of the most popular structure-based aggregation predictors because of its performance, modular functionalities, RESTful service for extensive screenings, and intuitive user interface. Building on this foundation, we introduce Aggrescan4D (A4D), significantly extending A3D’s functionality. A4D is aimed at predicting the pH-dependent aggregation of protein structures, and features an evolutionary-informed automatic mutation protocol to engineer protein solubility without compromising structure and stability. It also integrates precalculated results for the nearly 500,000 jobs in the A3D Model Organisms Database and structure retrieval from the AlphaFold database. Globally, A4D constitutes a comprehensive tool for understanding, predicting, and designing solutions for specific protein aggregation challenges. The A4D web server and extensive documentation are available at https://biocomp.chem.uw.edu.pl/a4d/. This website is free and open to all users without a login requirement.
PROSCA: an online platform for humanized scaffold mining facilitating rational protein engineering
Authors: Wang Xiaona , Zhang Yintao , Li Zengpeng , Duan Zixin , Guo Menghan , Wang Zhen , Zhu Feng , Xue Weiwei
Published: May 2024

Protein scaffolds with small size, high stability and low immunogenicity show important applications in the field of protein engineering and design. However, no relevant computational platform has been reported yet to mining such scaffolds with the desired properties from massive protein structures in human body. Here, we developed PROSCA, a structure-based online platform dedicated to explore the space of the entire human proteome, and to discovery new privileged protein scaffolds with potential engineering value that have never been noticed. PROSCA accepts structure of protein as an input, which can be subsequently aligned with a certain class of protein structures (e.g. the human proteome either from experientially resolved or AlphaFold2 predicted structures, and the human proteins belonging to specific families or domains), and outputs humanized protein scaffolds which are structurally similar with the input protein as well as other related important information such as families, sequences, structures and expression level in human tissues. Through PROSCA, the user can also get excellent experience in visualizations of protein structures and expression overviews, and download the figures and tables of results which can be customized according to the user's needs. Along with the advanced protein engineering and selection technologies, PROSCA will facilitate the rational design of new functional proteins with privileged scaffolds. PROSCA is freely available at https://idrblab.org/prosca/.
Healthcare worker burnout during a persistent crisis: a case–control study
Authors: Appelbom S , Nordström A , Finnes A , Wicksell R K , Bujacz A
Published: May 2024

Background

During the immediate outbreak of the COVID-19 pandemic, burnout symptoms increased among healthcare workers. Knowledge is needed on how early symptoms developed during the persistent crisis that followed the first pandemic wave.

Aims

To investigate if high levels of burnout symptoms during the first pandemic wave led to high burnout and depressive symptoms up to a year later, and if participation in psychological support was related to lower levels of symptoms.

Methods

A longitudinal case–control study followed 581 healthcare workers from two Swedish hospitals. Survey data were collected with a baseline in May 2020 and three follow-up assessments until September 2021. The case group was participants reporting high burnout symptoms at baseline. Logistic regression analyses were performed separately at three follow-ups with case–control group assignment as the main predictor and burnout and depression symptoms as outcomes, controlling for frontline work, changes in work tasks and psychological support participation.

Results

One out of five healthcare workers reported high burnout symptoms at baseline. The case group was more likely to have high burnout and depressive symptoms at all follow-ups. Participation in psychological support was unrelated to decreased burnout and depressive symptoms at any of the follow-ups.

Conclusions

During a persistent crisis, healthcare organizations should be mindful of psychological reactions among staff and who they place in frontline work early in the crisis. To better prepare for future healthcare crises, preventive measures on burnout are needed, both at workplaces and as part of the curricula in medical and nursing education.
Putative rhamnogalacturonan-II glycosyltransferase identified through callus gene editing which bypasses embryo lethality
Authors: Zhang Yuan , Sharma Deepak , Liang Yan , Downs Nick , Dolman Fleur , Thorne Kristen , Black Ian M , Pereira Jose Henrique , Adams Paul , Scheller Henrik V , O’Neill Malcolm , Urbanowicz Breeanna , Mortimer Jenny C
Published: May 2024

Rhamnogalacturonan II (RG-II) is a structurally complex and conserved domain of the pectin present in the primary cell walls of vascular plants. Borate cross-linking of RG-II is required for plants to grow and develop normally. Mutations that alter RG-II structure also affect cross-linking and are lethal or severely impair growth. Thus, few genes involved in RG-II synthesis have been identified. Here, we developed a method to generate viable loss-of-function Arabidopsis (Arabidopsis thaliana) mutants in callus tissue via CRISPR/Cas9-mediated gene editing. We combined this with a candidate gene approach to characterize the male gametophyte defective 2 (MGP2) gene that encodes a putative family GT29 glycosyltransferase. Plants homozygous for this mutation do not survive. We showed that in the callus mutant cell walls, RG-II does not cross-link normally because it lacks 3-deoxy-D-manno-octulosonic acid (Kdo) and thus cannot form the α-L-Rhap-(1→5)-α-D-kdop-(1→sidechain). We suggest that MGP2 encodes an inverting RG-II CMP-β-Kdo transferase (RCKT1). Our discovery provides further insight into the role of sidechains in RG-II dimerization. Our method also provides a viable strategy for further identifying proteins involved in the biosynthesis of RG-II.
SMEs, Trade Finance Markets and Instruments: A Review of the Issues with Reference to Asia
Authors: Cavoli Tony , Christian David , Shrestha Rashesh
Published: May 2024

Small and Medium Enterprises (SMEs) are an important source of employment and economic activity, but their expansion and growth may be limited by the existence of trade finance constraints due mainly to a lack of access to external sources of finance. We present a conceptual framework for understanding trade finance transactions, instruments, and participants; and map this framework to the available data used to measure trade finance. Finally, we present some stylized facts on the relationship between various trade finance instruments, and their possible links to SME outcomes with reference to ASEAN countries. We find that there are many (though imperfect) proxies for trade finance activities; and that improving trade finance is associated with more desirable SME outcomes.
“The primacy of labor over profits”: Thomas Mahony, the Beet Field Workers of Colorado, and Visions for a Consumerist Democracy, 1902–1957
Authors: Cain Ellen
Published: May 2024

During the first half of the twentieth century, ethnic Mexican beet workers in Colorado endured a daunting array of challenges that included dismal housing, meager wages, and a family labor system that forced children as well as adults to labor relentless hours in the sugar-beet fields. In response to these conditions, Catholic reformer Thomas Mahony promoted a vision of the American economy in which marginalized populations like the beet laborers would take their rightful place as healthy consumers and effective family providers. His vision was shaped by the Catholic social justice movement of the Progressive Era, as well as by a career in agricultural consumerism. From 1910 to 1913, for example, he served as director of exhibits for the Chicago Land Show, a position that immersed him in a world that marketed farm lands as idealized consumer commodities while rendering invisible the struggles of propertyless farm workers. When Mahony began his reform career a decade later, he strove to do exactly the opposite: make beet field workers as visible as possible in his blueprint for a vigorous consumerist democracy. At the same time, however, Mahony’s intense fears of radicalism overshadowed his reform impulses, reflecting profound tensions within the Catholic reform ethos that shaped him: a yearning for spiritual and social regeneration in constant battle with a dread of social upheaval. Mahony’s story therefore helps to illuminate the considerable potential of twentieth-century religious reform, even as his obsessive fears highlight the perils of antiradicalism in the U.S. West.
Mechanical stretch preconditioned adipose‐derived stem cells elicit polarization of anti‐inflammatory M2‐like macrophages and improve chronic wound healing
Authors: He Jiahao , Shan Shengzhou , Jiang Taoran , Zhou Sizheng , Qin Jiaqi , Li Qingfeng , Yu Zheyuan , Cao Dejun , Fang Bin
Published: May 2024

Transplantation of adipose‐derived stem cells (ASCs) is a promising option in the field of chronic wounds treatment. However, the effectiveness of ASCs therapies has been hampered by highly inflammatory environment in chronic wound areas. These problems could be partially circumvented using efficient approaches that boost the survival and anti‐inflammatory capacity of transplanted ASCs. Here, by application of mechanical stretch (MS), we show that ASCs exhibits increased survival and immunoregulatory properties in vitro. MS triggers the secretion of macrophage colony stimulating factor (M‐CSF) from ASCs, a chemokine that is linked to anti‐inflammatory M2‐like macrophages polarization. When the MS‐ASCs were transplanted to chronic wounds, the wound area yields significantly faster closure rate and lower inflammatory mediators, largely due to macrophages polarization driven by transplanted MS‐ASCs. Thus, our work shows that mechanical stretch can be harnessed to enhance ASCs transplantation efficiency in chronic wounds treatment.
Multifactoral immune modulation potentiates durable remission in multiple models of aggressive malignancy
Authors: Halpert Matthew M. , Burns Briana A. , Rosario Spencer R. , Withers Henry G. , Trivedi Akshar J. , Hofferek Colby J. , Gephart Benjamin D. , Wang Haotong , Vazquez‐Perez Jonathan , Amanya Sharon B. , Hyslop Sean T. , Yang Jianhua , Kemnade Jan O. , Sandulache Vlad C. , Konduri Vanaja , Decker William K.
Published: May 2024

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single‐agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor‐prognosis tumor types including the non‐immunogenic 4T‐1 model of TNBC, the aggressive MOC‐2 model of HNSCC, and the high‐risk MYCN‐amplified model of neuroblastoma. A course of therapy optimized for TNBC cured a majority of tumors in both ectopic and orthotopic settings and eliminated metastatic spread in all animals tested at the highest doses. Immune responses were transferable between therapeutic donor and naïve recipient through adoptive transfer, and a sizeable abscopal effect on distant, untreated lesions could be demonstrated experimentally. Similar results were observed in HNSCC and neuroblastoma models, with characteristic remodeling of the tumor microenvironment documented in all model systems. scRNA‐seq analysis implicated upregulation of innate immune responses and antigen presentation in tumor cells and the myeloid cell compartment as critical early events. This analysis also highlighted the potential importance of the autonomic nervous system in the governance of inflammatory processes. The data indicate that the targeting of multiple pathways and mechanisms of action can result in substantial synergistic antitumor effects and suggest follow‐up in the neoadjuvant setting may be warranted.
Creating an Assignment to Incorporate Antiracist Pedagogy Into an Undergraduate Introductory Nursing Course
Authors: Mangino Heather
Published: May 2024

Antiracist pedagogy was incorporated into an undergraduate introductory nursing course using National League for Nursing diversity and inclusion initiatives and academic nurse educator competencies as a framework. This article describes the reflective process and steps taken to select Taylor’s memoir, Reminiscences of My Life in Camp, as a required text for an introductory nursing course. By incorporating antiracism into an introductory nursing course, educators can assist novice nursing students from diverse groups to envision themselves as nurses, role model allyship for White students, and create a more inclusive teaching environment.
Transcriptional Profiling Underscores the Role of Preprocurement Allograft Metabolism and Innate Immune Status on Outcomes in Human Liver Transplantation
Authors: Kim Joohyun , Zimmermann Michael T. , Mathison Angela J. , Lomberk Gwen , Urrutia Raul , Hong Johnny C.
Published: May 2024

Objective:

The adverse effects of ischemia-reperfusion injury (IRI) remain a principal barrier to a successful outcome after lifesaving orthotopic liver transplantation (OLT). Gene expression during different phases of IRI is dynamic and modified by individual exposures, making it attractive for identifying potential therapeutic targets for improving the number of suitable organs for transplantation and patient outcomes. However, data remain limited on the functional landscape of gene expression during liver graft IRI, spanning procurement to reperfusion and recovery. Therefore, we sought to characterize transcriptomic profiles of IRI during multiple phases in human OLT.

Methods:

We conducted clinical data analyses, histologic evaluation, and RNA sequencing of 17 consecutive human primary OLT. We performed liver allograft biopsies at 4 time points: baseline (B, before donor cross-clamp), at the end of cold ischemia (CI), during early reperfusion (ER, after revascularization), and during late reperfusion (LR). Data were generated and then recipients grouped by post-OLT outcomes categories: immediate allograft function (IAF; n = 11) versus early allograft dysfunction (EAD; n = 6) groups.

Results:

We observed that CI (vs B) modified a transcriptomic landscape enriched for a metabolic and immune process. Expression levels of hallmark inflammatory response genes were higher transitioning from CI to ER and decreased from ER to LR. IAF group predominantly showed higher bile and fatty acid metabolism activity during LR compared with EAD group, while EAD group maintained more immunomodulatory activities. Throughout all time points, EAD specimens exhibited decreased metabolic activity in both bile and fatty acid pathways.

Conclusions:

We report transcriptomic profiles of human liver allograft IRI from prepreservation in the donor to posttransplantation in the recipient. Immunomodulatory and metabolic landscapes across ER and LR phases were different between IAF and EAD allografts. Our study also highlights marker genes for these biological processes that we plan to explore as novel therapeutic targets or surrogate markers for severe allograft injury in clinical OLT.
Subcutaneous Anterior Transposition With Modified Procedures to Prevent Recurrence Associated With the Transposed Ulnar Nerve
Authors: Shibuya Junichiro , Takahara Masatoshi , Satake Hiroshi , Takagi Michiaki
Published: May 2024

Subcutaneous anterior transposition of the ulnar nerve is a common surgical treatment for cubital tunnel syndrome. However, there are surgical failures associated with the new compressive sites at the edge of flexor carpi ulnaris (FCU) and resubluxation posterior to the medial epicondyle of the transposed nerve. To reduce the muscle volume at the edge of FCU, we approach the ulnar nerve by dividing the muscle belly of the FCU humeral heads. This procedure can reduce repeated traction forces on the transposed nerve at the edge of the FCU. To keep the transposed ulnar nerve anteriorly, we use a fat flap including the membranous superficial fascia. This flap can softly stabilize the ulnar nerve and act as a pliable cover to prevent perineural scarring or further constriction around the flap. Ninety-three elbows in 90 patients who had undergone this procedure for cubital tunnel syndrome were evaluated. According to Messina’s criteria, the numbers of patients showing excellent, good, fair, and poor recovery were 41 (44%), 47 (51%), 5 (5%), and 0 (0%), respectively. Most patients experience resolution of symptoms and good functional outcomes. None of the patients suffered recurrence, infection, or nerve injury.
The switch triggering the invasion process: Lipid metabolism in the metastasis of hepatocellular carcinoma
Authors: Zhang Jiaqian , Zhang Zhicheng , Wu Zhangfan , Wang Yufei , Zhang Zerui , Xia Limin
Published: May 2024

In humans, the liver is a central metabolic organ with a complex and unique histological microenvironment. Hepatocellular carcinoma (HCC), which is a highly aggressive disease with a poor prognosis, accounts for most cases of primary liver cancer. As an emerging hallmark of cancers, metabolic reprogramming acts as a runaway mechanism that disrupts homeostasis of the affected organs, including the liver. Specifically, rewiring of the liver metabolic microenvironment, including lipid metabolism, is driven by HCC cells, propelling the phenotypes of HCC cells, including dissemination, invasion, and even metastasis in return. The resulting formation of this vicious loop facilitates various malignant behaviors of HCC further. However, few articles have comprehensively summarized lipid reprogramming in HCC metastasis. Here, we have reviewed the general situation of the liver microenvironment and the physiological lipid metabolism in the liver, and highlighted the effects of different aspects of lipid metabolism on HCC metastasis to explore the underlying mechanisms. In addition, we have recapitulated promising therapeutic strategies targeting lipid metabolism and the effects of lipid metabolic reprogramming on the efficacy of HCC systematical therapy, aiming to offer new perspectives for targeted therapy.
DIAGNOSTIC YIELD OF AN INHERITED RETINAL DISEASE GENE PANEL IN RETINOPATHY OF UNKNOWN ORIGIN
Authors: Abramowicz Stéphane , Meunier Audrey , Postelmans Laurence , Caspers Laure , Corazza Francis , De Bruyne Marieke , Van de Sompele Stijn , De Baere Elfride , Leroy Bart P. , Willermain François , Draganova Dafina
Published: May 2024

Purpose:

Evaluating the presence of class 3, 4, and 5 genetic variants in inherited retinal disease (IRD) genes in patients with retinopathy of unknown origin (RUO).

Methods:

Multicentric retrospective study of RUO cases diagnosed between January 2012 and February 2022. General and ophthalmologic history, complete ophthalmologic examination, antiretinal antibodies, and IRD gene panel results were analyzed in every patient. Four RUO categories were defined: nonparaneoplastic autoimmune retinopathy, unilateral pigmentary retinopathy, asymmetrical pigmentary retinopathy, and acute zonal occult outer retinopathy.

Results:

The authors included 12 patients (9 females) across these four RUO categories. Mean age at inclusion was 45.6 years (20–68 years). Seven patients demonstrated class 3 variants in IRD genes. Of these, two also demonstrated class 5 variants in other IRD genes. The remaining five patients had negative panel results. IRD gene panel analysis allowed diagnosis refinement in 1 (8.3%) nonparaneoplastic autoimmune retinopathy patient in the RUO cohort. When considering the nonparaneoplastic autoimmune retinopathy subpopulation only, a higher diagnostic yield of 20% (1/5 patients) was achieved.

Conclusion:

Every suspected nonparaneoplastic autoimmune retinopathy patient should benefit from gene panel testing to not overlook undiagnosed IRDs. By contrast, unilateral pigmentary retinopathy, asymmetrical pigmentary retinopathy, and acute zonal occult outer retinopathy subpopulations did not benefit from genetic testing in this study.
Blink Lagophthalmos in Graves Orbitopathy
Authors: Guimarães Juliana A. , Garcia Denny M. , Cruz Antonio Augusto Velasco e
Published: May 2024

Purpose:

To investigate the relationship between the kinematics of spontaneous blinks and the anterior area of the levator palpebrae superioris muscle in patients with Graves orbitopathy (GO).

Methods:

This is a case-control study. The authors measured the margin reflex distance of the upper eyelid (margin reflex distance 1), the kinematics of spontaneous blinks, and the anterior area of levator palpebrae superioris muscle in CT coronal scans of patients with Graves upper eyelid retraction (GO) and a control group. The eye with the greatest margin reflex distance 1 was selected for analysis in each group.

Results:

A total of 68 participants were included, with 36 in the GO group and 32 in the control group. In the GO group, the mean margin reflex distance 1 measured 6.5 mm, while in the control group, it was 3.9 mm. Almost all parameters related to the closing phase of spontaneous blinking activity, including amplitude, velocity, blinking rate, and interblink time, did not differ between the two groups. However, the effectiveness of the blink’s amplitude (ratio of blink amplitude to margin reflex distance 1) and the main sequence (relationship between amplitude and velocity) were significantly reduced in the GO group compared with the control group. The area of the levator palpebrae superioris muscle was significantly larger in GO than in controls, with 71.4% of patients’ muscles outside of the maximum range of the controls.

Conclusions:

In patients with GO, there is a reduction in blinking effectiveness, also known as blink lagophthalmos, which is a factor in the common occurrence of ocular surface symptoms. The increase in velocity with amplitude is also reduced in GO.
Clinical outcomes of the light-adjustable lens in eyes with a history of prior corneal refractive surgery
Authors: Jones Marlee , Terveen Daniel C. , Berdahl John P. , Thompson Vance , Kramer Brent A. , Ferguson Tanner J.
Published: May 2024

Purpose:

To evaluate the visual and refractive outcomes in eyes with a history of laser corneal refractive surgery implanted with the second-generation light-adjustable lens (LAL).

Setting:

Private practice, Sioux Falls, South Dakota.

Design:

Retrospective, consecutive case series.

Methods:

Eyes with a history of prior corneal refractive surgery that underwent cataract surgery with implantation of the LAL and were targeted for plano were included. Data on the type and number of prior refractive surgeries were collected, in addition to the timing and number of postoperative adjustments. The primary outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity, and the percentage (%) of eyes within ±0.25 diopter (D), ±0.50 D, and ±1.00 D of their refractive target.

Results:

76 eyes from 70 patients were included. A total of 45 eyes with a history of 1 prior refractive surgery and 31 eyes with a history of ≥2 refractive surgeries were included. 74% (n = 56) of all eyes achieved UDVA of 20/20 or better, 88% (n = 67) achieved 20/25 UDVA or better, and 93% (n = 71) were correctable to 20/20 or better postoperatively. For refractive outcomes, 66% of eyes (n = 50) were within ±0.25 D and 86% (n = 65) were within ±0.50 D of refractive target.

Conclusions:

Patients with a history of laser corneal refractive surgery achieved favorable visual and refractive outcomes with the LAL. This intraocular lens (IOL), which affords postoperative adjustability, is a promising option for patients with a history of corneal refractive surgery who maintain high expectations for functional uncorrected acuity after cataract surgery.
The Development of an Opioid Misuse Training Program for Physical Therapists: A Learning Community Approach
Authors: Magel John , Siantz Elizabeth , Blosser Priscilla , Fritz Julie M. , Gordon Adam J.
Published: May 2024

Introduction.

Musculoskeletal pain and opioid misuse frequently co-occur.

Review of the Literature.

The US Preventive Services Task Force calls for all health care providers to be trained to screen for misuse and/or opioid use disorder. The purpose of this study was to develop and implement an opioid misuse training program that could be used by physical therapists.

Subjects.

Thirteen practicing physical therapists were invited to participate in a curriculum development project.

Methods.

Using the Curriculum Framework, a collaborative learning approach was used to develop an opioid misuse training program and training manual for physical therapists. Four training sessions were provided virtually every 2 weeks. Topics included an introduction to the opioid crisis, screening, assessing, and communicating with patients and with the health care team about opioid misuse. Each didactic session was followed by a participant feedback session where participants provided recommendations on improving the training content and their impressions on the barriers and facilitators to incorporating the training into practice. A companion training manual was created and sent to participants for comment. Participants were asked over email to describe whether and how they incorporated training materials into clinical practice during the training curriculum.

Results.

All participants attended sessions 1–3. Twelve (92.3%) attended the fourth session. Based on the participants' feedback, training sessions were edited, and a companion training manual was finalized and distributed to each participant. After the fourth session, 9 participants (69.2%) reported using what they learned in the training. During the participant feedback sessions, participants regarded the training as important. Some participants expressed barriers to discussing opioids with patients and concerns about whether the training was within physical therapists' scope of practice.

Discussion and Conclusion.

An iteratively developed training program for physical therapists to address opioid misuse was acceptable, feasible, and provided immediate practice change by most participants.
Impact of prior coronary artery bypass grafting and coronary lesion complexity on outcomes of transcatheter aortic valve replacement for severe aortic stenosis
Authors: Yamashita Yoshiyuki , Sicouri Serge , Baudo Massimo , Dokollari Aleksander , Rodriguez Roberto , Gnall Eric M. , Coady Paul M. , Jarrett Harish , Abramson Sandra V. , Hawthorne Katie M. , Goldman Scott M. , Gray William A. , Ramlawi Basel
Published: May 2024

Objective

To investigate the impact of prior coronary artery bypass grafting (CABG) and coronary lesion complexity on transcatheter aortic valve replacement (TAVR) outcomes for aortic stenosis.

Methods

Clinical outcomes of TAVR were retrospectively compared between patients with and without prior CABG, and between patients with prior CABG and without coronary artery disease (CAD). The impact of the CABG SYNTAX score was also evaluated in patients with prior CABG.

Results

The study included 1042 patients with a median age and follow-up of 82 years and 25 (range: 0–72) months, respectively. Of these, 175 patients had a history of CABG, while 401 were free of CAD. Patients with prior CABG were more likely to be male and had higher rates of diabetes, peripheral artery disease and atrial fibrillation compared with patients without prior CABG. After 2 : 1 propensity score matching, all-cause mortality (P = 0.17) and the composite of all-cause mortality, stroke and coronary intervention (P = 0.16) were similar between patients with (n = 166) and without (n = 304) prior CABG. A 1 : 1 propensity score-matched analysis, however, showed lower rates of all-cause mortality (P = 0.04) and the composite outcome (P = 0.04) in patients with prior CABG (n = 134) compared with patients without CAD (n = 134). The median CABG SYNTAX score was 16 (interquartile range: 9.0–23), which was not associated with better/worse clinical outcomes in patients with prior CABG.

Conclusion

Prior CABG may positively affect mid-term TAVR outcomes for aortic stenosis compared with no CAD when adjusted for other comorbidities. The CABG SYNTAX score did not influence the prognosis after TAVR.
Teaching Evidence-Based Practice Competencies to Meet Professional Practice Needs
Authors: Bourgault Annette M. , Penoyer Daleen , Conner Norma E.
Published: May 2024

Background:

Evidence-based practice (EBP) is a major concept threaded throughout nursing education, yet competencies are not clearly identified in The Essentials.

Purpose:

Nurse leaders‘EBP competency expectations for professional practice were explored to inform competency-based education for students and practicing nurses. A secondary aim explored potential effects of misinformation on EBP.

Methods:

Descriptive qualitative inquiry was performed with a focus group of 6 clinical nurse leaders.

Results:

EBP expectations were identified, discriminating between novice entry level and advanced-level nurses. Participants emphasized asking questions, linking evidence to practice, and acknowledging that evidence changes over time. All advanced-level nurses were expected to apply, lead, and teach EBP. Post pandemic, nurses need to reclaim evidence-based practices, critically appraise evidence, and educate patients and families to address misinformation.

Conclusions:

Information learned will inform competency-based EBP education for students and nurses in academic and clinical settings.
Morphologic Features of Invasion in Lung Adenocarcinoma: Diagnostic Pitfalls
Authors: Thunnissen Erik , Noguchi Masayuki , Berezowska Sabina , Papotti Mauro Giulio , Filipello Federica , Minami Yuko , Blaauwgeers Hans
Published: May 2024

Reproducibility of pulmonary invasive adenocarcinoma diagnosis is poor when applying the World Health Organization (WHO) classification. In this article, we aimed first to explain by 3-dimensional morphology why simple pattern recognition induces pitfalls for the assessment of invasion as applied in the current WHO classification of pulmonary adenocarcinomas. The underlying iatrogenic-induced morphologic alterations in collapsed adenocarcinoma in situ overlap with criteria for invasive adenocarcinoma. Pitfalls in seemingly acinar and papillary carcinoma are addressed with additional cytokeratin 7 and elastin stains. In addition, we provide more stringent criteria for a better reproducible and likely generalizable classification.
Sarcomatoid and Rhabdoid Renal Cell Carcinoma
Authors: Adeniran Adebowale J. , Shuch Brian , Humphrey Peter A.
Published: May 2024

Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid morphologies has an aggressive biological behavior and a typically poor prognosis. The current 2022 WHO classification of renal tumors does not include them as distinct histologic entities but rather as transformational changes that may arise in a background of various distinct histologic types of RCC. The sarcomatoid component shows malignant spindle cells that may grow as intersecting fascicles, which is reminiscent of pleomorphic undifferentiated sarcoma. The rhabdoid cells are epithelioid cells with eccentrically located vesicular nuclei with prominent nucleoli and large intracytoplasmic eosinophilic inclusions. Studies have shown that RCCs with sarcomatoid and rhabdoid differentiation have distinctive molecular features. Sarcomatoid RCC harbors shared genomic alterations in carcinomatous and rhabdoid components, but also enrichment of specific genomic alterations in the sarcomatoid element, suggesting molecular pathways for development of sarcomatoid growth from a common clonal ancestor. Rhabdoid differentiation also arises through clonal evolution although less is known of specific genomic alterations in rhabdoid cells. Historically, treatment has lacked efficacy, although recently immunotherapy with PD-1/PD-L1/CTLA-4 inhibitors has produced significant clinical responses. Reporting of sarcomatoid and rhabdoid features in renal cell carcinoma is required by the College of American Pathologists and the International Collaboration on Cancer Reporting. This manuscript reviews the clinical, pathologic, and molecular features of sarcomatoid RCC and rhabdoid RCC with emphasis on the morphologic features of these tumors, significance of diagnostic recognition, the molecular mechanisms of tumorigenesis and differentiation along sarcomatoid and rhabdoid lines, and advances in treatment, particularly immunotherapy.
Has Propranolol Eradicated the Need for Surgery in the Management of Infantile Hemangioma?
Authors: Coulie Julien , Dekeuleneer Valérie , Gerdom Alexander , Roggen Mieke , Bataille Anne-Christine , Moniotte Stéphane , Coyette Maude , De Roo An-Katrien , Boon Laurence M.
Published: May 2024

Background:

The authors assessed the impact of propranolol as the first-line treatment of infantile hemangioma (IH) on the need for surgery in the management of IH.

Methods:

In this retrospective study, 420 patients with IH referred to a multidisciplinary center between January of 2005 and August of 2014 were included. Clinical data, including sex; age at first consultation and at treatment initiation; location, size, number, aspect, and complications of IH; and type of treatment were collected. Statistical analyses were conducted considering each patient and each tumor independently.

Results:

A total of 625 IHs (420 patients) were reviewed; 113 patients had more than 1 IH (26.91%). Median age at first consultation was 7 months. Overall, 243 patients were treated (57.86%) using surgery (n = 128 patients, 141 IHs), propranolol (n = 79 patients, 89 IHs), corticosteroids (n = 51 patients, 56 IHs), or laser (n = 34 patients, 36 IHs). Propranolol was effective in all but 2 infants with IH. Seven of 79 patients (8.86%) initially treated with propranolol still required surgery, in contrast to 18 of 51 patients (35.29%) initially treated with corticosteroids and 103 of 290 patients (35.51%) with no medical treatment. Since the availability of propranolol, patients were less likely to undergo surgery (48 versus 80 patients; P < 0.001). This demonstrated that the use of propranolol reduced the need for surgery (P < 0.001; OR, 0.177; 95% CI, 0.079 to 0.396).

Conclusions:

Propranolol dramatically reduced the need for surgery, regarding indications and number of patients. Surgical correction remains important for sequelae management, nonresponders, or strawberry-like IH.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Use of Auricular Composite Graft in Rib Cartilage–Based Rhinoplasty for Contracted Nose Correction
Authors: Kim Young Chul , Choi Jong Woo
Published: May 2024

Background:

This study investigated the effects of combining an auricular composite graft with rib cartilage–based rhinoplasty to correct contracted noses in Asian patients with a history of multiple previous operations.

Methods:

A total of 43 patients were included in the retrospective analysis of secondary rhinoplasty procedures. The surgical approach involved short-nose correction, using rib cartilage for septal extension grafts and chondrocutaneous composite grafts harvested from the conchal part of the ear for internal nasal lining reconstruction. The authors’ assessment encompassed clinical outcomes, the occurrence of complications; and the use of 3-dimensional photography for nasal measurements at the preoperative, 3-month, and 1-year postoperative stages.

Results:

With regard to graft survival, 12 patients (27.9%) showed greater than 80% graft engraftment, 29 patients (67.4%) showed 50% to 80% graft engraftment, and 2 patients (4.6%) showed 20% to 50% graft engraftment. Two of these patients required wound irrigation for infection control and additional repair and were finally discharged without significant nasal deformity. At 3 months postoperatively, 3-dimensional anthropometry showed significant differences in nasal dorsum length (4.46 ± 1.79 mm), nasal height (1.25 ± 1.25 mm), nasal tip projection (4.06 ± 1.76 mm), and columellar-labial angle (22.75 ± 14.19 degrees). No significant relapse of nasal parameters was noted 1 year postoperatively.

Conclusions:

Auricular composite graft combined with rib cartilage–based rhinoplasty enables the comprehensive restoration of nasal structures, addressing the inner, intermediate, and outer layers. This approach can serve as an effective and sustainable option for correcting contracted noses in Asian patients who have undergone multiple operations.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Development of an Algorithm to Determine Which Costal Cartilage to Harvest
Authors: Tiftikcioglu Yigit O. , Yegin Ecem E. , Yegin M. Emre , Topaloglu Ege , Canbolat Ozan C. , Gur Ersin , Ceylan Naim
Published: May 2024

Rib graft is a common source of cartilage in rhinoplasty. Donor site choices for this resource were identified according to the authors who presented the introduction of this technique. However, the scientific basis of this valuable method lacks information, including the anatomical properties of costal cartilage. In this study, cartilage radioanatomy is examined and tested for if any estimators are present. A total of 148 thoracal CT scans of patients who applied to our facility were analyzed. Patients were divided per their sex and age of 35, and rib cartilage dimensions, including axial length between the sternal and costal ends of the cartilage (TotL), posteroanterior diameters at the sternal end (StDia), costal end (CosDia), the thickest part (MaxDia) as diametrical parameters and vertical height at the thickest part (h) were recorded. Length of the sternum (St), the axial length of the clavicle (ClavL), the distance of the sixth rib from the anterior axillary border (AntAx), and thorax circumferences at the level of both pectoralis major muscle origin (ThC) and nipples (BrC) were recorded. Statistical analyses were done for correlations. St, ClavL, ThC, and BrC were found to have the most correlated measurements in groups with the age of 35 and less of both genders, and the relations were lost in older groups. Thorax shape may change after the age of 35 years, but in younger patients, St in females and ClavL in males can be used as estimators of cartilage amount.
Contemporary Surgical Management of Craniofacial Fibrous Dysplasia Using Computer-Assisted Surgery and Intraoperative Navigation
Authors: Best David L. , Lee Kevin C. , Reynolds Renée M. , Piccillo Ellen , Behar Philomena , Markiewicz Michael R.
Published: May 2024

Craniofacial fibrous dysplasia (CFD) is a rare developmental disease of bone, which typically presents as a painless, expansile mass causing deformity of the craniofacial skeleton. In rare circumstances, compression of neurovascular structures may arise, causing symptoms such as pain, visual impairment, and hearing loss. Traditionally, CFD debulking has been performed with “freehand” techniques using preoperative imaging and anthropometric norms to determine the ideal amount of tissue removal. The advent of computer-assisted surgery, computer-aided design, and computer-aided manufacturing (CAD/CAM) has revolutionized the management of CFD. Surgeons can now fabricate patient-specific osteotomy/ostectomy guides, allowing for increased accuracy in bone removal and improved cosmetic outcomes. This series of 3 cases describe our institution’s technique using patient-specific ostectomy “depth guides”, which allow for maximum removal of fibro-osseous tissue while sparing deep and adjacent critical structures. These techniques can be widely applied to the craniofacial skeleton to assist in the surgical management of CFD.
Correlation of Orthognathic Surgical Movements to Perception of Facial Appearance in Patients With Cleft Lip and Palate
Authors: Wang Ellen , Tran Joseph T. , Chapa Elysa M. , Cody Ryan , Greives Matthew R. , Nguyen Phuong D.
Published: May 2024

Study Design:

Cephalometric scans were compared before and after surgery to assess the degree of correction. Correlations between skeletal movements and survey outcomes were determined using multivariate regression analysis.

Objective:

This study aims to identify relationships between subjective observer-reported improvements in esthetics and emotional appearance with specific surgical movements.

Methods:

Ten patients at a single tertiary institution (average age: 18.1 ± 0.8), 9 males and 1 female, underwent orthognathic repair and had comprehensive cephalometric records. Standardized anterior posterior and lateral pre and postoperative photographs of patients were included in a survey to clinicians to assess noncognitive domains on a Likert Scale (1–10). CLEFT-Q was administered to gauge patient satisfaction in categories of appearance, speech, and quality of life.

Results:

Per clinicians, multiple domains increased including facial attractiveness (4.1 ± 0.7 versus 7.3 ± 0.7, P < 0.001), friendliness (4.5 ± 0.4 versus 7.3 ± 0.5, P < 0.001), confidence (4.1 ± 0.4 versus 7.1 ± 0.4, P < 0.001), and recommendation for surgery decreased (8.9 ± 0.1 versus 3.6 ± 0.5, P < 0.001). Speech distress decreased with increased SNA and convexity, whereas Psychological and Social scores decreased with an increased ANB. Functional eating and drinking scores increased with maxillary depth.

Conclusions:

Orthognathic surgery improves many noncognitive domains in patients with cleft lip and palate as assessed by both patients and clinicians on all aspects of facial attractiveness and perception. These findings demonstrate objective bases of skeletal adjustments for perceived improvements in facial appearance and emotion.
Mini Endoscopic Septoplasty for High Localized Nasal Septum Deviation: Surgical Technique, Outcomes, and Comparison With Regular Septoplasty
Authors: Liu Jianfeng , Zhao Jianhui , Wang Yibei , Zhao Yu , Han Jun , Yang Dazhang , Chen Yihan
Published: May 2024

Objectives:

This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty.

Methods:

Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months.

Results:

Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma.

Conclusion:

Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.