bluuebunny/crossref_metadata_2025 huggingface dataset:
First-line Immunotherapy for Metastatic Merkel Cell Carcinoma
Authors: Kakish Hanna , Sun James , Ammori John B. , Hoehn Richard S. , Rothermel Luke D.
Published: April 2024

Background:

Immune checkpoint inhibitors are a promising new therapy for advanced Merkel Cell Carcinoma (MCC). We investigated real-world utilization and survival outcomes of first-line immunotherapies in a contemporary cohort.

Methods:

Using the National Cancer Database (NCDB), we identified 759 patients with MCC between 2015 and 2020 with stage IV disease and known status of first-line systemic therapy. Univariable and multivariable analyses were used to determine predictors of immunotherapy usage. Overall survival (OS) was compared for patients receiving immunotherapy, chemotherapy, or no systemic therapies.

Results:

We identified 759 patients meeting our inclusion criteria: 329 patients received immunotherapy, 161 received chemotherapy, and 269 received no systemic therapy. Adjusting for demographic, clinical, and facility factors, high facility volume significantly predicted first-line immunotherapy use (OR 1.99; P=0.017). Median OS was 16.2, 12.3, and 8.7 months, among patients who received immunotherapy, chemotherapy, or no systemic therapy, respectively (P<0.001). On Cox multivariable survival analysis, first-line immunotherapy treatment (HR=0.79, P=0.041) and treatment at high-volume centers (HR=0.58, P=0.004) were associated with improved OS.

Conclusions:

Consistent with clinical trial results, first-line immunotherapy associated with improvement in median overall survival for patients with stage IV MCC, significantly outperforming chemotherapy in this real-world cohort. Treatment at high-volume centers associated with first-line immunotherapy utilization suggesting that familiarity with this rare disease is important to achieving optimal outcomes for metastatic MCC.
Sentinel Node Navigation Surgery for Early Gastric Cancer
Authors: Zhou Jiajie , Li Ruiqi , Zhao Shuai , Sun Longhe , Wang Jie , Fu Yayan , Wang Daorong
Published: April 2024

Early gastric cancer (EGC) refers to malignant tumor lesions that are limited to the mucosa and submucosa layers, regardless of the presence of lymph node metastasis. Typically, EGC has a low rate of perigastric lymph node metastasis, and long-term survival outcomes are good after radical surgical treatment. The primary objective of surgical treatment for EGC is to achieve functional preservation while ensuring a radical cure. Sentinel node navigation surgery (SNNS) is a surgical technique used in the treatment of EGC. This approach achieves functional preservation by limiting lymph node dissection and performing restrictive gastrectomy guided by intraoperative negative sentinel node (SN) biopsy. Despite the apparent improvement in the detection rate of SN with the emergence of various tracing dyes and laparoscopic fluorescence systems, the oncological safety of SNNS remains a controversial research topic. SNNS, as a true form of stomach preservation surgery that enhances the quality of life, has become a topic of interest in the EGC field. In recent years, scholars from Japan and South Korea have conducted extensive research on the feasibility and safety of SNNS in the treatment of EGC. This article aims to provide reference choices for surgeons treating EGC by reviewing relevant research on SNNS for EGC in recent years.
Plasmapheresis as therapeutic option in a 16-year-old with EVALI
Authors: Gaik Christine , Arndt Christian , Mand Nadine , Bauck Monika , Schwerk Nicolaus , Westhoff Christina , Bittmann Iris , Wulf Hinnerk
Published: April 2024

Since 2019 when a cluster of cases with acute respiratory distress syndrome (ARDS) associated with e-cigarettes in the United States was reported, there have been increasing numbers of reports. Electronic-cigarette or Vaping Use-associated Lung Injury (EVALI) represents a recent entity of respiratory clinical syndromes, primarily in young adults. We report a previously healthy 16-year-old boy who developed severe ARDS following a brief nonspecific prodromal phase after excessive consumption of e-cigarettes. Despite maximum intensive care therapy, including several weeks of venovenous extracorporeal membrane oxygenation, plasmapheresis and repeated administration of immunoglobulins seemed the only way to achieve therapeutic success. Although many case reports have been published, to our knowledge, there are none to date on the therapeutic use of plasmaphoresis in severe EVALI. This case highlights the clinical features of EVALI and the diagnostic dilemma that can arise with EVALI occurring against the background of an expired SARS-CoV-2 infection, with a paediatric inflammatory syndrome (PIMS) as differential diagnosis. EVALI is a diagnosis of exclusion, and the medical history of vaping and e-cigarette use can provide valuable clues.

Ethical approval for this case report (protocol number 23–145 RS) was provided by the Ethical Committee of the Department of Medicine, Philipps-Universität Marburg, Germany on 13th of June 2023. Written informed consent to publish this case and the associated images was obtained from the patient and his mother.
Reconstruction of a Large Composite Hemicraniofacial Defect with Bipedicled DIEP/TRAM Flaps
Authors: Chia Jake , Soliman Bishoy , Hsieh Frank
Published: April 2024

Head and neck reconstructions are often challenging due to the mix of functional and aesthetic goals. It can be tricky when different tissue types are required to reconstruct each subunit. Craniofacial reconstructions require a large volume of tissue to cover defects that span across a large convex area. The latissimus dorsi muscle flap is a workhorse free flap used frequently by surgeons due to its ability to cover over a large surface area. However, there are unique situations when even the latissimus dorsi muscle is not enough to provide the bulk cover for the craniofacial defect. We present a complex case of a hemicraniofacial reconstruction after a hemifacial orbital exenteration and cranial resection of a large neglected basal cell carcinoma.
Ulnar Ray Deficiency: A New Classification and a Unique Case Report
Authors: Al-Qattan Mohammad M. , Al-Abidien Nowar Zain , Al-Mohrij Saad A. , Al-Qattan Ahmed M.
Published: April 2024

Ulnar ray deficiency is a rare congenital upper limb defect. We report on a unique case with hand-on-flank deformity on the one side and limb truncation on the contralateral side. The standard of care for the hand-on-flank deformity is to do humerus osteotomy to reposition the hand anteriorly. However, the right limb truncation in our patient made the senior author decide not to do the osteotomy. Final assessment showed that the posterior hand position enabled the patient to reach the ano-genital areas, the pocket, and the mouth. It was concluded that in case of hand-on-flank deformity in one limb and limb truncation of the contralateral limb, osteotomies to bring the hand anteriorly are not advised.
Lessons Learned From the Development of an ABOG Subspecialty
Authors: FENNER DEE E.
Published: April 2024

As I reflect on my 30 years in academic medicine, my professional journey is uniquely intertwined with the growth and development of the field of urogynecology and the ultimate subspecialty recognition by the American Board of Obstetrics and Gynecology (ABOG), the Association of American Medical Colleges (AAMC), and the American Board of Medical Specialties (ABMS). In this article, I will retrace that journey from personal memories and notes, conversations with the leaders in the room, and documents and minutes generously provided by ABOG and the American Urogynecologic Society (AUGS). There were many leadership lessons learned, and I hope sharing them will enable the readers to do this type of transformational work in their own institution and broadly as advocates of women’s health.
Morphological Differentiation of Corneal Inflammatory Cells
Authors: Schmitz Fynn , Klimas Rafael , Spenner Marie , Schumacher Aurelian , Hieke Alina , Greiner Tineke , Enax-Krumova Elena , Sgodzai Melissa , Fels Miriam , Brünger Jil , Huckemann Sophie , Stude Philipp , Tegenthoff Martin , Gold Ralf , Philipps Jörg , Fisse Anna Lena , Grüter Thomas , Pitarokoili Kalliopi , Motte Jeremias , Sturm Dietrich
Published: April 2024

Purpose:

Corneal confocal microscopy is a noninvasive imaging technique to analyze corneal nerve fibers and corneal inflammatory cells (CICs). The amount of CICs is a potential biomarker of disease activity in chronic autoinflammatory diseases. To date, there are no standardized criteria for the morphological characterization of CICs. The aim was to establish a protocol for a standardized morphological classification of CICs based on a literature search and to test this protocol for applicability and reliability.

Methods:

A systematic review of the literature about definitions of CICs was conducted. Existing morphological descriptions were translated into a structured algorithm and applied by raters. Subsequently, the protocol was optimized by reducing and defining the criteria of the cell types. The optimized algorithm was applied by 4 raters. The interrater reliability was calculated using Fleiss kappa (K).

Results:

A systematic review of the literature revealed no uniform morphological criteria for the differentiation of the individual cell types in CICs. Our first protocol achieved only a low level of agreement between 3 raters (K = 0.09; 1062 rated cells). Our revised protocol was able to achieve a higher interrater reliability with 3 (K = 0.64; 471 rated cells) and 4 (K = 0.61; 628 rated cells) raters.

Conclusions:

The indirect use of criteria from the literature leads to a high error rate. By clearly defining the individual cell types and standardizing the protocol, reproducible results were obtained, allowing the introduction of this protocol for the future evaluation of CICs in the corneal confocal microscopy.
The Impact of Involvement in Whole Health System for Veterans or Participating in It for Oneself on Job Attitudes in VA Employees
Authors: Schult Tamara M. , Mohr David C. , Greenfield Russell H. , Reddy Kavitha P.
Published: April 2024

Objective

The aim of the study is to examine how involvement in the Whole Health System of care, clinically and personally (through employee-focused activities), would affect employee satisfaction, engagement, burnout, and turnover intent in the Veterans Health Administration.

Methods

Multivariate logistic regression analysis of cross-sectional survey from Veterans Health Administration employees was used to determine the influence of Whole Health System involvement and Employee Whole Health participation on job attitudes.

Results

Whole Health System involvement was associated higher job satisfaction, higher levels of engagement, lower burnout, and lower turnover intent. A similar pattern of results was identified when looking specifically at Employee Whole Health participation and associated job attitudes.

Conclusions

Employees who are either directly involved in delivering Whole Health services to veterans or who have participated in Whole Health programming for their own benefit may experience a meaningful positive impact on their well-being and how they experience the workplace.
The Effects of Slope-Adaptive Prosthetic Ankle-Feet on Sloped Gait Performance and Quality in Unilateral Transtibial Prosthesis Users: A Scoping Review
Authors: Mueller Emily , Major Matthew J.
Published: April 2024

Introduction

In nonimpaired human locomotion, sagittal-plane slope adaptation of the ankle-foot complex is a function driven by neuromotor control to support upright posture and forward ambulation. Loss of this adaptation due to transtibial amputation can lead to instability and compensatory motions as most commercially available prosthetic feet do not permit automatic slope adjustments. A selection of slope-adaptive ankle-feet (SAAF) has been developed to promote biomimetic ankle motion while ambulating over slopes. This review evaluated the current literature to assess the effects of SAAF prostheses on sloped gait performance in unilateral transtibial prosthesis users.

Methods

Four databases (PubMed, Embase, CINAHL, IEEE Xplore) were searched on April 28, 2022, for relevant articles. Search keywords covered the general terms “transtibial,” “amputation,” “slope,” “adaptive,” and “gait,” and included articles comparing an SAAF prosthesis to a non-SAAF prosthesis condition. Data were extracted for analysis, and results were grouped according to outcomes to identify trends and aid interpretation of slope adaptation effects on gait.

Results

Of the 672 articles screened, 24 met the selection criteria and were included in this review, published between 2009 and 2022. The non-SAAF condition included dynamic response feet and SAAF prostheses with the adaptability function inactive.

Outcomes included biomechanical variables (joint dynamics, gait symmetry, toe clearance), clinical outcome measures, and energy expenditure. All SAAF demonstrated some form of foot-ankle slope gradient adaptability, but effects on other joint dynamics were inconsistent. Minimum toe clearance during incline and decline walking was greater when using SAAF compared with non-SAAF in all reporting studies.

Conclusions

Results generally suggest improvements in gait quality, comfort, and safety with use of SAAF compared with non-SAAF during sloped walking. However, variations in tested SAAF and walking gradients across studies highlight the need for research to elucidate walking condition effects and advantages of specific designs.

Clinical Relevance

Slope-adaptive prosthetic ankle-feet may improve user gait quality and comfort and enhance gait safety by increasing minimum toe clearance. Patients who encounter slopes regularly should be considered as potential users of SAAF if indicated appropriately.
Improving care in lung cancer surgery: a review of quality measures and evolving standards
Authors: Lee Rachel M. , Rajaram Ravi
Published: April 2024

Purpose of review

Lung cancer is the leading cause of cancer-related death in the United States. Pulmonary resection, in addition to perioperative systemic therapies, is a cornerstone of treatment for operable patients with early-stage and locoregional disease. In recent years, increased emphasis has been placed on surgical quality metrics: specific and evidence-based structural, process, and outcome measures that aim to decrease variation in lung cancer care and improve long term outcomes. These metrics can be divided into potential areas of intervention or improvement in the preoperative, intraoperative, and postoperative phases of care and form the basis of guidelines issued by organizations including the National Cancer Center Network (NCCN) and Society of Thoracic Surgeons (STS). This review focuses on established quality metrics associated with lung cancer surgery with an emphasis on the most recent research and guidelines.

Recent findings

Over the past 18 months, quality metrics across the peri-operative care period were explored, including optimal invasive mediastinal staging preoperatively, the extent of intraoperative lymphadenectomy, surgical approaches related to minimally invasive resection, and enhanced recovery pathways that facilitate early discharge following pulmonary resection.

Quality metrics in lung cancer surgery is an exciting and important area of research. Adherence to quality metrics has been shown to improve overall survival and guidelines supporting their use allows targeted quality improvement efforts at a local level to facilitate more consistent, less variable oncologic outcomes across centers.
Radioguided surgery for lymph node metastases in prostate cancer
Authors: Knipper Sophie , Falkenbach Fabian , Maurer Tobias
Published: April 2024

Purpose of review

This review highlights recent advancements in radioguided surgery (RGS) for prostate cancer. Our objective is to provide expert insights into the state of research, as reflected in the selected articles, and to offer perspectives on the clinical implications and future directions that emerge from this rapidly evolving domain.

Recent findings

Key findings include the potential of PSMA-RGS surgery to improve the detection of lymph node invasion in primary prostate cancer, to guide successful removal of metastatic lesions in oligorecurrent patients with acceptable complications, and the feasibility of robot-assisted PSMA-RGS using a miniaturized gamma probe. Additionally, the development of novel PSMA ligands and the integration of fluorescence imaging offer promising improvements in imaging and surgical guidance.

PSMA-RGS is an emerging approach that shows promise for improving lymph node assessment and treatment outcomes in prostate cancer. However, its effect on cancer-specific as well as overall survival are still being investigated, and PSMA-targeted surgery remains an area of active research.
Psychometric properties and factor structure of the traditional Chinese version of the Community Integration Questionnaire-Revised in traumatic brain injury survivors
Authors: Chen Pin-Yuan , Wei Li , Su Yu-Kai , Lin Jiann-Her , Jang Jing-Wen , Hou Wen-Hsuan , Hsu Li-Fang , Chiu Hsiao-Yean
Published: April 2024

This study aimed to translate and validate the traditional Chinese version of the Community Integration Questionnaire-Revised (TC-CIQ-R) in patients with traumatic brain injury (TBI). We included participants aged ≥20 years and diagnosed as having TBI for ≥6 months from neurosurgical clinics. The 18-item TC-CIQ-R, Participation Measure – 3 Domains, 4 Dimensions (PM-3D4D), Extended Glasgow Outcome Scale (GOSE), and Taiwanese Quality of Life After Brain Injury (TQOLIBRI) were completed. The sample included 180 TBI survivors (54% male, mean age 47 years) of whom 87% sustained a mild TBI. Exploratory factor analysis extracted four factors – home integration, social integration, productivity, and electronic social networking – which explained 63.03% of the variation, after discarding the tenth item with a factor loading of 0.25. For criterion-related validity, the TC-CIQ-R was significantly correlated with the PM-3D4D; convergent validity was exhibited by demonstrating the associations between the TC-CIQ-R and TQOLIBRI. Known-group validity testing revealed significant differences in the subdomain and total scores of the TC-CIQ-R between participants with a mean GOSE score of ≤6 and >7 (all P < 0.001). The TC-CIQ-R exhibited acceptable Cronbach’s α values (0.68–0.88). We suggest the 17-item TC-CIQ-R as a valid tool for rehabilitation professionals, useful for both clinical practice and research in assessing community integration levels following TBI.
Expression of TGF-β1 in Gastrointestinal Stromal Tumor (GIST) and the Occurrence of Frequent Desmoplasia
Authors: Mochizuki Kunio , Oishi Naoki , Tahara Ippei , Inoue Tomohiro , Kondo Tetsuo
Published: April 2024

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms with variable behavior characterized by differentiation toward the interstitial cells of Cajal occurring anywhere in the gastrointestinal stromal tract. Frequently, GISTs have fibrous stroma within tumor cell proliferation areas, which is unlike other types of malignant tumors. If this desmoplasia is active, there is a possibility that some sort of transmitter exists between GIST cells and cells related to fibrosis in the tumor cell proliferation areas. Transforming growth factor (TGF)-β isoforms, particularly TGF-β1, are critical for fibrosis pathogenesis. TGF-β1 regulation of myofibroblasts and fibroblasts during fibrosis is well described. The induced fibroblast activation resulting in myofibroblast differentiation has been reported as an important source of collagen, glycoproteins, proteoglycans, and matrix metallopeptidases in wound healing and fibrosis. However, there are a few reports on the relationship between TGF-β1 and GISTs. This study aims to clarify TGF-β1 expression in 30 gastric GISTs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we also enrolled 30 samples of gastric tubular adenocarcinoma (GTAC). We confirmed TGF-β1 expression (H-score ≥50 points) in 57% of GIST and 13% of GTAC samples, a significant difference between the 2 tumor types (P=0.001). We examined the TGF-β1 mRNA expression of 3 representative GIST samples, each having their respective immunostained areas detected by RT-PCR. Finding TGF-β1 expression may indicate that this cytokine plays a part in the formation of desmoplasia within GIST cell proliferative areas.
An Innovative Technique of Presurgical Lip, Alveolus, and Nose Approximation (PLANA) for Infants with Clefts
Authors: Shetye Pradip R.
Published: April 2024

The innovative technique of “presurgical lip, alveolus, and nose approximation” (PLANA) offers a new approach within the domain of presurgical infant orthopedics for infants born with cleft lip and palate. Presurgical lip, alveolus, and nose approximation introduces the utilization of the NoseAlign device in conjunction with medical adhesive tapes, designed to approximate and support displaced soft tissue nasolabial structures in patients with cleft, without an intraoral plate. The NoseAlign device, constructed from medical-grade silicone, consists of 2 tubular portions that fit into the nostrils, connected by a columella band. Notably, it also features a wave-shaped and curved horizontal lip band, resting on the upper lip, with elastic clasps for secure attachment to the face with medical adhesive tapes. Presurgical lip, alveolus, and nose approximation therapy employs the NoseAlign device to support the collapsed nasal alar rim and cartilage, the displaced columella, the deviated nasal septum, and the displaced nasal alar base. This innovative approach minimizes the need for frequent office visits, making it particularly suitable for patients residing at a distance from specialized cleft centers. The prefabricated NoseAlign device offers effective support to nasal structures, making it suitable for unilateral and bilateral clefts. Importantly, the absence of an intraoral plate ensures it does not interfere with feeding. Presurgical lip, alveolus, and nose approximation therapy, initiated as early as 1 to 2 weeks, leverages the plasticity of nasal soft tissue and cartilage to achieve the desired nasal form before primary surgery. Although presurgical lip, alveolus, and nose approximation therapy does have some limitations, particularly in cases of medially collapsed alveolar segments, its simplicity, universal applicability, and patient-friendliness make it a promising technique in the presurgical infant orthopedics field.
Positive allosteric modulation of a GPCR ternary complex
Authors: Burger Wessel A.C. , Draper-Joyce Christopher J. , Valant Celine , Christopoulos Arthur , Thal David M.
Published: April 2024

The activation of a G protein-coupled receptor (GPCR) leads to the formation of a ternary complex between agonist, receptor, and G protein that is characterised by high-affinity binding. Allosteric modulators bind to a distinct binding site from the orthosteric agonist and can modulate both the affinity and the efficacy of orthosteric agonists. The influence allosteric modulators have on the high-affinity active state of the GPCR-G protein ternary complex is unknown due to limitations on attempting to characterize this interaction in recombinant whole cell or membrane-based assays. Here, we use purified M2muscarinic acetylcholine receptor (mAChR) reconstituted into nanodiscs to show that once the agonist-bound high-affinity state is promoted by the G protein, positive allosteric modulators stabilise the ternary complex that, in the presence of nucleotides leads to an enhanced initial rate of signalling. Our results enhance our understanding of how allosteric modulators influence orthosteric ligand signalling and will aid the design of allosteric therapeutics.

Teaser

Allostery from top and bottom, the combined influence of positive allosteric modulators on receptor signalling.
Prevalence and population attributable fractions of potentially modifiable risk factors for dementia in Canada: a cross-sectional analysis of the Canadian Longitudinal Study on Aging
Authors: Dolatshahi Yasaman , Mayhew Alexandra , O’Connell Megan E. , Liu-Ambrose Teresa , Taler Vanessa , Smith Eric E. , Hogan David B. , Kirkland Susan , Costa Andrew P. , Wolfson Christina , Raina Parminder , Griffith Lauren , Jones Aaron
Published: April 2024

Background

Identification and assessment of modifiable risk factors for dementia is a public health priority in Canada and worldwide. We investigated the prevalence and population attributable fraction (PAF) of 12 potentially modifiable risk factors for all-cause dementia in middle-aged and older Canadians.

Methods

We conducted a cross-sectional study of data from the Comprehensive cohort of the Canadian Longitudinal Study on Aging, a national sample of 30,097 individuals between the ages of 45 and 85 at baseline (2011-2015). Risk factors and associated relative risks were taken from a highly cited systematic review published by an international commission on dementia prevention. We estimated the prevalence of each risk factor using sampling weights to be more generalizable to the Canadian population. Individual PAFs were calculated both crudely and weighted for communality, and combined PAFs were calculated with methods reflecting both multiplicative and additive interaction assumptions. Analyses were additionally performed stratified by household income and were repeated at CSLA’s first three-year follow-up (2015-2018).

Results

The most prevalent risk factors at baseline were physical inactivity (63.8%; 95% CI, 62.8% – 64.9%), hypertension (32.8%; 31.7% – 33.8%), and obesity (30.8%; 29.7% – 31.8%). The highest crude PAFs were for physical inactivity (19.9%), traumatic brain injury (16.7%), and hypertension (16.6%). The highest weighted PAFs were for physical inactivity (11.6%), depression (7.7%), and hypertension (6.0%). We estimated that the 12 risk factors combined accounted for 43.4% (37.3%-49.0%) of dementia cases assuming weighted multiplicative interactions and 60.9% (55.7%-65.5%) assuming additive interactions. There was a clear gradient of increasing prevalence and PAF with decreasing income for 9 of the 12 risk factors.

Interpretation

The findings of this study can inform individual and population-level dementia prevention strategies in Canada, focusing efforts on risk factors with the largest impact on the number of dementia cases. Differences in the impact of individual risk factors between this study and other international and regional studies highlight the importance of tailoring national dementia strategies to the local distribution of risk factors.
Comparative Application of the Fluctuation Test to the data of Morbidity by COVID-19 in United States of America, United Kingdom, Taiwan and China 2020-2023
Authors: López-Ramírez Anyi Yannire , Grassi Hilda Cristina , de Jesús Andrades Efrén , Andrades-Grassi Jesús Enrique
Published: April 2024

In this work the Luria and Delbruck Fluctuation Test was comparatively applied to the data of Morbidity by COVID-19 in the United States of America (USA), United Kingdom (UK), Taiwan and China from 2020 to 2023. Three types of data were used:es.statista.com,datosmacro.expansion.comand larepublica.co without modification, but trying to avoid and justify the anomalies and inconsistencies observed. The methods originally used to establish the interactions of two populations were evaluated: the viral population with that of its host and the drift of both organisms. Only the interactive fluctuations of the weekly Variance of daily increase of Cases (Morbidity) were studied. The results showed that the Fluctuation Test is applicable to the selected data from USA, UK, Taiwan and China and other data from several countries used as controls. The study was separated into two approaches: First, comparison of the total or partial logarithmic profile of fluctuations of Variance of Cases (Morbidity) of USA, UK, Taiwan and China. Second, comparison of the values of the first fluctuation of Variance of Cases (Morbidity) in the boreal winter of 2020 for USA, UK, Taiwan, China and several countries used as controls. The results obtained for Morbidity demonstrate that USA and UK present a similar bimodal profile. China shows an inverted profile and Taiwan shows an intermediate profile between both tendencies. However, it was possible to detect some anomalies and uncertainties that were possibly derived from inconsistencies in the original data. Only USA shows a value of the first fluctuation comparable to the order of magnitude of the value of the first fluctuation of the Variance of Cases of China, in the northern winter of 2020. In the First Approach USA, UK and China had two important fluctuations: the first in the northern winter of 2020 before week 16 and the second at the beginning of northern winter of 2022, more than 100 weeks later. Taiwan showed only the latter. This latest fluctuation coincides with two events: the possible achievement of herd immunity and the emergence of Omicron variant. In this work we have evaluated whether this coincidence is casual or causal. The results obtained in the Second Approach aim to confirm the hypothesis of the animal origin of the first variant of SARS CoV-2.
Teaching Uncommon Diseases in Surgery: Conceptual Framework for the Development of a Peritoneal Surface Malignancy Curriculum
Authors: Godley Frederick A , Bansal Varun V , Su David G. , Gushchin Vadim , Moller Mecker G , Shah Rupen , Gangi Alexandra , Magge Deepa , Blazer Dan G , Eng Oliver S , Lambert Laura , Dineen Sean , Abdel-Misih Sherif , Encandela John , Turaga Kiran K
Published: April 2024

Background

There is a critical need for contemporary education to address peritoneal surface malignancies (PSM). This study delineates the development of an online PSM curriculum for surgical trainees, in conjunction with a national consortium.

Methods

A needs assessment survey was administered to attending surgical oncologists and trainees within the consortium, with a focus on current educational practices and preferences for PSM training. The identified focus areas informed the formulation of specific learning objectives and content.

Results

The survey was completed by of 86/171 (48.5%) attending surgical oncologists in the group and 70 surgical trainees (56 residents and 14 fellows) from 31 unique institutions. Attending surgical oncologists emphasized trainee familiarity with general PSM principles and peritoneal metastases from lower gastrointestinal and gastric cancers when compared to gynecologic cancers and uncommon primaries (p < 0.001). Attending expectations increased incrementally with the trainee level in the knowledge and patient care domains. Attendings and trainees identified didactics and textbooks as primary modes of learning, although trainees reported using mobile learning tools more frequently. Disease site-specific educational content aligned with learning objectives was uploaded to a previously piloted online learning management system. Clinical management pathways and rotation guides were integrated to enhance the clinical applicability and consistency.

Conclusions

Designing a PSM curriculum tailored to the educational needs of both attendants and trainees is feasible by using established pedagogical methods. This study provides a framework for teaching about complex diseases with limited educational literature.
Differential Expression Analysis of Cannabis sativa response to thermotherapy of Hops Latent Viroid (HLVd) infection and clearance of the viroid in Tissue Culture Micropropagation
Authors: Torres Anthony , Pauli Chris , Sarmiento Carolina , Zalewski Chris , Gaudino Reggie
Published: April 2024

Increased farming and cultivation ofCannabis sativais rapidly pushing Cannabis (Cannabis sativaL.) towards becoming a commercial agricultural commodity. Large-scale cultivation facilities maintain thousands of clonal varieties of recreational and medicinal cannabis and there is a strong market-driven motivation to maintain a commercial pipeline of clean healthy vigorously growing plants free of pathogens. However, mass production and high-capacity cultivation create an environment that is susceptible to highly transmissible pathogens and infectious entities such as Hop Latent Viroid (HLVd). From nurseries to cultivation facilities, it’s become increasingly important to maintain a routine testing regimen and ensure cultivation facilities are HLVd-free environments. One method to address the problem of infected plants is to perform thermotherapy onC. sativaexplants under tissue culture conditions and isolate clean tissue to multiply productive and healthy mature plants. We carried out a novel thermotherapy method using tissue culture in 5 varieties of type III cannabis that were HLVd positive to document the degree of success of the treatment at the RNA level. We observed that following thermotherapy treatment we were able to decrease the level of HLVd positive tests in select varieties and observed some varieties were highly susceptible and unable to clear the viroid. Plants were tested using a one-step RT-qPCR method, developed and validated, in part, along with this work, and present the results as well as an exploratory transcriptome analysis of an internally developed variety, AnnaLee, which tested negative for HLVd following thermotherapy treatment, and explore possible genes of interest for viroid infection, clearance, and mitigation.

Author Summary

RT-qPCR and transcriptome analysis of Hops latent viroid (HLVd) in infected and non-infectedCannabisvarieties. A thermotherapy procedure was conducted on HLVd infectedCannabis sativameristem tissue maintained through tissue culture micropropagation techniques. Total RNA was isolated from the cultured plantlet stocks and evaluated by a real-time reverse transcriptase assay for HLVd. Infection status post thermotherapy was assessed, and viroid-free plants were maintained and subsequently tested. A single thermotherapy-treated cultivar, Anna Lee was selected for transcriptomics, and an analysis of the genes that were differentially regulated in infected and non-infected treated plants is discussed.
Principles of ion binding to RNA inferred from the analysis of a 1.55 Å resolution bacterial ribosome structure – Part I: Mg2+
Authors: Leonarski Filip , Henning-Knechtel Anja , Kirmizialtin Serdal , Ennifar Eric , Auffinger Pascal
Published: April 2024

The importance of Mg2+ions for RNA structure and function can difficultly be overstated. Several attempts were made to establish a comprehensive Mg2+binding site classification. However, such descriptions were hampered by poorly modelled ion binding sites. Recently, ribosome cryo-EM structures with resolutions < 2.0 Å allowed better descriptions of site-bound ions. However, in a recent cryo-EM 1.55 ÅE. coliribosome structure, incomplete ion assignments prevented a full understanding of their binding modes. We revisited this model to establish general binding principles applicable to any RNA of sufficient resolution. These principles rely on the 2.9 Å distance separating two Mg2+-boundcis-water molecules. By applying these rules, we could assign all Mg2+ions bound with 2 to 4 non-water oxygens. We also uncovered unanticipated motifs where up to five adjacent nucleotides wrap around a single ion. The formation of these complex motifs involves a hierarchical dehydration of the Mg2+ions, a process that plays a significant role in ribosome biogenesis and in the folding of large RNAs. These binding principles enhance our understanding of the roles of ions in RNA structure and will help refining the solvation shell of different ribosomes and of RNAs with complex topologies.
A Step-Emulsion Based Digital-RPA for Pathogenic Bacteria Detection
Authors: jin Jing , Lu Ling , Chen Huicheng , Wang Yunhua , Zheng Gouxia
Published: April 2024

Foodborne bacteria are major causes that affect human health. Development of new method that could achieve Rapid, sensitive and quantitative detection of pathogen is urgently needed. In this research, a step emulsion microfluidic,combined with droplet-based digital-RPA, was developed to detectVibrio parahaemolyticus, a major seafood-borne pathogenic bacteria. Specific and rapid detection ofVibrio parahaemolyticusin 30 min has been achieved by this new device, with a detection limit of 10 CFU/μL, about 10-times lower than classical tube-based RPA. This device was demonstrated to be a promising tool for detection of pathogenic bacteria.
SBT5.2s are the major active extracellular subtilases processing IgG antibody 2F5 in theNicotiana benthamianaapoplast
Authors: Beritza Konstantina , Buscaill Pierre , Song Shi-Jian , Jutras Philippe V. , Huang Jie , Mach Lukas , Dong Suomeng , van der Hoorn Renier A. L.
Published: April 2024

Plants offer a powerful platform for recombinant protein production but degradation of recombinant proteins by endogenous proteases is causing severe yield losses. Here, we introduce triple knockout lines for SBT5.2, the major active subtilases in the apoplast of agroinfiltratedNicotiana benthamiana. HIV-neutralising IgG antibody 2F5 is no longer cleaved in the apoplast ofsbt5.2mutants and these mutants accumulate 3-fold more 2F5 upon transient expression but grow normally. Remarkably, however, 2F5 does not accumulate in the apoplast and is not exposed to SBT5.2 when transiently expressed, uncovering an important controversy regarding the subcellular localisation of IgGs in agroinfiltrated plants.
WITHDRAWN: Immune regulatorsEDS1andPAD4constrainADR1-dependent disease resistance in rice
Authors: Fernandes Joel , Wang Junli , Su Rong , Lee Tak , Zheng Zichao , Perin Silvina , Cesari Stella , Jalilian Ahmad , Sciallano Coline , Szurek Boris , Cui Haitao , Kroj Thomas , Parker Jane E.
Published: April 2024

Withdrawal Statement

The authors have withdrawn this manuscript owing to finding inconsistencies in genotyping of kitaake rice eds1 pad4 double mutant lines and to establishing that combined loss of EDS1 and PAD4 does not underlie the stunted ‘autoimmune-like’ phenotype reported in this preprint. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding authors: Jane Parker, Thomas Kroj and Haitao Cui (co-corresponding)
Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype
Authors: Nuechterlein Nicholas , Shelbourn Allison , Szulzewsky Frank , Arora Sonali , Casad Michelle , Pattwell Siobhan , Merino-Galan Leyre , Sulman Erik , Arowa Sumaita , Alvinez Neriah , Jung Miyeon , Brown Desmond , Tang Kayen , Jackson Sadhana , Stoica Stefan , Chittaboina Prashant , Banasavadi-Siddegowda Yeshavanth K. , Wirsching Hans-Georg , Stella Nephi , Shapiro Linda , Paddison Patrick , Patel Anoop P. , Gilbert Mark R. , Abdullaev Zied , Aldape Kenneth , Pratt Drew , Holland Eric C. , Cimino Patrick J.
Published: April 2024

Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR–Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominatePDE10Aas a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro. Cell culture analysis showed that decreased Pde10a expression led to increased PI3K/AKT signaling in a Pten-independent manner, a response blocked by selective PI3K inhibitors. Single-nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation, further showed that Pde10a suppression was associated with a proneural-to-mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. Our results indicate that glioblastoma patients harboringPDE10Aloss have worse outcomes and potentially increased sensitivity to PI3K inhibition.
Multimodule microwave assembly for fast readout and charge-noise characterization of silicon quantum dots
Authors: von Horstig Felix-Ekkehard , Ibberson David J. , Oakes Giovanni A. , Cochrane Laurence , Wise David F. , Stelmashenko Nadia , Barraud Sylvain , Robinson Jason A.W. , Martins Frederico , Gonzalez-Zalba M. Fernando
Published: April 2024

Fast measurements of quantum devices is useful in areas such as quantum sensing, quantum computing, and nanodevice quality analysis. Here, we develop a superconductor-semiconductor multimodule microwave assembly to demonstrate charge-state readout at the state of the art. The assembly consist of a superconducting readout resonator interfaced to a silicon-on-insulator (SOI) chiplet containing quantum dots (QDs) in a high-κ nanowire transistor. The superconducting chiplet contains resonant and coupling elements as well as LC filters that, when interfaced with the silicon chip, result in a resonant frequency f=2.12 GHz, a loaded quality factor Q=850, and a resonator impedance Z=470Ω. Combined with the large gate lever arms of SOI technology, we achieve a minimum integration time for single and double QD transitions of 2.77 and 13.5 ns, respectively. We utilize the assembly to measure charge noise over 9 decades of frequency up to 500 kHz and find a 1/f dependence across the whole frequency spectrum as well as a charge-noise level of 4μeV/Hz at 1 Hz. The modular microwave circuitry presented here can be directly utilized in conjunction with other quantum devices to improve the readout performance as well as enable large bandwidth noise spectroscopy, all without the complexity of superconductor-semiconductor monolithic fabrication.

Published by the American Physical Society
2024
Solitons in binary compounds with stacked two-dimensional honeycomb lattices
Authors: Muten James H. , Frankland Louise H. , McCann Edward
Published: April 2024

We model the electronic properties of thin films of binary compounds with stacked layers where each layer is a two-dimensional honeycomb lattice with two atoms per unit cell. The two atoms per cell are assigned different on-site energies in order to consider six different stacking orders: ABC, ABA, AA, ABC′, ABA′, and AA′. Using a minimal tight-binding model with nearest-neighbor hopping, we consider whether a fault in the texture of on-site energies in the vertical, stacking direction supports localized states, and we find localized states within the bulk band gap for ABC, ABA, and AA′ stacking. Depending on the stacking type, parameter values, and whether the soliton is atomically sharp or a smooth texture, there are a range of different band structures including soliton bands that are either isolated or that hybridize with other states, such as surface states, and soliton bands that are either dispersive or flat, the latter yielding narrow features in the density of states. We discuss the relevance of our results to specific materials including graphene, hexagonal boron nitride, and other binary compounds.

Published by the American Physical Society
2024
JLab spectral functions of argon in nuwro and their implications for MicroBooNE
Authors: Banerjee Rwik Dharmapal , Ankowski Artur M. , Graczyk Krzysztof M. , Kowal Beata E. , Prasad Hemant , Sobczyk Jan T.
Published: April 2024

The Short-Baseline Neutrino program in Fermilab aims to resolve the nature of the low-energy excess events observed in LSND and MiniBooNE, and analyze with unprecedented precision neutrino interactions with argon. These studies require a reliable estimate of neutrino cross sections, in particular for charged current quasielastic scattering (CCQE). Here, we report updates of the uro Monte Carlo generator that, most notably, bring the state-of-the-art spectral functions to model the ground state properties of the argon nucleus, and improve the accuracy of the cross sections at low energies by accounting for the effects of the nuclear Coulomb potential. We discuss these developments in the context of electron and neutrino interactions, by comparing updated uro predictions to experimental data from Jefferson Laboratory Hall A and MicroBooNE. The MicroBooNE CCQE-dominated data are described with the χ2 per degree of freedom of 0.7, compared with 1.0 in the local Fermi gas model. The largest improvement is observed for the angular distributions of the produced protons, where the χ2 reduces nearly by half. Being obtained using the axial form factor parametrization from MINERvA, our results indicate a consistency between the CCQE measurements in MINERvA and MicroBooNE.

Published by the American Physical Society
2024
Supersymmetry with scalar sequestering
Authors: Baer Howard , Barger Vernon , Martinez Dakotah
Published: April 2024

Supersymmetric models with a strongly interacting superconformal hidden sector (HS) may drive soft supersymmetry (SUSY) breaking scalar masses, bilinear soft term Bμ and Higgs combinations mHu,d2+μ2 to small values at some intermediate scale, leading to unique sparticle mass spectra along with possibly diminished fine-tuning in spite of a large superpotential μ parameter. We set up a computer code to calculate such spectra, which are then susceptible to a variety of constraints: (1) possible charge-or-color breaking (CCB) minima in the scalar potential, (2) unbounded from below (UFB) scalar potential, (3) improper electroweak symmetry breaking, (4) a charged or sneutrino lightest SUSY particle (LSP), (5) generating mh∼125  GeV, (6) consistency with LHC sparticle mass limits, and (7) naturalness. We find this bevy of constraints leaves little or no viable parameter space for the case where hidden sector dynamics dominates minimal supersymmetric standard model (MSSM) running, even for the case of nonuniversal gaugino masses. For the case with moderate HS running with comparable MSSM running, and with universal gaugino masses, then the fine-tuning is ameliorated, but nonetheless remains high. Viable spectra with moderate HS running and with low fine-tuning and large μ can be found for nonuniversal gaugino masses.

Published by the American Physical Society
2024
Probing Zee-Babu states at muon colliders
Authors: Jueid Adil , Chowdhury Talal Ahmed , Nasri Salah , Saad Shaikh
Published: April 2024

The Zee-Babu model is a minimal realization of radiative neutrino mass generation mechanism at the two-loop level. We study the phenomenology of this model at future multi-TeV muon colliders. After imposing all theoretical and low-energy experimental constraints on the model parameters, we find that the Zee-Babu states are expected not to reside below the TeV scale, making it challenging to probe them at the LHC. We first analyze the production rates for various channels, including multi singly charged and/or doubly charged scalars at muon colliders. For concreteness, we study several benchmark points that satisfy neutrino oscillation data and other constraints and find that most channels have large production rates. We then analyze the discovery reach of the model using two specific channels: the pair production of singly and doubly charged scalars. For the phenomenologically viable scenarios considered in this study, charged scalars with masses up to O(3–4)  TeV can be probed for the center-of-mass energy of 10 TeV and total luminosity of 10  ab−1.

Published by the American Physical Society
2024