bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients’ Preference for Physician Attire in the Internal Medicine Outpatient Department
Authors: Zou Yiyan , Wang Yiyou , Song Yang , Liu Sen , Zhang Zhiyuan , Wang Limei , Zhang Jieshi , Geng Ruixuan , Zheng Zhibo , Chen Yeye
Published: January 2023

Objective. To investigate patients’ preference and the attitude towards physician attire in an internal medicine clinic in China. Methods. This study was conducted from 1 January 2021 to 30 June 2021 in a tertiary care hospital in China. We surveyed 126 patients in the hospital with 6 sets of pictures of commonly worn physician attires in the hospital setting with a two‐part questionnaire. The first part listed respondent demographics to collect basic information. The second part of the questionnaire was administered to adult patients who received care in the internal medicine clinics (outpatients). Survey forms collected demographic data (age, gender, patient age, education, marital status, and employment status), asked questions regarding 6 specific attires (scrubs, scrubs and white coat, casual, casual and white coat, business suit, and formal and white coat), and behavioral items (professional, responsible, reliable, knowledgeable, succession rate, and medical safety), finally, to assess the preference of attire on overall perception. Results. Scrubs and white coat scored the highest through 6 domains about physicians’ attire (professional, reliable, responsible, knowledgeable, medical safety, and succession rate, p < 0.05 for all comparisons). A casual suit without a white coat was the least preferred across the surveyed attributes. There was a significant preference gap between wearing a white coat and not wearing a white coat (p < 0.001). Physician attire to white coat was considered as more professional, reliable, responsible, knowledgeable, having greater medical safety, and a higher success rate than attires without white coat. Conclusion. Patients felt that the physician wearing a white coat was better than other attires. Scrubs and white coat was the most popular attire. Hospital or related authorities may promote the standardized wearing of white coats, leading in a greater patient‐physician relationship.
The High Expression of p53 Is Predictive of Poor Survival Rather TP53 Mutation in Esophageal Squamous Cell Carcinoma
Authors: Jin Yan , Zhao Xueke , Song Xin , Wang Ran , Fan Zongmin , Wang Panpan , Yang Miaomiao , Zhou Fuyou , Bao Qide , Wang Lidong
Published: January 2023

TP53 is a well-known tumor suppressor gene and one of the most common genetic alterations in human cancers. However, the role of p53 as a prognostic marker of esophageal squamous cell carcinoma (ESCC) is controversial in the association between TP53 alterations and clinical outcomes. To address this issue, we evaluated TP53 mutations, p53 protein expression, clinicopathological parameters, and survivals rates in a large scale of patients with ESCC. Two cohorts were included in this study: TP53 mutations were detected by next-generation sequencing in 316 ESCC patients, and p53 protein expression was tested by immunohistochemistry in 6,028 ESCC patients. Survival analysis was performed using the Kaplan–Meier curve and the Cox proportional hazards model. TP53 mutations were found in ESCC patients from 241 of 316 (76.3%), and the rate of positive expression of p53 protein was 59.1% in 6,028 ESCC patients (including 1819 with high expression of p53 protein), respectively. Most mutations were missense, which has a high expression of p53 protein. Compared with wild-typeTP53, TP53 gene mutations were not significantly associated with survival time (

p
=
0.083

). In multivariate analysis, the p53 protein expression was an independent prognostic factor for ESCC. The high-expression group of p53 protein has poor survival (

p
<
0.001

) compared to low-expression group in patients with ESCC. The high expression of the p53 protein, not the TP53 mutation, is predictive of poor survival in patients with ESCC, and p53 protein expression might have the potential to be a prognosis biomarker and therapy target in ESCC.
Experience of the Postoperative Intensive Care Treatment of Stanford Type A Aortic Dissection
Authors: Bai Lei , Ge Lijuan , Zhang Yujing , Li Mingliang , Jiang Bo , Song Yanyan
Published: January 2023

Objective. To summarize the experience of the postoperative intensive care treatment of Stanford type A aortic dissection (STAAD) following Sun’s procedure. Methods. A total of 124 patients with STAAD who underwent Sun’s procedure from January 2014 to December 2021 at the General Hospital of Ningxia Medical University were retrospectively analyzed. All patients were admitted to the cardiac surgery intensive care unit (ICU) after surgery. According to the perioperative characteristics of the patients with STAAD, intensive care treatment was given to actively prevent the occurrence of postoperative complications. Results. In all the cases enrolled in this study, the causes of aortic dissection comprised hypertension (105 cases), trauma (six cases), Marfan’s syndrome (six cases), and aorto-arteritis (seven cases). The history of past illnesses comprised hypertension (105 cases), coronary disease (25 cases), diabetes mellitus (16 cases), and chronic obstructive pulmonary disease (six cases). There were some preoperative complications, such as cardiac insufficiency, acute liver insufficiency, acute renal insufficiency, pleural effusion, pericardial effusion, pulmonary infection, lower limb ischemia, mesenteric arterial embolism, and digestive tract hemorrhage. The average cardiopulmonary bypass time was 186 ± 32.1 min, the aortic clamp time was 74 ± 12.8 min, the deep hypothermic circulatory arrest time was 21 ± 2.6 min, and the mechanical ventilation time was 34 ± 2.8 h. The average ICU and hospital residence times were 7 ± 1.6 days and 12 ± 3.6 days, respectively. Postoperative complications comprised hypoxemia (34 cases), pulmonary infections (22 cases), tracheostomy (four cases), cerebral hemorrhage (four cases), cerebral infarction (four cases), transient delirium (eight cases), secondary thoracotomies due to bleeding (two cases), alimentary tract hemorrhage (eight cases), and acute renal insufficiency (38 cases). There was no occurrence of hoarseness or chylothorax. There were 15 cases of death, and the total mortality rate was 12.1%. In four cases, the cause of death was one postoperative complication (3.2%), and in 11 cases, the cause of death was multiple postoperative complications (8.9%). The other patients were discharged from the hospital with a good prognosis for full recovery. Conclusion. Postoperative intensive care treatment was an important part of the successful surgical treatment of STAAD.
A Dynamic Design Methodology for Large-Scale Complex Nonlinear Systems Based on Orthogonal Decomposition Technique
Authors: Wang Qi-Bin , Piao Si-Yang , Piao Ming-Wei , Dang Peng , Li Qiu-Ze , Ren Jing-Ying
Published: January 2023

HSRS is taken as a typical research case of large-scale complex nonlinear systems, and the re-innovation of associated imported technologies needs to be combined with the particularities of Chinese HSR practices, seeking a more suitable dynamic design methodology to conduct the self-adaptive improved design. Different from the troublesomeness of the primary hunting phenomenon, the self-adaptive improved design can decrease considerably the impact of car body instability on ride comfort merely by applying the semiactive damping technique between intervehicles, to promote scientifically the limit and construction speeds under the rational conditions of wheel-rail matching, i.e., λeN ≥ λemin, λemin = (0.03–0.05). The researching viewpoint of hunting kinematics makes the investigations on the geometric nonlinearity of the wheel-rail contacts contrary to the hypothesis of small creepage and no spin. Since the technical prototype of German ICE3 serial bogies has the design default of the primary hunting phenomenon, the improved design of the wheel-rail relationship has simply abandoned the high-quality technical resources of wheel-rail matching conditions at low conicity. On the contrary, the dynamic simulation analyses of MC01-TC02-MC03 three-vehicles trainset show that the semiactive damping technique between intervehicles takes advantage of Izz >> Ixx to improve the impacts of car body instability on ride comfort, and the self-adaptive improved design has consequently the ability to achieve the technical goal of uniform wear at low conicity. On the premise of meeting the requirements of crossing over different speed grade dedicated lines and realizing the running operations on three-speed levels of 160/250/350 km/h, the self-adaptive higher-/high-speed bogies can conditionally satisfy the economic reprofiling requirements of wheelsets through the optimal routing planning.
Ethiopian Medicinal Plants Used for Respiratory Tract Disorders: Ethnomedicinal Review
Authors: Teka Alemtshay , Maryo Melesse
Published: January 2023

Respiratory tract infections (RTIs) refer to infections in any part of the respiratory tract, which are common, with most of the world’s population contracting at least one infection annually. These infections are becoming important causes of death and morbidity due to the rapid development of antimicrobial resistance that has resulted in reduced efficacy of existing drugs. Different local societies residing in Ethiopia have been reported to use traditional medicinal plants to treat RTIs. Nevertheless, up‐to‐date summarized data on the diversity of plants used in the traditional medicine system to treat RTIs in Ethiopia are lacking. The purpose of this review was to assess plant species used in traditional medicine to treat respiratory tract infections in Ethiopia. It attempts to compile available data required for undertaking further scientific investigations. The data were collected by searching for published scientific articles and other grey literature. Following this, medicinal plant (MP) diversity, growth forms, plant parts used, modes of remedy preparation and application, sources and distributions, and frequently treated respiratory disorders were examined. An Excel spreadsheet and SigmaPlot software were used to summarize and present the data. Two hundred twenty‐nine (229) plant species that have been used to treat respiratory disorders in Ethiopia were documented. Lamiaceae was the most cited family (27 species), followed by Asteraceae (23 species), and Fabaceae (18 species), whereas cough was primarily cited as being treated by MPs and scored the highest frequency of citation (FOC = 243), followed by the common cold (FOC = 151) and asthma (FOC = 63). The top‐cited plant species used in the treatment of RTIs were Eucalyptus globulus (6.8%), Allium sativum (5.5%), Zingiber officinale (4.2%), Ruta chalepensis (3.8%), and Ocimum lamiifolium (2.8%). Herbs were the dominant plant growth form (46%) used to treat respiratory diseases, and the most commonly used MP parts were leaves (37%). The leading traditional method used for preparation was decoction (25.5%), and the remedies were usually administered orally (64.6%). The MP origin reported was mainly from the wild (59%). High diversity of medicinal plants was reported as being used to treat various RTIs in Ethiopia. Information obtained from this review could be used as a reference for the selection of plants for further pharmacological, phytochemical, and toxicological investigations for their possible therapeutic applications and the development of new plant‐based drugs.
Integrative Bioinformatics Analysis Identifies DDX60 as a Potential Biomarker for Systemic Lupus Erythematosus
Authors: Chen Wu , Li Zhi-Yu , Huang Lin , Zhou Dong-Hai , Luo Wen-Qing , Zhang Xu-Feng , Li Lin , Wen Cheng-Ping , Wang Qiao
Published: January 2023

Background. Systemic lupus erythematosus (SLE) is an autoimmune disease with strong heterogeneity, leading to variable clinical symptoms, which makes diagnosis and activity evaluation difficult. Methods. The original dataset of GSE88884 was analyzed to screen differentially expressed genes (DEGs) of SLE and the correlation between DEGs and clinical parameters (SLEDAI, anti-dsDNA, C3, and C4). The result was validated by microarray GSE121239 and SLE patients with RT-qPCR. Next, receiver operator characteristic (ROC) analysis, correlation analysis, and ordinal logistic regression were applied, respectively, to evaluate the capability of diagnosis and prediction of the candidate biomarker. Subsequently, the biological functions of the candidate biomarker were investigated through KEGG and GO enrichment, protein–protein interaction network, and the correlation matrix. Results. A total of 283 DEGs were screened, and seven of them were overlapped with SLE-related genes. DDX60 was identified as the candidate biomarker. Analyses of GSE88884, GSE121239, and SLE patients with RT-qPCR indicated that DDX60 expression level is significantly higher in patients with high disease activity. ROC analysis and the area under the ROC curve (

AUC
=
0.8818

) suggested that DDX60 has good diagnostic performance. DDX60 expression level was positively correlated with SLEDAI scores (

r
=
0.24

). For every 1-unit increase in DDX60 expression value, the odds of a higher stage of activity of SLE disease are multiplied by 1.47. The function of DDX60 mainly focuses on IFN-I-induced antiviral activities, RIG-I signaling, and innate immune. Moreover, DDX60 plays a synergistic role with DDX58, IFIH1, OASL, IFIT1, and other related genes in the SLE pathogenesis. Conclusions. DDX60 is differently expressed in SLE, and it is significantly related to both serological indicators and the disease activity of SLE. We suggested that DDX60 might be a potential biomarker for SLE diagnosis and management.
The Multiple Scattering of Laser Beam Propagation in Advection Fog and Radiation Fog
Authors: Xu Qiang , Cao Yunhua , Zhang Yuanyuan , Yan Shaohui , Han Yiping , Wu Zhensen
Published: January 2023

The laser beams were scattered and attenuated when they propagate in fogs for laser communication, laser remote sensing detection. For different density and droplets distribution of fogs, the laser scatter and attenuation are different, the correspond mechanism need thorough investigation. The characteristics of laser beam scattering in different types of fogs are studied based on the droplet size characteristics of advection fog and radiation fog, the scattering coefficients of droplets with different laser wavelengths(0.86 μm, 0.91 μm, 1.06 μm, 1.3015, and 10.6 μm) are calculated, the multi scattering of laser beam is studied by the Monte Carlo method, the propagation path and scattering direction of photons is analyzed, relations between asymmetry factor, albedo of fog droplets, and the visibility are presented, and the forward scattering intensity and the backward scattering intensity versus scattering angle are gotten and discussed.
Schisandrin B Alleviates Diabetic Cardiac Autonomic neuropathy Induced by P2X7 Receptor in Superior Cervical Ganglion via NLRP3
Authors: Zhang Zhihua , Guo Hongmin , Hu Zihui , Zhou Congfa , Hu Qixing , Peng Hao , Tang Gan , Xiao Zehao , Pi Lingzhi , Li Guilin
Published: January 2023

Diabetic cardiovascular autonomic neuropathy (DCAN) is a common complication of diabetes mellitus which brings about high mortality, high morbidity, and large economic burden to the society. Compensatory tachycardia after myocardial ischemia caused by DCAN can increase myocardial injury and result in more damage to the cardiac function. The inflammation induced by hyperglycemia can increase P2X7 receptor expression in the superior cervical ganglion (SCG), resulting in nerve damage. It is proved that inhibiting the expression of P2X7 receptor at the superior cervical ganglion can ameliorate the nociceptive signaling dysregulation induced by DCAN. However, the effective drug used for decreasing P2X7 receptor expression has not been found. Schisandrin B is a traditional Chinese medicine, which has anti-inflammatory and antioxidant effects. Whether Schisandrin B can decrease the expression of P2X7 receptor in diabetic rats to protect the cardiovascular system was investigated in this study. After diabetic model rats were made, Schisandrin B and shRNA of P2X7 receptor were given to different groups to verify the impact of Schisandrin B on the expression of P2X7 receptor. Pathological blood pressure, heart rate, heart rate variability, and sympathetic nerve discharge were ameliorated after administration of Schisandrin B. Moreover, the upregulated protein level of P2X7 receptor, NLRP3 inflammasomes, and interleukin-1β in diabetic rats were decreased after treatment, which indicates that Schisandrin B can alleviate the chronic inflammation caused by diabetes and decrease the expression levels of P2X7 via NLRP3. These findings suggest that Schisandrin B can be a potential therapeutical agent for DCAN.
Challenges to Using Big Data in Cancer
Authors: Sweeney Shawn M. , Hamadeh Hisham K. , Abrams Natalie , Adam Stacey J. , Brenner Sara , Connors Dana E. , Davis Gerard J. , Fiore Louis , Gawel Susan H. , Grossman Robert L. , Hanlon Sean E. , Hsu Karl , Kelloff Gary J. , Kirsch Ilan R. , Louv Bill , McGraw Deven , Meng Frank , Milgram Daniel , Miller Robert S. , Morgan Emily , Mukundan Lata , O'Brien Thomas , Robbins Paul , Rubin Eric H. , Rubinstein Wendy S. , Salmi Liz , Schaller Teilo , Shi George , Sigman Caroline C. , Srivastava Sudhir
Published: January 2023

Big data in healthcare can enable unprecedented understanding of diseases and their treatment, particularly in oncology. These data may include electronic health records, medical imaging, genomic sequencing, payor records, and data from pharmaceutical research, wearables, and medical devices. The ability to combine datasets and use data across many analyses is critical to the successful use of big data and is a concern for those who generate and use the data. Interoperability and data quality continue to be major challenges when working with different healthcare datasets. Mapping terminology across datasets, missing and incorrect data, and varying data structures make combining data an onerous and largely manual undertaking. Data privacy is another concern addressed by the Health Insurance Portability and Accountability Act, the Common Rule, and the General Data Protection Regulation. The use of big data is now included in the planning and activities of the FDA and the European Medicines Agency. The willingness of organizations to share data in a precompetitive fashion, agreements on data quality standards, and institution of universal and practical tenets on data privacy will be crucial to fully realizing the potential for big data in medicine.
Elucidating Analytic Bias Due to Informative Cohort Entry in Cancer Clinico-genomic Datasets
Authors: Kehl Kenneth L. , Uno Hajime , Gusev Alexander , Groha Stefan , Brown Samantha , Lavery Jessica A. , Schrag Deborah , Panageas Katherine S.
Published: January 2023

Background:

Oncologists often order genomic testing to inform treatment for worsening cancer. The resulting correlation between genomic testing timing and prognosis, or “informative entry,” can bias observational clinico-genomic research. The efficacy of existing approaches to this problem in clinico-genomic cohorts is poorly understood.

Methods:

We simulated clinico-genomic cohorts followed from an index date to death. Subgroups in each cohort who underwent genomic testing before death were “observed.” We varied data generation parameters under four scenarios: (i) independent testing and survival times; (ii) correlated testing and survival times for all patients; (iii) correlated testing and survival times for a subset of patients; and (iv) testing and mortality exclusively following progression events. We examined the behavior of conditional Kendall tau (Tc) statistics, Cox entry time coefficients, and biases in overall survival (OS) estimation and biomarker inference across scenarios.

Results:

Scenario #1 yielded null Tc and Cox entry time coefficients and unbiased OS inference. Scenario #2 yielded positive Tc, negative Cox entry time coefficients, underestimated OS, and biomarker associations biased toward the null. Scenario #3 yielded negative Tc, positive Cox entry time coefficients, and underestimated OS, but biomarker estimates were less biased. Scenario #4 yielded null Tc and Cox entry time coefficients, underestimated OS, and biased biomarker estimates. Transformation and copula modeling did not provide unbiased results.

Conclusions:

Approaches to informative clinico-genomic cohort entry, including Tc and Cox entry time statistics, are sensitive to heterogeneity in genotyping and survival time distributions.

Impact:

Novel methods are needed for unbiased inference using observational clinico-genomic data.
Alpelisib Efficacy without Cherry-PI3King Mutations
Authors: Tau Steven , Miller Todd W.
Published: January 2023

The PI3K inhibitor alpelisib is clinically approved for the treatment of metastatic estrogen receptor–positive breast cancers harboring hotspot mutations in PIK3CA, which encodes a subunit of PI3K. Prospective clinical trial results demonstrated benefit from alpelisib for the treatment of advanced ER+ breast cancers harboring PIK3CA mutations in the hotspots of exons 7, 9, and 20. However, 20% of PIK3CA mutations occur in non-hotspot regions. A recent article demonstrated that patients with cancers bearing non-hotspot PIK3CA mutations also derived benefit from alpelisib, which will inform clinical decision-making moving forward.

See related article by Rugo et al., p. 1056
A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma
Authors: Chiu Daniel , Qi Jingjing , Thin Tin Htwe , Garcia-Barros Monica , Lee Brian , Hahn Mary , Mandeli John , Belani Puneet , Nael Kambiz , Rashidipour Omid , Ghatan Saadi , Hadjipanayis Constantinos G. , Yong Raymund L. , Germano Isabelle M. , Brody Rachel , Tsankova Nadejda M. , Gnjatic Sacha , Kim-Schulze Seunghee , Hormigo Adília
Published: January 2023

Purpose:

The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.

Patient and Methods:

Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.

Results:

A total of 12 patients (median age 64; range, 37–73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4–16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5–4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.

Conclusions:

Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.

Significance:

Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.
A Surgical and Clinical Approach to Persistent Müllerian Duct Syndrome: Laparoscopic, Histological, and Molecular Findings
Authors: Mattone María Celeste , Lobo de la Vega María Victoria , Redondo Emiro J. , D’Alessandro Pablo , Perez Garrido Natalia , Galluzzo María Laura , Costanzo Mariana , Zaidman Verónica , Lazzati Juan Manuel , Berensztein Esperanza , Ramirez Pablo , Marino Roxana , Belgorosky Alicia , Ciaccio Marta , Bailez Marcela , Guercio Gabriela
Published: January 2023

Background: Persistent müllerian duct syndrome (PMDS) is characterized by the persistence of müllerian duct derivatives in otherwise normally virilized 46,XY males. Biallelic mutations of the anti-müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes lead to PMDS type 1 and 2, respectively. Aim: The aims of the study were to report the clinical, hormonal, and genetic findings in a patient with PMDS and discuss surgical strategies to achieve successful orchidopexy. Results: A 4-year-old boy was evaluated after the incidental finding of müllerian derivates during laparoscopy for nonpalpable gonads. Karyotype was 46,XY and laboratory tests revealed normal serum gonadotropin and androgen levels but undetectable serum AMH levels. PMDS was suspected. Molecular analysis revealed a novel variant c.902_929del in exon 5 and a previously reported mutation (c.367C>T) in exon 1 of the AMH gene. Successful orchidopexy was performed in two sequential surgeries in which the müllerian duct structure was preserved and divided to protect the vascular supply to the gonads. Histological evaluation of the testicular biopsy showed mild signs of dysgenesis. Doppler ultrasound showed blood flow in both testes positioned in the scrotum 1.5 years after surgery. Conclusion: PMDS is a rare entity that requires a high index of suspicion (from surgeons) when evaluating a patient with bilateral cryptorchidism. Surgical treatment is challenging and long-term follow-up is essential. Histological evaluation of the testis deserves further investigation.
Beyond Usual Geographical Scales of Analysis: Implications for Healthcare Management and Urban Planning
Authors: Morais Liliane , Lopes António , Rocha Jorge , Nogueira Paulo Jorge
Published: January 2023

Introduction: In the context of climate emergency, advances in geographic information systems, geocoding, and geomedicine allow us to go beyond the conventional usual scales and be aligned with people’s needs, improving knowledge and accuracy of the spatial pattern of health outcomes. This study shows that the geographical scale of analysis affects the interpretation of health outcomes. Methods: All mortality that occurred in Portugal in 2014–2017 was geocoded. From 435,291 addresses, 412,608 were geocoded with success. As an example, we use the spatial patterns of the elderly’s heat-related cardiorespiratory mortality. Results: It is shown: (i) it is possible to have high quality and accuracy of spatial data used in health outcomes analysis; (ii) how geographic scales reveal different degrees of detail in health outcomes analysis; (iii) the neighbourhood scale revealed different patterns of cardiorespiratory mortality from the usually available scale (parish). Discussion: Our findings suggest the relevance of geocoding health outcomes with a finer scale in tackling the challenges of the healthcare sector, and in support of planning decision-making, closely matching citizens’ needs. Without running the risk of losing potentially major prospects, better healthcare management is achievable, with optimal resource allocation, and improved detailed and informed policymaking, allowing enhanced climate health equity in cities promotion.
Rehabilitation Nursing Program in Oncological Surgery of the Head and Neck: A Retrospective Cohort Study
Authors: Moreira José , Soares Patrícia , Gomes Sandra , Nunes Baltazar
Published: January 2023

Background: Head and neck cancer (HNC) has a considerable mortality and morbidity rate. Surgery is one of the most effective treatments; however, it may compromise the independence of patients after its performance. Early start rehabilitation is essential for the recovery of these patients, preventing functional capacity limitations. Objective: The objective of this study was to compare the independence between hospitalized patients who underwent rehabilitation nurse (RN) intervention versus general health care after HNC surgery. Methods: Patients submitted to different types of HNC surgery were divided into two groups intervention by the RN versus general health care, the outcome was the independence categorized as dichotomic to assess the patient independence at discharge and their differences calculated by statistical analysis. To analyze the effect of the RN intervention on independence, a Poisson regression model was used, adjusting the confounding factors initial Barthel Index and age in the variable Barthel Index independence. Results: Independence at discharge (p = 0.01) improved significantly in the RN intervention group compared to the general health care group. The intervention of the RN after surgery had a positive effect on the independence of the patients, after adjusting the confounding factors (RR: 1.47; 95% CI: [1.02; 2.12]). In the middle/late postoperative period, in the group with RN intervention (n = 79), the hospitalization time was reduced by 4.29 days versus general health care (n = 72). Conclusion: The RN intervention is an added value in the independence of the patient submitted to HNC surgery. It is an innovative study in patients after diagnosis of HNC, showing that the intervention of RN through rehabilitation programs allows independence after his surgery.
Factors That Can Prolong Ocular Treatment Duration in Age-Related Macular Degeneration
Authors: Kaiser Peter K. , Giani Andrea , Fuchs Holger , Chong Victor , Heier Jeffery S.
Published: January 2023

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are used to treat wet age-related macular degeneration (wAMD); however, they are associated with a considerable treatment burden and poor real-world outcomes. The molecular size and charge of anti-VEGF agents influence drug pharmacokinetics in the vitreous and peak drug efficacy. This article reviews the established and novel strategies to prolong drug action, in the vitreal cavity, and thus reduce dosing frequency. Increased ocular residency can be attained by increasing drug size as with large molecules, such as KSI-301; adding polyethylene glycol to pegcetacoplan (APL-2) or avacincaptad pegol to increase molecular size; or binding to other targets that increase molecular size, such as vitreal albumin in the case of BI-X. Faricimab is a bispecific antibody in which the fragment crystallizable portion is engineered to prolong ocular residency and reduce systemic exposure. Conversely, small VEGF-binding molecules, such as brolucizumab, can be administered at higher clinical doses, with the potential for prolonged clinical activity versus larger molecules. Other important considerations include sustained drug delivery routes, such as the ranibizumab port delivery system or subconjunctival or suprachoroidal injection. More effective and longer-lasting treatments are needed for wAMD to prolong drug action and reduce dosing frequency. Several strategies are under investigation and the prevention of vision loss in patients with AMD or other retinal diseases may be attainable in the near future.
Asbestos Exposure and Malignant Pleural Mesothelioma: A Systematic Review of Literature
Authors: Santos Cátia , Dixe Maria dos Anjos , Sacadura-Leite Ema , Astoul Philippe , Sousa-Uva António
Published: January 2023

Background:The relationship between exposure to asbestos and malignant pleural mesothelioma (MPM) is already well established. Nevertheless, much remains to be known about exposure thereto and the incidence and mortality from MPM. Objective: This systematic review aims to map the relationship between asbestos and MPM by studying the exposure to asbestos and the incidence and mortality of MPM. Methods: A systematic review was conducted relating asbestos and MPM. Exposure to asbestos, incidence, and mortality by MPM was reviewed. PubMed, Web of Science, Cochrane Library, RCAAP, DART-Europe, and the reference lists of included studies were searched, from January 1, 1960, to December 31, 2020. Methodological quality was checked, the risk of bias analysis was performed, a level of evidence grade was assigned, and descriptive data analysis was performed. Results: 3,484 unique citations were identified, which included seventeen observational studies that met inclusion criteria with a total of 1,104 patients. Heterogeneity is present between the included studies which range from a case series of 16 retrospective studies and 1 prospective study. Studies were mostly conducted in Europe, particularly in Italy (6), and were published between 1969 and 2020. The mean age of patients is approximately 66 years with a latency period between the first exposure and diagnosis of approximately 42 years. 14 studies present data regarding the occupational context and chrysotile and crocidolite are the most studied types of fibre. The incidence of cases occurred between the interval 1966 and 2014 and in 9 studies the mortality rate was 100% of patients. Conclusion: There is high evidence to support the relationships between asbestos and MPM. However, the relatively scant information provided by the studies reinforces the need for well-conducted research and implementation of National Mesothelioma Surveillance Centres at a global level.
Diagnostic Value of Epithelial Cell Adhesion Molecule Flow Cytometry for Diagnosis of Metastatic Carcinoma in Serous Effusions
Authors: Khodadadi Neda , Mokhtari Maral
Published: January 2023

Introduction: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids. Methods: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(−) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity. Results: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively. Conclusion: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity.
Four Limb Amputation Secondary to Symmetrical Peripheral Gangrene in a Polytrauma Patient: A Case Report
Authors: Alborno Yahya , Moghamis Isam Sami , Kayali Hammam , Babikir Elhadi , Hameed Shamsi , Al-dosari Mohammed
Published: January 2023

Symmetrical peripheral gangrene (SPG) is a rare condition. At present, there is no clear etiology for this condition; however, it has been associated with multiple risk factors, including sepsis and coagulopathy. We present a patient who sustained a polytrauma with multiple organ injuries. During hospitalization, he developed septic and cardiogenic shock complications by disseminated intravascular coagulopathy, which led to ischemic changes in all four limbs. The patient underwent bilateral – trans-tibial and trans-radial – amputation. High level of suspicion and awareness are required to detect such a devastating condition in order to mitigate complications. We conclude that ischemic changes secondary to SPG are irreversible; subsequently, halting the disease progression is the mainstay of treatment.
Comprehensive Review of Anal Cytology
Authors: Hopp Amanda M. , Puzyrenko Andrii , Giorgadze Tamara
Published: January 2023

Background: The incidence of anal cancer has increased over at least the past decade, with estimates of a continued increase in the coming years. Women are more commonly affected than men in the general population; separate high-risk populations have also been identified. While the pathophysiology of anal cancer is thought to be similar to its cervical counterpart, well-defined and standardized screening guidelines have not been established as is seen in cervical cancer prevention. Nonetheless, multiple screening modalities have been examined and are components of proposed institutional and societal screening programs. Summary: Anal cytology is one modality that is a mainstay of many suggested screening guidelines. Interpretation and reporting follow current criteria for cervical/vaginal cytology per the Bethesda System, with site-specific alterations and changes in adequacy criteria to better accommodate some of the confounding factors encountered in anal cytology. While there are some limitations, such as a tendency to underestimate the degree of dysplasia and variable interobserver concordance rates, anal cytology, especially liquid-based preparations, overall performs well in detecting anal abnormalities and acts as an adequate screening tool. Importantly, most anal squamous dysplasias and cancers are also associated with human papillomavirus (HPV) infection, raising the possibility of HPV testing or genotyping as a component of screening and/or follow-up. Studies have also shown the efficacy of HPV vaccination in preventing anal lesions. Digital anorectal exam as well as anoscopy, particularly high-resolution anoscopy, are also often components of screening and follow-up. Management guidelines such as those put forth by the American Society for Colposcopy and Cervical Pathology (ASCCP) for cervical cancer are also not established for anal cancer. However, studies such as the Anal Cancer HSIL Outcomes Research (ANCHOR) trial have made significant strides in demonstrating successes in follow-up and treatment of anal lesions, findings that are crucial for establishing prevention and management guidelines going forward.
Association of Locus Xq26.1–27.3 with Erosive Tooth Wear Phenotypes in a Group of Adolescents
Authors: Mulic Aida , Vieira Alexandre R. , Bezamat Mariana , Søvik Jenny B. , Sehic Amer , Tulek Amela
Published: January 2023

Erosive tooth wear is a multifactorial condition of an increasing prevalence. There is a need for discovering individual genetic predisposition for the development of this condition. Considering that the chromosome X locus was previously shown to be associated with dental caries, the aim of the present study was to look for the association between this locus and erosive tooth wear when dietary habits are considered as a co-factor. Saliva samples, erosive wear experience data, and dietary information from 16- to 18-year-old dental patients (n = 705) were used. Genotyping analyses were performed, and thereafter, analyses considering diet and oral hygiene data, using logistic regression, with the assumption that erosive tooth wear is a complex gene-environment model. Genotypic analyses revealed an association between chromosome X marker rs1324156 and erosive tooth wear phenotype. Logistic regression analysis showed that, in the presence of less common allele of rs12687601 and rs1324156, erosive tooth wear more likely develops when associated with numerous dietary variables from the questionnaire. These results indicate that erosive tooth wear may be the result of gene-environment interactions.
O "eu-Desconhecido" em Cecília Meireles
Authors: Casaroto Filho Cesar Marcos
Published: January 2023

No presente artigo, à luz especialmente de Gilles Deleuze, Friedrich Nietzsche, Giorgio Agamben, Charles Baudelaire e Vladimir Safatle, viso analisar o “eu-Desconhecido” na obra Cânticos, de Cecília Meireles, aquele que, tal qual o flâneur, sem um eu-fixo encapsulado em uma forma de vida que só faz repetir velhas formas, reinventa a si mesmo por meio de uma linguagem que revela uma voz singular e criadora.
Os contornos cambiantes da filosofia: no rastro de Hegel
Authors: Waszek Norbert , Mira Lutti , Hauck Eveline
Published: January 2023

Tradução de "The Shifting Contours of Philosophy. In the wake of Hegel”. In: Rinaldi, G.; Cerretani, G. Etica, Politica, Storia universale. Atti del Congresso Internazionale (Urbino, 24-27 ottobre 2018). Canterano: Aracne editrice, 2020, p. 135-156.
Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation
Authors: Tousif Sultan , Singh Anand P. , Umbarkar Prachi , Galindo Cristi , Wheeler Nicholas , Toro Cora Angelica , Zhang Qinkun , Prabhu Sumanth D. , Lal Hind
Published: January 2023

Background:

The tyrosine kinase inhibitor ponatinib is the only treatment option for chronic myelogenous leukemia patients with T315I (gatekeeper) mutation. Pharmacovigilance analysis of Food and Drug Administration and World Health Organization datasets has revealed that ponatinib is the most cardiotoxic agent among all Food and Drug Administration–approved tyrosine kinase inhibitors in a real-world scenario. However, the mechanism of ponatinib-induced cardiotoxicity is unknown.

Methods:

The lack of well-optimized mouse models has hampered the in vivo cardio-oncology studies. Here, we show that cardiovascular comorbidity mouse models evidence a robust cardiac pathological phenotype upon ponatinib treatment. A combination of multiple in vitro and in vivo models was employed to delineate the underlying molecular mechanisms.

Results:

An unbiased RNA sequencing analysis identified the enrichment of dysregulated inflammatory genes, including a multifold upregulation of alarmins S100A8/A9, as a top hit in ponatinib-treated hearts. Mechanistically, we demonstrate that ponatinib activates the S100A8/A9-TLR4 (Toll-like receptor 4)-NLRP3 (NLR family pyrin domain–containing 3)-IL (interleukin)-1β signaling pathway in cardiac and systemic myeloid cells, in vitro and in vivo, thereby leading to excessive myocardial and systemic inflammation. Excessive inflammation was central to the cardiac pathology because interventions with broad-spectrum immunosuppressive glucocorticoid dexamethasone or specific inhibitors of NLRP3 (CY-09) or S100A9 (paquinimod) nearly abolished the ponatinib-induced cardiac dysfunction.

Conclusions:

Taken together, these findings uncover a novel mechanism of ponatinib-induced cardiac inflammation leading to cardiac dysfunction. From a translational perspective, our results provide critical preclinical data and rationale for a clinical investigation into immunosuppressive interventions for managing ponatinib-induced cardiotoxicity.
Prescribing Trends of Oral Anticoagulants in US Patients With Cirrhosis and Nonvalvular Atrial Fibrillation
Authors: Simon Tracey G. , Schneeweiss Sebastian , Singer Daniel E. , Sreedhara Sushama Kattinakere , Lin Kueiyu Joshua
Published: January 2023

Background

Many patients with cirrhosis have concurrent nonvalvular atrial fibrillation (NVAF). Data are lacking regarding recent oral anticoagulant (OAC) usage trends among US patients with cirrhosis and NVAF.

Methods and Results

Using MarketScan claims data (2012–2019), we identified patients with cirrhosis and NVAF eligible for OACs (CHA
2
DS
2
‐VASc score ≥2 [men] or ≥3 [women]). We calculated the yearly proportion of patients prescribed a direct OAC (DOAC), warfarin, or no OAC. We stratified by high‐risk features (decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease, or end‐stage renal disease). Among 32 487 patients (mean age=71.6 years, 38.5% women, 15.1% with decompensated cirrhosis, mean CHA
2
DS
2
‐VASc=4.2), 44.6% used OACs within 180 days of NVAF diagnosis, including DOACs (20.2%) or warfarin (24.4%). Compared with OAC nonusers, OAC users were less likely to have decompensated cirrhosis (18.6% versus 10.7%), thrombocytopenia (19.5% versus 12.5%), or chronic kidney disease/end‐stage renal disease (15.5% versus 14.0%). Between 2012 and 2019, warfarin use decreased by 21.0% (32.0% to 11.0%), whereas DOAC use increased by 30.6% (7.4% to 38.0%), and among all DOACs between 2012 and 2019, apixaban was the most commonly prescribed (46.1%). Warfarin use decreased and DOAC use increased in all subgroups, including in compensated and decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease/end‐stage renal disease, and across CHA
2
DS
2
‐VASc categories. Among OAC users (2012–2019), DOAC use increased by 58.9% (18.7% to 77.6%). Among DOAC users, the greatest proportional increase was with apixaban (61.2%;
P
<0.001).

Conclusions

Among US patients with cirrhosis and NVAF, DOAC use has increased substantially and surpassed warfarin, including in decompensated cirrhosis. Nevertheless, >55% of patients remain untreated, underscoring the need for clearer treatment guidance.
US Trends in Cholesterol Screening, Lipid Levels, and Lipid‐Lowering Medication Use in US Adults, 1999 to 2018
Authors: Gao Yumin , Shah Lochan M. , Ding Jie , Martin Seth S.
Published: January 2023

Background

Understanding current trends in cholesterol screening, lipid levels, and lipid management therapies may inform health policy and practice.

Methods and Results

In 50 928 US adult National Health and Nutrition Examination Survey (NHANES) participants, trends were assessed in cholesterol screening, mean levels of total cholesterol, triglycerides, low‐density‐lipoprotein cholesterol, and lipid‐lowering medication use from 1999 through 2018. Point estimates were also calculated using the 2017 to March 2020 prepandemic data set. The age‐ and sex‐adjusted proportion of having cholesterol screened within 5 years increased from 63.2% (95% CI, 60.0–66.3) in 1999 to 2000 to 72.5% (95% CI, 69.5–75.3) in 2017 to 2018 (
P
<0.001 for linear trend). Mean total cholesterol decreased from 203.3 mg/dL (95% CI, 201.0–205.7) in 1999 to 2000 to 188.4 mg/dL in 2017 to 2018 (95% CI, 185.4–191.5) (
P
<0.001 for nonlinear trend). The mean triglyceride level decreased from 121.3 mg/dL (95% CI, 116.4–126.4) in 1999 to 2000 to 91.4 mg/dL (95% CI, 88.4–94.6) in 2017 to 2018 (
P
<0.001 for nonlinear trend). Low‐density lipoprotein cholesterol decreased from 127.9 mg/dL (95% CI, 125.3–130.5) in 1999 to 2000 to 111.7 mg/dL (95% CI, 109.0–114.4) in 2017 to 2018 (
P
<0.001 for nonlinear trend). Among statin‐eligible US adults, the proportion of statin use increased from 14.9% (95% CI, 12.2–17.9) in 1999 to 2000 to 27.8% (95% CI, 23.0–33.2) in 2017 to 2018 (
P
<0.001 for nonlinear trend). Statin use increased in adults with diabetes aged 40 to 75 years from 21.4% in 1999 to 2000 to 51.9% in 2017 to 2018 (
P
<0.001 for overall linear trend). Statin use plateaued in all other groups. The proportions of using ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors were 3.7% (95% CI, 1.3–9.8) and 0.03% (95% CI, 0.01–0.15) in 2017 to March 2020, respectively.

Conclusions

From 1999 through 2018, cholesterol screening increased while mean total cholesterol, triglycerides, and low‐density lipoprotein cholesterol levels decreased, with a modest increase in statin use and low uptake of nonstatin therapy in the US population.