bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of metabolic memory on inflammation and fibrosis associated with diabetic kidney disease: an epigenetic perspective
Authors: Zheng Wen , Guo Jia , Liu Zhang-Suo
Published: April 2021

Diabetic kidney disease (DKD) is one of the most common microvascular complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and the leading cause of end-stage renal disease (ESRD) worldwide. Persistent inflammation and subsequent chronic fibrosis are major causes of loss of renal function, which is associated with the progression of DKD to ESRD. In fact, DKD progression is affected by a combination of genetic and environmental factors. Approximately, one-third of diabetic patients progress to develop DKD despite intensive glycemic control, which propose an essential concept “metabolic memory.” Epigenetic modifications, an extensively studied mechanism of metabolic memory, have been shown to contribute to the susceptibility to develop DKD. Epigenetic modifications also play a regulatory role in the interactions between the genes and the environmental factors. The epigenetic contributions to the processes of inflammation and fibrogenesis involved in DKD occur at different regulatory levels, including DNA methylation, histone modification and non-coding RNA modulation. Compared with genetic factors, epigenetics represents a new therapeutic frontier in understanding the development DKD and may lead to therapeutic breakthroughs due to the possibility to reverse these modifications therapeutically. Early recognition of epigenetic events and biomarkers is crucial for timely diagnosis and intervention of DKD, and for the prevention of the progression of DKD to ESRD. Herein, we will review the latest epigenetic mechanisms involved in the renal pathology of both type 1 (T1DN) and type 2 diabetic nephropathy (T2DN) and highlight the emerging role and possible therapeutic strategies based on the understanding of the role of epigenetics in DKD-associated inflammation and fibrogenesis.
Quality of opioid prescribing in older adults with or without Alzheimer disease and related dementia
Authors: Wei Yu-Jung Jenny , Schmidt Siegfried , Chen Cheng , Fillingim Roger B. , Reid M. Carrington , DeKosky Steven , Solberg Laurence , Pahor Marco , Brumback Babette , Winterstein Almut G.
Published: April 2021

Background

Pain is common among individuals with Alzheimer’s disease and related dementias (ADRD), and use of opioids has been increasing over the last decade. Yet, it is unclear to what extent opioids are appropriately prescribed for patients with ADRD and whether the appropriateness of opioid prescribing differs by ADRD status. The objective of this study is to compare the quality of opioid prescribing among patients with or without ADRD who have chronic noncancer pain.

Methods

A nationally representative cohort study of Medicare beneficiaries aged 50 years or older who had chronic pain but who had no cancer, hospice, or palliative care from 2011 to 2015. Four indicators of potentially inappropriate opioid prescribing were measured in patients residing in communities (75,258 patients with and 435,870 patients without ADRD); five indicators were assessed in patients in nursing homes (NHs) (37,117 patients with and 5128 patients without ADRD). Each indicator was calculated as the proportion of eligible patients with inappropriate opioid prescribing in the year after a chronic pain diagnosis. Differences in proportions between ADRD and non-ADRD groups were estimated using a generalized linear model adjusting for covariates through inverse probability weighting.

Results

Patients with ADRD versus those without had higher concurrent use of opioids and central nervous system–active drugs (community 44.1% vs 33.3%; NH 58.8% vs 54.1%, bothP < 0.001) and no opioids or scheduled pain medications for moderate or severe pain (NH 60.1% vs 52.5%,P < 0.001). The ADRD versus non-ADRD group had higher use of long-term opioids for treating neuropathic pain in communities (21.7% vs 19.5%,P = 0.003) but lower use in NHs (26.9% vs 36.0%,P < 0.001). Use of strong or high-dose opioids when naive to opioids (community 1.5% vs 2.8%; NH 2.5% vs 3.5%) and use of contraindicated opioids (community 0.08% vs 0.12%; NH 0.05% vs 0.21%) were rare for either group.

Conclusion

Potential inappropriate opioid prescribing in 2 areas of pain care was more common among patients with ADRD than among patients without ADRD in community or NH settings. Further studies aimed at understanding the factors and effects associated with opioid prescribing patterns that deviate from guidelines are warranted.
Resolution of enuresis with aripiprazole in children with psychiatric disorders: two case reports
Authors: Nardello Rosaria , Guccione Fulvio , Gliubizzi Claudia , Marino Antonio , Capizzi Mariarita , Mangano Salvatore
Published: April 2021

Background

Aripiprazole is a third-generation atypical antipsychotic drug that acts as a stabilizer of the dopaminergic and serotonergic system. As partial agonist of the dopamine (D2) and serotonin (5-HT1A) receptors, it appears to be effective in reducing mania in patients with bipolar disorder, tics in Tourette Syndrome, aggression in schizophrenia and autism spectrum disorder. Enuresis has been reported among its side effects. Only a few studies, with conflicting results, have investigated the relationship between aripiprazole and enuresis.

Case presentation

We report the disappearance of enuresis in a Caucasian girl with intellectual disability and oppositional defiant disorder and in a Caucasian boy with intellectual disability and early-onset psychosis, both following initiation of treatment with aripiprazole.

Conclusion

The aim of this study was to contribute to the literature on the use of aripripazole in subjects with enuresis. Our findings lead us to suggest that aripiprazole is less burdened with side effects, including bedwetting, than other antipsychotic drugs.
Mayer-Rokitansky-Küster-Hauser syndrome with 22q11.21 microduplication: a case report
Authors: Dell’Edera Domenico , Allegretti Arianna , Ventura Mario , Mercuri Ludovica , Mitidieri Angela , Cuscianna Giacinto , Epifania Annunziata Anna , Morizio Elisena , Alfonsi Melissa , Guanciali-Franchi Paolo
Published: April 2021

Background

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (Online Mendelian Inheritance in Man [OMIM] #277000) is a congenital condition characterized by the total or partial agenesis of vagina and uterus. Agenesis can be isolated (MRKH 1) or associated with other renal, vertebral or cardiac defects (MRKH 2).

Case presentation

In this paper, we report a case of a Caucasian patient showing the clinical signs associated with MRKH. Array-based comparative genomic hybridization (a-CGH) analysis revealed a microduplication of approximately 3.01 megabases (Mb) located on the long arm of chromosome 22 (22q11.21). Microduplications affecting the 22q11.21 region have been shown to be associated with MRKH syndrome and Müllerian aplasia. The phenotype of patients with 22q11.2 duplication (OMIM #608363) appears extremely variable, ranging from apparently normal to mild learning difficulties or with multiple defects, sharing features with DiGeorge/velocardiofacial (DGS/VCFS) syndrome.

Conclusions

The altered gene expression together with other genetic, nongenetic, epigenetic or environmental factors can cause the extremely variable phenotype in patients carrying such duplication. Therefore, we can consider MRKH syndrome to be one of the clinical features of DGS/VCFS syndrome.
Correlation of [18F]florbetaben textural features and age of onset of Alzheimer’s disease: a principal components analysis approach
Authors: Li Jing , Antonecchia Emanuele , Camerlenghi Marco , Chiaravalloti Agostino , Chu Qian , Costanzo Alfonso Di , Li Zhen , Wan Lin , Zhang Xiangsong , D’Ascenzo Nicola , Schillaci Orazio , Xie Qingguo
Published: April 2021

Background

When Alzheimer’s disease (AD) is occurring at an early onset before 65 years old, its clinical course is generally more aggressive than in the case of a late onset. We aim at identifying [$$^{18}$$

18

F]florbetaben PET biomarkers sensitive to differences between early-onset Alzheimer’s disease (EOAD) and late-onset Alzheimer’s disease (LOAD). We conducted [$$^{18}$$

18

F]florbetaben PET/CT scans of 43 newly diagnosed AD subjects. We calculated 93 textural parameters for each of the 83 Hammers areas. We identified 41 independent principal components for each brain region, and we studied their Spearman correlation with the age of AD onset, by taking into account multiple comparison corrections. Finally, we calculated the probability that EOAD and LOAD patients have different amyloid-$$\beta$$
β
($$A\beta$$

A
β

) deposition by comparing the mean and the variance of the significant principal components obtained in the two groups with a 2-tailed Student’s t-test.

Results

We found that four principal components exhibit a significant correlation at a 95% confidence level with the age of onset in the left lateral part of the anterior temporal lobe, the right anterior orbital gyrus of the frontal lobe, the right lateral orbital gyrus of the frontal lobe and the left anterior part of the superior temporal gyrus. The data are consistent with the hypothesis that EOAD patients have a significantly different [$$^{18}$$

18

F]florbetaben uptake than LOAD patients in those four brain regions.

Conclusions

Early-onset AD implies a very irregular pattern of $$A\beta$$

A
β

deposition. The authors suggest that the identified textural features can be used as quantitative biomarkers for the diagnosis and characterization of EOAD patients.
Assessment of exposure to influenza A viruses in pigs between weaning and market age
Authors: Ferreira Juliana Bonin , Poljak Zvonimir , Friendship Robert , Nagy Éva , Wideman Greg , Grgić Helena
Published: April 2021

Influenza A viruses (IAVs) are common causes of respiratory infection in pigs. The objective of this study was to characterize the circulation of IAVs between weaning and market age on the basis of development of antibody response and molecular epidemiology of detected viruses. Two batches of weaned pigs were followed in the nursery and finisher barns with a sample of 81 and 75 pigs. Nasal swabs and blood samples were collected from individual pigs for virological and serological analyses. A H3N2 subtype virus, of cluster IV, was detected in Study 1, with a maximum of 97.9% identity to HA gene of viruses previously isolated in Ontario. In Study 2, a H1N1 subtype virus, of 2009 H1N1 pandemic lineage, was detected, with a maximum of 97.8% identity to HA gene of viruses previously isolated in Ontario. On the basis of HA gene, it was observed that pigs were being detected with the same virus over time. The existence of antibody titers for IAV other than the isolated one confirmed that more than one subtype can circulate in the same population. In Study 1, pigs with higher numbers of IAV detection had lower serological titers for the same virus that was confirmed to circulate in the nursery (P < 0.01). Thorough knowledge of all endemic viral strains is fundamental for development of infection and disease control, particularly in complex production systems. This may include consideration of sampling and testing strategies which could detect circulation of all IAV variants, even if they have low prevalence.
Radial variations in xylem sap flux in a temperate red pine plantation forest
Authors: Bodo Alanna V. , Arain M. Altaf
Published: April 2021

Background

Scaling sap flux measurements to whole-tree water use or stand-level transpiration is often done using measurements conducted at a single point in the sapwood of the tree and has the potential to cause significant errors. Previous studies have shown that much of this uncertainty is related to (i) measurement of sapwood area and (ii) variations in sap flow at different depths within the tree sapwood.

Results

This study measured sap flux density at three depth intervals in the sapwood of 88-year-old red pine (Pinus resinosa) trees to more accurately estimate water-use at the tree- and stand-level in a plantation forest near Lake Erie in Southern Ontario, Canada. Results showed that most of the water transport (65%) occurred in the outermost sapwood, while only 26% and 9% of water was transported in the middle and innermost depths of sapwood, respectively.

Conclusions

These results suggest that failing to consider radial variations in sap flux density within trees can lead to an overestimation of transpiration by as much as 81%, which may cause large uncertainties in water budgets at the ecosystem and catchment scale. This study will help to improve our understanding of water use dynamics and reduce uncertainties in sap flow measurements in the temperate pine forest ecosystems in the Great Lakes region and help in protecting these forests in the face of climate change.
Mitochondrial metabolism as a target for acute myeloid leukemia treatment
Authors: Panina Svetlana B. , Pei Jingqi , Kirienko Natalia V.
Published: April 2021

Acute myeloid leukemias (AML) are a group of aggressive hematologic malignancies resulting from acquired genetic mutations in hematopoietic stem cells that affect patients of all ages. Despite decades of research, standard chemotherapy still remains ineffective for some AML subtypes and is often inappropriate for older patients or those with comorbidities. Recently, a number of studies have identified unique mitochondrial alterations that lead to metabolic vulnerabilities in AML cells that may present viable treatment targets. These include mtDNA, dependency on oxidative phosphorylation, mitochondrial metabolism, and pro-survival signaling, as well as reactive oxygen species generation and mitochondrial dynamics. Moreover, some mitochondria-targeting chemotherapeutics and their combinations with other compounds have been FDA-approved for AML treatment. Here, we review recent studies that illuminate the effects of drugs and synergistic drug combinations that target diverse biomolecules and metabolic pathways related to mitochondria and their promise in experimental studies, clinical trials, and existing chemotherapeutic regimens.
Bayesian negative binomial logit hurdle and zero-inflated model for characterizing smoking intensity
Authors: Workie Mekuanint Simeneh , Azene Abebaw Gedef
Published: April 2021

Smoking invariably has environmental, social, economic and health consequences in Ethiopia. Reducing and quitting cigarette smoking improves individual health and increases available household funds for education, food and better economic productivity. Therefore, this study aimed to apply the Bayesian negative binomial logit hurdle and zero-inflated model to determine associated factors of the number of cigarette smokers per day using the smoking intensity data of 2016 Ethiopia Demographic and Health Survey. The survey was a community-based cross-sectional study conducted from January 18 to June 27, 2016. The survey used two stage stratified sampling design. Bayesian analysis of Negative Binomial Logit Hurdle and Zero-inflated models which incorporate both overdispersion and excess zeros and carry out estimation using Markov Chain Monte Carlo techniques. About 94.2% of them never cigarettes smoked per day and the data were found to have excess zeros and overdispersion. Therefore, after considering both the zero counts and the enduring overdispersion, according to the AIC and Vuong tests, the Zero-inflated Negative Binomial and Negative Binomial Logit Hurdle model best fit to the data. The finding Bayesian estimation technique is more robust and precisely due to that it is more popular data analysis method. Furthermore; using Bayesian Zero-inflation and Zero hurdle model the variable: age, residence, education level, internet use, wealth index, marital status, chewed chat, occupation, the media were the most statistically significant determinate factors on the smoking intensity.
Observation of the long-period monotonic seismic waves of the November 11, 2018, Mayotte event by Iranian broadband seismic stations
Authors: Sadeghi Hossein , Suzuki Sadaomi
Published: April 2021

On November 11, 2018, an event generating long-lasting, monotonic long-period surface waves was observed by seismographs around the world. This event occurred at around 09:28 UTC east of the Mayotte Island, in the Indian Ocean off the coast of East Africa. This event is unusual due to the absence of body waves in the seismograms and no feeling of earth shaking by people locally. The purpose of this study is to investigate this unusual event using the waveforms recorded by 26 stations of the Iranian National Broadband Seismic Network. The stations are located at epicentral distances ranging from 4542 to 5772 km north-northeast of the event’s epicenter. The arrival of monochromatic long-period signals is visible around 10 UTC in the recordings of all the stations and the signals lasted for more than 30 min. Frequency analysis of the seismograms shows a clear peak at 0.064 Hz (15.6 s/cycle). The maximum amplitude of the transverse components is less than a half of the radial components. This is in agreement with the theoretical radiation pattern of Rayleigh and Love waves at a frequency of 0.06 Hz for a vertical compensated linear vector dipole source mechanism. The average apparent phase velocities were calculated as 3.31 and 2.97 km/s, in the transverse and radial directions, corresponding, respectively, to Love and Rayleigh waves in the frequency range of 0.05–0.07 Hz. A surface wave magnitude of Ms 5.07 ± 0.22 was estimated. Just before the monochromatic signal arrives, there is some dispersion in the surface waves. This observation may suggest a regular earthquake of Ms 4.3 ± 0.11 that triggered the November 11, 2018, event. The difference between the arrival times of the recorded surface waves of the two events is estimated to be less than 31 s, and most likely of ~ 7 s only.
First reference on reproductive biology of Butis koilomatodon in Mekong Delta, Vietnam
Authors: Dinh Quang M. , Lam Tran T. H. , Nguyen Ton H. D. , Nguyen Thanh M. , Nguyen Tien T. K. , Nguyen Nam T.
Published: April 2021

Background

The key to fishery management is knowing the appropriate reproductive strategies of the targeted fish. For most gobiid species, the iteroparous pattern is dominant compared to semelparity. Albeit Butis koilomatodon plays an important role in the Mekong Delta’s food supply, its reproductive biological data have not been known. Hence, this study was conducted to provide new fundamental knowledge of reproductive traits of Butis koilomatodon in the Mekong Delta.

Results

A total of 1314 individuals (903 males and 411 females) were monthly collected by bottom gill nets from July 2019 to June 2020 at six sampling sites along estuarial and coastal regions, from Tra Vinh to Ca Mau provinces, southern of Vietnam. pH and salinity of these six sampling sites are 7.72–7.93 pH and 11.17–26.17‰, respectively. The pH varies with sites, but not seasons; whereas a reverse case is found in salinity. Different types of oocytes are found in histological specimens of ovaries prove that B. koilomatodon is a multi-spawner. The gonadosomatic index value, together with the monthly presence of mature ovaries reveal that this species spawns throughout the year. The length at first mature male Butis koilomatodon (5.1–8.6 cm) is higher than that of females (4.8–6.7 cm), except in Hoa Binh and Dong Hai. Batch fecundity (3085 to 32,087 eggs/female) increases with fish weight (1.48–12.30 g) and length (4.8–9.0 cm) due to high determination values (r2 > 0.6).

Conclusion

Knowledge of reproductive traits gained from this study was a reference source for future studies and helped manage this species’ resources.
Systematic review of three-dimensional printing for simulation training of interventional radiology trainees
Authors: Tenewitz Chase , Le Rebecca T. , Hernandez Mauricio , Baig Saif , Meyer Travis E.
Published: April 2021

Rationale and objectives

Three-dimensional (3D) printing has been utilized as a means of producing high-quality simulation models for trainees in procedure-intensive or surgical subspecialties. However, less is known about its role for trainee education within interventional radiology (IR). Thus, the purpose of this review was to assess the state of current literature regarding the use of 3D printed simulation models in IR procedural simulation experiences.

Materials and methods

A literature query was conducted through April 2020 for articles discussing three-dimensional printing for simulations in PubMed, Embase, CINAHL, Web of Science, and the Cochrane library databases using key terms relating to 3D printing, radiology, simulation, training, and interventional radiology.

Results

We identified a scarcity of published sources, 4 total articles, that appraised the use of three-dimensional printing for simulation training in IR. While trainee feedback is generally supportive of the use of three-dimensional printing within the field, current applications utilizing 3D printed models are heterogeneous, reflecting a lack of best practices standards in the realm of medical education.

Conclusions

Presently available literature endorses the use of three-dimensional printing within interventional radiology as a teaching tool. Literature documenting the benefits of 3D printed models for IR simulation has the potential to expand within the field, as it offers a straightforward, sustainable, and reproducible means for hands-on training that ought to be standardized.
Patient-reported outcomes in breast cancer FDA drug labels and review documents
Authors: Hong Kyungwan , Majercak Kayleigh R. , Villalonga-Olives Ester , Perfetto Eleanor M.
Published: April 2021

Background

Patient-reported outcomes (PROs) can provide valuable information about drug benefit-risk tradeoffs from the patient perspective and are particularly important to patients with breast cancer due to its symptoms and adverse events from breast cancer treatments. The United States Food and Drug Administration (U.S. FDA) has acknowledged PROs as important approval endpoints used in clinical trials of cancer drugs. However, previous studies found that PROs are rarely mentioned in cancer drug labels, a widely used and trusted source of information about drugs. Our objectives were to compare PRO data reported in FDA labeling versus FDA medical review documents for breast cancer drugs approved in the U.S. between 2000 and 2019 to identify possible causes for PRO-data labeling exclusions.

Methods

We included new molecular entities (NMEs) and biologic license applications (BLAs) initially approved for breast cancer treatment by the FDA between 1/1/2000 and 12/31/2019. Product labeling and FDA medical review documents were collected from the FDA-Approved Drugs database (Drugs@FDA). From these resources, details on PRO measures used in trials, design of trials using PRO measures, PRO-endpoint status, analytical methods, and FDA reviewer comments regarding PRO measurement were extracted.

Results

Of 633 FDA-approved drugs, 13 were indicated for breast cancer treatment; none of their prescribing information contained information about PROs. However, 11 of 13 (85%) included PRO measures and endpoint information in FDA medical review documents. PRO measures were used in 14 different clinical trials, and FDA reviewers’ comments regarding PRO measurement were related to lack of meaningfulness and clinical significance, lack of content validity, and inadequate analytical methods.

Conclusions

Despite the importance of PROs to patients with breast cancer, PRO measures were only described in FDA medical review documents of breast cancer drugs, but not in drug product labeling. Therefore, it appears that PRO data are often collected in breast cancer trials, but have not been methodologically acceptable to FDA reviewers. Collaborative efforts between the FDA and industry are warranted to increase the number of breast cancer drug applications with appropriate use of PRO measures and endpoints.
Outcomes and issues of 12 chordomas treated in a single center
Authors: Karampouga Maria , Tsetsos Fotis , Sakellariou Pavlos , Baltas Ioannis
Published: April 2021

Background

Chordomas stem from notochordal vestiges and rank as low-grade bone malignancies although fraught with high risk of recurrence. This study assesses the clinical outcomes of twelve chordoma cases treated in our clinic, in an effort to shed light on the often under-represented pool of results deriving from non-referral centers.

Methods

We reviewed the clinicopathological traits of all chordoma patients registered in our center since 1991. Major endpoints were overall survival (OS) and progression-free survival (PFS) estimated using the Kaplan–Meier and Nelson–Aalen methods.

Results

Twelve patients, aged on average 47.9 years, were treated for primary or recurrent disease. Seven had chordomas originating in the cranium, 5 in the spine, including a bifocal tumor, and the mean time lapse between the beginning of symptoms and diagnosis was 15.4 months, marked by dull ache. Subtotal resection was achieved in 5 cases, incomplete in 5, while in 2, only biopsy was accomplished. Conformal radiotherapy was administered to 5 and stereotactic radiosurgery to 2 in the setting of recurrence. Protons were used once and targeted agents induced no clinical response in 3 patients. Median OS and PFS were 36 and 12 months, respectively, with the best outlook linked to maximal resection, spinal location, and good preoperative functional status. In all, 6 patients died of chordoma, 4 are alive, and 1 was lost. Relapse was the rule for most cases, except 2, and pulmonary metastases were ascertained in 1.

Conclusions

Our cases were typical of chordomas, implying that inadequate surgical margins and successive recurrence are negative determinants of prognosis and that interinstitutional cooperation counterbalances shortages in non-referral institutes.
Assessment the role of tranexamic acid in prevention of postpartum hemorrhage
Authors: Fahmy Nevein Gerges , Eskandar Fahmy Saad Latif , Khalil Walid Albasuony Mohammed Ahmed , Sobhy Mohammed Ibrahim Ibrahim , Amin Amin Mohammed Al Ansary
Published: April 2021

Background

Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality and morbidity worldwide. It is believed that hemostatic imbalance secondary to release of tissue plasminogen activator (tPA) and subsequent hyperfibrinolysis plays a major role in PPH pathogenesis. Antifibrinolytic drugs such as tranexamic acid (TXA) are widely used in hemorrhagic conditions associated with hyperfibrinolysis. TXA reduced maternal death due to PPH and its use as a part of PPH treatment is recommended, and in recent years, a number of trials have investigated the efficacy of prophylactic use of TXA in reducing the incidence and the severity of PPH.

The study is aiming to assess the efficacy of tranexamic acid in reducing blood loss throughout and after the lower segment cesarean section and reducing the risk of postpartum hemorrhage.

Results

The amount of blood loss was significantly lower in the study group than the control group (416.12±89.95 and 688.68±134.77 respectively). Also the 24-h postoperative hemoglobin was significantly higher in the study group (11.66±0.79 mg/dl) compared to the control group (10.53±1.07mg/dl), and the 24-h postoperative hematocrit value was significantly higher in the study group (34.99±2.40) compared to control (31.62±3.22).

Conclusion

Prophylactic administration of tranexamic acid reduces intraoperative and postoperative bleeding in cesarean section and the incidence of postpartum hemorrhage.
How artificial intelligence can help us ‘Choose Wisely’
Authors: Mehta Nishila , Born Karen , Fine Benjamin
Published: April 2021

The overuse of low value medical tests and treatments drives costs and patient harm. Efforts to address overuse, such as Choosing Wisely campaigns, typically rely on passive implementation strategies- a form of low reliability system change. Embedding guidelines into clinical decision support (CDS) software is a higher leverage approach to provide ordering suggestions through an interface embedded within the clinical workflow. Growth in computing power is increasingly enabling artificial intelligence (AI) to augment such decision making tools. This article offers a roadmap of opportunities for AI-enabled CDS to reduce overuse, which are presented according to a patient’s journey of care.
Biochemical differences between nano- and normal formulation of tamoxifen and other natural bioactive materials ameliorate breast cancer in experimental rats
Authors: Ezzat Afaf , Abdelhamid Abdou Osman , El Awady Mostafa K. , Dawood Reham M. , Mohammed Dina Mostafa
Published: April 2021

Background

Human breast cancer is the most prevalent malignancy in women all-over the world. The aim is to look further into the effectiveness of the nanoformulation of tamoxifen and even certain bioactive compounds (yeast, isoflavone, and silymarin) and their impacts on diminishing the breast cancer progression. A single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) was administered intragastrically by fifty-four female Sprague–Dawley rats. After fourteen days of DMBA admission, the procedure protocol actually started out. At long last, all of the experimental findings assessed, tabulated, and statistically analyzed.

Results

In contrast to the normal groups, a substantial elevation in apoptosis and lipid peroxide was observed in all nanogroups.

Conclusion

The best biochemical outcome and beneficial factors which elevate the occurrence and activation of the apoptosis process have been demonstrated by nanotamoxifen.
Adolescent and adult laryngotracheal stenosis: a review
Authors: Klopper Gerhard Johan , Adeniyi Oladele Vincent , Stephenson Kate
Published: April 2021

Background

The larynx has multiple composite functions which include phonation, airway protection, and sensory control of respiration. Stenosis of the larynx and trachea were first recorded by O’Dwyer in 1885 and by Colles in 1886, respectively. Initially, the aetiology of laryngotracheal stenosis was predominantly infective. Currently, the leading cause is iatrogenic injury to the laryngotracheal complex secondary to prolonged ventilation in an intensive care unit.

Main body

Laryngotracheal stenosis is a complex and diverse disease. It poses a major challenge to the surgeon and can present as an airway emergency. Management typically demands the combined involvement of various disciplines including otorhinolaryngology, cardiothoracic surgery, anaesthesiology, interventional pulmonology, and radiology. Both the disease and its management can impact upon respiration, voice, and swallowing. The incidence of iatrogenic laryngotracheal stenosis has reflected the evolution of airway and intensive care whilst airway surgery has advanced concurrently over the past century. Correction of laryngotracheal stenosis requires expansion of the airway lumen; this is achieved by either endoscopic or open surgery. We review the relevant basic science, aetiopathogenesis, diagnosis, management, and treatment outcomes of LTS.

Conclusion

The choice of surgical procedure in the management of laryngotracheal stenosis is often dictated by the individual anatomy and function of the larynx and trachea, together with patient factors and available facilities. Regardless of how the surgeon chooses to approach these lesions, prevention of iatrogenic laryngotracheal damage remains of primary importance.
National Maintenance Cost for Precision Diagnostics Under the Verifying Accurate Leading-Edge In Vitro Clinical Test Development (VALID) Act of 2020
Authors: Huang Richard , Lasiter Laura , Bard Adam , Quinn Bruce , Young Christina , Salgado Roberto , Allen Jeff , Lennerz Jochen K.
Published: April 2021

PURPOSE:

The proposed legislation Verifying Accurate and Leading-edge In vitro clinical test Development (VALID) clarifies the US Food and Drug Administration's authority to regulate laboratory-developed tests. Many stakeholders have pointed out that the lack of direct US Food and Drug Administration oversight has led to erroneous results that have serious patient consequences—in particular for patients with cancer. Technology Certification is a key provision proposed in VALID to navigate the balance between safety, patient access, and innovation; however, the maintenance cost of the proposed framework after implementation is unclear.

METHODS:

On the basis of 2019 retrospective data from a laboratory-developed test–based cancer diagnostics laboratory, we expressed laboratory complexity by the number and complexity of assays and in vitro diagnostic technologies. We estimated the national health care cost increase by modeling three stringencies of complying with the Act. We performed sensitivity analysis of our regulatory stringency model taking into account number of patients tested, materials, submission cost, and labor using extra cost per patient as the output.

RESULTS:

We estimate the national health care cost increase to range from $33M US dollars (USD) to $1,110M USD or $0.21 USD to $0.70 USD per employed person in the United States. Sensitivity analysis demonstrates that regulatory stringency is the primary driver of extra cost per patient. Cancer testing does not reflect all areas of in vitro diagnostics affected by VALID; nonetheless, concrete cost models are paramount in informing the ongoing legislative negotiations.

CONCLUSION:

Our findings show the critical importance of clarity in the legislative language to ensure balance between VALID's goals of assuring high-quality test performance and the burden to laboratories and overall health care cost.
Evolution and Current Status of the Multidisciplinary Management of Locally Advanced Rectal Cancer
Authors: Deschner Benjamin W. , VanderWalde Noam A. , Grothey Axel , Shibata David
Published: April 2021

The management of locally advanced rectal cancer has grown in both complexity and quality since the first proctectomy. What once was a malignancy with a fairly consistent treatment algorithm for decades, a recent paradigm shift in the care of these patients has led to a more personalized, multidisciplinary approach with variations in timing, sequence, duration, and potential exclusion of multimodality therapies. This review summarizes the most important evidence behind these developing overarching concepts to provide a context for this paradigm shift.
Surface growth on tree-like lattices and the upper critical dimension of the KPZ class
Authors: Oliveira Tiago J.
Published: April 2021

Aiming to investigate the upper critical dimension, d

u
, of the KPZ class, in Saberi A. A., EPL, 103 (2013) 10005, some growth models were numerically analyzed using Cayley trees (CTs) as substrates, as a way to access their behavior in the infinite-dimensional limit, and some unexpected results were reported: logarithmic roughness scaling, differing for EW and KPZ models (indicating that even at

the KPZ nonlinearity is still relevant); beyond asymptotically rough EW surfaces above the upper critical dimension of the EW class. Motivated by these strange findings, I revisit these growth models here to show that such results are simple consequences of boundary effects, inherent to systems defined on CTs. In fact, I demonstrate that the anomalous boundary of the CT leads the growing surfaces to develop curved shapes, which explains the strange behaviors previously found for these systems, once the global “roughness” was analyzed for non-flat surfaces in the study above. Importantly, by measuring the height fluctuations at the central site of the CT, which can be seen as an approximation for the Bethe lattice, smooth surfaces are found for both EW and KPZ classes, consistently with the behavior expected for growing systems in dimensions

. Interesting features of the 1-point height fluctuations, such as the possibility of non-saturation in the steady state regime, are also discussed for substrates in general.
Sequencing Cell-free Fetal DNA in Pregnant Women With GCK-MODY
Authors: Kwak Soo Heon , Powe Camille E , Jang Se Song , Callahan Michael J , Bernstein Sarah N , Lee Seung Mi , Kang Sunyoung , Park Kyong Soo , Jang Hak C , Florez Jose C , Kim Jong-Il , Chae Jong Hee
Published: April 2021

Context

Individuals with monogenic diabetes due to inactivating glucokinase (GCK) variants typically do not require treatment, except potentially during pregnancy. In pregnancy, fetal GCK genotype determines whether treatment is indicated, but noninvasive methods are not clinically available.

Objective

This work aims to develop a method to determine fetal GCK genotype noninvasively using maternal cell-free fetal DNA.

Methods

This was a proof-of-concept study involving 3 pregnant women with a causal GCK variant that used information from 1) massive parallel sequencing of maternal plasma cell-free DNA, 2) direct haplotype sequences of maternal genomic DNA, and 3) the paternal genotypes to estimate relative haplotype dosage of the pathogenic variant-linked haplotype. Statistical testing of variant inheritance was performed using a sequential probability ratio test (SPRT).

Results

In each of the 3 cases, plasma cell-free DNA was extracted once between gestational weeks 24 and 36. The fetal fraction of cell-free DNA ranged from 21.8% to 23.0%. Paternal homozygous alleles that were identical to the maternal GCK variant-linked allele were not overrepresented in the cell-free DNA. Paternal homozygous alleles that were identical to the maternal wild-type–linked allele were significantly overrepresented. Based on the SPRT, we predicted that all 3 cases did not inherit the GCK variant. Postnatal infant genotyping confirmed our prediction in each case.

Conclusion

We have successfully implemented a noninvasive method to predict fetal GCK genotype using cell-free DNA in 3 pregnant women carrying an inactivating GCK variant. This method could guide tailoring of hyperglycemia treatment in pregnancies of women with GCK monogenic diabetes.
Tracheal Dilatation of an Idiopathic Subglottic Stenosis in a Near-Term Parturient at 36 Weeks of Gestation Using SponTaneous Respiration Using Intravenous Anesthesia and Hi-Flow Nasal Oxygen: A Case Report
Authors: Schulze Melanie G. , Young Mark G.
Published: April 2021

Hi-flow nasal oxygen (HFNO) has revolutionized tubeless field anesthesia for airway surgery without the complications of jet ventilation. However, its use in third trimester parturients undergoing open airway surgery has been limited to an apneic technique (Transnasal Humidified Rapid-Insufflation Ventilatory Exchange [THRIVE]) in current publications. We used SponTaneous Respiration using IntraVEnous anesthesia and Hi-flow nasal oxygen (STRIVE Hi) in the management of tracheal dilatation in a near-term parturient at 36 weeks of gestation. Transferring this established protocol for spontaneous ventilation in the obstructed airway onto near-term parturients may mitigate the risks of apnea with hypercapnia, subsequent acidosis, and potential fetal harm.
Ultrasound as a Useful Tool in Hydrocephalus Management During Pregnancy: A Case Report
Authors: Geraldini Federico , De Cassai Alessandro , Ciccarino Pietro , Calabrese Fabrizia , Chioffi Franco , Munari Marina
Published: April 2021

A 38-year-old pregnant woman in her 24th week of gestation was admitted to our neurosurgical intensive care unit with a 5-cm cerebellar hemangioblastoma and acute hydrocephalus. Initial management included the placement of an external ventricular drain to prevent neurological deterioration. Five days after the initial diagnosis, the patient successfully underwent a neurosurgical intervention to remove the lesion. Transcranial ultrasound was used to determine the optimal ventricular drain level and facilitate weaning, bypassing the need for cerebral computed tomography and cerebral magnetic resonance imaging, which would have otherwise been necessary in postoperative follow-up.
Determination of Mass of Nerve-cell Components
Authors: Hydén Holger
Published: April 2021

The method for determination of mass in biological material described by Engström & Lindström (1950) is founded on the fact that the absorption of X-radiation at 8-10 Å is proportional to the mass of the biological substance. In elaborating this method for quantitative analysis of nerve-cells and their components (Brattgård & Hydén, 1952) we found it important to consider the following sources of error:

The reference system. The photographic process and the photometry. The treatment of the material.
Roles of neuroepithelial cell rearrangement and division in shaping of the avian neural plate
Authors: Schoenwolf Gary C. , Alvarez Ignacio S.
Published: April 2021

Shaping of the neural plate, one of the most striking events of neurulation, involves rapid craniocaudal extension. In this study, we evaluated the roles of two processes in neural plate extension: neuroepithelial cell rearrangement and cell division. Quail epiblast plugs of constant size were grafted either just rostral to Hensen’s node or paranodally and the resulting chimeras were examined at selected times postgrafting. By comparing the size of the original plug, the number of cells it contained and the distribution of cells within it to those same features of the grafts in chimeras, we were able to ascertain that, during transformation of the flat neural plate into the closed neural tube (a period requiring 24 h), the graft undergoes a maximum of 3 rounds of craniocaudal extension (each round of craniocaudal extension was defined as a doubling of graft length, so 3 rounds equaled an 8-fold increase in length). Such extension is accompanied by 2 rounds of cell rearrangement and 2–3 rounds of cell division (cell rearrangement occurred mediolaterally, so each round was defined as a halving of the number of cells in the width of the graft and a doubling of the number of cells in its length; each round of cell division was defined as a doubling of graft cell number). Modeling studies demonstrate that these amounts of cell rearrangement and division are sufficient to approximate the shaping of the neural plate that normally ensues during neurulation, provided that some of the cell division occurs within the longitudinal plane of the neural plate and some within its transverse plane: longitudinal cell division results in craniocaudal extension of the neural plate, whereas transverse cell division results in lateral expansion of the neural plate such as that occurring at its cranial end; cell rearrangement results in craniocaudal extension of the neural plate as well as in its narrowing. In conclusion, our results provide evidence that shaping of the neural plate involves mediolateral cell rearrangement and cell division, with the latter occurring within both the longitudinal and transverse planes of the neural plate.
MRI-based radiomics as response predictor to radiochemotherapy for metastatic cervical lymph node in nasopharyngeal carcinoma
Authors: Xu Hao , Liu Jieke , Huang Ying , Zhou Peng , Ren Jing
Published: April 2021

Objective:

To establish and substantiate MRI-based radiomic models to predict the treatment response of metastatic cervical lymph node to radiochemotherapy in patients with nasopharyngeal carcinoma (NPC).

Methods:

A total of 145 consecutive patients with NPC were enrolled including 102 in primary cohort and 43 in validation cohort. Metastatic lymph nodes were diagnosed according to radiologic criteria and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors. A total of 2704 radiomic features were extracted from contrast-enhanced T  1 weighted imaging (CE- T  1WI) and T  2 weighted imaging (T  2WI) for each patient, and were selected to construct radiomic signatures for CE-T  1WI, T  2WI, and combined CE-T  1WI and T  2WI, respectively. The area under curve (AUC) of receiver operating characteristic, sensitivity, specificity, and accuracy were used to estimate the performance of these radiomic models in predicting treatment response of metastatic lymph node.

Results:

No significant difference of AUC was found among radiomic signatures of CE-T  1WI, T  2WI, and combined CE-T  1WI and T  2WI in the primary and validation cohorts (all p > 0.05). For combined CE-T  1WI and T  2WI data set, 12 features were selected to develop the radiomic signature. The AUC, sensitivity, specificity, and accuracy were 0.927 (0.878–0.975), 0.911 (0.804–0.970), 0.826 (0.686–0.922), and 0.872 (0.792–0.930) in primary cohort, and were 0.772 (0.624–0.920), 0.792 (0.578–0.929), 0.790 (0.544–0.939), and 0.791 (0.640–0.900) in validation cohort.

Conclusion:

MRI-based radiomic models were developed to predict the treatment response of metastatic cervical lymph nodes to radiochemotherapy in patients with NPC, which might facilitate individualized therapy for metastatic lymph nodes before treatment.

Advances in knowledge:

Predicting the response in patients with NPC before treatment may allow more individualizing therapeutic strategy and avoid unnecessary side-effects and costs. Radiomic features extracted from metastatic cervical lymph nodes showed promising application for predicting the treatment response in NPC.
The incidence and relevance of non-fatty components in trunk and extremity lipomatous soft tissue masses
Authors: Berkeley Rupert , Okereke Odinakachukwu , Malhotra Karan , Saifuddin Asif
Published: April 2021

Objectives:

To determine the incidence and diagnostic relevance of non-fatty ‘solid appearing’ components within lipomatous tumours of the trunk and extremity.

Methods and materials:

Retrospective review of patients referred to a specialist musculoskeletal oncology service over a 12-month period with a lipomatous trunk or extremity soft tissue tumour. The presence and morphology (solitary/multifocal; homogeneous/heterogeneous; well-defined/poorly defined) of non-fatty components was recorded based on MRI and compared with the final histological diagnosis.

Results:

213 patients with 217 lipomatous tumours were included, 119 (55.9%) males and 94 (44.1%) females with mean age of 54.6 years (range 7–93 years). Seventy-seven (35.5%) lesions arose superficial to the fascia and 139 (64.1%) deep, while a single case involved both compartments. Mean maximal tumour dimension was 94.9 mm (range 12–288 mm). Non-fatty ‘solid appearing’ components were identified in 28 (12.9%) cases, of which eight were solitary and 20 were multifocal, six had homogeneous SI and 22 had heterogeneous SI, and eight had well-defined margins, while 20 had poorly defined margins. Histological diagnosis was available in 20 of the tumours containing non-fatty components, 16 of which were benign, two intermediate grade and two malignant (a dedifferentiated liposarcoma and a myxoid liposarcoma). The commonest diagnosis was spindle cell lipoma, which accounted for 10 of 20 (50%) cases with confirmed histology.

Conclusions:

Non-fatty components are identified in ~13% of trunk and extremity lipomatous tumours. The majority of such lesions are benign lipoma variants, most commonly spindle cell lipoma.

Advances in knowledge:

Solid non-fatty components are identified in approximately 13% of lipomatous tumours referred to a specialist sarcoma service. Despite the concern that these may represent dedifferentiated liposarcomas, high-grade tumours were seen in only two cases, the commonest diagnosis being a spindle cell lipoma.