bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonin Transporter Gene Promoter Hypomethylation as a Predictor of Antidepressant Treatment Response in Major Depression: A Replication Study
Authors: Schiele M A , Zwanzger P , Schwarte K , Arolt V , Baune B T , Domschke K
Published: October 2020

Background

The serotonin transporter gene (SLC6A4; 5-HTT; SERT) is considered a prime candidate in pharmacogenetic research in major depressive disorder (MDD). Besides genetic variation, recent advances have spotlighted the involvement of epigenetic mechanisms such as DNA methylation in predicting antidepressant treatment response in “pharmaco-epigenetic” approaches. In MDD, lower SLC6A4 promoter methylation has been suggested to predict impaired response to serotonergic antidepressants. The present study sought to replicate and extend this finding in a large, independent sample of MDD patients.

Methods

The sample comprised n = 236 Caucasian patients with MDD receiving antidepressant medication in a naturalistic treatment setting. Functional DNA methylation of 9 CpG sites located in the SLC6A4 promoter region was analyzed via direct sequencing of sodium bisulfite– treated DNA extracted from blood cells. Patients were assessed over the course of a 6-week in-patient treatment using the Hamilton Depression Scale (HAM-D).

Results

Results confirm relative SLC6A4 hypomethylation to predict impaired antidepressant response both dimensionally and categorically (HAM-D reductions < 50%) and to furthermore be indicative of nonremission (HAM-D > 7). This also held true in a homogenous subgroup of patients continuously treated with selective serotonin reuptake inhibitors or serotonin/noradrenaline reuptake inhibitors (n = 110).

Conclusions

Impaired response to serotonergic antidepressants via SLC6A4 hypomethylation may be conveyed by increased gene expression and consequently decreased serotonin availability, which may counteract the effects of serotonergic antidepressants. The present results could in the future inform clinical decision-making towards a more personalized treatment of MDD.
Three Outcomes of Contentious Elections
Authors: Frank Richard W
Published: October 2020

Elections are contentious by design, but contentious election outcomes—from democratic backsliding to widespread protests and violence—occur regularly and represent significant challenges to both domestic and international stability. This review essay explores three specific outcomes of contentious elections (i.e., failed democratization, democracy protests, and election violence) using three recent, influential books on these topics. It highlights several, overlapping causal mechanisms, including those focusing on structural characteristics, actor behavior, and election cycle dynamics. It also explores four cross-cutting themes (i.e., democratization, electoral history, structural constraints, and money in politics), as well as three areas for future research (i.e., overlooked actors, election integrity, and international factors).
Tutorial for the Characterization of Fatty Acid Methyl Esters by Gas Chromatography with Highly Polar Capillary Columns
Authors: Delmonte Pierluigi , Milani Andrea , Kramer John K G
Published: October 2020

The fatty acid composition of fats and oils is commonly determined by gas chromatography after preparing fatty acid methyl esters (FAME). Capillary columns coated with polyethylene glycol emerged as the preferred separation tool for the quantification of the polyunsaturated fatty acids contained primarily in marine oils. However, their selectivity is inadequate for measuring the trans fatty acids (TFA) contained in refined vegetable oils, dairy fats, and marine oils. Highly polar 100% poly(biscyanopropyl siloxane) capillary columns provide the necessary selectivity, but small differences in the phase polarity caused by column age, conditioning, or manufacturing variations affect the reproducibility of their separations of these complex samples. In this study, a simple procedure is described to compensate for small variations in column selectivity by adjusting the elution temperature. The balance between the dipole-induced dipole interactions and dispersive interactions was determined by measuring selectivity factors [SF(i)] corresponding to the elution of an unsaturated FAME such as 18:3n-3 relative to two saturated FAME such as 20:0 and 22:0. Knowing the SF(i) provided by the installed capillary column at a given elution temperature, and the SF(i) of the target separation, we propose a simple calculation to determine the necessary elution temperature adjustment to achieve (or restore) the desired separation. After determining the SF(i) which provides the optimal separation of TFA, the novel methodology was applied to the separation of refined vegetable oils, butter fats, and marine oils.
Induced pluripotent stem cells from farm animals
Authors: Su Yue , Zhu Jiaqi , Salman Saleh , Tang Young
Published: October 2020

The development of the induced pluripotent stem cells (iPSCs) technology has revolutionized the world on the establishment of pluripotent stem cells (PSCs) across a great variety of animal species. Generation of iPSCs from domesticated animals would provide unrestricted cell resources for the study of embryonic development and cell differentiation of these species, for screening and establishing desired traits for sustainable agricultural production, and as veterinary and preclinical therapeutic tools for animal and human diseases. Induced PSCs from domesticated animals thus harbor enormous scientific, economical, and societal values. Although much progress has been made toward the generation of PSCs from these species, major obstacles remain precluding the exclamation of the establishment of bona fide iPSCs. The most prominent of them remain the inability of these cells to silence exogenous reprogramming factors, the obvious reliance on exogenous factors for their self-renewal, and the restricted development potential in vivo. In this review, we summarize the history and current progress in domestic farm animal iPSC generation, with a focus on swine, ruminants (cattle, ovine, and caprine), horses, and avian species (quails and chickens). We also discuss the problems associated with the farm animal iPSCs and potential future directions toward the complete reprogramming of somatic cells from farm animals.
Direct inversion for reservoir parameters from prestack seismic data
Authors: Zhang Fanchang , Yang Jingyang , Li Chuanhui , Li Dong , Gao Yang
Published: October 2020

Reliably estimating reservoir parameters is the final target in reservoir characterisation. Conventionally, estimating reservoir characters from seismic inversion is implemented by indirect approaches. The indirect estimation of reservoir parameters from inverted elastic parameters, however, will produce large bias due to the propagation of errors in the procedure of inversion. Therefore, directly obtaining reservoir parameters from prestack seismic data through a rock-physical model and prestack amplitude variation with offset (AVO) inversion is proposed. A generalised AVO equation in terms of oil-porosity (OP), sand indicator (SI) and density is derived by combining a physical rock model and the Aki–Richards equation in a whole system. This makes it possible to perform direct inversion for reservoir parameters. Next, under Bayesian theorem, we develop a robust prestack inversion approach based on the new AVO equation. Tests on synthetic seismic gathers show that it can dramatically reduce the prediction error of reservoir parameters. Furthermore, field data application illustrates that reliable reservoir parameters can be directly obtained from prestack inversion.
Using Geospatial Analysis to Map Forest Change in New Hampshire: 1996–Present
Authors: Grybas Heather , Congalton Russell G , Howard Andrew F
Published: October 2020

New Hampshire’s forests are vitally important to the state’s economy; however, there are indications that the state is experiencing a continuous loss in forest cover. We sought to investigate forest cover trends in New Hampshire. A baseline trend in forest cover between 1996 and 2010 was established using National Oceanic and Atmospheric Administration Coastal Change Analysis Program land cover data. A land cover map was then generated from Landsat imagery to extend the baseline trend to 2018. Results show that the state has experienced a continual decline in forest cover with the annual net loss steadily increasing from 0.14% between 1996 and 2001 to 0.27% between 2010 and 2018. Additionally, the more urbanized counties in southern New Hampshire are experiencing some of the greatest rates of net forest loss, most likely because of urbanization and agricultural expansion. This study demonstrated an effective methodology for tracking forest cover change and will hopefully inform future forest use policies.
Laparoscopic treatment of a gastro-gastric fistula after Roux-en-Y gastric bypass—report of two cases
Authors: Gaspar Joana Raquel Rodrigues , Marques Paula , Mesquita Isabel , Marcos Mário , Santos Jorge , Nogueira Carlos
Published: October 2020

The most frequently performed bariatric surgery is the laparoscopic Roux-en-Y gastric bypass (LRYGB). An uncommon complication of LRYGB is gastro-gastric fistula (GGF). Possible causes of GGF include incomplete transection of the stomach during the initial surgery, staple-line leaks in the post-operative period and marginal ulcers. The optimal management of GGF is still under debate, with medical, endoscopic and surgical treatment modalities available. The authors present two cases of a GGF successfully managed with a laparoscopic surgical approach, after failed medical and endoscopic treatment.
Leiomyosarcoma of the inferior vena cava: a case report
Authors: Graves Alexander , Longoria James , Graves Gregory , Ianiro Cora
Published: October 2020

Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is an extremely rare malignancy with <400 cases reported. We present a 42-year-old woman with a 3-day history of vague and non-specific abdominal pain. Examination revealed mild tenderness to the epigastrium and right upper quadrant with no other findings. Abdominal ultrasound was performed, which revealed a large hypoechoic mass overlying the IVC. Abdominal computed tomography (CT) was performed which revealed an 8.9 × 7.9 × 9 cm multilobulated lesion encasing the IVC. A CT-guided biopsy was performed which revealed a primary LMS of the IVC. Surgical en bloc excision was performed with an end-to-end Dacron graft for IVC reconstruction. Histopathology confirmed LMS of the vessel wall with negative surgical margins.
Survival in melanoma brain metastases in the era of novel systemic therapies
Authors: Merola Joseph P , Ocen Joanita , Kumar Satish , Powell James , Hayhurst Caroline
Published: October 2020

Background

Melanoma brain metastases (MBMs) have historically poor overall survival (OS). Recently introduced systemic anticancer therapies (SACTs), namely targeted therapies such as BRAF inhibitors and immunotherapy, to control advanced disease have shown improved survival. Today, increasingly aggressive strategies are sought for MBM. We review outcomes in MBM after surgery or stereotactic radiosurgery (SRS) and the survival impact in advanced systemic disease when combined with novel anticancer therapies.

Methods

A retrospective cohort study of patients referred to a regional neuro-oncology multidisciplinary team (MDT) meeting with MBM. Demographic data, extent of systemic disease, and data on surgical and oncological management were collected, plus the use of SACT. The primary outcomes were median OS, 12- and 24-month survival, and progression-free survival.

Results

Between 2010 and 2018, 142 patients with MBM were referred. Following the introduction of SACT, the rate of referrals to MDT more than doubled from 11.6 to 25.7 patients per year. Focal brain metastasis was treated surgically in 23 (16.2%) patients and by SRS in 29 (20.4%). Fifty-six (39.4%) patients underwent palliative whole-brain radiotherapy and 34 (23.9%) did not receive treatment. Median OS was 11 months for the surgical cohort, 9 months for the SRS cohort, and increased when treatment with or without SACT was considered to 23 and 12 months, respectively.

Conclusion

In the setting of SACTs, survival in MBM is significantly improved after surgery or SRS even in patients with advanced and uncontrolled systemic disease at the time of presentation, supporting an aggressive approach to MBM management.
Antimicrobial Stewardship Practice in the Ambulatory Setting From a National Cohort
Authors: Eudy Joshua L , Pallotta Andrea M , Neuner Elizabeth A , Brummel Gretchen L , Postelnick Michael J , Schulz Lucas T , Spivak Emily S , Wrenn Rebekah H
Published: October 2020

Background

The majority of antimicrobial use occurs in the ambulatory setting. Antimicrobial stewardship programs (ASPs) are effective in improving appropriate prescribing and are now required by accreditation bodies.

Methods

This was a cross-sectional, multicenter survey describing the current state of ambulatory ASPs in a national cohort of Vizient member hospitals with ambulatory healthcare settings and serves as a benchmark for stewardship strategies related to program effectiveness.

Results

One hundred twenty-nine survey responses from a variety of institution types across 44 states were received. Survey respondents reported a fully functioning ASP in 7% (9 of 129) of ambulatory practices compared with 88% (114 of 129) of inpatient institutions. Effectiveness in at least 1 antibiotic use-related outcome (ie, utilization, resistance, Clostridioides difficile infection, or cost) in the past 2 years was reported in 18% (18 of 100) of ambulatory and 84% (103 of 123) of inpatient ASPs. Characteristics of ambulatory ASPs demonstrating effectiveness were institution guidelines (89%, 16 of 18), rapid diagnostic testing for respiratory viruses or group A Streptococcus (89% 16 of 18), outpatient antibiograms (78% 14 of 18), and dedicated pharmacist support (72%, 13 of 18). Ambulatory ASP effectiveness was shown to increase as programs met more of the Centers for Disease Control and Prevention (CDC) Core Elements of Outpatient Antimicrobial Stewardship (P < .001).

Conclusions

Antimicrobial stewardship programs are needed in the ambulatory setting, but they are not common. Currently, few ambulatory ASPs in this survey self-identify as fully functioning. The CDC Core Elements of antimicrobial stewardship should remain foundational for ASP development and expansion.
DEVELOPMENT OF NACL-BASED OPTICALLY STIMULATED LUMINESCENT PHOSPHORS FOR THE POSSIBLE APPLICATIONS IN DOSIMETRY
Authors: Gaikwad S U , Patil R R , Kulkarni M S , Dudhe C M , Moharil S V
Published: October 2020

New highly sensitive optically stimulated luminescent phosphors with NaCl moiety and dopants Ca,Cu,P/Mg,Cu,P are developed. These phosphors show very high optically stimulated luminescence (OSL) sensitivity. The dose response for NaCl:Ca,Cu,P is linear up to 1.2 Gy and for NaCl:Mg,Cu,P is slightly sub linear from 0.2 Gy. These phosphors show 30% fading during first 4 and later signal gets stabilised with no further signal loss. These sensitive phosphors will find applications in radiation dosimetry using OSL.
Advances in engineering CRISPR-Cas9 as a molecular Swiss Army knife
Authors: Meaker Grace A , Hair Emma J , Gorochowski Thomas E
Published: October 2020

The RNA-guided endonuclease system CRISPR-Cas9 has been extensively modified since its discovery, allowing its capabilities to extend far beyond double-stranded cleavage to high fidelity insertions, deletions and single base edits. Such innovations have been possible due to the modular architecture of CRISPR-Cas9 and the robustness of its component parts to modifications and the fusion of new functional elements. Here, we review the broad toolkit of CRISPR-Cas9-based systems now available for diverse genome-editing tasks. We provide an overview of their core molecular structure and mechanism and distil the design principles used to engineer their diverse functionalities. We end by looking beyond the biochemistry and toward the societal and ethical challenges that these CRISPR-Cas9 systems face if their transformative capabilities are to be deployed in a safe and acceptable manner.
Predictors of engagement in an internet-based cognitive behavioral therapy program for veterans with chronic low back pain
Authors: Solar Chelsey , Halat Allison M , MacLean R Ross , Rajeevan Haseena , Williams David A , Krein Sarah L , Heapy Alicia A , Bair Matthew J , Kerns Robert D , Higgins Diana M
Published: October 2020

Internet-based interventions for chronic pain have demonstrated efficacy and may address access barriers to care. Participant characteristics have been shown to affect engagement with these programs; however, limited information is available about the relationship between participant characteristics and engagement with internet-based programs for self-management of chronic pain. The current study examined relationships between demographic and clinical characteristics and engagement with the Pain EASE program, a self-directed, internet-based cognitive behavioral therapy intervention for veterans with chronic low back pain (cLBP). Veterans with cLBP were enrolled in a 10 week trial of the Pain EASE program. Engagement measures included the number of logins, access to coping skill modules, and completed study staff-initiated weekly check-in calls. Regression analyses were conducted to identify significant predictors of engagement from hypothesized predictors (e.g., race/ethnicity, age, depressive symptom severity, and pain interference). Participants (N = 58) were 93% male, 60.3% identified as White, and had a mean age of 54.5 years. Participants logged into the program a median of 3.5 times, accessed a median of 2 skill modules, and attended a median of 6 check-in calls. Quantile regression revealed that, at the 50th percentile, non-White-identified participants accessed fewer modules than White-identified participants (p = .019). Increased age was associated with increased module use (p = .001). No clinical characteristics were significantly associated with engagement measures. White-identified race/ethnicity and increased age were associated with greater engagement with the Pain EASE program. Results highlight the importance of defining and increasing engagement in internet-delivered pain care.
Behavioral medicine challenges in the shadow of a global pandemic
Authors: Brooks Alyssa T , Allen Hannah K , Thornton Louise , Trevorrow Tracy
Published: October 2020

Health behavior researchers should refocus and retool as it becomes increasingly clear that the challenges of the COVID-19 pandemic surpass the direct effects of COVID-19 and include unique, drastic, and ubiquitous consequences for health behavior. The circumstances of the pandemic have created a natural experiment, allowing researchers focusing on a wide range of health behaviors and populations with the opportunity to use previously collected and future data to study: (a) changes in health behavior prepandemic and postpandemic, (b) health behavior prevalence and needs amidst the pandemic, and (c) the effects of the pandemic on short- and long-term health behavior. Our field is particularly challenged as we attempt to consider biopsychosocial, political, and environmental factors that affect health and health behavior. These realities, while daunting, should call us to action to refocus and retool our research, prevention, and intervention efforts
Combined 3-dimensional printing model and 3-dimensional fluoroscopic navigation to assist C2 pedicle screw insertion
Authors: Xu Hao-Tian , Zheng Shuang , Dong Rong-Peng , Yu Tong , Zhao Jian-Wu
Published: October 2020

Rationale:

The misplaced cervical screw can cause catastrophic surgical complications, such as nerve root damage, vertebral artery compromise, spinal cord injury, and even paraplegia. Thus, the present study aims to describe a novel technique of 3-dimensional printing model (3DPM) combined with 3-dimensional fluoroscopic navigation (3DFN) to facilitate C2 pedicle screw insertion.

Patient concerns:

A 56-year-old male patient presented hypoesthesia of the trunk and extremities, accompanied by a walking disorder.

Diagnoses:

Congenital atlantoaxial malformation with atlantoaxial dislocation.

Interventions:

He underwent an occipital cervical fusion. We used 3DPM and 3DFN technology to guide C2 pedicle screws insertion.

Outcomes:

We inserted 2 pedicle screws and 4 lateral mass screws using the combined 3DPM and 3DFN technology. All screws were classified as excellent position postoperatively. The surgical duration, total fluoroscopic time, and the bleeding volume were 258 minutes, 3.9 minutes, and 237 mL, respectively. No surgical complications, such as neurological compromise, nonunion, dysphagia, infection, polypnea, fixation failure, pseudarthrosis formation, or revision surgery, were observed. The follow-up duration lasted 30 months.

Lessons:

The combination of 3DPM and 3DFN to promote C2 pedicle screws implantation is a safe, accurate, reliable, and useful technology, which can achieve an excellent therapeutic effect and avoid surgical complications. However, using the 3DPM and 3DFN technology may increase the financial burden of patients.
Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome
Authors: Nabeya Daijiro , Kinjo Takeshi , Yamaniha Kazutaka , Yamazato Shoshin , Tome Reo , Miyagi Kazuya , Nakamura Hideta , Kinjo Tetsu , Haranaga Shusaku , Higa Futoshi , Fujita Jiro
Published: October 2020

Introduction:

Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge.

Patient concerns:

A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital.

Diagnosis:

A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB.

Interventions:

Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)].

Outcomes:

After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later.

Conclusion:

We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.
Psychological impact of high-quality nursing care on patients with esophageal cancer during perioperative period
Authors: Liu Xiu-yu , Jiao Chuan-hua , Zhao Dan , Chen Yan , Zhang Hong-mei
Published: October 2020

Background:

This study is designed to systematically assess the psychological impact of high-quality nursing care (HQNC) on patients with esophageal cancer during perioperative period (ECPP).

Methods:

Several electronic databases will be searched to collect randomized controlled trials (RCTs) or case-control studies (CCSs) on HQNC in the management of ECPP from inception to present: Cochrane Library, PUBMED, EMBASE, SinoMed, Web of Science, WANGFANG, and China National Knowledge Infrastructure. We will not apply any language limitation to all literature searches. Two authors will independently perform literature selection, data extraction and literature quality evaluation. All disagreements will be resolved by a third author through discussion. Cochrane risk of bias tool will be employed to assess trial quality, and RevMan 5.3 software will be utilized to carry out statistical analysis.

Results:

This study will summarize the current evidence to appraise of the psychological impact of HQNC in the management of ECPP.

Conclusion:

The findings of this study may help to explicit whether HQNC is effective on psychological problem in ECPP. It will also provide scientific evidence for the clinical practice and future researches.

Study registration:

INPLASY202080071.
Vici syndrome with pathogenic homozygous EPG5 gene mutation
Authors: Abidi Kamal T. , Kamal Naglaa M. , Bakkar Ayman A. , Almarri Saad , Abdullah Rehab , Alsufyani Maram , Alharbi Arwa
Published: October 2020

Rationale:

Vici syndrome (VICIS) is a rare, autosomal recessive neurodevelopmental disorder with multisystem involvement characterized by agenesis of the corpus callosum, congenital cataracts, cardiomyopathy, combined immunodeficiency, significant developmental delay, and hypopigmentation and in some cases loss of hearing. It is caused by mutations in Ectopic P-granules protein 5 gene, which is responsible for regulating autophagy activity.

Patient concern:

We report a 6-month-old Saudi female patient who was the second-born baby of first cousins. She was born by normal spontaneous vertex vaginal delivery. Parents noticed that she had global developmental delay and recurrent hospital admissions due to chest infections.

Diagnosis:

Brain magnetic resonance imaging showed brain atrophy with corpus callosum agenesis. Ophthalmology examination revealed bilateral congenital cataract. Molecular genetic testing identified the pathogenic homozygous variant c.4751T>A p. (Leu1584∗) on exon 27 of the EPG5 gene and confirmed the diagnosis of Vici syndrome.

Interventions:

Supportive multidisciplinary care plan was initiated to this untreatable syndrome.

Outcomes:

The patient died at the age of 6 months due to sepsis with uncompensated septic shock.

Lessons:

VICIS is a rare untreatable disorder with worldwide distribution. High index of suspicion is needed to diagnose it and family genetic counselling is crucial.
Association between frailty and vitamin B12 in the older Korean population
Authors: Soh Yunsoo , Won Chang Won
Published: October 2020

Frailty is a common geriatric condition due to aging and defined as a decline in strength and a decrease in the physiologic ability to maintain the homeostasis. Vitamin B12 (B12), water-soluble vitamins, are a cofactor in DNA synthesis and involved in the metabolism of every cell in the human body, including the central nervous system. Demyelination neuromuscular symptoms observed in the peripheral nervous system, along with signs of significant damage to nerve fibers, often cause weakness, numbness in distal limbs, impaired balance, gait ataxia, and even physical frailty. In this cross-sectional study, we aimed to investigate the relationship between frailty and B12 level in community-dwelling Korean older adults.

Using the data from the Korean Frailty and Aging Cohort Study, 2938 participants (1400 men and 1538 women) were recruited in this study. To evaluate frailty, we compared the frail group and not-frail group based on the modified Korean version of the cardiovascular health study frailty index developed by Fried. SARC-F is used to screen for sarcopenia. The short physical performance battery (SPPB) timed up and go (TUG) test and activities-specific balance confidence scale used to evaluate the physical function and fall risk of participants. B12 concentrations were classified into clinically relevant categories: insufficient (<350 pg/mL) and sufficient (≥350 pg/mL). Linear and logistic regression analyses were used to evaluate the relationship between frailty and B12 levels.

The mean age of the frail group was 77.8 (standard deviation = 3.7) years, while that of the not-frail group was 76.7 (SD = 4.0); of which the frail group's mean age was significantly high. In the unadjusted model, frailty was highly prevalent in the B12 insufficient group (odds ratio = 1.298). In the model fully adjusted for demographic data and comorbidities, these associations were attenuated. The B12 sufficiency group showed better total SPPB and TUG test scores. However, they were not statistically significant in the fully adjusted model.

In this cross-sectional study, low B12 increased the incidence of frailty and affected physical performance, but it does not increase the incidence of frailty when considering the confounding factors. Frailty is caused by several factors rather than 1 factor, and B12 is one of these factors.
Targeting of protease activator receptor-2 (PAR-2) antagonist FSLLRY-NH2 as an asthma adjuvant therapy
Authors: Ocasio-Rivera Marinel , Marin-Maldonado Frances , Trossi-Torres Geraline , Ortiz-Rosado Angely , Rodríguez-Irizarry Valerie , Rodriguez-Lopez Eric , Martínez Sahayra , Almodóvar Sharilyn , Suarez-Martínez Edu
Published: October 2020

Asthma is a chronic inflammatory and multifactorial respiratory tract disease. It affects over 18 million adults and 6 million children in the USA with Puerto Ricans showing the highest prevalence (12%–19%). This airways illness can be triggered by an environmental stimulus such as grass pollen, fungi spores, cockroaches allergens, dust mites metabolic compounds, and importantly, by environmental proteases such as trypsin and tryptase. Because of the pivotal role of proteases in the onset of asthma pathophysiology, we focused this study on the serine Protease Activated Receptor-2 (PAR-2), a G-protein-coupled receptor widely expressed in cells across the respiratory tract. Herein, we measured the activation of PAR-2 on primary pulmonary bronchial/tracheal epithelial cells, human small airway epithelial cells, lung bronchial smooth muscle cells (with and without asthma). We tested human-derived eosinophils from 61 Puerto Rican participants (33 asthmatic and 28 non-asthmatic). As surrogate of PAR-2 activation or inhibition we used intracellular calcium mobilization assay. We hypothesized that following exposure of the PAR-2 agonist (AC264613), the studied human primary cell types will increase the mobilization of intracellular calcium levels. In contrast, we expected a decrease of the intracellular calcium levels upon exposure to a PAR-2 antagonist (FSLLRY-NH2). The Puerto Rican-derived eosinophils were analyzed for the proinflammatory markers MAPK/PI3K using flow cytometry (n = 8). As expected, the PAR-2 agonist significantly increased the activation of PAR-2 on the bronchial/tracheal epithelial cells, bronchial smooth muscle cells and human small airway epithelial cells (P = .01). The PAR-2 antagonist significantly decreased the intracellular calcium levels of these lung primary down to undetectable levels (P = .01). Remarkably, the asthmatic-derived eosinophils showed a striking 300% increase of intracellular calcium mobilization suggesting a severe response to the PAR-2 agonist stimuli in asthmatics. In contrast, there were no significant changes between groups after adding the PAR-2 antagonist. Our outcomes revealed that PAR-2 antagonist effectively inhibited the studied primary cells, expecting to decrease the immune response of eosinophils. Most importantly, our results reveal a promising role for the PAR-2 antagonist in targeting bronchial/tracheal epithelial cells, human small airway epithelial cells and bronchial smooth muscle cells with the potential to oblige an asthma adjuvant therapy.
Predicting length of stay in patients admitted to stroke rehabilitation with severe and moderate levels of functional impairments
Authors: García-Rudolph Alejandro , Cegarra Blanca , Opisso Eloy , Tormos Josep María , Bernabeu Montserrat , Saurí Joan
Published: October 2020

Severe stroke patients are known to be associated with larger rehabilitation length of stay (LOS) but other factors besides severity may be contributing. We aim to identify LOS predictors within a population of mostly severe patients and analyze the impact of socioeconomic situation in functionality at admission.

A retrospective observational cohort study was conducted including 172 inpatients admitted to a rehabilitation center between 2007 and 2019. Associations with LOS were examined among 30 potential predictor variables using bivariate correlations. Significantly correlated (P < .002, Bonferroni adjustment) variables were entered into 9 different multiple linear regression models.

No mild participants were included, 63.37% severe and 36.63% moderate. Most significant LOS determinants were: 1) total functional independence measure (FIM) (P < .001) and hemiparesis (P = .0108) (adjusted R2 = 0.24), 2) cognitive FIM (P = .002) and severity (P = .001) (adjusted R2 = 0.22), and 3) home accessibility (P = .043) and hemiparesis (P = 0.032) (adjusted R2 = 0.19).

Known LOS predictors (e.g., depression, ataxia) within the full stroke severities were not found significant in our dataset.

Socioeconomic situation was found moderately correlated with total FIM (r = −0.32, P < .0001).

When stratifying the patients’ socioeconomic situation into mild, important, and severe social risk, their respective median total FIM at admission were 61.5, 50, and 41, with significant differences between the mild and important group (P < .001); also significant differences were found between mild and severe groups (P < .001).

A few of the variables identified in the literature as significant predictors of LOS within the full stroke population were also significant for our dataset (National Institutes of Health Stroke Scale, FIM, home accessibility) explaining less than 25% of the LOS variance. Most of the 30 analyzed known predictors were not significant (e.g., depression, age, recurrent stroke, ataxia, orientation, verbal communication, etc) suggesting that factors outside functional, socioeconomic, medical, and demographics not included in this study (e.g., rehabilitation sessions intensity) have important influences on LOS for severe patients.

Patients at mild social risk obtained significantly higher total FIM at admission than patients at important and severe social risk. The importance of socioeconomic situation has been scarcely studied in the literature in relation to functionality at admission; our results suggest that it requires to be considered.
The undiagnosed potential clinically significant incidental findings of neck CTA
Authors: Chen Guangliang , Xue Yunjing , Wei Jin , Duan Qing
Published: October 2020

To assess the prevalence and missed reporting rate of potential clinically-significant incidental findings (IFs) in the neck CTA scans.

All consecutive patients undergoing neck CTA imaging, from January 1, 2017 to December 31, 2018, were retrospectively evaluated by a radiologist for the presence of incidental findings in the upper chest, lower head and neck regions. These incidental findings were subsequently classified into 3 categories in terms of clinical significance: Type I, highly significant, Type II, moderately significant; and Type III, mildly or not significant. Type I and Type II IFs were determined as potential clinically significant ones and were retrospectively analyzed by another 2 radiologists in consensus. The undiagnosed findings were designated as those that were not reported by the initial radiologists. The differences in the rate of unreported potential clinically significant IFs were compared between the chest group and head or neck group.

A total of 376 potential clinically significant IFs were detected in 1,698 (91.19%) patients, of which 175 IFs were classified as highly significant findings (Type I), and 201 (53.46%) as moderately significant findings (Type II). The most common potential clinically significant findings included thyroid nodules (n = 88, 23.40%), pulmonary nodules (n = 56, 14.89%), sinus disease (n = 39, 10.37%), intracranial or cervical artery aneurysms (n = 30, 7.98%), enlarged lymph nodes (n = 24, 6.38%), and pulmonary embolism (n = 19, 5.05%). In addition, 184 (48.94%) of them were not mentioned in the initial report. The highest incidence of missed potential clinical findings were pulmonary embolism and pathologic fractures and erosions (100% for both). The unreported rate of the chest group was significantly higher than that of the head or neck one, regardless of Type I, Type II or all potential clinically significant IFs (χ2 = 32.151, χ2 = 31.211, χ2 = 65.286, respectively; P < .001 for all).

Important clinically significant incidental findings are commonly found in a proportion of patients undergoing neck CTA, in which nearly half of these patients have had potential clinically significant IFs not diagnosed in the initial report. Therefore, radiologists should beware of the importance of and the necessity to identify incidental findings in neck CTA scans.
Relationship between calcifications and structural lesions on hand radiography and axial calcifications on CT-scan
Authors: Bauer Elodie , Fauny Marine , Tanguy Maurice , Albuisson Eliane , Mandry Damien , Huttin Olivier , Chabot Francois , Deibener Joelle , Chary-Valckenaere Isabelle , Loeuille Damien
Published: October 2020

The objectives of this study were to describe the prevalence and characteristics of radiographic lesions of the hands, and calcifications of the spine on computer tomography scans (CT-scans), and to investigate the relationships between radiographic and CT-scan abnormalities and clinical features in a population of patients with systemic sclerosis (SSc).

Subjects underwent X-ray examination of the hands, and thoracic or thoraco-abdominal and pelvic CT scan or lumbar CT scan in the year. Structural lesions on hand X ray was scored and spinal calcifications were evaluated in the anterior, intracanal and posterior segments. Intra and inter-reliability was tested for radiography and CT- scan. Prognostic factors considered were interstitial pulmonary lesions on the CT scan, pulmonary arterial hypertension (PAH) and death.

This study involved 77 SSc patients, 58 (75%) with limited cutaneous SSc (lcSSc) and 19 (25%) with diffuse SSc (dSSc). The prevalences of radiographic lesions of the hand were 28.6% for periarticular calcifications and 26% for calcinosis. On CT scan, 64 (83%) patients exhibited at least 1 calcification. Spine calcifications were depicted in 80.5%, 27.3%, and 35.1% at the anterior, intracanal and posterior segments respectively. Calcifications were mainly localized on thoracic spine. Inter reader reliabilities were good for hands and moderate for spine respectively. Spine calcifications and periarticular calcifications in the hands were associated (P = .012). Calcinosis in the hands was related to PAH (P = .02). Posterior calcification segment and foraminal calcifications were associated with interstitial lung disease (ILD) (P = .029) and death (P = .001).

More than 80% of systemic sclerosis patients presented spine calcifications. A significant association between hands and spinal calcifications were confirmed and some localization in the posterior segment considered as a bad prognostic factor.
Prostate cancer: a risk factor for COVID-19 in males?
Authors: Mou Ruiyu , Jin Xinyao , Li Wenjie , Wu Mingxin , Liu Xiaodi , Liu Zhao , Guo Shanqi , Li Xiaojiang , Jia Yingjie
Published: October 2020

Introduction:

COVID-19 is now a global pandemic. Although there are very few studies describing the characteristics of SARS-CoV-2 infections in patients with prostate cancer, these patients are likely to be more susceptible to COVID-19 than healthy people because of their immunosuppressed state. However, there is no evidence that prostate cancer is a risk factor for COVID-19.

Methods:

We searched the Wanfang database, the China Science Journal Citation Report (VIP database), the China National Knowledge Infrastructure (CNKI), Web of Science, EMBASE, PubMed, and the Cochrane Library for studies related to the topic. We designed a standardized data extraction sheet and used Epidata software 3.1 for data extraction. In accordance with the Cochrane 5.1.0 standard, both a quality assessment and a risk assessment were carried out for the research meeting the inclusion criteria. The data were analyzed using Revman 5.3 and Stata 13.0 software.

Results:

The study integrated existing research findings and a meta-analysis of the data to investigate the prevalence of prostate cancer in males infected with SARS-CoV-2 and the adverse clinical outcomes in male patients with or without COVID-19.

Conclusion:

The results of this research may provide a basis for judging if prostate cancer is a risk factor for males infected with SARS-CoV-2, and the findings can effectively help to prevent COVID-19 in patients with prostate cancer.

Ethics and dissemination:

Ethics approval is not required for this systematic review as it will involve the collection and analysis of secondary data. The results of the review will be reported in international peer-reviewed journals

PRORPERO registration number:

CRD42020194071.
The efficacy of gefitinib supplementation for breast cancer
Authors: Ye Jing , Tian Tian , Chen Xiaopin
Published: October 2020

Introduction:

The efficacy of gefitinib supplementation for breast cancer remains controversial. We conduct a systematic review and meta-analysis to explore the influence of gefitinib supplementation vs placebo on the efficacy of breast cancer.

Methods:

We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through February 2019 and included randomized controlled trials assessing the effect of gefitinib supplementation vs placebo on overall response for breast cancer patients. This meta-analysis was performed using the random-effect model.

Results:

Seven randomized controlled trials involving 927 patients were included in the meta-analysis. Overall, compared with control group for breast cancer, gefitinib supplementation revealed no obvious impact on complete response (risk ration [RR] = 1.19; 95% confidence interval [CI] = 0.58 to 2.44; P = .63), progressive disease (RR = 0.81; 95% CI = 0.59–1.11; P = .18), partial response (RR = 0.67; 95% CI = 0.36–1.25; P = .21), stable disease (RR = 1.02; 95% CI = 0.65–1.60; P = .92), nausea or vomiting (RR = 0.99; 95% CI = 0.73–1.33; P = .93), but was associated with increased incidence of diarrhea (RR = 2.80; 95% CI = 2.23–3.52; P < .00001), decreased incidence of hot flash (RR = 0.53; 95% CI = 0.37–0.78; P = .001), and improved incidence of adverse events (RR = 1.12; 95% CI = 1.05–1.19; P = .0006).

Conclusions:

Gefitinib supplementation may provide no positive effect on complete response, progressive disease, partial response or stable disease for breast cancer patients, but with the increase in adverse events.
Comparing the utility of 30- and 60-minute cortisol levels after the standard short synacthen test to determine adrenal insufficiency
Authors: Butt Muhammad Imran , Alzuhayri Nouf , Amer Lama , Riazuddin Muhammad , Aljamei Hadeel , Khan Muhammad Sohaib , Abufarhaneh Mohammed , Alrajhi Eman , Alnassar Anhar , Alahmed Reem , Aljayar Dina Mahmoud Ahmad , Abothenain Fayha Farraj , De Vol Edward
Published: October 2020

Short Synacthen test (SST) involves measuring the baseline, 30-, and 60-minute serum cortisol levels, after injecting 250 μg of synthetic adrenocorticotropic hormone or Synacthen (ACTH). This study aimed to review the current clinical practice of performing SST to establish a standardized test protocol and to additionally test the hypothesis regarding performing the 60-minute cortisol test alone and the dependence of overall SST result on baseline cortisol level.

Patients >14 years who underwent SST from January 2010 to December 2017 were included. Pearson's chi-square cross-tabulation was used to identify individuals with inconsistent 30- and 60-minute serum cortisol test results. Logistic regression analysis was performed to predict normal responses based on the baseline cortisol value.

Of the 965 patients identified from pharmacy, medical, and laboratory records, 849 were included. Mean baseline, 30-, and 60-minute cortisol levels after ACTH injection were 394 ± 286.58, 722 ± 327.11, and 827 ± 369.30 nmol/L, respectively. Overall, 715 (84%) and 134 (16%) patients had normal and abnormal responses, respectively. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35%, respectively, while ACTH levels were not measured in 55% of the patients. Overall, 9.49% (n = 72) of the patients had a suboptimal response at 30 minutes, but reached the threshold value of 550 nmol/L at 60 minutes. This particular subgroup's mean change (240 nmol/L) in cortisol level from baseline to 30-minute was higher than that observed in patients with abnormal response at both time-points (mean change, 152 nmol/L). No patient with 30-minute optimal responses had 60-minute suboptimal responses. The baseline serum cortisol threshold of ≥226 nmol/L had 80% sensitivity, 71% specificity, and 93% positive predictive value for detecting a normal SST (P-value < .0001).

Relying on a 60-minute cortisol level can identify all normal and abnormal responses, while relying on 30-minute cortisol level alone may produce false-positives. Additionally, a baseline cortisol level of ≥226 nmol/L is a reliable threshold for determining adequate adrenal function, particularly with a low pretest hypoadrenalism probability.