bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining the association between fibromyalgia, the gut microbiome and its biomarkers: A systematic review
Authors: Erdrich Sharon , Hawrelak Jason A. , Myers Stephen P. , Harnett Joanna E.
Published: March 2020

Background

The association between fibromyalgia and irritable bowel syndrome is well-established. Alterations in the composition and diversity of the gut microbiome in irritable bowel syndrome have been reported, however, this association is poorly understood in fibromyalgia.

Our aim was to summarise the research reporting on the gastrointestinal microbiome and its biomarkers in people with fibromyalgia.

Methods

A systematic review of published original research reporting on the gastrointestinal microbiota and its biomarkers in adults with a diagnosis of fibromyalgia was undertaken.

Results

From 4771 studies, 11 met our inclusion criteria and were separated into four main groups: papers reportingHelicobacter pylori; other gut bacterial markers; metabolomics and other biomarkers, which included intestinal permeability and small intestinal bacterial overgrowth.

Conclusion

The results suggest there is a paucity of quality research in this area, with indications that the gut microbiota may play a role in fibromyalgia within the emerging field of the gut-musculoskeletal axis. Further investigations into the relationship between the gut microbiota, gut dysfunction and fibromyalgia are warranted.
A lower cut-off for lymph node harvest predicts for poorer overall survival after rectal surgery post neoadjuvant chemoradiotherapy
Authors: Yeo Charleen Shanwen , Syn Nicholas , Liu Huimin , Fong Sau Shung
Published: March 2020

Background

A lymph node harvest (LNH) of < 12 is a predictor for poor prognosis in rectal cancer patients. However, neoadjuvant chemoradiotherapy (NACRT) is known to decrease LNH; hence, a cut-off of 12 is inappropriate in such patients. This paper aims to establish a LNH cut-off predictive for disease-free and overall survival in NACRT patients.

Methods

A retrospective review of patients who underwent elective surgery for rectal cancer from 2006 to 2013 was performed. All patients with R1/2 resections and presence of metastases and those operated on for recurrence were excluded. Patient demographics, clinical features, operative details, LNH, 30-day mortality and disease-free and overall survival were recorded. P values of < 0.05 were considered significant.

Results

A total of 257 patients were studied, with 174 (68%) males and a median age of 66 years. Ninety-four (37%) patients received long-course NACRT, and 122 (48%) patients were stage 2 and below. Median LNH was 17, which was reduced in the NACRT group (14 versus 23, P < 0.01). Average length of stay was 9 ± 8 days, with a major post-operative complication rate of 4%. Using hazard ratio plots for the NACRT subgroup, LNH cut-offs of 16.5 and 8.5 were obtained for disease-free survival (DFS) and overall survival (OS) respectively. Survival analysis showed that a LNH cut-off of 8.5 was a significant predictor of OS (P < 0.001).

Conclusion

LNH is reduced in patients receiving NACRT before rectal cancer surgery. A LNH of 9 and above is associated with improved overall survival. We propose that this can be used as a tool for prognosis.
Circular RNA hsa_circ_0004812 impairs IFN-induced immune response by sponging miR-1287-5p to regulate FSTL1 in chronic hepatitis B
Authors: Zhang Liangdong , Wang Zichao
Published: March 2020

Background

The present study aims to explore the functions of circular RNA hsa_circ_0004812 in chronic hepatitis B (CHB) and its underlying molecular mechanisms.

Methods

The expression of circular RNA (circRNA)_0004812 was examined using qRT-PCR and Western blot in blood and liver tissues from CHB patients and healthy volunteers. In the in vitro study, the expression levels of circular RNA hsa_circ_0004812, miR-1287-5p, interferon (IFN)-α, IFN-β were determined using qRT-PCR and Western blotting in HBV-infected hepatoma cells, respectively. Luciferase and biotin pull-down assays were used to investigate the interactions between miR-1287-5p and circ_0004812.

Results

Levels of circ_0004812 were upregulated in CHB patients and HBV-infected hepatoma cells. Knockdown of circ_0004812 increased the expression of IFN-α and IFN-β in HBV-infected Huh7 cells. MiR-1287-5p was identified as a target of circ_0004812 whose overexpression inhibited the expression of miR-1287-5p. Additionally, circ_0004812 promoted the expression of Follistatin-related protein (FSTL) 1 through inhibiting miR-1287-5p. Circ_0004812/miR-1287-5p/FSTL1 axis regulated HBV-induced immune suppression.

Conclusion

Circ_0004812 was identified as a potential target for CHB infection. Circ_0004812 promoted the expression of FSTL1 by inhibiting miR-1287-5p.
Downregulation of miR-484 is associated with poor prognosis and tumor progression of gastric cancer
Authors: Li Ying , Liu Yusong , Yao Jie , Li Rui , Fan Xiaocheng
Published: March 2020

Background

Gastric cancer is one of the most common cancers leading to high cancer mortality. MicroRNA-484 (miR-484) has been evaluated as a biomarker for various types of cancers. The subject of this study is to investigate the functional role of miR-484 in gastric cancer.

Methods

The expression of miR-484 in gastric cancer was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Kaplan-Meier survival and Cox regression analyses were employed to explore the prognostic significance of miR-484 in gastric cancer. The functional role of miR-484 in gastric cancer was determined by CCK-8 and Transwell assays.

Results

The results showed that miR-484 was significantly downregulated in gastric cancer tissues and cell lines. The downregulation of miR-484 was closely related to differentiation, lymph node metastasis, TNM stage, and poor prognosis. Cox regression analyses demonstrated that miR-484 was an independent prognosis indicator for gastric cancer patients. Additionally, the downregulation of miR-484 enhanced cell proliferation, migration, and invasion in gastric cancer cells.

Conclusion

These data demonstrated that miR-484 can serve as a potential prognostic biomarker and therapeutic target for gastric cancer and it may be involved in the progression of gastric cancer.
High frequency optogenetic activation of inputs to the lateral amygdala forms distant association with foot-shock
Authors: Li Fei , Jia Chun-Hui , Huang Jun , Bi Guo-Qiang , Lau Pak-Ming
Published: March 2020

Aim

A hallmark of classical conditioning is that conditioned stimulus (CS) must be tightly coupled with unconditioned stimulus (US), often requiring temporal overlap between the two, or a short gap of several seconds. In this study, we investigate the temporal requirements for fear conditioning association between a strong artificial CS, high-frequency optogenetic activation of inputs into the lateral amygdala of rats, and a foot-shock to the animal with delays up to many minutes.

Methods

AAV-oChIEF-tdTomato viruses were injected into the auditory cortex and the medial geniculate nucleus of rats. An optical fiber was implanted just above the lateral amygdala of the animal. Optogenetic high-frequency stimuli (oHFS; containing five 1-s trains of 100 Hz laser pulses) were delivered to the lateral amygdala, before or after (with varying intervals) a foot-shock that elicits fear responses in the animal. Pre-trained lever-press behavior was used to assess the degree of fear recall by optogenetic test stimuli (OTS; 10 Hz for 2 min) 24 h after the association experiment.

Results

In contrast to the tight temporal requirement for classical conditioning with paired optogenetic moderate-frequency stimuli (oMFS; 10 Hz for 20 s) and foot-shock, oHFS followed by foot-shock with a 5-min or even 1-h (but not 3-h) interval could successfully establish an association to be recalled by OTS the next day. Meanwhile, foot-shock followed by oHFS with a 5-min (but not 1-h) interval could also establish the conditioning. Thus, distant association may be formed between temporally distant stimuli when the CS is strong.
A mutant vesicular stomatitis virus with reduced cytotoxicity and enhanced anterograde trans-synaptic efficiency
Authors: Lin Kunzhang , Zhong Xin , Ying Min , Li Lei , Tao Sijue , Zhu Xutao , He Xiaobin , Xu Fuqiang
Published: March 2020

Understanding the connecting structure of brain network is the basis to reveal the principle of the brain function and elucidate the mechanism of brain diseases. Trans-synaptic tracing with neurotropic viruses has become one of the most effective technologies to dissect the neural circuits. Although the retrograde trans-synaptic tracing for analyzing the input neural networks with recombinant rabies and pseudorabies virus has been broadly applied in neuroscience, viral tools for analyzing the output neural networks are still lacking. The recombinant vesicular stomatitis virus (VSV) has been used for the mapping of synaptic outputs. However, several drawbacks, including high neurotoxicity and rapid lethality in experimental animals, hinder its application in long-term studies of the structure and function of neural networks. To overcome these limitations, we generated a recombinant VSV with replication-related N gene mutation, VSV-NR7A, and examined its cytotoxicity and efficiency of trans-synaptic spreading. We found that by comparison with the wild-type tracer of VSV, the NR7A mutation endowed the virus lower rate of propagation and cytotoxicity in vitro, as well as significantly reduced neural inflammatory responses in vivo and much longer animal survival when it was injected into the nucleus of the mice brain. Besides, the spreading of the attenuated VSV was delayed when injected into the VTA. Importantly, with the reduced toxicity and extended animal survival, the number of brain regions that was trans-synaptically labeled by the mutant VSV was more than that of the wild-type VSV. These results indicated that the VSV-NR7A, could be a promising anterograde tracer that enables researchers to explore more downstream connections of a given brain region, and observe the anatomical structure and the function of the downstream circuits over a longer time window. Our work could provide an improved tool for structural and functional studies of neurocircuit.
Coexistence of cerebral hypometabolism and neuroinflammation in the thalamo-limbic-brainstem region in young women with functional somatic syndrome
Authors: Matsudaira Takashi , Terada Tatsuhiro , Obi Tomokazu , Yokokura Masamichi , Takahashi Yukitoshi , Ouchi Yasuomi
Published: March 2020

Background

Functional somatic syndrome (FSS) is a disorder characterized by clusters of medically unexplained symptoms. Some women suffer from persistent FSS after human papillomavirus (HPV) vaccination. However, a causal relationship has not been established, and the pathophysiology of FSS remains elusive. Here, we aimed to identify the brain regions showing altered cerebral metabolism and neuroinflammation in patients with FSS and to correlate the measures of positron emission tomography (PET) with clinical data. Twelve women diagnosed with FSS following HPV vaccination (FSS group) underwent both [18F]FDG-PET to measure glucose metabolism and [11C]DPA713-PET to measure neuroinflammation. [18F]FDG standardized uptake value ratio (SUVR) and [11C]DPA713 binding potential (BPND) values were compared voxel-wise between the FSS and control groups (n = 12 for [18F]FDG, n = 16 for [11C]DPA713). A region-of-interest (ROI)-based analysis was performed to correlate PET parameters with clinical scores. Statistical significance was set at p < 0.05 corrected for multiple comparisons.

Results

Statistical parametric mapping revealed a concomitant significant decrease of [18F]FDG SUVR and increase of [11C]DPA713 BPND in the regions covering the thalamus, mesial temporal area, and brainstem in the FSS group. Correlation analysis revealed that intelligence and memory scores were significantly positively correlated with [18F]FDG SUVR and negatively so with [11C]DPA713 BPND in these regions. A direct comparison between [18F]FDG SUVR and [11C]DPA713 BPND revealed a significant positive correlation in the right hippocampus and amygdala.

Conclusions

Cerebral hypometabolism with neuroinflammation occurring in the thalamo-limbic-brainstem region may reflect the pathophysiology of FSS.
Effects of siRNA silencing on the susceptibility of the fish cell line CHSE-214 to Yersinia ruckeri
Authors: Menanteau-Ledouble Simon , Schachner Oskar , Lawrence Mark L. , El-Matbouli Mansour
Published: March 2020

Yersinia ruckeriis a facultative intracellular enterobacterium mostly known as the causative agent of enteric redmouth disease in salmonid fish. In the present study, we applied RNA inhibition to silence twenty pre-selected genes on the genome of a fish cell line (CHSE-214) followed by a gentamicin assay to quantify the effect of silencing on the cells’ susceptibility to infection and found that silencing of 18 out of 20 genes significantly reduced the number ofY. ruckerirecovered. These findings improve our understanding of the infection process byY. ruckeriand of the interactions between this bacterial pathogen and host cells.
New approaches for the solution of space-time fractional Schrödinger equation
Authors: Demir Ali , Bayrak Mine Aylin , Ozbilge Ebru
Published: March 2020

The aim of this study is to establish the solution of the time-space fractional Schrödinger equation subject to initial and boundary conditions which has many applications in science such as nonlinear optics, plasma physics, super conductivity, based on the residual power series method (RPSM). We first apply suitable transformations to make the order of one of the fractional derivatives integer to implement the RPSM easily to construct the fractional power series solution. The method proposed in this article gives highly encouraging results. Illustrative examples show that this method is compatible with solving such fractional differential equations.
Shannon type inequalities via time scales theory
Authors: Ansari Iqrar , Khan Khuram Ali , Nosheen Ammara , Pečarić Ðilda , Pečarić Josip
Published: March 2020

The aim of present paper is to obtain Shannon type inequalities using the extended version of Jensen’s inequality in time scales settings. The concept of differential entropy of a continuous random variable on time scales is introduced, and its bounds for some particular distributions are also estimated.
Discovery of a novel integron-borne aminoglycoside resistance gene present in clinical pathogens by screening environmental bacterial communities
Authors: Böhm Maria-Elisabeth , Razavi Mohammad , Marathe Nachiket P. , Flach Carl-Fredrik , Larsson D. G. Joakim
Published: March 2020

Background

New antibiotic resistance determinants are generally discovered too late, long after they have irreversibly emerged in pathogens and spread widely. Early discovery of resistance genes, before or soon after their transfer to pathogens could allow more effective measures to monitor and reduce spread, and facilitate genetics-based diagnostics.

Results

We modified a functional metagenomics approach followed by in silico filtering of known resistance genes to discover novel, mobilised resistance genes in class 1 integrons in wastewater-impacted environments. We identified an integron-borne gene cassette encoding a protein that conveys high-level resistance against aminoglycosides with a garosamine moiety when expressed in E. coli. The gene is named gar (garosamine-specific aminoglycoside resistance) after its specificity. It contains none of the functional domains of known aminoglycoside modifying enzymes, but bears characteristics of a kinase. By searching public databases, we found that the gene occurs in three sequenced, multi-resistant clinical isolates (two Pseudomonas aeruginosa and one Luteimonas sp.) from Italy and China, respectively, as well as in two food-borne Salmonella enterica isolates from the USA. In all cases, gar has escaped discovery until now.

Conclusion

To the best of our knowledge, this is the first time a novel resistance gene, present in clinical isolates, has been discovered by exploring the environmental microbiome. The gar gene has spread horizontally to different species on at least three continents, further limiting treatment options for bacterial infections. Its specificity to garosamine-containing aminoglycosides may reduce the usefulness of the newest semisynthetic aminoglycoside plazomicin, which is designed to avoid common aminoglycoside resistance mechanisms. Since the gene appears to be not yet common in the clinics, the data presented here enables early surveillance and maybe even mitigation of its spread.
Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer
Authors: English Krystal , Shepherd Andrew , Uzor Ndidi-Ese , Trinh Ronnie , Kavelaars Annemieke , Heijnen Cobi J.
Published: March 2020

Neurodegenerative disorders, including chemotherapy-induced cognitive impairment, are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health.

We used an in vitro system in which astrocytes containing mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons damaged by cisplatin. Culture of primary cortical neurons with cisplatin reduced neuronal survival and depolarized neuronal mitochondrial membrane potential. Cisplatin induced abnormalities in neuronal calcium dynamics that were characterized by increased resting calcium levels, reduced calcium responses to stimulation with KCl, and slower calcium clearance. The same dose of cisplatin that caused neuronal damage did not affect astrocyte survival or astrocytic mitochondrial respiration. Co-culture of cisplatin-treated neurons with astrocytes increased neuronal survival, restored neuronal mitochondrial membrane potential, and normalized neuronal calcium dynamics especially in neurons that had received mitochondria from astrocytes which underlines the importance of mitochondrial transfer. These beneficial effects of astrocytes were associated with transfer of mitochondria from astrocytes to cisplatin-treated neurons. We show that siRNA-mediated knockdown of the Rho-GTPase Miro-1 in astrocytes reduced mitochondrial transfer from astrocytes to neurons and prevented the normalization of neuronal calcium dynamics.

In conclusion, we showed that transfer of mitochondria from astrocytes to neurons rescues neurons from the damage induced by cisplatin treatment. Astrocytes are far more resistant to cisplatin than cortical neurons. We propose that transfer of functional mitochondria from astrocytes to neurons is an important repair mechanism to protect the vulnerable cortical neurons against the toxic effects of cisplatin.
Low incidence of maxillary hypoplasia in isolated cleft palate
Authors: Azouz Vitali , Ng Marilyn , Patel Niyant , Murthy Ananth S.
Published: March 2020

Background

The cause of maxillary growth restriction in patients with cleft lip and palate remains controversial. While studies have investigated the effects surgical technique and timing have on maxillary growth, few focus on patients with isolated cleft palate (ICP). The purpose of this study was to determine the impact palate repair and its associated complications may have on maxillary growth.

Methods

A retrospective chart review of ICP patients who underwent palatoplasty from 1962 to 1999 at Akron Children’s Hospital was performed. Patient demographics, Veau type, age at primary repair, closure technique, presence of fistula or velopharyngeal insufficiency (VPI), number of palatal operations, maxillary hypoplasia (MH) frequency, and follow-up were recorded. Exclusion criteria included patients with cleft lip, submucous cleft, or syndromes.

Results

Twenty-nine non-syndromic ICP patients were identified; 62% (n = 18) had Veau type 1 and 38% (n = 11) had Veau type 2. All patients underwent 2-flap or Furlow palatoplasty with mobilization of mucoperiosteal flaps. Vomerine flaps were used in all Veau 2 cleft palate closures. Palatoplasty was performed at a mean age of 19.9 ± 8.2 months. Average follow-up was 209 ± 66.5 months. The rate of VPI was 59% (n = 17) and the rate of oronasal fistula was 14% (n = 4).

Conclusions

There was a low incidence of MH despite complications after initial palate closure. Our results seem to suggest that age at palate closure, type of cleft palate, and type of surgical technique may not be associated with MH. Additionally, subsequent procedures and complications after primary palatoplasty such as VPI and palatal fistula may not restrict maxillary growth.
Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma
Authors: Rodríguez-Cid Jeronimo Rafael , Campos-Gomez Saul , García-Montes Vanessa , Magallanes-Maciel Manuel , Flores-Mariñelarena Rodrigo Rafael , Fernández-Garibay Valeria Michelle , González-Espinoza Iván Romarico , Ceja-García Juan Paulo , Cázarez-Price Juan Carlos , Martínez-Barrera Luis , Barriguete-Parra Leopoldo , Zuloaga-Fernandez Carlos Jose , Kuri-Exsome Roberto , Suárez-García David , Gonzalez-Villanueva Jorge Ignacio , Flores-Anaya Noé , Acevedo-Delgado Jose Antonio , Astorga-Ramos Alma Magdalena , Gerson-Cwilich Raquel , Villalobos-Prieto Alberto , Rodríguez-Silva Claudia , Noriega-Iriondo Maria Fernanda , Vázquez-Cortés Leticia , Perales-Rodríguez Eusebio , Acosta-Espinoza Alicia , Perez-Lozano Yareni , Capdeville-García Daniel , Alatorre-Alexander Jorge Arturo
Published: March 2020

PURPOSE

The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies.

METHODS

This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point.

RESULTS

After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%).

CONCLUSION

Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.
Comparative Safety and Health Care Expenditures Among Patients With Chronic Myeloid Leukemia Initiating First-Line Imatinib, Dasatinib, or Nilotinib
Authors: Cole Ashley L. , Wood William A. , Muluneh Benyam , Lund Jennifer L. , Elston Lafata Jennifer , Dusetzina Stacie B.
Published: March 2020

PURPOSE:

Tyrosine kinase inhibitors (TKIs) have dramatically improved survival for patients with chronic myeloid leukemia (CML). No overall survival differences were observed between patients initiating first- and second-generation TKIs in trials; however, real-world safety and cost outcomes are unclear. We evaluated comparative safety and health care expenditures between first-line imatinib, dasatinib, and nilotinib among patients with CML.

PATIENTS AND METHODS:

Eligible patients had one or more fills for imatinib, dasatinib, or nilotinib in the MarketScan Commercial and Medicare Supplemental databases between January 1, 2011, and December 31, 2016 (earliest fill is the index date), 6 months pre-index continuous enrollment, CML diagnosis, and no TKI use in the pre-index period. Hospitalizations or emergency department visits (safety events) were compared across treatment groups using propensity-score-weighted 1-year relative risks (RRs) and subdistribution hazard ratios (HRs). Inflation-adjusted annual health care expenditures were compared using quantile regression.

RESULTS:

Eligible patients included 1,417 receiving imatinib, 1,067 receiving dasatinib, and 647 receiving nilotinib. The 1-year risk of safety events was high: imatinib, 37%; dasatinib, 44%; and nilotinib, 40%, with higher risks among patients receiving dasatinib (RR, 1.17; 95% CI, 1.06 to 1.30) and nilotinib (RR, 1.07; 95% CI, 0.93 to 1.23) compared with those receiving imatinib. Over a median of 1.7 years, the cumulative incidence of safety events was higher among patients receiving dasatinib (HR, 1.23; 95% CI, 1.10 to 1.38) and nilotinib (HR, 1.08; 95% CI, 0.95 to 1.24) than among those receiving imatinib. One-year health care expenditures were high (median, $125,987) and were significantly higher among patients initiating second-generation TKIs compared with those receiving imatinib (difference in medians: dasatinib v imatinib, $22,393; 95% CI, $17,068 to $27,718; nilotinib v imatinib, $19,463; 95% CI, $14,689 to $24,236).

CONCLUSION:

Patients receiving imatinib had the lowest risk of hospitalization or emergency department visits and 1-year health care expenditures. Given a lack of significant differences in overall survival, imatinib may represent the ideal first-line therapy for patients, on average.
Assessing the Impact of Early Identification of Patients Appropriate for Palliative Care on Resource Use and Costs in the Final Month of Life
Authors: Look Hong Nicole J. , Liu Ning , Wright Frances C. , MacKinnon Marnie , Seung Soo Jin , Earle Craig C. , Gradin Sharon , Sati Saurabh , Buchman Sandy , Mittmann Nicole
Published: March 2020

PURPOSE:

This study evaluates whether an intervention to identify Canadian patients eligible for a palliative approach changes the use of health care resources and costs within the final month of life.

METHODS:

Between 2014 and 2017, physicians identified 1,187 patients in family practice units and cancer centers who were likely to die within 1 year based on diagnosis, symptom assessment, and performance status. A multidisciplinary intervention that included activation of community resources and initiation of palliative planning was started. By using propensity-score matching, patients in the intervention group were matched 1:1 with nonintervention controls selected from provincial administrative data. We compared health care use and costs (using 2017 Canadian dollars) for 30 days before death between patients who died within the 1-year follow-up and matched controls.

RESULTS:

Groups (n = 629 in each group) were well-balanced in sociodemographic characteristics, comorbidities, and previous health care use. In the last 30 days, there was no differences in proportions between the two groups of patients regarding emergency department visits, intensive care unit admissions, or inpatient hospitalizations. However, patients in the intervention group had greater use of palliative physician encounters, community home care visits, and/or physician home visits (92.8% v 88.4%; P = .007). In the 507 pairs with cancer, more patients in the intervention group underwent chemotherapy (44% v 33%; P < .001) and radiation (18.7% v 3.2%; P = .043) in the last 30 days. Mean cost per patient was similar for the intervention group (mean, $17,231; 95% CI, $16,027 to $18,436) and for the control group (mean, $16,951; 95% CI, $15,899 to $18,004).

CONCLUSION:

Even with the limitations in our observational study design, identification of palliative patients did not significantly change overall costs but may shift resources toward palliative services.
Utilization of Clinical Pathways Can Reduce Drug Spend Within the Oncology Care Model
Authors: Hertler Andrew , Chau Sang , Khetarpal Rani , Bassin Ed , Dang Jeff , Koppel Daniel , Damarla Vijay , Wade James
Published: March 2020

PURPOSE:

Reducing drug spend is one of the greatest challenges for practices participating in the Oncology Care Model (OCM). Evidence-based clinical pathways have the potential to decrease drug spend while maintaining clinical outcomes consistent with published evidence. The goal of this study was to determine whether voluntary use of clinical pathways by a practice can maximize OCM episodic cost savings.

METHODS AND MATERIALS:

A community oncology practice used evidence-based clinical pathways for OCM-attributed patients. All treatment plans were submitted to the pathway vendor in real time for clinical pathway adherence measurement. Analysis was conducted before implementation and on an ongoing daily and weekly basis to identify cases in which higher cost drugs or regimens were ordered. A clinical data governance committee met biweekly to review clinical pathway performance metrics and drug utilization.

RESULTS:

From quarter 1 of 2017 to quarter 1 of 2019, the median drug spend increased less rapidly for Cancer Care Specialists of Illinois (CCSI; 18.6%) compared with OCM (34.4%). Furthermore, the percent difference in drug spend for CCSI relative to OCM decreased from 13.5% to 0.1% ( P < .001). Each quarter, there was approximately a 1.7% decrease (95% CI, 1.0% to 2.4%) in drug spend for CCSI relative to OCM. Additional analyses found that, over a 15-month period (October 2017 through December 2019), CCSI achieved an increase in pathway adherence from 69% to 81%.

CONCLUSION:

Reduction in drug spend is possible within a value-based care model, using evidence-based clinical pathways.
Spinal Anesthetic in a Patient With a Platelet Count of 7000 × 109/L and Undiagnosed Thrombotic Thrombocytopenic Purpura: A Case Report
Authors: Straube Lacey E. , de Ridder Gustaaf G. , Huber Christopher A. , Blacker Samuel N.
Published: March 2020

A parturient with unknown thrombotic thrombocytopenic purpura (TTP) received spinal anesthesia for cesarean delivery with subsequent discovery of a platelet count of 7000 × 109/L. Neurologic recovery was normal. Limited data exist to determine the risk of spinal epidural hematoma (SEH) in severely thrombocytopenic patients because they often receive alternate labor analgesia or general anesthesia during cesarean delivery. There is reporting bias in the literature toward cases in which severely thrombocytopenic patients sustain complications after regional anesthesia. It is important to report all cases of neuraxial anesthesia in severely thrombocytopenic patients, including those such as ours, wherein patients recover normally.
Management of Quebec Platelet Disorder for Cervical Facet Injections in the Outpatient Setting: A Case Report
Authors: Lee Debbie , Walega David R.
Published: March 2020

Quebec platelet disorder (QPD) is a condition that causes delayed-onset bleeding after hemostatic challenges. While there are interventional spine procedure (ISP) guidelines for managing patients on blood thinners or with common bleeding disorders, there are none for approaching patients with unique coagulopathies. We report a patient with QPD and extensive history of postprocedural bleeding complications (PPBCs) who presented with chronic cervical facet pain. After consulting a hematologist and administering antifibrinolytic agent with platelet transfusions, the patient underwent medial branch nerve blocks (MBNBs) followed by radiofrequency ablation (RFA) without experiencing PPBCs. A comprehensive team approach is critical to maximize patient safety when performing an ISP in such a population.
Quantifying the Mitigating Effects of Whole-Breast Radiotherapy and Systemic Treatments on Regional Recurrence Incidence Among Breast Cancer Patients
Authors: van Steenhoven Julia E. C. , Kuijer Anne , van Maaren Marissa C. , Roos Marleen , Elias Sjoerd G. , van Diest Paul J. , Siesling Sabine , Smidt Marjolein L. , Boersma Liesbeth J. , van Dalen Thijs
Published: March 2020

Background

Despite the potential for residual lymph node metastases after a negative or positive sentinel lymph node biopsy (SLNB), breast cancer patients rarely experience regional recurrences (RRs). This study aimed to quantify the effects of nonsurgical treatments on RR incidence among SLNB-negative (SLNB N0) breast cancer patients.

Methods

All primary SLNB N0-staged breast cancer patients with a diagnosis between 2005 and 2008 and 5-year follow-up data on recurrences were selected from the Netherlands Cancer Registry. The cumulative incidence function (CIF) for RR was calculated as the first event at 5 years, taking into account any other first-event (local or distant recurrence, contralateral breast cancer, or death) as competing risk. Cox regression analysis was used to model the cause-specific hazard of RR developing as the first event to quantify the effect of adjuvant systemic therapy and whole-breast radiotherapy (RT) on RR incidence at 5 years.

Results

The study included 13,512 patients. Of these patients, 162 experienced an RR. The CIF of RR at 5 years was 1.3% (95% confidence interval [CI], 1.1–1.5%), whereas the CIFs for death and other events were 4.4% and 9.5%, respectively. Cox regression analysis showed hazard ratios (HRs) of 0.46 (95% CI 0.33–0.64), 0.31 (95% CI 0.18–0.55), and 0.40 (95% CI 0.24–0.67) respectively for patients treated by RT as a routine part of breast-conserving therapy (BCT), chemotherapy, and hormonal therapy.

Conclusion

RT as routine part of BCT, chemotherapy, and hormonal therapy independently exerted a mitigating effect on the risk for the development of RR. The three methods at least halved the risk.
Casein Ingestion Does Not Increase Muscle Connective Tissue Protein Synthesis Rates
Authors: TROMMELEN JORN , HOLWERDA ANDREW M. , SENDEN JOAN M. , GOESSENS JOY P. B. , VAN KRANENBURG JANNEAU , GIJSEN ANNEMIE P. , VERDIJK LEX B. , VAN LOON LUC J. C.
Published: March 2020

Purpose

This study aimed to assess the effect of dietary protein ingestion on intramuscular connective tissue protein synthesis rates during overnight recovery from a single bout of resistance exercise.

Methods

Thirty-six healthy, young males were randomly assigned to one of three treatments. One group ingested 30 g intrinsically L-[1-13C]-phenylalanine-labeled casein protein before sleep (PRO, n = 12). The other two groups performed a bout of resistance exercise in the evening and ingested either placebo (EX, n = 12) or 30 g intrinsically L-[1-13C]-phenylalanine-labeled casein protein before sleep (EX + PRO, n = 12). Continuous intravenous infusions of L-[ring-2H5]-phenylalanine and L-[1-13C]-leucine were applied, and blood and muscle tissue samples were collected to assess connective tissue protein synthesis rates and dietary protein-derived amino acid incorporation in the connective tissue protein fraction.

Results

Resistance exercise resulted in higher connective tissue protein synthesis rates when compared with rest (0.086 ± 0.017%·h−1 [EX] and 0.080 ± 0.019%·h−1 [EX + PRO] vs 0.059 ± 0.016%·h−1 [PRO]; P < 0.05). Postexercise casein protein ingestion did not result in higher connective tissue protein synthesis rates when compared with postexercise placebo ingestion (P = 1.00). Dietary protein-derived amino acids were incorporated into the connective tissue protein fraction at rest, and to a greater extent during recovery from exercise (P = 0.002).

Conclusion

Resistance exercise increases intramuscular connective tissue protein synthesis rates during overnight sleep, with no further effect of postexercise protein ingestion. However, dietary protein-derived amino acids are being used as precursors to support de novo connective tissue protein synthesis.
CT features of electronic-cigarette or vaping-associated lung injury (EVALI); our experience during the recent outbreak
Authors: Girvin Francis , Naidich David
Published: March 2020

As an emerging clinical syndrome, our knowledge of the clinical, pathologic and radiologic features of electronic-cigarette or vaping-associated lung injury is evolving. CT appearances are described in six cases imaged at our institution (NYU Langone Health, New York) in the cluster of 2019.
Collection of practical work on higher mathematics. Functions of a complex variable. Operational calculus
Authors: Andreischeva Elena
Published: March 2020

The purpose of manuals is to provide the cadets of the training and methodological assistance in preparing for practical classes and during these classes to help to develop their independence, initiative and creativity in solving problems, to acquire the necessary practical skills.
Intended for basic guidance in solving both typical and common tasks of one of the sections of the course mathematics "Functions of a complex variable. Operational calculus".
Physoglossus: A new ground beetle genus of the enigmatic tribe Physocrotaphini Chaudoir, 1862 (Carabidae: Anthiinae) from the Western Ghats, a global hotspot of Biodiversity in south west India
Authors: SV AKHIL , SABU THOMAS K.
Published: March 2020

A new genus of enigmatic tribe Physocrotaphini, Physoglossus gen. nov., with a new species Ph. devagiriensis sp. nov. from a dry deciduous forest in the rain shadow belt of the south Western Ghats in south west India is described. Presence of mentum with bifid median tooth and large oval depression with dense patch of filamentous setae on 2nd and 3rd male sternites makes it intermediate to the Physocrotaphini genera, Pogonoglossus, Foveocrotaphus and Physocrotaphus. Key words: new ground beetle species, Anthiinae, the Western Ghats, India
Multifocal recurrence of medulloblastoma: a long follow-up case study
Authors: Zulkarnaien Benny , Suharlim Edwin , Susanto Eka , Gondhowiardjo Soehartati Argadikoesoema
Published: March 2020

Medulloblastoma is the most common malignant brain tumor in pediatric patients. Leptomeningeal dissemination often occurs in the spinal canal and rarely into the supratentorial as an extra-axial lesion. This study followed an 8-year progression of multifocal medulloblastoma recurrence as supratentorial metastasis that mimics an intra-axial mass of the temporal lobe. Pathologic examination of the temporal mass showed densely packed small round blue cells that are distributed in a ribboning pattern with areas of necrosis, rosette formation, and mitosis. Ki-67 immunohistochemical staining of the tumor showed a high proliferation index of 40% and revealed positive results for synaptophysin and negative results for glial fibrillary acidic protein and β-catenin. A long follow-up is essential to diagnose the recurrence and elucidate the progression of medulloblastoma.
Eating behavior affects cardio-metabolic risk in high school teenagers in a developing country
Authors: Suhadi Rita , Hendra Phebe , Virginia Dita Maria , Setiawan Christianus Heru
Published: March 2020

BACKGROUND Modernization negatively changes lifestyle, characterized by excessive eating and reduced energy consumption, and concurrently increases the cardiometabolic risk. This study was aimed to evaluate the association between eating behavior and cardio-metabolic risk factors including body mass index (BMI) in percentile, blood pressure (BP) in percentile, waist circumference, and heart rate in total subjects and gender sub-groups.

METHODS This analytical cross-sectional study was done from July to November 2018. High schools in four provinces of Indonesia and students were selected using purposive sampling. Subjects’ profiles were collected from interview and cardio-metabolic parameters were measured at the study sites. Data were analyzed with chi-square and independent t-test.

RESULTS Subjects who were overweight/obese and had high BP accounted for 27.1% and 9.3–12.0% of the total subjects (n = 768), respectively. Subjects who having breakfast tended to have lower BMI (p = 0.006), and the lower consumption of western meals had lower heart rate (p = 0.02). Male subjects had more meal frequency and had less quantity of snacks than female subjects (p<0.001). Male subjects with routine intake of vegetables had low heart rate (p = 0.03). Female subjects with routine breakfast had better BMI (p<0.001), and lower diastolic BP (p = 0.004) and waist circumference (p = 0.02), whereas those who consumed Western meals had higher heart rate (p = 0.046) and waist circumference (p = 0.001).

CONCLUSIONS Eating behaviors are likely to affect cardio-metabolic risk factors, and the effects vary within gender groups.
Genes predisposing to type 1 diabetes mellitus and pathophysiology: a narrative review
Authors: Yahaya Tajudeen , Salisu Titilola
Published: March 2020

The possibility of targeting the causal genes along with the mechanisms of pathogenically complex diseases has led to numerous studies on the genetic etiology of some diseases. In particular, studies have added more genes to the list of type 1 diabetes mellitus (T1DM) suspect genes, necessitating an update for the interest of all stakeholders. Therefore this review articulates T1DM suspect genes and their pathophysiology. Notable electronic databases, including Medline, Scopus, PubMed, and Google-Scholar were searched for relevant information. The search identified over 73 genes suspected in the pathogenesis of T1DM, with human leukocyte antigen, insulin gene, and cytotoxic T lymphocyte-associated antigen 4 accounting for most of the cases. Mutations in these genes, along with environmental factors, may produce a defective immune response in the pancreas, resulting in β-cell autoimmunity, insulin deficiency, and hyperglycemia. The mechanisms leading to these cellular reactions are gene-specific and, if targeted in diabetic individuals, may lead to improved treatment. Medical practitioners are advised to formulate treatment procedures that target these genes in patients with T1DM.
Extended field-of-view adaptive optics in microscopy via numerical field segmentation
Authors: Rajaeipour Pouya , Dorn Alex , Banerjee Kaustubh , Zappe Hans , Ataman Çağlar
Published: March 2020

Sample-induced optical aberrations in microscopy are, in general, field dependent, limiting their correction via pupil adaptive optics (AO) to the center of the available field-of-view (FoV). This is a major hindrance, particularly for deep tissue imaging, where AO has a significant impact. We present a new wide-field AO microscopy scheme, in which the deformable element is located at the pupil plane of the objective. To maintain high-quality correction across its entirety, the FoV is partitioned into small segments, and a separate aberration estimation is performed for each via a modal-decomposition-based indirect wavefront sensing algorithm. A final full-field image is synthesized by stitching of the partitions corrected consecutively and independently via their respective measured aberrations. The performance and limitations of the method are experimentally explored on synthetic samples imaged via a custom-developed AO fluorescence microscope featuring an optofluidic refractive wavefront modulator.
Sensing and switching capabilities of a graphene-based perfect dual-band metamaterial absorber with analytical methods
Authors: Nejat Mohamad , Nozhat Najmeh
Published: March 2020

In this paper, the simultaneous sensing and switching performance of a graphene-based plasmonic dual-band absorber in the terahertz region has been demonstrated and investigated. Due to the high confinement of graphene surface plasmons and the hydrophobic nature of graphene, the structure can be used as a refractive index sensor in biomedical applications such as detection of impurities of water, cancer cells, and STMV virus. The simulation results show an ultrahigh sensitivity of 360 THz/RIU and figure of merit of

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. Moreover, variation of the graphene chemical potential leads to a switching function between the perfect absorption and total reflection states, with the high extinction ratio of 12.15 dB and ultrafast response time of 1.5 ps. Two analytical methods of equivalent circuit model and transmission matrix have been used to validate the suggested idea of the proposed graphene-based structure. We have shown that there is a good agreement between the theoretical and simulation results. The specifications of our suggested structure are tunability, ultrahigh sensitivity, high extinction ratio, ultrafast response time, and simple design, which pave the ways for design and implementation of other multi-application terahertz plasmonic structures based on graphene in the future.
Extra-cavity-enhanced difference-frequency generation at 1.63  µm
Authors: Yang Chen , Liu Shi-Long , Zhou Zhi-Yuan , Li Yan , Li Yin-Hai , Liu Shi-Kai , Xu Zhao-Huai , Guo Guang-Can , Shi Bao-Sen
Published: March 2020

A 1632 nm laser has highly important applications in interfacing the wavelength of rubidium-based quantum memories (795 nm) and the telecom band (typically 1550 nm) by frequency conversion in a three-wave mixing processes. A 1632 nm laser source based on pump-enhanced difference-frequency generation is demonstrated. It has 300 mW of output power, in agreement with simulations, and a 55% quantum efficiency. An average power fluctuation of 0.51% over 1 h was observed, and 200 kHz linewidth was measured using a delayed self-heterodyne method.
Passive radiative cooling and other photonic approaches for the temperature control of photovoltaics: a comparative study for crystalline silicon-based architectures
Authors: Perrakis George , Tasolamprou Anna C. , Kenanakis George , Economou Eleftherios N. , Tzortzakis Stelios , Kafesaki Maria
Published: March 2020

The radiative cooling of objects during daytime under direct sunlight has recently been shown to be significantly enhanced by utilizing nanophotonic coatings. Multilayer thin film stacks, 2D photonic crystals, etc. as coating structures improved the thermal emission rate of a device in the infrared atmospheric transparency window reducing considerably devices’ temperature. Due to the increased heating in photovoltaic (PV) devices – that has signiﬁcant adverse consequences on both their efficiency and life-time – and inspired by the recent advances in daytime radiative cooling, we developed a coupled thermal-electrical modeling to examine the physical mechanisms on how a radiative cooler affects the overall efficiency of commercial photovoltaic modules and how the radiative cooling impact is compared with the impact of other photonic strategies for reducing heat generation within PVs, such as ultraviolet and sub-bandgap reflection. Employing our modeling, which takes into account all the major intrinsic processes affected by the temperature variation in a PV device, we additionally identified the validity regimes of the currently existing PV-cooling models which treat the PV coolers as simple thermal emitters. Finally, we assessed some realistic photonic coolers from the literature, compatible with photovoltaics, to implement the radiative cooling requirements and the requirements related to the reduction of heat generation, and demonstrated their associated impact on the temperature reduction and PV efficiency. Consistent with previous works, we showed that combining radiative cooling with sub-bandgap reflection proves to be more promising for increasing PVs’ efficiency. Providing the physical mechanisms and requirements for reducing PV operating temperature, our study provides guidelines for utilizing suitable photonic structures for enhancing the efficiency and the lifetime of PV devices.