bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection Criteria of Program Directors for Dermatopathology Fellows
Authors: Wang Jordan V. , Doan Linda , Lee Jason B.
Published: December 2018

Dermatopathology represents a unique field at the intersection of dermatology and pathology. Although programs are approved by the ACGME, there is neither uniformity in application materials, timetables, and deadlines, nor a centralized application process. Despite the competitive nature of dermatopathology fellowships, no formal studies have thoroughly examined the selection criteria by program directors. Our study fills this gap in the literature and evaluates the impact of selection criteria for dermatopathology fellows. Applicants can now gain insight into the most important and meaningful aspects of their application.
Efficacy of Minimally Invasive Intervention in Patients With Acute Cerebral Infarction
Authors: Li Lirong , Ren Shaohua , Hao Xudong , Zhen Zigang , Ji Hongming
Published: December 2018

Our aim was to explore the efficacy of minimally invasive intervention in patients with acute cerebral infarction (ACI). Seventy patients with ACI were randomized into either an experimental group or a control group. In addition to the regular treatment, patients in the control group also received intravenous thrombolysis with urokinase, while patients in the other group underwent percutaneous transluminal cerebral angioplasty and stenting. Metrics included recanalization rate, serum cytokines, fibrinolytic markers, and 36-Item Short Form Health Survey score and were compared between the 2 groups. After treatment, patients in the experimental group had better recanalization rate, higher SF-36 score and greater levels of vascular endothelial growth factors, neurotrophic factors, and nerve growth factors than those in the control group. Moreover, the values of fibrinolytic markers changed significantly in both groups after treatment. Compared with the control group, the experimental group had lower levels of tissue polypeptide antigen and plasminogen activator inhibitor-1 and a higher level of von Willebrand factor after treatment. In sum, the application of minimally invasive intervention can increase both the recanalization rate and concentrations of serum cytokines, can improve the quality of life in patients with ACI, and has small impacts on the fibrinolytic system in patients.
LongShengZhi Capsule Reduces Established Atherosclerotic Lesions in apoE-Deficient Mice by Ameliorating Hepatic Lipid Metabolism and Inhibiting Inflammation
Authors: Ma Jing , Zhao Dan , Wang Xiaolin , Ma Chuanrui , Feng Ke , Zhang Shuang , Chen Yuanli , Zhu Yan , Gao Xiumei , Zhao Buchang , Wang Yong , Qian Ke , Li Xiaoju , Duan Yajun , Han Jihong , Yang Xiaoxiao
Published: December 2018

Disorders of lipid metabolism and inflammation play an important role in atherosclerosis. LongShengZhi (LSZ) capsule, a Chinese herbal medicine, has been used for treatment of patients with vascular diseases for many years. In this article, we determined the effect of LSZ on the progression of established atherosclerotic lesions in apoE-deficient (apoE−/−) mice. ApoE−/− mice were prefed high-fat diet (HFD) for 8 weeks to induce atherosclerosis, then started with LSZ treatment contained in HFD for 10 weeks. Although LSZ had little effect on HFD-induced hypercholesterolemia, it substantially reduced en face and sinus aortic lesions. The reduction of lesions was associated with reduced macrophage/foam cell accumulation by activating ABCA1/ABCG1 expression. LSZ maintained the integrity of arterial wall by increasing collagen or smooth muscle cell content and inhibiting cell apoptosis. LSZ also attenuated HFD-induced fatty liver by down-regulating expression of lipogenic and cholesterol synthetic genes while activating expression of triglyceride catabolism genes. Moreover, LSZ demonstrated potent anti-inflammatory effects. In vivo, LSZ reduced serum TNF-α levels, infiltration of neutrophils, Kupffer cells, and expression of inflammatory cytokines in the liver. In vitro, it inhibited lipopolysaccharide or palmitate-induced expression of inflammatory cytokines in macrophages. Therefore, LSZ reduces atherosclerosis by ameliorating hepatic lipid metabolism and inhibiting inflammation.
Biomarkers of Drug-Induced Kidney Toxicity
Authors: Griffin Benjamin R. , Faubel Sarah , Edelstein Charles L.
Published: December 2018

Blood urea nitrogen and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and nonrenal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than blood urea nitrogen and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Other biomarkers of drug-induced kidney toxicity that have been detected in the urine of rodents or patients include IL-18, neutrophil gelatinase-associated lipocalin, netrin-1, liver-type fatty acid–binding protein (L-FABP), urinary exosomes, and TIMP2 (insulin-like growth factor–binding protein 7)/IGFBP7 (insulin-like growth factor–binding protein 7), also known as NephroCheck, the first Food and Drug Administration–approved biomarker testing platform to detect acute kidney injury in patients. In the future, a combined use of functional and damage markers may advance the field of biomarkers of drug-induced kidney toxicity. Earlier detection of drug-induced kidney toxicity with a kidney-specific biomarker may result in the avoidance of nephrotoxic agents in clinical studies and may allow for earlier intervention to repair damaged kidneys.
Poly-ADP-ribosyl-polymerase inhibitor resistance mechanisms and their therapeutic implications
Authors: McCann Kelly E.
Published: December 2018

Purpose of review

Poly-ADP-ribosyl-polymerase (PARP) inhibitors are an increasingly-utilized therapy in women with high-grade serous ovarian carcinoma, but tumor resistance to PARP inhibitor monotherapy is inevitable.

Recent findings

PARP inhibitors have been most studied in patients with breast and ovarian cancers associated with deleterious germline BRCA1 or BRCA2 mutations, though their role has expanded to include use as maintenance therapy in women with platinum-sensitive high-grade serous ovarian cancer due to the high propensity of such cancers to have defects in DNA repair by homologous recombination. As mechanisms of PARP inhibitor resistance are elucidated, rationale combination strategies can be devised to extend therapeutic benefits and to abrogate resistance.

Mechanisms of resistance include restoration of homologous recombination repair proficiency, loss of cancer cell reliance on PARP, and increased intracellular signaling through cell growth pathways.
Self-awareness and the evaluation of hot flash severity: observations from the Seattle Midlife Women's Health Study
Authors: Taylor-Swanson Lisa Jean , Pike Kenneth , Mitchell Ellen Sullivan , Herting Jerald R. , Woods Nancy Fugate
Published: December 2018

Objective:

The purpose of this study was to test the association of two dimensions of self-awareness with hot flash (HF) severity.

Methods:

A subset of women from the Seattle Midlife Women's Health Study (N = 232) provided data for these analyses. Structural equation modeling was used to evaluate two dimensions of self-awareness (Internal States Awareness [ISA] and Self-Reflectiveness [SR]), and secondary factors of perceived stress, anxiety, and attitudes toward menopause as continuous with earlier life, health perceptions, and menopausal stage with respect to HF severity. The measurement and structural models were tested with a maximum likelihood missing values estimator and displayed good model fit.

Results:

Women with greater ISA reported greater HF severity (β = 0.17, P < 0.05). In addition, women in later menopausal transition stages reported greater HF severity and those with attitudes of continuity toward menopause reported less severe HFs (β = 0.20, P < 0.01, β = −0.30, P < 0.001, respectively). SR was not related to HF severity. Women with higher levels of SR reported greater perceived stress levels (β = .51, P < 0.001), and those with greater perceived stress reported greater anxiety levels (β = 0.63, P < 0.001) and attitudes of continuity toward menopause as less continuous with earlier life (β = −0.30, P < 0.001).

Conclusions:

ISA (balanced self-awareness) was associated with greater HF severity, suggesting that enhanced balanced self-awareness may promote women's ability to evaluate their symptom experience. A multidimensional construct of self-awareness, perceived stress, anxiety, and attitude toward menopause are all plausible targets for future intervention studies of symptom management.
Women's experience of vulvovaginal symptoms associated with menopause
Authors: Shifren Jan L. , Zincavage Rebekah , Cho Ellen L. , Magnavita Ashley , Portman David J. , Krychman Michael L. , Simon James A. , Kingsberg Sheryl A. , Rosen Raymond C.
Published: December 2018

Objective:

This study describes women's experiences of the genitourinary syndrome of menopause (GSM) elicited through focus groups and cognitive debriefing sessions during development of a novel patient-reported outcome measure (PROM) designed for use in both clinical care and research.

Methods:

A draft questionnaire to identify and assess bothersome genitourinary symptoms associated with estrogen deficiency in menopausal women was developed in five discrete phases from multiple sources of information in accordance with standards for PROM development. GSM was confirmed by report of symptoms in conjunction with a confirmatory pelvic examination and laboratory assessments.

Results:

Qualitative content interviews were completed in 36 menopausal women with GSM. Cognitive testing of draft PROM items was performed in nine focus groups, including 26 menopausal women with and 15 without GSM. Participants reported a range of symptoms and described associated impacts on more than 15 quality-of-life domains. The majority of women reported that their symptoms impacted their sexual functioning and had a negative effect on their overall quality of life. GSM affected many aspects of menopausal women's lives beyond sexual function, with descriptions of pain when walking, urinating, wearing tight clothes, and with other activities of daily living.

Conclusions:

Women's own words methodically recorded and analyzed during qualitative interviews and cognitive debriefing focus groups illuminate the subjective experience of women with GSM. It is hoped that the PROM currently in development will provide an effective tool for increasing our understanding of the prevalence, predictors, and impact of GSM in menopausal women's lives.
Can the use of probiotics in association with isoflavone improve the symptoms of genitourinary syndrome of menopause? Results from a randomized controlled trial
Authors: Ribeiro Ana Elisa , Monteiro Naice Eleidiane Santana , Moraes Anna Valéria Gueldini de , Costa-Paiva Lucia Helena , Pedro Adriana Orcesi
Published: December 2018

Objective:

To evaluate the effect of isoflavone administration, either in conjunction with probiotic use or not, on the symptoms of genitourinary syndrome of menopause, and compare the effects with those of hormone therapy.

Methods:

A randomized clinical trial was conducted on 60 postmenopausal women aged 40 to 60 years, randomly assigned to receive oral isoflavone (150 mg dry extract of glycine max) alone or isoflavone plus probiotic (Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Bifidobacterium bifidum, and Bifidobacterium lactis) or hormone therapy (1 mg estradiol and 0.5 mg norethisterone acetate). The urogenital symptom subscale of the Menopause Rating Scale and International Consultation on Incontinence Questionnaire-Short Form were used to assess genitourinary symptoms. Vaginal maturation value, pH, vaginal health score, and vaginal flora were used to evaluate vaginal atrophy. Equol, equol intermediate, O-dimethylangolensin, and aglycones were measured using gas chromatography coupled to mass spectrometry.

Results:

After 16 weeks of treatment, the urogenital symptoms, mainly vaginal dryness and sexual problem complaints, improved significantly in the hormone therapy group. There was a significant increase in the daidzein, glycitein, equol intermediate, and O-dimethylangolensin contents after 16 weeks in the isoflavone plus probiotic group. The maturation value, vaginal pH, and vaginal flora improved in the hormone therapy group. The vaginal health score increased in the isoflavone and hormone therapy groups.

Conclusions:

Probiotics improved the metabolism of isoflavones after 16 weeks of treatment. However, the increase in the contents of isoflavones and their metabolites failed to yield an estrogenic effect on the urogenital tract and relieve the vulvovaginal symptoms.
Ahmed Glaucoma Valve Revision Versus Visco-Trabeculotomy After Failed Ahmed Glaucoma Valve in Refractory Pediatric Glaucoma
Authors: Elwehidy Ahmed S. , Badawi Amani E. , Hagras Sherein M. , Bayoumi Nader H.L.
Published: December 2018

Purpose:

To compare the outcome of the intraocular pressure (IOP) of Ahmed glaucoma valve (AGV) revision to visco-trabeculotomy (VT) in children’s eyes with failed AGV.

Patients and Methods:

A prospective randomized study conducted on 41 children (41 eyes) with uncontrolled glaucoma with an AGV presenting to the pediatric ophthalmology clinic of Mansoura Ophthalmic Center between 2011 and 2016. Study eyes were randomized to AGV revision or VT. Success (true and qualified) (IOP<21 mm Hg without any sight-threatening complications) was studied at the end of 12-month follow-up. Operative complications were noted. The primary outcome was the IOP before and after the study intervention.

Results:

The mean±SD age of the study children was 7.9±2.6 and 7.7±2.6 years in the AGV revision (19 eyes) and VT groups (22 eyes), respectively (P=0.654). The most common glaucoma type was primary congenital glaucoma in both groups. The mean±SD of the duration between the last glaucoma procedure and the current study intervention was 24.9±4.8 and 25.2±5.8 months in the AGV revision and VT groups, respectively. The mean±SD preoperative IOP and at 12-month follow-up was 32.1±3.2 and 23.2±3.5 mm Hg in the AGV revision group and was 33.3±2.2 and 20.0±3.5 mm Hg in the VT group. The total success rates at 12 months were 31.6% and 63.7% in the AGV revision and VT groups, respectively.

Conclusions:

Both VT and AGV revision are reasonably successful and safe interventions for refractory childhood glaucoma after the failure of an AGV. VT is significantly better than AGV revision, resulting in higher success rates and a decrease in IOP-lowering medication use.
Short-term Optic Disc Cupping Reversal in a Patient With Mild Juvenile Open-angle Glaucoma Due to Early Idiopathic Intracranial Hypertension
Authors: Umfress Allison C. , Mawn Louise A. , Joos Karen M.
Published: December 2018

Purpose:

The purpose of this study was to report a case of optic disc cupping reversal in an adult without significant intraocular pressure–lowering treatment.

Patient:

A 20-year-old female with a history of mild juvenile open-angle glaucoma who developed subjective blurred vision and a decrease in cupping of her optic discs.

Results:

Dilated examination demonstrated decreased cup-to-disc ratios in both eyes with a slight blurring of the disc margin in the right eye. The appearance of both optic discs returned to baseline after weight loss therapy.

Conclusions:

An unexplained reduction of optic nerve cup-to-disc ratio should prompt a workup for other etiologies, such as increased intracranial pressure. Baseline photographs not subjected to computerized scan obsolescence are extremely useful in monitoring the long-term appearance of asymmetric optic discs as an adjunct to the clinical examination.
Patient-reported Outcomes, Functional Assessment, and Utility Values in Glaucoma
Authors: Skalicky Simon E. , Lamoureux Ecosse L. , Crabb David P. , Ramulu Pradeep Y.
Published: December 2018

In clinical glaucoma research, the measurement of patient reported outcomes, functional assessment of disability, and health economic impact is critical. However, valid, time-efficient and comprehensive tools are not available and several current instruments lack in the appropriate precision for measuring the various dimensions of glaucoma-related quality of life (QoL), including functioning and mobility. Furthermore, statistical methods are inconsistently and sometimes incorrectly used in otherwise sound clinical studies. Standardizing and improving methods of patient-centered data collection and analysis in glaucoma studies are imperative. This paper outlines recommendations and provides a discussion of some of the pertinent issues relating to the optimization of patient-reported outcomes research in glaucoma.
Predicting the Therapeutic Efficacy of Laser Peripheral Iridotomy for Individuals With Asymptomatic Narrow Angle: The Triple Hump Sign
Authors: Na Kyeong Ik , Ha Ahnul , Baek Sung Uk , Lee Won June , Kim Dai Woo , Jeoung Jin Wook , Park Ki Ho , Kim Young Kook
Published: December 2018

Purpose:

To evaluate the clinical efficacy of a novel screening sign [ie, the triple hump (TH) sign] for prediction of laser peripheral iridotomy (LPI)’s intraocular pressure (IOP)-lowering effectiveness in subjects with asymptomatic narrow angles.

Methods:

This cross-sectional study was conducted from 2010 to 2015 in a hospital setting. Eighty-four eyes of 84 primary angle-closure suspect (PACS) patients were imaged before LPI using anterior segment optical coherence tomography. The “positive-TH sign” was defined, on anterior segment optical coherence tomography–generated cross-sectional scans, as the characteristic configuration formed by the angulations between the crystalline lens’s central anterior surface and both sides of the iris pigment epithelium. After LPI, the extent of IOP reduction was compared between the positive- and negative-TH groups.

Results:

The positive-TH eyes did not significantly differ from the negative-TH ones in pre-LPI IOP (P=0.200). In the positive-TH group, IOP decreased significantly after LPI (by 6.42%±17.96%, from 14.07±3.11 to 12.88±2.65 mm Hg, P=0.002). In the negative-TH group, IOP did not change significantly after LPI (by 4.66%±25.97%, from 13.23±2.42 to 13.52±3.01 mm Hg, P=0.624).

Conclusion:

PACS eyes indicating the positive-TH sign showed, at post-LPI 1 month, a greater IOP decrease. On this basis, the TH sign may be a useful screening tool for predicting the effect of LPI and determining the treatment plan in PACS patients.
Tripolar Stimulation Improves Polyphonic Pitch Detection in Cochlear Implant Users
Authors: Chari Divya A. , Jiradejvong Patpong , Limb Charles J.
Published: December 2018

Objective:

Cochlear implant (CI) users struggle with pitch perception, particularly for polyphonic stimuli. Tripolar (TP) stimulation has been proposed as a way to mitigate the broad spread of neural excitation observed in traditional monopolar (MP) stimulation, thereby potentially improving perception of polyphony.

Study Design:

Prospective cohort study.

Setting:

Tertiary academic center.

Patients:

Eleven postlingually deafened adults with Advanced Bionics HiRes 90K CIs.

Intervention(s):

We performed pitch ranking and polyphonic pitch detection testing under MP and TP configurations. To assess pitch ranking, users were asked to identify the higher pitch between two notes. In polyphonic pitch detection, users were asked to distinguish between single-pitch tones and two-pitch tones. Two-pitch stimuli consisted of one pitch of three base frequencies (392, 523, 740 Hz) and a second pitch between 1 and 12 semitones above the base frequency.

Main Outcome Measure:

Pitch performance was analyzed as a function of current delivery mode (tripolar vs. monopolar), with smaller semitone interval pitch resolution indicating better performance.

Results:

In pitch ranking tasks, TP configuration did not confer an advantage over MP stimulation. In polyphonic perception, however, tripolar stimulation improved performance in lower frequencies and resulted in statistically significant (p < 0.05) improvement at the highest base frequency, 740 Hz.

Conclusions:

These data suggest that TP configuration may confer an advantage in the perception of polyphonic pitch, which may not be observed in monophonic pitch ranking tasks. Since music is typically polyphonic, such data offer approaches toward improving perception of real-world musical stimuli.
Functional Status Is Associated With 30-Day Potentially Preventable Readmissions Following Home Health Care
Authors: Middleton Addie , Downer Brian , Haas Allen , Knox Sara , Ottenbacher Kenneth J.
Published: December 2018

Background:

Beginning in 2019, home health agencies’ rates of potentially preventable hospital readmissions over the 30 days following discharge will be publicly reported.

Objectives:

Our primary objective was to determine the association between patients’ functional status at discharge from home health care and 30-day potentially preventable readmissions. A secondary objective was to identify the most common conditions resulting in potentially preventable readmissions.

Design:

This was a retrospective cohort study.

Participants:

A total of 1,510,297 Medicare fee-for-service beneficiaries discharged from home health care in 2013–2015. Average age was 75.9 (SD, 10.9) years, 60.0% were female, and 84.2% non-Hispanic white.

Measurements:

Thirty-day potentially preventable readmissions following home health discharge. Functional status measures included mobility, self-care, and impaired cognition.

Results:

The overall rate of 30-day potentially preventable readmissions was 2.6% (N=39,452), which accounted for 40% of all 30-day readmissions. After adjusting for sociodemographic and clinical characteristics, the odds ratios for the most dependent score quartile versus the most independent was 1.58 [95% confidence interval (CI), 1.53–1.63] for mobility and 1.65 (95% CI, 1.59–1.69) for self-care. The odds ratios for impaired versus intact cognition was 1.21 (95% CI, 1.18–1.24). The 5 most common conditions resulting in a potentially preventable readmission were congestive heart failure (23.6%), septicemia (16.7%), bacterial pneumonia (9.8%), chronic obstructive pulmonary disease (9.4%), and renal failure (7.5%).

Conclusions:

Functional limitations at discharge from home health are associated with increased risk for potentially preventable readmissions. Future research is needed to determine whether improving functional independence decreases the risk for potentially preventable readmissions following home health care.
Delayed graft function in kidney transplantation
Authors: Bahl Disha , Haddad Zaid , Datoo Asma , Qazi Yasir A.
Published: December 2018

Purpose of review

Delayed graft function (DGF) has several long-term graft implications in the field of kidney transplantation and remains a challenge. The incidence of DGF is on the rise because of an increasing use of marginal kidneys in an era of organ shortage. Risk factors for DGF are numerous and stem from multiple sources in the transplant chain starting from the donor to its final allocation in the recipient. There is no FDA-approved therapy for DGF, and several therapies are being studied to mitigate ischemic injury and prolong graft survival.

Recent findings

Published data from studies suggest that ischemia–reperfusion injury (IRI) and immune responses to transplants are the leading cause of DGF, which in turn is associated with an increased incidence in acute renal rejection. Several novel methods are being developed and are undergoing further clinical validation to prove as an effective therapy against DGF.

Recent studies have proposed several different mechanisms to mitigate ischemic injury to prevent acute renal injury, both of which are representative of DGF. New therapies must be effectively reviewed to ensure advancement of DGF prevention. A number of immunotherapies targeted towards inhibition of complement activation in addition to other novel therapies might prove promising towards mitigating DGF.
Isolated Superior Rectus Muscle Hematoma Following Blunt Orbital Trauma
Authors: Friehmann Asaf , Peled Alon , Ela-Dalman Noa , Nemet Arie Y.
Published: December 2018

Isolated ocular muscle hematoma due to blunt trauma is very rare. In this study, a 15-year-old patient presented with an isolated superior rectus hematoma due to an orbital hit from a cellular phone. He was treated with oral corticosteroids alone. Marked improvement in symptoms and eye movements was observed.
Combined Primary Cleft Lip and Palate Repair: Is It Safe?
Authors: Kantar Rami S. , Rifkin William J. , Cammarata Michael J. , Maliha Samantha G. , Diaz-Siso J. Rodrigo , Farber Scott J. , Flores Roberto L.
Published: December 2018

Background:

Single-stage primary cleft lip and palate (PCLP) repair is controversial in the United States, and most patients are treated with a staged approach. In this study, early postoperative complications of the single-stage approach as compared to primary cleft lip (PCL) or primary cleft palate (PCP) alone were evaluated. This study represents the largest cohort of patients undergoing combined cleft lip and palate repair.

Methods:

The American College of Surgeons National Surgical Quality Improvement Program-Pediatric database was used to identify patients undergoing single-stage PCLP, PCL, or PCP repairs. Preoperative factors and postoperative outcomes were compared between the 3 groups, as well as within the PCLP group between patients with and without complications. Univariate and multivariate analyses were performed.

Results: A total of:

181 patients were included in the single-stage PCLP group, 1007 in the PCP group and 783 in the PCL group. There was no difference in the rates of early complications between the 3 groups. Within the PCLP group, cardiac risk factors (β = 35.19; 95% confidence interval [CI] 7.88–75.21; P = 0.04) and complications (β = 77.31; 95% CI 35.82–118.79; P < 0.001) were significant risk factors for longer operative time.

Conclusion:

Analysis of a national database showed that single-stage PCLP repair is not associated with increased risk of early postoperative complications as compared to primary lip or palate repair alone. In-depth long-term analyses of craniofacial morphology, fistulae rate, speech, and dental outcomes are essential for a comprehensive assessment of the effects of combined cleft lip and palate repair.
A New Aortic Arch Inclusion Technique With Frozen Elephant Trunk for Type A Aortic Dissection
Authors: Liu Kexiang , Zhu Cuilin , Zheng Xiaomei , Wang Tiance , Xu Rihao , Zhu Zhicheng , Li Dan , Piao Hulin , Li Bo , Wang Yong , Zhang Shudong , Sun Weihong
Published: December 2018

Objective:

Our aims were to describe a new surgical technique for the treatment of type A aortic dissection (TAAD) and to report the operative outcomes of 154 patients.

Summary Background Data:

Surgical treatment of TAAD is complicated and carries a high mortality risk. To lower this risk, we developed a simplified procedure in which a stent graft was implanted as frozen elephant trunk (FET), and the proximally trimmed vascular graft was sutured from the inside of the aortic arch using the inclusion technique under moderate hypothermic circulatory arrest and antegrade selective cerebral perfusion.

Methods:

We conducted a retrospective analysis of 154 cases of TAAD treated with our novel technique (93 men and 61 women, 52.5 ± 11.4 years). Computed tomography angiography was performed before discharge and at 6 months postoperatively.

Results:

In-hospital mortality rate was 5.19%, with paraplegia occurring in 2 patients (1.3%) and stroke in 6 (3.9%). The rate of closure of the aortic arch false lumen was 77.8%, with a 69.2% rate of descending thoracic aorta thrombosis at discharge. The survival rate was 91.1% at a mean follow-up of 21 ± 10 months, with rates of aortic arch false lumen closure of 92.4% and descending thoracic aorta thrombosis of 74.3% at 6 months postoperatively.

Conclusions:

The aortic arch inclusion technique with FET provides a safe alternative for TAAD treatment, with satisfactory operative results. Short-term follow-up results are encouraging, and long-term outcomes need further evaluation.
Triple Stimulation Technique in Amyotrophic Lateral Sclerosis
Authors: Wang Yue , Wang Han , Cui Li-Ying
Published: December 2018

Purpose:

To identify upper motor neuron (UMN) dysfunction using the triple stimulation technique (TST) in amyotrophic lateral sclerosis (ALS).

Methods:

Fifty ALS and 42 non-ALS patients were examined clinically, using conventional transcranial magnetic stimulation and TST.

Results:

For ALS patients presenting with UMN in tested limb, the TST amplitude ratio was abnormal in 25 of 28 patients (89.3%). For ALS patients without UMN signs, 6 of 22 patients (27.3%) had an abnormal TST ratio. When clinical signs were not present, both abnormal resting motor threshold and TST indicated a UMN involvement. In non-ALS patients with central motor conduction disorders, the percentage of patients with an abnormal TST was higher for those presenting with clinical UMN signs (9/12, 75.0%) than for those without these signs (1/8, 12.5%).

Conclusions:

Triple stimulation technique appears to be an accurate, early measure for detecting clinical and subclinical UMN abnormalities in ALS. Triple stimulation technique could also be useful to investigate central motor conduction abnormalities in other disorders.
EXtrACtor, a tool for multiple queries and data extractions from the EXAC and gnomAD database
Authors: Mulder Flip , Koeleman Bobby P.C.
Published: December 2018

EXtrACtor provides an easy and flexible way to perform multiple queries of the ExAC and gnomAD databases (Lek M, al. e, 2016) and process the results. The ExAC browser is an often-used tool to gather information from a large number of exomes while the gnomAD database expands on this by increasing the number of exomes but also adding genomes. However the websites only allow the users to query a single gene, transcript or location at a time. On the other hand downloading the entire database results in other challenges for the average user, especially with the download size for the gnomAD database approaching 100GB. EXtrACtor allows the user to supply a list of genes, transcripts or regions to be queried against either the ExAC or the gnomAD database. At the same time it gives the user a flexible user interface in order to quickly filter on various properties such as cohort, variant type and more.
Exploration in the wild
Authors: Schulz Eric , Bhui Rahul , Love Bradley C , Brier Bastien , Todd Michael T , Gershman Samuel J
Published: December 2018

Making good decisions requires people to appropriately explore their available options and generalize what they have learned. While computational models have successfully explained exploratory behavior in constrained laboratory tasks, it is unclear to what extent these models generalize to complex real world choice problems. We investigate the factors guiding exploratory behavior in a data set consisting of 195,333 customers placing 1,613,967 orders from a large online food delivery service. We find important hallmarks of adaptive exploration and generalization, which we analyze using computational models. We find evidence for several theoretical predictions: (1) customers engage in uncertainty-directed exploration, (2) they adjust their level of exploration to the average restaurant quality in a city, and (3) they use feature-based generalization to guide exploration towards promising restaurants. Our results provide new evidence that people use sophisticated strategies to explore complex, real-world environments.
VAPPER: High-throughput Variant Antigen Profiling in African trypanosomes
Authors: Silva Pereira Sara , Heap John , Jones Andrew R , Jackson Andrew P.
Published: December 2018

Background: Analysing variant antigen gene families on a population scale is a difficult challenge for conventional methods of read mapping and variant calling due to the great variability in sequence, copy number and genomic loci. In African trypanosomes, hemoparasites of humans and animals, this is complicated by variant antigen repertoires containing hundreds of genes subject to various degrees of sequence recombination. Findings: We introduce Variant Antigen Profiler (VAPPER), a tool that allows automated analysis of variant antigen repertoires of African trypanosomes. VAPPER produces variant antigen profiles for any isolate of the veterinary pathogens Trypanosoma congolense and Trypanosoma vivax from genomic and transcriptomic sequencing data and delivers publication-ready figures that show how the queried isolate compares with a database of existing strains. VAPPER is implemented in Python. It can be installed to a local Galaxy instance from the ToolShed (https://toolshed.g2.bx.psu.edu/) or locally on a Linux platform via the command line (https://github.com/PGB-LIV/VAPPER). The documentation, requirements, examples, and test data are provided in the Github repository. Conclusion: Our approach is the first to allow large-scale analysis of trypanosome variant antigens and establishes two different methodologies that may be applicable to other multi-copy gene families that are otherwise refractory to high-throughput analysis.
Defining the design requirements for an assistive powered hand exoskeleton
Authors: Boser Quinn A , Dawson Michael R , Schofield Jonathon S , Dziwenko Gwen , Hebert Jacqueline S
Published: December 2018

The goal of this study was to identify design criteria for the development of an assistive powered hand exoskeleton by consulting with potential end users. Structured interviews with clinicians and patients with hand impairment were carried out and the results were tabulated. Three participants with impaired hand function also underwent a quantitative measurement session regarding hand function. The objective of the measurement sessions was to understand the characteristics, abilities and limitations of the upper limb of individuals who could benefit from a hand exoskeleton device, in order to better define design criteria and control options for such a device. For the most part, clinicians and participants with hand impairment agreed on expectations for a hand exoskeleton device on topics including important grasp patterns, wear time, and grip strength. However, their expectation seemed to diverge on the topic of control, where clinicians felt simple reliable control strategies would be preferred, but patients desired intuitive control. This research has identified key features of hand exoskeleton design requirements that will need to be met in order to have acceptable clinical translation to patient populations. Including end-users in the design of such a device is essential for successful patient-oriented technology development.
Targeting the CaVα-β interaction yields a selective antagonist of the N-type CaV2.2 channel with broad antinociceptive efficacy
Authors: Chefdeville Aude , Yu Jie , Yang Xiaofang , Moutal Aubin , Gokhale Vijay , Shuja Zunaira , Chew Lindsey A. , Bellampalli Shreya S. , Luo Shizhen , François-Moutal Liberty , Ha Taehwan , Perez-Miller Samantha , Park Ki Duk , Patwardhan Amol M. , Streicher John M. , Colecraft Henry M. , Khanna May , Khanna Rajesh
Published: December 2018

Inhibition of voltage-gated calcium (CaV) channels is a potential therapy for many neurological diseases including chronic pain. Neuronal CaV1/CaV2 channels are composed of α, β and α2δ subunits. The β-subunits of CaV channels are cytoplasmic proteins that increase the surface expression of the pore-forming α subunit of CaV. We targeted the high-affinity protein-protein interface of CaVβ’s pocket within the CaVα-subunit. Structure-based virtual screening of 50,000 small molecule library docked to the β-subunit led to the identification of 2-(3,5-dimethylisoxazol-4-yl)-N-((4-((3-phenylpropyl)amino)quinazolin-2-yl)methyl)acetamide (compound 45). This small molecule bound to CaVβ and inhibited its coupling with N-type voltage-gated calcium (CaV2.2) channels, leading to a reduction in CaV2.2 currents in rat dorsal root ganglion (DRG) sensory neurons, decreased pre-synaptic localization of CaV2.2 in vivo, decreased frequency of spontaneous excitatory post-synaptic potentials (sEPSC), and inhibited release of the nociceptive neurotransmitter calcitonin gene related peptide (CGRP) from spinal cord. 45 was antinociceptive in naïve animals and reversed allodynia and hyperalgesia in models of acute (post-surgical) and neuropathic (spinal nerve ligation, chemotherapy- and gp120-induced peripheral neuropathy, and genome-edited neuropathy) pain. 45 did not cause akinesia or motor impairment, a common adverse effect of CaV2.2 targeting drugs, when injected into the brain. 45, a quinazoline analog, represents a novel class of CaV2.2-targeting compounds that may serve as probes to interrogate CaVα-β function and ultimately be developed as a non-opioid therapeutic for chronic pain.
Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems
Authors: Harding Rachel J. , Loppnau Peter , Ackloo Suzanne , Lemak Alexander , Hutchinson Ashley , Hunt Brittany , Holehouse Alex S. , Ho Jolene C. , Fan Lixin , Toledo-Sherman Leticia , Seitova Alma , Arrowsmith Cheryl H.
Published: December 2018

The gene mutated in Huntington’s disease (HD) patients encodes the 348 kDa huntingtin (HTT) protein. The pathogenic HD CAG-expansion mutation causes a polyglutamine (polyQ) tract at the N-terminus of the HTT protein to expand above a critical threshold of ~35 glutamine residues. The effect of HD mutations on HTT is not well understood, in part due to difficulties in carrying out biochemical, biophysical and structural studies of this large protein. To facilitate such studies, we have generated expression constructs for the scalable production of HTT in multiple eukaryotic expression systems. Our set of HTT expression clones comprises both N and C-terminally FLAG-tagged HTT constructs with polyQ lengths representative of the general population, HD patients, juvenile HD patients as well as the more extreme polyQ expansions used in some HD tissue and animal models. These reagents yield milligram quantities of pure recombinant HTT protein, including many of the previously mapped posttranslational modifications. We have characterised both apo and HTT-HAP40 complex samples produced using this HD resource, demonstrating that this toolkit can be used to generate physiologically meaningful complexes of HTT. We demonstrate how these resources can produce sufficient material for protein-intensive experiments such as small angle X-ray scattering (SAXS), providing biochemical insight into HTT protein structure. The work outlined in this manuscript and the tools generated, lay a foundation for further biochemical and structural work on the HTT protein and its functional interactions with other biomolecules.
The algae community in taxon Haptophyceae at the early bloom stage of Phaeocystis globosa in Northern Beibu Gulf in winter
Authors: Gong Bin , Wu Haiping , Ma Jixian , Luo Meimiao , Li Xin ,   Bin Gong1,2*?Haiping Wu*2?Jixian Ma4?Meimiao Luo2?Xin Li2
Published: December 2018

Phaeocystis globosa (Order Phaeocystales, family Phaeocystaceae) caused significant impact on aquaculture farming, global climate change and industry. Since the year 2010, intensive red tides of P. globosa began to appear in Beibu Gulf, where previously free of harmful algal blooms, and posed great threats to the cooling systems of a nuclear power plant in 2014 and 2015. In order to discover the bloom mechanism, the community structure of marine microalgae, with a focus on Haptophyceae taxa, in winter in the northern Beibu Gulf near the Qinzhou Bay, Sanniang Bay (SNB) and Dafenjiang River Estuary (DRE), were explored via 18S ribosomal DNA analysis of the V4 region using the Illumina-Based Sequencing platform. The correlation between the relative abundance of five kinds of Haptophyceae algae and environmental factors of seawater were analyzed. The most abundant Haptophyceae-related OTU in terms of number of reads was identified as Phaeocystis and Chrysochromulina. The abundance for other Haptophyceae class was relatively low, such as Haptolina, Prymnesium and Isochrysis. Phaeocystis was present in all samples sites except S6, S11, S12, S14 and S15, and particularly abundant at S8, nearly 29 times more than the second most abundant site. Most notably, the results showed that Phaeocystis displayed highly positive linear correlation with the concentration of NO3--N (Pearson r=0.856, p<0.01). Linear regression analysis indicated that Phaeocystis was significantly linearly related to the NO3--N (R2=0.732; Y=-0.005 + 0.410*X, Y is the relative abundance of P.globosa, X is the concentration of NO3--N; F=38.227, P<0.05) and NO3--N has a significant positive effect on P.globosa (regression coefficient is 0.410, P=0.000). Moreover, the relative abundance of Phaeocystis was significant related to temperature of sea water (Pearson r=-0.882,p<0.01). Water temperature can explain the 77.8% change reason for the P.globosa (R2=0.778), and has a significant effect on P. globosa (Y=0.169-0.009*X, F=49.031,P<0.05), and the regression coefficient is -0.009 (P=0.000) which indicated a significant negative impact relationship between them. Our high throughput sequencing (HTS) based research illustrated how the P. globosa bloom generated and its relationship with NO3--N and temperature of sea water in northern Beibu Gulf for the first time, and bringing hope for solving this big problem.
Complex dietary-polysaccharide modulates gut immune function and microbiota, and promotes protection from autoimmune diabetes
Authors: Gudi Radhika , Perez Nicolas , Johnson Benjamin M. , Sofi M.Hanief , Brown Robert , Quan Songhua , Karumuthil-Melethil Subha , Vasu Chenthamarakshan
Published: December 2018

Since the dietary supplement and prebiotic value of β-glucan-rich products have been widely recognized and the dietary approaches for modulating autoimmunity have been increasingly explored, we assessed the impact of oral administration of high-pure yeast β-glucan (YBG) on gut immune function, microbiota and type 1 diabetes (T1D) using mouse models. Oral administration of this non-digestible complex polysaccharide caused a Dectin-1-dependent immune response involving increased expression of IL10, retinaldehyde dehydrogenase (Raldh) and pro-inflammatory cytokines in the gut mucosa. YBG-exposed intestinal DCs induced/expanded primarily Foxp3+, IL10+ and IL17+ T cells, ex vivo. Importantly, prolonged oral administration of low-dose YBG at pre-diabetic stage suppressed insulitis and significantly delayed the T1D incidence in non-obese diabetic (NOD) mice. Further, prolonged treatment with YBG showed increased Foxp3+ T cell frequencies, and a significant change in the gut microbiota, particularly an increase in the abundance of Bacteroidetes and a decrease in the Firmicute members. Oral administration of YBG, together with Raldh-substrate and β-cell antigen, resulted in a better protection of NOD mice from T1D. These observations suggest that YBG not only has a prebiotic property, but also has an oral tolerogenic-adjuvant-like effect, and these features could be exploited for modulating autoimmunity in T1D.
A chromosome-scale assembly of the major African malaria vector Anopheles funestus
Authors: Ghurye Jay , Koren Sergey , Small Scott T , Redmond Seth , Howell Paul , Phillippy Adam M , Besansky Nora J
Published: December 2018

Background: Anopheles funestus is one of the three most consequential and widespread vectors of human malaria in tropical Africa. However, the lack of a high-quality reference genome has hindered the association of phenotypic traits with their genetic basis in this important mosquito. Findings: Here we present a new high-quality An. funestus reference genome (AfunF3) assembled using 240x coverage of long-read single-molecule sequencing for contigging, combined with 100x coverage of short-read Hi-C data for chromosome scaffolding. The assembled contigs total 446 Mbp of sequence and contain substantial duplication due to alternative alleles present in the sequenced pool of mosquitos from the FUMOZ colony. Using alignment and depth-of-coverage information, these contigs were deduplicated to a 211 Mbp primary assembly, which is closer to the expected haploid genome size of 250 Mbp. This primary assembly consists of 1,053 contigs organized into 3 chromosome-scale scaffolds with an N50 contig size of 632 kbp and an N50 scaffold size of 93.811 Mbp, representing a 100-fold improvement in continuity versus the current reference assembly, AfunF1. Conclusion: This highly contiguous and complete An. funestus reference genome assembly will serve as an improved basis for future studies of genomic variation and organization in this important disease vector.
Development and use of Lentiviral Vectors Pseudotyped with Influenza B Haemagglutinins: application to vaccine immunogenicity, mAb potency and sero-surveillance studies
Authors: Ferrara Francesca , Carnell George , Kinsley Rebecca , Bottcher-Friebertshauser Eva , Pohlmann Stefan , Scott Simon , Fereidouni Sasan , Corti Davide , Kellam Paul , Gilbert Sarah , Temperton Nigel J
Published: December 2018

Influenza B viruses cause respiratory disease epidemics in human populations and are included in seasonal influenza vaccines. Serological methods are employed to evaluate vaccine immunogenicity prior to licensure. However, the haemagglutination inhibition assay, which represents the gold standard for assessing the immunogenicity of influenza vaccines, has been shown to be relatively insensitive for the detection of antibodies against influenza B viruses. Furthermore, this assay, and the serial radial haemolysis assay are not able to detect stalk-directed cross-reactive antibodies. For these reasons there is a need to develop new assays that can overcome these limitations. The use of replication-defective viruses, such as lentiviral vectors pseudotyped with influenza A haemagglutinins, in microneutralization assays is a safe and sensitive alternative to study antibody responses elicited by natural infection or vaccination. We have produced Influenza B haemagglutinin-pseudotypes using plasmid-directed transfection. To activate influenza B haemagglutinin, we have explored the use of proteases by adding relevant encoding plasmids to the transfection mixture. When tested for their ability to transduce target cells, the newly produced influenza B pseudotypes exhibit tropism for different cell lines. Subsequently the pseudotypes were evaluated as surrogate antigens in microneutralization assays using reference sera, monoclonal antibodies, human sera collected during a vaccine immunogenicity study and surveillance sera from seals. The influenza B pseudotype virus neutralization assay was found to effectively detect neutralizing and cross-reactive responses despite lack of significant correlation with the haemagglutinin inhibition assay.