bluuebunny/crossref_metadata_2025 huggingface dataset:
Superior Mesenteric Vein-First Approach to Robotic Complete Mesocolic Excision for Right Colectomy: Technique and Preliminary Outcomes
Authors: Yang Yun , Malakorn Songphol , Zafar Syed Nabeel , Nickerson T. Paul , Sandhu Lakhbir , Chang George J.
Published: June 2019

INTRODUCTION:

There is growing evidence supporting complete mesocolic excision as the optimal surgical approach for right-sided colon cancer to improve oncologic outcomes in comparison with conventional surgical resection. Although the feasibility of a minimally invasive approach to complete mesocolic excision has been reported, obesity has been associated with increased difficulty for finding the correct plane for dissection and delineating the vascular anatomy. We describe a novel approach with early identification of and dissection along the superior mesenteric vein during robotic complete mesocolic excision surgery, for all patients, regardless of BMI.

TECHNIQUE:

The dissection is initiated with identification of the superior mesenteric vein as the starting point. Then, the vascular dissection is performed along the anterior superior mesenteric vein plane while observing complete mesocolic excision principles. The anterior superior mesenteric vein plane is an optimal and safe dissection plane because there are no anterior tributaries. The ileocolic vein and artery are ligated separately at their junction with the superior mesenteric vein and superior mesenteric artery. The dissection is then continued cephalad along the superior mesenteric vein, identifying additional colic arteries, including the middle colic arterial trunk as well as the venous tributaries to the superior mesenteric vein such as the gastrocolic trunk. The superior right colic vein is then ligated at the gastrocolic confluence and the middle colic vessels are ligated. After the vascular dissection is completed, the colon is then mobilized.

RESULTS:

A total of 66 patients received the “superior mesenteric vein-first” approach for robotic colectomy between 2013 and 2018, including 40.9% patients with BMI >30 kg/m2. Median lymph node yield was 32 (interquartile range, 25–40). The median distance to the high vascular tie was 12 cm (interquartile range, 7–19). Median estimated blood loss was 33 mL (interquartile range, 25–50). Overall rate of grade ≥3 complications was 3.0%.

CONCLUSIONS:

Using the superior mesenteric vein-first approach, robotic complete mesocolic excision for right colectomy can be performed on patients with high or low BMI with excellent short-term oncologic outcomes and acceptable morbidity. See Video Abstract at http://links.lww.com/DCR/A960.
Change over time in patient-reported symptoms and quality of life in Edmonton interdisciplinary menopause clinics: preliminary cohort study of clinic patients and waitlist patients
Authors: Sydora Beate C. , Yuksel Nese , Chadha Vikas , Battochio Lori , Reich-Smith Lori , Hagen Shelly , Yaskina Maryna , Shandro Tami , Ross Sue J.
Published: June 2019

Objective:

Specialized interdisciplinary menopause clinics in Edmonton provide care for women suffering from severe menopausal symptoms. Our objectives were to evaluate changes over time in patient-reported menopause symptoms and quality of life (QOL) in a cohort of clinic patients, compared to a cohort of women recruited from the clinic waitlists.

Methods:

We conducted a prospective study of consecutive new patients in two clinics. Consenting women completed a generic menopause symptom severity questionnaire (MSSQ) and the menopause-specific quality of life (MENQOL) questionnaire at their first clinic and at a follow-up visit. Demographics, medical and obstetric histories, and medication use were extracted from patient charts. Women on the clinics’ waitlists were enrolled as controls; corresponding data for baseline and follow-up were collected in mailed-in surveys. Descriptive and paired statistics were used for data analysis. Agreement plot was created to visualize the agreement between MSSQ and MENQOL scores.

Results:

A total of 139 women were recruited: 98 attended the clinic and 41 were from the waitlist. Follow-up data were available for 99 women (71 clinic and 28 waitlist). There were no significant differences between clinic and waitlist patient characteristics. Women attending the clinics experienced significant reduction in symptom severity (mean MSSQ scores) and improvement in QOL (reduced MENQOL “bother” scores). Women on the clinic waitlist did not demonstrate significant changes over a similar timeframe. MENQOL correlated well with menopause symptom severity assessment.

Conclusion:

Women attending specialized menopause clinics experienced improvement in symptoms and QOL, whereas women on the waitlists did not experience these changes.

Video Summary:
Supplemental Digital Content 1, http://links.lww.com/MENO/A418.
An individualized approach to the management of vaginal atrophy in Latin America
Authors: Palacios Santiago , Nappi Rossella E. , Shapiro Marla , de Melo Nilson Roberto , Wender María Celeste Osorio , Fernandes César Eduardo , Pardini Dolores , Machado Rogério Bonassi , Kulak Jaime , Celis-González Cuauhtémoc , Martino Mabel T. , Pizzi Rita R. , Villaseca Paulina , Storch Eduardo , Danckers Luis Fernando , Hernández-Bueno José Alberto
Published: June 2019

Objective:

In the absence of guidelines specific for Latin America, a region where the impact of menopause is becoming increasingly important, an evidence-based specialist opinion on management of vaginal atrophy will help improve outcomes.

Methods:

An advisory board meeting was convened in São Paulo, Brazil, to discuss practical recommendations for managing vaginal atrophy in women in Latin America. Before the meeting, physicians considered various aspects of the condition, summarizing information accordingly. This information was discussed during the meeting. The expert consensus is now summarized.

Results:

In Latin America, given the relatively early age of menopause, it will be beneficial to raise awareness of vaginal atrophy among women before they enter menopause, considering cultural attitudes and involving partners as appropriate. Women should be advised about lifestyle modifications, including attention to genital hygiene, clothing, and sexual activity, and encouraged to seek help as soon as they experience vaginal discomfort. Although treatment can be started at any time, prompt treatment is preferable. A range of treatments is available. By addressing the underlying pathology, local estrogen therapy can provide effective symptom relief, with choice of preparation guided by patient preference. An individualized treatment approach should be considered, giving attention to patients’ specific situations.

Conclusions:

It is critical that women are empowered to understand vaginal atrophy. Educating women and healthcare providers to engage in open dialogue will facilitate appreciation of the benefits and means of maintaining urogenital health, helping to improve outcomes in middle age and beyond. Women should receive this education before menopause.
Concepts of Organizational Excellence in Medical Associations
Authors: Huynh Kristine A. , Chung Kevin C.
Published: June 2019

Professional associations are integral to the field of medicine; every physician becomes affiliated with at least 1 association throughout his/her entire career. Obtaining membership in such groups advances career development, engages in mentorship, and contributes in legislation and advocacy. Numerous studies have reported the benefits of teamwork in health care, but few have thoroughly investigated the characteristics that lead to organizational success. This article aims to provide a conceptual model for successful high-performing organizations and discuss their fundamental qualities, including structure, trust, productive conflict, accountability, collective success, and leadership. Additionally, we shared evidence-based techniques to establish and maintain these ideals.
Effects of Brimonidine and Timolol on the Progression of Visual Field Defects in Open-angle Glaucoma: A Single-center Randomized Trial
Authors: Yokoyama Yu , Kawasaki Ryo , Takahashi Hidetoshi , Maekawa Shigeto , Tsuda Satoru , Omodaka Kazuko , Nakazawa Toru
Published: June 2019

Précis:

Instillation of brimonidine or timolol slowed visual field deterioration in patients with open-angle glaucoma; both brimonidine and timolol might improve the mean deviation (MD) slopes.

Purpose:

The purpose of this study was to investigate and compare the effects of 0.1% brimonidine and 0.5% timolol on the progressing visual field defects in open-angle glaucoma.

Patients and Methods:

We evaluated 1 eye each of 68 glaucoma patients who were treated with at least 1 prostaglandin analog. Their baseline MD slopes were < −0.5 dB/y based on at least 5 Humphrey field analyzer measurements within 3 years. Eligible eyes were randomly assigned to brimonidine or timolol treatment groups and treatments were administered without the wash-out period. Clinical examinations were performed every 4 months for 2 years. We designated the MD slope as the primary endpoint.

Results:

Ultimately, 56 eyes (brimonidine:timolol=26:30) were included in the present study (mean age=65.2 y). Dropout rates of brimonidine and timolol treatment groups were 27.8% and 6.3%, respectively. There were no significant differences in baseline intraocular pressure or MD slopes between brimonidine and timolol groups (12.7 and 12.9 mm Hg, P=0.77, and −1.22 and −1.08 dB/y, P=0.43, respectively). Intraocular pressure decreased significantly in the brimonidine group at 4, 8, 12, and 16 months, and in the timolol group at 4 months, without significant differences between the drugs (P=0.20). MD slopes significantly improved in both groups (brimonidine: −0.38 dB/y, P<0.001; timolol: −0.52 dB/y, P=0.04). Furthermore, there was no significant difference between groups in the primary endpoint (P=0.59).

Conclusion:

Brimonidine and timolol treatments improved MD slopes in open-angle glaucoma.
Efficacy of Goniotomy With Kahook Dual Blade in Patients With Uveitis-associated Ocular Hypertension
Authors: Miller Victoria J. , Young Cara E. Capitena , SooHoo Jeffrey R. , Seibold Leonard K. , Kahook Malik Y. , Pecen Paula E. , Palestine Alan G. , Pantcheva Mina B.
Published: June 2019

Precis:

In a small case series of patients with uveitis-associated ocular hypertension (OHTN) or glaucoma, goniotomy with Kahook Dual Blade (KDB) was an effective surgical treatment option for lowering intraocular pressure (IOP).

Purpose:

The purpose of this study is to review the success of goniotomy using the KDB with trabecular meshwork (TM) excision in lowering the IOP of patients with uveitis-associated OHTN or glaucoma.

Materials and Methods:

A retrospective chart review was completed for all patients with uveitis-associated OHTN or glaucoma who underwent KDB goniotomy with TM excision alone or in combination with phacoemulsification cataract surgery at a single institution. The study included 12 patients (16 eyes). Patients were followed for a minimum of 5 months postoperatively. The main outcome measures of this case series included postoperative IOPs, percent IOP reduction, and reduction of glaucoma medications.

Results:

The mean maximum IOP of the patients before maximum-tolerated medical therapy or surgery was 35.6±5.8 mm Hg. The mean preoperative IOP at the clinical office visit before surgery of these patients was 28.1±8.5 mm Hg on maximum-tolerated medical therapy. Ten eyes (62.5%) have maintained an IOP at or below their goal through their most recent follow-up visit (mean follow-up time of 9.6±5.6 mo). The mean number of glaucoma medications was significantly reduced from 3.6±0.9 medications to 2.1±1.7 medications, for a mean reduction of 1.5±1.4 medications (P=0.004).

Conclusions:

On the basis of this small case series, KDB goniotomy may be a safe, less invasive, and effective first-line surgical alternative for patients with uveitis-associated OHTN or glaucoma refractory to medical therapy.
A randomised, double-blind, placebo-controlled crossover trial of the influence of the HCN channel blocker ivabradine in a healthy volunteer pain model: an enriched population trial
Authors: Lee Michael C. , Bond Simon , Wheeler Daniel , Scholtes Ingrid , Armstrong Graham , McNaughton Peter , Menon David
Published: June 2019

Preclinical studies suggest that type 2 hyperpolarization-activated cyclic nucleotide gated ion channels (HCN2) are necessary for neuropathic pain. This trial assessed the influence of ivabradine, a nonselective HCN channel blocker, on capsaicin-induced hyperalgesia and pain in healthy human subjects. An enriched population comprising subjects who developed >20 cm2 of punctate hyperalgesia from topical capsaicin (0.5% cream applied onto 9 cm2 area) was identified. These subjects then received ivabradine (15 mg) or placebo 1 hour before capsaicin application in randomly allocated order in a crossover study. The forearm site for capsaicin alternated with each application of the cream. The interval of time from screening to the first and to the second treatment visits was at least 3 and 5 weeks, respectively, to minimize carryover effects. Fifty-five participants were screened, of which 25 completed at least 1 treatment visit. Intention-to-treat hierarchical analysis revealed no significant effects of the drug on primary trial outcome, defined as a difference in effects of placebo and ivabradine on the area of punctate hyperalgesia (ivabradine − placebo: mean = 3.22 cm2, 95% confidence interval: = −4.04 to 10.48, P = 0.37). However, ivabradine caused a slowing of heart rate (difference of 10.10 beats per minute [95% confidence interval −6.48 to −13.73; P‐value <0.0001]). We conclude that ivabradine lacks analgesic effects in the capsaicin pain model at a dose that caused appreciable slowing of heart rate and, hence, is unlikely to prove a useful analgesic in humans. More selective drugs are required to establish a role of HCN2 for pain in humans.
The glutamine debate in surgery and critical care
Authors: Wischmeyer Paul E.
Published: June 2019

Purpose of review

Glutamine (GLN) is a versatile amino acid, long believed to have important implications in ICU and surgical patients. An extensive body of data examining GLN supplementation of TPN demonstrated a consistent signal of improved outcomes. However, recently signals of risk have come from two large-scale multicenter trials evaluating GLN (and other nutrients) at high dose and as primary pharmaconutrients, not as supplementation to complete nutrition. These trials indicate a risk of increased mortality when GLN is given to patients in shock, renal failure, and early in acute phase of critical care.

Recent findings

Recent literature continues to confirm that low and high admission GLN levels are associated with increased ICU mortality and adverse outcomes. Further, a recent meta-analysis examined trials utilizing GLN-supplemented TPN in stabile ICU patients consistent with current clinical guidelines. This analysis showed GLN supplementation of TPN led to reduced infections, LOS and hospital mortality.

Three recent meta-analyses have confirmed traditional GLN-supplemented (or ‘GLN-Complemented’ – providing GLN for completeness of amino acid content) TPN is safe, reduces mortality and improves outcome in surgical and ICU patients. Patients in need of TPN, burns, trauma or malignancies should continue to benefit from supplemental GLN, administered either intravenously at less than 0.35 g/kg/day or enterally at less than 0.5 g/kg/day. Further, a large trial of EN GLN supplementation in burns is ongoing. Thus, when used per guideline recommendations, the GLN story is likely still relevant to ICU outcomes and research.
Type-Specific Human Papillomavirus Prevalence, Incident Cases, Persistence, and Associated Pregnancy Outcomes Among HIV-Infected Women in Kenya
Authors: Vyankandondera Joseph , Wambua Sammy , Irungu Eunice , Mandaliya Kishor , Temmerman Marleen , Ryan Claire , Mohamed Yasmin , Vanden Broeck Davy , Verhelst Rita , Chersich Matthew F. , Luchters Stanley
Published: June 2019

Background

Persistent infection with high-risk types of human papillomavirus (HPV) is the preeminent factor driving the development of cervical cancer. There are large gaps in knowledge about both the role of pregnancy in the natural history of HPV infection and the impact of HPV on pregnancy outcomes.

Methods

This single-site prospective cohort substudy, nested within an international multisite randomized controlled trial, assessed prevalence, incident cases, and persistence of type-specific HPV infection, and the association between persistence of high-risk HPV infection with pregnancy outcomes among HIV-infected pregnant women in Kenya, including HIV transmission to infants. Type-specific HPV was assessed using a line probe assay in pregnancy and again at 3 months after delivery. HIV status of children was determined using polymerase chain reaction at 6 weeks.

Results

In total, 84.1% (206/245) of women had a high-risk HPV infection at enrollment. Three quarters (157/206) of these infections persisted postpartum. Persistence of HPV16 and/or HPV18 types was observed in more than half (53.4%; 39/73) of women with this infection at enrollment. Almost two-thirds had an incident high-risk HPV infection postpartum, which was not present in pregnancy (62.5%), most commonly HPV52 (19.0%). After adjustments, no association was detected between persistent high-risk HPV and preterm birth. All mothers of the 7 cases of infant HIV infection had persistent high-risk HPV infection (P= 0.044).

Conclusions

High levels of high-risk HPV infection and type-specific persistence were documented, heightening the urgency of mass role out of HPV vaccination. The association between HPV persistence and HIV transmission is a novel finding, warranting further study.
Self-Reported Extragenital Chlamydia and Gonorrhea Testing in the Past 12 Months Among Men Who Have Sex with Men in the United States—American Men's Internet Survey, 2017
Authors: de Voux Alex , Bernstein Kyle T. , Kirkcaldy Robert D. , Zlotorzynska Maria , Sanchez Travis
Published: June 2019

Background

Current guidelines recommend that sexually active men who have sex with men (MSM) be screened at least annually for bacterial sexually transmitted infections (STIs) at sites of sexual contact regardless of condom use. Extragenital (rectal and pharyngeal) STI are common in MSM and associated with an increased risk of human immunodeficiency virus. We describe the prevalence of MSM who reported any STI test and an extragenital STI test in the past 12 months (p12m) in the United States.

Methods

Data were obtained from the 2017 American Men's Internet Survey, an annual cross-sectional behavioral internet survey of MSM in the United States. We examined the prevalence of MSM who reported any STI test and an extragenital STI test in the p12m and compared the prevalence across demographic, clinical, and behavioral factors.

Results

Of 10,049 sexually active MSM who participated in American Men's Internet Survey 2017, 42% reported any STI test in the p12m and 16% reported an extragenital (rectal or pharyngeal) STI test in the p12m. Among those who reported getting an extragenital STI test in the p12m, 19% reported providing a throat swab only, 14% reported providing a rectal swab only, and 68% reported providing both a rectal and throat swab for STI testing.

Conclusions

In a large sample of internet-using MSM in the United States, levels of STI screening were suboptimal, with fewer than half (42%) of MSM reporting any STI test and even fewer reporting an extragenital STI test in the p12m. Increased efforts are needed to ensure annual STI screening guidelines among MSM are implemented.
Clinical Characteristics and Microsurgery Treatment of Anterior Cranial Fossa Dural Arteriovenous Fistula
Authors: Zhang Li , Wang Handong , Pan Yunxi , Mao Lei , Ding Ke , Zhu Jianhong
Published: June 2019

Anterior cranial fossa dural arteriovenous fistulas (DAVFs) represent 6% of all intracranial DAVFs and have a high risk of intracranial hemorrhage. To analyze the clinical characteristics and microsurgery treatment of anterior cranial fossa DAVFs, a retrospective review of 21 patients with anterior cranial fossa DAVFs undergoing microsurgery was performed, including 8 bleeding patients and 13 non-bleeding patients. The Glasgow coma scale (GCS) scores were used to evaluate the conscious states of 8 bleeding patients before and after operation. All patients had no obvious complications and the clinical symptoms were improved after operation. No abnormal fistulas and drainage veins were detected by digital subtraction angiography postoperatively. The GCS scores of 8 bleeding patients showed that the conscious states became better than pre-operation. Of the 21 patients, 9 patients were followed up without recurrence. Taken together, microsurgery is an effective method for the treatment of anterior cranial fossa DAVFs and it is very important for the improvement of bleeding patients’ conscious states.
TGF-β Pathway Inhibition Protects the Diaphragm From Sepsis-Induced Wasting and Weakness in Rat
Authors: Jude Baptiste , Tissier Florine , Dubourg Audrey , Droguet Michael , Castel Thomas , Léon Karelle , Giroux-Metges Marie-Agnès , Pennec Jean-Pierre
Published: June 2019

Sepsis is a frequent complication in patients in intensive care units (ICU). Diaphragm weakness, one of the most common symptoms observed, can lead to weaning problems during mechanical ventilation. Over the last couple of years, members of the transforming growth factor (TGF) β family, such as myostatin, activin A, and TGF-β1, have been reported to strongly trigger the activation of protein breakdown involved in muscle wasting. The aim of this study was to investigate the effect of TGF-β inhibitor LY364947 on the diaphragm during chronic sepsis.

Rats were separated into four groups exposed to different experimental conditions: Control group, Septic group, Septic group with inhibitor from day 0 (LY D0), and Septic group with inhibitor from day 1 (LY D1). Sepsis was induced in rats by cecal ligation and puncture, and carried out for 7 days.

Chronic sepsis was responsible for a decrease in body weight, food intake and diaphragm's mass. The inhibitor was able to abolish diaphragm wasting only in the LY D1 group. Similarly, LY364947 had a beneficial effect on the diaphragm contraction only for the LY D1 group. SMAD3 was over-expressed and phosphorylated within rats in the Septic group; however, this effect was reversed by LY364947. Calpain-1 and -2 as well as MAFbx were over-expressed within individuals in the Septic group. Yet, calpain-1 and MAFbx expressions were decreased by LY364947.

With this work, we demonstrate for the first time that the inhibition of TGF-β pathway during chronic sepsis protects the diaphragm from wasting and weakness as early as one day post infection. This could lead to more efficient treatment and care for septic patients in ICU.
Prospective Comparison of the Prognostic Relevance of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow of a Single Patient's Cohort With Esophageal Cancer
Authors: Konczalla Leonie , Ghadban Tarik , Effenberger Katharina E. , Wöstemeier Anna , Riethdorf Sabine , Uzunoglu Faik G. , Izbicki Jakob R. , Pantel Klaus , Bockhorn Maximilian , Reeh Matthias
Published: June 2019

Objective:

Aim of this prospective study was to evaluate the prognostic significance of disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) in 1 cohort of patients with esophageal cancer (EC).

Background:

Hematogenous tumor cell dissemination is a key event in tumor progression, and clinical significance of DTCs and CTCs are controversially discussed in the literature. However, evaluation of both biomarker in 1 patient's cohort has not been described before.

Methods:

In this prospective, single-center study, 76 patients with preoperatively nonmetastatic staged EC were included. The CellSearch system was used to enumerate CTCs. Bone marrow was aspirated from the iliac crest and cells were enriched by Ficoll density gradient centrifugation. DTCs were immunostained with the pan-keratin antibody A45-B/B3.

Results:

Fifteen of 76 patients (19.7%) harbored CTCs, whereas in 13 of 76 patients (17.1%), DTCs could be detected. In only 3 patients (3.9%), CTCs and DTCs were detected simultaneously, whereas concordant results (DTC/CTC negative and DTC/CTC positive) were found in 54 patients (71.1%). Surprisingly, only patients with CTCs showed significant shorter overall and relapse-free survival (P = 0.038 and P = 0.004, respectively). Multivariate analyses revealed that only the CTC status was an independent predictor of overall and relapse-free survival (P = 0.007 and P < 0.001, respectively).

Conclusions:

This is the first study analyzing CTC and DTC status in 1 cohort of nonmetastatic patients with EC. In this early disease stage, only the CTC status was an independent, prognostic marker suitable and easy to use for clinical staging of patients with EC.
Modeling missing cases and transmission links in networks of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa
Authors: Nelson Kristin N. , Gandhi Neel R. , Mathema Barun , Lopman Benjamin A. , Brust James C.M. , Auld Sara C. , Ismail Nazir , Omar Shaheed Vally , Brown Tyler S. , Allana Salim , Campbell Angie , Moodley Pravi , Mlisana Koleka , Shah N. Sarita , Jenness Samuel M.
Published: June 2019

The transmission patterns of drug-resistant tuberculosis (TB) remain poorly understood, despite over half a million incident cases in 2017. Modeling TB transmission networks can provide insight into the nature and drivers of transmission, but incomplete and non-random sampling of TB cases can pose challenges to making inferences from epidemiologic and molecular data. We conducted a quantitative bias analysis to assess the effect of missing cases on a transmission network inferred fromMtbsequencing data on extensively drug-resistant (XDR) TB cases in South Africa. We tested scenarios in which cases were missing at random, differentially by clinical characteristics, or differentially by transmission (i.e., cases with many links were under or over-sampled). Under the assumption cases were missing at random, cases in the complete, modeled network would have had a mean of 20 or more transmission links, which is far higher than expected, in order to reproduce the observed, partial network. Instead, we found that the most likely scenario involved undersampling of high-transmitting cases, and further models provided evidence for superspreading behavior. This is, to our knowledge, the first study to define and assess the support for different mechanisms of missingness in a study of TB transmission. Our findings should caution interpretation of results of future studies of TB transmission in high-incidence settings, given the potential for biased sampling, and should motivate further research aimed at identifying the specific host, pathogen, or environmental factors contributing to superspreading.
Hand Knob Area of Motor Cortex in People with Tetraplegia Represents the Whole Body in a Modular Way
Authors: Willett Francis R. , Deo Darrel R. , Avansino Donald T. , Rezaii Paymon , Hochberg Leigh , Henderson Jaimie , Shenoy Krishna
Published: June 2019

Decades after the motor homunculus was first proposed, it is still unknown how different body parts are intermixed and interrelated in human motor cortex at single-neuron resolution. Using microelectrode arrays, we studied how face, head, arm and leg movements on both sides of the body are represented in hand knob area of precentral gyrus in people with tetraplegia. Contrary to the traditional somatotopy, we found strong representation of all movements. Probing further, we found that ipsilateral and contralateral movements, and homologous arm and leg movements (e.g. wrist and ankle), had a correlated representation. Additionally, there were neural dimensions where the limb was represented independently of the movement. Together, these patterns formed a “modular” code that might facilitate skill transfer across limbs. We also investigated dual-effector movement, finding that more strongly represented effectors suppressed the activity of weaker effectors. Finally, we leveraged these results to improve discrete brain-computer interfaces by spreading targets across all limbs.
Quantification of anticipation of excitement with three-axial model of emotion with EEG
Authors: Machizawa Maro G. , Lisi Giuseppe , Kanayama Noriaki , Mizuochi Ryohei , Makita Kai , Sasaoka Takafumi , Yamawaki Shigeto
Published: June 2019

Objectives

Multiple facets of human emotions underlie diverse and sparse neural mechanisms. Amongst many models of emotions, the circumplex model of emotion is one of a significant theory. The use of the circumplex model allows us to model variable aspects of emotion; however, such momentary expression of one’s internal mental state still lacks to consider another, the third dimension of time. Here, we report an exploratory attempt to build a three-axial model of human emotion to model our sense of anticipatory excitement, “Waku-Waku (in Japanese),” when people are predictively coding upcoming emotional events.

Approach

Electroencephalography (EEG) was recorded from 28 young adult participants while they mentalized upcoming emotional pictures. Three auditory tones were used as indicative cues, predicting the likelihood of valence of an upcoming picture, either positive, negative, or unknown. While seeing an image, participants judged its emotional valence during the task, and subsequently rated their subjective experiences on valence, arousal, expectation, and Waku-Waku immediately after the experiment. The collected EEG data were then analyzed to identify contributory neural signatures for each of the three axes.

Main Results

A three axial model was built to quantify Waku-Waku. As was expected, this model revealed considerable contribution of the third dimension over the classical two-dimension model. Distinctive EEG components were identified. Furthermore, a novel brain-emotion interface is proposed and validated within the scope of limitations.

Significance

The proposed notion may shed new light on the theories of emotion and supports multiplex dimensions of emotion. With an introduction of the cognitive domain for a brain-computer-interface, we propose a novel brain-emotion-interface. Limitations and potential applications are discussed.
CLIJ: GPU-accelerated image processing for everyone
Authors: Haase Robert , Royer Loic A. , Steinbach Peter , Schmidt Deborah , Dibrov Alexandr , Schmidt Uwe , Weigert Martin , Maghelli Nicola , Tomancak Pavel , Jug Florian , Myers Eugene W.
Published: June 2019

Graphics processing units (GPU) allow image processing at unprecedented speed. We present CLIJ, a Fiji plugin enabling end-users with entry level experience in programming to benefit from GPU-accelerated image processing. Freely programmable workflows can speed up image processing in Fiji by factor 10 and more using high-end GPU hardware and on affordable mobile computers with built-in GPUs.
A universal scaling method for biodiversity-ecosystem functioning relationships
Authors: Barry K.E. , Pinter G.A. , Strini J.W. , Yang K. , Lauko I.G. , Schnitzer S.A. , Clark A.T. , Cowles J. , Mori A.S. , Williams L. , Reich P.B. , Wright A.J.
Published: June 2019

Global biodiversity is declining at rates faster than at any other point in human history. Experimental manipulations of biodiversity at small spatial scales have demonstrated that communities with fewer species consistently produce less biomass than higher diversity communities. However, understanding how the global extinction crisis is likely to impact global ecosystem functioning will require applying these local and largely experimental findings to natural systems at substantially larger spatial and temporal scales. Here we propose that we can use two simple macroecological patterns – the species area curve and the biomass-area curve – to upscale the species richness-biomass relationship. We demonstrate that at local spatial scales, each additional species will contribute more to biomass production with increasing area sampled because the species-area curve saturates and the biomass-area curve increases monotonically. We use species-area and biomass-area curves from a Minnesota grassland and a Panamanian tropical dry forest to examine the species richness – biomass relationship at three and ten sampling extents, respectively. In both datasets, the observed relationship between biodiversity and biomass production at every sampling extent was predicted from simple species-area and biomass-area relationships. These findings suggest that macroecological patterns like the species-area curve underpin the scaling of biodiversity-ecosystem functioning research and can be used to predict these relationships at the global scales where they are relevant for species loss.
Defining functional neuraminidase inhibitor drug resistance motifs in avian influenza viruses and the consequential impact on virus fitness in chicken cells
Authors: Bialy Dagmara , Shelton Holly
Published: June 2019

Neuraminidase inhibitors (NAIs) are antiviral agents recommended worldwide to treat or prevent influenza virus infections in humans. Mapping of functional resistance to currently licensed NAIs has been limited to human influenza viruses with only sporadic reports investigating avian influenza viruses (AIV). However past pandemics as well as the increasing number of humans infected with AIV have shown the importance of having information about avian NAs that could cross the species barrier. In this study we introduced four NAI resistance-associated mutations previously found in human strains into the NA of six prevalent AIV subtypes that threaten the poultry industry and human health: H7N9, H6N1, H4N6 and highly pathogenic H5N8, H5N6 and H5N2. Using the established MUNANA assay we show that R292K substitution significantly impaired NA activity in all strains, whereas E119V, H274Y and N294S have more variable effects on NA activity. The impact of these mutations on NAI susceptibility was drug- and strain-specific. We have shown that despite compromised NA activity drug-resistant H5N6 and H6N1 viruses replicated to comparable or significantly higher titres in primary chicken cells as compared to wild type. The replicative fitness of NAI-resistant H5N6 was also confirmedin ovo. Two drug resistant H5N6 viruses had single amino acid substitutions in their haemagglutinin (HA) which reduced receptor binding properties. Our results demonstrate that there are no universal NAI resistance determinants for all strains and although some are clearly deleterious for the virus, others can be rapidly compensated by acquiring concurrent changes in other gene segments.

IMPORTANCE

The number of human infections caused by avian influenza viruses (AIV) keeps increasing. This together with the rapid emergence of influenza strains resistant to neuraminidase inhibitor drugs (NAIs) observed in the past raises a significant concern to public health. We studied the NAI resistance-associated molecular changes, previously reported in neuraminidase (NA) of human influenza, in AIV background. We found that single amino acid substitution can confer a multidrug resistance, or lead to a single-drug resistance across multiple virus subtypes. We also found that the drug-resistant viruses retained or showed enhanced fitness properties as compared to the corresponding wild-type, and this could be achieved by quick acquisition of concurrent mutations in haemagglutinin. Our study highlights the need for constant monitoring of NAI-resistance in AIV and understanding the molecular basis of antiviral resistance, as such information would be invaluable for pandemic preparedness and may facilitate the development of novel therapeutics.
Species-specific recognition of Sulfolobales mediated by UV-inducible pili and S-layer glycosylation patterns
Authors: van Wolferen Marleen , Shajahan Asif , Heinrich Kristina , Brenzinger Susanne , Black Ian M. , Wagner Alexander , Briegel Ariane , Azadi Parastoo , Albers Sonja-Verena
Published: June 2019

The UV-inducible pili system of Sulfolobales (Ups) mediates the formation of species-specific cellular aggregates. Within these aggregates, cells exchange DNA in order to repair DNA double strand breaks via homologous recombination. Substitution of theS. acidocaldariuspilin subunits UpsA and UpsB with their homologs fromSulfolobus tokodaiishowed that these subunits facilitate species-specific aggregation. A region of low conservation within the UpsA homologs is primarily important for this specificity. Aggregation assays in the presence of different sugars showed the importance ofN-glycosylation in the recognition process. In addition, theN-glycan decorating the S-layer ofS. tokodaiiis different from the one ofS. acidocaldarius. Therefore, eachSulfolobusspecies seems to have developed a unique UpsA binding pocket and uniqueN-glycan composition to ensure aggregation and consequently also DNA exchange with cells from only the same species, which is essential for DNA repair by homologous recombination.

Importance

Type IV pili can be found on the cell surface of many archaea and bacteria where they play important roles in different processes. The Ups-pili from the crenarchaeal Sulfolobales species are essential in establishing species-specific mating partners, ensuring genome stability. With this work, we show that differentSulfolobusspecies have species-specific regions in their Ups-pilin subunits, which allow them to interact only with cells from the same species. Additionally, differentSulfolobusspecies all have unique S-layerN-glycosylation patterns. We propose that the unique features of each species allow the recognition of specific mating partners. This knowledge for the first time gives insights into the molecular basis of archaeal self-recognition.
The Geometry of Masking in Neural Populations
Authors: Ringach Dario L.
Published: June 2019

We introduce a geometric approach to study the representation of orientation by populations of neurons in primary visual cortex in the presence and absence of an additive mask. Despite heterogeneous effects at the single cell level, a simple geometric model explains how population responses are transformed by the mask and reveals how changes in discriminability and bias relate to each other. We propose that studying the geometry of neural populations can yield insights into the role of contextual modulation in the processing of sensory signals.
A luciferase-based assay identifies niclosamide derivatives antagonizing Mcl-1 through post-translational down-regulation
Authors: Liu Qiang , Atkinson Jennifer M. , Gebru Melat T. , Clements Kristen , Moldovan George L. , Wang Hong-Gang
Published: June 2019

The up-regulation of Mcl-1 expression is a major mechanism of cancer cell survival and therapy resistance. However, the underlying molecular mechanism remains incompletely understood, limiting the number of druggable approaches to selectively inhibit Mcl-1 function. In this study, we designed and employed a novel mechanistic high-throughput screening system to selectively uncover post-translational modulators of Mcl-1. We generated a cell-based high-throughput screening assay in which myeloid leukemia K562 cells constitutively express Mcl-1 or Bcl-xL fused with luciferase (Luc-Mcl-1 or Luc-Bcl-xL, respectively) under a viral promoter. 1,650 bioactive compounds were screened for their ability to selectively induce Mcl-1 down-regulation in a 2-hour assay. A family of niclosamide derivatives were eventually identified for their remarkable ability to decrease Mcl-1 protein stability, exemplified by N007. These salicylate derivatives did not alter Mcl-1 mRNA levels, but selectively induced proteasome-dependent Mcl-1 down-regulation independent of Noxa, Mule, or GSK3β. We also demonstrate that N007 potently induced cell death in leukemia cell lines, including those resistant to Bcl-2 inhibitors. Our work highlights the versatility of the mechanistic high-throughput screening approach as a valuable tool in identifying novel agents with the ability to down-regulate proteins crucial to human diseases.
The NKCC1 Antagonist Bumetanide Mitigates Interneuronopathy Associated with Ethanol Exposure In Utero
Authors: Skorput Alexander G. J. , Lee Stephanie M. , Yeh Pamela W. L. , Yeh Hermes H.
Published: June 2019

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.
Impaired Desynchronization of Beta Activity Underlies Memory Deficits in People with Parkinson’s Disease
Authors: MacDonald Hayley J. , Brittain John-Stuart , Spitzer Bernhard , Hanslmayr Simon , Jenkinson Ned
Published: June 2019

There is a pressing need to better understand the mechanisms underpinning the increasingly recognised non-motor deficits in Parkinson’s disease. Brain activity during Parkinson’s disease is excessively synchronized within the beta range (12–30Hz). However, relatively little is known about how the abnormal beta rhythms impact on non-motor symptoms. In healthy adults, beta desynchronization is necessary for successful episodic memory formation. We investigated whether there was a direct relationship between decreased beta modulation and memory formation in Parkinson’s disease. Electroencephalography recordings were made during an established memory-encoding paradigm. Parkinson’s participants showed impaired memory strength (P = 0.023) and reduced beta desynchronization (P = 0.014) relative to controls. Longer disease duration was correlated with a larger reduction in beta desynchronization, and a concomitant reduction in memory performance. These novel results extend the notion that pathological beta activity is causally implicated in the motor and (lesser appreciated) non-motor deficits inherent to Parkinson’s disease.
Non-uniform distribution of myosin-mediated forces governs red blood cell membrane curvature through tension modulation
Authors: Alimohamadi Haleh , Smith Alyson S. , Nowak Roberta B. , Fowler Velia M. , Rangamani Padmini
Published: June 2019

The biconcave disk shape of the mammalian red blood cell (RBC) is unique to the RBC and is vital for its circulatory function. Due to the absence of a transcellular cytoskeleton, RBC shape is determined by the membrane skeleton, a network of actin filaments cross-linked by spectrin and attached to membrane proteins. While the physical properties of a uniformly distributed actin network interacting with the lipid bilayer membrane have been assumed to control RBC shape, recent experiments reveal that RBC biconcave shape also depends on the contractile activity of nonmuscle myosin IIA (NMIIA) motor proteins. Here, we use the classical Helfrich-Canham model for the RBC membrane to test the role of heterogeneous force distributions along the membrane and mimic the contractile activity of sparsely distributed NMIIA filaments. By incorporating this additional contribution to the Helfrich-Canham energy, we find that the RBC biconcave shape depends on the ratio of forces per unit volume in the dimple and rim regions of the RBC. Experimental measurements of NMIIA densities at the dimple and rim validate our prediction that (a) membrane forces must be non-uniform along the RBC membrane and (b) the force density must be larger in the dimple than the rim to produce the observed membrane curvatures. Furthermore, we predict that RBC membrane tension and the orientation of the applied forces play important roles in regulating this force-shape landscape. Our findings of heterogeneous force distributions on the plasma membrane for RBC shape maintenance may also have implications for shape maintenance in different cell types.
An X-ray gas monitor for free-electron lasers
Authors: Sorokin Andrey A. , Bican Yilmaz , Bonfigt Susanne , Brachmanski Maciej , Braune Markus , Jastrow Ulf Fini , Gottwald Alexander , Kaser Hendrik , Richter Mathias , Tiedtke Kai
Published: June 2019

A novel X-ray gas monitor (XGM) has been developed which allows the measurement of absolute photon pulse energy and photon beam position at all existing and upcoming free-electron lasers (FELs) over a broad spectral range covering vacuum ultraviolet (VUV), extreme ultraviolet (EUV) and soft and hard X-rays. The XGM covers a wide dynamic range from spontaneous undulator radiation to FEL radiation and provides a temporal resolution of better than 200 ns. The XGM consists of two X-ray gas-monitor detectors (XGMDs) and two huge-aperture open electron multipliers (HAMPs). The HAMP enhances the detection efficiency of the XGM for low-intensity radiation down to 105 photons per pulse and for FEL radiation in the hard X-ray spectral range, while the XGMD operates in higher-intensity regimes. The relative standard uncertainty for measurements of the absolute photon pulse energy is well below 10%, and down to 1% for measurements of relative pulse-to-pulse intensity on pulses with more than 1010 photons per pulse. The accuracy of beam-position monitoring in the vertical and horizontal directions is of the order of 10 µm.
A study on product assembly and disassembly time prediction methodology based on virtual maintenance
Authors: Cai Kaijun , Zhang Weiming , Chen Wenzhuo , Zhao Hongfei
Published: June 2019

Purpose

Based on virtual maintenance, this paper aims to propose a time prediction method of assembly and disassembly (A&D) actions of product maintenance process to enhance existing methods’ prediction accuracy, applicability and efficiency.

Design/methodology/approach

First, a framework of A&D time prediction model is constructed, which describes the time prediction process in detail. Then, basic maintenance motions which can comprise a whole A&D process are classified into five categories: body movement, working posture change, upper limb movement, operation and grasp/placement. A standard posture library is developed based on the classification. Next, according to motion characteristics, different time prediction methods for each motion category are proposed based on virtual maintenance simulation, modular arrangement of predetermined time standard theory and the statistics acquired from motion experiment. Finally, time correction based on the quantitative evaluation method of motion time influence factors is studied so that A&D time could be predicted with more accuracy.

Findings

Case study of time prediction of products’ various A&D processes is conducted by implementing the proposed method. The prediction process of diesel cooling fan disassemble time is presented in detail. Through comparison, the advantages and effectiveness of the method are demonstrated.

Originality/value

This paper proposes a more accurate, efficient and applicable product A&D time prediction method. It can help designers predict A&D time of a product maintenance accurately in early design phases without a physical prototype. It can also provide basis for the verification of maintainability, the balance of the design of product structure and system layout.