bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and effectiveness of the self-aPposing, bAlloon-delivered, siRolimus-eluting stent for the Treatment of the coronary Artery disease: SPARTA, a multicenter experience
Authors: Montefusco Antonio , De Filippo Ovidio , Gili Sebastiano , Mancone Massimo , Calcagno Simone , Cirillo Plinio , Esposito Giovanni , Poli Arnaldo , Ferrara Erika , Smolka Grzegorz , Wanha Wojciech , Palmieri Cataldo , Pastormerlo Luigi Emilio , Baumbach Andreas , Sganzerla Paolo , Tamburino Corrado , Bruno Francesco , Secco Gioel Gabrio , Nicolino Annamaria , Yew Kuang Leon , di Palma Gaetano , Wojakowski Wojciech , Sardella Gennaro , Rinaldi Mauro , Cortese Bernardo , D’Ascenzo Fabrizio
Published: October 2019

Aims:

To assess the long-term outcomes of patients treated with sirolimus-eluting Stentys stent in a real-life setting.

Background:

Few data regarding the safety and effectiveness of self-apposing sirolimus-eluting Stentys stent are available.

Methods:

278 patients (30% stable coronary artery disease, 70% acute coronary syndromes, and 54% on unprotected left main) treated with sirolimus eluting Stentys stent were retrospectively included in the self-aPposing, bAlloon-delivered, siRolimus-eluting stent for the Treatment of the coronary Artery disease multicenter registry. Major adverse cardiovascular events (MACE, a composite of cardiac death, myocardial infarction, target lesion revascularization, stent thrombosis) were the primary end-point, single components of MACE were the secondary ones.

Results:

After 13 months (interquartile range 5–32), MACE was 14%. Stent thrombosis occurred in 3.9% of the patients (2.5% definite stent thrombosis and 1.4% probable stent thrombosis), 66% of them presenting with ST-segment elevation myocardial infarction (STEMI) at admission. Cardiovascular death, target lesion revascularization and myocardial infarction was 4.7%, 8.3%, and 7.2%, respectively. At multivariate analysis, risk of MACE was increased by diabetes (hazard ratios 4.76; P = 0.002) but was not affected by the indication leading to sirolimus-eluting Stentys stent implantation (marked vessel tapering vs. coronary ecstasies, hazard ratios 0.74, P = 0.71).

Conclusion:

Sirolimus-eluting Stentys stent may represent a potential solution for specific coronary anatomies such as bifurcation, ectasic, or tapered vessels. Risk of stent thrombosis appears related to clinical presentation with STEMI and to anatomic features, stressing the importance of the use of intracoronary imaging for self-expandable stents implantation.
The effect of complete revascularization in patients with ST-segment elevation myocardial infarction with Killip class ≥ III
Authors: Lee Wei-Chieh , Chen Tien-Yu , Chen Chien-Jen , Yang Cheng-Hsu , Fang Chih-Yuan , Wu Chiung-Jen , Fang Hsiu-Yu
Published: October 2019

Background:

The effect of complete revascularization (CR) on high-risk patients with ST-segment elevation myocardial infarction (STEMI) has remains a controversial issue, especially on patients in a critical condition. The aim of this study was to explore the effect of CR on patients with STEMI with Killip class ≥ III.

Methods:

From January 2008 to December 2014, 185 patients diagnosed with STEMI with Killip class ≥ III and multiple vessel coronary artery disease received primary percutaneous coronary intervention (PCI). Eighty-nine patients underwent culprit-only PCI, and the remaining 96 patients underwent immediate or staged PCI for CR. Out of the 96 patients in the CR group, 51 patients underwent immediate CR, and 45 patients underwent CR during the same hospitalization. Thirty-day and 1-year clinical outcomes were compared between the culprit-only PCI group and the CR group as well as between the immediate CR group and staged CR group.

Results:

There was a trend toward a lower incidence of post-PCI acute kidney injury in the culprit-only PCI group when compared with the CR group (14.8% vs. 26.0%; P = 0.069). Thirty-day and 1-year cardiovascular mortality and all-cause mortality were similar between the culprit-only PCI group and CR group. Decreased 1-year cardiovascular mortality and all-cause mortality were noted in the staged CR group compared with the immediate CR group.

Conclusion

was associated a higher possibility of post-PCI acute kidney injury and did not seem to improve 30-day or 1-year clinical outcomes. Patients undergoing staged CR during the same hospitalization had better clinical outcomes.
Anatomical features and clinical outcome of a honeycomb-like structure in the coronary artery: reports from 16 consecutive patients
Authors: Xu Tian , Shrestha Rajiv , Pan Tao , Huang Xiaoyu , Xu Haimei , Zhang Jun-Jie , Tao Ling , Han Yaling , Chen Shao-Liang
Published: October 2019

Background:

Recanalization of thrombus in coronary artery tree is defined as a honeycomb-like structure. However, the anatomic features and appropriate treatment of honeycomb-like structure still remain largely unclear.

Methods and results:

Between 2014 July and 2017 December, 17 honeycomb-like structure in 16 patients based on optical coherence tomography and intravascular ultrasound were included. Fractional flow reserve was measured for patients who had thrombolysis in myocardial infarction flow grade 3. Angiographic and optical coherence tomography/intravascular ultrasound-derived variables were studied. Clinical events (until to 2018 December) were collected. Honeycomb-like structures mostly involved left anterior descending artery (68.8%) and localized at proximal-mid (88.2%) segment of vessels. Eight patients had a side branch ≥ 2 mm in diameter taking from honeycomb-like structure. Only one patient had a normal fractional flow reserve. Fifteen patients underwent implantation of a stent. Stent implantation was associated with side branch compromise or closure (4 in each). Of 4 patients with side branch closure, all had a creatine kinase myocardial band > 5 times increase in hospital, with 3 deaths and 1 target lesion revascularization during follow-up.

Conclusions:

Despite the presence of recanalization, most honeycomb-like structure lesion have a positive fractional flow reserve. Further study is required to address how to protect a large side branch taking from honeycomb-like structure.
Six months follow-up of protected high-risk percutaneous coronary intervention with the microaxial Impella pump: results from the German Impella registry
Authors: Baumann Stefan , Werner Nikos , Al-Rashid Fadi , Schäfer Andreas , Bauer Timm , Sotoudeh Ramin , Bojara Waldemar , Shamekhi Jasmin , Sinning Jan-Malte , Becher Tobias , Eder Frederik , Akin Ibrahim
Published: October 2019

Background:

Percutaneous coronary intervention (PCI) represents an important alternative to coronary bypass surgery for the treatment of patients with complex coronary artery disease and high perioperative risk. Protected percutaneous coronary intervention applies temporary percutaneous ventricular assist devices to mitigate potential hemodynamic compromise in high-risk patients. The Impella system is currently the most commonly used device for protected percutaneous coronary intervention and showed improved hemodynamic parameters in earlier trials.

Methods:

This study was designed as a retrospective, observational multi-center registry conducted in ten hospitals in Germany. We included consecutive patients undergoing protected high-risk percutaneous coronary intervention with Impella support. The primary endpoint was defined as the occurrence of a major adverse cardiac event defined as all-cause mortality, ST-elevation myocardial infarction, or stroke during a postprocedural 180-day follow-up period.

Results:

In total, 157 patients (80.3% male; mean age 71.8 ± 10.8 years) were included in the present study, and 180-day follow-up was complete for 149 patients (94.9%). At baseline, the patients had a median left ventricular ejection fraction of 39.0% (interquartile range, 25.0–50.0%). The median SYNergy between PCI with TAXUS and Cardiac Surgery-Score I was 33.0 (interquartile range, 24.0–40.5) and the median EuroSCORE II was 7.2% (interquartile range, 3.2-17.1%). During postprocedural follow-up, 34 patients (22.8%) suffered a major adverse cardiac event. All-cause mortality was 18.1% (27 patients). Nine patients (6.0%) sustained a ST-elevation myocardial infarction, while 4 patients (2.7%) had a stroke.

Conclusions:

Patients undergoing protected high-risk percutaneous coronary intervention with Impella support showed an acceptable 180-day clinical outcome regarding major adverse cardiac event and mortality.
Clinical benefits of prolonged dual antiplatelet therapy following complex percutaneous coronary intervention
Authors: Subhaharan Deloshaan , Mridha Naim , Singh Kuljit
Published: October 2019

Aims

Prolonged dual antiplatelet therapy (DAPT) requires consideration of both reduced thrombotic events and increased bleeding risk. The associated subtle balance between the benefits and harms depends upon patient's clinical factors and complexity of the coronary anatomy. Our aim was to assess the safety and efficacy of prolonged (>12 months) DAPT in patients undergoing complex percutaneous coronary intervention (PCI).

Methods and Results

A thorough computer-based search was performed using four major databases. Complex PCI was defined as a procedure with at least one of the following angiographic characteristics: 3 vessels treated, >3 stents implanted, >3 lesions treated, bifurcation lesions, total stent length >60 mm, left main or proximal left anterior descending, a vein graft stent, or chronic total occlusion as target lesion. Of the 3543 titles searched, 5 studies met the inclusion criteria comparing short and prolonged DAPT therapy. We applied a random-effects model to acknowledge the variation in study design, treatment duration, and length of follow-up among studies. There was a reduction in cardiac mortality [odds ratio (OR) 0.57, 95% confidence interval (CI): 0.35–0.92; P = 0.02, I
2 = 0%] and major adverse cardiovascular events (OR 0.76, 95% CI: 0.59–0.96; P = 0.02, I
2 = 22%) with prolonged DAPT. Major bleeding was increased with prolonged DAPT (OR 1.75, 95% CI: 1.20–2.20; P = 0.004, I
2 = 0%). There was no difference in the all-cause mortality (OR 0.86, 95% CI: 0.61–1.22; P = 0.41, I
2 = 0%).

Conclusion

Prolonged DAPT reduces cardiac mortality and major adverse cardiovascular events in complex PCI. The results would need confirmation in a larger randomized study.
Exploration of interventional therapy strategy for portal vein occlusion: a case series study
Authors: Liu Jiacheng , Zhou Chen , Shi Qin , Ma Jinqiang , Ye Tianhe , Zheng Chuansheng , Feng Gansheng , Xiong Bin
Published: October 2019

Objectives

To explore the candidates, efficacy and safety of interventional therapies in the treatment of portal vein occlusion (PVO).

Methods

In our study, 13 patients diagnosed with PVO were included. Of all 13 patients, two received percutaneous portal vein recanalization (PVR), 10 received PVR and transjugular intrahepatic portosystemic shunt (PVR-TIPS), and one underwent intrahepatic portal branch-large collateral vessel shunt.

Results

Interventional approaches were completed in all patients, and the technical success rate was 100%. The portal pressure gradient of patients treated with PVR-TIPS fell from 31 ± 4 to 12 ± 3 mmHg. During the procedures, no life-threatening complications occurred. All the clinical symptoms were effectively controlled after the interventional therapies and all the patients survived during the follow-up, with no rebleeding or overt hepatic encephalopathy. But stent thrombosis occurred in one patient, the cumulative rate of stent patency was 92%.

Conclusion

Interventional therapy was proved to be a well tolerated and effective strategy for PVO. For PVO patients without high intrahepatic resistance, if the patient is equipped with available portal inflow tract (superior mesenteric vein or splenic vein) and outflow tract (intrahepatic portal branches), PVR is the first choice; if the outflow tract is completely blocked with only available inflow tract, PVR-TIPS can be considered. For PVO patients with high intrahepatic resistance, as long as there is an available portal inflow tract, PVR-TIPS can be adopted.
Effectiveness of the virtual reality on cognitive function of children with hemiplegic cerebral palsy: a single-blind randomized controlled trial
Authors: Aran Orkun Tahir , Şahin Sedef , Köse Barkin , Ağce Zeynep Bahadir , Kayihan Hülya
Published: October 2019

Cerebral palsy is a term covering non-progressive motor and cognitive impairments caused by lesions of the brain. This study aims to evaluate the effectiveness of virtual reality-based rehabilitation program for children with hemiplegic cerebral palsy on cognitive functions. Ninety children (47 boys, 43 girls) with hemiplegic cerebral palsy were randomized to either study (n = 45; 11.18 ± 3.37 years) or control (n = 45; 11.06 ± 3.24 years) groups. The study group received virtual reality intervention in addition to Traditional Occupational Therapy intervention, and the control group received Traditional Occupational Therapy for 20 sessions. Both groups were evaluated by blinded assessors with Dynamic Occupational Therapy Cognitive Assessment for Children to collect information on cognitive functioning. Both groups' cognitive functions were improved after 10 weeks of interventions. The between-group comparison revealed significantly greater improvements in all subtest of cognitive functions in the virtual reality group than in the Traditional Occupational Therapy group (P < 0.001). Our results showed that 10 weeks of virtual reality-based rehabilitation enhanced cognitive functions in children with hemiplegic cerebral palsy. Using virtual reality applications in cognitive rehabilitation was recommended to improve spatial perception, praxis, visuomotor construction and thinking operations in children with cerebral palsy.
Posttraumatic Stress and Depression Among Syrian Refugees Living in Turkey
Authors: Kaya Edip , Kiliç Cengiz , Karadağ Çaman Özge , Üner Sarp
Published: October 2019

Although most of the 3.6 million Syrian refugees in Turkey live outside refugee camps, most mental health research is on camp residents and few are on those living in cities. We aimed to assess the prevalence and predictors of posttraumatic stress disorder (PTSD) and depression in Syrian refugees living in an urban area in Turkey. A total of 420 adult Syrians living in Ankara were assessed using the Harvard Trauma Questionnaire and the Beck Depression Inventory. Probable PTSD and depression rates were 36.5% and 47.7%, respectively. Female sex, physical illness, and greater number of potentially traumatic events predicted both PTSD and depression. PTSD was additionally predicted by past psychiatric illness, and depression was predicted by lower economic status. Interestingly, lower economic status predicted depression among men, but not among women. Studies on refugees should be sensitive to factors that could have a significant effect on mental health such as sex or residence.
Extracorporeal Membrane Oxygenation Support After Heart Transplantation in Children—Outcomes of a Single Center Cohort
Authors: Nair Asha G. , Sleeper Lynn A. , Smoot Leslie B. , Wigmore Daniel , Mecklosky Jessica , Andren Kristofer , Bastardi Heather J. , Blume Elizabeth D. , Fynn-Thompson Francis , Thiagarajan Ravi R. , Alexander Peta M. A.
Published: October 2019

Objectives:

Extracorporeal membrane oxygenation is used for postcardiotomy low cardiac output but is less established following heart transplantation. We characterized outcomes for children supported with extracorporeal membrane oxygenation after heart transplantation.

Design:

Single-center retrospective study.

Setting:

Large pediatric cardiac referral center.

Patients:

All patients who received heart transplantation and were cannulated to extracorporeal membrane oxygenation between 1995 and 2016.

Interventions:

Primary outcome measure was mortality 12 months postextracorporeal membrane oxygenation. Patient characteristics were analyzed for association with outcome according to early graft failure (extracorporeal membrane oxygenation ≤ 7 d after heart transplantation), or late graft failure.

Measurements and Main Results:

There were 246 heart transplants during the study period and 50 extracorporeal membrane oxygenation runs in 44 patients. Median time from transplant to extracorporeal membrane oxygenation was 1 day (range, 0–11.7 yr), with early graft failure in 28 patients (median 1, range 0–2 d) and 22 extracorporeal membrane oxygenation runs in 20 late graft failure patients (median, 0.8 yr; range, 8 d to 11.7 yr), including four patients with prior extracorporeal membrane oxygenation for early graft failure. Twenty-six patients (59%) survived to hospital discharge, and survival 12 months postextracorporeal membrane oxygenation was 24 patients (55%), lower in those with late graft failure (40% vs 67%; p 0.02). Independent risk factors for 12-month mortality were congenital heart disease, higher pulmonary vascular resistance indexed to body surface area (> 2.2 Woods U/m2), and higher creatinine. Higher panel reactive antibody levels were associated with 12-month mortality in the late graft failure group only.

Conclusions:

Extracorporeal membrane oxygenation can be effectively used to rescue patients with graft dysfunction after heart transplantation but is associated with high early mortality. Factors associated with mortality within 12 months include presence of congenital heart disease, renal dysfunction, elevated pulmonary vascular resistance indexed to body surface area and in those supported with extracorporeal membrane oxygenation late after heart transplantation, significant human leukocyte antigen sensitization.
Missed Study Visits and Subsequent HIV Incidence Among Women in a Predominantly Sex Worker Cohort Attending a Dedicated Clinic Service in Kampala, Uganda
Authors: Kasamba Ivan , Nash Stephen , Shahmanesh Maryam , Baisley Kathy , Todd Jim , Kamacooko Onesmus , Mayanja Yunia , Seeley Janet , Weiss Helen A.
Published: October 2019

Background:

There is limited evidence on the relationship between sustained exposure of female sex workers (FSWs) to targeted HIV programmes and HIV incidence. We investigate the relationship between the number of missed study visits (MSVs) within each episode of 2 consecutively attended visits (MSVs) and subsequent HIV risk in a predominantly FSW cohort.

Methods:

Women at high risk of HIV are invited to attend an ongoing dedicated clinic offering a combination HIV prevention intervention in Kampala, Uganda. Study visits are scheduled once every 3 months. The analysis included HIV-seronegative women with ≥1 follow-up visit from enrollment (between April 2008 and May 2017) to August 2017. Cox regression models were fitted adjusted for characteristics on sociodemographic, reproductive, behavioral, and sexually transmitted infections (through clinical examination and serological testing for syphilis).

Findings:

Among 2206 participants, HIV incidence was 3.1/100 (170/5540) person-years [95% confidence interval (CI): 2.6 to 3.5]. Incidence increased from 2.6/100 person-years (95% CI: 2.1 to 3.2) in episodes without a MSV to 3.0/100 (95% CI: 2.2 to 4.1) for 1–2 MSVs and 4.3/100 (95% CI: 3.3 to 5.6) for ≥3 MSVs. Relative to episodes without a MSV, the hazard ratios (adjusted for confounding variables) were 1.40 (95% CI: 0.93 to 2.12) for 1–2 MSVs and 2.00 (95% CI: 1.35 to 2.95) for ≥3 MSVs (P-trend = 0.001).

Conclusion:

Missing study visits was associated with increased subsequent HIV risk. Although several factors may underlie this association, the finding suggests effectiveness of targeted combination HIV prevention. But exposure to targeted interventions needs to be monitored, facilitated, and sustained in FSWs.
Hypertension Control and Retention in Care Among HIV-Infected Patients: The Effects of Co-located HIV and Chronic Noncommunicable Disease Care
Authors: Osetinsky Brianna , Genberg Becky L. , Bloomfield Gerald S. , Hogan Joseph , Pastakia Sonak , Sang Edwin , Ngressa Anthony , Mwangi Ann , Lurie Mark N. , McGarvey Stephen T. , Galárraga Omar
Published: October 2019

Background:

As the noncommunicable disease (NCD) burden is rising in regions with high HIV prevalence, patients with comorbid HIV and chronic NCDs may benefit from integrated chronic disease care. There are few evaluations of the effectiveness of such strategies, especially those that directly leverage and extend the existing HIV care system to provide co-located care for NCDs.

Setting:

Academic Model of Providing Access to Healthcare, Kenya, provides care to over 160,000 actively enrolled patients in catchment area of 4 million people.

Methods:

Using a difference-in-differences design, we analyzed retrospective clinical records of 3603 patients with comorbid HIV and hypertension during 2009─2016 to evaluate the addition of chronic disease management (CDM) to an existing HIV care program. Outcomes were blood pressure (BP), hypertension control, and adherence to HIV care.

Results:

Compared with the HIV standard of care, the addition of CDM produced statistically significant, although clinically small improvements in hypertension control, decreasing systolic BP by 0.76 mm Hg (P < 0.001), diastolic BP by 1.28 mm Hg (P < 0.001), and increasing the probability of BP <140/90 mm Hg by 1.51 percentage points (P < 0.001). However, sustained control of hypertension for >1 year improved by 7 percentage points (P < 0.001), adherence to HIV care improved by 6.8 percentage points (P < 0.001) and retention in HIV care with no gaps >6 months increased by 10.5 percentage points (P < 0.001).

Conclusion:

A CDM program that co-locates NCD and HIV care shows potential to improve BP and retention in care. Further evaluation of program implementation across settings can inform how to maximize hypertension control among patients with comorbid HIV, and better understand the effect on adherence.
Implementation of a Community-Based Hybrid HIV Testing Services Program as a Strategy to Saturate Testing Coverage in Western Kenya
Authors: Truong Hong-Ha M. , Akama Eliud , Guzé Mary A. , Otieno Frankline , Obunge Duncan , Wandera Esther , Nsengiyumva Ntwali Placide , Obabo Sammy , Bushman Dena , Kadede Kevin , Bukusi Elizabeth A. , Oyaro Patrick , Cohen Craig R.
Published: October 2019

Background:

Knowledge of HIV status is the entry point for linkage to prevention, care, and treatment, and the first step toward achieving the UNAIDS 90-90-90 targets. Most countries rely on proxies for estimating testing saturation, including periodic population-based sampling and yield (number positive among those tested). We conducted a community-based “Hybrid” HIV testing services (HTS) program to identify persons unaware of their HIV-positive status.

Setting:

Homa Bay County, Kenya; July–September, 2016.

Methods:

We conducted community mapping, household census, multi-disease community health campaigns (CHCs), and home-based tracking. HIV testing eligibility was based on 2015 national guidelines. The previously unidentified fraction (PUF) was defined as the proportion of newly identified persons living with HIV (PLWH) out of all previously identified and newly identified PLWH.

Results:

The Hybrid HTS program reached 28,885 persons in total: 25,340 residents and 3545 nonresidents. There were 19,288 persons reached through CHCs and tracking. Of 11,316 individuals eligible for HIV testing, 9463 (83%) accepted testing, including 1230 (13%) first-time testers. There were 115 newly identified PLWH of 1589 total HIV-positive persons, representing a 7.2% PUF. Of 93 newly identified PLWH at the CHCs, 68% initiated same-day antiretroviral therapy.

Conclusion:

The Hybrid HTS program identified persons previously unaware of their HIV-positive status, thereby enabling linkage to care and same-day treatment and reducing onward transmission risk. An approach focused on identifying persons unaware of their HIV-positive status in combination with ascertaining the PUF has the potential to better target testing strategies to identify >90% of PLWH in a community.
Importance of HIV/AIDS-Related Behavioral and Social Sciences Research at the NIH and Beyond
Authors: Goodenow Maureen M. , Gaist Paul
Published: October 2019

Opportunity Statement:

Key topics discussed in this article were previously presented at the Center for AIDS Research Social and Behavioral Sciences Network's 12th National Scientific Meeting in August 2018. This article highlights the importance of behavioral and social sciences research (BSSR) in addressing the HIV/AIDS pandemic.

Approach:

NIH has made significant investments in HIV/AIDS-related BSSR. These investments support the development of effective, evidence-based sociobehavioral HIV prevention, treatment, and care strategies.

Discussion:

The implementation and use of evidence-based sociobehavioral approaches in combination with biomedical strategies provide the availability of multiple tools to end the HIV epidemic in the United Sates and the pandemic globally.

Future Directions:

BSSR-related opportunities to mitigate the persistent challenges HIV/AIDS presents include, but are not limited to, further incorporating BSSR into HIV vaccine and cure research; improving interventions that address stigma and the social determinants of health that perpetuate HIV transmission within key populations; and conducting implementation science research that shapes national and international policies impacting HIV prevention, treatment, and care.
Response to the HIV Epidemic: Perspectives From a Retired NIH Project Officer
Authors: Newcomer Susan F.
Published: October 2019

An informal narrative from a retired National Institute of Child Health and Human Development program officer providing perspective on her time at National Institute of Child Health and Human Development. There are anecdotes and advice about wise approaches to the challenges of writing and managing National Institutes of Health grants.
PrEP 1.0 and Beyond: Optimizing a Biobehavioral Intervention
Authors: Mayer Kenneth H. , Allan-Blitz Lao-Tzu
Published: October 2019

Background:

Tenofovir disoproxil fumarate coformulated with emtricitabine (TDF/FTC) was shown to be effective in preventing HIV acquisition when used for pre-exposure prophylaxis (PrEP), but questions have arisen regarding optimal PrEP implementation strategies.

Methods:

A narrative review of literature since 2010 regarding PrEP effectiveness, implementation, and new prevention modalities was undertaken to summarize lessons learned, and to review potential benefits and challenges.

Results:

Although daily TDF/FTC is safe, well tolerated, and highly effective in preventing HIV transmission, it has been initiated by only 200,000 Americans, and a comparable number of individuals in other countries, meaning that 80%–90% of those at greatest risk globally have not benefitted yet. Barriers to PrEP uptake have included medication and care costs, anticipated side effects, stigma, and unsupportive health care systems. Innovations to increase PrEP uptake and adherence have included engaging nonmedical staff (eg, pharmacists, social workers, and peer navigators), economic assistance programs, and new technologies (eg, text messaging support and dedicated apps). Pericoital PrEP dosing seems to be effective in preventing HIV transmission among men who have sex with men, but has not been evaluated in women. Investigational PrEP approaches include antiretrovirals delivered by injection, implant, vaginal rings, rectal douches, and immunoprophylaxis. Some of these approaches may allow for infrequent dosing, whereas others may be more congruent with patterns of sexual behavior.

Conclusions:

PrEP has been shown to be safe and effective when used consistently, but new approaches to enhance uptake, adherence, and convenience with less-frequent dosing are under study, suggesting that new models and modalities will evolve to optimize impact.
The Mid-Atlantic Center for AIDS Research Consortium Scholars Program: A Multi-Institutional Approach to Mentoring the Next Generation of Underrepresented Scientists
Authors: Limaye Rupali J. , Magnus Manya , Metzger David , Blank Michael B. , Davis Wendy , Celentano David D. ,   for the Mid-Atlantic Center for AIDS Research Consortium
Published: October 2019

Background:

There is an urgent need to intentionally develop and expand mentoring for junior faculty from underrepresented communities in the area of HIV research. Such a goal is increasingly recognized as essential across all scientific fields because profound disparities exist regarding which doctorally prepared individuals ultimately end up entering research fields in academic settings. The purpose of this article is to describe a novel inter-Center for AIDS Research (CFAR) program designed to support underrepresented scientists in research to address the HIV epidemic in the Mid-Atlantic region.

Methods:

Three CFARs in the Mid-Atlantic region (the District of Columbia, Johns Hopkins University CFAR, and University of Pennsylvania CFARs) developed a Scholars program designed for underrepresented minority scholars interested in studying the HIV epidemic in the region. The program provided resources for scholarship as well as cross-institutional mentoring and training.

Results:

Scholars in the first cohort have been successful in implementing novel research that informs our understanding of the HIV epidemic in the region as well as increasing skills, publications, and grant submissions and funded applications. Lessons learned from the first cohort will inform future years of the MACC Scholars Program.

Conclusions:

The MACC Scholars Program offers a model for other inter-CFAR collaborations wishing to find novel ways to support the next generation of scientists.
On the concept of dynamical reduction: the case of coupled oscillators
Authors: Kuramoto Yoshiki , Nakao Hiroya
Published: October 2019

An overview is given on two representative methods of dynamical reduction known as
centre-manifold reduction
and
phase reduction
. These theories are presented in a somewhat more unified fashion than the theories in the past. The target systems of reduction are coupled limit-cycle oscillators. Particular emphasis is placed on the remarkable structural similarity existing between these theories. While the two basic principles, i.e. (i) reduction of dynamical degrees of freedom and (ii) transformation of reduced evolution equation to a canonical form, are shared commonly by reduction methods in general, it is shown how these principles are incorporated into the above two reduction theories in a coherent manner. Regarding the phase reduction, a new formulation of perturbative expansion is presented for discrete populations of oscillators. The style of description is intended to be so informal that one may digest, without being bothered with technicalities, what has been done after all under the word
reduction
.

This article is part of the theme issue ‘Coupling functions: dynamical interaction mechanisms in the physical, biological and social sciences’.
State-dependent effective interactions in oscillator networks through coupling functions with dead zones
Authors: Ashwin Peter , Bick Christian , Poignard Camille
Published: October 2019

The dynamics of networks of interacting dynamical systems depend on the nature of the coupling between individual units. We explore networks of oscillatory units with coupling functions that have ‘dead zones’, that is the coupling functions are zero on sets with interior. For such networks, it is convenient to look at the effective interactions between units rather than the (fixed) structural connectivity to understand the network dynamics. For example, oscillators may effectively decouple in particular phase configurations. Along trajectories, the effective interactions are not necessarily static, but the effective coupling may evolve in time. Here, we formalize the concepts of dead zones and effective interactions. We elucidate how the coupling function shapes the possible effective interaction schemes and how they evolve in time.

This article is part of the theme issue ‘Coupling functions: dynamical interaction mechanisms in the physical, biological and social sciences’.
IBA endogenous auxin regulates Arabidopsis root system development in a glutathione-dependent way and is important for adaptation to phosphate deprivation
Authors: Trujillo-Hernandez José A. , Bariat Laetitia , Strader Lucia C. , Reichheld Jean-Philippe , Belin Christophe
Published: October 2019

Root system architecture results from a highly plastic developmental process to perfectly adapt to environmental conditions. In particular, the development of lateral roots (LR) and root hair (RH) growth are constantly optimized to the rhizosphere properties, including biotic and abiotic constraints. Every step of root system development is tightly controlled by auxin, the driving morphogenic hormone in plants. Glutathione, a major thiol redox regulator, is also critical for root system development but its interplay with auxin is still scarcely understood. Indeed, previous works showed that glutathione deficiency does not alter root responses to exogenous indole acetic acid (IAA), the main active auxin in plants. Because indole butyric acid (IBA), another endogenous auxinic compound, is an important source of IAA for the control of root development, we investigated the crosstalk between glutathione and IBA during root development. We show that glutathione deficiency alters LR and RH responses to exogenous IBA but not IAA. Although many efforts have been deployed, we could not identify the precise mechanism responsible for this control. However, we could show that both glutathione and IBA are required for the proper responses of RH to phosphate deprivation, suggesting an important role for this glutathione-dependent regulation of auxin pathway in plant developmental adaptation to its environment.
A metallo-beta-lactamase with both beta-lactamase and ribonuclease activity is linked with traduction in giant viruses
Authors: Colson Philippe , Pinault Lucile , Azza Said , Armstrong Nicholas , Chabriere Eric , La Scola Bernard , Pontarotti Pierre , Raoult Didier
Published: October 2019

Enzymatic proteins with a metallo-beta-lactamase (MBL) fold have been essentially studied in bacteria for their activity on beta-lactam antibiotics. However, the MBL fold is ancient and highly conserved, and these proteins are capable of cleaving a broad range of substrates. It has recently been shown that MBLs are present in a wide array of cellular organisms, including eukaryotes and archaea. We show here that Tupanvirus deep ocean, a giant virus, also encodes a protein with a MBL fold. Phylogeny showed its clustering with transfer ribonucleases (RNases) and the presence of orthologs in other giant viruses, mainly those harboring the largest sets of translation components. In addition, it suggests an ancient origin for these genes and a transfer between giant viruses and Acanthamoeba spp., a host of many giant viruses. Biologically, after its expression in Escherichia coli, the tupanvirus protein was found to hydrolyse nitrocefin, a chromogenic beta-lactam. We also observed an hydrolysis of penicillin G (10 μg/mL) and detected the metabolite of penicillin G hydrolysis, benzylpenilloic acid. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, we tested the degradation of single-stranded DNA, double-stranded DNA, and RNAs, and observed a strong activity on RNAs from seven bacteria with G+C varying from 42% to 67%, and from Acanthamoeba castellanii, the tupanvirus host. This was not inhibited by sulbactam or ceftriaxone. RNase activity was estimated to be 0.45±0.15 mU/mg using a fluorescence-based assay. Our results still broaden the range of hosts of MBL fold proteins and demonstrate that such protein can have dual beta-lactamase/nuclease activities. We suggest that they should be annotated according to this finding to avoid further confusion.
Senescence of alveolar stem cells drives progressive pulmonary fibrosis
Authors: Yao Changfu , Guan Xiangrong , Carraro Gianni , Parimon Tanyalak , Liu Xue , Huang Guanling , Soukiasian Harmik J. , David Gregory , Weigt Stephen S. , Belperio John A. , Chen Peter , Jiang Dianhua , Noble Paul W. , Stripp Barry R.
Published: October 2019

Tissue fibrosis is a common pathological outcome of chronic disease that markedly impairs organ function leading to morbidity and mortality. In the lung, idiopathic pulmonary fibrosis (IPF) is an insidious and fatal interstitial lung disease associated with declining pulmonary function. Here, we show that alveolar type 2 (AT2) stem cells isolated from IPF lung tissue exhibit characteristic transcriptomic features of cellular senescence. We used conditional loss of Sin3a in adult mouse AT2 cells to initiate a program of p53-dependent cellular senescence, AT2 cell depletion, and spontaneous, progressive pulmonary fibrosis. We establish that senescence rather than loss of epithelial stem cells serves as a proximal driver of Tgfβ activation and progressive fibrosis and show that either genetic or pharmacologic interventions targeting p53 activation, senescence, or downstream Tgfβ activation, block fibrogenesis.
Coordination of NDC80 and Ska complexes at the kinetochore-microtubule interface in human cells
Authors: Wimbish Robert , DeLuca Keith F. , Mick Jeanne E. , Himes Jack , Sánchez Ignacio J. , Jeyaprakash A. Arockia , DeLuca Jennifer G.
Published: October 2019

The conserved kinetochore-associated NDC80 complex (comprised of Hec1/Ndc80, Nuf2, Spc24, and Spc25) has well-documented roles in mitosis including (1) connecting mitotic chromosomes to spindle microtubules to establish force-transducing kinetochore-microtubule attachments, and (2) regulating the binding strength between kinetochores and microtubules such that correct attachments are stabilized and erroneous attachments are released. Although the NDC80 complex plays a central role in forming and regulating attachments to microtubules, additional factors support these processes as well, including the spindle and kinetochore-associated (Ska) complex. Multiple lines of evidence suggest that Ska complexes strengthen attachments by increasing the ability of NDC80 complexes to bind microtubules, especially to depolymerizing microtubule plus-ends, but how this is accomplished remains unclear. Using cell-based and in vitro assays, we demonstrate that the Hec1 tail domain is dispensable for Ska complex recruitment to kinetochores and for generation of kinetochore-microtubule attachments in human cells. We further demonstrate that Hec1 tail phosphorylation regulates kinetochore-microtubule attachment stability independently of the Ska complex. Finally, we map the location of the Ska complex in cells to a region near the coiled-coil domain of the NDC80 complex, and demonstrate that this region is required for Ska complex recruitment to the NDC80 complex-microtubule interface.
A microplate screen to estimate metal-binding affinities of metalloproteins
Authors: Diep Patrick , Mahadevan Radhakrishnan , Yakunin Alexander F.
Published: October 2019

Solute-binding proteins (SBPs) from ATP-binding cassette (ABC) transporters play crucial roles across all forms of life in transporting compounds against chemical gradients. Some SBPs have evolved to scavenge metal substrates from the environment with nanomolar and micromolar affinities (KD). There exist well established techniques like isothermal titration calorimetry for thoroughly studying these metalloprotein interactions with metal ions, but they are low-throughput. For protein libraries comprised of many metalloprotein homologues and mutants, and for collections of buffer conditions and potential ligands, the throughput of these techniques is paramount. In this study, we describe an improved method termed the microITFQ-LTA and validated it using CjNikZ, a well-characterized nickel-specific SBP (Ni-BP) from Campylobacter jejuni. We then demonstrated how the microITFQ-LTA can be designed to screen through a small collection of buffers and ligands to elucidate the binding profile of a putative Ni-BP from Clostridium carboxidivorans that we call CcSBPII. Through this study, we showed CcSBPII can bind to various metal ions with KD ranged over 3 orders of magnitude. In the presence of L-histidine, CcSBPII could bind to Ni2+ over 2000-fold more tightly, which was 11.6-fold tighter than CjNikZ given the same ligand.

Highlights

an improved version of a high-throughput screen (microITFQ-LTA) is described for multiplexed elucidation of metalloprotein binding profiles

validation was accomplished with the previously characterized CjNikZ; testing was accomplished with an uncharacterized homologue herein named CcSBPII

CcSBPII is shown to bind to multiple transition metal ions with a large range of affinities, and potentially overcome mismetallation using a simple histidine metallophore
Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins
Authors: Tayri-Wilk Tamar , Slavin Moriya , Zamel Joanna , Blass Ayelet , Cohen Shon , Motzik Alex , Sun Xue , Shalev Deborah E. , Ram Oren , Kalisman Nir
Published: October 2019

Formaldehyde is a widely used fixative in biology and medicine. The current mechanism of formaldehyde cross-linking of proteins is the formation of a methylene bridge that incorporates one carbon atom into the link. Here, we present mass spectrometry data that largely refute this mechanism. Instead, the data reveal that cross-linking of structured proteins mainly involves a reaction that incorporates two carbon atoms into the link. Under MS/MS fragmentation, the link cleaves symmetrically to yield previously unrecognized fragments carrying a modification of one carbon atom. If these characteristics are considered, then formaldehyde cross-linking is readily applicable to the structural approach of cross-linking coupled to mass spectrometry. Using a cross-linked mixture of purified proteins, a suitable analysis identifies tens of cross-links that fit well with their atomic structures. A more elaboratein situcross-linking of human cells in culture identified 469 intra-protein and 90 inter-protein cross-links, which also agreed with available atomic structures. Interestingly, many of these cross-links could not be mapped onto a known structure and thus provide new structural insights. For example, two cross-links involving the protein βNAC localize its binding site on the ribosome. Also of note are cross-links of actin with several auxiliary proteins for which the structure is unknown. Based on these findings we suggest a revised chemical reaction, which has relevance to the reactivity and toxicity of formaldehyde.
Cross-kingdom regulation of tRNAs/tRFs derived from Chinese yew
Authors: Cao Kai-Yue , Yan Tong-Meng , Zhang Ji-Zhou , Chan Ting-Fung , Li Jie , Li Chong , Leung Elaine Lai-Han , Jiang Zhi-Hong
Published: October 2019

Plants containing countless chemical constituent have benefited mankind since the origin of life. Although secondary metabolites in plants, such as morphine, artemisinin and taxol, have been developed as therapeutic drugs for clinical therapy, few study focuses on the pharmacological activities of plant small RNAs with function of cross-kingdom regulations. Yew is widely considered as a “superstar” plant due to the discovery of paclitaxel, or taxol, which is a well-known natural drug for the treatment of multiple types of cancer1. Here we show the surprising finding that an RNA fragment, named tRF-T11, derived from tRNAHis(GUG) of Chinese yew strongly suppressed human ovarian cancer progression. In A2780 cells, tRF-T11 mimic (a double-stranded RNA with tRF-T11 as antisense chain) exhibited potent cytotoxicity comparable to that of taxol, but no significant cytotoxicity to normal ovarian surface epithelial cells. Moreover, the cytotoxicity of tRF-T11 mimic is 80-fold stronger than that of taxol in taxol-resistant A2780 cells. Bioinformatic and molecular biological studies revealed that tRF-T11 targets transient receptor potential cation channel subfamily A member 1 (TRPA1) to inhibit its expression levels. In a further in vivo investigation, the growth rate of ovarian tumor xenografts in nude mice was significantly reduced by treatment with tRF-T11 mimic, and the TRPA1 protein expression in tumors treated with tRF-T11 mimic was also down-regulated. Our findings are the first to provide evidence that plant-derived tRFs can regulate the expression of target genes in vitro and in vivo, indicating that they may become as a new source of druggable siRNA. Moreover, this discovery demonstrated a pilot example of an innovative approach for not only identifying pharmacologically-active tRFs from plants, but also for improving the efficiency and possibilities of discovering new drug target.
2′-5′-Oligoadenylate synthetase-like protein inhibits intracellular M. tuberculosis replication and promotes proinflammatory cytokine secretion
Authors: Leisching G. , Ali A. , Cole V. , Baker B.
Published: October 2019

Host cytoplasmic surveillance pathways are known to elicit type I interferon (IFN) responses which are crucial to antimicrobial defense mechanisms. Oligoadenylate synthetase-like (OASL) protein has been extensively characterized as a part of the anti-viral mechanism, however a number of transcriptomic studies reveal its upregulation in response to infection with a wide variety of intracellular bacterial pathogens. To date, there is no evidence documenting the role (if any) of OASL during mycobacterium tuberculosis infection. Using two pathogenic strains differing in virulence only, as well as the non-pathogenic M. bovis BCG strain, we observed that pathogenicity and virulence strongly induced OASL expression after 24 h of infection. Further, we observed that OASL knock down led to a significant increase in M. tb CFU counts 96 h post-infection in comparison to the respective controls. Luminex revealed that OASL silencing significantly decreased IL-1β, TNF-α and MCP-1 secretion in THP-1 cells and had no effect on IL-10 secretion. We therefore postulate that OASL regulates pro-inflammatory mediators such as cytokines and chemokines which suppress intracellular mycobacterial growth and survival.
A structure equation model of indicators driving BIM adoption in the Bahraini construction industry
Authors: Ahmed Shurooq H.A. , Suliman Saad M.A.
Published: October 2019

Purpose

This study aims to establish an adoption model using Structural Equation Modeling (SEM) that examines the relationship between several key indicators that drive building information modeling (BIM) adoption.

Design/methodology/approach

The study was carried out using quantitative approaches through the Delphi method and questionnaire survey. A total of 272 completed responses were collected and analyzed through the SEM technique using SPSS 25 and AMOS software.

Findings

The structural model shows that “environment” and partially “people” indicators are the leading indicators driving BIM adoption with path coefficient values of 0.280 and 0.332, respectively.

Originality/value

It is expected that these conclusions will lead the Bahraini construction industry stakeholders to raise the level of BIM adoption.