bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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

AbstractRoot 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

ABSTRACTEnzymatic 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

AbstractTissue 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

AbstractThe 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

AbstractSolute-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.Highlightsan improved version of a high-throughput screen (microITFQ-LTA) is described for multiplexed elucidation of metalloprotein binding profilesvalidation was accomplished with the previously characterized CjNikZ; testing was accomplished with an uncharacterized homologue herein named CcSBPIICcSBPII 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

AbstractFormaldehyde 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.