bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open-label placebo for chronic low back pain: a 5-year follow-up
Authors: Carvalho Claudia , Pais Maria , Cunha Lidia , Rebouta Paula , Kaptchuk Ted J. , Kirsch Irving 
Published: December 2020

Abstract
Long-term follow-up of patients treated with open-label placebo (OLP) are nonexistent. In this article, we report a 5-year follow-up of a 3-week OLP randomized controlled trial (RCT) in patients with chronic low back pain. We recontacted the participants of original RCT and reassessed their pain, disability, and use of pain medication. We obtained follow-up data from 55 participants (82% of those who took OLP during the parent RCT), with a mean elapsed time between the end of the 3 weeks placebo trial and the follow-up interview of 55 months (SD = 7.85). We found significant reductions in both pain and disability between the baseline assessment immediately before the 3 weeks trial with placebo pills and the original trial endpoint (P < 0.00001 for the 2 primary outcomes of pain and disability). At the 5-year follow-up, we found no significant differences in either outcome between original trial endpoint and follow-up. Improvements persisted after 5 years and were accompanied by substantial reductions compared with baseline in the use of pain medication (from 87% to 38%), comprising analgesics (from 80% to 31%), antidepressants (from 24% to 11%), and benzodiazepines (from 15% to 5%). By contrast, the use of alternative approaches to pain management increased (from 18% to 29%). Although the reduction in pain and medication is comparable with the improvements that occurred in the original study, a major limitation of this long-term follow-up is the absence of controls for spontaneous improvement and new cointerventions. Nonetheless, our data suggest that reductions in pain and disability after OLP may be long lasting.
Who Is Practicing Expedited Partner Therapy and Why? Insights From Providers Working in Specialties With High Volumes of Sexually Transmitted Infections
Authors: McCool-Myers Megan , Goedken Peggy , Henn Megan C. , Sheth Anandi N. , Kottke Melissa J. 
Published: December 2020

Background
Expedited partner therapy (EPT), the practice of prescribing antibiotics for sexual partners of patients, is underutilized in Georgia. This qualitative study in a large urban institution aimed to (1) characterize the clinical specialties that predominantly treat sexually transmitted infections (STIs), (2) identify perceived barriers to EPT, and (3) describe strategies to advance routine EPT use.

Methods
Providers in obstetrics/gynecology (OB/GYN), infectious disease (ID), and emergency medicine (EM) were interviewed using a structured discussion guide. Transcripts were double-coded and iteratively analyzed using qualitative content analysis. Barriers and strategies were summarized and supported with quotes from providers (n = 23).

Results
Perceived EPT barriers overlapped across OB/GYN, ID, and EM, yet the settings were diverse in their patient populations, resources, and concerns. Providers in OB/GYN were the only ones practicing EPT, yet there was a lack of standardization. Providers in ID noted that an EPT prescription from an ID provider could inadvertently disclose the HIV status of a patient to a sexual partner, posing an ethical dilemma. Providers in EM exhibited readiness for EPT, although routine empiric treatment for index patients in EM (estimated at 90%) gave some providers pause in prescribing for partners: “I do not know what I’m treating.” Point-of-care testing could increase providers’ confidence in prescribing EPT, yet some worried it could contribute to overutilization of the emergency department as a sexually transmitted infection clinic. All settings prioritized setting-specific training and protocols.

Conclusions
Providers in OB/GYN, ID, and EM report unique hurdles, specific to their settings and patient populations; tailored EPT implementation strategies, particularly provider training, are urgently needed to improve patient/partner outcomes.
Brief Report: Impact of ART on Maternal Health After Cessation of Breastfeeding
Authors: Brummel Sean S. , Taha Taha E. , Angelidou Konstantia (Nadia) , Saidi Friday , Atuhaire Patience , Dula Dingase , Moodley Dhayendre , Matubu Allen , Chareka Gift , Nevrekar Neetal , Vhembo Tichaona , Fairlie Lee , Theron Gerhard , Mlay Pendo , George Kathleen , Basar Michael , Chakhtoura Nahida , Browning Renee , Fowler Mary Glenn , Currier Judith S. ,   for the IMPAACT 1077BF/FF PROMISE Study Team
Published: December 2020

Abstract:
IMPAACT PROMISE 1077BF/FF was a sequentially randomized study of pregnant and postpartum women living with HIV to investigate the efficacy and safety of antiretroviral therapy (ART). This Maternal Health Component investigated efficacy for the risk of developing AIDS or death; and safety among women randomized to continue ART (CTART: N = 289) or discontinue ART (N = 268) after cessation of breastfeeding or after confirmation of infant infection. No AIDS-defining illnesses were reported during follow-up in either arm. Adverse events of grade 3 or higher were more frequent in the CTART arm [hazard ratio = 1.78, 95% confidence interval: (1.05 to 3.02), P-value = 0.03]. The difference in adverse events in the 2 groups was mostly driven by moderate weight loss for women on the CTART arm.
Trauma results in immune cell-induced intestinal epithelial damage with subsequently increased sepsis rate
Authors: Mauser Martin , Kruger Deirdré , Pather Sugeshnee , Plani Frank 
Published: December 2020

BACKGROUND
The detrimental effect of trauma on the immune system has been a subject of interest for decades. The gut-associated lymphoid tissue (GALT) of the bowel that encompasses different lymphocyte subpopulations may be an important pillar of human immunity in the context of trauma. Neither the short-term histological trauma-induced changes in the GALT nor its impact on the outcome after trauma surgery has been investigated.

METHODS
This prospective, longitudinal proof-of-concept study included patients who required damage-control surgery after abdominal gunshot wounds with small bowel involvement. Bowel specimens were obtained during the index and relook operations, and the T-lymphocytic quantity therein was analyzed via immunohistochemistry. We scrutinized how the lymphocyte structure and numbers of the GALT altered, and whether the extent and nature of these changes had an impact on the postoperative outcome with regard to septic and surgical complications.

RESULTS
A total of 31 damage-control patients were recruited for the study. The main histological changes between the index and relook specimen was a shift of CD8+ T cells from the lamina propria (LP) into the epithelium and a decrease of T lymphocytes in the LP. The significant increase of the intraepithelial CD8+ T cells was associated with a more extensive enterocyte apoptosis, and correlated significantly, positively with the number of postoperative septic complications.

CONCLUSION
Our data support that trauma induces an immune cell-driven impairment of the intestinal epithelium, as well as an increased apoptosis of lymphocytes in the LP, which is associated with a worse clinical outcome. The underlying mechanism suggests that a therapeutic approach to minimize apoptosis in the intestine may impact the outcome of severely injured trauma patients.

LEVEL OF EVIDENCE
Therapeutic/care/management, level lV.
Model-based evaluation of the impact of noncompliance with public health measures on COVID-19 disease control
Authors: Stoddard Madison , Van Egeren Debra , Johnson Kaitlyn , Rao Smriti , Furgeson Josh , White Douglas E. , Nolan Ryan P. , Hochberg Natasha , Chakravarty Arijit 
Published: December 2020

AbstractThe word ‘pandemic’ conjures dystopian images of bodies stacked in the streets and societies on the brink of collapse. Despite this frightening picture, denialism and noncompliance with public health measures are common in the historical record, for example during the 1918 Influenza pandemic or the 2015 Ebola epidemic. The unique characteristics of SARS-CoV-2—its high reproductive number (R0), time-limited natural immunity and considerable potential for asymptomatic spread—exacerbate the public health repercussions of noncompliance with biomedical and nonpharmaceutical interventions designed to limit disease transmission. In this work, we used game theory to explore when noncompliance confers a perceived benefit to individuals, demonstrating that noncompliance is a Nash equilibrium under a broad set of conditions. We then used epidemiological modeling to explore the impact of noncompliance on short-term disease control, demonstrating that the presence of a noncompliant subpopulation prevents suppression of disease spread. Our modeling shows that the existence of a noncompliant population can also prevent any return to normalcy over the long run. For interventions that are highly effective at preventing disease spread, however, the consequences of noncompliance are borne disproportionately by noncompliant individuals. In sum, our work demonstrates the limits of free-market approaches to compliance with disease control measures during a pandemic. The act of noncompliance with disease intervention measures creates a negative externality, rendering COVID-19 disease control ineffective in the short term and making complete suppression impossible in the long term. Our work underscores the importance of developing effective strategies for prophylaxis through public health measures aimed at complete suppression and the need to focus on compliance at a population level.
Effects of maternal deprivation and complex housing on pro-social behavior in rats: An automated, operant task examining motivation to liberate a trapped conspecific
Authors: Kalamari Aikaterini , Kentrop Jiska , Danesi Chiara Hinna , Graat Evelien J.M. , van IJzendoorn Marinus H. , Bakermans-Kranenburg Marian J. , Joëls Marian , van der Veen Rixt 
Published: December 2020

AbstractEarly life environment influences the development of various aspects of social behavior, particularly during sensitive developmental periods. Here, we aimed to study how challenges in the early postnatal period or (early) adolescence affect pro-social behavior. To this end, we adapted an existing paw operated liberation task to an automated operant task, to measure motivation (by progressively increasing required lever pressing) to liberate a trapped conspecific. Liberation of the trapped rat resulted either in social contact, or in liberation into a separate compartment. Additionally, a condition was tested in which both rats could freely move in two separate compartments and lever pressing resulted in social contact. When partners were not trapped, rats were more motivated to press the lever for opening the door than in either of the trapped configurations. Contrary to our expectation, the trapped configuration resulted in areducedmotivation to act. Early postnatal stress (24h maternal deprivation on postnatal day 3) did not affect behavior in the liberation task. However, rearing rats from early adolescence onwards in complex housing conditions (Marlau cages) reduced the motivation to door opening, both in the trapped and freely moving conditions, while motivation for a sucrose reward was not affected.
Chemical exhaustion of RPA in cancer treatment
Authors: VanderVere-Carozza Pamela S. , Pawelczak Katherine S. , Gavande Navnath S. , Jalal Shadia I. , Pollok Karen E. , Ekinci Elmira , Heyza Joshua , Patrick Steve M. , Turchi John J. 
Published: December 2020

AbstractReplication protein A (RPA) plays essential roles in DNA replication, repair, recombination and the DNA-damage response (DDR). We have developed second generation RPA inhibitors (RPAi’s) that block the RPA-DNA interaction. These DNA-binding inhibitors (DBi’s) can elicit a state of cellular RPA exhaustion resulting in single agentin vitroanticancer activity across a broad spectrum of cancers andin vivoactivity in two non-small cell lung cancer models. The cellular response to RPAi treatment suggests a threshold exists before RPA inhibition induces cell death. Chemical RPA exhaustion potentiates the anticancer activity of other DDR inhibitors as well as traditional DNA damaging cancer therapeutics. Consistent with the chemical RPA exhaustion model, we demonstrate that the effects of RPAi on replication fork dynamics and DNA damage signaling are similar to other known DDR inhibitors. In accordance with the RPA threshold model, retrospective analysis of lung cancer patient data demonstrates high RPA expression as a negative prognostic biomarker for overall survival in smoking-related lung cancers. Similarly, relative expression of RPA is a predictive marker for response to chemotherapy. These observations are consistent with the increase in RPA expression serving as an adaptive mechanism that allows tolerance of the genotoxic stress resulting from carcinogen exposure. These data demonstrate a unique mechanism of action of RPAi’s eliciting a state of RPA exhaustion that impacts the DDR and may provide an effective therapeutic option for difficult to treat lung cancers.Graphical Abstract
Modified N-linked glycosylation status predicts trafficking defective human Piezo1 channel mutations
Authors: Li Jinyuan Vero , Ng Chai-Ann , Cheng Delfine , Yao Mingxi , Guo Yang , Yu Ze-Yan , Ramaswamy Yogambha , Ju Lining Arnold , Kuchel Philip W , Feneley Michael P , Fatkin Diane , Cox Charles D 
Published: December 2020

AbstractMechanosensitive channels are integral membrane proteins that sense mechanical stimuli. Like all membrane proteins, they pass through biosynthetic quality control in the endoplasmic reticulum and Golgi that results in them reaching their destination at the plasma membrane. Here we show that N-linked glycosylation of two highly conserved asparagine residues in the ‘cap’ region of mechanosensitive Piezo1 channels are necessary for the mature protein to reach the plasma membrane. Both mutation of these asparagines (N2294Q/N2331Q) and treatment with an enzyme that hydrolyses N-linked oligosaccharides (PNGaseF) eliminates the fully glycosylated mature Piezo1 protein. The N-glycans in the cap are a pre-requisite for higher-order glycosylation in the ‘propeller’ regions, which are present in loops that are essential for mechanotransduction. Importantly, trafficking-defective Piezo1 variants linked to generalized lymphatic dysplasia and bicuspid aortic valve display reduced fully N-glycosylated protein. The higher order glycosylation statusin vitrocorrelates with efficient membrane trafficking and will aid in determining the functional impact of Piezo1 variants of unknown significance.
Subtle changes in crosslinking drive diverse anomalous transport characteristics in actin-microtubule networks
Authors: Anderson S. J. , Garamella J. , Adalbert S. , McGorty R. J. , Robertson-Anderson R. M. 
Published: December 2020

AbstractAnomalous diffusion in crowded and complex environments is widely studied due to its importance in intracellular transport, fluid rheology and materials engineering. Specifically, diffusion through the cytoskeleton, a network comprised of semiflexible actin filaments and rigid microtubules that interact both sterically and via crosslinking, plays a principal role in viral infection, vesicle transport and targeted drug delivery. Here, we elucidate the impact of crosslinking on particle diffusion in composites of actin and microtubules with actin-actin, microtubule-microtubule and actin-microtubule crosslinking. We analyze a suite of complementary transport metrics by coupling single-particle tracking and differential dynamic microscopy. Using these orthogonal techniques, we find that particles display non-Gaussian and non-ergodic subdiffusion that is markedly enhanced by cytoskeletal crosslinking of any type, which we attribute to suppressed microtubule mobility. However, the extent to which transport deviates from normal Brownian diffusion depends strongly on the crosslinking motif – with actin-microtubule crosslinking inducing the most pronounced anomalous characteristics – due to increased actin fluctuation heterogeneity. Our results reveal that subtle changes to actin-microtubule interactions can have dramatic impacts on diffusion in the cytoskeleton, and suggest that less mobile and more locally heterogeneous networks lead to more strongly anomalous transport.
AC. elegansgenome-wide RNAi screen for altered levamisole sensitivity identifies genes required for muscle function
Authors: Chaya Timothy , Patel Shrey , Smith Erin M. , Lam Andy , Miller Elaine N. , Clupper Michael , Kervin Kirsten , Tanis Jessica 
Published: December 2020

AbstractAt the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at theCaenorhabditis elegansNMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homologepn-1had opposing effects on the levels of postsynaptic L-AChRs and GABAAreceptors, resulting in increased and decreased abundance, respectively. This disrupts the balance of postsynaptic excitatory and inhibitory signaling, causing levamisole hypersensitivity. We also examined other genes that resulted in a levamisole hypersensitive phenotype when knocked down includinggas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.
Implementing process improvement initiative: the role of visualisation and standardisation methods
Authors: Abubakre Mumin , Fayoumi Amjad , Eleburuike Ismail 
Published: December 2020

PurposeDue to the difficulties organisations face in implementing process improvement initiatives (PIIs), this research explores how visualisation and standardisation of business processes help organisations achieve PIIs to improve organisational performance.Design/methodology/approachA multi-staged case study strategy that analyse qualitative data and performs a process modelling analysis of quantitative data.FindingsThe paper makes two main contributions to existing knowledge. Firstly, it explains how taking the visualised and standardised methods on PIIs can reduce service delivery times and enhance organisational performance. Secondly, it demonstrates how adopting these dual methods offers a better chance of increasing organisational performance than using only a single method.Research limitations/implicationsAlthough the paper considers the flexibility in the standardisation of business processes as it gives scope for innovation and creativity on the part of the process, it did not consider if flexibility is possible without breaking the standardised working way. Hence, future research can consider this. Also, future research can hypothesise the BPM model and test for statistical generalisability.Originality/valueThe research offers new insight into how and when both visualisation and standardisation of PIIs can benefit organisations.
Effects of the poverty alleviation relocation program on diet quality among low-income households
Authors: Qiu Huanguang , Leng Ganxiao , Feng Xiaolong , Yang Sansi 
Published: December 2020

PurposeThis paper aims to examine impacts of the poverty alleviation relocation (PAR) program on diet quality of low-income households in China. We explore the impact mechanism of relocation on diet quality and the heterogeneous effects of different relocation modes.Design/methodology/approachA fixed effects model is constructed using panel data of 1126 low-income households collected over three years in eight provinces of China. The PAR program provides a natural experiment which dramatically changes the living conditions surrounding farmers. We are able to identify the causal effects of relocation on diet quality free from selection bias.FindingsThe empirical results show that the PAR program improves diet quality of low-income households and that better market access and increasing incomes induced by relocation play an important role in this improvement. Improved market access significantly reduces the over-consumption of staple foods, whereas higher income significantly reduces the intake divergences of non-staple foods. The impacts of different relocation modes on diet quality are highly heterogeneous.Practical implicationsOur findings indicate that the PAR program benefits diet quality of low-income households through greater market access and increases in total household income. Market improvements and food subsidies are conducive to improving the diet quality of the low income.Originality/valueDespite widespread evidences of healthy diets being associated with household environments and income, selection bias remains. This paper utilizes an exogenous program to explore the causal impacts of market access and family income on diet quality and to separate their different effects.
Article 786 of the Jordanian civil code: a potential gold mine for employers and a potential minefield for contractors
Authors: Haloush Haitham A. , Alhusban Ahmad Abed Alla , Massadeh Ali Abdel Mahdi 
Published: December 2020

Purpose
This paper aims to highlight how the prevention principle may affect the rights and responsibilities of contractors under Jordanian law. In many instances, the application of legal theories and terminology of the Jordanian civil code (JCC), such as penalty clauses and produces a similar result to that under common law, such as prevention principle, and even if in some cases the route by which the result is reached differs.

Design/methodology/approach
This paper is based upon library research on primary and secondary sources. The author adopted the interpretive paradigm with its underlying subjectivist assumption. This paradigm creates different meanings and therefore different realities. This is particularly evident when studying legal notions, such as parties’ autonomy and decennial liability, from a comparative law perspective.

Findings
In many instances, the application of legal theories and terminology of the JCC, such as penalty clauses and produces a similar result to that under common law, such as the prevention principle, and even if in some cases the route by which the result is reached differs. However, it is difficult for judges and lawyers in Jordan to understand the legal principles of certain terms in the common law. This requires, to a certain extent, an understanding of the legal terms and concepts, particularly those originated from English law. For example, a thorough grasp of the prevention principle in Jordanian law remains unclear. Apparently, this can be met by training and capacity building sessions.

Originality/value
As far as the author is aware, this issue has not been researched comprehensively before from technical and legal standpoints. This paper represents the first attempt to examine the issues arising in this difficult and important subject.