bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain perception with cervical tenaculum placement during intrauterine device insertion: a randomised controlled trial
Authors: Lambert Tashima , Truong Tracy , Gray Beverly 
Published: October 2019

Introduction'Slow’ and ‘cough’ techniques for tenaculum placement are commonly used. This trial sought to determine if one method of placement resulted in less pain for patients.MethodsThis study was a randomised controlled trial of patients presenting for intrauterine device placement. Sixty-six participants were randomised to tenaculum placement via the 'slow' method (closure of tenaculum over a 5-s period) versus the 'cough' method (closure of tenaculum at the time of patient’s cough). The primary outcome was pain at time of tenaculum placement measured on a 100 mm visual analogue scale. The study was powered to detect a 16 mm difference in pain. Secondary outcomes included pain with insertion and provider satisfaction with tenaculum grasp. Pain scores were analysed with Wilcoxon rank-sum test.ResultsSixty-six women were enrolled, 33 randomised to each group. Demographics were similar in each group. The primary outcome of pain with tenaculum placement showed a median pain score of 44 (IQR=21, 63) with slow placement and 32 (IQR=19, 54) with cough placement. There was no significant difference in pain scores between methods of tenaculum placement (p=0.16). There was no significant difference in overall pain scores (p=0.12). Provider satisfaction was not associated with one method of placement (p=1). Pre-procedure anxiety was significantly associated with pain at the time of tenaculum placement (p=0.01).ConclusionsNeither the slow method nor cough method is superior for pain reduction or provider satisfaction. Pain with tenaculum use is significantly associated with anxiety.Clinical trial registrationNCT02969421.
The “T’s” of snakebite injury in the USA: fact or fiction?
Authors: Jaramillo Joshua D , Hakes Nicholas A , Tennakoon Lakshika , Spain David , Forrester Joseph D 
Published: October 2019

BackgroundVenomous snakebites can result in serious morbidity and mortality. In the USA, the “T’s of snakebites” (testosterone, teasing, touching, trucks, tattoos & toothless (poverTy), Texas, tequila, teenagers, and tanks) originate from anecdotes used to colloquially highlight venomous snakebite risk factors. We performed an epidemiologic assessment of venomous snakebites in the USA with the objective of evaluating the validity of the “T’s of snakebites” at a national level.MethodsWe performed a retrospective analysis of the National Emergency Department Sample. Data from January 1, 2016 to December 31, 2016 were obtained. All emergency department (ED) encounters corresponding to a venomous snakebite injury were identified using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes. Primary outcomes were mortality and inpatient admission. Demographic, injury, and hospital characteristics were assessed. Data were analyzed according to survey methodology. Weighted values are reported.ResultsIn 2016, 11 138 patients presented to an ED with a venomous snakebite. There were 4173 (37%) persons aged 18 to 44, and 7213 (65%) were male. Most snakebites were reported from the South (n=9079; 82%), although snakebites were reported from every region in the USA. Only 3792 (34%) snakebites occurred in rural counties. Persons in the lowest income quartile by zip code were the most heavily represented (n=4337; 39%). The most common site of injury was the distal upper extremity (n=4884; 44%). Multivariate analysis revealed that species of snake (OR=0.81; 95% CI 0.73 to 0.88) and older age (OR=1.42; 95% CI 1.08 to 1.87) were associated with hospital admission. There were <10 inpatient deaths identified, and no variables were predictive of death.DiscussionSome of the “T’s of snakebites” may be valid colloquial predictors of the risk for venomous snakebites. Based on national data, common demographics of venomous snakebite victims include lower income, Caucasian, and adult men in the South who are bit on the upper extremity. Understanding common demographics of venomous snakebite victims can effectuate targeted public health prevention messaging.Level of evidenceIV.
Pain management of a mandibular fracture in an alpaca (Vicugna pacos) via epidural catheter placement in the mandibular foramen
Authors: Stathopoulou Thaleia , Seymour Christopher , McSloy Alex , Adams James , Viscasillas Jaime 
Published: October 2019

A nine‐year‐old female alpaca with a history of a recurrent tooth root abscess presented for further investigation of a swelling of the left mandible and possible tooth extraction. During the manipulation of the mandible in surgery, the mandibular body fractured, and due to active infection it was left to heal by secondary intention. After surgery, the alpaca became dull and inappetent. Analgesic drugs included buprenorphine and meloxicam, which were ineffective according to the alpaca’s clinical appearance. An inferior alveolar nerve block was achieved by repeated administration of local anaesthetic (ropivacaine 0.75 per cent) every six hours via an epidural catheter placed in the mandibular foramen under CT guidance. Despite the adequate level of comfort achieved, discharge from surgical site resumed and the owner elected euthanasia. In conclusion, the placement of an epidural catheter in the mandibular canal, under CT guidance, was proven to successfully provide analgesia to an alpaca suffering from mandibular fractures.
A Coumarin-Based Fluorescence Probe for Selective Recognition of Cu2+ Ions and Live Cell Imaging
Authors: He Guangjie , Ma Nana , Li Linlin , Xie Chenyan , Yang Linlin , Xu Jinhe , Wang Junli 
Published: October 2019

A new fluorescence probe L was rationally designed and synthesized for the recognition of Cu2+ ions by the combination of coumarin hydrazide and 2-acetylpyrazine. The photochemical properties and selectivity of L for Cu2+ ions in a CH3CN/HEPES (3 : 2, v/v) buffer were investigated by UV-vis absorption and fluorescence emission spectra. A highly selective and sensitive response of L for Cu2+ ions over other competing metal ions was observed with limit of detection in 3 μM. The coordination stoichiometry of L to Cu2+ ions was determined to be 1 : 1 by the UV-vis absorption spectrum, the fluorescence titrations, and density functional theory (DFT) calculations. Moreover, L was applied successfully for recognition of intracellular Cu2+ ions in living cells.
Night-Shift Work Duration and Risk of Colorectal Cancer According to IRS1 and IRS2 Expression
Authors: Shi Yan , Liu Li , Hamada Tsuyoshi , Nowak Jonathan A. , Giannakis Marios , Ma Yanan , Song Mingyang , Nevo Daniel , Kosumi Keisuke , Gu Mancang , Kim Sun A. , Morikawa Teppei , Wu Kana , Sui Jing , Papantoniou Kyriaki , Wang Molin , Chan Andrew T. , Fuchs Charles S. , Meyerhardt Jeffrey A. , Giovannucci Edward , Ogino Shuji , Schernhammer Eva S. , Nishihara Reiko , Zhang Xuehong 
Published: October 2019

Abstract

Background:
We hypothesized that the risk of colorectal cancer in night-shift workers might be different according to insulin receptor substrate status.

Methods:
Among 77,470 eligible women having night work assessed in the Nurses' Health Study, we documented a total of 1,397 colorectal cancer cases, of which 304 or 308 had available data on IRS1 and IRS2, respectively. We used duplication-method Cox proportional hazards regression analysis for competing risks to calculate HRs and 95% confidence intervals (CI) for each colorectal cancer subtype. We measured tumor IRS1 or IRS2 expression by immunohistochemistry (IHC).

Results:
Compared with women who never worked night shifts, those working ≥15 years night shifts had a marginal trend of increased overall risk of colorectal cancer (Ptrend = 0.06; multivariable HR = 1.20; 95% CI, 0.99–1.45). Longer duration of night-shift work was associated with a higher risk of IRS2-positive tumors (multivariable HR = 2.69; 95% CI, 1.48–4.89; Ptrend = 0.001, ≥15 years night shifts vs. never) but not with IRS2-negative tumors (multivariable HR = 0.90; 95% CI, 0.54–1.51; Ptrend = 0.72; Pheterogeneity for IRS2 = 0.008). Similarly, the corresponding multivariable HRs were 1.81 for IRS1-positive tumors (95% CI, 0.94–3.48; Ptrend = 0.06) and 1.13 for IRS1-negative tumors (95% CI, 0.71–1.80; Ptrend = 0.56; Pheterogeneity for IRS1 = 0.02).

Conclusions:
Our molecular pathologic epidemiology data suggest a potential role of IRS in mediating carcinogenesis induced by night-shift work.

Impact:
Although these findings need validation, rotating night shift might increase colorectal cancer risk in women with abnormal insulin receptor pathways.
Impact and Cost-Effectiveness of Human Papillomavirus Vaccination Campaigns
Authors: Portnoy Allison , Campos Nicole G. , Sy Stephen , Burger Emily A. , Cohen Jamie , Regan Catherine , Kim Jane J. 
Published: October 2019

Abstract

Background:
Data to inform evidence-based policy of human papillomavirus (HPV) vaccine delivery strategies in low- and middle-income countries are limited. We examined the cost-effectiveness of campaign compared with routine delivery strategies of adolescent female HPV vaccination in Uganda.

Methods:
We used a multiple modeling approach that captured HPV transmission, cervical carcinogenesis, and population demographics to project health and economic outcomes associated with HPV vaccination. Costs included vaccination and operational costs and cervical cancer costs over the lifetimes of the current female population in Uganda. Health outcomes included number of cervical cancer cases and disability-adjusted life years (DALY). Incremental cost-effectiveness ratios (i.e., cost per DALY averted) were calculated and compared against gross domestic product (GDP) per capita.

Results:
Compared with routine HPV vaccination of 9-year-old girls at 70% coverage, campaign vaccination yielded greater health benefits if campaigns occurred frequently and targeted a wide age range. Campaign delivery strategies were both less costly and more effective than routine HPV vaccination. Campaign vaccination of 9- to 30-year-old girls/women at a 3-year frequency (40% coverage) was considered cost-effective compared with the GDP per capita threshold for Uganda ($674 in U.S. 2015 dollars).

Conclusions:
We projected that campaign HPV vaccination would provide substantial population health benefits compared with routine vaccination. Expanding the target age range of campaign vaccination up to age 30 years may be an efficient strategy, depending on the achievable coverage level and campaign frequency.

Impact:
In settings where routine health systems infrastructure may be limited, reaching adolescent populations with a campaign delivery strategy may be an efficient use of resources.
Understanding the Right to Try Act
Authors: Agarwal Rajiv , Saltz Leonard B. 
Published: October 2019

Abstract
Patients with cancer who have exhausted standard treatments often seek access to investigational drugs. Often, however, such access is unavailable, due to either the unavailability of a trial, lack of an open recruiting spot on the trial, even when the trial itself is open, or the inability of the patient to meet one or more trial eligibility criteria. In such settings patients often seek access to investigational agents outside of a trial. The federal “Right to Try” legislation was passed to create an additional avenue, different from the FDA's Expanded Access, or “Compassionate Use” Program, through which patients might obtain access to investigational drugs. A year after this legislation was signed into law, there remains both a limited awareness of it and a substantial degree of misunderstanding on the part of those who are aware of it. The law creates an avenue to greatly facilitate off-study administration when patient, physician, and the manufacturer are all in agreement regarding the off study use of an eligible investigational agent. The law does not, however, empower a patient to impose a demand on either a provider or a drug manufacturer, nor does it require any entity to provide financial coverage for the drug. Eligible drugs are those which are not approved by the FDA for any indication, have completed a phase I trial, have an ongoing pivotal trial, and have an active registration plan. We review the specific law with commentary on its implications for improved access to investigational drugs outside of clinical trials.
Clinical Utility of Plasma Cell-Free DNA in Adult Patients with Newly Diagnosed Glioblastoma: A Pilot Prospective Study
Authors: Bagley Stephen J. , Nabavizadeh S. Ali , Mays Jazmine J. , Till Jacob E. , Ware Jeffrey B. , Levy Scott , Sarchiapone Whitney , Hussain Jasmin , Prior Timothy , Guiry Samantha , Christensen Theresa , Yee Stephanie S. , Nasrallah MacLean P. , Morrissette Jennifer J.D. , Binder Zev A. , O'Rourke Donald M. , Cucchiara Andrew J. , Brem Steven , Desai Arati S. , Carpenter Erica L. 
Published: October 2019

AbstractPurpose:The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS).Experimental Design:We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel.Results:Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P &lt; 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (&gt;13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053).Conclusions:Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.
XPO1 Inhibitor Selinexor Overcomes Intrinsic Ibrutinib Resistance in Mantle Cell Lymphoma via Nuclear Retention of IκB
Authors: Ming Mei , Wu Wenjun , Xie Bingqing , Sukhanova Madina , Wang Weige , Kadri Sabah , Sharma Shruti , Lee Jimmy , Shacham Sharon , Landesman Yosef , Maltsev Natalia , Lu Pin , Wang Y. Lynn 
Published: October 2019

Abstract
Inhibition of B-cell receptor (BCR) signaling through the BTK inhibitor, ibrutinib, has generated a remarkable response in mantle cell lymphoma (MCL). However, approximately one third of patients do not respond well to the drug, and disease relapse on ibrutinib is nearly universal. Alternative therapeutic strategies aimed to prevent and overcome ibrutinib resistance are needed. We compared and contrasted the effects of selinexor, a selective inhibitor of nuclear export, with ibrutinib in six MCL cell lines that display differential intrinsic sensitivity to ibrutinib. We found that selinexor had a broader antitumor activity in MCL than ibrutinib. MCL cell lines resistant to ibrutinib remained sensitive to selinexor. We showed that selinexor induced apoptosis/cell-cycle arrest and XPO-1 knockdown also retarded cell growth. Furthermore, downregulation of the NFκB gene signature, as opposed to BCR signature, was a common feature that underlies the response of MCL to both selinexor and ibrutinib. Meanwhile, unaltered NFκB was associated with ibrutinib resistance. Mechnistically, selinexor induced nuclear retention of IκB that was accompanied by the reduction of DNA-binding activity of NFκB, suggesting that NFκB is trapped in an inhibitory complex. Coimmunoprecipitation confirmed that p65 of NFκB and IκB were physically associated. In primary MCL tumors, we further demonstrated that the number of cells with IκB nuclear retention was linearly correlated with the degree of apoptosis. Our data highlight the role of NFκB pathway in drug response to ibrutinib and selinexor and show the potential of using selinexor to prevent and overcome intrinsic ibrutinib resistance through NFκB inhibition.
The Chronic Adverse Effect of Chloroquine on Kidney in Rats through an Autophagy Dependent and Independent Pathways
Authors: Wang Bin , Guo Honglei , Ling Lilu , Ji Jialing , Niu Jianying , Gu Yong 
Published: October 2019

<b><i>Background:</i></b> Chloroquine (CQ), a classic autophagy inhibitor, is used clinically for malaria prophylaxis and pulmonary hypertension treatment. The adverse effects of CQ on morphological and functional changes in the kidney were investigated in the current study due to CQ accumulation in the kidney. <b><i>Methods:</i></b> Twelve male Sprague-Dawley rats were randomly divided into 2 groups for 4 weeks: group 1, control (<i>n</i> = 6); and group 2, CQ administration group (50 mg<sup>–1</sup>·kg per day ip; <i>n</i> = 6). Serum aldosterone and vasopressin were measured by radioimmunoassay. Immunofluorescence was used to colocalize Tunel with aquaporin 1, aquaporin 2 (AQP2), and Tamm-Horsfall protein. Expression of AQP2 and mineralocorticoid (MR) was detected by western blot and immunohistochemistry. <b><i>Results:</i></b> In the present study, 4 weeks of CQ administration were shown to induce severe kidney injury, including glomerular sclerosis and tubular cells apoptosis, especially distal tubular cells. Decreased expression of LC3II/I and p-AKT was demonstrated in CQ-treated rats. Glomerular and proximal tubule injury were associated with impaired autophagy flux, and distal tubule injury may be associated with downregulated cyclic adenosine monophosphate (cAMP)/PKA/AKT signaling. Both MR and AQP2, which are mainly located in the distal tubule and collecting duct, were significantly reduced in CQ-treated rats, thus leading to increased exosomal secretion of AQP2 in urine. Additionally, chronic CQ administration increased aldosterone and vasopressin levels in serum, but lowered the blood pressure, glomerular filtration rate, and urine concentration. <b><i>Conclusions:</i></b> CQ administration damages glomerular, proximal tubule autophagy, and severe distal tubular cells apoptosis by inhibiting cAMP/PKA/AKT signaling.
Towards a History of the National-Popular in Bolivia, 1879–1980(Excerpt)
Authors: Zavaleta Mercado René 
Published: October 2019

Abstract
In this passage, Zavaleta describes the connections between the moment of real subsumption, social totalisation, the production of social-scientific knowledge that takes the resultant totality as its object, including Marxist theory, and finally, the emergence of a broad intersubjectivity with the capacity to become a revolutionary historical actor.
Ancient Art Meets Modern Science: American Medicine Investigates Acupuncture, 1970–1980
Authors: Jones Kelly Hacker 
Published: October 2019

Abstract
In the early 1970s, the so-called “acupuncture craze” swept America, introducing many Americans for the first time to this supposedly ancient therapy. Acupuncture was advertised as a cure-all, effective for everything from arthritis to smoking cessation, much to the dismay of the American Medical Association and other professional organizations. By April 1973, Nevada had passed a bill that legalized the use of acupuncture and established a State Board for Chinese Medicine, independent of its State Board for Medicine. In response, American physicians pursued two courses of action: they initiated biomedical studies that aimed at proving either a physiological or psychological effect generated by acupuncture, and they advocated for state-level regulations that restricted the use of acupuncture as an experimental therapy. Building on the work of historians of alternative medicine—including Anne Harrington and James Whorton—this paper contributes to our understanding of the position of alternative therapies within American medical practice.
The Life Sciences, 1900–2000: Analysis and Social Welfare from Mendel and Koch to Biotech and Conservation
Authors: Manning Patrick 
Published: October 2019

Abstract
The life sciences underwent a dramatic transformation during the twentieth century, with an expansion in fundamental knowledge of the process of evolution and its molecular basis, through advances in health care that greatly extended human life, and by the combination of these advances to address the problem of conserving the many forms of life threatened by expanding human society. The essay highlights the worldwide emphasis on social welfare in the years 1945–1980 and the expanding role of international collaboration, especially in the International Biological Program and its advances in ecology and the notion of the biosphere, and in the emergence of molecular biology. This was also the era of the Cold War, yet military confrontation had fewer implications for life sciences than for the natural sciences in that era. After 1980, deregulation and neoliberalism weakened programs for social welfare, yet links among the varying strands of life sciences continued to grow, bringing the development of genomics and its many implications, expanding epidemiology to include reliance on social sciences, and deepening ecological studies as the Anthropocene became more and more prevalent. In sum, the experience of the life sciences should make it clear to world historians that scientific advance goes beyond the achievements of brilliant but isolated researchers: those same advances rely substantially on social movements, migration, and the exchange of knowledge across intellectual and physical boundaries.
Historical Study of Societal Transformations in the Extended Indian Ocean Realm
Authors: Hall Kenneth R. 
Published: October 2019

Abstract
Western historiography placed the indigenous Asia beyond the court political centers and the most commercially prominent ports-of-trade in the background of an exogenous (colonial) foreground. Western historical research from the sixteenth century onward privileged selected aspects and voices of the exogenous, focusing on the Arabic and Persian Middle East, India, China, and the West, represented from the nineteenth century onward by the terms Islamization, Indianization, Sinification, and Westernization. Today, historians who study the Indian Ocean give “agency” to things indigenous when they are juxtaposed to things exogenous. Local activities, events, beliefs, institutions, communities, individuals, and historical narratives are emphasized, given weight, and “privileged” over dependency on the exogenous. Simply taking agency away from the exogenous and giving it to the indigenous may seem to be a more realistic approach to overcoming the “from the deck of a ship” critique, but the issue of emphasis and privileging at the expense of “another” remains. Historians researching the non-West have tempered their previously held stance on this issue and now admit the depth and scale of influence that major exogenous civilizations (e.g., the Middle East, China, India, and the West) have had on some local cultures.
Anahilapura: Understanding Its Expansive Network during the Time of the Chaulukyas
Authors: Ghosh Suchandra 
Published: October 2019

Abstract
Gujarat’s role in the international trade network has long been researched. During the first half of the second millennium CE, the Indian Ocean emerged as a vast trading zone; its western termini were Siraf/Basra/Baghdad in the Persian Gulf zone and Alexandria/Fustat (old Cairo) in the Red Sea area, while the eastern terminus extended up to the ports in China. However, this essay privileges a single place, Anahilapura, which acted as a hinterland to many of the ports of Gujarat.