bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of a Junior Faculty Fellowship Award on Academic Advancement and Retention
Authors: Connelly Maureen T. , Sullivan Amy M. , Chinchilla Manuel , Dale Margaret L. , Emans S. Jean , Nadelson Carol Cooperman , Notman Malkah Tolpin , Tarbell Nancy J. , Zigler Corwin M. , Shore Eleanor G. 
Published: January 2017

Purpose
Academic faculty experience barriers to career development and promotion. In 1996, Harvard Medical School (HMS) initiated an intramural junior faculty fellowship to address these obstacles. The authors sought to understand whether receiving a fellowship was associated with more rapid academic promotion and retention.

Method
Junior faculty fellowship recipients and all other instructor and assistant professors at HMS between 1996 and 2011 were identified. Using propensity score modeling, the authors created a matched comparison group for the fellowship recipients based on educational background, training, academic rank, department, hospital affiliation, and demographics. Time to promotion and time to leaving were assessed by Kaplan-Meier curves.

Results
A total of 622 junior faculty received fellowships. Faculty who received fellowships while instructors (n = 480) had shorter times to promotion to assistant professor (P < .0001) and longer retention times (P < .0001) than matched controls. There were no significant differences in time to promotion for assistant professors who received fellowships (n = 142) compared with matched controls, but assistant professor fellowship recipients were significantly more likely to remain longer on the faculty (P = .0005). Women instructors advanced more quickly than matched controls, while male instructors’ rates of promotions did not differ.

Conclusions
Fellowships to support junior faculty were associated with shorter times to promotion for instructors and more sustained faculty retention for both instructors and assistant professors. This suggests that relatively small amounts of funding early in faculty careers can play a critical role in supporting academic advancement and retention.
Immune checkpoint inhibitors in first-line therapy of advanced non-small cell lung cancer
Authors: Remon Jordi , Besse Benjamin 
Published: January 2017

Purpose of review
Evading immune destruction is a hallmark of cancer. The first therapeutic wave in immunotherapies comprised a series of monoclonal antibodies directed against the immune checkpoint molecules cytotoxic T-lymphocyte-associated protein 4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1) revolutionizing the therapeutic landscape of advanced non-small cell lung cancer. They were validated initially as second-line treatment, becoming the new standard of care.

Recent findings
Based on immunotherapies efficacy, different strategies are being successfully investigated in first-line treatment, including frontline immune checkpoint inhibitors, and combination with chemotherapy or with other immune checkpoint inhibitors. In accordance with recent results, US Food and Drug Administration approved a checkpoint inhibitor for first-line treatment of metastatic non-small cell lung cancer whose tumors have high PD-L1 expression, and European Medicines Agency approval is expected in early 2017.

Summary
In this review, we summarize the main results of the various strategic clinical development approaches used to date, as well as in ongoing clinical trials.
A review of serious adverse effects under treatment with checkpoint inhibitors
Authors: Heinzerling Lucie , Goldinger Simone M. 
Published: January 2017

Purpose of review
The aim of this article is to raise awareness of physicians for the serious side-effects of immune-checkpoint blocking antibodies. As checkpoint inhibitors can induce severe side-effects and are increasingly being used also in subspecialties besides dermatology and oncology, with less experience with these drugs available, knowledge has to be spread. Early recognition and adequate management is essential.

Recent findings
Recent reports on side-effects document cases of serious side-effects involving all organ systems. These include formerly little referenced and life-threatening side-effects such as cardiotoxicity and neurotoxicity. Furthermore, important additional findings are the inclusion of CMV reactivation in the differential diagnosis or the side-effect profile in special patient populations, that is, in transplant patients, patients with autoimmune disease or previous toxicity to ipilimumab.

Summary
Checkpoint inhibitor treatment induces a wide range of serious side-effects. However, with prompt diagnosis and adequate treatment these can mostly be safely managed. Documentation and reporting of serious side-effects remains important to share knowledge and thus ensure optimal patient care.
Squamous Cell Carcinoma In Situ Upstaged to Invasive Squamous Cell Carcinoma: A 5-Year, Single Institution Retrospective Review
Authors: Eimpunth Sasima , Goldenberg Alina , Hamman Michael Shane , Oganesyan Gagik , Lee Robert A. , Hunnangkul Saowalak , Song Silvia Soohyun , Greywal Tanya , Jiang Shang I Brian 
Published: January 2017

BACKGROUND
Shave biopsy may not be able to accurately distinguish squamous cell carcinoma in situ (SCCIS) from invasive squamous cell carcinoma (SCC). Information on the incidence of biopsy-proven SCCIS upstaged to SCC after a more complete histologic examination is limited.

OBJECTIVE
To determine the incidence and clinical risk factors associated with upstaging the biopsy diagnosis of SCCIS into invasive SCC based on findings during Mohs micrographic surgery (MMS).

METHODS
All MMS cases of SCCIS performed between March 2007 and February 2012 were identified, MMS operative notes were examined, and invasive dermal components were confirmed by the MMS slide review. Upstaged SCCIS was defined as biopsy-diagnosed SCCIS subsequently found to be an invasive SCC during MMS.

RESULTS
From 566 cases with the preoperative diagnosis of SCCIS, 92 (16.3%) cases were SCCIS upstaged to SCC. Location of ears, nose, lips, and eyelids, preoperative diameter >10 mm, and biopsy report mentioning a transected base were significant predictors of upstaged SCCIS.

CONCLUSION
Considering the possibility that over 16% of SCCIS may be truly invasive SCC, biopsy-proven SCCIS should be treated adequately with margin-assessed treatment modalities such as surgical excision or Mohs surgery when indicated.
Epidemiology and Molecular Characteristics of Mycoplasma pneumoniae During an Outbreak of M. pneumoniae-associated Stevens-Johnson Syndrome
Authors: Watkins Louise K. Francois , Olson Daniel , Diaz Maureen H. , Lin Xia , Demirjian Alicia , Benitez Alvaro J. , Winchell Jonas M. , Robinson Christine C. , Bol Kirk A. , Glodé Mary P. , Dominguez Samuel R. , Miller Lisa A. , Kutty Preeta K. 
Published: January 2017

Background:An increase inMycoplasma pneumoniae-associated Stevens-Johnson syndrome (SJS) cases at a Colorado pediatric hospital led to an outbreak investigation. We describe the epidemiologic and molecular characteristics ofM. pneumoniaeamong SJS case-patients and surrounding community members during the outbreak.Methods:M. pneumoniaepolymerase chain reaction-positive respiratory specimens from 5 Colorado hospitals and 4 referral laboratories underwent confirmatory polymerase chain reaction testing; positive specimens then underwent multilocus variable-number tandem-repeat analysis (MLVA) and macrolide resistance testing. Three SJS-M. pneumoniaecase-patient households were surveyed using a standardized questionnaire, and nasopharyngeal/oropharyngeal swabs were obtained from all consenting/assenting household contacts. International Classification of Diseases, 9th revision codes were used to identify pneumonia cases among Colorado patients 5–21 years of age from January 2009 to March 2014.Results:Three differentM. pneumoniaeMLVA types were identified among the 5 SJS case-patients with confirmed infection; MLVA type 3-X-6-2 was seen more commonly in SJS case-patients (60%) than in 69 non-SJS community specimens (29%). Macrolide resistance was identified in 7% of community specimens but not among SJS case-patients. Of 15 household contacts, 5 (33%) wereM. pneumoniaepositive; all MLVA types were identical to those of the corresponding SJS case-patient, although the specimen from 1 contact was macrolide resistant. Overall pneumonia cases as well as those caused byM. pneumoniaespecifically peaked in October 2013, coinciding with the SJS outbreak.Conclusions:The outbreak ofM. pneumoniae-associated SJS may have been associated with a community outbreak ofM. pneumoniae; clinicians should be aware of theM. pneumoniae–SJS relationship. Household transmission ofM. pneumoniaewas common within the households investigated.
Serious Adverse Reactions From Anti-tuberculosis Drugs Among 599 Children Hospitalized for Tuberculosis
Authors: Li Yiyuan , Zhu Yu , Zhong Qin , Zhang Xiaojun , Shu Min , Wan Chaomin 
Published: January 2017

Background:
The purpose of the study was to summarize the clinical characteristics of serious adverse reactions (ARs) related to anti-tuberculosis (TB) drugs in children hospitalized for TB. A comprehensive understanding of these drug-related ARs may serve to improve patient prognosis.

Methods:
Inpatients diagnosed with TB from 2008 to 2013 were enrolled retrospectively. The patients’ demographics, diagnosis and ARs were recorded and analyzed for comprehensive evaluation.

Results:
Of the 599 enrolled patients, 3.51% (21 of 599) developed serious ARs related to anti-TB drugs. Hepatotoxicity was the most common reaction (1.84%, 11 of 599). The incidence of rash with or without fever was 1% (6 of 599), and that of auditory impairments and renal injury was 0.33% (2 of 599) and 0.17% (1 of 599), respectively. One patient experienced hepatotoxicity, rash and fever. Hospital stay of inpatients with serious ARs was significantly longer (median: 24 days; range: 8–62 days) than that of those without reactions (median: 11 days; range: 1–83 days), though no distinctions were observed between the 2 groups with regard to average age, gender or involved organs. Hepatotoxicity occurred 6–30 days after the start of anti-TB treatment (median: 6 days) and 75% of the inpatients remained asymptomatic. Hepatotoxicity was traced to the drugs isoniazid, rifampin and pyrazinamide, while fever was mainly linked to pyrazinamide. In addition, streptomycin and amikacin led to auditory impairments and renal injury, respectively. Serious ARs of all inpatients were controlled and managed successfully.

Conclusions:
The incidence of serious ARs from anti-TB drugs among children inpatients was 3.5% and mainly consisted of hepatotoxicity. Inpatients with serious ARs tended to have longer hospital stays.
Estimating Pertussis Susceptibility Among 0–23-Month-Old Children in the United States
Authors: Childs Lana , Bednarczyk Robert A. 
Published: January 2017

Background:
Despite high pertussis-containing vaccine coverage in the United States, children who are unvaccinated or not fully vaccinated remain susceptible to pertussis. Over multiple birth cohorts of incomplete vaccination, the number of children not immune to pertussis will accumulate because of factors such as age-specific vaccination status and dose-specific vaccine effectiveness. The total number of pertussis-susceptible children 0–23 months of age in the United States is unknown.

Methods:
Using data on age-specific pertussis-containing vaccine receipt among children evaluated in the 2013 National Immunization Survey (born between February 2011 and June 2012) and accounting for vaccine effectiveness and maternal transfer of antipertussis antibodies, we estimated the cumulative number of pertussis-susceptible children 0–23 months of age.

Results:
Of an estimated 7,905,672 children 0–23 months of age in the United States, we estimated that approximately 22% (1,716,429) are susceptible to pertussis. Age was a large factor in susceptibility, with 89% of children less than 2 months of age not immune to pertussis compared with 7% of children 21–23 months of age. In sensitivity analysis, increasing maternal pertussis vaccination coverage from 10% to 42% decreased susceptibility in children less than 2 months of age to 68%. When considering waning immunity after the fourth dose of vaccine, the herd protection threshold was no longer reached.

Conclusions:
These estimates underscore the need to monitor age-specific pertussis vaccine coverage, to increase childhood and maternal pertussis vaccine coverage, to maintain population-level immunity and to prevent the spread of pertussis among young children.
Chikungunya Infection in Hospitalized Febrile Infants Younger Than 3 Months of Age
Authors: Elenga Narcisse , Folin Marion , Vandamme Yves-Marie , Cuadro-Alvarez Emma , Long Laurence , Njuieyon Falucar , Martin Elise , Kom-Tchameni Rémi , Defo Antoine , Herinantenaina Razafindrakoto Sitraka , Mrsic Yajaira , Couppie Pierre , Nacher Mathieu , Dufour Julie 
Published: January 2017

Background:
Fever in infants younger than 3 months is generally a cause for concern because of the risk for a serious bacterial infection. The aim of this study was to describe clinical and biologic features of Chikungunya infection in infants <3 months of age hospitalized in Cayenne Hospital during the 2014–2015 outbreak.

Methods:
We performed a preliminary retrospective study followed by a prospective study from March 2014 to February 2015. All infants younger than 3 months presenting with fever and hospitalized in Cayenne Hospital were included. The main diagnostic criteria were fever and positive Chikungunya polymerase chain reaction.

Results:
One hundred and twenty infants were hospitalized with fever. The mean age was 46 days (standard deviation ± 22 days). The mean hospitalization duration was 7.4 days (standard deviation ± 6.1 days). Chikungunya infection was diagnosed in 26 children. The most important clinical findings were high [80.8% (77.5–84)] and prolonged fever [76.9% (73.4–80.4)], irritability [96.2% (94.5–97.7)] and skin rash [69.2% (65.4–73)]. Half of the infants presented edema of the extremities (hands and feet principally). However, in 15% of infants, Chikungunya infection was associated with a serious bacterial infection. Infants who presented with irritability, high fever and elevated PCT were at high risk for Chikungunya: OR 39 (9.2–243; P < .001), with a specificity of 96.7% and a negative predictive value of 89.4%. The area of the receiver operating characteristic curve was 0.96.

Conclusions:
Our results confirm that Chikunguyna infection is a cause of high fever in infants younger than 3 months. Our data should be confirmed by larger studies.
Therapeutic benefits of the methyl donor S-adenosylmethionine on nerve injury–induced mechanical hypersensitivity and cognitive impairment in mice
Authors: Grégoire Stéphanie , Millecamps Magali , Naso Lina , Do Carmo Sonia , Cuello A. Claudio , Szyf Moshe , Stone Laura S. 
Published: January 2017

Abstract
Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains elusive. Comorbid conditions including anxiety, depression, and cognitive impairment further impact quality of life. Chronic pain is associated with reversible changes in brain anatomy and function and with long-term changes in gene expression. Epigenetic mechanisms, including DNA methylation, contribute to wide-spread and long-lasting reprogramming of gene expression. We previously reported decreases in global DNA methylation in the mouse frontal cortex 6 months after induction of neuropathic pain using the spared nerve injury (SNI) model. Here, we examined the therapeutic effect of increasing DNA methylation using the methyl donor S-adenosylmethionine (SAM). S-adenosylmethionine is marketed as a nutritional supplement for a range of conditions including liver disease, depression, osteoarthritis, fibromyalgia, and dementia. Three months after SNI or sham surgery, animals were treated with SAM (20 mg/kg, 3×/week) or saline orally for 4 months, and the impact on sensory, motor, motivational, and cognitive indices was measured. S-adenosylmethionine attenuated SNI-induced mechanical hypersensitivity and reduced active avoidance of mechanical stimuli but had no effect on cold sensitivity or motor capacity. S-adenosylmethionine completely blocked nerve injury–induced cognitive impairment and attenuated SNI-induced decreases in global DNA methylation in the frontal cortex. In summary, chronic oral administration of the methyl donor, SAM, attenuated sensory and cognitive symptoms associated with nerve injury in mice. These effects may be mediated, in part, through modulation of DNA methylation in the central nervous system by systemic administration of the methyl donor SAM.
Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial
Authors: Deer Timothy R. , Levy Robert M. , Kramer Jeffery , Poree Lawrence , Amirdelfan Kasra , Grigsby Eric , Staats Peter , Burton Allen W. , Burgher Abram H. , Obray Jon , Scowcroft James , Golovac Stan , Kapural Leonardo , Paicius Richard , Kim Christopher , Pope Jason , Yearwood Thomas , Samuel Sam , McRoberts W. Porter , Cassim Hazmer , Netherton Mark , Miller Nathan , Schaufele Michael , Tavel Edward , Davis Timothy , Davis Kristina , Johnson Linda , Mekhail Nagy 
Published: January 2017

Abstract
Animal and human studies indicate that electrical stimulation of dorsal root ganglion (DRG) neurons may modulate neuropathic pain signals. ACCURATE, a pivotal, prospective, multicenter, randomized comparative effectiveness trial, was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia in the lower extremities. Subjects received neurostimulation of the DRG or dorsal column (spinal cord stimulation, SCS). The primary end point was a composite of safety and efficacy at 3 months, and subjects were assessed through 12 months for long-term outcomes and adverse events. The predefined primary composite end point of treatment success was met for subjects with a permanent implant who reported 50% or greater decrease in visual analog scale score from preimplant baseline and who did not report any stimulation-related neurological deficits. No subjects reported stimulation-related neurological deficits. The percentage of subjects receiving ≥50% pain relief and treatment success was greater in the DRG arm (81.2%) than in the SCS arm (55.7%, P < 0.001) at 3 months. Device-related and serious adverse events were not different between the 2 groups. Dorsal root ganglion stimulation also demonstrated greater improvements in quality of life and psychological disposition. Finally, subjects using DRG stimulation reported less postural variation in paresthesia (P < 0.001) and reduced extraneous stimulation in nonpainful areas (P = 0.014), indicating DRG stimulation provided more targeted therapy to painful parts of the lower extremities. As the largest prospective, randomized comparative effectiveness trial to date, the results show that DRG stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to SCS.
The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine
Authors: Iyengar Smriti , Ossipov Michael H. , Johnson Kirk W. 
Published: January 2017

AbstractCalcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.
Multicenter Study of Adverse Events After Intravenous Tissue-Type Plasminogen Activator Treatment of Acute Ischemic Stroke
Authors: Fernandez-Gotico Hannah , Lightfoot Tiffany , Meighan Melissa 
Published: January 2017

ABSTRACT

Background and Purpose: The approved treatment by the Food and Drug Administration for acute ischemic stroke is intravenous tissue-type plasminogen activator (IV tPA). After IV tPA administration, patients are monitored for adverse events using an American Heart Association/American Stroke Association guideline instituted in 1996. There is limited evidence describing the safest and most efficient method to monitor patients during the first 24 hours after tPA administration. Although the overall rates of adverse events have been reported, the time when patients may be at most risk for an event has not been studied. The purpose of this study was to identify the time of adverse event occurrences in the first 24 hours after IV tPA administration. Method: This was a descriptive, retrospective chart review study of patients admitted to an integrated health system and treated with IV tPA for acute stroke between July 2010 and July 2012. Charts were reviewed for adverse events using the Institute for Healthcare Improvement’s Global Trigger Tool for Measuring Adverse Events. Possible chart indicators of adverse events or “triggers” included neurological decline, vital signs elevated above specified parameters, and emergent imaging. Adverse events included episodes of neurological decline, angioedema, allergic reactions, bleeding, and intracerebral hemorrhage (ICH). The timing of each detected event was determined, and descriptive statistics were used for data analysis. Results: Fourteen adverse events (2.8%) were detected in a population of 498 patients. Reactions consisted of allergic reaction (n = 1), angioedema (n = 1), neurological decline without ICH (n = 1), gastrointestinal bleeding (n = 1), bleeding gums (n = 1), and high-risk ICH (n = 9). Thirteen of the 14 adverse events (92.9%) occurred within the first 12 hours after IV tPA administration. Conclusion: Close monitoring during the first 12 hours after IV tPA treatment may be essential. However, close monitoring after 12 hours may not contribute significantly to improved patient outcomes. Larger studies may provide evidence for the safest and most efficient monitoring protocol for patients treated with IV tPA for ischemic stroke.