bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4 cell count at initiation of ART, long-term likelihood of achieving CD4 >750 cells/mm3 and mortality risk
Authors: Palella F. J. , Armon C. , Chmiel J. S. , Brooks J. T. , Hart R. , Lichtenstein K. , Novak R. M. , Yangco B. , Wood K. , Durham M. , Buchacz K. 
Published: June 2016

Abstract

Objectives
We sought to evaluate associations between CD4 at ART initiation (AI), achieving CD4 >750 cells/mm3 (CD4 >750), long-term immunological recovery and survival.

Methods
This was a prospective observational cohort study. We analysed data from ART-naive patients seen in 1996–2012 and followed ≥3 years after AI. We used Kaplan–Meier (KM) methods and log-rank tests to compare time to achieving CD4 >750 by CD4 at AI (CD4-AI); and Cox regression models and generalized estimating equations to identify factors associated with achieving CD4 >750 and mortality risk.

Results
Of 1327 patients, followed for a median of 7.9 years, >85% received ART for ≥75% of follow-up time; 64 died. KM estimates evaluating likelihood of CD4 >750 during 5 years of follow-up, stratified by CD4-AI <50, 50–199, 200–349, 350–499 and 500–750, were 20%, 25%, 56%, 80% and 87%, respectively (log-rank P < 0.001). In adjusted models, CD4-AI ≥200 (versus CD4-AI <200) was associated with achievement of CD4 >750 [adjusted HR (aHR) = 4.77]. Blacks were less likely than whites to achieve CD4 >750 (33% versus 49%, aHR = 0.77). Mortality rates decreased with increasing CD4-AI (P = 0.004 across CD4 strata for AIDS causes and P = 0.009 for non-AIDS death causes). Among decedents with CD4-AI ≥50, 56% of deaths were due to non-AIDS causes.

Conclusions
Higher CD4-AI resulted in greater long-term CD4 gains, likelihood of achieving CD4 >750, longer survival and decreased mortality regardless of cause. Over 80% of persons with CD4-AI ≥350 achieved CD4 >750 by 4 years while 75% of persons with CD4-AI <200 did not. These data confirm the hazards of delayed AI and support early AI.
Genistein sensitizes sarcoma cells in vitro and in vivo by enhancing apoptosis and by inhibiting DSB repair pathways
Authors: Liu X.X. , Sun C. , Jin X.D. , Li P. , Zheng X.G. , Zhao T. , Li Q. 
Published: June 2016

AbstractThe aim of this work was to investigate the radiosensitization effects of genistein on mice sarcoma cells and the corresponding biological mechanisms in vitro and in vivo . Using the non-toxic dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at 50% cell survival (IC 50 ) was 1.45 for S180 cells. For mice cotreated with genistein and X-rays, the excised tumor tissues had reduced blood vessels and decreased size and volume compared with the control and irradiation-only groups. Moreover, a significant increase in apoptosis was accompanied by upregulation of Bax and downregulation of Bcl-2 in the mitochondria, and lots of cytochrome c being transferred to the cytoplasm. Furthermore, X-rays combined with genistein inhibited the activity of DNA-PKcs, so DNA-injured sites were dominated by Ku70/80, leading to incompleteness of homologous recombination (HR) and non-homologous end-joining (NHEJ) repairs and the eventual occurrence of cell apoptosis. Our study, for the first time, demonstrated that genistein sensitized sarcoma cells to X-rays and that this radiosensitizing effect depended on induction of the mitochondrial apoptosis pathway and inhibition of the double-strand break (DSB) repair pathways.
Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro
Authors: Maeda Kenichiro , Yasui Hironobu , Matsuura Taeko , Yamamori Tohru , Suzuki Motofumi , Nagane Masaki , Nam Jin-Min , Inanami Osamu , Shirato Hiroki 
Published: June 2016

Abstract
Variations in relative biological effectiveness (RBE) from a fixed value of 1.1 are critical in proton beam therapy. To date, studies estimating RBE at multiple positions relative to the spread-out Bragg peak (SOBP) have been predominantly performed using passive scattering methods, and limited data are available for spot-scanning beams. Thus, to investigate the RBE of spot-scanning beams, Chinese hamster fibroblast V79 cells were irradiated using the beam line at the Hokkaido University Hospital Proton Therapy Center. Cells were placed at six different depths, including the entrance of the proton beam and the proximal and distal part of the SOBP. Surviving cell fractions were analyzed using colony formation assay, and cell survival curves were obtained by the curve fitted using a linear–quadratic model. RBE 10 and RBE 37 were 1.15 and 1.21 at the center of the SOBP, respectively. In contrast, the distal region showed higher RBE values (1.50 for RBE 10 and 1.85 for RBE 37 ). These results are in line with those of previous studies conducted using passive scattering proton beams. Taken together, these data strongly suggest that variations in RBE should be considered during treatment planning for spot-scanning beams as well as for passive scattering proton beams.
The Neurologic Examination
Authors: Gelb Douglas J. 
Published: June 2016

Abstract
A careful history can elicit most of the information necessary to localize a patient’s lesion, especially if you follow up open-ended questions with questions that focus on specific nervous system pathways. No matter how accurate and detailed the history, however, you will need to perform a neurologic examination. This is the most reliable way to identify certain abnormalities, such as subtle weakness, eye movement abnormalities, sensory deficits, and asymmetric reflexes. This examination will include patient consent and rely on patient observations. Key areas of a neurologic examination include mental status examination, cranial nerve examination, motor examination, reflex examination, sensory examination
Incontinence
Authors: Gelb Douglas J. 
Published: June 2016

Abstract
Incontinence is a particularly distressing symptom for patients and their families, and this would be reason enough to evaluate it promptly. In addi- tion, although incontinence is not an emergency in and of itself, it some- times indicates the presence of an underlying neurologic condition that must be addressed urgently. Neurologic conditions more often produce urinary incontinence than fecal incontinence, and when both occur, urinary incontinence generally appears first.
Pediatric Neurology
Authors: Gelb Douglas J. 
Published: June 2016

Abstract
Developmental plasticity is the main feature distinguishing pediatric neurology from adult neurology. The diagnostic principles presented in the first three chapters of this book still apply, but many of the nervous system functions typically assessed in adults are not fully operational until months or years after birth. Obvious examples are walking, talking, and control of bladder and bowel function. Thus, a child’s developmental stage determines how the exami- nation is interpreted and how it is performed.
Geriatric Neurology
Authors: Gelb Douglas J. 
Published: June 2016

Abstract
Three principles distinguish the neurologic assessment of older patients. First, and most important, people accumulate more diseases the longer they live. Second, some diseases occur primarily in the elderly. Third, even in the absence of any apparent disease, some components of the aging nervous system gradually deteriorate. As a consequence, older patients often have numerous symptoms referable to more than one organ system. The standard approach of trying to localize all symptoms to a single lesion is untenable in many cases. Instead, the question is whether the patient has a degenerative disease affecting sites distributed diffusely throughout the nervous system or a combination of unrelated diseases. The neurologic examination provides useful information for answering this question, but accurate interpretation of the examination requires knowledge of the changes that occur during normal aging.
Mentoring Early-Career Faculty Researchers Is Important—But First “Train the Trainer”
Authors: Sood Akshay , Tigges Beth , Helitzer Deborah 
Published: June 2016

It has long been known that mentoring is critical to the success of junior faculty researchers. The controlled intervention study by Libby et al published in this issue of Academic Medicine demonstrates that institutional investment in a mentored research career development program for early-career faculty investigators provided significant long-term gains in grant productivity. Academic institutions hoping to replicate this program’s success by launching similar mentoring programs for their junior faculty investigators will, however, find that the Achilles’ heel lies in the scarcity of skilled research mentors and the relative lack of attention to and recognition of the importance of a supportive institutional climate for mentoring. It is essential, therefore, to begin by developing programs to “train the trainer” as well as programs and policies to support mentors. As a recent trial at 16 Clinical and Translational Science Award institutions demonstrated, competency-based, structured research mentor training can improve mentors’ skills.
In this Commentary, the authors offer a comprehensive two-pronged framework for mentor development with elements that address both individual mentoring competencies and the institutional climate for mentoring. The framework depicts the gaps, activities, and outcomes that a mentor development program can address. Activities directed at changing the institutional climate related to mentor development should complement training activities for individual mentors. The authors propose that employing this framework’s approach to mentor development will lead to the desired impact: to increase the competence, productivity, and retention of a diverse clinical and translational research workforce.
Variability in Women Faculty’s Preferences Regarding Mentor Similarity: A Multi-Institution Study in Academic Medicine
Authors: Carapinha René , Ortiz-Walters Rowena , McCracken Caitlin M. , Hill Emorcia V. , Reede Joan Y. 
Published: June 2016

Purpose
To investigate which mentor-similarity characteristics women faculty in academic medicine rate most important and to determine whether this importance differs among women faculty on the basis of current and prior mentoring, demographic and personal factors, and career factors.

Method
Cross-sectional survey data from 3,100 women faculty at 13 purposively sampled U.S. medical schools were collected in 2012. The preferences of participants regarding the importance of mentor similarity in terms of race/ethnicity, gender, personal and career interests, and department and institution were studied. Analysis entailed chi-square tests and multivariable ordered logistic models.

Results
Overall, respondents ranked having a mentor in the same department and institution as most important. Same department and institution were less important for those without a current mentor and for senior faculty, and were more important for Asian faculty. Same career and personal interests were less important for older faculty and more important for those with a doctorate only. Same gender was more important for black faculty, faculty at the rank of instructor, and those without current mentoring. Overall, same race/ethnicity was rated least important; however, it was more important for racial–ethnic minorities, U.S.-born faculty, and those who had never had a mentor.

Conclusions
Mentor preferences, as indicated by level of importance assigned to types of mentor similarity, varied among women faculty. To advance effective mentoring, characterized by good mentor–mentee fit, the authors provide recommendations on matching strategies to be used in academic medicine when considering the diverse mentor preferences of women faculty.
Opening a New Level II Trauma Center Near an Established Level I Trauma Center: Is This Good for Trauma Care?
Authors: Martin Cody L. , Aldridge Petra J. , Harris Anthony M. , Perkins Christopher H. 
Published: June 2016

Objectives:
To describe how the initiation and later removal of a provisional level II trauma center (PL2TC) status at a community hospital affected the volume and severity of injured patients seen at an established academic level 1 trauma center (AL1TC).

Methods:
Census data including counts of injury ICD-9 codes and patients seen in the emergency department (ED) and trauma center at an AL1TC were collected monthly from January 2010 to October 2014. An interrupted time series analysis was used to model the monthly census data with 2 time interruptions to describe the change in patient volume at the interruptions. The interruptions were (1) the initiation of the PL2TC status at a nearby community hospital and (2) the subsequent removal of the PL2TC status.

Results:
The number of diagnoses, encounters, and patients seen at the AL1TC ED decreased while the PL2TC was operating. After the removal of the PL2TC status, there was a 19.4% increase in the ED patient volume per month at the AL1TC. The number of orthopaedic trauma patients seen through the ED at the AL1TC dropped 11.1% per month when the PL2TC began functioning as a trauma center. However, the volume of orthopaedic patients at the AL1TC did not recuperate after the PL2TC lost level 2 status.

Conclusions:
A significant decrease in patient volume was seen at the AL1TC with the initiation of the PL2TC in close proximity. Orthopaedic patient volume did not recuperate after the removal of the PL2TC status.
TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma
Authors: Czapiewski Piotr , Majewska Hanna , Kutzner Heinz , Kazakov Dmitry , Renkielska Alicja , Biernat Wojciech 
Published: June 2016

Abstract:
Thyroid transcription factor-1 (TTF-1) is a marker of tumors of pulmonary and thyroid origin, and its expression practically excludes diagnosis of Merkel cell carcinoma (MCC). However, TTF-1 expression in combined MCC was recently reported. PAX5 is a marker of B-cell origin that is also expressed in most classical MCC cases; however, its expression was not described in combined MCC. The authors decided to evaluate the expression of both these markers in a group of 5 combined MCCs (2 with invasive squamous cell carcinoma, 2 with squamous cell carcinoma in situ, and 1 with basal cell carcinoma). Expression of TTF-1 was found in 4 of 5 cases; in 3 cases, the marker was shown in the MCC component (weakly in 2 cases and strongly in 1 case), whereas the non-MCC component presented TTF-1 expression in 2 cases. A weak-to-moderate immunoreactivity for PAX5 was identified in all cases of the MCC component but in none of the non-MCC component. The results show that the expression of TTF-1 is a frequent finding in combined MCC and can be present in the neuroendocrine component, which differs from the conventional MCC. In contrast, PAX5 expression pattern is similar to that of the classical MCC.
Photodynamic Therapy: A Clinical Consensus Guide
Authors: Ozog David M. , Rkein Ali M. , Fabi Sabrina G. , Gold Michael H. , Goldman Mitchel P. , Lowe Nicholas J. , Martin George M. , Munavalli Girish S. 
Published: June 2016

BACKGROUNDThe American Society of Dermatologic Surgery (ASDS) periodically develops consensus documents for its members concerning various aspects of dermatologic surgery. Advances in photodynamic therapy (PDT) have been many and PDT use has been established in a variety of skin conditions.OBJECTIVEThe ASDS board of directors proposed a committee of experts in the field to develop consensus documents on different treatments. An expert panel reviewed the literature on PDT and discussed the findings. The consensus was reached with evidence-based recommendations on different clinical applications for PDT.PATIENTS AND METHODSThis consensus document includes discussions regarding PDT, including different photosensitizers and various light source activators, historical perspective, mechanism of action, various therapeutic indications and expected outcomes, pre- and post-care, and management of adverse outcomes.RESULTSPhotodynamic therapy is highly effective for pre-cancerous lesions, superficial nonmelanoma skin cancers, inflammatory acne vulgaris and other conditions. New protocols including laser mediated PDT significantly improve results for several indications.CONCLUSIONThe ASDS consensus document on PDT will be helpful for educating members on safe and effective PDT for a variety of indications.
Estrogen and DPP4 inhibitor, but not metformin, exert cardioprotection via attenuating cardiac mitochondrial dysfunction in obese insulin-resistant and estrogen-deprived female rats
Authors: Sivasinprasasn Sivaporn , Sa-nguanmoo Piangkwan , Pongkan Wanpitak , Pratchayasakul Wasana , Chattipakorn Siriporn C. , Chattipakorn Nipon 
Published: June 2016

Abstract

Objective:
Cardiac function was markedly compromised in obese insulin-resistant and estrogen-deprived rats. Metformin and dipeptidyl peptidase-4 inhibitor (vildagliptin) were reported to improve cardiac function in insulin-resistant rats. Their effects on the heart under estrogen-deprived conditions are, however, unknown. Therefore, the effects of metformin, vildagliptin, and estrogen on the cardiac function in estrogen-deprived insulin-resistant female rats were investigated.

Methods:
Bilateral ovariectomized female rats (n = 48) were divided to be fed with either a normal diet (ND) or a high-fat diet (HFD) for 12 weeks. Then, both ND- and HFD-fed groups were subdivided to receive a vehicle, estrogen (50 μg/kg), metformin (30 mg/kg), or vildagliptin (3 mg/kg) for 4 weeks (n = 6/group). Heart rate variability, echocardiography, metabolic and biochemical parameters, cardiac function, and mitochondrial function were determined. Sham-operated female rats (n = 6) were used as a control.

Results:
Both ND- and HFD-fed ovariectomized rats developed insulin resistance, depressed heart rate variability, and decreased cardiac contractility. Although treatment with metformin, vildagliptin, and estrogen improved metabolic status and cardiac function, only estrogen and vildagliptin improved diastolic blood pressure and left ventricular ±dP/dt, and also reduced mitochondrial impairment, apoptosis, and oxidative stress in HD-fed ovariectomized rats.

Conclusions:
Treatment with estrogen and vildagliptin provided more beneficial effects in the inhibition of oxidative stress, apoptosis, and cardiac mitochondrial dysfunction, and preserved cardiac contractile performance in estrogen-deprived insulin-resistant female rats.
Varied Definitions of Nasolabial Angle: Searching for Consensus Among Rhinoplasty Surgeons and an Algorithm for Selecting the Ideal Method
Authors: Harris Ryan , Nagarkar Purushottam , Amirlak Bardia 
Published: June 2016

Background:
The nasolabial angle (NLA) is an important aesthetic metric for nasal assessment and correction. Although the literature offers many definitions, none has garnered universal acceptance.

Methods:
To gauge the consensus level among practitioners, surveys were administered to a convenience sample of rhinoplasty surgeons soliciting practice characteristics, self-assessment of rhinoplasty experience and expertise, and preferred NLA definition. Choices of NLA definition included the angle between: (A) columella and line intersecting subnasale and labrale superius; (B) columella and line tangent to philtrum; (C) nostril long axis and Frankfort perpendicular; and (D) nostril long axis and vertical facial plane.

Results:
Of the 82 total respondents, mean age was 50 years (range, 30–80years), and mean professional experience was 17 years (range, 0–67 years). Nineteen described themselves as novice rhinoplasty surgeons, 27 as intermediates, and 36 as experts. Mean number of lifetime rhinoplasties performed was 966 (range, 0–10,000). Twenty respondents (24%) agreed with definition A, 27 (33%) with B, 16 (20%) with C, and 13 (16%) with D. Six chose “other,” offering their own explanations of NLA. Self-identified novices were more likely to prefer definition D than were experts (P = 0.009).

Conclusions:
No majority consensus was reached regarding the definition of NLA. Each method has its benefits and drawbacks, and establishing a single one may be unnecessary and even counterproductive in some cases. Having options available means that surgeons can tailor to each encounter, as long as they adopt a systematic methodology. We submit an algorithm to facilitate this effort.
Iron Status at Age 6 Months in Colombian Infants Exclusively Breast‐fed for 4 to 5 Versus 6 Months
Authors: Olaya Gilma A. , Lawson Margaret , Fewtrell Mary 
Published: June 2016

ABSTRACTObjectives:The optimal age for introducing complementary feeding to breast‐fed infants may differ depending on the setting. Prolonged exclusive breast‐feeding (EBF) protects against infection but may increase the risk of iron deficiency (ID)/anaemia (IDA) in vulnerable infants. The aim of the present study was to compare haemoglobin (Hb), serum ferritin (SF), anaemia (Hb < 11 g/L), ID (SF < 12 μg/L) and IDA (Hb < 10.5 g/dL + Hct < 33% + ID) using observational analyses in 6‐month old infants from Bogota, Colombia who were EBF for 4 to 5 versus 6 months or older, and examine predictors.Methods:Infant feeding was recorded, anthropometry performed, and blood obtained for Hb and SF at 6 months in healthy term infants (birth weight > 2500 g), all EBF for ≥4 months.Results:One hundred eight infants (54% boys) were recruited; 46% EBF for 4 to 5 months, 54% EBF at 6 months. Prevalence of anaemia, ID, and IDA was 20%, 10%, and 5%, with no significant difference between EBF4–5 and EBF6 groups. In multivariate models, anaemia/ID were predicted by greater weight gain from 0 to 6 months, and anaemia also by caesarean delivery; Hb was lower in infants with higher intake of cows’ milk; SF was lower in boys and those with greater weight gain. EBF4–5 versus EBF6 was not a significant predictor of any outcome.Conclusions:Anaemia and ID were common at 6 months but were not affected by EBF for 4 to 5 versus 6 months, suggesting 6 months EBF is safe in this population. Further research is, however, required to examine effects on later iron status. The findings highlight the need to emphasise avoidance of cow's milk before 12 months.
A Clinical and Molecular Genetic Study in 11 Chinese Children With Peutz‐Jeghers Syndrome
Authors: Zheng Bixia , Wang Chunli , Jia Zhanjun , Liu Zhifeng , Li Mei , Jin Yu , Pan Jian 
Published: June 2016

ABSTRACTObjectives:Peutz‐Jeghers syndrome (PJS) is caused by the germline mutations in serine/threonine kinase 11 (STK11) gene. The aim of the present study was to investigate the spectrum of STK11 gene mutations using multiplex ligation–dependent probe amplification (MLPA) assay in combination with direct sequencing in Chinese children with PJS.Methods:Nine children who met the clinical criteria for PJS and 2 presumed patients with PJS were enrolled in the present study. Patients’ clinical information on polyp characteristics, polyp‐related complications, family histories, and so on were reviewed and analyzed. After obtaining informed consent, we performed a mutation analysis of STK11 gene in 11 Chinese patients using MLPA assay and direct sequencing.Results:By means of MLPA method, we detected exonic deletions in 5 patients. In details, 1 patient had the complete deletion of all 10 exons, 3 patients showed deletions of promoter region and exon 1, and 1 patient had exon deletions from 1 to 9. By direct sequencing of the coding region of STK11 gene, we identified point mutations in 4 patients at c.548T>G/p.Leu183Arg, c.580G>T/p.Asp194Tyr, c.152_153insGG/Asp53GlyfsX12, and c.631delC/Arg211GlyfsX76, respectively, and 3 of them are novel mutations. We failed to find any mutation in left 2 patients who met the clinical criteria of PJS.Conclusions:MLPA plus direct sequencing revealed large genomic deletions of STK11 gene in Chinese children with PJS and increased the detecting rate of STK11 gene mutations in Chinese patients with PJS. MLPA combined with direct sequencing could serve as a better strategy for the genetic diagnosis of PJS in Chinese population.