bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare driver alterations in nonsmall cell lung cancer: novel targeted drugs
Authors: Kauffmann-Guerrero Diego , Tufman Amanda 
Published: November 2021

Purpose of review
The current review presents clinically relevant driver alterations in nonsmall cell lung cancer (NSCLC) and the targeted treatments currently available for clinical use as well as those in clinical trials and advanced stages of drug development.

Recent findings
Mesenchymal–epithelial transition factor, human epidermal growth factor receptor 2, proto-oncogene B-RAF (BRAF), proto-oncogene tyrosine-protein kinase ROS (ROS1), rearranged during transfection (RET) and neurotrophic tyrosine kinase are rare genetic driver alterations, each present in a small subset of patients with NSCLC. Treatments targeting BRAF, ROS1, RET and neurotrophic tyrosine kinase are approved in Europe, and promising treatments targeting mesenchymal–epithelial transition factor and human epidermal growth factor receptor 2 are available in clinical trials and compassionate use programs. The response rates, duration of response and tolerability observed in trials of targeted drugs in this setting are presented in detail here.

Summary
While rare driver alterations are, by definition, rare, their recognition can change the course of NSCLC for those patients affected. Targeted treatments for many rare driver alterations are well tolerated and effective. Screening for molecular changes in advanced NSCLC should include screening for rare drivers, and patients should be directed to clinical trials in setting where treatment of the driver alterations is not otherwise available.
Outcome of Lamellar Graft Patching for the Treatment of Noninfectious Corneal Perforations
Authors: Suzuki Takanori , Yamaguchi Takefumi , Tomida Daisuke , Fukui Masaki , Shimazaki Jun 
Published: November 2021

Purpose:
The aims of this study were to evaluate the clinical outcome of lamellar graft patching used for treating noninfectious corneal perforations and to determine the clinical factors affecting tectonic integrity.

Methods:
This retrospective study includes a total of 71 eyes of 67 patients who underwent lamellar graft patching for the treatment of corneal perforations due to persistent epithelial defects secondary to limbal stem cell deficiency (LSCD, 21 eyes; 29.6%), peripheral ulcerative keratitis (17 eyes; 23.9%), neurotrophic keratitis due to herpes simplex keratitis (HSK, 14 eyes; 19.7%), and other causes (19 eyes; 26.8%). We evaluated the tectonic integrity of the globe, visual outcomes, and postoperative complications.

Results:
Tectonic integrity was achieved in 53 eyes (74.6%). The survival proportions of eyes that achieved clear grafts were 77.8% and 65.2% at 12 and 24 months, respectively. Graft failure was observed in 19 eyes (26.8%). The survival rate of tectonic integrity and eyes that finally achieved a clear graft was significantly worse in eyes with LSCD compared with those without (P < 0.001). The logarithm of minimal angle resolution improved significantly from 1.79 ± 0.98 to 1.22 ± 0.87 at 12 months and 1.08 ± 0.81 at 24 months. Postoperative complications included cataract formation (32 eyes, 45.1%), intraocular pressure rise (23 eyes, 32.4%), recurrent perforations (15 eyes, 21.1%), infectious keratitis (14 eyes, 19.7%), recurrence of herpes simplex keratitis (7 eyes, 9.9%), and traumatic graft dehiscence (1 eye, 1.4%).

Conclusions:
Lamellar graft patching is an effective and safe surgical treatment for noninfectious corneal perforations; however, careful attention to severe complications is necessary, especially in eyes with LSCD.
Pre-Exposure Prophylaxis Stigma and Beliefs in the Efficacy of Pre-Exposure Prophylaxis: An Analysis of a Cross-Sectional Survey of Male Couples in the United States
Authors: Stephenson Rob , Chavanduka Tanaka M. D. , Sullivan Stephen P. , Mitchell Jason W. 
Published: November 2021

Abstract
Increasing the use of pre-exposure prophylaxis (PrEP) among male couples is critical to the success of the United States' Ending the HIV Epidemic campaign. By leveraging dyadic data from a larger cross-sectional study of male couples, the present analysis examined individual, partner, and relationship characteristics associated with PrEP stigma and perceived efficacy of PrEP. Actor–Partner Independence Models were fit separately for both outcomes. Individual and partner risk behaviors, including substance use, binge drinking, and higher number of condomless casual sex partners, were associated with lower levels of both PrEP stigma and belief in the efficacy of PrEP. Networks that supported PrEP use were associated with decreased PrEP stigma and increased belief in PrEP efficacy. Stigma-informed PrEP interventions for couples should be considered foundational to the success of the United States' Ending the HIV Epidemic campaign.
Electronic Messaging for Gonorrhea and Chlamydia Test Result Notification, Improving Treatment and Patient Satisfaction
Authors: Rahman Mohammad M. , Johnson Chaquetta , Whyte Martha , Ewell Joy , Cope Anna B. , Chandler Yolanda , Bennett Tammy S. , Gray Terri , Gruber DeAnn , Peterman Thomas A. 
Published: November 2021

Background
Approximately 20% of chlamydia (CT) and gonorrhea (GC) cases in Louisiana are diagnosed at Parish Health Units. Patient notification of CT and GC test results involves nurses' phone calls and letters to positive patients, which is time-consuming and inefficient.

Methods
In December 2018, electronic results notification was implemented in Caddo Parish Health Unit using Chexout software to notify enrolled patients via text or email when test results are ready to view in a patient portal. We compared the timeliness of GC/CT results notification and treatment pre-Chexout (December 2017 to November 2018) and post-Chexout (December 2018 to November 2019) implementation. A random sample of patients was interviewed to assess acceptability.

Results
During December 2018 to November 2019, 5432 patients were tested for CT/GC, 3924 (72%) enrolled in Chexout, and notifications were sent to 3884 (99%). Among CT-positives, 472 of 568 (83%) viewed results in the portal compared with 2451 of 3356 (73%) CT-negatives. Among GC-positives, 300 of 353 (85%) viewed results compared with 2657 of 3571 (74%) GC-negatives. Treatment success for CT improved from 493 of 670 (74%) to 506 of 568 (89%), and for GC, from 332 of 409 (81%) to 325 of 353 (92%). Mean time to treatment decreased for CT (13.4–10.7 days) and GC (11.3–9.2 days). Enrolled patients found Chexout notification satisfactory in 168 of 169 (99%) and easy to use in 130 of 141 (92%). Reasons for declining electronic notification included lack of personal cell phone for 55 of 86 (64%) and confidentiality concerns for 42 of 86 (49%).

Conclusions
Electronic messaging decreased time to notification and increased treatment success. Nurses spent less time notifying patients leaving more time for patient care.
Pain, numbness, or both? Distinguishing the longitudinal course and predictors of positive, painful neuropathic features vs numbness after breast cancer surgery
Authors: Flowers K. Mikayla , Beck Meghan , Colebaugh Carin , Haroutounian Simon , Edwards Robert R. , Schreiber Kristin L. 
Published: November 2021

Introduction:
Both positive (burning, stabbing, and allodynia) and negative (numbness) neuropathic symptoms may arise after surgery but likely contribute differently to patients' postoperative pain experience. Numbness has been identified as divergent from positive neuropathic symptoms and therefore excluded from some neuropathic assessment tools (Neuropathic Pain Scale for PostSurgical patients [NeuPPS]).

Objectives:
In this prospective longitudinal study of patients undergoing breast surgery, we aimed to delineate the time course of numbness and its coincidence with NeuPPS and to contrast the association of surgical, psychosocial, and psychophysical predictors with the development of negative vs positive neuropathic symptoms.

Methods:
Patients reported surgical area sensory disturbances at 2 weeks and 3, 6, and 12 months postoperatively. Association of baseline demographic, surgical, psychosocial, and psychophysical factors with NeuPPS and numbness across time was investigated using generalized estimating equation linear and logistic regression.

Results:
Numbness was consistently reported by 65% of patients; positive neuropathic symptoms were less common, often decreasing over time. Neuropathic Pain scale for PostSurgical patients and numbness co-occurred in half of patients and were both associated with greater clinical pain severity and impact, younger age, axillary surgery, and psychosocial factors. More extensive surgery and chemotherapy were only associated with numbness. Conversely, other chronic pain, lower physical activity, perioperative opioid use, negative affect, and lower baseline pressure pain threshold and tolerance were only associated with NeuPPS. Patients reporting numbness alone did not endorse substantial clinical pain.

Conclusions:
Differentiation of predictors, prevalence, and time course of numbness vs NeuPPS in breast surgical patients revealed important distinctions, suggesting that their independent assessment is worthwhile in future studies of postsurgical pain.
Selection of Optimal Functional Lymphatic Vessel Cutoff Size in Supermicrosurgical Lymphaticovenous Anastomosis in Lower Extremity Lymphedema
Authors: Yang Johnson Chia-Shen , Wu Shao-Chun , Hayashi Akitatsu , Lin Wei-Che , Wang Yu-Ming , Luo Sheng-Dean , Chiang Min-Hsien , Hsieh Ching-Hua 
Published: November 2021

Background:
Functional lymphatic vessels are essential for supermicrosurgical lymphaticovenous anastomosis. Theoretically, the larger the lymphatic vessel, the better the flow. However, large lymphatic vessels are not readily available. Since the introduction of lymphaticovenous anastomosis, no guidelines have been set as to how small a lymphatic vessel is still worthwhile for anastomosis.

Methods:
In this longitudinal cohort study, unilateral lower limb lymphedema patients who underwent lymphaticovenous anastomosis between March of 2016 and January of 2019 were included. Demographic data and intraoperative findings including the number and size of lymphatic vessels were recorded. The cutoff size was determined by receiver operating characteristic curve analysis, based on the functional properties of lymphatic vessels. Clinical correlation was made with post–lymphaticovenous anastomosis volume measured by magnetic resonance volumetry.

Results:
A total of 141 consecutive patients (124 women and 17 men) with a median age of 60.0 years (range, 56.7 to 61.2 years) were included. The cutoff size for a functional lymphatic vessel was determined to be 0.50 mm (i.e., lymphatic vessel0.5) from a total of 1048 lymphatic vessels. Significant differences were found between the number of lymphatic vessels0.5 anastomosed (zero to one, two to three, and greater than over equal to four lymphatic vessels0.5), the median post–lymphaticovenous anastomosis volume reduction (in milliliters) (p < 0.001), and the median percentage volume reduction (p = 0.012).

Conclusions:
Lymphatic vessel0.5 can be a valuable reference for lymphaticovenous anastomosis. Post–lymphaticovenous anastomosis outcome can be enhanced with the use of lymphatic vessel0.5 for anastomoses.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, II.
Prognostic Values of Platelet Distribution Width and Platelet Distribution Width-to-Platelet Ratio in Severe Burns
Authors: Lin Jian-Chang , Wu Guo-Hua , Zheng Jian-Jun , Chen Zhao-Hong , Chen Xiao-Dong 
Published: November 2021

ABSTRACT

Background:
Platelet distribution width (PDW) and PDW-to-platelet ratio (PPR) have been proven to be good prognostic indicators for many diseases. However, their prognostic values in severe burns have not been reported.

Objective:
To investigate the early time course of PDW and PPR in severe burn patients and investigate their prognostic values.

Methods:
This is a 16-year, single-center retrospective study of 590 severe burn patients. The complete blood count parameters on day 1, day 3, and day 7 postburn, including PDW and PPR, were collected. Receiver operating characteristic curves (ROC) analysis, multiple logistic regression analysis and Kaplan–Meier survival analysis were performed to evaluate the prognostic values of PDW and PPR in severe burn patients.

Results:
According to 120-day follow-up records, 96 patients were nonsurvivors and 494 patients were survivors. ROC and area under the curve (AUC) analysis showed that, for predicting 120-day prognosis, the AUC of PDW (0.782) and PPR (0.816) on day 3 was the highest, followed by the AUC of PDW (0.764) and PPR (0.750) on day 7. The ROC–AUC of PPR (0.816) on day 3 was very close to that of the ABSI score (0.818). Multiple logistic regression analysis showed that the PDW (P = 0.033 and P = 0.009) and PPR (P = 0.052 and P = 0.046) on day 3 and day 7 were all significantly independently positively associated with 120-day mortality. Kaplan–Meier survival analysis showed that high PDW and PPR were both significantly associated with a high 120-day mortality rate on day 3 and day 7.

Conclusion:
PDW and PPR on day 3 and day 7 were independent risk factors for 120-day mortality in severe burn patients. These objective and readily available prognostic indicators may be more clinically favored.
Ophthalmological Evaluation in Children Presenting With a Primary Brain Tumor
Authors: Nuijts Myrthe A. , Stegeman Inge , Porro Giorgio L. , Duvekot Josje C. , van Egmond-Ebbeling Michelle B. , van der Linden Denise C. P. , Hoving Eelco W. , Schouten-van Meeteren Antoinette Y. N. , Imhof Saskia M. 
Published: November 2021

Background:
Children with a brain tumor are prone to develop visual impairment, which to date is often underestimated and unrecognized. Our aim was to assess the prevalence of ophthalmological evaluation and abnormal ophthalmological findings, and investigate whether demographic and tumor-related characteristics are associated with abnormal ophthalmological findings in children presenting with a primary brain tumor.

Methods:
Medical records of all 90 children diagnosed with a primary brain tumor between June 2018 and May 2019 and treated at the Princess Máxima Center for Pediatric Oncology, a tertiary referral center in the Netherlands, were retrospectively reviewed. Univariate regression analysis was used to investigate associations between demographic, tumor-related and clinical characteristics, and abnormal ophthalmological findings.

Results:
Sixty children (34 male [56.7%]; median [range] age, 9.3 [0–16.9] years) underwent ophthalmological evaluation within 6 weeks before or after diagnosis, 11 children (5 male [45.5%]; median [range] age, 5.7 [0.1–17.2] years) were seen more than 6 weeks before or after diagnosis, and 19 children (7 male [36.8%]; median [range] age, 7.2 [1.9–16.6] years) did not receive ophthalmological evaluation within at least 6 months from diagnosis. A total of 19 children (21.1%) presented with visual symptoms as first sign leading to the diagnosis of a brain tumor. Children who presented with visual symptoms (odds ratio [OR], 22.52; 95% confidence interval [CI], 4.90–103.60) and/or hydrocephalus (OR, 3.60; 95% CI, 1.38–9.36) at diagnosis were more often seen for ophthalmological evaluation. The most common abnormal ophthalmological findings were eye movement disorders (66.0%), papilledema (44.1%), and visual field defects (58.1%). Eye movement disorders occurred more frequently in patients with an infratentorial tumor (OR, 4.71; 95% CI, 1.03–21.65). The risk of papilledema was associated with older age (OR, 1.19; 95% CI, 1.05–1.34), hydrocephalus (OR, 9.63; 95% CI, 2.68–34.61), and infratentorial (OR, 9.11; 95% CI, 1.77–46.78) and supratentorial (OR, 13.13; 95% CI, 1.92–89.52) tumors.

Conclusions:
In this study, most children with a primary brain tumor underwent ophthalmological evaluation around diagnosis, 21% of the children were not evaluated. The high prevalence of abnormal ophthalmological findings stresses the importance of early standardized ophthalmological evaluation to detect visual impairment and provide timely treatment to potentially prevent permanent visual loss.
Translation of scientific evidence into cardiovascular guidelines
Authors: Koller Akos , Takács Johanna 
Published: November 2021

ABSTRACT

Introduction and aims:
Research evidence is the basis of guidelines used by healthcare professionals to make difficult decisions every day. We hypothesized that due to the available evidence the four selected cardiovascular guidelines have different degrees of certainty for making efficient decisions.

Methods:
We conducted an analytic study on the guidelines on arterial hypertension (AH), myocardial revascularization, syncope and cardiovascular diseases during pregnancy to assess the levels of evidence (LEVEL) and the classes of the recommendations (CLASS).

Results:
A total of 636 LEVEL and CLASS data were analyzed. To define certainty, LEVEL areas under CLASS were calculated. The frequency of LEVEL by CLASS showed that AH had the highest rate of evidence A in each CLASS. Myocardial revascularization showed a frequency pattern similar to that of AH. In syncope and pregnancy, the percentage of evidence B and/or C was the highest in each class; the percentages of certainty were 24.3% – pregnancy and 75.7% – AH. Deviations from an optimal decision revealed that the observed percentages of certainty were significantly lower on higher LEVEL than the expected percentages.

Conclusion:
Analyzing recommended procedures for diagnosis and treatments revealed a great disparity of certainty among the guidelines, and that the guideline of AH is superior to other guidelines, probably due to the substantial scientific evidence available in this field. Revealing the ratio of certainty/uncertainty in guidelines can identify issues to be clarified and investigated in future studies.
Overprotection and overcontrol in childhood: An evaluation on reliability and validity of 33-item Expanded Childhood Trauma Questionnaire (CTQ-33), Chinese version
Authors: Wu Zhipeng , Liu Zhening , Jiang Zhengqian , Fu Xingzi , Deng Qian , Palaniyappan Lena , Xiang Zhibiao , Huang Danqing , Long Yicheng 
Published: November 2021

AbstractOverprotection and overcontrol from parents or other family members, which are not rare in the Chinese culture, have been suggested to be traumatic experiences for some children. However, research on overprotection/overcontrol is much rarer in China compared with other childhood trauma subtypes. One of the possible reasons for this is the lack of easy and feasible screening tools. In this study, we therefore translated and validated a Chinese version of the 33-item Childhood Trauma Questionnaire (CTQ-33), which was expanded from the widely-used 28-item CTQ with an additional overprotection/overcontrol subscale. A total of 248 young healthy participants were recruited and completed the Chinese version of CTQ-33, and 50 of them were retested after an interval of two weeks. At baseline, all participants also completed the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder Scale to assess their depression and anxiety, respectively. Our main findings include that: (1) the Chinese version of CTQ-33 showed a good internal consistency (Cronbach’s α coefficient = 0.733) and an excellent test-retest reliability over a two-week period (ICC = 0.861); (2) the previously reported significant associations between the overprotection/overcontrol and other subtypes of childhood trauma (abuse and neglect), as well as psychopathological conditions such as depression can all be replicated using the Chinese version of CTQ-33. These results suggest that the Chinese version of CTQ-33 would be a promising tool for assessing various subtypes of childhood adversities, especially the overprotection/overcontrol experiences in Chinese populations.
Pausing methotrexate improves immunogenicity of COVID-19 vaccination in elderly patients with rheumatic diseases
Authors: Arumahandi de Silva AN , Frommert LM , Albach FN , Klotsche J , Scholz V , Jeworowski LM , Schwarz T , ten Hagen A , Zernicke J , Corman VM , Drosten C , Burmester GR , Biesen R 
Published: November 2021

ABSTRACTObjectiveTo study the effect of methotrexate (MTX) and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD).MethodsIn this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 rheumatic patients on methotrexate therapy, 31 of whom temporarily paused medication without a fixed regimen. The control group consisted of 21 AIRD patients without immunosuppressive medication.ResultsMTX patients showed a significantly lower mean antibody response compared to AIRD patients without immunosuppressive therapy (71.8 % vs 92.4 %, p<0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49; p<0.001). All nine patients with antibody levels below the cut-off were older than 60 years. Patients who held MTX during at least one vaccination showed significantly higher mean neutralising antibody levels after second vaccination, compared to patients who continued MTX therapy during both vaccinations (83.1 % vs 61.2 %, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8 % vs 51.9 %, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days.ConclusionMTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination significantly improves the antibody response in patients over 60 years of age.
Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity
Authors: Si Longlong , Bai Haiqing , Oh Crystal Yuri , Zhang Tian , Hong Fan , Jiang Amanda , Ye Yongxin , Jordan Tristan X. , Logue James , McGrath Marisa , Belgur Chaitra , Nurani Atiq , Cao Wuji , Prantil-Baun Rachelle , Gygi Steven P , Powers Rani K. , Frieman Matthew , tenOever Benjamin R. , Ingber Donald E. 
Published: November 2021

ABSTRACTThe current COVID-19 pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III), in a wide range of human cell types. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5’-C, antisense strand: 3’-GGG) that mediates end-to-end dimer self-assembly of these RNAs by Hoogsteen G-G base-pairing. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory siRNAs, their activity is independent of TLR7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad spectrum inhibition of infections by many respiratory viruses with pandemic potential, including SARS-CoV-2, SARS-CoV, MERS-CoV, and influenza A, as well as the common cold virus HCoV-NL63 in both cell lines and human Lung Chips that mimic organ-level lung pathophysiology. These short dsRNAs can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics at low cost.