bluuebunny/crossref_metadata_2025 huggingface dataset:
The BFK20 phage replication origin confers a phage-encoded resistance phenotype to the industrial strain Brevibacterium flavum
Authors: Bukovska Gabriela , Ugorcakova Jana , Halgasova Nora , Bocanova Lucia , Tkacova Adela
Published: April 2019

The phage BFK20 replication origin was identified using bioinformatics tools and a fragment with the origin nucleotide sequence was cloned into the tetracycline resistance gene of Escherichia coli vector pBR328, to make the plasmid pBOS. After transformation into the host strain Brevibacterium flavum CCM 251, pBOS was able to replicate, showing that the cloned region may function as a replication origin. The presence of the BFK20 origin sequence in a pBOS plasmid isolated from B. flavum CCM 251 was confirmed by Southern hybridisation. Monitoring pBOS stability in corynebacterial hosts showed that pBOS was stable in Corynebacterium glutamicum RM3 for 20 generations and in B. flavum CCM 251 for 10 generations. The effect of the cloned BFK20 replication origin on host resistance to BFK20 infection was tested. Growth of a B. flavum CCM 251 strain harbouring pBOS stopped after phage infection, but without complete lysis. Five hours after infection, the viability of the modified strain was about five times higher than the viability of wild-type B. flavum CCM 251. Thus, the ability of the BFK20 replication origin to confer the origin-derived phage-encoded resistance phenotype to B. flavum CCM 251 was confirmed.
Biophysical Effects on the Scaling of Plant Growth, Form, and Ecology
Authors: Niklas K J , Hammond S T
Published: April 2019

Physical laws and processes influence the ability of plants to exchange mass and energy with their external environments, thereby directly influencing global ecosystem functions such as water and CO2 cycles. Six fundamental physical laws and processes (e.g., Fick’s law of diffusion and the Euler–Greenhill equation for elastic self-similarity) are reviewed in the context of how they affect growth, body size, shape, and ecology. This review shows that biophysical effects on energy–mass exchange rates significantly influence the scaling of plant growth and form, while simultaneously providing opportunities for adaptation and the exploration of unoccupied regions in the plant morphospace.
Non-lytic antibiotic treatment in community-acquired pneumococcal pneumonia does not attenuate inflammation: the PRISTINE trial
Authors: Groeneveld Geert H , van der Reyden Tanny J , Joosten Simone A , Bootsma Hester J , Cobbaert Christa M , de Vries Jutte J C , Kuijper Ed J , van Dissel Jaap T
Published: April 2019

Background

The inflammatory response in pneumococcal infection is primarily driven by immunoreactive bacterial cell wall components [lipoteichoic acid (LTA)]. An acute release of these components occurs when pneumococcal infection is treated with β-lactam antibiotics.

Objectives

We hypothesized that non-lytic rifampicin compared with lytic β-lactam antibiotic treatment would attenuate the inflammatory response in patients with pneumococcal pneumonia.

Methods

In the PRISTINE (Pneumonia treated with RIfampicin aTtenuates INflammation) trial, a randomized, therapeutic controlled, exploratory study in patients with community-acquired pneumococcal pneumonia, we looked at LTA release and inflammatory and clinical response during treatment with both rifampicin and β-lactam compared with treatment with β-lactam antibiotics only. The trial is registered in the Dutch trial registry, number NTR3751 (European Clinical Trials Database number 2012-003067-22).

Results

Forty-one patients with community-acquired pneumonia were included; 17 of them had pneumococcal pneumonia. LTA release, LTA-mediated inflammatory responses, clinical outcomes, inflammatory biomarkers and transcription profiles were not different between treatment groups.

Conclusions

The PRISTINE study demonstrated the feasibility of adding rifampicin to β-lactam antibiotics in the treatment of community-acquired pneumococcal pneumonia, but, despite solid in vitro and experimental animal research evidence, failed to demonstrate a difference in plasma LTA concentrations and subsequent inflammatory and clinical responses. Most likely, an inhibitory effect of human plasma contributes to the low immune response in these patients. In addition, LTA plasma concentration could be too low to mount a response via Toll-like receptor 2 in vitro, but may nonetheless have an effect in vivo.
Temperature-sensitive mutants of MscL mechanosensitive channel
Authors: Owada Naoto , Yoshida Megumi , Morita Kohei , Yoshimura Kenjiro
Published: April 2019

MscL is a mechanosensitive channel that undergoes a global conformational change upon application of membrane stretching. To elucidate how the structural stability and flexibility occur, we isolated temperature-sensitive (Ts) mutants of Escherichia coli MscL that allowed cell growth at 32°C but not at 42°C. Two Ts mutants, L86P and D127V, were identified. The L86P mutation occurred in the second transmembrane helix, TM2. Substitution of residues neighbouring L86 with proline also led to a Ts mutation, but the substitution of L86 with other amino acids did not result in a Ts phenotype, indicating that the Ts phenotype was due to a structural change of TM2 helix by the introduction of a proline residue. The D127V mutation was localized in the electrostatic belt of the bundle of cytoplasmic helices, indicating that stability of the pentameric bundle of the cytoplasmic helix affects MscL structure. Together, this study described a novel class of MscL mutations that were correlated with the thermodynamic stability of the MscL structure.
Gene–Environment Correlation in Humans: Lessons from Psychology for Quantitative Genetics
Authors: Saltz Julia B
Published: April 2019

Evolutionary biologists have long been aware that the effects of genes can reach beyond the boundary of the individual, that is, the phenotypic effects of genes can alter the environment. Yet, we rarely apply a quantitative genetics approach to understand the causes and consequences of genetic variation in the ways that individuals choose and manipulate their environments, particularly in wild populations. Here, I aim to stimulate research in this area by reviewing empirical examples of such processes from the psychology literature. Indeed, psychology researchers have been actively investigating genetic variation in the environments that individuals experience—a phenomenon termed “gene–environment correlation” (rGE)—since the 1970s. rGE emerges from genetic variation in individuals’ behavior and personality traits, which in turn affects the environments that they experience. I highlight concepts and examples from this literature, emphasizing the relevance to quantitative geneticists working on wild, nonhuman organisms. I point out fruitful areas of crossover between these disciplines, including how quantitative geneticists can test ideas about rGE in wild populations.
Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis
Authors: Janssen Quisette P , Buettner Stefan , Suker Mustafa , Beumer Berend R , Addeo Pietro , Bachellier Philippe , Bahary Nathan , Bekaii-Saab Tanios , Bali Maria A , Besselink Marc G , Boone Brian A , Chau Ian , Clarke Stephen , Dillhoff Mary , El-Rayes Bassel F , Frakes Jessica M , Grose Derek , Hosein Peter J , Jamieson Nigel B , Javed Ammar A , Khan Khurum , Kim Kyu-Pyo , Kim Song Cheol , Kim Sunhee S , Ko Andrew H , Lacy Jill , Margonis Georgios A , McCarter Martin D , McKay Colin J , Mellon Eric A , Moorcraft Sing Yu , Okada Ken-Ichi , Paniccia Alessandro , Parikh Parag J , Peters Niek A , Rabl Hans , Samra Jaswinder , Tinchon Christoph , van Tienhoven Geertjan , van Veldhuisen Eran , Wang-Gillam Andrea , Weiss Matthew J , Wilmink Johanna W , Yamaue Hiroki , Homs Marjolein Y V , van Eijck Casper H J , Katz Matthew H G , Groot Koerkamp Bas
Published: April 2019

Background

FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated.

Methods

We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III–IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method.

Results

We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III–IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX.

Conclusions

This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.
Functional divergence between soybean FLOWERING LOCUS T orthologues FT2a and FT5a in post-flowering stem growth
Authors: Takeshima Ryoma , Nan Haiyang , Harigai Kohei , Dong Lidong , Zhu Jianghui , Lu Sijia , Xu Meilan , Yamagishi Noriko , Yoshikawa Nobuyuki , Liu Baohui , Yamada Tetsuya , Kong Fanjiang , Abe Jun
Published: April 2019

Genes in the FLOWERING LOCUS T (FT) family integrate external and internal signals to control various aspects of plant development. In soybean (Glycine max), FT2a and FT5a play a major role in floral induction, but their roles in post-flowering reproductive development remain undetermined. Ectopic overexpression analyses revealed that FT2a and FT5a similarly induced flowering, but FT5a was markedly more effective than FT2a for the post-flowering termination of stem growth. The down-regulation of Dt1, a soybean orthologue of Arabidopsis TERMINAL FLOWER1, in shoot apices in early growing stages of FT5a-overexpressing plants was concomitant with highly up-regulated expression of APETALA1 orthologues. The Dt2 gene, a repressor of Dt1, was up-regulated similarly by the overexpression of FT2a and FT5a, suggesting that it was not involved in the control of stem termination by FT5a. In addition to the previously reported interaction with FDL19, a homologue of the Arabidopsis bZIP protein FD, both FT2a and FT5a interacted with FDL12, but only FT5a interacted with FDL06. Our results suggest that FT2a and FT5a have different functions in the control of post-flowering stem growth. A specific interaction of FT5a with FDL06 may play a key role in determining post-flowering stem growth in soybean.
Cellular and molecular characterization of a thick-walled variant reveal a pivotal role of shoot apical meristem in transverse development of bamboo culm
Authors: Wang Yujun , Sun Xuepeng , Ding Yulong , Fei Zhangjun , Jiao Chen , Fan Mingyuan , Yao Bingfan , Xin Peiyong , Chu Jinfang , Wei Qiang
Published: April 2019

Little is known about the mechanisms underlying the development of bamboo culm. Using anatomical, mathematical modeling, and genomics methods, we investigated the role of shoot apical meristem (SAM) in the development of the transverse morphology of bamboo culm and explored the underlying cellular and molecular processes. We discovered that maintenance of SAM morphology that can produce circular culm and increase in SAM cell numbers, especially corpus cells, is the means by which bamboo makes a larger culm with a regular pith cavity and culm wall during development. A less cellular form of SAM with a lower proportion of corpus cells causes an abnormal higher ratio of wall component cells to pith cells, which breaks the balance of their interaction and triggers the random invasion of wall component cells into pith tissues during development, and finally results in the various thick culm walls of Phyllostachys nidularia f. farcta. The smaller SAM also results in a lower level of hormones such as cytokinin and auxin, and down-regulates hormone signaling and the downstream functional genes such as those related to metabolism, which finally results in a dwarf and smaller diameter culm with lower biomass. These results provide an important perspective on the culm development of bamboo, and support a plausible mechanism causing the size-reduced culm and various thick culm walls of P. nidularia f. farcta.
Feedback Informed Treatment
Authors: Maeschalck Cynthia L. , Prescott David S. , Miller Scott D.
Published: April 2019

Feedback Informed Treatment (FIT) involves clinicians gathering on-going real time feedback from clients to determine what is working and what is not working in therapy. This chapter provides an overview of feedback informed treatment (FIT), including its historical evolution, guiding principles, and central tenets. It lays out how FIT is applied and integrated into practice, including how client feedback is obtained. The authors describe how it can guide treatment decisions in a variety of settings and with diverse populations. A case example illustrates FIT in practice. Finally, the authors review the outcome research on FIT and share ideas about its future directions.
International Themes in Psychotherapy Integration
Authors: Gómez Beatriz , Iwakabe Shigeru , Vaz Alexandre
Published: April 2019

Interest in psychotherapy integration has steadily expanded over the past decades, reaching most continents of the world and more mental health professionals than ever. Nevertheless, a country’s cultural and historical background significantly influences the nurturance or hindrance of integrative endeavors. This chapter seeks to explicate the current climate of psychotherapy integration in different continents and specific countries. With the aid of local integrative scholars, brief descriptions are presented on integrative practice, training, and research, as well as on cultural and sociopolitical issues that have shaped this movement’s impact around the world.
OrthoVenn2: a web server for whole-genome comparison and annotation of orthologous clusters across multiple species
Authors: Xu Ling , Dong Zhaobin , Fang Lu , Luo Yongjiang , Wei Zhaoyuan , Guo Hailong , Zhang Guoqing , Gu Yong Q , Coleman-Derr Devin , Xia Qingyou , Wang Yi
Published: April 2019

OrthoVenn is a powerful web platform for the comparison and analysis of whole-genome orthologous clusters. Here we present an updated version, OrthoVenn2, which provides new features that facilitate the comparative analysis of orthologous clusters among up to 12 species. Additionally, this update offers improvements to data visualization and interpretation, including an occurrence pattern table for interrogating the overlap of each orthologous group for the queried species. Within the occurrence table, the functional annotations and summaries of the disjunctions and intersections of clusters between the chosen species can be displayed through an interactive Venn diagram. To facilitate a broader range of comparisons, a larger number of species, including vertebrates, metazoa, protists, fungi, plants and bacteria, have been added in OrthoVenn2. Finally, a stand-alone version is available to perform large dataset comparisons and to visualize results locally without limitation of species number. In summary, OrthoVenn2 is an efficient and user-friendly web server freely accessible at https://orthovenn2.bioinfotoolkits.net.
AlloDriver: a method for the identification and analysis of cancer driver targets
Authors: Song Kun , Li Qian , Gao Wei , Lu Shaoyong , Shen Qiancheng , Liu Xinyi , Wu Yongyan , Wang Binquan , Lin Houwen , Chen Guoqiang , Zhang Jian
Published: April 2019

Identifying the variants that alter protein function is a promising strategy for deciphering the biological consequences of somatic mutations during tumorigenesis, which could provide novel targets for the development of cancer therapies. Here, based on our previously developed method, we present a strategy called AlloDriver that identifies cancer driver genes/proteins as possible targets from mutations. AlloDriver utilizes structural and dynamic features to prioritize potentially functional genes/proteins in individual cancers via mapping mutations generated from clinical cancer samples to allosteric/orthosteric sites derived from three-dimensional protein structures. This strategy exhibits desirable performance in the reemergence of known cancer driver mutations and genes/proteins from clinical samples. Significantly, the practicability of AlloDriver to discover novel cancer driver proteins in head and neck squamous cell carcinoma (HNSC) was tested in a real case of human protein tyrosine phosphatase, receptor type K (PTPRK) through a L1143F driver mutation located at the allosteric site of PTPRK, which was experimentally validated by cell proliferation assay. AlloDriver is expected to help to uncover innovative molecular mechanisms of tumorigenesis by perturbing proteins and to discover novel targets based on cancer driver mutations. The AlloDriver is freely available to all users at http://mdl.shsmu.edu.cn/ALD.
Light-Induced Artemisinin Biosynthesis Is Regulated by the bZIP Transcription Factor AaHY5 in Artemisia annua
Authors: Hao Xiaolong , Zhong Yijun , N�tzmann Hans-Wilhelm , Fu Xueqing , Yan Tingxiang , Shen Qian , Chen Minghui , Ma Yanan , Zhao Jingya , Osbourn Anne , Li Ling , Tang Kexuan
Published: April 2019

Artemisinin, the frontline drug against malaria, is a sesquiterpenoid extracted from Artemisia annua. Light has been proposed to play an important role in the activation of artemisinin biosynthesis. Here, we report the basic leucine zipper transcription factor (TF) AaHY5 as a key regulator of light-induced biosynthesis of artemisinin. We show that AaHY5 transcription overlaps with that of artemisinin biosynthesis genes in response to light and in A. annua tissues. Analysis of AaHY5 overexpression and RNAi-suppression lines suggests that AaHY5 is a positive regulator of the expression of artemisinin biosynthesis genes and accumulation of artemisinin. We show that AaHY5 complements the hy5 mutant in Arabidopsis thaliana. Our data further suggest that AaHY5 interacts with AaCOP1, the ubiquitin E3 ligase CONSTITUTIVE PHOTOMORPHOGENIC1 in A. annua. In yeast one-hybrid and transient expression assays, we demonstrate that AaHY5 acts via the TF GLANDULAR TRICHOME-SPECIFIC WRKY 1 (AaGSW1) in artemisinin regulation. In summary, we present a novel regulator of artemisinin gene expression and propose a model in which AaHY5 indirectly controls artemisinin production in response to changing light conditions.
Vortioxetine in the Treatment of Mood Disorders Associated with Burning Mouth Syndrome: Results of an Open-Label, Flexible-Dose Pilot Study
Authors: Adamo Daniela , Pecoraro Giuseppe , Aria Massimo , Favia Gianfranco , Mignogna Michele Davide
Published: April 2019

Objective

To evaluate the efficacy of a new multimodal antidepressant, vortioxetine (VO), in the management of burning mouth syndrome (BMS).

Design

Longitudinal single-assessment open-label pilot study.

Setting

University hospital. Subjects. Thirty BMS patients were enrolled.

Methods

BMS patients were treated with topical clonazepam and a flexible dose of VO (10 mg, 15 mg, or 20 mg). The visual analog scale (VAS), the Total Pain Rating Index (T-PRI), the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A), and the Pittsburgh Sleep Quality Index (PSQI) were performed at baseline (time 0) and after two (time 1), four (time 2), six (time 3), and 12 months (time 4) of treatment. Descriptive statistics and the Wilcoxon nonparametric test for two paired samples were used.

Results

The BMS patients showed a statistically significant improvement in VAS and T-PRI scores from baseline (median [interquartile range {IQR}] = 10.0 [10–10] and 22.0 [20–24], respectively) to time 4 (median [IQR] = 0.0 [0–0] and 8.0 [7–9], P < 0.001, respectively). Similarly, the HAM-A and HAM-D and PSQI scores showed an improvement from time 0 (median [IQR] = 20 [15.8–22], 19 [16–20.3], and 4.0 [4–7.3], respectively) to time 4 (median [IQR] = 6.0 [6–7], 6.0 [6–7], and 3.0 [3–4], respectively, P < 0.001).

Conclusions

VO is efficacious and well tolerated in the treatment of BMS in firstline therapy on account of its better receptor pharmacological profile and in second-line treatment for patients who have only partially responded or have reported adverse effects to previous treatments.
Managing a Pregnancy With Maternal Amelia
Authors: Siwatch Sujata , Gainder Shalini , Prasad Gurgunjakunta Ramabhadraraju Venkateshwara , Jain Vanita , Rohilla Meenakshi , Kuberan Aswini
Published: April 2019

INTRODUCTION:

Amelia, the complete absence of a limb, presents various management issues in pregnancy and delivery.

CASE:

A woman with amelia of both lower limbs and flipper-like upper limb buds (phocomelia) presented in her first pregnancy at 19 weeks of gestation. Challenging issues encountered in the care of the patient included venous access, reliable blood pressure measurement, recommendations regarding mode of delivery, and preparation for caring for the child. The patient had abnormalities of the pelvis but an adequate midpelvis, so she was able to deliver vaginally without complication.

CONCLUSION:

Careful planning to allow necessary modification of intrapartum management can allow for normal vaginal birth for a patient with severe limb reduction abnormalities such as amelia and phocomelia.
Delaying Surgery in Type III Supracondylar Humerus Fractures Does Not Lead to Longer Surgical Times or More Difficult Reduction
Authors: Prabhakar Pooja , Ho Christine A.
Published: April 2019

Objective:

To determine if delay in surgical treatment of type III supracondylar humerus fracture would affect the length of operative time.

Design:

Retrospective cohort study.

Setting:

Level 1 trauma center.

Patients/Participants:

This is a series of 309 modified Gartland type III supracondylar fractures treated operatively from 2011 to 2013.

Intervention:

Fifteen hours was defined as the cutoff between early and delayed treatment. A total of 53.7% (166/309) fractures were treated early, and 46.4% (143/309) were delayed.

Main Outcome Measurements:

Surgical time was defined as “incision start” to “incision close.” Fluoroscopy time was used as a surrogate for difficulty of reduction.

Results:

Time from injury to operating room was shorter for high-energy fractures (fractures with soft-tissue or neurovascular injury) versus low-energy fractures (12.9 vs. 15.3 hours, P < 0.0001); however, surgical time (37.3 vs. 31.8 minutes, P = 0.004) and fluoroscopy time (54.6 vs. 48.6 seconds, P = 0.027) were longer in high-energy fractures versus low-energy fractures. Among low-energy fractures, no significant difference was detected in the surgical time between the early and delayed treatment groups or in the fluoroscopy time. In addition, there was no statistically significant difference found in the surgical or fluoroscopy time with the presence of a surgical assistant.

Conclusions:

Delay in surgery did not result in a longer surgical time or more difficult reduction for type III supracondylar humerus fracture. Patients with low-energy fractures still underwent a shorter operative time even with delay from injury to surgery.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assessing the Need for Common Perioperative Laboratory Tests in Pediatric Patients With Femoral Shaft Fractures
Authors: Adams Alexander J. , Baldwin Keith D. , Arkader Alexandre , Sankar Wudbhav N.
Published: April 2019

Background:

Femoral shaft fractures are a common cause for hospital admission and surgery in pediatric patients, and laboratory studies are often ordered for historical concerns of excessive bleeding. Recent literature has challenged these assumptions, and unnecessary testing causes undue pain and costs in children. No previous studies have offered evidence-based recommendations for perioperative laboratories in isolated pediatric femoral shaft fractures.

Methods:

We retrospectively reviewed all patients presenting with femoral shaft fractures at our pediatric trauma center between 2013 and 2017. Patients with multitrauma injuries, metabolic/neuromuscular diseases, or intensive care unit stays were excluded. Necessity of laboratory tests was determined by rates of anemia, blood transfusions, specialist consultations, and delayed surgeries. Ordering patterns were recorded, with cost estimation based on Healthcare Bluebook.

Results:

We reviewed 95 patients (mean age, 7.9±4.8 y; 70 males). Treatments included elastic nails (33/95, 34.7%), reamed intramedullary nails (24/95, 25.3%), plates/screws (12/95, 12.6%), and spica casting (26/95, 27.4%). Of 32 patients with preoperative coagulation laboratories, 11 were abnormal; however none resulted in hematology consultations or procedure delays. Seventy-five patients (78.9%) and 15 patients (15.8%) had complete blood counts preoperatively and postoperative day 1, respectively. Four patients (4.2%) had hemoglobin<8 g/dL postoperatively, however, there were no perioperative blood transfusions. Of these 4, 3 underwent either reamed intramedullary nails or open reduction internal fixation with plates/screws. Twenty-six patients (27.4%) had preoperative basic metabolic panels that did not alter medical care. On the basis of our criteria, over 72% of laboratories appeared unnecessary, with a total potential cost of $8567. Over 80% of orders were from the emergency department by residents or attending physicians.

Conclusions:

Perioperative laboratory orders may be unnecessary in most isolated pediatric femoral shaft fractures, subjecting patients to extraneous costs, and associated pain. However, laboratories may be justified based on clinical circumstances or for older patients treated with reamed nails or plates/screws. Evidence-based recommendations for perioperative laboratory orders offer the potential to improve quality and value and minimize harm in pediatric orthopaedic trauma.

Level of Evidence:

Level III—retrospective comparative study (therapeutic).
Challenges Experienced By North Korean Refugee Doctors in Acquiring a Medical License in South Korea: A Qualitative Analysis
Authors: Ha Shin , Choi Hui Ran , Lee Jong Koo , Lee Yo Han
Published: April 2019

Introduction:

In general, refugee doctors encounter difficulties in regularly practicing medicine in their host countries. In particular, many barriers impede the efforts of North Korean refugee doctors (NKRDs) who have settled in South Korea to acquire a medical license in the country. This study examines the experiences and opinions of NKRDs in their attempts to acquire permission to legally practice medicine in South Korea and the opinions of South Korean experts regarding this matter.

Methods:

In-depth interviews were conducted among 23 participants divided into 2 groups. The first group comprised 16 NKRDs recruited through snowball sampling, whereas the second group included 7 South Korean doctors experienced in operating programs assisting NKRDs in license acquisition.

Results:

All participating NKRDs perceived that they face grave difficulties at every stage of acquiring a South Korean medical license and, particularly, in gaining recognition for their educational credentials. Furthermore, South Korean experts expressed the necessity of supporting, establishing, and expanding a system in the country whereby NKRDs can acquire a medical license.

Discussion:

Strengthening and changing their clinical competency to meet South Korean standards is the best option for NKRDs to acquire a medical license. Furthermore, the study reveals that the government should eliminate the obstacles in medical license acquisition by NKRDs and support the latter in their efforts to improve and demonstrate their competency.
Adnexal tumors in menopausal women: surgery or surveillance?
Authors: Burgess Brian T. , Ueland Frederick R.
Published: April 2019

Asymptomatic ovarian tumors in menopausal women do not always require surgical removal. Experts recommend an initial evaluation with transvaginal ultrasound to help characterize the tumor's malignant risk. Low-risk tumors can be monitored with ultrasound, whereas high-risk tumors should be referred to a gynecologic oncologist. Indeterminate tumors require secondary testing with the strategies outlined in this Practice Pearl.
Treatment of menorrhagia due to aplastic anemia by hysteroscopic resection of endometrial functional layer and levonorgestrel-releasing intra-uterine system
Authors: Yang Huadi , Xu Xuqun , Jiang Xuelu , Yao Zhitao
Published: April 2019

Rationale

In women, menorrhagia associated with aplastic anemia (AA) is secondary to thrombocytopenia and can be acute and severe. Endometrial ablation or hysterectomy has been reported to achieve beneficial results. However, serious limitations and long-term complications exist. We report this clinical case series with the aim of sharing our experiences and exploring a safe and effective way to treat abnormal uterine bleeding (AUB) AA women with future fertility desire.

Patient concerns

The 3 young patients aged 25 to 29 years old suffered from AUB secondary to AA.

Diagnosis

They were diagnosed with AA by bone marrow biopsy and presented with symptoms and signs of AUB without other identified causations.

Interventions

When the platelet count was between 30∗109 /L∼50∗109 /L after a blood transfusion, each patient received a hysteroscopic resection of endometrial functional layer and was fitted a levonorgestrel-releasing intra-uterine system (LNG-IUS) in uterine cavity following the surgery.

Outcomes

All the patients recovered without incident and were discharged in clinically stable conditions.

Lessons

In conclusion, AUB secondary to AA can be acute and severe. Hemostasis is more difficult due to progressive pancytopenia. For young women with future fertility desire, LNG-IUS following hysteroscopic resection of endometrial functional layer is a safe and effective way against endometrial ablation or hysterectomy.
Effects of mirror therapy on muscle activity, muscle tone, pain, and function in patients with mutilating injuries
Authors: Yun Da-Eun , Kim Myoung-Kwon
Published: April 2019

Background:

This study assessed the effectiveness of mirror therapy (MT) on muscle elasticity, pain, and function in patients with mutilating injuries.

Methods:

Thirty patients with impaired function due to mutilating injuries were assigned randomly to experimental or control group. The experimental group (n = 15) received MT (30 minutes a day, 3 days a week for 4 weeks) and conventional physical therapy after each MT session while the control group (n = 15) only received conventional physical therapy.

Results:

There were significant differences in pain and hand function within each group (pre-intervention vs post-intervention) and between groups (experimental vs control) (P < .05). However, there was no significant difference in muscle elasticity between groups (P > .05).

Conclusion:

Although MT cannot result in significant changes in muscle elasticity in a clinical setting, it does have positive effects by reducing pain and improving hand function. Thus, MT can be effective for patients with impaired function due to mutilating injuries.
Impact of inflammation-mediated response on pan-coronary plaque vulnerability, myocardial viability and ventricular remodeling in the postinfarction period - the VIABILITY study
Authors: Morariu Mirabela , Hodas Roxana , Benedek Theodora , Benedek Imre , Opincariu Diana , Mester Andras , Chitu Monica , Kovacs Istvan , Rezus Ciprian , Pasaroiu Dan , Mitra Noemi , Szilágyi Sándor M. , Georgescu Dan , Rezus Elena
Published: April 2019

Introduction:

While the role of inflammation in acute coronary events is well established, the impact of inflammatory-mediated vulnerability of coronary plaques from the entire coronary tree, on the extension of ventricular remodeling and scaring, has not been clarified yet.

Materials and methods:

The present manuscript describes the procedures of the VIABILITY trial, a descriptive prospective single-center cohort study. The main purpose of this trial is to assess the link between systemic inflammation, pan-coronary plaque vulnerability (referring to the plaque vulnerability within the entire coronary tree), myocardial viability and ventricular remodeling in patients who had suffered a recent ST-segment elevation acute myocardial infarction (STEMI). One hundred patients with STEMI who underwent successful revascularization of the culprit lesion in the first 12 hours after the onset of symptoms will be enrolled in the study. The level of systemic inflammation will be evaluated based on the serum biomarker levels (hs-CRP, matrix metalloproteinases, interleukin-6) in the acute phase of the myocardial infarction (MI) and at 1 month. Pan-coronary plaque vulnerability will be assessed based on serum biomarkers known to be associated with increased plaque vulnerability (V-CAM or I-CAM) and at 1 month after infarction, based on computed tomographic angiography analysis of vulnerability features of all coronary plaques. Myocardial viability and remodeling will be assessed based on 3D speckle tracking echocardiography associated with dobutamine infusion and LGE-CMR associated with post-processing imaging methods. The study population will be categorized in 2 subgroups: subgroup 1 - subjects with STEMI and increased inflammatory response at 7 days after the acute event (hs-CRP ≥ 3 mg/dl), and subgroup 2 - subjects with STEMI and no increased inflammatory response at 7 days (hs-CRP < 3 mg/dl). Study outcomes will consist in the rate of post-infarction heart failure development and the major adverse events (MACE) rate.

Conclusion:

VIABILITY is the first prospective study designed to evaluate the influence of infarct-related inflammatory response on several major determinants of post-infarction outcomes, such as coronary plaque vulnerability, myocardial viability, and ventricular remodeling.
Capecitabine versus 5-fluorouracil in neoadjuvant chemoradiotherapy of locally advanced rectal cancer
Authors: Zhu Jinfeng , Zeng Wei , Ge Lei , Yang Xinhui , Wang Qisan , Wang Haijiang
Published: April 2019

Background:

The differences in efficacy between capecitabine and 5-fuorouracil (5-FU) in neoadjuvant chemoradiotherapy (CRT) of locally advanced rectal cancer (LARC) are not well recognized. We performed this meta-analysis to analyze the effect of capecitabine and 5-FU on neoadjuvant CRT to more accurately understand the differences between the 2 drugs.

Methods:

MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database were performed to identify all published studies investigating the efficacy of capecitabine in neoadjuvant CRT of LARC versus 5-FU before August, 2017. Primary endpoint was the odds ratio (OR) for improving pathological complete response (pCR) rate of patients with LARC. Secondary endpoints were the ORs of efficiency for downstaging tumor and increasing R0 resection in patients with LARC. Safety analyses were also performed. The OR was the principal measurement of effect, which was calculated as capecitabine group versus 5-FU group, and was presented as a point estimate with 95% confidence intervals (CIs). All calculations and statistical tests were performed using RevMan 5.3 software.

Results:

In all, 2916 patients with LARC enrolled in the 10 studies were divided into capecitabine group (n = 1451) and 5-FU group (n = 1465). The meta-analysis showed that capecitabine improved pCR (OR 1.34, 95% CI 1.10–1.63), and R0 resection rate (OR 1.92, 95% CI 1.10–3.36). There were no statistically significant differences either in overall downstaging rate (OR 1.31, 95% CI 0.79–2.16) or in the tumor downstaging rate (OR 1.24, 95% CI 0.79–1.92), but there was a significant difference of the nodal downstaging rate between the 2 groups (OR 1.68, 95% CI 1.11–2.54). There was no statistically significant difference in sphincter preservation rate between the 2 groups (OR 1.36, 95% CI 0.96–1.92). No obvious safety concerns about mortality and complications were raised in these studies. There were no statistically significant differences in 3-year disease-free-survival (OR 1.29, 95% CI 0.75–2.20), and in grade 3 to 4 acute toxicity during CRT (OR 0.63, 95% CI 0.31–1.30).

Conclusions:

Compared with 5-FU-based neoadjuvant CRT, capecitabine-based neoadjuvant CRT can safely improve pCR, nodal down-staging, ad R0 resection of patients with LARC.
Ectopic liver tissue in the esophagus
Authors: Zhang Zi-Li , Wang Jin-Liang , Guo Chun-Li , Li Qi , Li Lin , Pang Yi , Meng Xiang-Chao
Published: April 2019

Introduction:

Ectopic liver (EL) is a rare entity, which is reported to develop at various sites, such as the abdominal cavity, the retroperitoneal cavity, the pleural cavity, and the mediastinum.

Patient concerns:

A 27-year-old previously healthy Chinese man suffered from a discontinuous abdominal pain in the upper abdomen for 2 months.

Diagnosis:

The upper gastrointestinal endoscopy revealed there was a polypoid mucosal uplift on the distal region of the esophagus near the cardia.

Interventions:

Endoscopic polypectomy was performed.

Outcomes:

Pathology examination showed the liver tissue.

Conclusion:

EL should be excised as it may possibly lead to the development of a malignancy. Endoscopic resection was found to be safe and reliable in this case.
A case report dysregulated neutrophil extracellular traps in a patient with propylthiouracil-induced anti-neutrophil cytoplasmic antibody-associated vasculitis
Authors: Watanabe-Kusunoki Kanako , Abe Nobuya , Nakazawa Daigo , Karino Kohei , Hattanda Fumihiko , Fujieda Yuichiro , Nishio Saori , Yasuda Shinsuke , Ishizu Akihiro , Atsumi Tatsuya
Published: April 2019

Rationale:

Neutrophil extracellular traps (NETs) are immune defence systems that release extracellular chromatin and myeloid granules including myeloperoxidase (MPO) to kill pathogens. An experimental animal study recently demonstrated that disordered NETs induced by propylthiouracil (PTU) could contribute to the production of MPO anti-neutrophil cytoplasmic antibody (ANCA) and the development of ANCA-associated vasculitis (AAV). However, the role of dysregulated NETs in the pathogenesis of human AAV remains unclear.

Patient concerns:

We report a 19-year-old woman with Graves’ disease on PTU presented fever, polyarthralgia, and lung hemorrhage with high titer of MPO-ANCA. This patient had a variety of atypical ANCAs and disordered NETs in vitro.

Diagnoses:

A diagnosis of PTU-induced AAV (PTU-AAV).

Interventions:

The PTU was discontinued and she was treated with immunosuppressants and plasmapheresis for reducing pathogenic autoantibodies.

Outcomes:

Clinical manifestations including fever, polyarthralgia, and lung hemorrhage were on remission with a decrease of dysregulated NETs.

Lessons:

The clinical course of this PTU-AAV case indicated that dysregulated NETs would play a role in the development of ANCA and the pathogenesis of AAV.
(CONSORT) Wound closure using Dermabond after excision of hemangioma on the lip
Authors: Chang Jung Woo , Cho Kyu Sang , Heo Woong , Lee Jang Hyun
Published: April 2019

Background:

As the lip contains ample blood supply, hemangiomas often occur in this area. When surgical excision is performed, wound closure is important. To prevent infection from saliva and food, watertight wound closure is needed. The purpose of this study is to demonstrate the usefulness of Dermabond for wound closure after hemangioma excision on the lip.

Methods:

Between December 2015 and August 2017, 11 patients with lip hemangioma underwent surgical excision. When closing the wound, Dermabond was used for skin closure after subcutaneous sutures. Demographic data and complications were recorded. Scars were evaluated with the Vancouver scar scale (VSS), and the postoperative shape of the lip was assessed on a 10-point satisfaction scale at 1 month and 6 months postoperatively.

Results:

All cases completely healed without any complications, such as wound dehiscence or infection. There were no recurrences at postoperative 1 month during the follow-up period. The aesthetic results of the scars were also excellent. The average VSS score on postoperative 1 month was 4.2, and it decreased to 2.2 at postoperative 6 months. The average patient satisfaction score at postoperative 1 month was 7.4, and it increased to 9.5 at postoperative 6 months.

Conclusion:

Dermabond is useful for wound closure after hemangioma excision on the lip. It prevents wound contamination, and yields acceptable aesthetic results.
A novel AVPR2 missense mutation in an Asian family with inherited nephrogenic diabetes insipidus
Authors: Zhang Min , Yu Qin , Chen Chen , Han Jian , Cheng Bin , Tian Dean
Published: April 2019

Rationale:

X-linked nephrogenic diabetes insipidus (NDI) is a rare inherited disease, and is characterized by renal resistance to arginine vasopressin (AVP). Its diagnosis can be clinically challenging. The application of molecular genetic analysis can provide a rapid and definitive diagnosis.

Patient concerns:

A 75-year-old woman presented with recurrent nausea and vomiting was admitted to the Department of Gastroenterology. The patient had a strong family history of polydipsia and polyuria. Sequencing analysis of the antidiuretic hormone arginine vasopressin receptor 2 (AVPR2) revealed the novel missense mutation p. Trp164Cys (c.492G>G/C) in exon 2. There was a heterozygous mutation in the patient's sister and niece, while there was a mutation in her sons, brother and nephews. The locus is located on the X chromosome Xq28, and its mutation can lead to X linked recessive NDI. The p. Trp164Cys mutation of AVPR2 gene has not been reported in literature before. The mutation was predicted to be probably damaging by several prediction methods, including SIFT and PolyPhen-2. There was no significant abnormal variation in other detection regions of the gene. And there was also no abnormal variation in AVP and AQP2 genes in this family.

Diagnosis:

X-linked NDI was diagnosed according to the patient's family history and DNA sequencing analysis.

Interventions and outcomes:

After treated with desmopressin, antiemetic drugs and massive infusion glucose transfusion, the patient's urine volume decreased and electrolyte disturbance was corrected, and the symptoms of nausea and vomiting gradually disappeared.

Lessons:

The patients with suspected congenital NDI should undergo genetic sequencing analysis of AVPR2, AVP and AQP2 genes. A definitive diagnosis can benefit patient and avoid unnecessary investigations.
Efficacy of submucosal bupivacaine injection for pain relief after endoscopic submucosal dissection
Authors: Jung Jang Han , Jang Hyun Joo , Bang Chang Seok , Baik Gwang Ho , Park Se Woo
Published: April 2019

Background and aim:

Although abdominal pain is a common adverse event related to endoscopic submucosal dissection (ESD), it can be sometimes underestimated by endoscopists. There are some endoscopic interventions available for the prevention of post-ESD pain, but their efficacy has not been established. We investigated whether a submucosal injection of bupivacaine (BP) can reduce procedure-related abdominal pain compared with the standard method.

Methods:

We performed a multicenter, double-blinded, randomized controlled trial of 86 adult patients referred for ESD as treatment for gastric neoplasms. Patients were randomly assigned to either the BP submucosal or conventional solution group. Questionnaires were collected when the study began (baseline) and immediately after ESD, as well as at 6, 12, and 24 hours post-operatively. The primary outcome was indicated by the visual analog scale (VAS) evaluated at 6 hours after procedure.

Results:

There were no significant differences in primary outcomes between groups and among all time points (immediately, 12, and 24 hours after ESD). The VAS and short-form McGill pain (SF-MP) scores were higher immediately after ESD than at 6, 12, or 24 hours post-operatively. The incidence of abdominal pain immediately after ESD was 94.0% (78/83) for all patients of both groups, and there was no significant difference between the 2 groups in the rate of abdominal pain immediately after ESD (BP group 37/40 [92.5%] versus non-BP group 41/43 [95.3%], P = .934). In univariable and multivariable analyses, BP did not have protective effect on post-ESD abdominal pain.

Conclusions:

Submucosal BP injection does not promote pain relief or mitigate the effects of post-ESD abdominal pain.
A novel prognostic model for diagnosing atypical bile duct hyperplasia in patients with intrahepatic lithiasis
Authors: Lu Hongcheng , Yang Hao , Wu Linquan , Liao Wenjun , He Xianping , Li Enliang , Wu Rongshou , Shi Shidai , Yang Zhilong
Published: April 2019

There is no specific method for the preoperative diagnosis of atypical bile duct hyperplasia, which is a precursor of cholangiocarcinoma. This study aimed to create a new model for diagnosing atypical bile duct hyperplasia based on routine laboratory tests in patients with intrahepatic lithiasis.

The new diagnostic model was developed with a derivation cohort that included 375 patients with intrahepatic lithiasis. Clinical and pathological data were retrospectively collected. Prognostic factors were evaluated with univariate and logistic regression analyses. The validation cohort included 136 patients who were retrospectively screened to quantify the model's predictive value.

Age and Carbohydrate Antigen 19-9 (CA-199) were revealed to be diagnostic indicators of atypical bile duct hyperplasia in patients with intrahepatic lithiasis. The new diagnostic model was created with the formula: −6.612 + (0.002 × CA-199) + (0.072 × Age). The area under the receiver operating curve of the model was 0.721. With 0.25 as the cutoff point, the sensitivity and specificity of this model in the derivation cohort were 13.9% and 95.9%, respectively. In the validation cohort, these values were 28.5% and 88.7%, respectively. The novel model has an acceptable and stable ability to predict atypical hyperplasia in the intrahepatic bile duct.

This novel model provides a simple system for diagnosing atypical bile duct hyperplasia before surgery in patients with intrahepatic lithiasis.