bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Father, father, where are you going?’: Epicurean Deism and Absent Fathers in Blake’s Songs of Innocence and of Experience
Authors: Codsi Stephanie
Published: July 2019

This article explores the connection between the absent deity of Epicurean Deism and the father figure in Blake's Songs of Innocence and of Experience (1789–1794). The absent, elusive or indifferent God – which I trace back to Epicurean theology and its theory of atoms – plays out in Blake's depiction of a father whose absence or neglect is an implied cause of man's alienation. The article firstly looks at the inheritance of Epicureanism in 17–18th century Deist texts, then considers Blake s references to Epicureanism in his works, and finally argues that Blake critiques such concepts of God and fatherhood in a selection of Songs.
Placental and breastmilk transfer of voriconazole to offspring from pregnant and lactating bottlenose dolphins (Tursiops truncatus)
Authors: Ohno Yoshito , Kobayashi Marisa , Akune Yuichiro , Inoshima Yasuo
Published: July 2019

Fungal pneumonia is a common disease in bottlenose dolphins (Tursiops truncatus), including pregnant and lactating ones. Voriconazole (VRCZ) is commonly used to treat respiratory fungal infections in this species; however, it is unknown whether VRCZ is transferred via the placenta and breastmilk and whether its usage is safe in pregnant and lactating dolphins. We measured VRCZ concentrations in breastmilk and dams’, umbilical cord, and calves’ plasma samples from four dam-calf dolphin pairs in the Port of Nagoya Public Aquarium, Japan, treated with or without VRCZ. Three pregnant and/or lactating dams were administered VRCZ (loading dose 1.5–2.3 mg/kg, for 3 days; maintenance dose 1.5–3.1 mg/kg, every 5–18 days), twice daily, orally, without side effects in dams or calves. VRCZ was detected in two dams’ umbilical cord plasma (0.14 and 2.35 μg/ml) and in one calf's plasma (0.18 μg/ml), collected immediately after birth. Further, VRCZ was detected in breastmilk samples (maximum 13.45 μg/ml) from three VRCZ-administered dams and in plasma from three calves (maximum 7.54 μg/ml) given or nursed from VRCZ-administered dams’ breastmilk. The calves’ plasma VRCZ concentrations varied, depending on the amount of breastmilk and food consumed. VRCZ concentrations were higher in breastmilk samples than in dams’ plasma. To our knowledge, this is the first report on placental and breastmilk VRCZ transfer to offspring in bottlenose dolphins. During VRCZ medication in pregnant and lactating bottlenose dolphins, it is crucial to monitor plasma VRCZ concentrations and any side effects in dams as well as in their calves.
Is the dark-matter halo spin a predictor of galaxy spin and size?
Authors: Jiang Fangzhou , Dekel Avishai , Kneller Omer , Lapiner Sharon , Ceverino Daniel , Primack Joel R , Faber Sandra M , Macciò Andrea V , Dutton Aaron A , Genel Shy , Somerville Rachel S
Published: July 2019

The similarity between the distributions of spins for galaxies (λgal) and for dark-matter haloes (λhalo), indicated both by simulations and observations, is naively interpreted as a one-to-one correlation between the spins of a galaxy and its host halo. This is used to predict galaxy sizes in semi-analytic models via Re ≃ fjλhaloRvir, where Re is the half-mass radius of the galaxy, fj is the angular momentum retention factor, and Rvir is the halo radius. Using two suites of zoom-in cosmological simulations, we find that λgal and the λhalo of its host halo are in fact barely correlated, especially at z ≥ 1, in line with previous indications. Since the spins of baryons and dark matter are correlated at accretion into Rvir, the null correlation in the end reflects an anticorrelation between fj and λhalo, which can arise from mergers and a ‘wet compaction’ phase that many high-redshift galaxies undergo. It may also reflect that unrepresentative small fractions of baryons are tapped to the galaxies. The galaxy spin is better correlated with the spin of the inner halo, but this largely reflects the effect of the baryons on the halo. While λhalo is not a useful predictor for Re, our simulations reproduce a general relation of the form of Re = ARvir, in agreement with observational estimates. We find that the relation becomes tighter with A = 0.02(c/10)−0.7, where c is the halo concentration, which in turn introduces a dependence on mass and redshift.
Post-transcriptional gene silencing triggers dispensable DNA methylation in gene body in Arabidopsis
Authors: Taochy Christelle , Yu Agnès , Bouché Nicolas , Bouteiller Nathalie , Elmayan Taline , Dressel Uwe , Carroll Bernard J , Vaucheret Hervé
Published: July 2019

Spontaneous post-transcriptional silencing of sense transgenes (S-PTGS) is established in each generation and is accompanied by DNA methylation, but the pathway of PTGS-dependent DNA methylation is unknown and so is its role. Here we show that CHH and CHG methylation coincides spatially and temporally with RDR6-dependent products derived from the central and 3′ regions of the coding sequence, and requires the components of the RNA-directed DNA methylation (RdDM) pathway NRPE1, DRD1 and DRM2, but not CLSY1, NRPD1, RDR2 or DCL3, suggesting that RDR6-dependent products, namely long dsRNAs and/or siRNAs, trigger PTGS-dependent DNA methylation. Nevertheless, none of these RdDM components are required to establish S-PTGS or produce a systemic silencing signal. Moreover, preventing de novo DNA methylation in non-silenced transgenic tissues grafted onto homologous silenced tissues does not inhibit the triggering of PTGS. Overall, these data indicate that gene body DNA methylation is a consequence, not a cause, of PTGS, and rule out the hypothesis that a PTGS-associated DNA methylation signal is transmitted independent of a PTGS signal.
EVALUATION OF RADIATION DOSES AND HAZARD INDICES IN CRUSHED ROCKS FROM SOME QUARRIES IN IBADAN SOUTHWESTERN NIGERIA
Authors: Alausa S K , Eluyera F O , Coker J O
Published: July 2019

The radiological assessment of rock samples from four quarry sites in Ibadan have been carried out. The mean activity concentrations of 40K, 226Ra and 232Th were 377.0 ± 37.9, 17.7 ± 3.6 and 4.98 ± 2.1 Bq kg−1, respectively, for Ratcon Quarry (RQ); 408.0 ± 28.7, 16.6 ± 1.6 and 10.6 ± 2.3 Bq kg−1, respectively, for Dekit Quarry; 388.0 ± 26.6, 15.7 ± 1.9 and 9.85 ± 3.9 Bq kg−1, respectively, for Hajaig Quarry; and 388.084 ± 55.9, 16.2 ± 3.9 and 12.1 ± 3.8 Bq kg−1, respectively, for NSCE Quarry (NQ). The highest mean outdoor effective dose of 0.038 ± 0.005 mSv y−1 and the minimum of 0.033 ± 0.004 mSv y−1 were obtained at NQ and RQ, respectively. The radiological hazard indices recorded in each site were <1.0. The results show lower radioactivity levels than the world average values; therefore, no serious radiological health effect is expected when the crushed rocks from the quarries are used for buildings construction.
Two‐way crosstalk between BER and c‐NHEJ repair pathway is mediated by Pol‐β and Ku70
Authors: Xia Wen , Ci Shusheng , Li Menghan , Wang Meina , Dianov Grigory L. , Ma Zhuang , Li Lulu , Hua Ke , Alagamuthu Karthick Kumar , Qing Lihong , Luo Libo , Edick Ashlin M. , Liu Lingjie , Hu Zhigang , He Lingfeng , Pan Feiyan , Guo Zhigang
Published: July 2019

Multiple DNA repair pathways may be involved in the removal of the same DNA lesion caused by endogenous or exogenous agents. Although distinct DNA repair machinery fulfill overlapping roles in the repair of DNA lesions, the mechanisms coordinating different pathways have not been investigated in detail. Here, we show that Ku70, a core protein of nonhomologous end‐joining (NHEJ) repair pathway, can directly interact with DNA polymerase‐β (Pol‐β), a central player in the DNA base excision repair (BER), and this physical complex not only promotes the polymerase activity of Pol‐β and BER efficiency but also enhances the classic NHEJ repair. Moreover, we find that DNA damages caused by methyl methanesulfonate (MMS) or etoposide promote the formation of Ku70‐Pol‐β complexes at the repair foci. Furthermore, suppression of endogenous Ku70 expression by small interfering RNA reduces BER efficiency and leads to higher sensitivity to MMS and accumulation of the DNA strand breaks. Similarly, Pol‐β knockdown impairs total‐NHEJ capacity but only has a slight influence on alternative NHEJ. These results suggest that Pol‐β and Ku70 coordinate 2‐way crosstalk between the BER and NHEJ pathways.—Xia, W., Ci, S., Li, M., Wang, M., Dianov, G. L., Ma, Z., Li, L., Hua, K., Alagamuthu, K. K., Qing, L., Luo, L., Edick, A. M., Liu, L., Hu, Z., He, L., Pan, F., Guo, Z. Two‐way crosstalk between BER and c‐NHEJ repair pathway is mediated by Pol‐β and Ku70. FASEB J. 33, 11668‐11681 (2019). www.fasebj.org
Expression of the LRRC52 g subunit (g2) may provide Ca2+‐independent activation of BK currents in mouse inner hair cells
Authors: Lang Isabelle , Jung Martin , Niemeyer Barbara A. , Ruth Peter , Engel Jutta
Published: July 2019

Mammalian inner hair cells (IHCs) transduce sound into depolarization and transmitter release. Big conductance and voltage‐ and Ca2+‐activated K+ (BK) channels are responsible for fast membrane repolarization and small time constants of mature IHCs. For unknown reasons, they activate at around ‐75 mV with a voltage of half‐maximum activation (Vhalf) of ‐50 mV although being largely insensitive to Ca2+ influx. Ca2+‐independent activation of BK channels was observed by others in heterologous expression systems if γ subunits leucine‐rich repeat‐containing protein (LRRC)26 (γ1) and LRRC52 (γ2) were coexpressed with the pore‐forming BKα subunit, which shifted Vhalf by ‐140 and ‐100 mV, respectively. Using nested PCR, we consistently detected transcripts for LRRC52 but not for LRRC26 in IHCs of 3‐wk‐old mice. Confocal immunohistochemistry showed synchronous up‐regulation of LRRC52 protein with BKα at the onset of hearing. Colocalization of LRRC52 protein and BKα at the IHC neck within ≤40 nm was specified using an in situ proximity ligation assay. Mice deficient for the voltage‐gated Cav1.3 Ca2+ channel encoded by Cacna1d do not express BKα protein. LRRC52 protein was neither expressed in IHCs of BKα nor in IHCs of Cav1.3 knockout mice. Together, LRRC52 is a γ2 subunit of BK channel complexes and is a strong candidate for causing the Ca2+‐independent activation of BK currents at negative membrane potentials in mouse IHCs.—Lang, I., Jung, M., Niemeyer, B. A., Ruth, P., Engel, J. Expression of the LRRC52 γ subunit (γ2) may provide Ca2+‐independent activation of BK currents in mouse inner hair cells. FASEB J. 33, 11721‐11734 (2019). www.fasebj.org
Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?
Authors: Thuringer Dominique , Garrido Carmen
Published: July 2019

Brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form the blood–brain barrier (BBB). Their compromised function alters the BBB integrity, which is associated with early events in the pathogenesis of cancer, neurodegenerative diseases, and epilepsy. Interestingly, these conditions also induce the expression of heat shock proteins (HSPs). Here we review the contribution of major HSP families to BMEC and BBB function. Although investigators mainly report protective effects of HSPs in brain, contrasted results were obtained in BMEC, which depend both on the HSP and on its location, intra‐ or extracellular. The therapeutic potential of HSPs must be scrupulously analyzed before targeting them in patients to reduce the progression of brain lesions and improve neurologic outcomes in the long term.—Thuringer, D., Garrido, C. Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection? FASEB J. 33, 11629–11639 (2019). www.fasebj.org
“A Friendly Place to Grow as an Educator”: A Qualitative Study of Community and Relationships Among Medical Student Coaches
Authors: Sheu Leslie , Hauer Karen E. , Schreiner Katherine , van Schaik Sandrijn M. , Chang Anna , O’Brien Bridget C.
Published: July 2019

Purpose

The rise of coaching programs in medical education sparks questions about ways to support physician coaches in learning new educational practices specific to coaching. How coaches learn from one another is of particular interest considering the potential value of social learning. Using communities of practice as a conceptual framework, the authors examine the sense of community and relationships among coaches in a new medical student coaching program, the value of this community, and the facilitators and barriers influencing community development.

Method

In this qualitative study, investigators conducted 34 interviews with physician coaches at 1 institution over 2 years (2017–2018) and observed 36 coach meetings. Investigators analyzed interview transcripts using thematic analysis and used observation field notes for context and refinement of themes.

Results

Coaches described a sense of community based on regular interactions; shared commitment to medical education; and new roles with similar experiences, joys, and challenges. They valued the sense of camaraderie and support, learning from one another, and opportunities for professional growth that strengthened their identities as educators and enhanced job satisfaction. Facilitators of community included regular meetings, leadership and administrative support, and informal opportunities to interact outside of meetings. Barriers included time constraints and geographic challenges for coaches at off-site locations.

Conclusions

The sense of community among coaches was a valued and beneficial part of their coaching experience. Coaches’ interactions and relationships promoted skill acquisition, knowledge transfer, professional development, and career satisfaction. Thus, incorporating support for social learning in coaching programs promotes coach faculty development.
Uncertainty in Decision Making in Medicine: A Scoping Review and Thematic Analysis of Conceptual Models
Authors: Helou Marieka A. , DiazGranados Deborah , Ryan Michael S. , Cyrus John W.
Published: July 2019

Purpose

The practice of medicine is rarely straightforward. Data used to facilitate medical decision making may be conflicting, ambiguous, or scarce, and providing optimal care requires balancing clinicians’ expertise and available evidence with patients’ preferences. To explore uncertainty in decision making across disciplines, the authors performed a scoping review and thematic analysis of the literature to formulate a model describing the decision-making process in medicine under uncertain conditions.

Method

In 2016, the authors performed a comprehensive search of key databases using a combination of keywords and controlled vocabulary. They identified and reviewed 3,398 records. After applying their inclusion and exclusion criteria to the titles and abstracts and then full texts, 19 articles were selected. The authors applied a qualitative thematic analysis to these articles, using codes to extract themes related to uncertainty in decision making.

Results

The 19 articles spanned 6 fields of study and 5 disciplines within the health sciences. The thematic analysis revealed 6 main themes: recognition of uncertainty, classification of uncertainty, stakeholder perspectives, knowledge acquisition, decision-making approach, and evaluation of the decision-making process.

Conclusions

Based on the themes that emerged from their thematic analysis of the literature characterizing the effects of uncertainty and ambiguity on the decision-making process, the authors developed a framework depicting the interplay between these themes with a visual representation of the decision-making process under uncertain conditions. Future research includes further development and validation of this framework to inform medical school curricula.
Type 2 diabetes and depression in the African American population
Authors: Ajuwon Abidemi Mary , Love Rene
Published: July 2019

Background and purpose:

Type 2 diabetes mellitus (T2DM) affects 30.3 million people (9.4%) in the United States. African Americans are twice as likely to be diagnosed with diabetes and have two to four times the rates of T2DM-associated complications. Depression has long been associated with poor outcomes of diabetic self-management and glycemic control. Comorbidity of T2DM and depression worsen effective self-management of these conditions in the African American population. The purpose of the study was to synthesize the literature with practice recommendations of care related to T2DM and depression in the African American population.

Methods:

A literature search was conducted using PRISMA in June 2018 with PubMed, Google Scholar, Cochrane, Scopus, Embase, and PsycINFO databases using the years from 2008 through 2018. The following terms and combination of terms were used to identify articles for the review: (a) diabetes mellitus, type 2, (b) diabetes type 2 and depression, and (c) diabetes mellitus type 2, depression, African America.

Conclusions:

The overall prevalence of depression with T2DM in African Americans is about 25%. The quality of care received by African Americans is lower when compared with non-Hispanic Whites, resulting in more emergency department visits and fewer physician visits per year. African Americans require supportive and trusting collaboration with providers for the ongoing optimal management of these complex conditions.

Implication for practice:

Culturally relevant education on lifestyle modification may help mitigate barriers to management of T2DM and depression in the African American population. Using the diabetes self-management education/support to help empower African Americans may be essential for effective self-management strategies of T2DM and depression.
Partial Epithelial–Mesenchymal Transition Was Observed Under p63 Expression in Acquired Middle Ear Cholesteatoma and Congenital Cholesteatoma
Authors: Takahashi Masahiro , Yamamoto-Fukuda Tomomi , Akiyama Naotaro , Motegi Masaomi , Yamamoto Kazuhisa , Tanaka Yasuhiro , Yamamoto Yutaka , Kojima Hiromi
Published: July 2019

Introduction:

Partial epithelial–mesenchymal transition (p-EMT) is a process by which epithelial cells partially lose their intercellular adhesion and change to obtain migration ability. The transcription factor p63 regulates the expression of cadherin family and induces epithelial cell proliferation. In this study, we hypothesized that p-EMT under p63 expression may be a key factor in epithelial cell growth in middle ear cholesteatoma.

Methods:

Specimens were surgically excised from patients with congenital cholesteatoma (CC) (n = 48), acquired middle ear cholesteatoma (AC) (n = 120), and normal skin tissue (n = 34). We analyzed immunohistochemically for the EMT marker (N-cadherin), adherence junction marker (E-cadherin), and tight junction marker (claudin-1, claudin-4, occludin). We also examined the labeling index (LI) of p63 and Proliferating cell nuclear antigen (PCNA) (late S phase marker), and Snail expression as a mobility marker.

Results:

The expression of p63 (CC 51.0 ± 7.4%, AC 50.0 ± 5.9%) was significantly higher in the thickened epithelium of CC and AC compared with normal skin tissue (p < 0.0001). The loss of E-cadherin was observed (CC 50.0%, AC 55.8%) but the expression patterns in the tight junction were almost normal. N-cadherin was partially detected in the basal and upper layer of epithelium in CC and AC. In contrast to that of normal skin tissue, the LI of PCNA was significantly higher in AC (p < 0.0001). The positive rate of Snail was significantly higher in CC (p < 0.0001).

Conclusion:

This study indicates that p-EMT via the p63 signaling pathway might playsan essential role in epithelial growth in AC and CC formation, although tight junction formation and terminal differentiation were not affected in those processes.
Robotic cholecystectomy for acute cholecystitis
Authors: Milone M. , Vertaldi S. , Bracale U. , D’Ambra M. , Cassese G. , Manigrasso M. , De Palma G.D.
Published: July 2019

Introduction:

Nowadays laparoscopic cholecystectomy is considered as criterion standard for surgical treatment of acute calculous cholecystitis. During the last few years, there has been growing interest about the robotic approach. Several authors have reported the superiority of robotic cholecystectomy, associated with a lower percentage of conversion especially in patients with intraoperative diagnosis of acute or gangrenous cholecystitis. We report 3 case reports of moderate acute cholecystitis successfully treated by robotic cholecystectomy.

Patient Concerns:

Three patients presented moderate acute calculous cholecystitis with leukocytosis, fever, nausea, vomiting, and pain.

Diagnosis:

Three patients of our study population had clinical and laboratory suspicion of moderate acute calculous cholecystitis verified by abdominal ultrasound examination, which found out cholelitiasis in all 3 cases. Final diagnosis was confirmed by intraoperative findings and histopathological examination, with two empyematous cholecystitis and one perforated cholecystitis.

Interventions:

All patients underwent robotic cholecystectomy with the da Vinci Robotic Surgical System. The entire procedure required a mean operation time of 128 minutes and the average blood loss was 60 mL, without any intraoperative complications.

Outcomes:

In all 3 cases postoperative period was uneventfull. All the patients were discharged within 24 hours and no readmissions were reported during a 30 days’ follow-up.

Conclusions:

Robotic cholecystectomy for ACC is feasible and safe. Several studies have demonstrated that robotic approach reduces the risk of conversion to open surgery in case of acute or gangrenous cholecystitis. Our results are in line with current literature. In fact, we have successfully treated 2 patients with empyematous acute cholecystitis and 1 with gangrenous cholecystitis with a totally robotic approach, without any complications or need of conversion to open surgery. In conclusion, our results confirm that it is the time to include robotic surgery in the emergency setting.
Can the prognosis of mantle cell lymphoma be predicted by simple CBC counts?
Authors: Haydaroglu Sahin Handan
Published: July 2019

Mantle cell lymphoma (MCL) exhibits a heterogenous clinical course. The MCL International Prognostic Index (MIPI) is the most commonly used risk classification system in MCL. However, it does not contain a parameter associated with the tumor microenvironment. The aim of this study was to develop a more powerful prognostic index by evaluating the absolute monocyte count (AMC), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) at diagnosis in conjunction with the clinical and laboratory parameters.

The data of 96 MCL patients with newly diagnosed from January 2014 to December 2018 were retrospectively evaluated in this study. The AMC, NLR, and PLR cut-off values were determined using the receiver operating characteristic (ROC) analysis.

The clinical behavior and results of the disease exhibited significant variation in high and low value groups at the time of diagnosis. In univariate analysis, the AMC ≥ 580, NLR ≥ 2.43, and PLR ≥ 120.85 were determined as negative prognostic factors for 5-year progression free survival (PFS) (AMC: PFS, P < .001; NLR: PFS, P < .001; PLR: PFS, P < .001) and for 5-year overall survival (OS) (P < .001, P < .001, P < .001, respectively). Beta-2 microglobulin (B2-MG), and MIPI for PFS, and for OS were found to be independent risk factors in the multivariate analysis (for PFS: P = .006, P = .002, respectively; and for OS: P = .007, P = .001, respectively). The 5-year OS was 20% in the group with B2-MG ≥ 3.5. The patients in high-risk MIPI group had poorer 5-year OS (median OS: 40 months, P < .001).

The results stated that the use of B2-MG in conjunction with MIPI was a more sensitive method in determining the prognosis in MCL (median OS: 12 months in high-risk MIPI group with a B2-MG ≥3.5, P < .001). Additionally, it was found that parameters reflecting the tumor microenvironment such as AMC, NLR, and PLR increased the risk of progression in MCL. In view of these findings, in addition B2-MG to the MIPI to create a more sensitive prognostic scoring system may provide an insight into personalization of treatment with early recognition of patients with poor prognosis.
Impact of anesthesia management during cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis on intra- and postoperative outcomes
Authors: Idrissi Moulay , Espitalier Fabien , Coveney Richard , Bélanger Marie-Eve , Gobert Quentin , Sidéris Lucas , Dubé Pierre , Verdonck Olivier , Fortier Louis-Philippe , Richebé Philippe
Published: July 2019

Background:

The impact of the anesthesia management during cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis (CRPC) on postoperative outcomes might be of major importance in the process of postoperative recovery. It might have a significant impact on intra- and postoperative outcomes, but the evaluation of this impact seems to be under-reported. To investigate the question whether the anesthesia management was reported in previous studies done in this population and if it had any impact on postoperative outcomes, we propose to conduct a systematic review of the published literature.

Methods:

For this review, we will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Medline/PubMed, Embase, EBM Reviews and the Cochrane Database of Systematic Reviews (CDSR) will be systematically consulted for eligible studies without age, gender, ethnic, and language restriction. The goal of this review will be to assess whether anesthesia monitoring, dosing, and analgesia protocols were reported in this literature on this specific procedure and whether the impact of the anesthesia management on intraoperative safety and postoperative recovery was evaluated.

Results:

The results of this systematic review will allow to answer the initial question: has the impact of anesthesia management on intraoperative safety and patients’ postoperative recovery already been studied and reported in the past for this type of major surgery? And does anesthesia have any impact on postoperative outcomes?

Discussion:

In the hypothesis that the impact of anesthesia management on patients’ postoperative recovery has never been studied, or very little reported in previous studies in this type of major surgery, it would be justified to conduct a randomized controlled trial on this specific objective.

Registration:

This systematic review protocol was registered in PROSPERO, under the registration number CRD42019124162.
Efficacy of laser acupuncture for carpal tunnel syndrome
Authors: Chen Chuan-Chih , Wu Yung-Tsan , Su Yu-Chi , Shen Yu-Ping , Chen Fang-Pey
Published: July 2019

Introduction:

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy that causes hand discomfort and work disability. Since no satisfactory conventional treatments for mild to moderate CTS exist, we apply complementary alternative medicine (CAM) to this problem. Laser acupuncture (LA), a new, non-invasive therapy which uses low-level-laser therapy (LLLT) in acupuncture could help to manage CTS. However, only one small randomized, double-blind and crossover trial had been conducted, which is not enough to provide an evidence-based assessment of the effects of LA on CTS.

Objectives:

The aim of this study protocol is to investigate the efficacy of LA therapy on patients with mild to moderate CTS through sonography of the median nerve and offer clear parameters of LLLT.

Methods:

This study protocol is a prospective double-blind randomized controlled trial. Forty subjects aged 20 to 80 years old and diagnosed as having mild to moderate CTS will be randomly assigned to the intervention group (real LA, 3-sessions a week for 2 weeks) and control group (sham LA, 3-sessions a week for 2 weeks). All subjects will be asked to wear night splints as the fundamental management approach. The laser parameters will include a wavelength of 808 nm, power output of 300 mW and power density of 300 mW/mm2, with ten seconds of treatment for each acupuncture point (PC4, PC6, PC7, PC8, LI4, LI10, LI11, HT3, HT7, and LU10). Sham LA treatment will be applied without any laser power output. The primary outcome will be based the Boston Carpal Tunnel Syndrome Questionnaire and secondary outcomes included a visual analog scale, cross sectional area of median nerve by sonography and electrophysiological test before interventions and after 2, 4, 8, 12 weeks postintervention.

Trial registration:

ClinicalTrials.gov (Identifier: NCT03580265).
Diagnostic value of MRI combined with ultrasound for lymph node metastasis in breast cancer
Authors: Cai Dechun , Lin Tong , Jiang Kailin , Sun Zhizhong
Published: July 2019

Background:

Early diagnosis and treatment of breast cancer are important to prevent fatal tumor progression. Axillary lymph node (ALN) status is the most significant prognostic factor for diagnosing overall survival in breast cancer patients. Axillary lymph node dissection (ALND) is regarded as the reference standard for determining ALN status. However, ALND is an invasive therapy with high morbidity and complications such as lymphedema, seroma and nerve injury. Comparatively, magnetic resonance imaging (MRI) and ultrasound are noninvasive and non-radiative techniques that are common imaging methods to diagnose breast cancer lymph node metastasis. Many studies have investigated the diagnostic value of MRI combined with ultrasound for breast cancer ALN metastasis, but the evidence has been insufficient to apply these modalities when diagnosing new patients.

Methods:

We will search electronic databases including PubMed, EMbase, The Cochrane Library, Chinese Biomedical Database, WangFang Database, and China National Knowledge Infrastructure. The language of studies is limited in English or Chinese. The final search includes articles published in June, 2018. Stata 14.0 software will be used for all statistical analyses, and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) will be utilized to evaluate the quality of the included studies. Meta-regression and subgroup analyses will be performed to explore heterogeneity, which will be derived from the different countries of origin of the included studies. Deeks’ funnel plot asymmetry test will be demonstrated the inexistence of publication bias.

Result:

This study will provide a rational synthesis of current evidences for magnetic resonance imaging combined with ultrasound for breast cancer.

Conclusion:

The conclusion of this study will provide evidence for the diagnostic value of MRI combined with ultrasound for lymph node metastasis in breast cancer.

Registration:

PROS-PERO CRD42019134474
Endoscopic papillary balloon dilation decreases the risk of bleeding in cirrhotic patients compared with endoscopic biliary sphincterotomy
Authors: Hung Tsung-Hsing , Tseng Chih-Wei , Chen Yen-Chun , Tseng Kuo-Chih , Hsieh Yu-Hsi , Tsai Chih-Chun
Published: July 2019

Although endoscopic papillary balloon dilation (EPBD) seems to cause fewer instances of bleeding, there are insufficient data to determine the optimal methods for decreasing the risk of bleeding in cirrhotic patients.

In this study, we compared the bleeding risks following endoscopic biliary sphincterotomy (EST) vs EPBD in cirrhotic patients and identified clinical factors associated with bleeding and 30-day mortality.

Taiwan's National Health Insurance Database was used to identify 3201 cirrhotic patients who underwent EST or EPBD between January 1, 2010, and December 31, 2013.

We enrolled 2620 patients receiving EST and 581 patients receiving EPBD. The mean age was 63.1 ± 13.9 years, and 70.4% (2252/3201) were men. The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding was higher among patients treated with EST than those treated with EPBD (EST vs EPBD: 3.5% vs 1.9%). Independent predisposing factors for bleeding included EST, renal function impairment, and antiplatelet or anticoagulant therapy. The overall 30-day mortality was 4.0% (127/3201). Older age, renal function impairment, hepatic encephalopathy, bleeding esophageal varices, ascites, hepatocellular carcinoma, biliary malignancy, and pancreatic malignancy were associated with higher risks for 30-day mortality.

To decrease post-ERCP hemorrhage, EPBD is the preferred method in patients with cirrhosis, especially for those who have renal function impairment or are receiving antiplatelet or anticoagulant therapy.
Identification of microRNA biomarkers in atrial fibrillation
Authors: Shen Nan-Nan , Zhang Zai-Li , Li Zheng , Zhang Chi , Li Hao , Wang Jia-Liang , Wang Jun , Gu Zhi-Chun
Published: July 2019

Background:

Atrial fibrillation (AF) is recognized as the most prevalent arrhythmia, and its subsequently serious complications of heart failure and thromboembolism always raise the social attention. To date, the molecular pathogenesis of AF has largely remained unclear. Publications of contemporary studies have evaluated individual miRNAs expression signatures for AF, and findings of different studies are inconsistent and not all miRNAs reported are actually important in the pathogenesis of AF.

Methods:

Medline, Embase, and Cochrane Library databases will be comprehensively searched (up to April 30, 2019) for studies identifying miRNA expression profiling in subjects with and without AF. Log10 odds ratios (logORs) and associated 95% confidence interval (95%CI) will be calculated using random-effects models. Subgroup analysis will be performed according to miRNA detecting methods, species, sample types, and ethnicities. Sensitivity analysis will be conducted to detect the robustness of the findings. The methodological quality of studies will be independently assessed using criteria adopted from the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Furthermore, bioinformatics analysis will be performed to identify the potential target genes in AF and the corresponding pathways of dysregulated miRNAs. Two reviewers will independently screen potential studies and extract data in a structured eligibility items, with any disagreements being resolved by consensus.

Results:

The present systematic review will identify potential biomarkers by pooling all differentially expressed miRNAs in AF studies, as well as to predict miRNA-target interactions and to identify the potential biometric functions using bioinformatics analysis.

Conclusions:

This systematic review and bioinformatics analysis will identify several miRNAs as potential biomarkers for AF, and explore the biological pathways regulated by the eligible miRNAs.

PROSPERO registration number:

CRD42019127594
Real-world experience with pembrolizumab in patients with advanced melanoma
Authors: Liu Frank Xiaoqing , Ou Wanmei , Diede Scott J. , Whitman Eric D.
Published: July 2019

Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.

Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan–Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.

Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18–84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids <3 months before initiating pembrolizumab. Median study follow-up was 12.9 months (range, 0.03–39.6). Median OS was 21.8 months (95% confidence interval [CI] 16.8–29.1); KM 1-year and 2-year survival rates were 61% and 48%, respectively; and median time on pembrolizumab treatment was 4.9 months (95% CI 3.7–5.5). Median OS for first-line pembrolizumab was not reached, and for second-line and third-line/later was 13.9 and 12.5 months, respectively (log-rank P = .0095). Significantly better OS (all P ≤.0014, log-rank test) was evident for patients with ECOG performance status (PS) of 0 to 1 (vs >1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription <3 months before. No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).

These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.
Multi-route applications of tranexamic acid to reduce blood loss after total knee arthroplasty: a randomized controlled trial
Authors: Zhang Shenqi , Wang Chengbin , Shi Lei , Xue Qingyun
Published: July 2019

Background:

Perioperative bleeding during total knee arthroplasty (TKA) is an ongoing problem for surgeons. Intravenous or topical application of tranexamic acid (TXA) can effectively stop bleeding, but there is still no uniform standard for the best method of administration and dose.

Methods:

From October 2016 to September 2018, 218 patients with unilateral primary knee osteoarthritis requiring knee replacement were enrolled and randomly divided into four groups. Group 1 (n = 55) received intra-articular injection (IAI) of TXA and peri-articular injection (PAI) of placebo, group 2 (n = 55) received IAI of placebo and PAI of TXA, group 3 (n = 51) received IAI of TXA and PAI of TXA, and group 4 (n = 57) received double placebo (IAI of placebo and PAI of placebo). The demographic characteristics, surgical indices, hematological indices, wound healing history, and thromboembolic events were investigated.

Results:

Eight patients were lost to follow-up and 210 patients were included in the analysis. The median TBLs in patients who received IAI of TXA and PAI of placebo and those who received IAI of placebo and PAI of TXA were 470.81 ml and 481.54 ml, respectively. These TBL levels were significantly higher compared to those in patients who received IAI of TXA and PAI of TXA (359.18 ml, P ≤ .001), but significantly lower compared to those in patients who received the double placebo (522.71 ml, P ≤ .001). Compared to other groups, more patients in the double placebo group needed a blood transfusion (P = .013). In the short-term, the double placebo group had higher VAS pain scores and less ROM after surgery (P = .011 and P = .001, respectively). In the long-term (6-month follow-up), there were no significant differences in ROM, VAS, DVT, PE, or wound-related complications.

Conclusion:

The combined use of IAI and PAI of TXA can significantly reduce the TBL and the need for blood transfusion without delaying wound healing or increasing the risk of DVT and PE. In the short-term after surgery, this combined method reduces the pain VAS scores and improves the ROM; however, there are no long-term effects on VAS and ROM.
Efficacy and safety of dapagliflozin as monotherapy in patients with type 2 diabetes mellitus
Authors: Feng Miao , Lv Haihong , Xu Xia , Wang Jue , Lyu Wenyi , Fu Songbo
Published: July 2019

Background:

Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs.

Methods:

We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software.

Results:

Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: –0.60%; 95% confidence interval [CI]: –0.67%, –0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: –1.30 mmol/L; 95% CI: –1.52, –1.08; P < .00001), and body weight (WMD: –1.50 kg; 95% CI: –1.67, –1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001).

Conclusions:

Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.
Efficacy and safety of eradication therapy for elderly patients with helicobacter pylori infection
Authors: Kobayashi Satoshi , Joshita Satoru , Yamamoto Chikara , Yanagisawa Takumi , Miyazawa Takayuki , Miyazawa Megumi , Kubota Daisuke , Sato Junichi , Umemura Takeji , Tanaka Eiji
Published: July 2019

Helicobacter pylori (H. pylori) is the most prevalent chronic bacterial infection and is associated with chronic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Although eradication therapy is widely performed for H. pylori infection, adverse events (AEs) are of particular concern in the elderly. This study investigated the efficacy and safety of H. pylori eradication therapy for elderly patients.

Retrospective investigation of 1271 cases (median age: 61 years, 730 male) of H. pylori infection was performed to compare clinical indications and outcomes among the younger group (<65 years old), elderly group (65–74 years old), and super-elderly group (>75 years old).

Chronic gastritis (77.0%) and gastric and/or duodenal ulcer (16.4%) were the most frequent indications for eradication therapy in the cohort. The respective eradication and AE rates for the first and second treatment regimens were 92.1% (1044 of 1133 cases) and 9.1% (103 of 1133 cases) and 84.2% (123 of 146 cases) and 8.9% (13 of 146 cases). No significant differences were detected for eradication rate or AE frequency between the super-elderly group and the other groups. Prior to therapy, the super-elderly group had significantly less frequent chronic gastritis than the other groups but more frequent gastric or duodenal ulcer and post-gastric cancer treatment (all P < .001), indicating a reluctance for clinicians to treat very old patients, possibly due to unfounded concerns of complications.

Triple therapy for H. pylori eradication is effective and safe, even for elderly patients.
Occult papillary thyroid cancer presenting as cystic metastasis of the lateral neck
Authors: Schwaiger Karl , Koeninger Fabian , Wimbauer Julia , Heinrich Klemens , Gala-Kokalj Alexandra , Wechselberger Gottfried
Published: July 2019

Rationale:

Papillary thyroid cancer accounts for up to 85% of all cases of thyroid carcinoma. This disease entity is notorious for metastatic invasion of adjacent lymph nodes, including the cervical lymph nodes, potentially presenting as a growing lateral neck mass. However, these lesions tend to be recognized and diagnosed soon due to the palpable mass.

Patient concerns:

This report describes a very rare case of a huge slow-growing neck metastasis based on a 6 mm papillary thyroid microcarcinoma. This patient presented with a painless, but continuously growing right lateral neck mass. Aside from that, no specific complaints were mentioned.

Diagnosis:

The underlying cause of this patient's neck mass turned out to be an occult papillary thyroid microcarcinoma (Ø 6 mm) with metastatic invasion and subsequent cystic degeneration of cervical lymph nodes. Accurate diagnosis was made after surgical intervention through histopathological analysis.

Interventions:

The patient underwent complete resection of the cervical mass in conjunction with total thyroidectomy and right cervical neck dissection, followed by adjuvant iodine- and chemotherapy.

Outcome:

Margin free surgical resection without any postoperative complications could be achieved. The patient received iodine supplementation and remained free of recurrence during regular clinical follow-ups for 2 years. The therapy was curative.

Lessons:

This case report emphasizes the importance of a thorough diagnostic work-up including preoperative tissue sampling of any cervical neck mass, since a benign appearance on imaging does not exclude a malignant process.
Comprehensive analysis of competing endogenous RNA network and 3-mRNA signature predicting survival in papillary renal cell cancer
Authors: Zhu Xin , Tan Jianyu , Liang Zongjian , Zhou Mi
Published: July 2019

Long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to exert significant roles in regulating the expression of mRNAs by sequestering and binding miRNAs. To elucidate the functional roles and regulatory mechanism of lncRNAs in papillary renal cell cancer (pRCC), we conducted a comprehensive analysis of ceRNA network and constructed a mRNA signature to predict prognosis of pRCC.

We collected mRNAs and lncRNAs expression profiles of 289 pRCC samples and 32 normal renal tissues, and miRNA expression profiles of 292 pRCC samples and 34 normal samples from The Cancer Genome Atlas (TCGA) database. Differential expressions of RNAs were evaluated by the “edgeR” package in R. Functional enrichment analysis of DEmRNA was performed by DAVID 6.8 and KEGG, while PPI network of top 200 DEmRNAs was conducted using the STRING database. The univariate and multivariate Cox regression were conducted to figure out the candidate DEmRNAs with predictive values in prognosis. Receiver operator characteristic (ROC) curve estimation was performed to achieve the area under the curve (AUC) of the ROC curve to judge mRNA-associated prognosic model. A ceRNA network was established relying on the basis of combination of lncRNA-miRNA interactions and miRNA-mRNA interactions.

A total of 1928 DEmRNAs, 981 DElncRNAs, and 52 DEmiRNAs were identified at significance level of |log2Fold Change |>2 and adjusted P-value < .01. A 3-mRNA signatures consisting of ERG, RRM2, and EGF was constructed to predict survival in pRCC. Moreover, a pRCC-associated ceRNA network was constructed, with 57 lncRNAs, 11 miRNAs, and 28 mRNAs.

Our study illustrated the regulatory mechanism of ceRNA network in papillary renal cancer. The identified mRNA signatures could be used to predict survival of pRCC.