bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining the optimal bilirubin level before hepatectomy for hilar cholangiocarcinoma
Authors: She Wong Hoi , Cheung Tan To , Ma Ka Wing , Tsang Simon H. Y. , Dai Wing Chiu , Chan Albert C. Y. , Lo Chung Mau
Published: September 2020

Background

In the management of operable hilar cholangiocarcinoma (HC) patients with hyperbilirubinemia, preoperative biliary drainage is a measure to bring down the bilirubin to a certain level so as to avoid adverse postoperative outcomes that would otherwise result from hyperbilirubinemia. A cutoff value of bilirubin level in this context is needed but has not been agreed upon without controversy. This retrospective study aimed to identify a cutoff of preoperative bilirubin level that would minimize postoperative morbidity and mortality.

Methods

Data of patients having hepatectomy with curative intent for HC were analyzed. Discriminative analysis was performed to identify the preoperative bilirubin level that would make a survival difference. The identified level was used as the cutoff to divide patients into two groups. The groups were compared.

Results

Ninety patients received hepatectomy with curative intent for HC. Their median preoperative bilirubin level was 23 μmol/L. A cutoff preoperative bilirubin level of 75 μmol/L was derived from Youden’s index (sensitivity 0.333; specificity 0.949) and confirmed to be optimal by logistic regression (relative risk 9.250; 95% confidence interval 1.932–44.291; p = 0.005), with mortality shown to be statistically different at 90 days (p = 0.008). Patients were divided into Group A (≤75 μmol/L; n = 82) and Group B (> 75 μmol/L; n = 8). Group B had a higher preoperative bilirubin level (p < 0.001), more intraoperative blood loss (3.12 vs 1.4 L; p = 0.008), transfusion (100% vs 42.0%; p = 0.011) and replacement (2.45 vs 0.0 L; p < 0.001), more postoperative renal complications (p = 0.036), more in-hospital deaths (50% vs 8.5%; p = 0.004), and more 90-day deaths (50% vs 9.8%; p = 0.008). Group A had a longer follow-up period (p = 0.008). The groups were otherwise comparable. Disease-free survival was similar between groups (p = 0.142) but overall survival was better in Group A (5-year, 25.2% vs 0%; p < 0.001). On multivariate analysis, preoperative bilirubin level and intraoperative blood replacement were risk factors for 90-day mortality.

Conclusion

A cutoff value of preoperative bilirubin level of 75 μmol/L is suggested, as the study showed that a preoperative bilirubin level ≤ 75 μmol/L resulted in significantly less blood replacement necessitated by blood loss during operation and significantly better patient survival after surgery.
Clinical practice guideline on the prevention and management of neonatal extravasation injury: a before-and-after study design
Authors: Chan Kam Ming , Chau Janita Pak Chun , Choi Kai Chow , Fung Genevieve Po Gee , Lui Wai Wa , Chan Meme Suk Ying , Lo Suzanne Hoi Shan
Published: September 2020

Background

Extravasation injury resulting from intravenous therapies delivered via peripheral intravenous catheters or umbilical and peripherally inserted central venous catheters is a common iatrogenic complication occurring in neonatal intensive care units. This study aimed to evaluate the effectiveness of an evidence-based clinical practice guideline in the prevention and management of neonatal extravasation injury by nurses.

Methods

A controlled before-and-after study was conducted in a neonatal unit. The clinical practice guideline was developed, and a multifaceted educational program was delivered to nurses. Neonatal outcomes, including the rates of peripheral intravenous extravasation and extravasation from a central line, were collected at the pre- and post-intervention periods. Post-intervention data for nurses, including the nurses’ level of knowledge and adherence, were collected at six months after the program.

Results

104 and 109 neonates were recruited in the pre-intervention period (control) and the post-intervention period (intervention), respectively. The extravasation rate before and after the intervention was 14.04 and 2.90 per 1,000 peripheral intravenous catheters days, respectively. The adjusted odds ratio of peripheral intravenous extravasation post-intervention compared with that of pre-intervention was 0.20 (95% confidence interval: 0.05–0.74; p = 0.02) after adjusting for peripheral intravenous catheter days. The extravasation from a central line rate of the control and intervention groups post-intervention was 4.94 and zero per 1,000 central venous catheter days, respectively. Fifty-nine registered nurses were recruited. At six months post-program, there were significant improvements in the nurses’ level of knowledge and adherence.

Conclusions

These findings suggest that the implementation of an evidence-based clinical practice guideline significantly reduced the rate of peripheral intravenous extravasation and extravasation from a central line in neonates. However, to maintain nurses’ knowledge and adherence to the evidence-based practice, the educational program will have to be conducted periodically and incorporated into the nurses’ induction program.

Trial registration

ClinicalTrials.gov, Identifiers: NCT04321447. Registered 20 March 2020 - Retrospectively registered.
Professional development arising from multiple-site workplace learning: boundary crossing between the education and clinical contexts
Authors: Barry Margot , Kuijer-Siebelink Wietske , Niewenhuis Loek A. F. M. , Scherpbier Nynke
Published: September 2020

Background

This research explores the value of an inter-organisational jurisdiction, on the professional development of faculty members in their roles of researcher and educator. Faculty members from a Dutch university of applied sciences, who work in both the education and clinical practice contexts, participated in this research.

Methods

Individual semi-structured interview were conducted with nine faculty members, from various academic health professions, on their experiences of professional development arising from working in both the clinical and education contexts. In this exploratory, post-positive interview study, interview transcripts were analysed thematically.

Results

Participants reported that working in two organisational contexts, whilst performing two faculty roles that span both contexts, enhances their ability to broker connections between research, teaching and practice. The boundary crossing activities which participants performed, contributed to professional development in all faculty roles. The broker role was not seen as being a unique role which is distinct from research and practice roles. Broker activities were seen as generic and supportive of the roles that bestow academic status and expertise.

Conclusions

To the participants in this research, the relevance of the broker role in professional development is not as evident as the relevance of roles that enhance specialisation and subject specific expertise. They consider broker activities as supportive to the roles of researcher and teacher. The broker role is time consuming, but not yet visible as a distinct professionalisable work-package in its own right. It is also not well defined in literature. A better understanding of the broker role could lead to its development in order to harness its professional development potential tenably across academic roles.
Patients’ experiences with the advanced practice nurse role in Swiss family practices: a qualitative study
Authors: Schönenberger Nicole , Sottas Beat , Merlo Christoph , Essig Stefan , Gysin Stefan
Published: September 2020

Background

Considering shortages of general practitioners (GP) and strategies for improving the quality of health care provision, many countries have implemented interprofessional care models with advanced practice nurses (APN). International evidence suggests that APN care results in high patient satisfaction. In Switzerland, the role is still new, and the patient perspective has not yet been researched. Our aim was therefore to explore patients’ experiences with the APN role in Swiss family practices.

Methods

We conducted 22 semi-structured interviews in four different family practices with patients aged 18 to 97 suffering from minor acute to multiple chronic diseases, and who had at least one consultation with an APN. All interviews were audiotaped, transcribed verbatim, and analysed using qualitative content analysis.

Results

The analysis resulted in five themes: Despite the unfamiliarity, all patients were willing to be consulted by an APN because it was recommended by their GP (1); after several encounters, most participants perceived differences between the APN and the GP consultation in terms of the length and style of the consultations as well as the complexity of their tasks (2); the interviewees emphasised coaching, guidance, care coordination, and GP-assisting tasks as APN core competencies and attributed the characteristics empathetic, trustworthy, and competent to the APN role (3); most patients especially valued home visits and the holistic approach of the APNs, but they also noticed that in certain cases GP supervision was required (4); and due to the close collaboration between the APN and the GP, patients felt safe, well cared for and experienced improvements in physical and psychological well-being as well as in daily activities (5).

Conclusion

Our results suggested that patients value the APNs’ competencies, despite their initial lack of role knowledge. Trust in the GP seemed to be the most important factor for patients’ receptiveness toward the APN role. Overall, patients perceived an added value due to the enlargement of the scope of practice offered by APNs. The patient perspective might provide valuable insights for further APN role implementation in Swiss family practices.
Lung function, pharmacokinetics, and tolerability of inhaled indacaterol maleate and acetate in asthma patients
Authors: Miller David , Vaidya Soniya , Jauernig Juergen , Ethell Brian , Wagner Kristina , Radhakrishnan Rajkumar , Tillmann Hanns-Christian
Published: September 2020

Background

Indacaterol maleate delivered with the Breezhaler® inhalation device is a long-acting β2-agonist approved for chronic obstructive pulmonary disease. In the development of a once daily, inhaled fixed dose combination (FDC) of indacaterol, glycopyrronium bromide (a long-acting muscarinic antagonist), and mometasone furoate (an inhaled corticosteroid [ICS]) for the treatment of patients with asthma, the acetate salt of indacaterol is used instead of the maleate salt. Here, we investigated the lung function, pharmacokinetics (PK) and safety of indacaterol maleate 150 μg once daily (o.d.) and indacaterol acetate 150 μg o.d. in comparison with placebo.

Methods

This was a randomised, double-blind, three-period crossover study (ClinicalTrials.gov identifier, NCT03257995) in patients with asthma on background ICS therapy. Patients with percent predicted pre-bronchodilator forced expiratory volume per second (FEV1) ≥50% and ≤ 90% were included in the study. Patients received indacaterol maleate 150 μg o.d., indacaterol acetate 150 μg o.d., or placebo on top of stable background ICS in randomised sequence. Trough FEV1 was assessed after 14 days of treatment. PK of indacaterol salts were assessed at steady state after 14 days of treatment; peak expiratory flow (PEF) rate and rescue medication use were collected with a combined PEF-meter/electronic diary throughout the study.

Results

Of the 54 adult patients (median age of 48 years), 51 patients completed the study. Both indacaterol salts demonstrated statistically significant improvements in trough FEV1 of 186 mL (maleate) and 146 mL (acetate) compared with placebo (both P < 0.001). FEV1 AUC0-4h improved by 248 mL (maleate) and 245 mL (acetate), and PEF by 33 L/min (maleate) and 30.8 L/min (acetate) versus placebo. Systemic exposure of indacaterol (AUC0-24h,ss and Cmax,ss on Day 14) was comparable after administration of both salt forms. Both salt forms demonstrated a good safety profile and were well tolerated, with a difference in the reporting frequency of AEs of coughing (maleate, 23.5%; acetate, 0%).

Conclusions

In patients with asthma, indacaterol maleate and acetate elicited comparable and significant improvements in lung function compared with placebo and achieved comparable systemic exposure. Both indacaterol salts were safe and well tolerated.

Trial registration

ClinicalTrials.gov NCT03257995 June 06, 2017
Correction to: Medical expenditure for patients with hemophilia in urban China: data from medical insurance information system from 2013 to 2015
Authors: Gong Guang-wen , Chen Ying-chun , Fang Peng-qian , Min Rui
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model
Authors: Friesner Isabel D. , Martinez Erik , Zhou Haocheng , Gould Jonathan Douglas , Li Anna , Chen Zhe Sage , Zhang Qiaosheng , Wang Jing
Published: September 2020

Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood at the network level. In this study, we recorded local field potentials from the ACC of freely moving rats. Animals were injected with complete Freund’s adjuvant (CFA) to induce persistent inflammatory pain. Mechanical stimulations were administered to the hind paw before and after CFA administration. We found a significant increase in the high-gamma band (60–100 Hz) power in response to evoked pain after CFA treatment. Ketamine, however, reduced the high-gamma band power in response to evoked pain in CFA-treated rats. In addition, ketamine had a sustained effect on the high-gamma band power lasting up to five days after a single dose administration. These results demonstrate that ketamine has the potential to alter maladaptive neural responses in the ACC induced by chronic pain.
Principal components of tau positron emission tomography and longitudinal tau accumulation in Alzheimer’s disease
Authors: Cho Hanna , Baek Min Seok , Lee Hye Sun , Lee Jae Hoon , Ryu Young Hoon , Lyoo Chul Hyoung
Published: September 2020

Background

We aimed to investigate the clinical correlates of principal components (PCs) of tau positron emission tomography (PET) and their predictability for longitudinal changes in tau accumulation in Alzheimer’s disease (AD).

Methods

We enrolled 272 participants who underwent two PET scans [18F-flortaucipir for tau and 18F-florbetaben for amyloid-β (Aβ)], brain magnetic resonance imaging, and neuropsychological tests as baseline assessments. Among them, 187 participants underwent the same follow-up assessments after an average of 2 years. Using Aβ-positive AD dementia-specific PCs obtained from the baseline scans of 56 Aβ-positive patients with AD dementia, we determined the expression of the first two PCs (PC1 and PC2) in all participants. We assessed the correlation of PC expression with baseline clinical characteristics and tau accumulation rates. Moreover, we investigated the predictability of PCs for the longitudinal tau accumulation in training and test sets.

Results

PC1 corresponded to the tau distribution pattern in AD, while the two PC2 extremes reflected the parietal or temporal predominance of tau distribution. PC1 expression increased with tau burden and decreased with cognitive impairment, while PC2 expression decreased with advanced age and visuospatial and attention function deterioration. The tau accumulation rate was positively correlated with PC1 expression (greater tau burden) and negatively correlated with PC2 expression (temporal predominance). A regression model using both PCs could predict longitudinal changes in the tau burden (intraclass correlation coefficient = 0.775, R2 = 0.456 in test set).

Conclusions

PC analysis of tau PET could be useful for evaluating disease progression, characterizing the tau distribution pattern, and predicting longitudinal tau accumulation.
Predictive value of a false-negative focused abdominal sonography for trauma (FAST) result in patients with confirmed traumatic abdominal injury
Authors: Alramdan Mohammed H. A. , Yakar Derya , IJpma Frank F. A. , Kasalak Ömer , Kwee Thomas C.
Published: September 2020

Objective

To investigate if patients with confirmed traumatic abdominal injury and a false-negative focused abdominal sonography for trauma (FAST) examination have a more favorable prognosis than those with a true-positive FAST.

Methods

This study included 97 consecutive patients with confirmed traumatic abdominal injury (based on computed tomography [CT] and/or surgical findings) who underwent FAST.

Results

FAST was false-negative in 40 patients (41.2%) and true-positive in 57 patients (58.8%). Twenty-two patients (22.7%) had an unfavorable outcome (defined as the need for an interventional radiologic procedure, laparotomy, or death due to abdominal injury). Univariately, a false-negative FAST (odds ratio [OR] 0.24; p = 0.017) and a higher systolic blood pressure (OR, 0.97 per mmHg increase; p = 0.034) were significantly associated with a favorable outcome, whereas contrast extravasation on CT (OR, 7.17; p = 0.001) and shock index classification (OR, 1.89 for each higher class; p = 0.046) were significantly associated with an unfavorable outcome. Multivariately, only contrast extravasation on CT remained significantly associated with an unfavorable outcome (OR, 4.64; p = 0.016). When excluding contrast extravasation on CT from multivariate analysis, only a false-negative FAST result was predictive of a favorable outcome (OR, 0.28; p = 0.038).

Conclusion

Trauma patients with confirmed abdominal injury and a false-negative FAST have a better outcome than those with a positive FAST. FAST may be valuable for risk stratification and prognostication in patients with a high suspicion of abdominal injury when CT has not been performed yet or when CT is not available.
Derivation and propagation of spermatogonial stem cells from human pluripotent cells
Authors: Xu Huiming , Yang Mengbo , Tian Ruhui , Wang Yonghui , Liu Linhong , Zhu Zijue , Yang Shi , Yuan Qingqing , Niu Minghui , Yao Chencheng , Zhi Erlei , Li Peng , Zhou Chenhao , He Zuping , Li Zheng , Gao Wei-Qiang
Published: September 2020

Objectives

This study is designed to generate and propagate human spermatogonial stem cells (SSCs) derived from human pluripotent stem cells (hPSCs).

Methods

hPSCs were differentiated into SSC-like cells (SSCLCs) by a three-step strategy. The biological characteristics of SSCLCs were detected by immunostaining with antibodies against SSC markers. The ability of self-renewal was measured by propagating for a long time and still maintaining SSCs morphological property. The differentiation potential of SSCLCs was determined by the generation of spermatocytes and haploid cells, which were identified by immunostaining and flow cytometry. The transcriptome analysis of SSCLCs was performed by RNA sequencing. The biological function of SSCLCs was assessed by xeno-transplantation into busulfan-treated mouse testes.

Results

SSCLCs were efficiently generated by a 3-step strategy. The SSCLCs displayed a grape-like morphology and expressed SSC markers. Moreover, SSCLCs could be propagated for approximately 4 months and still maintained their morphological properties. Furthermore, SSCLCs could differentiate into spermatocytes and haploid cells. In addition, SSCLCs displayed a similar gene expression pattern as human GPR125+spermatogonia derived from human testicular tissues. And more, SSCLCs could survive and home at the base membrane of seminiferous tubules.

Conclusion

SSCLCs were successfully derived from hPSCs and propagated for a long time. The SSCLCs resembled their counterpart human GPR125+spermatogonia, as evidenced by the grape-like morphology, transcriptome, homing, and functional characteristics. Therefore, hPSC-derived SSCLCs may provide a reliable cell source for studying human SSCs biological properties, disease modeling, and drug toxicity screening.
Stepwise differentiation and functional characterization of human induced pluripotent stem cell-derived choroidal endothelial cells
Authors: Mulfaul Kelly , Giacalone Joseph C. , Voigt Andrew P. , Riker Megan J. , Ochoa Dalyz , Han Ian C. , Stone Edwin M. , Mullins Robert F. , Tucker Budd A.
Published: September 2020

Background

Endothelial cells (ECs) are essential regulators of the vasculature, lining arteries, veins, and capillary beds. While all ECs share a number of structural and molecular features, heterogeneity exists depending on their resident tissue. ECs lining the choriocapillaris in the human eye are lost early in the pathogenesis of age-related macular degeneration (AMD), a common and devastating form of vision loss. In order to study the mechanisms leading to choroidal endothelial cell (CEC) loss and to develop reagents for repairing the choroid, a reproducible in vitro model, which closely mimic CECs, is needed. While a number of protocols have been published to direct induced pluripotent stem cells (iPSCs) into ECs, the goal of this study was to develop methods to differentiate iPSCs into ECs resembling those found in the human choriocapillaris specifically.

Methods

We transduced human iPSCs with a CDH5p-GFP-ZEO lentiviral vector and selected for transduced iPSCs using blasticidin. We generated embryoid bodies (EBs) from expanded iPSC colonies and transitioned from mTESR™1 to EC media. One day post-EB formation, we induced mesoderm fate commitment via addition of BMP-4, activin A, and FGF-2. On day 5, EBs were adhered to Matrigel-coated plates in EC media containing vascular endothelial cell growth factor (VEGF) and connective tissue growth factor (CTGF) to promote CEC differentiation. On day 14, we selected for CECs using either zeocin resistance or anti-CD31 MACS beads. We expanded CECs post-selection and performed immunocytochemical analysis of CD31, carbonic anhydrase IV (CA4), and RGCC; tube formation assays; and transmission electron microscopy to access vascular function.

Results

We report a detailed protocol whereby we direct iPSC differentiation toward mesoderm and utilize CTGF to specify CECs. The CDH5p-GFP-ZEO lentiviral vector facilitated the selection of iPSC-derived ECs that label with antibodies directed against CD31, CA4, and RGCC; form vascular tubes in vitro; and migrate into empty choroidal vessels. CECs selected using either antibiotic selection or CD31 MACS beads showed similar characteristics, thereby making this protocol easily reproducible with or without lentiviral vectors.

Conclusion

ECs generated following this protocol exhibit functional and biochemical characteristics of CECs. This protocol will be useful for developing in vitro models toward understanding the mechanisms of CEC loss early in AMD.
Transplanted hair follicle stem cells migrate to the penumbra and express neural markers in a rat model of cerebral ischaemia/reperfusion
Authors: Zhang Xuemei , Tang Hao , Mao Senlin , Li Bing , Zhou Yinglian , Yue Hui , Wang Duo , Wang Yifei , Fu Jin
Published: September 2020

Background

Ischaemic stroke has become the main cause of death and severe neurological disorders, for which effective restorative treatments are currently limited. While stem cell transplantation offers therapeutic potential through neural regeneration, this approach is associated with the challenges of limited applicable sources. Hair follicle stem cells (HFSCs) are multipotential cells that can differentiate into ectodermal and mesodermal lineages and proliferate for long periods. The therapeutic potentials of HFSCs have not been investigated in ischaemic stroke models, and therefore, in this study, we aimed to determine whether they could survive and migrate to ischaemic areas after a stroke attack.

Methods

A rat model of middle cerebral artery ischaemia/reperfusion was established and intravenously administered HFSCs. The potential of HFSCs to migrate and differentiate into neuron-like cells as well as their ability to reduce the infarct size was evaluated. Rat brain tissue samples were collected 2 weeks after cell transplantation and analysed via TTC staining, immunofluorescence and immunohistochemistry methods. The data were statistically analysed and presented as the means ± standard deviations.

Results

Intravenously administrated rat HFSCs were able to migrate to the penumbra where they expressed neuron-specific markers, reduced the infarct volume and promoted neurological recovery.

Conclusion

HFSC transplantation has therapeutic potential for ischaemic stroke and is, therefore, worthy of further investigation toward possible clinical development for treating stroke patients.
Both Wnt signaling and epidermal stem cell-derived extracellular vesicles are involved in epidermal cell growth
Authors: Leng Ling , Ma Jie , Lv Luye , Wang Wenjuan , Gao Dunqin , Zhu Yunping , Wu Zhihong
Published: September 2020

Millions suffer from skin diseases. Functional interfollicular epidermal stem cells are needed in skin therapy or drug screening in vitro. We obtained functional interfollicular epidermal stem cells with intact stemness and cell junctions by treating them with Wnt3a. Moreover, epidermal stem cell-derived extracellular vesicles were useful in epidermal cell growth. Finally, functional epidermal 3D organoids with polarity were cultured using Wnt3a and the supernatant derived from interfollicular epidermal stem cells and fresh medium in a 1:1 ratio. These results provide novel directions for the improvement of skin organoids and their potential in clinical application.
Compressed graph representation for scalable molecular graph generation
Authors: Kwon Youngchun , Lee Dongseon , Choi Youn-Suk , Shin Kyoham , Kang Seokho
Published: September 2020

Recently, deep learning has been successfully applied to molecular graph generation. Nevertheless, mitigating the computational complexity, which increases with the number of nodes in a graph, has been a major challenge. This has hindered the application of deep learning-based molecular graph generation to large molecules with many heavy atoms. In this study, we present a molecular graph compression method to alleviate the complexity while maintaining the capability of generating chemically valid and diverse molecular graphs. We designate six small substructural patterns that are prevalent between two atoms in real-world molecules. These relevant substructures in a molecular graph are then converted to edges by regarding them as additional edge features along with the bond types. This reduces the number of nodes significantly without any information loss. Consequently, a generative model can be constructed in a more efficient and scalable manner with large molecules on a compressed graph representation. We demonstrate the effectiveness of the proposed method for molecules with up to 88 heavy atoms using the GuacaMol benchmark.
Baseline total metabolic tumor volume combined with international peripheral T-cell lymphoma project may improve prognostic stratification for patients with peripheral T-cell lymphoma (PTCL)
Authors: Jiang Chong , Teng Yue , Chen Jieyu , Wang Zhen , Zhou Zhengyang , Ding Chongyang , Xu Jingyan
Published: September 2020

Purpose

The aim of this study was to explore the prognostic value of total metabolic tumor volume (TMTV) at baseline 18F-FDG PET/CT in patients diagnosed with peripheral T-cell lymphoma (PTCL).

Materials and methods

Eighty-four newly diagnosed PTCL patients who underwent baseline 18F-FDG PET/CT prior to treatment between March 2009 and January 2019 were enrolled in this retrospective study. The FDG-avid lesions in each patient were segmented using semiautomated software to calculate the maximum standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG) values using the boundaries of voxels presenting with the 41% SUVmax threshold method. Progression-free survival (PFS) and overall survival (OS) were used as end points to evaluate patient prognosis. The log-rank test and Cox regression analyses were used to evaluate PFS and OS.

Results

ROC curve analysis indicated an ideal TMTV cut-off value of 228.8 cm3. During the 4–131 months (29.2 ± 28.5 months) follow-up period, high TMTV was significantly associated with worse PFS and OS. TMTV and the international peripheral T-cell lymphoma project score (IPTCLP) were independent predictors of PFS and OS with multivariate analysis. The combination of TMTV and the IPTCLP may provide significantly better risk substratification in PFS and OS of PTCL patients.

Conclusions

Both TMTV and IPTCLP are independent predictors of PTCL patient survival outcomes. Moreover, the combination of TMTV and IPTCLP improved patient risk stratification and may contribute to personalized therapeutic regimens.
Millennial paleotsunami history at Minna Island, southern Ryukyu Islands, Japan
Authors: Fujita Ryosuke , Goto Kazuhisa , Iryu Yasufumi , Abe Tomoya
Published: September 2020

Huge tsunami waves have repeatedly bombarded the southern end of the Ryukyu Islands (Miyako and Yaeyama Islands, southwestern Japan) at several-hundred-year intervals. Therefore, clarifying the islands’ paleotsunami history is important for risk assessment. Nevertheless, discrepancies of paleotsunami histories exist among regional studies of tsunami boulders and sandy tsunami deposits. Radiocarbon ages of tsunami boulders indicate that tsunami events of the last 2400 years have occurred every 150–400 years, most recently the historical 1771 Meiwa tsunami. Sandy tsunami deposits at Yaeyama Islands show that four tsunami events of the last 2000 years struck the islands at approximately 600-year intervals. Sandy tsunami deposits of the Miyako Islands have been studied only rarely. Therefore, studying sandy tsunami deposits in the Miyako Islands is crucially important for clarifying the paleotsunami history of this region. We conducted a trench survey on Minna Island, located among the westernmost Miyako Islands, which revealed two sandy tsunami deposits under a coral tsunami boulder transported by the 1771 tsunami. The upper tsunami deposit was likely deposited by the 1771 tsunami, as inferred from stratigraphic correlation to the tsunami boulder. However, the lower tsunami deposit was probably deposited 700–1000 years ago, which is consistent with the age range of the paleotsunami reported for Yaeyama Islands. Because sandy tsunami deposits found in this and earlier studies are thick and deposited at high elevation and far inland, these are useful markers of large tsunami events similar to the 1771 event. However, the reported tsunami boulders of various sizes are deposited along the coast and reefs: they can be formed not only by large tsunami events but also by small ones. It is noteworthy that each tsunami deposit is coarse and thick (40–48 cm) relative to the island elevation (about 12 m maximum, 7 m above the mean sea level at the study site). By assuming that tsunamis have affected this region repeatedly during the past few thousand years at around 600-year intervals, tsunamis might have been important geomorphic agents for building up small reef-surrounded islands such as Minna Island.
Audit of electronic operative documentation in interventional radiology: the value of standardised proformas
Authors: Theodoulou Iakovos , Judd Rhys , Raja U. , Karunanithy N. , Sabharwal Tarun , Gangi Afshin , Diamantopoulos Athanasios
Published: September 2020

Background

On the background of the interventional radiology department of a tertiary hospital converting its periprocedural documentation from paper-based to electronic using a standardised proforma, a study was performed to ascertain the effects of this change on the standard of clinical documentation for radiologically-guided angiographic procedures. Using a retrospective approach, perioperative records were analysed in reverse chronological order for inclusion in the study. The standard for this audit was developed in the form of minimum criteria that all clinical documentation of angiographic procedures were expected to meet.

Results

The audit was performed at three equally spaced intervals of 6 months, yielding a total of 99 records. The baseline audit of paper-based records concluded > 80% completeness for 8 out of the 14 of parameters measured, with only two of parameters meeting the target of 100% completeness. The second audit cycle performed on electronic records found 7 out of 14 parameters demonstrating absolute improvement in completeness, when compared to paper-based, but with the number of parameters exceeding 80% completeness falling to only 4 out of 14. Again, 100% completeness was observed in only 2 of the parameters. In the final audit cycle, after the introduction of a standardised electronic proforma, performance improved in every dimension with 6 out of 14 parameters reaching completeness of 100% and the 80% completeness threshold met by 12 out of 14 parameters.

Conclusion

The construction of a procedure-specific perioperative electronic proforma can save clinicians valuable time and encourage safe and effective clinical documentation.
High-yield production and biochemical characterization of α-galactosidase produced from locally isolated Penicillium sp.
Authors: Kote Naganagouda , Manjula A. C. , Vishwanatha T. , Patil Aravind Gouda G.
Published: September 2020

Background

α-Galactosidase is widely used in various biotechnological applications such as food processing, beet sugar, the pulp and paper industries, synthesis of oligosaccharides by trans-galactosylation, hydraulic fracturing of oil and gas wells, and medical applications.

Results

Screening and identification of fungi for α-galactosidase activity was performed. The isolate Penicillium sp. showed good α-galactosidase activity. α-Galactosidase production by the fungal strain Penicillium sp. cultivated in solid state fermentation (SSF) conditions using copra mannan extract as nutrient medium was investigated. The maximum α-galactosidase activity of 5.391 U/mL was obtained in defatted copra meal (dFCO) as carbon source, which is 2–3% greater as compared with commercial mannans and unprocessed copra meal. The highest product yield of α-galactosidase was obtained with media containing yeast extract (6.672 U/ml) as organic nitrogen and ammonium nitrate (6.325 U/ml) and as inorganic nitrogen source with media pH 5.5, and the time course of enzyme production was at the 5th day of fermentation, respectively. The optimum pH of α-galactosidase was obtained at pH 5 and optimum temperature at 60 °C. The enzyme was stable between pH 4 and 6 and retained more than 50% of residual activity for an 8-h incubation period. The Ca+2 ions enhanced the enzyme activity and Mn+2 ions have not altered the enzyme activity, whereas Hg+2 strongly inhibited the enzyme activity.

Conclusions

The findings of present investigations on α-galactosidase are of particular interest for its application in the food processing industry.
Immunostimulant as an adjuvant therapy on Toll-like receptor concentration in children with acute otitis media
Authors: El Hamshary Ashraf S. , Abdel Rahman Hesham A. , Aboelsoued Mohamed , Elsayed Rasha A. , Elwany Abdelhakim F.
Published: September 2020

Background

Acute otitis media (AOM) is the commonest pediatric bacterial infection, affecting up to 75% of children at some time before age 5 years. AOM is among the primary reasons for antibiotic prescriptions in pediatric outpatients. This study aimed to detect the value of immunostimulant as an adjuvant therapy with antibiotics for treatment of acute otitis media in children. This study included 60 children suffering from acute otitis media; their age ranged from 3 to 5 years during the period from May 2018 to March 2019. The patients in this study were divided into 2 groups: group A included 30 patients with AOM who received amoxicillin and clavulanic acid antibiotic at attack of AOM. Group B included 30 patients with AOM who received the same antibiotic with immunostimulant (Echinacea extract) for 3 months. Samples of blood were taken from all patients to detect the level of Toll-like receptor by real-time PCR, before and after 3 months of antibiotic and immunostimulant therapy. All cases underwent assessment including complete history taking, otoscopic examination of the ear, and blood sample to detect the level of Toll-like receptor (TLR) before and after the therapy by real-time PCR.

Results

There was a significant (P < 0.05) decrease in the TLR2 expression in antibiotic-treated patients than its expression before treatment. On the other hand, there was a significant (P < 0.05) increase in the TLR2 expression in immunostimulant plus antibiotic-treated patients than its expression before treatment; there was a high significant (P < 0.001) increase in the expression of TLR2 in the immunostimulant plus antibiotic than the antibiotic-treated patients.

Conclusion

The role of antibiotics against bacterial infection causing acute otitis media can be enhanced by immunostimulant which increases the expression of Toll-like receptors which play a major role stimulating immune system to resist bacterial infection.
A qualitative exploration of the barriers to and facilitators of clozapine monitoring in a secure psychiatric setting
Authors: Blagden Sarah , Beenstock Jane , Auld Natalie , Noblett Steve , Limmer Mark
Published: September 2020

Aims and method

To explore the beliefs and understanding of staff and patients at a secure mental health unit regarding clozapine monitoring, and to identify barriers to and facilitators of monitoring. Qualitative semi-structured interviews and focus groups were conducted with 17 staff members and six patients.

Results

Six key themes were identified. The key facilitator of effective monitoring was the motivation of staff to help patients to become independent and facilitate recovery. An important barrier was a lack of clarity around the roles of different staff groups in monitoring. Staff and patients widely supported the establishment of an in-patient clozapine clinic and perceived that it would prepare patients for discharge.

Clinical implications

An in-patient clozapine clinic is a robust mechanism for clozapine monitoring in secure settings. The barriers and facilitators identified here could be applied to other secure units to guide their systems of clozapine monitoring.
Trends in (not) using scales in major depression: A categorization and clinical orientation
Authors: Demyttenaere Koen , Jaspers Liesbeth
Published: September 2020

Background

Standard depression rating scales like the Hamilton Depression Rating Scale and the Montgomery–Åsberg Depression Rating Scale were developed more than 40 years ago. They are mandatory in clinical trials but are for a variety of reasons seldom used in clinical practice. Moreover, most clinicians are less familiar with more recent trends or with some dilemmas in assessment tools for major depression.

Methods

Narrative review.

Results

Asssessment tools can be observer-rating or self-rating scales, disease-specific or non–disease-specific scales, subjective scales or objective lab assessments, standard questionnaires or experience sampling methods. An overarching question is to what degree current assessment methods really address the individual patient’s needs and treatment expectations.

Conclusions

The present paper aims to offer a framework for understanding the current trends in assessment tools that can orientate and guide the clinician.
Developmental programming of the adrenocortical stress response by yolk testosterone depends on sex and life history stage
Authors: Schwabl H. , Partecke J.
Published: September 2020

Developmental exposure of embryos to maternal hormones such as testosterone (T) in the avian egg influences the expression of multiple traits, with certain effects being sex-specific and lasting into adulthood. This pleiotropy, sex dependency, and persistency may be the consequence of developmental programming of basic systemic processes like adrenocortical activity or metabolic rate. We investigated if experimentally increased in ovo exposure to T influences hypothalamus-pituitary-adrenal function, i.e. baseline and stress-induced corticosterone (Cort) secretion, and resting metabolic rate (RMR) of adult male and female House sparrows (Passer domesticus). In previous experiments with this passerine bird we demonstrated effects of embryonic T exposure on adult agonistic and sexual behavior and survival. Here we report that baseline Cort levels and the stress secretion profile of Cort are modified by in ovo T in a sex-specific and life-history stage dependent manner. Compared to controls, males from T-treated eggs had higher baseline Cort levels whereas females from T-treated eggs showed prolonged stress-induced Cort secretion during the reproductive but not the non-reproductive phase. Adult RMR was unaffected by in ovo T-treatment but correlated with integrated Cort stress secretion levels. We conclude that exposure of the embryo to T programs the hypothalamus-pituitary-adrenal axis in a sex-specific manner that in females depends, in expression, on reproductive state. The modified baseline Cort levels in males respectively stress-induced Cort levels in females may explain some of the long-lasting effects of maternal T in the egg on behavior and could be linked to previously observed reduced mortality of T-treated females.
Cytoskeletal and synaptic polarity of LWamide-like+ ganglion neurons in the sea anemone Nematostella vectensis
Authors: Stone Michelle C. , Kothe Gregory O. , Rolls Melissa M. , Jegla Timothy
Published: September 2020

The centralized nervous systems of bilaterian animals rely on directional signaling facilitated by polarized neurons with specialized axons and dendrites. It is not known whether axo-dendritic polarity is exclusive to bilaterians or was already present in early metazoans. We therefore examined neurite polarity in the starlet sea anemone Nematostella vectensis (Cnidaria). Cnidarians form a sister clade to bilaterians and share many neuronal building blocks characteristic of bilaterians including channels, receptors and synaptic proteins, but their nervous systems comprise a comparatively simple net distributed throughout the body. We developed a tool kit of fluorescent polarity markers for live imaging analysis of polarity in an identified neuron type, large ganglion cells of the body column nerve net that express the LWamide-like neuropeptide. Microtubule polarity differs in bilaterian axons and dendrites, and this in part underlies polarized distribution of cargo to the two types of processes. However, in LWamide-like+ neurons, all neurites had axon-like microtubule polarity suggesting that they may have similar contents. Indeed, presynaptic and postsynaptic markers trafficked to all neurites and accumulated at varicosities where neurites from different neurons often crossed, suggesting the presence of bidirectional synaptic contacts. Furthermore, we could not identify a diffusion barrier in the plasma membrane of any of the neurites like the axon initial segment barrier that separates the axonal and somatodendritic compartments in bilaterian neurons. We conclude that at least one type of neuron in Nematostella vectensis lacks the axo-dendritic polarity characteristic of bilaterian neurons.
Skeletal muscle metabolism in sea-acclimatized king penguins: II. Improved efficiency of mitochondrial bioenergetics
Authors: Roussel Damien , Marmillot Vincent , Monternier Pierre-axel , Bourguignon Aurore , Toullec Gaëlle , Romestaing Caroline , Duchamp Claude
Published: September 2020

At fledging, juvenile king penguins (Aptenodytes patagonicus) must overcome the tremendous energetic constraints imposed by their marine habitat, including during sustained extensive swimming activity and deep dives in cold seawater. Both endurance swimming and skeletal muscle thermogenesis require high mitochondrial respiratory capacity while the submerged part of dive cycles repeatedly and greatly reduce oxygen availability imposing a need for solutions to conserve oxygen. The aim of the present study was to determine in vitro whether skeletal muscle mitochondria become more “thermogenic” to sustain heat production or more “economical” to conserve oxygen in sea-acclimatized immature penguins as compared with terrestrial juveniles. Rates of mitochondrial oxidative phosphorylation were measured in permeabilized fibers and mitochondria from the pectoralis muscle. Mitochondrial ATP synthesis and coupling efficiency were measured in isolated muscle mitochondria. The mitochondrial activities of respiratory chain complexes and citrate synthase were also assessed. The results showed that respiration, ATP synthesis and respiratory chain complex activities in pectoralis muscles were increased by sea acclimatization. Further, muscle mitochondria were on average 30% to 45% more energy efficient in sea-acclimatized immatures than in pre-fledging juveniles, depending on the respiratory substrate used (pyruvate; palmitoyl-carnitine). Hence, sea acclimatization favors the development of economical management of oxygen, decreasing the oxygen needed to produce a given amount of ATP. This mitochondrial phenotype may improve dive performance during the early marine life of king penguins, by extending their aerobic dive limit.
NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal–ventral patterning
Authors: Rathore Om Singh , Silva Rui D. , Ascensão-Ferreira Mariana , Matos Ricardo , Carvalho Célia , Marques Bruno , Tiago Margarida N. , Prudêncio Pedro , Andrade Raquel P. , Roignant Jean-Yves , Barbosa-Morais Nuno L. , Martinho Rui Gonçalo
Published: September 2020

The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. DuringDrosophilamidblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, theDrosophilaortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron ofgurken. Germline depletion of Salsa and splice site mutations withingurkenfirst intron impair both adult female fertility and oocyte dorsal–ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal–ventral patterning defects observed after Salsa depletion could be suppressed by the expression of agurkenconstruct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron ofgurkenmRNA. Retention ofgurkenfirst intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5′UTR.
Some unrestricted Fibonacci and Lucas hyper-complex numbers
Authors: Bilgici Göksal , Daşdemir Ahmet
Published: September 2020

A number of studies have investigated the Fibonacci quaternions and octonions that include consecutive terms of the Fibonacci sequence. This paper presents a new generalization of Fibonacci quaternions, octonions and sedenions, where non-consecutive Fibonacci numbers are used. We present the Binet formulas, generating functions and some identities for these new types of hyper-complex numbers.
Necessary and sufficient Tauberian conditions for weighted mean methods of summability in two-normed spaces
Authors: Çanak İbrahim , Erikli Gizem , Sezer Sefa Anıl , Yaraşgil Ece
Published: September 2020

We first define the concept of weighted mean method of summability and then present necessary and sufficient Tauberian conditions for the weighted mean summability of sequences in two-normed spaces. As corollaries, we establish two-normed analogues of two classical Tauberian theorems.