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It is believed that space charge build-up in cross-linked polyethylene (XLPE) insulation is the main cause of premature failure of underground power cables. The space charge activities in XLPE depend on many factors such as additives, material treatment, ambient temperature, insulator/electrode interface, etc. Degassing is the process of subjecting the XLPE to a moderately high temperature, thereby removing volatile residual by-products and additives that are commonly employed in cable manufacturing to improve insulation performance. While there have been reports comparing space charge activities (as-received) un-degassed and degassed samples, little attention has been placed on degassing conditions effect on space charge. In this paper, investigations of morphology and space charge distribution of planar XLPE samples was carried out as parameters such as degassing temperature, degassing duration and sample thickness were adjusted. Changes in the morphological structure of the material were probed with the differential scanning calorimeter and the transmission electron microscopy, whereas space charge distribution of the samples subjected to dc electric stress was monitored for 24 h using the laser induced pressure pulsed technique. It was revealed that degassing temperature, duration and the thickness of the degassed sample has a direct effect on the morphological structure and space charge distributions of the samples. It is believed that the presence and amount of by-products takes precedence over the morphology of the material as far as space charge evolution is concerned. [ABSTRACT FROM AUTHOR]

Reduced generation of multiple motile cilia (RGMC) represents a rare variant of Primary Ciliary Dyskinesia (PCD), associated with CYCLIN-O (CCNO) mutations. We report a novel compound mutation in the CCNO gene in an adult Chinese Singaporean exhibiting chronic productive cough since childhood and recurrent sino-pulmonary infections. Low nasal nitric oxide and bronchiectasis suggests PCD. Bronchoscopy for epithelial and nasal brushings for ciliary studies were repeated after adequate treatment of lower respiratory tract infections. Demonstration of oligo-cilia via transmission electron microscopy, and detection of CCNO mutation through genetic analysis were utilized to diagnose RGMC. Repeated courses of antibiotics including nebulised antibiotics were used to treat recurrent infections and exacerbations. Airway clearance techniques, immunizations and collaboration with otorhinolaryngologist form part of the long-term management. Heightened clinical suspicion and adherence to established diagnostic algorithms are essential for timely recognition of this entity., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

The production of food, feed, fiber, and fuel is a key task of agriculture, which has to cope with many challenges in the upcoming decades, e.g., a higher demand, climate change, lack of workers, and the availability of arable land. Vision systems can support making better and more sustainable field management decisions, but also support the breeding of new crop varieties by allowing temporally dense and reproducible measurements. Recently, agricultural robotics got an increasing interest in the vision and robotics communities since it is a promising avenue for coping with the aforementioned lack of workers and enabling more sustainable production. While large datasets and benchmarks in other domains are readily available and enable significant progress, agricultural datasets and benchmarks are comparably rare. We present an annotated dataset and benchmarks for the semantic interpretation of real agricultural fields. Our dataset recorded with a UAV provides high-quality, pixel-wise annotations of crops and weeds, but also crop leaf instances at the same time. Furthermore, we provide benchmarks for various tasks on a hidden test set comprised of different fields: known fields covered by the training data and a completely unseen field.

Background: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized., Methods and Results: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization., Conclusion: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Testicular cancer (TCa) commonly presents as a painless scrotal mass. It has been suggested that testicular self-examination (TSE) can help in early detection and thus potentially improve treatment outcomes and prognosis. While TSE is more well established in guideline recommendations for patients with a known history of TCa, its role in healthy young men is less established and controversial. In this paper, we review contemporary data to provide an updated recommendation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: None

Purpose: The COVID-19 pandemic has led to competing strains on hospital resources and healthcare personnel. Patients with newly diagnosed invasive urothelial carcinomas of bladder (UCB) upper tract (UTUC) may experience delays to definitive radical cystectomy (RC) or radical nephro-ureterectomy (RNU) respectively. We evaluate the impact of delaying definitive surgery on survival outcomes for invasive UCB and UTUC., Methods: We searched for all studies investigating delayed urologic cancer surgery in Medline and Embase up to June 2020. A systematic review and meta-analysis was performed., Results: We identified a total of 30 studies with 32,591 patients. Across 13 studies ( n  = 12,201), a delay from diagnosis of bladder cancer/TURBT to RC was associated with poorer overall survival (HR 1.25, 95% CI: 1.09-1.45, p  = 0.002). For patients who underwent neoadjuvant chemotherapy before RC, across the 5 studies ( n  = 4,316 patients), a delay between neoadjuvant chemotherapy and radical cystectomy was not found to be significantly associated with overall survival (pooled HR 1.37, 95% CI: 0.96-1.94, p  = 0.08). For UTUC, 6 studies ( n  = 4,629) found that delay between diagnosis of UTUC to RNU was associated with poorer overall survival (pooled HR 1.55, 95% CI: 1.19-2.02, p  = 0.001) and cancer-specific survival (pooled HR of 2.56, 95% CI: 1.50-4.37, p  = 0.001). Limitations included between-study heterogeneity, particularly in the definitions of delay cut-off periods between diagnosis to surgery., Conclusions: A delay from diagnosis of UCB or UTUC to definitive RC or RNU was associated with poorer survival outcomes. This was not the case for patients who received neoadjuvant chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Leow, Tan, Tan, Tan, Chan, Tikkinen, Kamat, Sengupta, Meng, Shariat, Roupret, Decaestecker, Vasdev, Chong, Enikeev, Giannarini, Ficarra and Teoh.)

Lithium sulfur batteries (LSBs) have attracted tremendous attention owing to their high theoretical specific capacity and specific energy. However, their practical applications are hindered by poor cyclic life, mainly caused by polysulfide shuttling. The development of advanced materials to mitigate the polysulfide shuttling effect is urgently demanded. Metal-organic frameworks (MOFs) have been exploited as multifunctional materials for the decoration of separators owing to their high surface area, structural diversity, tunable pore size, and easy tailor ability. In this review, we aim to present the state-of-the-art MOF-based separators for LSBs. Particular attention is paid to the rational design (pore aperture, metal node, functionality, and dimension) of MOFs with enhanced ability for anchoring polysulfides and facilitating Li + transportation. Finally, the challenges and perspectives are provided regarding to the future design MOF-based separators for high-performance LSBs., (© 2022 The Chemical Society of Japan & Wiley-VCH GmbH.)

Bacteria community provides essential ecological services to rice plants. The bacterial diversity of rice varies across host plant genotype and organs. This study employed 16S rDNA amplicon sequencing to characterise the bacterial community associated with three rice landraces using leaf blade and stem samples. The prokaryotic community found in these rice landraces comprised of two kingdoms, 12 phyla, 25 classes, 40 orders, 80 families, and 118 genera. Proteobacteria (53.9%) was the most abundant phylum. The most abundant genus was an undefined genus under Cyanobacteria (33.0%). Homogeneity of prokaryotic community was observed across the three rice landraces, which may suggest a high similarity in biological and genetical properties of the rice landraces. The difference in prokaryotic composition between leaf blade and stem was depicted based on principal coordinate analysis. This study observed that the prokaryotic inhabitants in rice plants is predominantly determined by rice plant organs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To explore the causes of ineffective or short-term recurrence (within 3 months)of trigeminal neuralgia treated by percutaneous microballoon compression(PBC), and to examine the reoperative strategies and clincal outcomes of modified PBC. Methods: The clinical data of 21 patients with ineffective or short-term recurrence after PBC treatment (5.7% of 369 patient received PBC) admitted to the Department of Neurosurgery,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University from June 2018 to June 2020 were retrospectively analyzed.There were 8 males and 13 females, mean aged 66.6 years (range:51 to 79 years).Among them,2 patients was ineffective after PBC and 19 patients relapsed within 3 months.The distribution of pain was along V 2 branches in 2 cases,V 3 branches in 3 cases,V 1 +V 2 branches in 1 case,and V 2 +V 3 branches in 15 cases.The mean time of recurrence was 46.8 days (range:23 to 76 days) among the 19 patients with short-term recurrence.The patients were divided into 4 types based on the causes of postoperative ineffectiveness or short-term recurrence.TypeⅠ:extracapsular false pear (1 case);Type Ⅱ:invalid true pear(2 cases);Type Ⅲ:capsular rupture (6 cases);Type Ⅳ:compression blind area (12 cases).The individualized modified PBC operation plans were used according to the types of the patients and the clinical effect and complications of the patients were observed. Results: The pain symptoms of the patients disappeared after the second operation with immediate effective rate of 100%. All patients had mild facial numbness after surgery.Five patients(23.8%,5/21) had masseter muscle weakness, 3 (14.3%,3/21) had peristomatous herpes, 1(4.8%, 1/21) had diplopia.No bleeding or other complications occurred.All patients were followed up for at least 12 months (range:13 to 28 months). One patient (4.8%,1/21) (compression blind area type) had pain recurrence 9 months after surgery, and cured by receiving the original modified PBC surgery again with no recurrence after another 13 months' follow-up. None of the other patients relapsed during the follow-up period.Up to the last follow-up,19 cases(90.5%,19/21) were cured,and 2 cases (9.5%,2/21) were relieved. Conclusions: The main reason for ineffective or short-term recurrence of PBC in trigeminal neuralgia patients is the ineffectively compressed of trigeminal ganglion.According to the different types of patients,the use of individualized modified surgical scheme can improve the efficacy of PBC surgery.

The vertebrate left-right axis is specified during embryogenesis by a transient organ: the left-right organizer (LRO). Species including fish, amphibians, rodents and humans deploy motile cilia in the LRO to break bilateral symmetry, while reptiles, birds, even-toed mammals and cetaceans are believed to have LROs without motile cilia. We searched for genes whose loss during vertebrate evolution follows this pattern and identified five genes encoding extracellular proteins, including a putative protease with hitherto unknown functions that we named ciliated left-right organizer metallopeptide (CIROP). Here, we show that CIROP is specifically expressed in ciliated LROs. In zebrafish and Xenopus, CIROP is required solely on the left side, downstream of the leftward flow, but upstream of DAND5, the first asymmetrically expressed gene. We further ascertained 21 human patients with loss-of-function CIROP mutations presenting with recessive situs anomalies. Our findings posit the existence of an ancestral genetic module that has twice disappeared during vertebrate evolution but remains essential for distinguishing left from right in humans., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Adaptive evolution to cellular stress is a process implicated in a wide range of biological and clinical phenomena. Two major routes of adaptation have been identified: non-genetic changes, which allow expression of different phenotypes in novel environments, and genetic variation achieved by selection of fitter phenotypes. While these processes are broadly accepted, their temporal and epistatic features in the context of cellular evolution and emerging drug resistance are contentious. In this manuscript, we generated hypomorphic alleles of the essential nuclear pore complex (NPC) gene NUP58. By dissecting early and long-term mechanisms of adaptation in independent clones, we observed that early physiological adaptation correlated with transcriptome rewiring and upregulation of genes known to interact with the NPC; long-term adaptation and fitness recovery instead occurred via focal amplification of NUP58 and restoration of mutant protein expression. These data support the concept that early phenotypic plasticity allows later acquisition of genetic adaptations to a specific impairment. We propose this approach as a genetic model to mimic targeted drug therapy in human cells and to dissect mechanisms of adaptation., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Motile cilia defects impair cerebrospinal fluid (CSF) flow and can cause brain and spine disorders. The development of ciliated cells, their impact on CSF flow, and their function in brain and axial morphogenesis are not fully understood. We have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricles undergo restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs co-exist with monociliated cells and generate directional flow patterns. These ciliated cells have different developmental origins and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from the tela choroida and choroid plexus or global perturbation of multiciliation does not affect overall brain or spine morphogenesis but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development., Competing Interests: Declaration of interests N.K., A.G., and B.S.N. are full-time employees of Resolve Biosciences GmbH., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Context: To improve the prognosis of upper tract urothelial carcinoma (UTUC), clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) before or after radical nephroureterectomy (RNU). Despite some new data, the evidence remains mixed on their efficacy., Objective: To update the current evidence on the role of NAC and AC for UTUC., Evidence Acquisition: We searched for all studies investigating NAC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings up to February 2020. A systematic review and meta-analysis was performed., Evidence Synthesis: For NAC, the pooled pathologic complete response rate (≤ypT0N0M0) was 11% (n = 811) and pathologic partial response rate (≤ypT1N0M0) was 43% (n = 869), both across 14 studies. Across six studies, the pooled hazard ratios (HRs) were 0.44 (95% confidence interval [CI]: 0.32-0.59, p <  0.001) for overall survival (OS) and 0.38 (95% CI: 0.24-0.61, p <  0.001) for cancer-specific survival (CSS) in favor of NAC. The evidence for NAC is at best level 2. As for AC, there was a benefit in OS (pooled HR 0.77; 95% CI: 0.64-0.92, p =  0.004 across 14 studies and 7983 patients), CSS (pooled HR 0.79; 95% CI: 0.69-0.91, p =  0.001 across 18 studies and 5659 patients), and disease-free survival (DFS; pooled HR 0.52; 95% CI: 0.38-0.70 across four studies and 602 patients). While most studies were retrospective (level 2 evidence), there were two prospective randomized trials providing level 1 evidence. There are currently four phase 2 trials on neoadjuvant immunotherapy and three phase 2 trials on adjuvant immunotherapy for UTUC., Conclusions: NAC for UTUC confers a favorable pathologic response and tumor downstaging rate, and an OS and CSS benefit compared with RNU alone. AC confers an OS, CSS, and DFS benefit compared with RNU alone. Currently, the evidence for AC appears stronger (with positive level 1 evidence) than that for NAC (at best level 2 evidence). Limited data are available for chemoimmunotherapy approaches, but preliminary data support an active research investment., Patient Summary: After a comprehensive search of the latest studies examining the role of neoadjuvant and adjuvant chemotherapy for upper tract urothelial cancer, the pooled evidence shows that perioperative chemotherapy was beneficial for prolonging survival; however, the evidence for adjuvant chemotherapy was stronger than that for neoadjuvant chemotherapy., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The Blueline Rasbora (Rasbora sarawakensis) is a small ray-finned fish categorized under the genus Rasbora in the Cyprinidae family. In this study, the complete mitogenome sequence of R. sarawakensis was sequenced using four primers targeting overlapping regions. The mitogenome is 16,709 bp in size, accommodating 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organisation was detected between this species and other genus counterparts. The heavy strand houses 28 genes while the light strand stores the other nine genes. Most protein-coding genes employ ATG as start codon, excluding COI gene, which utilizes GTG instead. The central conserved sequence blocks (CSB-F, CSB-E and CSB-D), variable sequence blocks (CSB-3, CSB-2 and CSB-1) as well as the terminal associated sequence (TAS) are conserved in the control region. The maximum likelihood phylogenetic tree revealed the divergence of R. sarawakensis from the basal region of the Rasbora clade, where its evolutionary relationships with R. maculatus and R. pauciperforata are poorly resolved as indicated by the low bootstrap values. This work acts as steppingstone towards further molecular evolution and population genetics studies of Rasbora genus in future., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Multiciliated cells (MCCs) differentiate hundreds of motile cilia that beat to drive fluid movement over various kinds of epithelia. In Xenopus, mice and human, the coiled-coil containing protein Mcidas (Mci) has been shown to be a key transcriptional regulator of MCC differentiation. We have examined Mci function in the zebrafish, another model organism that is widely used to study ciliary biology. We show that zebrafish mci is expressed specifically in the developing MCCs of the kidney tubules, but surprisingly, not in those of the nasal placodes. Mci proteins lack a DNA binding domain and associate with the cell-cycle transcription factors E2f4/5 for regulating MCC-specific gene expression. We found that while the zebrafish Mci protein can complex with the E2f family members, its sequence as well as the requirement and sufficiency for MCC differentiation has diverged significantly from Mci homologues of the tetrapods. We also provide evidence that compared to Gmnc, another related coiled-coil protein that has recently been shown to regulate MCC development upstream of Mci, the Mci protein originated later within the vertebrate lineage. Based on these data, we argue that in contrast to Gmnc, which has a vital role in the genetic circuitry that drives MCC formation, the requirement of Mci, at least in the zebrafish, is not obligatory., Competing Interests: Declaration of competing interest The authors declare they have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Wunderlich syndrome (WS) is a rare triad of flank pain, flank mass and hypovolemic shock and is classically attributed to angiomyolipomata or neoplasms. Treatment is guided by clinical severity: conservative, selective arterial embolization, or nephrectomy. We report an atypical case of a 69-year old man with a pre-existing 9 cm left renal tumor who developed WS secondary to anticoagulation and simple cyst rupture from his contralateral kidney, complicated by abdominal compartment syndrome with hemodynamic instability despite inotropic support and robust resuscitation. Early recognition and source control via radical nephrectomy were essential in securing a positive outcome.

The Trigonopoma pauciperforatum or the redstripe rasbora is a cyprinid commonly found in marshes and swampy areas with slight acidic tannin-stained water in the tropics. In this study, the complete mitogenome sequence of T. pauciperforatum was first amplified in two parts using two pairs of overlapping primers and then sequenced. The size of the mitogenome is 16,707 bp, encompassing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organisation was detected between this species and other family members. The heavy strand accommodates 28 genes while the light strand houses the remaining nine genes. Most protein-coding genes utilise ATG as start codon except for COI gene which uses GTG instead. The terminal associated sequence (TAS), central conserved sequence block (CSB-F, CSB-D and CSB-E) as well as variable sequence block (CSB-1, CSB-2 and CSB-3) are conserved in the control region. The maximum likelihood phylogenetic tree revealed the divergence of T. pauciperforatum from the basal region of the major clade, where its evolutionary relationships with Boraras maculatus , Rasbora cephalotaenia and R. daniconius are poorly resolved as suggested by the low bootstrap values. This work contributes towards the genetic resource enrichment for peat swamp conservation and comprehensive in-depth comparisons across other phylogenetic researches done on the Rasbora -related genus., (© Penerbit Universiti Sains Malaysia, 2020.)

The yellowtail rasbora ( Rasbora tornieri ) is a miniature ray-finned fish categorized under the genus Rasbora in the family of Cyprinidae. In this study, a complete mitogenome sequence of R. tornieri was sequenced using four primers targeting two halves of the mitogenome with overlapping flanking regions. The size of mitogenome was 16,573 bp, housing 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organization was detected between this species and other members of Rasbora genus. The heavy strand encompassed 28 genes while the light strand accommodated the other nine genes. Most protein-coding genes execute ATG as start codon, excluding COI and ND3 genes, which utilized GTG instead. The central conserved sequence blocks (CSB-E, CSB-F and CSB-D), variable sequence blocks (CSB-1, CSB-3 and CSB-2) as well as the terminal associated sequence (TAS) were conserved within the control region. The maximum likelihood phylogenetic family tree revealed the divergence of R. tornieri from the basal region of the Rasbora clade, where its evolutionary relationships with other Rasbora members are poorly resolved as indicated by the low bootstrap values. This work acts as window for further population genetics and molecular evolution studies of Rasbora genus in future.

Background: To report outcomes of localized prostate cancer treated with radical external beam radiation therapy (EBRT) in our institution over a 14-year period, and to determine the impact of dose escalation of prostate cancer outcomes., Methods: Patients with T1-T4 N0 M0 prostate cancer who received radical EBRT between January 2002 and December 2015 were reviewed retrospectively. Clinical data were obtained via the institutional electronic medical records. The primary endpoint was 5-year overall survival (OS). The secondary endpoints were 5-year freedom from biochemical failure (FFBF) and treatment toxicities., Results: A total of 200 eligible patients were identified. Median follow-up duration was 48 months. 13%, 36% and 51% of patients had low-, intermediate- and high-risk disease. Median dose was 79.2 Gy. The 5-year OS were 90%, 87% and 78% and FFBF were 94%, 100% and 81% for low-, intermediate- and high-risk patients, respectively. Multivariable analysis showed that Eastern Cooperate Oncology Group performance status 2 and Gleason grade group 5 were independent predictors of worse OS. The incidence of grade ≥2 proctitis was 24.5%. Dose escalation was significantly associated with increased incidence of grade ≥2 proctitis (odd ratio, 4.42; 95% confidence interval, 1.95-10.08; P < 0.01)., Conclusion: Men with localized prostate cancer treated with EBRT in our population had excellent 5-year OS and biochemical outcomes. Dose escalation did not significantly improve these outcomes but was associated with significantly increased risk of grade ≥2 proctitis in our population. Future studies should be performed to identify patients who will benefit the most from dose-escalated EBRT., (© 2019 John Wiley & Sons Australia, Ltd.)

Gastrointestinal nematodes can cause assorted health problems to human and other primates. The status of gastrointestinal nematodes in non-human primates remained less documented in Malaysia. This study aimed to determine the occurrence of gastrointestinal nematodes recovered from the fecal samples of captive non-human primates at the Matang Wildlife Centre (MWC), Sarawak. Fresh fecal samples were collected from 60 non-human primates of six species (i.e. Orangutan, Bornean gibbon, Silvered Leaf monkey, Slow loris, Pig-tailed macaque, and Long-tailed macaque) and processed using simple fecal floatation method and fecal sedimentation method. This study shows high prevalence of nematode infection (>=50%) and co-infection (22 from 45 infected individuals) in all species of captive non-human primates found in MWC, except one individual of young Silvered Leaf monkey was negative for nematode. From these, eight genera of 11 species and one unknown nematode larvae were recovered and among them Oesophagostomum sp., Ascaris sp., and Strongyloides sp. were the most common nematodes infecting the non-human primates. All the Bornean gibbon (n=7) were found to be infected with nematodes. Moreover, Long-tailed macaques at the centre were heavily infected by Ascaris sp. (number of total count, n t = 2132; total mean abundance, MA=113.70). This is the first report of high prevalence nematode infection on multiple species of captive non-human primates in a wildlife centre located in Sarawak. Some of the nematodes are of zoonotic potential. This information is important for health care management, both in-situ and ex-situ conservations of captive and free-ranging nonhuman primates.

Motile cilia on multiciliated cells (MCCs) function in fluid clearance over epithelia. Studies with Xenopus embryos and individuals with the congenital respiratory disorder reduced generation of multiple motile cilia (RGMC), have implicated the nuclear protein MCIDAS (MCI), in the transcriptional regulation of MCC specification and differentiation. Recently, a paralogous protein, geminin coiled-coil domain containing (GMNC), was also shown to be required for MCC formation. Surprisingly, in contrast to the presently held view, we find that Mci mutant mice can specify MCC precursors. However, these precursors cannot produce multiple basal bodies, and mature into single ciliated cells. We identify an essential role for MCI in inducing deuterosome pathway components for the production of multiple basal bodies. Moreover, GMNC and MCI associate differentially with the cell-cycle regulators E2F4 and E2F5, which enables them to activate distinct sets of target genes (ciliary transcription factor genes versus basal body amplification genes). Our data establish a previously unrecognized two-step model for MCC development: GMNC functions in the initial step for MCC precursor specification. GMNC induces Mci expression that drives the second step of basal body production for multiciliation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Multiciliated cells (MCCs) differentiate arrays of motile cilia that beat to drive fluid flow over epithelia. Recent studies have established two Geminin family coiled-coil containing nuclear regulatory proteins, Gmnc and Multicilin (Mci), in the specification and differentiation of the MCCs. Both Gmnc and Mci are devoid of a DNA binding domain: they regulate transcription by associating with E2f family transcription factors, notably E2f4 and E2f5. Here, we have studied the relative contribution of these two E2f factors in MCC development using the zebrafish embryo, which differentiates MCCs within kidney tubules and the nose. We found that while E2f4 is fully dispensable, E2f5 is essential for MCCs to form in the kidney tubules. Moreover, using a variety of double mutant combinations we show that E2f5 has a more prominent role in MCC development in the zebrafish than E2f4. This contrasts with current evidence from the mouse, where E2f4 seems to be more important. Thus, distinct combinatorial activities of the E2f4 and E2f5 proteins regulate the specification and differentiation of MCCs in zebrafish and mice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The Fanconi anemia (FA) pathway is a pivotal genome maintenance network that orchestrates the repair of DNA interstrand crosslinks (ICLs). The tumor suppressors RUNX1 and RUNX3 were shown to regulate the FA pathway independent of their canonical transcription activities, by controlling the DNA damage-dependent chromatin association of FANCD2. Here, in further biochemical characterization, we demonstrate that RUNX3 is modified by PARP-dependent poly(ADP-ribosyl)ation (PARylation), which in turn allows RUNX binding to DNA repair structures lacking transcription-related RUNX consensus motifs. SILAC-based mass spectrometric analysis revealed significant association of RUNX3 with core DNA repair complexes, including PARP1, even in unstressed cells. After DNA damage, the increased interaction between RUNX3 and BLM facilitates efficient FANCD2 chromatin localization. RUNX-Walker motif mutations from breast cancers are impaired for DNA damage-inducible PARylation, unveiling a potential mechanism for FA pathway inactivation in cancers. Our results reinforce the emerging paradigm that RUNX proteins are tumor suppressors with genome gatekeeper function., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The race for the discovery of enhancers at a genome-wide scale has been on since the commencement of next generation sequencing decades after the discovery of the first enhancer, SV40. A few enhancer-predicting features such as chromatin feature, histone modifications and sequence feature had been implemented with varying success rates. However, to date, there is no consensus yet on the single enhancer marker that can be employed to ultimately distinguish and uncover enhancers from the enormous genomic regions. Many supervised, unsupervised and semi-supervised computational approaches had emerged to complement and facilitate experimental approaches in enhancer discovery. In this review, we placed our focus on the recently emerged enhancer predictor tools that work on general enhancer features such as sequences, chromatin states and histone modifications, eRNA and of multiple feature approach. Comparisons of their prediction methods and outcomes were done across their functionally similar counterparts. We provide some recommendations and insights for future development of more comprehensive and robust tools., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Studies of genomic instability have historically focused on intrinsic mechanisms rather than extrinsic mechanisms based in the tumor microenvironment (TME). TGFβ is the most abundantly secreted cytokine in the TME, where it imparts various aggressive characteristics including invasive migration, drug resistance, and epithelial-to-mesenchymal transition (EMT). Here we show that TGFβ also promotes genomic instability in the form of DNA double strand breaks (DSB) in cancer cells that lack the tumor suppressor gene RUNX3 Loss of RUNX3 resulted in transcriptional downregulation of the redox regulator heme oxygenase-1 (HO-1 or HMOX1). Consequently, elevated oxidative DNA damage disrupted genomic integrity and triggered cellular senescence, which was accompanied by tumor-promoting inflammatory cytokine expression and acquisition of the senescence-associated secretory phenotype (SASP). Recapitulating the above findings, tumors harboring a TGFβ gene expression signature and RUNX3 loss exhibited higher levels of genomic instability. In summary, RUNX3 creates an effective barrier against further TGFβ-dependent tumor progression by preventing genomic instability. These data suggest a novel cooperation between cancer cell-extrinsic TGFβ signaling and cancer cell-intrinsic RUNX3 inactivation as aggravating factors for genomic instability. Significance: RUNX3 inactivation in cancer removes an antioxidant barrier against DNA double strand breaks induced by TGFβ expressed in the tumor microenvironment. Cancer Res; 78(1); 88-102. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Human bocavirus (HBoV) is a single-stranded DNA virus in Parvoviridae family, causing respiratory diseases in human. The recent identifications of genomic recombination among the four human bocavirus genotypes and related non-human primate bocaviruses have shed lights into the evolutionary processes underpinning the diversity of primate bocavirus. Among these reports, however, we found inconsistency and possible alternative interpretations of the recombination events. In this study, these recombination events were reviewed, and the related genome sequences were re-analysed, aiming to inform the research community of bocavirus with more consistent knowledge and comprehensive interpretations on the recombination history of primate bocavirus.

Little is known regarding infestation of ectoparasites in synanthropic rodents in Sarawak, Malaysia. A total of 44 rodents from three species (Rattus rattus, Rattus tiomanicus and Sundamys muelleri) were trapped from four residential areas in western Sarawak, Malaysia, for ectoparasites screening. A total of 117 ectoparasites from three hard tick species (Ixodes granulatus, Haemaphysalis sp. 1, Haemaphysalis sp. 2), three mesostigmatid mite species (Laelaps echidninus, Laelaps sedlaceki, and Laelaps nuttalli), one trombiculid mite (chigger species), and one louse species (Hoplopleura sp.), were recovered from 32 infected rodents (72.73% infestation). Infestations by multiple ectoparasite species on the same rodent individuals were recorded in R. rattus and R. tiomanicus (28.1%, n=9) in this study, while Sundamys muelleri was only infested with L. echidninus. One R. rattus individual was co-infected with ticks, louse, and mesostigmatid mite. L. echidninus was the generalist ectoparasite species that infected all three rodent species in three of the residential areas studied. Ectoparasite species diversity was significantly different among four residential areas based on Shannon index and diversity t-test (p-value <0.05). This study provides the first record of the association of synanthropic rodents with multiple ectoparasite infections in residential areas of western Sarawak, Malaysia.

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential ( n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) ( p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.

Purpose: We evaluated the current literature comparing outcomes of robotic vs laparoscopic partial nephrectomy., Materials and Methods: We performed a literature search according to Cochrane guidelines up to December 2015 including studies comparing robotic and laparoscopic partial nephrectomy, and we compared baseline patient and tumor characteristics. We performed a meta-analysis to evaluate safety, effectiveness and functional outcomes of robotic vs laparoscopic partial nephrectomy using weighted mean difference and inverse variance pooled risk ratios, respectively., Results: A total of 4,919 patients were included from 25 studies (robotic partial nephrectomy 2,681, laparoscopic partial nephrectomy 2,238). There were no significant differences between the 2 groups in terms of age, gender, laterality and final malignant pathology. Patients treated with robotic partial nephrectomy had larger tumors (WMD 0.17 cm, p=0.001) and higher mean R.E.N.A.L. nephrometry scores (WMD 0.59, p=0.002), and were associated with a decreased likelihood of conversion to laparoscopic/open surgery compared to laparoscopic partial nephrectomy (RR 0.36, p <0.001), any (Clavien 1 or greater) (RR 0.84, p=0.007) and major (Clavien 3 or greater) (RR 0.71, p=0.023) complications, positive margins (RR 0.53, p <0.001) and shorter warm ischemia time by 4.3 minutes (p <0.001). Both approaches had similar operative times (WMD -12.2 minutes, p=0.34), estimated blood loss (WMD -24.6 ml, p=0.15) and postoperative change in estimated glomerular filtration rate., Conclusions: This updated meta-analysis of retrospective cohort studies demonstrated that robotic partial nephrectomy confers a superior morbidity profile compared to laparoscopic partial nephrectomy in most of the examined perioperative outcomes. Despite being the strongest available evidence (Level 2b) for outcomes of robotic vs laparoscopic partial nephrectomy thus far, there have been no completed or ongoing randomized trials to lend Level 1 support for either approach., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Multiciliated cells (MCCs) differentiate hundreds of motile cilia that generate mechanical force required to drive fluid movement over epithelia [1, 2]. For example, metachronal beating of MCC cilia in the mammalian airways clears mucus that traps inhaled pathogens and pollutants. Consequently, abnormalities in MCC differentiation or ciliary motility have been linked to an expanding spectrum of human airway diseases [3–6]. The current view posits that MCC precursors are singled out by the inhibition of Notch signaling. MCC precursors then support an explosive production of basal bodies, which migrate to the apical surface, dock with the plasma membrane, and seed the growth of multiple motile cilia. At the center of this elaborate differentiation program resides the coiled-coil-containing protein Multicilin, which transcriptionally activates genes for basal body production and the gene for FoxJ1, the master regulator for basal body docking, cilia formation, and motility [7, 8]. Here, using genetic analysis in the zebrafish embryo, we discovered that Gmnc is a novel determinant of the MCC fate. Like Multicilin, Gmnc is a coiled-coil-containing protein of the Geminin family. We show that Gmnc functions downstream of Notch signaling, but upstream of Multicilin in the developmental pathway controlling MCC specification. Moreover, we find that loss of Gmnc in Xenopus embryos also causes loss of MCC differentiation and that overexpression of the protein is sufficient to induce supernumerary MCCs. Together, our data identify Gmnc as an evolutionarily conserved master regulator functioning at the top of the hierarchy of transcription factors involved in MCC differentiation.

Cyanobacteria have developed various response mechanisms in long evolution to sense and adapt to external or internal changes under abiotic stresses. The signal transduction system of a model cyanobacterium Synechocystis sp. PCC 6803 includes mainly two-component signal transduction systems of eukaryotic-type serine/threonine kinases (STKs), on which most have been investigated at present. These two-component systems play a major role in regulating cell activities in cyanobacteria. More and more co-regulation and crosstalk regulations among signal transduction systems had been discovered due to increasing experimental data, and they are of great importance in corresponding to abiotic stresses. However, mechanisms of their functions remain unknown. Nevertheless, the two signal transduction systems function as an integral network for adaption in different abiotic stresses. This review summarizes available knowledge on the signal transduction network in Synechocystis sp. PCC 6803 and biotechnological implications under various stresses, with focuses on the co-regulation and crosstalk regulations among various stress-responding signal transduction systems.

Our aim is to report our preliminary experience of a proctor-based team approach in robot-assisted laparoscopic prostatectomy (RALP) for the treatment of localized prostate cancer. Data was collected between December 2008 and February 2012. RALP was performed on 100 consecutive patients with prostate cancer by a team of five urologists proctored by two fellowship-trained surgeons from a single hospital. Clinical and pathological data of these patients were reviewed. The mean age of the patients was 66 years (range 48-76). Clinical stages were 82 % cT1c, 3 % cT1b, 13 % cT2a and 2 % cT3a disease. Preoperative mean prostate-specific antigen level was 11.33 ng/ml (SD 10.47). Mean operative time was 342 min and mean blood loss was 717 ml (SD 988). Mean hospital stay and duration of the indwelling catheter were 3.2 days (SD 1.8) and 12.6 days (SD 8.5), respectively. Pathological staging showed 65 patients with pT2a (65 %) disease and 33 patients with pT3a (33 %) disease. Thirty-five patients (35 %) had positive surgical margins. Eighteen patients underwent adjuvant radiotherapy. Overall postoperative complication rate was 14 %. There were six Clavien grade 1 complications, seven Clavien grade 2 complications and one Clavien grade 3 complication. At mean follow-up of 36 months, 100 % of patients remained free of biochemical recurrence with continence at 70 %. Our proctor-based team approach will continue to improve each surgeon's technical competency. He or she will continue to improve and gradually move on to achieving his or her outcomes learning curve.