Takshan/R1 huggingface dataset:
Identifying novel protein interactions: Proteomic methods, optimisation approaches and data analysis pipelines.

The technological revolution in high-throughput nucleic acid and protein analysis in the last 15years has launched the field of 'omics' and led to great advances in our understanding of cell biology. Consequently the study of the cellular proteome and protein dynamics, in particular interactomics, has been a matter of intense investigation, specifically the determination and description of complex protein interaction networks in the cell, not only with other proteins but also with RNA and DNA. The analysis of these interactions, beginning with their identification and ultimately resulting in structural level examination, is one of the cornerstones of modern biological science underpinning basic research and impacting on applied biology, biomedicine and drug discovery. In this review we summarise a selection of emerging and established techniques currently being applied in this field with a particular focus on affinity-based purification systems and their optimisation, including tandem affinity purification (TAP) tagging, isolation of proteins on nascent DNA (IPOND) and RNA-protein immunoprecipitation in tandem (RIPiT). The recent application of quantitative proteomics to improve stringency and specificity is also discussed, including the use of metabolic labelling by stable isotope labelling by amino acids in cell culture (SILAC), localization of organelle proteins by isotope tagging (LOPIT) and proximity-dependent biotin identification (BioID). Finally, we describe a range of software resources that can be applied to interactomics, both to handle raw data and also to scrutinise its broader biological context. In this section we focus especially on open-access online interactomic databases such as Reactome and IntAct.
SPA proteins: SPAnning the gap between visible light and gene expression.

MAIN CONCLUSION: In this review we focus on the role of SPA proteins in light signalling and discuss different aspects, including molecular mechanisms, specificity, and evolution. The ability of plants to perceive and respond to their environment is key to their survival under ever-changing conditions. The abiotic factor light is of particular importance for plants. Light provides plants energy for carbon fixation through photosynthesis, but also is a source of information for the adaptation of growth and development to the environment. Cryptochromes and phytochromes are major photoreceptors involved in control of developmental decisions in response to light cues, including seed germination, seedling de-etiolation, and induction of flowering. The SPA protein family acts in complex with the E3 ubiquitin ligase COP1 to target positive regulators of light responses for degradation by the 26S proteasome to suppress photomorphogenic development in darkness. Light-activated cryptochromes and phytochromes both repress the function of COP1, allowing accumulation of positive photomorphogenic factors in light. In this review, we highlight the role of the SPA proteins in this process and discuss recent advances in understanding how SPAs link light-activation of photoreceptors and downstream signaling.
Visualized analysis of developing trends and hot topics in natural disaster research.

This study visualized and analyzed the developing trends and hot topics in natural disaster research. 19694 natural disaster-related articles (January 1900 to June 2015) are indexed in the Web of Science database. The first step in this study is using complex networks to visualize and analyze these articles. CiteSpace and Gephi were employed to generate a countries collaboration network and a disciplines collaboration network, and then attached hot topics to countries and disciplines, respectively. The results show that USA, China, and Italy are the three major contributors to natural disaster research. " Prediction model", "social vulnerability", and "landslide inventory map" are three hot topics in recent years. They have attracted attention not only from large countries like China but also from small countries like Panama and Turkey. Comparing two hybrid networks provides details of natural disaster research. Scientists from USA and China use image data to research earthquakes. Indonesia and Germany collaboratively study tsunamis in the Indian Ocean. However, Indonesian studies focus on modeling and simulations, while German research focuses on early warning technology. This study also introduces an activity index (AI) and an attractive index (AAI) to generate time evolution trajectories of some major countries from 2000 to 2013 and evaluate their trends and performance. Four patterns of evolution are visible during this 14-year period. China and India show steadily rising contributions and impacts, USA and England show relatively decreasing research efforts and impacts, Japan and Australia show fluctuating activities and stable attraction, and Spain and Germany show fluctuating activities and increasing impacts.
Shining a light on the Arabidopsis circadian clock.

The circadian clock provides essential timing information to ensure optimal growth to prevailing external environmental conditions. A major time-setting mechanism (zeitgeber) in clock synchronisation is light. Differing light wavelengths, intensities and photoperiodic duration are processed for the clock-setting mechanism. Many studies on light-input pathways to the clock have focused on Arabidopsis thaliana. Photoreceptors are specific chromic proteins that detect light signals and transmit this information to the central circadian oscillator through a number of different signalling mechanisms. The most well characterised clock-mediating photoreceptors are cryptochromes and phytochromes, detecting blue, red and far-red wavelengths of light. Ultraviolet and shaded light are also processed signals to the oscillator. Notably, the clock reciprocally generates rhythms of photoreceptor action leading to so-called gating of light responses. Intermediate proteins, such as Phytochrome interacting factors (PIFs), constitutive photomorphogenic 1 (COP1) and EARLY FLOWERING 3 (ELF3), have been established in signalling pathways downstream of photoreceptor activation. However, the precise details for these signalling mechanisms are not fully established. This review highlights both historical and recent efforts made to understand overall light input to the oscillator, first looking at how each wavelength of light is detected, this is then related to known input mechanisms and their interactions.
Single incision multiport versus conventional laparoscopic inguinal hernia repair: A matched comparison.

BACKGROUND: The popularity of single-incision procedures is on the rise as wound cosmesis is increasingly being seen as an important body image-related outcome. In this study, we assess the potential benefits of single-incision multiport laparoscopic totally extra-peritoneal (S-TEP) without using specialised ports or instruments and compare the same with the conventional laparoscopic TEP (C-TEP) surgery in terms of operative time, post-operative pain, complications, cost and cosmesis. MATERIALS AND METHODS: This is a prospective case-matched study of the patients undergoing S-TEP versus C-TEP from June 2014 to December 2015. RESULTS: Each group had 36 patients. The two groups were comparable in the clinical characteristics. The mean duration of surgery for a unilateral hernia in C-TEP and S-TEP was 45.13 ± 10.58 min and 72.63 ± 15.23 min, respectively. The mean visual analogue scale (VAS) score for pain was significantly higher in S-TEP group at post-operative day (POD) 0 and 1. However, at POD 7, there was no significant difference between the groups. At 1st and 6-week post-surgery, the cosmetic results were significantly better in S-TEP group as compared to C-TEP, however, at 6 months, the scar was highly acceptable in both treatment groups. CONCLUSION: S-TEP, using conventional laparoscopic instruments, is safe and feasible even in resource challenged setting. However, there is a need to review the indications and advantages of single-incision laparoscopic surgery, as no difference in cosmetic outcome by VAS score in S-TEP versus conventional laparoscopic arm seen by the end of 1 month.
Randomized clinical trial of laparoscopic versus open pancreatoduodenectomy for periampullary tumours.

BACKGROUND: Laparoscopic resection as an alternative to open pancreatoduodenectomy may yield short-term benefits, but has not been investigated in a randomized trial. The aim of this study was to compare laparoscopic and open pancreatoduodenectomy for short-term outcomes in a randomized trial. METHODS: Patients with periampullary cancers were randomized to either laparoscopic or open pancreatoduodenectomy. The outcomes evaluated were hospital stay (primary outcome), and blood loss, radicality of surgery, duration of operation and complication rate (secondary outcomes). RESULTS: Of 268 patients, 64 who met the eligibility criteria were randomized, 32 to each group. The median duration of postoperative hospital stay was longer for open pancreaticoduodenectomy than for laparoscopy (13 (range 6-30) versus 7 (5-52) days respectively; P = 0·001). Duration of operation was longer in the laparoscopy group. Blood loss was significantly greater in the open group (mean(s.d.) 401(46) versus 250(22) ml; P < 0·001). Number of nodes retrieved and R0 rate were similar in the two groups. There was no difference between the open and laparoscopic groups in delayed gastric emptying (7 of 32 versus 5 of 32), pancreatic fistula (6 of 32 versus 5 of 32) or postpancreatectomy haemorrhage (4 of 32 versus 3 of 32). Overall complications (defined according to the Clavien-Dindo classification) were similar (10 of 32 versus 8 of 32). There was one death in each group. CONCLUSION: Laparoscopy offered a shorter hospital stay than open pancreatoduodenectomy in this randomized trial. Registration number: NCT02081131( http://www.clinicaltrials.gov).
Robotic-assisted minimally invasive oesophagectomy for cancer: An initial experience.

Background: The morbidity related to radical oesophagectomy can be reduced by adopting minimally invasive techniques. Over 250 thoraco-laparoscopic oesophagectomy (TLE) was done in our centre over the last 15 years, before adopting robotic surgery as the latest innovation in the field of minimally invasive surgery. Here, we share our initial experience of robotic-assisted minimally invasive oesophagectomy (RAMIE) for carcinoma oesophagus. Methods: A prospective observational study conducted from February to December 2017. A total of 15 patients underwent RAMIE in this period. Data regarding demography, clinical characteristics, investigations, operating techniques, and post-operative outcome were collected in detail. Results: There were 10 (66.7%) male patients and the median age of all patients was 62.9 (range 36-78) years. The median body mass index was 24.4 (range 15-32.8) kg/m2. Twelve (80.0%) patients had squamous cell carcinoma (SCC) of the oesophagus and 3 (20%) patients had adenocarcinoma (AC). Five (33.3%) patients received neoadjuvant therapy. All 15 patients underwent RAMIE. Patients with SCC underwent McKeown's procedure, and those with AC underwent Ivor Lewis procedure. Extended two-field lymphadenectomy (including total mediastinal lymphadenectomy) was done for all the patients. The median operating time was 558 (range 390-690) min and median blood loss was 145 (range 90-230) ml. There were no intra-operative adverse events, and none of them required conversion to open or total thoracolaparoscopic procedure. The most common post-operative complications were recurrent laryngeal nerve paresis (3 patients, 20.0%) and pneumonia (2 patients, 13.3%). The median hospital stay was 9 (range 7-33) days. In total, 9 (60%) patients required adjuvant treatment. Conclusion: Adequate experience in TLE can help minimally invasive surgeons in easy adoption of RAMIE with satisfactory outcome.
Sharing data from clinical trials: the rationale for a controlled access approach.

BACKGROUND: The move towards increased transparency around clinical trials is welcome. Much focus has been on under-reporting of trials and access to individual patient data to allow independent verification of findings. There are many other good reasons for data sharing from clinical trials. We describe some key issues in data sharing, including the challenges of open access to data. These include issues in consent and disclosure; risks in identification, including self-identification; risks in distorting data to prevent self-identification; and risks in analysis. These risks have led us to develop a controlled access policy, which safeguards the rights of patients entered in our trials, guards the intellectual property rights of the original researchers who designed the trial and collected the data, provides a barrier against unnecessary duplication, and ensures that researchers have the necessary resources and skills to analyse the data. METHODS: We briefly discuss the practicalities of our current approach to data sharing, including ensuring that data are discoverable and how to deal with old studies. We describe data sharing activities at the MRC Clinical Trials Unit. RESULTS: One hundred and three data sharing activities were logged from 2012 to 2014 from external and internal applicants. The motivations are varied, but none have been for replication of the primary results. CONCLUSIONS: For any request to share data, we note the important role of independent reviewers as well as reviewers who know the study well, and present some of the key questions that all reviewers should ask when deciding whether a request is reasonable. We consider the responsibilities of all parties. We highlight the potential for opportunity costs. Clinical trial data should be shared for reasonable requests but there are many practical issues that must be explicitly considered.
Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial.

BACKGROUND: Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) is a randomized controlled trial that follows a novel multi-arm, multi-stage (MAMS) design. We describe methodological and practical issues arising with (1) stopping recruitment to research arms following a pre-planned intermediate analysis and (2) adding a new research arm during the trial. METHODS: STAMPEDE recruits men who have locally advanced or metastatic prostate cancer who are starting standard long-term hormone therapy. Originally there were five research and one control arms, each undergoing a pilot stage (focus: safety, feasibility), three intermediate 'activity' stages (focus: failure-free survival), and a final 'efficacy' stage (focus: overall survival). Lack-of-sufficient-activity guidelines support the pairwise interim comparisons of each research arm against the control arm; these pre-defined activity cut-off becomes increasingly stringent over the stages. Accrual of further patients continues to the control arm and to those research arms showing activity and an acceptable safety profile. The design facilitates adding new research arms should sufficiently interesting agents emerge. These new arms are compared only to contemporaneously recruited control arm patients using the same intermediate guidelines in a time-delayed manner. The addition of new research arms is subject to adequate recruitment rates to support the overall trial aims. RESULTS: (1) Stopping Existing Therapy: After the second intermediate activity analysis, recruitment was discontinued to two research arms for lack-of-sufficient activity. Detailed preparations meant that changes were implemented swiftly at 100 international centers and recruitment continued seamlessly into Activity Stage III with 3 remaining research arms and the control arm. Further regulatory and ethical approvals were not required because this was already included in the initial trial design.(2) Adding New Therapy: An application to add a new research arm was approved by the funder, (who also organized peer review), industrial partner and regulatory and ethical bodies. This was all done in advance of any decision to stop current therapies. CONCLUSIONS: The STAMPEDE experience shows that recruitment to a MAMS trial and mid-flow changes its design are achievable with good planning. This benefits patients and the scientific community as research treatments are evaluated in a more efficient and cost-effective manner. TRIAL REGISTRATION: ISRCTN78818544, NCT00268476. First patient into trial: 17 October 2005. First patient into abiraterone comparison: 15 November 2011.
Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1.

Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. ' Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting.
Laparoscopic management of solid pseudo papillary neoplasm of pancreas in tertiary care center from south India.

BACKGROUND: Solid pseudo papillary neoplasm (SPN) of the pancreas which predominantly affects young women is a relatively indolent entity with favorable prognosis. Resection through minimal access approach helps to achieve better short term benefits. The aim of this study is to describe our experience in laparoscopic management of this disease. METHODS: A retrospective review of our prospectively maintained database revealed that 17 patients with SPN were managed with surgical resection between March 2009 and October 2016. The clinical data of these patients were then analyzed. RESULTS: Among the 17 cases of SPN, 14 were females and 3 were males. The mean age at presentation was 26.1 years (11-46 years). The most common presenting symptom was an abdominal pain (n = 10; 58.8%). A tumor was incidentally detected in 5 patients. The neoplasm was localized in the pancreatic head/neck in 6 patients and in the body/tail in 11. The median diameter of the tumors was 7.5 cm (2-13 cm). Five patients underwent pancreaticoduodenectomy, 10 had distal pancreatectomy, while median pancreatectomy or enucleation was performed in one each. All the patients were offered laparoscopic surgery; one distal pancreatectomy was converted to open in view of bleeding. The median length of stay was 7 days (5-28 days). The patients were followed up for a median period of 31 months (3-62 months). CONCLUSION: SPN is a rare neoplasm with low malignant potential and has an excellent prognosis. In our experience, laparoscopic surgical resection is safe and feasible, even for larger lesions.
Laparoscopic choledochoduodenostomy as a reliable rescue procedure for complicated bile duct stones.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with stone extraction is generally accepted as first line management for common bile duct (CBD) stones. CBD exploration, either by open or laparoscopic approach nowadays, is usually reserved for ERCP failures, complicated stone locations, along with altered anatomical situations. The aim of this study was to highlight the increasing role of laparoscopic choledochoduodenostomy which is not only a reliable but also as a rescue procedure for those failed ERCP cases due to complicated bile duct stones. MATERIALS AND METHODS: It is a retrospective review of the database, from a tertiary care teaching institution from India, from Jan 2012 up to December 2016. RESULTS: Out of total 30 patients who underwent laparoscopic choledochoduodenostomy, 28 had failed ERC stone clearance while two patients were directly offered drainage in view of unfavorable anatomy. The major reasons for failed ERC stone clearance were as follows-multiple large calculi (42.8%), recurrent stones (21.4%), and associated stricture (21.4%). Mean operating time was 130 (± 27) minutes with mean blood loss of 60 (± 19) ml. Stone extraction was successful, primarily by milking in 13 (43.33%) patients, rest required augmentation by Dormia basket/balloon. Two patients (6.66%) developed controlled bile leak which resolved with conservative treatment. The median length of hospital stay was 5 days (IQR 3-9). Mean duration of follow-up was 17 (± 3.2) months. CONCLUSION: Laparoscopic common bile duct exploration with choledochoduodenostomy has been shown to be a safe, reliable, and efficient method for treating complex CBDS, especially after failed ERCP procedures.
Population specificity of the DNAI1 gene mutation spectrum in primary ciliary dyskinesia (PCD).

BACKGROUND: Mutations in the DNAI1 gene, encoding a component of outer dynein arms of the ciliary apparatus, are the second most important genetic cause of primary ciliary dyskinesia (PCD), the genetically heterogeneous recessive disorder with the prevalence of ~1/20,000. The estimates of the DNAI1 involvement in PCD pathogenesis differ among the reported studies, ranging from 4% to 10%. METHODS: The coding sequence of DNAI1 was screened (SSCP analysis and direct sequencing) in a group of PCD patients (157 families, 185 affected individuals), the first ever studied large cohort of PCD patients of Slavic origin (mostly Polish); multiplex ligation-dependent probe amplification (MLPA) analysis was performed in a subset of ~80 families. RESULTS: Three previously reported mutations (IVS1+2-3insT, L513P and A538T) and two novel missense substitutions (C388Y and G515S) were identified in 12 families (i.e. ~8% of non-related Polish PCD patients). The structure of background SNP haplotypes indicated common origin of each of the two most frequent mutations, IVS1+2-3insT and A538T. MLPA analysis did not reveal any significant differences between patients and control samples. The Polish cohort was compared with all the previously studied PCD groups (a total of 487 families): IVS1+2-3insT remained the most prevalent pathogenetic change in DNAI1 (54% of the mutations identified worldwide), and the increased global prevalence of A538T (14%) was due to the contribution of the Polish cohort. CONCLUSIONS: The worldwide involvement of DNAI1 mutations in PCD pathogenesis in families not preselected for ODA defects ranges from 7 to 10%; this global estimate as well as the mutation profile differs in specific populations. Analysis of the background SNP haplotypes suggests that the increased frequency of chromosomes carrying A538T mutations in Polish patients may reflects local (Polish or Slavic) founder effect. Results of the MLPA analysis indicate that no large exonic deletions are involved in PCD pathogenesis.