-
Computers in Biology and Medicine Jun 2022Recent research on artificial intelligence indicates that machine learning algorithms can auto-generate novel drug-like molecules. Generative models have revolutionized... (Review)
Review
Recent research on artificial intelligence indicates that machine learning algorithms can auto-generate novel drug-like molecules. Generative models have revolutionized de novo drug discovery, rendering the explorative process more efficient. Several model frameworks and input formats have been proposed to enhance the performance of intelligent algorithms in generative molecular design. In this systematic literature review of experimental articles and reviews over the last five years, machine learning models, challenges associated with computational molecule design along with proposed solutions, and molecular encoding methods are discussed. A query-based search of the PubMed, ScienceDirect, Springer, Wiley Online Library, arXiv, MDPI, bioRxiv, and IEEE Xplore databases yielded 87 studies. Twelve additional studies were identified via citation searching. Of the articles in which machine learning was implemented, six prominent algorithms were identified: long short-term memory recurrent neural networks (LSTM-RNNs), variational autoencoders (VAEs), generative adversarial networks (GANs), adversarial autoencoders (AAEs), evolutionary algorithms, and gated recurrent unit (GRU-RNNs). Furthermore, eight central challenges were designated: homogeneity of generated molecular libraries, deficient synthesizability, limited assay data, model interpretability, incapacity for multi-property optimization, incomparability, restricted molecule size, and uncertainty in model evaluation. Molecules were encoded either as strings, which were occasionally augmented using randomization, as 2D graphs, or as 3D graphs. Statistical analysis and visualization are performed to illustrate how approaches to machine learning in de novo drug design have evolved over the past five years. Finally, future opportunities and reservations are discussed.
Topics: Artificial Intelligence; Drug Design; Drug Discovery; Machine Learning; Neural Networks, Computer
PubMed: 35339849
DOI: 10.1016/j.compbiomed.2022.105403 -
International Urogynecology Journal Nov 2017De novo overactive bladder (OAB) is a known complication of midurethral sling surgery for the treatment of stress urinary incontinence. To date, differences in the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION AND HYPOTHESIS
De novo overactive bladder (OAB) is a known complication of midurethral sling surgery for the treatment of stress urinary incontinence. To date, differences in the incidence of de novo OAB following the use of different types of midurethral sling remain relatively unknown. The purpose of the present systematic review was to evaluate this incidence and summarize current evidence.
METHODS
We systematically searched the literature using the MEDLINE, Embase, Scopus, ClinicalTrials.gov, LILACS and Cochrane Central Register of Controlled Trials databases as well as the grey literature and references from the electronically retrieved articles. For comparisons of proportions, we used the chi-squared test. All reported analyses were designed as two-tailed. Statistical significance was set at p < 0.05.
RESULTS
Finally, 32 studies were included in this systematic review, with a total of 3,139 patients who had undergone midurethral sling procedures that included transobturator tapes (TOT), retropubic tapes (TVT) or single-incision tapes (mini-slings). The overall incidence of de novo OAB was 11.5% in nonrandomized studies (280 women) and 6.4% in randomized studies (50 women). In relation to the type of midurethral sling, the incidence of de novo OAB was 9.7% for mini-slings, 11.2% for TVT-O, 8.7% for TOT and 9.8% for TVTs. The chi-squared test did not reveal significant differences (p = 0.58).
CONCLUSIONS
Current evidence suggests that the overall incidence of de novo OAB following midurethral sling procedures is approximately 9%. There is not enough evidence to support differences in the effects of the different types of sling with regard to this particular postoperative complication.
Topics: Female; Gynecologic Surgical Procedures; Humans; Postoperative Complications; Suburethral Slings; Urinary Bladder, Overactive; Urinary Incontinence, Stress
PubMed: 28780649
DOI: 10.1007/s00192-017-3417-1 -
Breast (Edinburgh, Scotland) Aug 2021Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Locoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).
METHODS
RCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.
RESULTS
Analyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14-0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65-1.43), triple negative (HR 1.4, 95% CI 0.50-3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68-1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62) and in visceral disease (HR = 1.02, 95% CI 0.77-1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.
CONCLUSIONS
LRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.
Topics: Breast Neoplasms; Female; Humans; Proportional Hazards Models; Radiotherapy, Adjuvant; Survival Rate
PubMed: 34158167
DOI: 10.1016/j.breast.2021.05.003 -
Hepatobiliary & Pancreatic Diseases... Oct 2015Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the efficacy and safety of everolimus in de novo liver transplant patients.
DATA SOURCES
Randomized controlled trials comparing everolimus for de novo liver transplant in PubMed, the Cochrane Library, and ScienceDirect published up to March 31, 2014 were searched by two independent reviewers. Mean differences and 95% confidence interval (95% CI) for renal function, relative risk (RR) and 95% CI for treated biopsy-proven acute rejection (tBPAR), graft loss, death, neoplasms/tumor recurrence, and adverse events were collected. Meta-analyses were performed with RevMan version 5.10.
RESULTS
A total of four randomized controlled trials covering 1119 cases were included. The meta-analyses revealed that compared with standard exposure of calcineurin inhibitors (CNIs), everolimus combined with reduced CNIs improved creatinine clearance (calculated with the Cockcroft-Gault formula) by 5.13 mL/min at one year (95% CI: 0.42-9.84; P=0.03), and decreased tBPAR (RR: 0.56; 95% CI: 0.35-0.90; P=0.02). Everolimus initiation with CNIs elimination improved glomerular filtration rate (GFR, measured with the modification of diet in renal disease formula) of 10.42 mL/min/1.73 m2 (95% CI: 3.44-17.41; P<0.01) one year after treatment, but increased tBPAR (RR: 1.71; 95% CI: 1.15-2.53; P<0.01). Everolimus decreased the risk of neoplasms/tumor recurrence after liver transplant (RR: 0.60; 95% CI: 0.34-1.03; P=0.06), but was associated with greater risk of adverse events which resulted in drug discontinuation (RR: 1.98; 95% CI: 1.49-2.64; P<0.01).
CONCLUSIONS
Early introduction of everolimus combined with low-dose or no CNI in de novo liver transplant significantly improves renal function one year post treatment. Everolimus combined with low-dose CNI decreases the risk of tBPAR one year after liver transplant, but everolimus administered without CNIs increases tBPAR.
Topics: Calcineurin Inhibitors; Drug Therapy, Combination; Everolimus; Graft Rejection; Humans; Immunosuppressive Agents; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 26459721
DOI: 10.1016/s1499-3872(15)60419-2 -
Frontiers in Pediatrics 2022Liver transplant (LT) recipients, particularly children, have an increased risk of developing food allergies (FAs) after transplantation both compared to all the other...
BACKGROUND
Liver transplant (LT) recipients, particularly children, have an increased risk of developing food allergies (FAs) after transplantation both compared to all the other transplant groups and to the general population. Little is known about the pathogenesis underlying this phenomenon and comprehensive recommendations or clinical practice guidelines are still lacking, mainly due to the scarcity of high-quality evidence.
AIM
We aimed to prepare a systematic review on FA in pediatric LT recipients to assess epidemiology and risk factors, evaluate the correlation to specific food groups, describe clinical manifestations, investigate the rate of tolerance acquisition over time and report available therapeutic strategies.
METHODS
We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, Scopus, Web of Science, Wiley online library, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for studies published from January 1980 to September 2021. All the articles were checked independently by two reviewers in two steps. A total of 323 articles were screened, and 40 were included for data extraction.
RESULTS AND CONCLUSIONS
We found that FAs develop in the 15% of pediatric LT recipients, especially in the first 2 years after surgery, with higher risk related to younger age at transplantation (especially <2 years of age) and tacrolimus immunosuppression. Subjects are often allergic to multiple foods, and 15% of them suffer from anaphylaxis. The majority of patients do not spontaneously outgrow their symptoms during follow-up. The discontinuation of tacrolimus in favor of cyclosporine or the association of tacrolimus with mycophenolate have been associated with the resolution or the improvement of FA in small retrospective case series and could be considered in case of severe or multiple, difficult to manage FAs. Prospective multicenter studies are needed to confirm these findings, guide the risk-based stratification of pediatric LT recipients, and provide for high-evidence therapeutic strategies for children with FA.
PubMed: 35633971
DOI: 10.3389/fped.2022.885942 -
Surgical Endoscopy Jan 2024Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open,... (Review)
Review
BACKGROUND
Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children.
METHODS
A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed.
RESULTS
After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction.
CONCLUSIONS
In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.
Topics: Adult; Child; Humans; Catheterization; Catheters, Indwelling; Kidney Failure, Chronic; Laparoscopy; Peritoneal Dialysis; Peritoneum
PubMed: 37989887
DOI: 10.1007/s00464-023-10550-8 -
Journal of the European Academy of... Sep 2023The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review... (Meta-Analysis)
Meta-Analysis Review
The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.
Topics: Child; Humans; Melanoma; Nevus; Nevus, Epithelioid and Spindle Cell; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 37210654
DOI: 10.1111/jdv.19220 -
World Journal of Clinical Cases Dec 2022As operative techniques and mortality rates of pancreatectomy have improved, there has been a shift in focus to maintaining and improving the nutritional status of these...
BACKGROUND
As operative techniques and mortality rates of pancreatectomy have improved, there has been a shift in focus to maintaining and improving the nutritional status of these patients as we continue to learn more about post-operative complications. Although pancreatic endocrine and exocrine insufficiencies are known complications of pancreatectomy, increased longevity of these patients has also led to a higher incidence of fatty liver disease which differs from traditional fatty liver disease given the lack of metabolic syndrome.
AIM
To identify and summarize patterns and risk factors of post-pancreatectomy fatty liver disease to guide future management.
METHODS
We performed a database search on PubMed selecting papers published between 2001 and 2022 in the English language. PubMed was last accessed 1 June 2022.
RESULTS
Various factors influence the development of fatty liver including indication for surgery (benign malignant), type of pancreatectomy, amount of pancreas remnant, and peri-operative nutritional status. With an incidence rate up to 75%, non-alcoholic fatty liver disease (NAFLD) can develop within 12 mo after pancreatectomy and various risk factors have been established including pancreatic resection line and remnant pancreas volume, peri-operative malnutrition and weight loss, pancreatic exocrine insufficiency (EPI), malignancy as the indication for surgery, and postmenopausal status.
CONCLUSION
Since majority of risk factors leads to EPI and malnutrition, peri-operative focus on nutrition and enzymes replacement is key in preventing and treating NAFLD after pancreatectomy.
PubMed: 36569000
DOI: 10.12998/wjcc.v10.i35.12946 -
Diabetes Therapy : Research, Treatment... Sep 2020Unhealthy behaviors, such as energy-dense food choices and a sedentary lifestyle, both of which are established risk factors for diabetes, are common and increasing... (Review)
Review
BACKGROUND
Unhealthy behaviors, such as energy-dense food choices and a sedentary lifestyle, both of which are established risk factors for diabetes, are common and increasing among Nepalese adults. Previous studies have reported a wide variation in the prevalence of prediabetes and diabetes in Nepal, and thus a more reliable pooled estimate is needed. Furthermore, Nepal underwent federalization in 2015, and the province-specific prevalence, which is necessary for the de novo provincial government to formulate local health policies, is lacking. This study aims to provide a comprehensive summary of the current literature on various aspects of diabetes in Nepal, i.e., the prevalence of prediabetes and diabetes as well as of the awareness, treatment, and control of diabetes in Nepal.
METHODS
This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched three electronic databases-PubMed, Scopus, and Web of Science-using a comprehensive search strategy to identify eligible studies published up to April 2, 2020. Data on prevalence estimates of prediabetes and diabetes were extracted and pooled in a meta-analysis using a random effect model. Subgroup analyses and meta-regression were conducted to assess heterogeneity across the studies. The quality of included studies was assessed using the New Castle-Ottawa scale.
RESULTS
We included 14 eligible studies that comprised a total of 44,129 participants and 3517 diabetes cases. Half of the included studies had good quality. Overall, the prevalence of prediabetes and diabetes was 9.2% (95% CI 6.6-12.6%) and 8.5% (95% CI 6.9-10.4%), respectively. Among the participants with diabetes, only 52.7% (95% CI 41.7-63.4%) were aware of their diabetes status, and 45.3% (95% CI 31.6-59.8%) were taking antidiabetic medications. Nearly one-third of those under antidiabetic treatment (36.7%; 95% CI 21.3-53.3%) had their blood glucose under control. The prevalence of prediabetes and diabetes gradually increased with increasing age and was more prevalent among males and urban residents. There was a wide variation in diabetes prevalence across the provinces in Nepal, the lowest 2% in Province 6 to the highest 10% in Province 3 and Province 4.
CONCLUSIONS
The prevalence of prediabetes and diabetes was high in Nepal, while its awareness, treatment, and control were low. Our findings call for urgent nationwide public health action in Nepal.
PubMed: 32712902
DOI: 10.1007/s13300-020-00884-0 -
Children (Basel, Switzerland) Dec 2021The available endoscopic techniques for ureterocele decompression include laser puncture (LP), electrosurgical incision (ES), and cold-knife incision. This systematic... (Review)
Review
De Novo Vesicoureteral Reflux Following Ureterocele Decompression in Children: A Systematic Review and Meta-Analysis Comparing Laser Puncture versus Electrosurgical Incision Techniques.
BACKGROUND
The available endoscopic techniques for ureterocele decompression include laser puncture (LP), electrosurgical incision (ES), and cold-knife incision. This systematic review was performed to compare the efficacy of LP versus ES techniques with special emphasis on de novo VUR.
METHODS
Four databases were systematically searched by the authors. The inclusion criteria were all comparative studies in which ureterocele decompression was performed by either LP or ES endoscopic techniques. Outcomes including the incidence of de novo VUR, the need for endoscopic retreatment of the ureterocele, and the need for secondary surgical procedures were studied. Risk ratios (RR) were calculated for all outcomes and the Mantel-Haenszel method was utilized for the estimation of pooled RR. The methodological quality was assessed by the Downs and Black scale.
RESULTS
Five studies were considered for systematic review, while four of them were included in the meta-analysis. Out of 202 children, 67 developed de novo VUR. Significantly lower rates of reflux were observed in the LP group vis-a-vis ES group (RR = 0.17, 95% CI 0.09 to 0.32, 0.00001). Endoscopic retreatment rates ( = 20) demonstrated no significant difference among the two patient groups (RR = 0.66, 95% CI 0.26-1.68, = 0.38). A total of 46 secondary procedures were performed in 170 children, mostly ureteral re-implantations, with a significantly lower need of secondary surgeries following LP versus ES (RR = 0.26, 95% CI 0.13-0.49, 0.0001). The risk of bias in the included studies was low-to-moderate.
CONCLUSIONS
When compared to the ES technique, the LP technique is associated with a significantly low incidence of de novo VUR and requirement for secondary surgeries (particularly anti-reflux surgeries). Endoscopic retreatment rates showed no significant difference between the two techniques. However, due to the moderate risk of bias in two out of four included studies, randomized controlled trials are needed in the future.
PubMed: 35053634
DOI: 10.3390/children9010010