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Accidents, trauma, bone defects, and oncological processes significantly impact patients' health and quality of life. While calcium phosphates and bioactive glasses are commonly used as bone fillers to facilitate bone regeneration in orthopedics and traumatology, they exhibit certain disadvantages compared to calcium silicophosphate phases. This study evaluates the in vitro cytocompatibility and in vivo osteogenic properties of two-third-generation ceramic phases: silicocarnotite (SC) and nagelschmidtite (Nagel). These phases were synthesized via a solid-state reaction and characterized using X-ray diffraction and scanning electron microscopy. In vitro behavior was assessed through bioactivity tests, cell viability, proliferation, and inflammatory profiles by detecting cytokines and reactive oxygen species. Osteogenic properties were evaluated by detecting bone-associated proteins in MG-G3, hFOB1.19, and MC3T3-E1 cell lines after 3, 7, and 14 days. 45S5 Bioactive glass (BG), hydroxyapatite (HAp), and osteogenic medium were employed as control standards for bone formation. SC and Nagel phases exhibited higher viability percentages as well as osteoconductive and osteoinductive behavior. Finally, SC and Nagel bone grafts were implanted in a Wistar rat model to assess their in vivo ability to induce bone formation, demonstrating complete osseointegration after 12 weeks. Histological evaluation revealed osteocytes forming osteons and the presence of blood vessels, particularly in rats implanted with Nagel. Given their favorable biological performance, SC and Nagel emerge as promising candidates for bone grafts in orthopedics, traumatology, and maxillofacial surgery.
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In this study, we conducted experimental and Monte Carlo simulation studies in the grand canonical ensemble (GCMC) to investigate the role of molecular orientation and surface heterogeneity on the adsorption of N2 at 77 K. Our research focused on a series of ordered nanoporous materials (SBA-15) with varying degrees of oxygen functionalities. Specifically, we examined the effects of surface heterogeneity on the calculation of pore size distribution (PSD) and the Brunauer-Emmett-Teller (BET) area of porous materials. To provide a comprehensive perspective, we compared our results with three levels of surface oxidation, including a pristine case without any surface oxidation. The results from both our experimental and simulation data reveal the importance of chemical heterogeneity in determining equilibrium properties such as molecular packing within the pores, differential enthalpies of adsorption, and N2 orientation distribution. Our findings suggest that accurate characterization of surface heterogeneity is crucial for understanding gas adsorption in nanoporous materials and for developing better models for predicting their performance in various applications. Moreover, our simulations revealed substantial changes in the molecular orientation of adsorbate particles with increasing surface heterogeneity. This insight provides valuable information about the behavior of molecules within the nanoporous materials, further enhancing our understanding of the complex adsorption processes in these systems.
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Zenker's diverticulum (ZD) is an uncommon disorder that can cause dysphagia with risk of aspiration. While surgical treatment has been the mainstay for many years, endoscopic diverticulotomy has emerged as a first-line option with favorable outcomes. We present the case of a 93-year-old woman with no significant past medical history who was diagnosed with a 6 cm ZD. Due to dysphagia, she experienced significant weight loss and was at risk of malnutrition. She developed aspiration pneumonia and required admission to our center. Given her condition and inability to swallow, a nasogastric tube was placed under radiological guidance for nutritional support pending definitive treatment. On radiographic localization of the ZD, a radiopaque metallic density image was observed that had not been identified in previous imaging. Suspecting a possible retained foreign body in the large diverticulum, a gastroscopy was performed. During the procedure, the ZD was accessed and a 10 mm metallic object was identified. The object was extracted using a Roth net, confirming the suspicion of a foreign body lodged in the ZD. The metallic piece was later identified as a patient's dental prosthesis. After resolution of the aspiration pneumonia, endoscopic-assisted diverticulotomy was performed. The procedure was carried out under deep sedation with cricopharyngeal myotomy without immediate complications. After 48 hours of hospitalization, the patient was discharged without requiring a nasogastric tube for feeding.
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The manuscript presents a novel approach to enhance the efficiency of continuous manual endoscopic suturing without compromising its effectiveness. This technique, still in its early stages of implementation across various centers, holds immense promise but faces the challenge of extended procedure times. The proposed method aims to address this limitation by streamlining specific steps, potentially leading to significant time saving.
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In the field of chronic myeloid leukemia (CML), new strategies are needed to increase the rate of successful treatment discontinuations, a crucial goal in this disease. Anti-PD-L1 checkpoint inhibitors are a promising therapeutic approach in CML after the demonstration of an increase of these inhibitory molecules in patients with CML. A phase Ib/II (NCT04793399, registration date March 11, 2021) open-label exploratory trial has been conducted to evaluate the safety of atezolizumab, a humanized anti-PD-L1 antibody, in combination with bosutinib in patients with newly diagnosed chronic phase CML. A total of 36 patients were planned to be enrolled, but the study had to be prematurely terminated due to safety concerns. Nine patients were included in the study, and only 8 went on to receive the combination with atezolizumab. There were a total of 44 adverse events (AEs) during the study period. The most frequent were gastrointestinal (50%), mostly mild (86% grade 1-2). The most serious AEs were hepatic. There were 17 hepatic AEs in 5 patients. Of the hepatic AEs 5 were during the bosutinib monotherapy phase and 12 during the combination phase (AST increase x4, ALT increase x4, blood bilirubin increase x1, alkaline phosphatase elevation x2, GGT increase x2), most of them grade 3-4. There were 2 patients who presented a dose-limiting toxicity; a grade 3 elevation of transaminases, that led to premature termination of the study. The combination of atezolizumab with bosutinib presents hepatotoxicity as a dose-limiting effect and therefore we do not recommend to explore this combination in future studies.
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Astrocitos , Núcleo Caudado , Trastornos Neurológicos de la Marcha , Corteza Motora , Plasticidad Neuronal , Enfermedad de Parkinson , Estimulación Magnética Transcraneal , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/fisiopatología , Plasticidad Neuronal/fisiología , Corteza Motora/fisiopatología , Masculino , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/fisiopatología , Persona de Mediana Edad , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/fisiopatología , Trastornos Neurológicos de la Marcha/terapia , Femenino , Anciano , Equilibrio Postural/fisiología , Trastornos de la Sensación/etiología , Trastornos de la Sensación/terapia , Trastornos de la Sensación/fisiopatologíaRESUMEN
This work presents the effect of the silicocarnotite (SC) and nagelschmidtite (Nagel) phases on in vitro osteogenesis. The known hydroxyapatite of biological origin (BHAp) was used as a standard of osteoconductive characteristics. The evaluation was carried out in conventional and osteogenic media for comparative purposes to assess the osteogenic ability of the bioceramics. First, the effect of the material on cell viability at 24 h, 7 and 14 days of incubation was evaluated. In addition, cell morphology and attachment on dense bioceramic surfaces were observed by fluorescence microscopy. Specifically, alkaline phosphatase (ALP) activity was evaluated as an osteogenic marker of the early stages of bone cell differentiation. Mineralized extracellular matrix was observed by calcium phosphate deposits and extracellular vesicle formation. Furthermore, cell phenotype determination was confirmed by scanning electron microscope. The results provided relevant information on the cell attachment, proliferation, and osteogenic differentiation processes after 7 and 14 days of incubation. Finally, it was demonstrated that SC and Nagel phases promote cell proliferation and differentiation, while the Nagel phase exhibited a superior osteoconductive behavior and could promote MC3T3-E1 cell differentiation to a higher extent than SC and BHAp, which was reflected in a higher number of deposits in a shorter period for both conventional and osteogenic media.
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Diferenciación Celular , Cerámica , Durapatita , Osteoblastos , Osteogénesis , Silicatos , Animales , Ratones , Durapatita/química , Durapatita/farmacología , Cerámica/química , Cerámica/farmacología , Osteoblastos/citología , Osteoblastos/metabolismo , Osteoblastos/efectos de los fármacos , Silicatos/química , Silicatos/farmacología , Diferenciación Celular/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Materiales Biocompatibles/química , Fosfatasa Alcalina/metabolismo , Compuestos de Calcio/farmacología , Compuestos de Calcio/química , Supervivencia Celular/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Matriz Extracelular/metabolismo , Células 3T3 , Línea CelularRESUMEN
Background: Although hearing aids (HAs) can compensate for reduced audibility, functional outcomes and benefits vary widely across individuals. As part of the Danish 'Better hEAring Rehabilitation' (BEAR) project, four distinct auditory profiles differing in terms of audiometric thresholds and supra-threshold hearing abilities were recently identified. Additionally, profile-specific HA-fitting strategies were proposed. The aim of the current study was to evaluate the self-reported benefit of these profile-based HA fittings in a group of new HA users. Methods: A total of 205 hearing-impaired older adults were recruited from two Danish university hospitals. Participants were randomly allocated to one of two treatment groups: (1) NAL-NL2 gain prescription combined with default advanced feature settings ('reference fitting') or (2) auditory profile-based fitting with tailored gain prescription and advanced feature settings ('BEAR fitting'). Two months after treatment, the participants completed the benefit version of the short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ12-B) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire. Results: Overall, participants reported a clear benefit from HA treatment. However, no significant differences in the SSQ12-B or IOI-HA scores between the reference and BEAR fittings were found. Conclusion: First-time users experience clear benefits from HA treatment. Auditory profile-based HA fitting warrants further investigation.
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Hearing aids provide nonlinear amplification to improve speech audibility and loudness perception. While more audibility typically increases speech intelligibility at low levels, the same is not true for above-conversational levels, where decreases in intelligibility ("rollover") can occur. In a previous study, we found rollover in speech intelligibility measurements made in quiet for 35 out of 74 test ears with a hearing loss. Furthermore, we found rollover occurrence in quiet to be associated with poorer speech intelligibility in noise as measured with linear amplification. Here, we retested 16 participants with rollover with three amplitude-compression settings. Two were designed to prevent rollover by applying slow- or fast-acting compression with a 5:1 compression ratio around the "sweet spot," that is, the area in an individual performance-intensity function with high intelligibility and listening comfort. The third, reference setting used gains and compression ratios prescribed by the "National Acoustic Laboratories Non-Linear 1" rule. Speech intelligibility was assessed in quiet and in noise. Pairwise preference judgments were also collected. For speech levels of 70â dB SPL and above, slow-acting sweet-spot compression gave better intelligibility in quiet and noise than the reference setting. Additionally, the participants clearly preferred slow-acting sweet-spot compression over the other settings. At lower levels, the three settings gave comparable speech intelligibility, and the participants preferred the reference setting over both sweet-spot settings. Overall, these results suggest that, for listeners with rollover, slow-acting sweet-spot compression is beneficial at 70â dB SPL and above, while at lower levels clinically established gain targets are more suited.
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Sordera , Audífonos , Pérdida Auditiva Sensorineural , Percepción del Habla , Humanos , Inteligibilidad del HablaRESUMEN
Case of a young female patient with reflux symptoms. During gastroscopy, the patient presented an episode of gastrointestinal bleeding after biopsy of a fundic lesion. Imaging tests were requested, showing a 8cm pancreatic cyst causing obstruction of the splenic vein with presence of portal hypertension and secondary gastric varices.
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Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.
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Perioperative myocardial injury (PMI) is a common cardiac complication. Recent guidelines recommend its systematic screening using high-sensitivity cardiac troponin (hs-cTn). However, there is limited evidence of local screening programs. We conducted a prospective, single-center study aimed at assessing the feasibility and outcomes of implementing systematic PMI screening. Hs-cTn concentrations were measured before and after surgery. PMI was defined as a postoperative hs-cTnT of ≥14 ng/L, exceeding the preoperative value by 50%. All patients were followed-up during the hospitalization, at one month and one year after surgery. The primary outcome was the incidence of death and major cardiovascular and cerebrovascular events (MACCE). The secondary outcomes focused on the individual components of MACCE. We included two-thirds of all eligible high-risk patients and achieved almost complete compliance with follow-ups. The prevalence of PMI was 15.7%, suggesting a higher presence of cardiovascular (CV) antecedents, increased perioperative CV complications, and higher preoperative hs-cTnT values. The all-cause death rate was 1.7% in the first month, increasing up to 11.2% at one year. The incidence of MACCE was 9.5% and 8.6% at the same time points. Given the observed elevated frequencies of PMI and MACCE, implementing systematic PMI screening is recommendable, particularly in patients with increased cardiovascular risk. However, it is important to acknowledge that achieving optimal screening implementation comes with various challenges and complexities.
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The International Prognostic Score of thrombosis in Essential Thrombocythemia (IPSET-thrombosis) and its revised version have been proposed to guide thrombosis prevention strategies. We evaluated both classifications to prognosticate thrombosis in 1366 contemporary essential thrombocythemia (ET) patients prospectively followed from the Spanish Registry of ET. The cumulative incidence of thrombosis at 10 years, taking death as a competing risk, was 11.4%. The risk of thrombosis was significantly higher in the high-risk IPSET-thrombosis and high-risk revised IPSET-thrombosis, but no differences were observed among the lower risk categories. Patients allocated in high-risk IPSET-thrombosis (subdistribution hazard ratios [SHR], 3.7 [95% confidence interval, CI, 1.6-8.7]) and high-risk revised IPSET-thrombosis (SHR, 3.2 [95% CI, 1.4-7.45]) showed an increased risk of arterial thrombosis, whereas both scoring systems failed to predict venous thrombosis. The incidence rate of thrombosis in intermediate risk revised IPSET-thrombosis (aged >60 years, JAK2-negative, and no history of thrombosis) was very low regardless of the treatment administered (0.9% and 0% per year with and without cytoreduction, respectively). Dynamic application of the revised IPSET-thrombosis showed a low rate of thrombosis when patients without history of prior thrombosis switched to a higher risk category after reaching 60 years of age. In conclusion, IPSET-thrombosis scores are useful for identifying patients at high risk of arterial thrombosis, whereas they fail to predict venous thrombosis. Controlled studies are needed to determine the appropriate treatment of ET patients assigned to the non-high-risk categories.
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(1) Background: The impact of SARS-CoV-2 has been variable over the time course of the pandemic and in different populations. The aim was to analyze the impact of COVID-19 infection in a known population of hemodialysis (HD) patients and professionals in Spain at different times of the pandemic. (2) Methods: We conducted an observational, descriptive study with a follow-up from 3 March 2020 to 23 April 2022 (776 days), using in average of 414 professionals and 1381 patients from 18 HD units in Spain. The data from the positive PCR or the rapid antigen detection test (RADT) subject were analyzed and segmented into six periods (waves). (3) Results: Of 703 positive COVID-19 tests, 524 were HD patients (74.5%), and 179 were HD professionals (25.5%). Overall, 38% of staff and 43% of patients were affected. Differences were observed in regard to incidence (21% vs. 13%), mortality (3.5% vs. 0%), and symptomatology between the patients and professionals and throughout the pandemic. (4) Conclusions: COVID-19 severity varied during different pandemic waves, with a greater impact seen in the first wave. HD professionals and patients had similar infection rates, but patients had higher mortality rates. Community transmission was the primary route of infection.
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Surface plasmon polaritons in graphene can enhance the performance of mid-infrared spectroscopy, which is key for the study of both the composition and the conformation of organic molecules via their vibrational resonances. In this paper, a plasmonic biosensor using a graphene-based van der Waals heterostructure on a piezoelectric substrate is theoretically demonstrated, where far-field light is coupled to surface plasmon-phonon polaritons (SPPPs) through a surface acoustic wave (SAW). The SAW creates an electrically-controlled virtual diffraction grating, suppressing the need for patterning the 2D materials, that limits the polariton lifetime, and enabling differential measurement schemes, which increase the signal-to-noise ratio and allow a quick commutation between reference and sample signals. A transfer matrix method has been used for simulating the SPPPs propagating in the system, which are electrically tuned to interact with the vibrational resonances of the analytes. Furthermore, the analysis of the sensor response with a coupled oscillators model has proven its capability of fingerprinting ultrathin biolayers, even when the interaction is too weak to induce a Fano interference pattern, with a sensitivity down to the monolayer limit, as tested with a protein bilayer or a peptide monolayer. The proposed device paves the way for the development of advanced SAW-assisted lab-on-chip systems combining the existing SAW-mediated physical sensing and microfluidic functionalities with the chemical fingerprinting capability of this novel SAW-driven plasmonic approach.
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Técnicas Biosensibles , Grafito , Sonido , Electricidad , AcústicaRESUMEN
Aims: To address the projected clinical benefits of dapagliflozin among patients with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF). Methods: A multicenter, prospective, cohort study of patients ≥50 years admitted with HF to Spanish internal medicine departments. The projected clinical benefits of dapagliflozin were calculated from the DELIVER trial. Results: A total of 4049 patients were included; 3271 (80.8%) were eligible for dapagliflozin treatment, according to DELIVER criteria. Within 1 year after discharge, 22.2% were rehospitalized for HF and 21.6% died. Implementation of dapagliflozin would translate into an absolute risk reduction of 1.3% for mortality and 5.1% for HF readmission. Conclusion: HF patients with preserved or mildly reduced ejection fraction have a high risk of events. The use of dapagliflozin could substantially reduce the HF burden.
Heart failure (HF) with preserved ejection fraction is frequent in clinical practice, particularly in the elderly. In HF with preserved ejection fraction, the heart still pumps a similar proportion of blood, but the heart muscle has become thicker. This means there is less space inside the heart to fill with blood, so too little is pumped out each time. Until very recently, no drugs had been shown to provide significant benefits on the outcome of the condition or the chance of recovery for these patients. Fortunately, recent clinical trials have demonstrated that treatment with drugs called SGLT2 inhibitors (e.g., dapagliflozin) could reduce the chance of being admitted to hospital or dying from HF. We investigated the benefits for patients who took dapagliflozin after being admitted to hospital and had HF with mildly reduced or preserved ejection fraction. We saw substantial benefits in this population.
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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Estudios de Cohortes , Estudios Prospectivos , Volumen SistólicoRESUMEN
A 76-year-old woman was being followed up for chronic anemia secondary to bleeding from vascular ectasias at the gastric antrum and the cardial and subcardial region. On several occasions the patient required fulguration of these lesions with conventional APC, which resulted in no clear improvement. Radiofrequency ablation of these lesions was then attempted using a 90-degree probe, which was successful on antral angiodysplasias but failed to remove lesions in the cardial and subcardial region since anatomy there prevented proper apposition of the probe onto the target mucosa. Given the absence of any improvement, it was decided to use fulguration for angiectasias at the cardial and subcardial level by means of Hybrid-APC, which consists of lifting the mucosa with an injection through the APC probe and then fulgurating in the pulsedAPC® mode, thus achieving a broader ablation area in a shorter time. During the subsequent review a clear reduction of vascular ectasias was observed.
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COVID-19 pandemic has put the protocols and the capacity of our Hospitals to the test. The management of severe patients admitted to the Intensive Care Units has been a challenge for all health systems. To assist in this challenge, various models have been proposed to predict mortality and severity, however, there is no clear consensus for their use. In this work, we took advantage of data obtained from routine blood tests performed on all individuals on the first day of hospitalization. These data has been obtained by standardized cost-effective technique available in all the hospitals. We have analyzed the results of 1082 patients with COVID19 and using artificial intelligence we have generated a predictive model based on data from the first days of admission that predicts the risk of developing severe disease with an AUC = 0.78 and an F1-score = 0.69. Our results show the importance of immature granulocytes and their ratio with Lymphocytes in the disease and present an algorithm based on 5 parameters to identify a severe course. This work highlights the importance of studying routine analytical variables in the early stages of hospital admission and the benefits of applying AI to identify patients who may develop severe disease.
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COVID-19 , Humanos , Inteligencia Artificial , Pandemias , Curva ROC , Hospitalización , Estudios RetrospectivosRESUMEN
PURPOSE: Pediatric intraoperative neurophysiological monitoring (IONM) has been shown to be effective in preventing and reversing postoperative neurological deficits in developed countries. There are currently no published studies from developing countries that describe neurophysiological findings and postoperative outcomes. Our study aims to address these gaps in children undergoing neurosurgical procedures in a single center. METHODS: We conducted a retrospective study of case series of children who underwent IONM (2014-2020) in the State of Mexico, Mexico. Sociodemographic characteristics, IONM modalities, changes during procedures, and short-term and long-term postoperative results were recorded. Descriptive statistics were used. RESULTS: We included 35 patients (≤18 years of age), 57% (20/35) boys. A relative increase of up to 5 times in the use of IONM is observed from 2014 (5.7%) to 2020 (25.7%) in our center. The most frequent preoperative pathologies were located at the infratentorial cranium (40%), followed by the spine and spinal cord (37.1%). The IONM modalities were as follows: free-running EMG 94.3%, transcranial electrical stimulation motor-evoked potentials 91.4%, somatosensory-evoked potentials 85.7%, triggered EMG 28.6%, EEG 25.7%, and visual-evoked potentials 5.7%. Only in 8.3%, we did not obtain sufficient evoked potential baseline signals. At 24 hours postoperatively true negatives were 100%. Long-term follow-up was completed in 22/35 (63%) at 3 months, 12/35 (34.2%) at 6 months, and 5/35 (14.3%) at 12 months with progressive motor and sensory improvement. CONCLUSIONS: Pediatric multimodal IONM in neurosurgeries from a single center in a developing country is mainly used in pathologies of the posterior fossa, spine, and spinal cord, with true negatives in 100% of those monitored, preventing and avoiding postoperative sequelae.
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Allosteric transcription factor (aTF) based biosensors can be used to engineer genetic circuits for a wide range of applications. The literature and online databases contain hundreds of experimentally validated molecule-TF pairs; however, the knowledge is scattered and often incomplete. Additionally, compared to the number of compounds that can be produced in living systems, those with known associated TF-compound interactions are low. For these reasons, new tools that help researchers find new possible TF-ligand pairs are called for. In this work, we present Sensbio, a computational tool that through similarity comparison against a TF-ligand reference database, is able to identify putative transcription factors that can be activated by a given input molecule. In addition to the collection of algorithms, an online application has also been developed, together with a predictive model created to find new possible matches based on machine learning.