One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon o...One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.展开更多
Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CN...Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).展开更多
Neurons are energy-demanding cells.Disruptions in energy metabolism can quickly interrupt neuronal function,leading to cell death and neurodegeneration.For instance,ischemia rapidly depletes adenosine triphosphate(ATP...Neurons are energy-demanding cells.Disruptions in energy metabolism can quickly interrupt neuronal function,leading to cell death and neurodegeneration.For instance,ischemia rapidly depletes adenosine triphosphate(ATP)thereby disrupting energy-dependent cellular processes crucial for homeostasis,and axon degeneration is preceded by a collapse of axonal ATP levels.展开更多
Base isolators used in buildings provide both a good acceleration reduction and structural vibration control structures.The base isolators may lose their damping capacity over time due to environmental or dynamic effe...Base isolators used in buildings provide both a good acceleration reduction and structural vibration control structures.The base isolators may lose their damping capacity over time due to environmental or dynamic effects.This deterioration of them requires the determination of the maintenance and repair needs and is important for the long-termisolator life.In this study,an artificial intelligence prediction model has been developed to determine the damage and maintenance-repair requirements of isolators as a result of environmental effects and dynamic factors over time.With the developed model,the required damping capacity of the isolator structure was estimated and compared with the previously placed isolator capacity,and the decrease in the damping property was tried to be determined.For this purpose,a data set was created by collecting the behavior of structures with single degrees of freedom(SDOF),different stiffness,damping ratio and natural period isolated from the foundation under far fault earthquakes.The data is divided into 5 different damping classes varying between 10%and 50%.Machine learning model was trained in damping classes with the data on the structure’s response to random seismic vibrations.As a result of the isolator behavior under randomly selected earthquakes,the recorded motion and structural acceleration of the structure against any seismic vibration were examined,and the decrease in the damping capacity was estimated on a class basis.The performance loss of the isolators,which are separated according to their damping properties,has been tried to be determined,and the reductions in the amounts to be taken into account have been determined by class.In the developed prediction model,using various supervised machine learning classification algorithms,the classification algorithm providing the highest precision for the model has been decided.When the results are examined,it has been determined that the damping of the isolator structure with the machine learning method is predicted successfully at a level exceeding 96%,and it is an effective method in deciding whether there is a decrease in the damping capacity.展开更多
Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent...Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.展开更多
Cardiac amyloidosis(CA)is caused by deposition of amyloid fibrils in the myocardium and has two main sub-types,transthyretin cardiac amyloidosis(ATTR)and immunoglobulin light chain cardiac amyloidosis(AL).ATTR is furt...Cardiac amyloidosis(CA)is caused by deposition of amyloid fibrils in the myocardium and has two main sub-types,transthyretin cardiac amyloidosis(ATTR)and immunoglobulin light chain cardiac amyloidosis(AL).ATTR is further dif-ferentiated into wild-type(wtATTR)and hereditary(hATTR),depending on the absence or presence of mutation in the trans-thyretin gene.The increased recognition of disease with the improvement in diagnostic armamentarium and serendipitous ad-vancements in the therapeutic landscape have changed the status of CA from being a rare and untreatable disease to being a not-so-rare and treatable disease.Both ATTR and AL have certain clinical aspects that can provide early clues for the disease.While electrocardiography followed by echocardiography and subsequently cardiac magnetic resonance can raise suspicion for CA,the definitive diagnosis of ATTR is non-invasively established by bone scintigraphy while that of AL always needs histological con-firmation.Severity of CA can be gauged by serum biomarker-based staging of both ATTR and AL.ATTR therapies work by silen-cing or stabilizing TTR or by degrading amyloid fibrils,while AL is managed with anti-plasma cell therapies and autologous stem cell transplant.展开更多
The phrase“Mens sana in corpore sano”taken from Juvenal's Satires(127 a.C.)represents one of the best-known and most used sentences of all time,whose meaning in the modern age refers to the importance of physica...The phrase“Mens sana in corpore sano”taken from Juvenal's Satires(127 a.C.)represents one of the best-known and most used sentences of all time,whose meaning in the modern age refers to the importance of physical activity for mental health and wellbeing.Robust literature demonstrated the positive role of exercise in counteracting several diseases,such as diabetes,cardiovascular diseases,neurodegenerative diseases,cancers and age-related disorders including muscle atrophy,the reduction of aerobic capacity,bone and cartilage loss.展开更多
BACKGROUND Literature focused on cancer screening and management is lacking in the transgender population.AIM To action to increase contributions to the scientific literature that drives the creation of cancer screeni...BACKGROUND Literature focused on cancer screening and management is lacking in the transgender population.AIM To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming(TGNC)patients.METHODS We performed a systematic search of PubMed on January 5th,2022,with the following terms:“TGNC”,OR“transgender”,OR“gender non-conforming”,OR“gender nonbinary”AND“cancer screening”,AND“breast cancer”,AND“cervical cancer”,AND“uterine cancer”,AND“ovarian cancer”,AND“prostate cancer”,AND“testicular cancer”,AND“surveillance”,AND“follow-up”,AND“management”.70 unique publications were used.The findings are discussed under“Screening”and“Management”categories.RESULTS Screening:Current cancer screening recommendations default to cis-gender protocols.However,long-term genderaffirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection.The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer.Management:Prior to undergoing Gender Affirmation Surgery(GAS),discussion should address cancer screening and management in the organs remaining in situ.Cancer treatment in this population requires consideration for chemotherapy,radiation,surgery and/or reconstruction.Modification of hormone therapy is decided on a case-by-case basis.The use of prophylactic vs aesthetic techniques in surgery is still debated.CONCLUSION When assessing transgender individuals for GAS,a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential.Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social,medical,surgical and gender affirming surgery related specifications.Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes.A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS.Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address.We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature.Further research is required to ensure more comprehensive and individualized care for this population.展开更多
BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors ...BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.展开更多
Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate d...Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate domain-specific design requirements,while at the same time satisfying aesthetic and functional principles of good design,can be a daunting task even for skilled visual designers.Presenting the annotations in 3D object space instead of projection space,allows for the preservation of spatial and depth cues.This results in stable layouts in dynamic environments,since the annotations are anchored in 3D space.Results In this paper we make two major contributions.First,we propose a technique for managing the layout and rendering of annotations in Virtual/Augmented Reality scenarios by manipulating the annotations directly in 3D space.For this,we make use of Artificial Potential Fields and use 3D geometric constraints to adapt them in 3D space.Second,we introduce PartLabeling:an open source platform in the form of a web application that acts as a much-needed generic framework allowing to easily add labeling algorithms and 3D models.This serves as a catalyst for researchers in this field to make their algorithms and implementations publicly available,as well as ensure research reproducibility.The PartLabeling framework relies on a dataset that we generate as a subset of the original PartNet dataset consisting of models suitable for the label management task.The dataset consists of 10003D models with part annotations.展开更多
Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite t...Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.展开更多
文摘One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.
文摘Axon disconnection in the central nervous system(CNS) usually causes signal transduction failure and severe functional deficits in patients with neurological disorders. Currently, there is no cure for patients with CNS axon injury and they usually suffer from life-long neurological defects(e.g., paralysis, loss of sensory function, and autonomic dysfunction) and life-threatening complications(e.g., autonomic dysreflexia).
基金supported by National Institute of Health awards NS118000 and NS128049 (to GG)。
文摘Neurons are energy-demanding cells.Disruptions in energy metabolism can quickly interrupt neuronal function,leading to cell death and neurodegeneration.For instance,ischemia rapidly depletes adenosine triphosphate(ATP)thereby disrupting energy-dependent cellular processes crucial for homeostasis,and axon degeneration is preceded by a collapse of axonal ATP levels.
基金the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(2020R1A2C1A01011131)the Energy Cloud R&D Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT(2019M3F2A1073164).
文摘Base isolators used in buildings provide both a good acceleration reduction and structural vibration control structures.The base isolators may lose their damping capacity over time due to environmental or dynamic effects.This deterioration of them requires the determination of the maintenance and repair needs and is important for the long-termisolator life.In this study,an artificial intelligence prediction model has been developed to determine the damage and maintenance-repair requirements of isolators as a result of environmental effects and dynamic factors over time.With the developed model,the required damping capacity of the isolator structure was estimated and compared with the previously placed isolator capacity,and the decrease in the damping property was tried to be determined.For this purpose,a data set was created by collecting the behavior of structures with single degrees of freedom(SDOF),different stiffness,damping ratio and natural period isolated from the foundation under far fault earthquakes.The data is divided into 5 different damping classes varying between 10%and 50%.Machine learning model was trained in damping classes with the data on the structure’s response to random seismic vibrations.As a result of the isolator behavior under randomly selected earthquakes,the recorded motion and structural acceleration of the structure against any seismic vibration were examined,and the decrease in the damping capacity was estimated on a class basis.The performance loss of the isolators,which are separated according to their damping properties,has been tried to be determined,and the reductions in the amounts to be taken into account have been determined by class.In the developed prediction model,using various supervised machine learning classification algorithms,the classification algorithm providing the highest precision for the model has been decided.When the results are examined,it has been determined that the damping of the isolator structure with the machine learning method is predicted successfully at a level exceeding 96%,and it is an effective method in deciding whether there is a decrease in the damping capacity.
文摘Non-descriptive and convenient labels are uninformative and unfairly project blame onto patients.The language clinicians use in the Electronic Medical Record,research,and clinical settings shapes biases and subsequent behaviors of all providers involved in the enterprise of transplantation.Terminology such as noncompliant and nonadherent serve as a reason for waitlist inactivation and limit access to life-saving transplantation.These labels fail to capture all the circum-stances surrounding a patient’s inability to follow their care regimen,trivialize social determinants of health variables,and bring unsubstantiated subjectivity into decisions regarding organ allocation.Furthermore,insufficient Medicare coverage has forced patients to ration or stop taking medication,leading to allograft failure and their subsequent diagnosis of noncompliant.We argue that perpetuating non-descriptive language adds little substantive information,in-creases subjectivity to the organ allocation process,and plays a major role in reduced access to transplantation.For patients with existing barriers to care,such as racial/ethnic minorities,these effects may be even more drastic.Transplant committees must ensure thorough documentation to correctly encapsulate the entirety of a patient’s position and give voice to an already vulnerable population.
文摘Cardiac amyloidosis(CA)is caused by deposition of amyloid fibrils in the myocardium and has two main sub-types,transthyretin cardiac amyloidosis(ATTR)and immunoglobulin light chain cardiac amyloidosis(AL).ATTR is further dif-ferentiated into wild-type(wtATTR)and hereditary(hATTR),depending on the absence or presence of mutation in the trans-thyretin gene.The increased recognition of disease with the improvement in diagnostic armamentarium and serendipitous ad-vancements in the therapeutic landscape have changed the status of CA from being a rare and untreatable disease to being a not-so-rare and treatable disease.Both ATTR and AL have certain clinical aspects that can provide early clues for the disease.While electrocardiography followed by echocardiography and subsequently cardiac magnetic resonance can raise suspicion for CA,the definitive diagnosis of ATTR is non-invasively established by bone scintigraphy while that of AL always needs histological con-firmation.Severity of CA can be gauged by serum biomarker-based staging of both ATTR and AL.ATTR therapies work by silen-cing or stabilizing TTR or by degrading amyloid fibrils,while AL is managed with anti-plasma cell therapies and autologous stem cell transplant.
基金funded by the University Research Project Grant(PIACERI Found–NATURE-OA–2020-2022)Department of Biomedical and Biotechnological Sciences(BIOMETEC),University of Catania,Italy(to GM)。
文摘The phrase“Mens sana in corpore sano”taken from Juvenal's Satires(127 a.C.)represents one of the best-known and most used sentences of all time,whose meaning in the modern age refers to the importance of physical activity for mental health and wellbeing.Robust literature demonstrated the positive role of exercise in counteracting several diseases,such as diabetes,cardiovascular diseases,neurodegenerative diseases,cancers and age-related disorders including muscle atrophy,the reduction of aerobic capacity,bone and cartilage loss.
文摘BACKGROUND Literature focused on cancer screening and management is lacking in the transgender population.AIM To action to increase contributions to the scientific literature that drives the creation of cancer screening and management protocols for transgender and gender nonconforming(TGNC)patients.METHODS We performed a systematic search of PubMed on January 5th,2022,with the following terms:“TGNC”,OR“transgender”,OR“gender non-conforming”,OR“gender nonbinary”AND“cancer screening”,AND“breast cancer”,AND“cervical cancer”,AND“uterine cancer”,AND“ovarian cancer”,AND“prostate cancer”,AND“testicular cancer”,AND“surveillance”,AND“follow-up”,AND“management”.70 unique publications were used.The findings are discussed under“Screening”and“Management”categories.RESULTS Screening:Current cancer screening recommendations default to cis-gender protocols.However,long-term genderaffirming hormone therapy and loss to follow-up from the gender-specific specialties contribute to a higher risk for cancer development and possible delayed detection.The only known screening guidelines made specifically for this population are from the American College of Radiology for breast cancer.Management:Prior to undergoing Gender Affirmation Surgery(GAS),discussion should address cancer screening and management in the organs remaining in situ.Cancer treatment in this population requires consideration for chemotherapy,radiation,surgery and/or reconstruction.Modification of hormone therapy is decided on a case-by-case basis.The use of prophylactic vs aesthetic techniques in surgery is still debated.CONCLUSION When assessing transgender individuals for GAS,a discussion on the future oncologic risk of the sex-specific organs remaining in situ is essential.Cancer management in this population requires a multidisciplinary approach while the care should be highly individualized with considerations to social,medical,surgical and gender affirming surgery related specifications.Special considerations have to be made during planning for GAS as surgery will alter the anatomy and may render the organ difficult to sample for screening purposes.A discussion with the patient regarding the oncologic risk of remaining organs is imperative prior to GAS.Other special considerations to screening such as the conscious or unconscious will to unassociated with their remaining organs is also a key point to address.We currently lack high quality studies pertinent to the cancer topic in the gender affirmation literature.Further research is required to ensure more comprehensive and individualized care for this population.
基金Supported by Veloxis Pharmaceuticals,Inc.1001 Winstead Drive Suite 310,Cary,NC 27513.
文摘BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.
文摘Background In this work,we focus on the label layout problem:specifying the positions of overlaid virtual annotations in Virtual/Augmented Reality scenarios.Methods Designing a layout of labels that does not violate domain-specific design requirements,while at the same time satisfying aesthetic and functional principles of good design,can be a daunting task even for skilled visual designers.Presenting the annotations in 3D object space instead of projection space,allows for the preservation of spatial and depth cues.This results in stable layouts in dynamic environments,since the annotations are anchored in 3D space.Results In this paper we make two major contributions.First,we propose a technique for managing the layout and rendering of annotations in Virtual/Augmented Reality scenarios by manipulating the annotations directly in 3D space.For this,we make use of Artificial Potential Fields and use 3D geometric constraints to adapt them in 3D space.Second,we introduce PartLabeling:an open source platform in the form of a web application that acts as a much-needed generic framework allowing to easily add labeling algorithms and 3D models.This serves as a catalyst for researchers in this field to make their algorithms and implementations publicly available,as well as ensure research reproducibility.The PartLabeling framework relies on a dataset that we generate as a subset of the original PartNet dataset consisting of models suitable for the label management task.The dataset consists of 10003D models with part annotations.
文摘Benzodiazepines and other benzodiazepine receptor agonists, such as the “Z” drugs, are widely prescribed medications mainly used for treating anxiety and seizures, and for inducing sedation. Unfortunately, despite their popularity, benzodiazepine prescribing often exceeds recommendations and the consequences can be severe. On September 23, 2020, the United States FDA announced a new requirement for a Boxed Warning for benzodiazepines prescribing. Along with this announcement, the FDA stated that relevant information regarding the initiation, continuation, and discontinuation of benzodiazepines is lacking. Here, we describe initial pilot studies intended to investigate the questions 1) can animal models be developed that demonstrate benzodiazepine physical dependence and/or withdrawal symptoms, and 2) determine whether translocator protein (TSPO) plays a role in benzodiazepine dependence and/or withdrawal processes. The former was demonstrated, methodological limitations prevented the latter.
