Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated durin...Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown.This study tested the hypothesis that progesterone(P4)and/or interferon tau(IFNT)regulate TNSALP activity during pregnancy in sheep.Methods In Exp.1,ewes were bred and received daily intramuscular injections of either corn oil vehicle(CO)or 25 mg progesterone in CO(P4)for the first 8 days of pregnancy and were hysterectomized on either Day 9,12,or 125 of gestation.In Exp.2,ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist(RU486)in CO from Days 8 to 15,and twice daily intrauterine injections of either control proteins(CX)or IFNT(25μg/uterine horn/d)from Days 11 to 15(treatment groups:P4+CX;P4+IFNT;RU486+P4+CX;and RU486+P4+IFNT)and were hysterectomized on Day 16.Results In Exp.1,endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12.TNSALP activity appeared greater in the epithelia,stratum compactum stroma,and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12.On Day 125,TNSALP activity localized to uterine epithelial and endothelial cells,independent of P4 treatment.TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes.In Exp.2,endometrial homogenates from ewes administered RU486+P4+CX had lower TNSALP activity those for P4+CX and P4+IFNT ewes.Immunoreactive TNSALP protein appeared greater in the mid-and deep-glandular epithelia in RU486+P4+CX treated ewes as compared to the other treatment groups.Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486+P4+CX compared to the other treatment groups.Conclusions These results suggest that P4,but not IFNT,regulates the expression and activity of TNSALP in uteroplacental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.展开更多
The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of Technology.We take an opportunity here to exa...The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of Technology.We take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this purpose.The National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in 2021.Therefore,we focus on this timespan.Data sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).展开更多
Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,...Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in mice.The cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)proteins.The cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).展开更多
The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a pati...The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.展开更多
The utilization of millimeter-wave frequencies and cognitive radio(CR)are promising ways to increase the spectral efficiency of wireless communication systems.However,conventional CR spectrum sensing techniques entail...The utilization of millimeter-wave frequencies and cognitive radio(CR)are promising ways to increase the spectral efficiency of wireless communication systems.However,conventional CR spectrum sensing techniques entail sampling the received signal at a Nyquist rate,and they are not viable for wideband signals due to their high cost.This paper expounds on how sub-Nyquist sampling in conjunction with deep learning can be leveraged to remove this limitation.To this end,we propose a multi-task learning(MTL)framework using convolutional neural networks for the joint inference of the underlying narrowband signal number,their modulation scheme,and their location in a wideband spectrum.We demonstrate the effectiveness of the proposed framework for real-world millimeter-wave wideband signals collected by physical devices,exhibiting a 91.7% accuracy in the joint inference task when considering up to two narrowband signals over a wideband spectrum.Ultimately,the proposed data-driven approach enables on-the-fly wideband spectrum sensing,combining accuracy,and computational efficiency,which are indispensable for CR and opportunistic networking.展开更多
Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with t...Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.展开更多
BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical ...BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.展开更多
Background MicroRNAs(miRNAs)are presented in the uterine lumen of many mammals,and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions.Our...Background MicroRNAs(miRNAs)are presented in the uterine lumen of many mammals,and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions.Our aim was to identify and contrast the miRNAs present in extracellular vesicles(EVs)in the uterine lumen fluid(ULF)at the onset of attachment in cattle pregnancies(gestation d 18)initiated by artificial insemination(AI)or by the trans-fer of an in vitro-produced blastocyst(IVP-ET).A third group had no conceptus after the transfer of an IVP embryo.Results The abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF.There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group,while 4 miRNAs had a lower abundance relative to the group not containing a conceptus.Additionally,4 miRNAs were more abun-dant in ULF EVs in the AI pregnant group relative to IVP-ET group(bta-mir-17,bta-mir-7-3,MIR7-1,MIR18A).Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endome-trium,including genes that are known to be their targets.Conclusions The results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation,as well as in endometrium receptivity.The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of cor-rective approaches to reduce conceptus losses during the first month of pregnancy in cattle.展开更多
基金supported by Agriculture and Food Research Initiative Competitive Grant 2016–67015-24958 from the USDA National Institute of Food and Agriculture。
文摘Background Tissue non-specific alkaline phosphatase(TNSALP;encoded by the ALPL gene)has a critical role in the postnatal regulation of p hospliate homeostasis,yet how TNSALP activity and expression are regulated during pregnancy remain largely unknown.This study tested the hypothesis that progesterone(P4)and/or interferon tau(IFNT)regulate TNSALP activity during pregnancy in sheep.Methods In Exp.1,ewes were bred and received daily intramuscular injections of either corn oil vehicle(CO)or 25 mg progesterone in CO(P4)for the first 8 days of pregnancy and were hysterectomized on either Day 9,12,or 125 of gestation.In Exp.2,ewes were fitted with intrauterine catheters on Day 7 of the estrous cycle and received daily intramuscular injections of 50 mg P4 in CO and/or 75 mg progesterone receptor antagonist(RU486)in CO from Days 8 to 15,and twice daily intrauterine injections of either control proteins(CX)or IFNT(25μg/uterine horn/d)from Days 11 to 15(treatment groups:P4+CX;P4+IFNT;RU486+P4+CX;and RU486+P4+IFNT)and were hysterectomized on Day 16.Results In Exp.1,endometria from ewes administered P4 had greater expression of ALPL mRNA than ewes administered CO on Day 12.TNSALP activity appeared greater in the epithelia,stratum compactum stroma,and endothelium of the blood vessels in the endometrium and myometrium from ewes administered P4 than ewes administered CO on Day 12.On Day 125,TNSALP activity localized to uterine epithelial and endothelial cells,independent of P4 treatment.TNSALP activity in placentomes appeared greater in P4 treated ewes and was detected in endothelial cells and caruncular tissue in P4 treated but not CO treated ewes.In Exp.2,endometrial homogenates from ewes administered RU486+P4+CX had lower TNSALP activity those for P4+CX and P4+IFNT ewes.Immunoreactive TNSALP protein appeared greater in the mid-and deep-glandular epithelia in RU486+P4+CX treated ewes as compared to the other treatment groups.Enzymatic activity appeared greater on the apical surface of the deep glandular epithelia in endometria from ewes treated with RU486+P4+CX compared to the other treatment groups.Conclusions These results suggest that P4,but not IFNT,regulates the expression and activity of TNSALP in uteroplacental tissues and has the potential to contribute to the regulation of phosphate availability that is critical for conceptus development during pregnancy.
文摘The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of Technology.We take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this purpose.The National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in 2021.Therefore,we focus on this timespan.Data sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).
基金supported by R01 NS093009 grant from NIH(to VVC).
文摘Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical neuroepithelium.One such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in mice.The cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)proteins.The cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).
文摘The critical role of patient-reported outcome measures(PROMs)in enhancing clinical decision-making and promoting patient-centered care has gained a profound significance in scientific research.PROMs encapsulate a patient's health status directly from their perspective,encompassing various domains such as symptom severity,functional status,and overall quality of life.By integrating PROMs into routine clinical practice and research,healthcare providers can achieve a more nuanced understanding of patient experiences and tailor treatments accordingly.The deployment of PROMs supports dynamic patient-provider interactions,fostering better patient engagement and adherence to tre-atment plans.Moreover,PROMs are pivotal in clinical settings for monitoring disease progression and treatment efficacy,particularly in chronic and mental health conditions.However,challenges in implementing PROMs include data collection and management,integration into existing health systems,and acceptance by patients and providers.Overcoming these barriers necessitates technological advancements,policy development,and continuous education to enhance the acceptability and effectiveness of PROMs.The paper concludes with recommendations for future research and policy-making aimed at optimizing the use and impact of PROMs across healthcare settings.
文摘The utilization of millimeter-wave frequencies and cognitive radio(CR)are promising ways to increase the spectral efficiency of wireless communication systems.However,conventional CR spectrum sensing techniques entail sampling the received signal at a Nyquist rate,and they are not viable for wideband signals due to their high cost.This paper expounds on how sub-Nyquist sampling in conjunction with deep learning can be leveraged to remove this limitation.To this end,we propose a multi-task learning(MTL)framework using convolutional neural networks for the joint inference of the underlying narrowband signal number,their modulation scheme,and their location in a wideband spectrum.We demonstrate the effectiveness of the proposed framework for real-world millimeter-wave wideband signals collected by physical devices,exhibiting a 91.7% accuracy in the joint inference task when considering up to two narrowband signals over a wideband spectrum.Ultimately,the proposed data-driven approach enables on-the-fly wideband spectrum sensing,combining accuracy,and computational efficiency,which are indispensable for CR and opportunistic networking.
文摘Human immunodeficiency virus(HIV)modifies CD4-positive cells,resulting in immunodeficiency and a wide range of gastrointestinal(GI)manifestations.The burden of HIV-related GI illnesses has significantly evolved with the widespread use of antiretroviral therapy(ART).While ART has effectively reduced the occurrence of opportunistic infections,it has led to an increase in therapy-related GI illnesses.Common esophageal conditions in HIV patients include gastroesophageal reflux disease,idiopathic esophageal ulcers,herpes simplex virus,cytomegalovirus(CMV),and candidal esophagitis.Kaposi’s sarcoma,a hallmark of acquired immunodeficiency syndrome,may affect the entire GI system.Gastritis and peptic ulcer disease are also frequently seen in patients with HIV.Diarrhea,often linked to both opportunistic infections and ART,requires careful evaluation.Bloody diarrhea,often a sign of colitis caused by bacterial infections such as Shigella or Clostridium difficile,is prevalent.Small bowel lymphoma,although rare,is increasing in prevalence.Anorectal disorders,including proctitis,fissures,and anal squamous cell carcinoma,are particularly relevant in homosexual men,underlining the importance of timely diagnosis.This review comprehensively explores the epidemiology,pathogenesis,and treatment considerations for the various GI disorders associated with HIV,highlighting the importance of accurate diagnosis and effective treatment to improve outcomes for HIV-infected patients.
文摘BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.
基金Agriculture and Food Research Initiative Competitive Grant no.2018-67015-31936 from the USDA National Institute of Food and Agriculture.
文摘Background MicroRNAs(miRNAs)are presented in the uterine lumen of many mammals,and in vitro experiments have determined that several miRNAs are important for the regulation of endometrial and trophoblast functions.Our aim was to identify and contrast the miRNAs present in extracellular vesicles(EVs)in the uterine lumen fluid(ULF)at the onset of attachment in cattle pregnancies(gestation d 18)initiated by artificial insemination(AI)or by the trans-fer of an in vitro-produced blastocyst(IVP-ET).A third group had no conceptus after the transfer of an IVP embryo.Results The abundance of 263 annotated miRNAs was quantified in the EVs collected from ULF.There was an increase in the transcript abundance of 20 miRNAs in the ULF EVs from the AI pregnant group,while 4 miRNAs had a lower abundance relative to the group not containing a conceptus.Additionally,4 miRNAs were more abun-dant in ULF EVs in the AI pregnant group relative to IVP-ET group(bta-mir-17,bta-mir-7-3,MIR7-1,MIR18A).Specific miRNAs in the ULF EVs were co-expressed with messenger RNAs expressed in extra-embryonic tissues and endome-trium,including genes that are known to be their targets.Conclusions The results provide biological insights into the participation of miRNAs in the regulation of trophoblast proliferation and differentiation,as well as in endometrium receptivity.The knowledge that in vitro cultured embryos can contribute to the altered abundance of specific miRNAs in the uterine lumen can lead to the development of cor-rective approaches to reduce conceptus losses during the first month of pregnancy in cattle.
文摘本文对生成式AI(Generative artificial intelligence,GenAI)的国内外发展现状进行了概述,重点分析了中美之间在算力、数据、算法、生态等方面存在的差距.为改变我国在生成式AI领域的落后现状,提出高能效算力建设、联邦数据、专业领域模型、基于TAO的联邦生态等应对策略,对大模型时代AI安全治理进行了论述,对通用人工智能(Artificial general intelligence,AGI)的未来发展进行了展望.
