From "Genes to Society":The logic and process of the New Johns Hopkins University School of Medicine curriculum

Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curriculum,which included serious study of basic science for two years,followed by 'learning by doing' in the 3d and 4th clinical years. After the Flexner report in 1910 which lauded the school as an exemplary model,this became the standard curricular structure of undergraduate medical education in the US. Since its founding Hopkins,like other medical schools,has struggled with burgeoning biomedical knowledge and the tension between time and content. The last curricular revision was implemented in 1992,and had several themes,including:(1) decreased lecture time and increased small group learning; (2) early clinical experience and more ambulatory clinical experience; (3) integration of the basic sciences to improve learning and reduce redundancy; (4) development of a longitudinal course for the social sciences,(named 'The Physician and Society' course); (5) a required thesis project for graduation. All but the last were implemented. Our students have done well in this curriculum. 98-100% pass the licensing board exams,and over 90% obtain their first choice for residency positions,often in highly competitive programs such as Dermatology,Neurosurgery and Ophthalmology. Approximately 30% of graduates are listed in the AAMC faculty roster-one of the highest percentages of graduates going to academic medicine in the country.

AfterWards:A Narrative Medicine Program at Johns Hopkins Medicine and in China

Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys benefits such as improved communication skills and personal and professional growth to physicians,medical students,and other health care providers.Narrative medicine can promote empathy and trust between patients and physicians and foster self-care.In 2014,the author and a colleague started an ongoing inter-disciplinary narrative medicine program in the Children’s Center of the Johns Hopkins Hospital called AfterWards.The program,which meets monthly,is open to all on a volunteer basis.Through literature,art,and writing,AfterWards nurtures empathy,encourages reflective practice,and builds community among a diverse group of health care providers.Through a series of lectures and workshops at Johns Hopkins Medicine,Peking Union Medical College,and Fudan Hospital in Shanghai,the author has introduced AfterWards to Chinese medical educators and clinicians.Working with Dr.Marta Hanson,she created an AfterWards Facilitator’s Guide for the use of Chinese practitioners.A recent White Paper on Chinese health care indicates that an infusion of humanities-based education,of which narrative medicine forms a part,can help rebuild patient-physician trust.Recently,there has been an increase in interest in narrative medicine in the United States and China.However,more research is needed to demonstrate the impact of programs like AfterWards.Challenges to the implementation of narrative medicine programs remain,most significantly in terms of expertise,resources,and time.

Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

The Two Cultures of Science: Implications for University-Industry Relationships in the U.S. Agriculture Biotechnology

Partnerships between U.S. universities and industries have existed for several decades and in recent years have become generally more varied, wider in scope, more aggressive and experimental and higher in public visibility. In addition, in the last few decades, public and private interests have advocated for government policies and laws to globally promote the commercialization of university science. This paper examines the persistence or convergence of the two cultures of science and the implications of this commercialization for university-industry relationships in agriculture biotechnology. The perceptions and values of over 200 U.S. university and industry scientists, managers and administrators who participate in or oversee research collaborations in agricultural biotechnology were analyzed. The findings revealed that the participants in these research relationships continue to perceive very distinct cultures of science and identify a wide range of concerns and disadvantages of these partnerships. Several actions were discussed to ensure that the two cultures serve complementary roles and that they maximize the public benefits from these increasing collaborations.

Conditioned medium from human dental pulp stem cells treats spinal cord injury by inhibiting microglial pyroptosis

Human dental pulp stem cell transplantation has been shown to be an effective therapeutic strategy for spinal cord injury.However,whether the human dental pulp stem cell secretome can contribute to functional recovery after spinal cord injury remains unclear.In the present study,we established a rat model of spinal cord injury based on impact injury from a dropped weight and then intraperitoneally injected the rats with conditioned medium from human dental pulp stem cells.We found that the conditioned medium effectively promoted the recovery of sensory and motor functions in rats with spinal cord injury,decreased expression of the microglial pyroptosis markers NLRP3,GSDMD,caspase-1,and interleukin-1β,promoted axonal and myelin regeneration,and inhibited the formation of glial scars.In addition,in a lipopolysaccharide-induced BV2 microglia model,conditioned medium from human dental pulp stem cells protected cells from pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway.These results indicate that conditioned medium from human dental pulp stem cells can reduce microglial pyroptosis by inhibiting the NLRP3/caspase-1/interleukin-1βpathway,thereby promoting the recovery of neurological function after spinal cord injury.Therefore,conditioned medium from human dental pulp stem cells may become an alternative therapy for spinal cord injury.

Mechanism of Cu entry into the brain:many unanswered questions

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

Upregulation of circ0000381 atienuates microglial/macrophage pyroptosis after spinal cord injury

Neuroinflammation exacerbates secondary damage after spinal cord injury,while microglia/macrophage pyroptosis is important to neuroinflammation.Circular RNAs(circRNAs)play a role in the central nervous system.However,the functional role and mechanism of circRNAs in regulating microglia/macrophage pyroptosis after spinal cord injury are still poorly studied.In the present study,we detected microglia/macrophage pyroptosis in a female rat model of spinal cord injury,along with upregulated levels of circ0000381 in the spinal cord.Our further experimental results suggest that circ0000381 may function as a sponge to sequester endogenous microRNA423-3p(miR-423-3p),which can increase the expression of NOD-like receptor 3(NLRP3),a pyroptosis marker.Therefore,upregulation of circ0000381 may be a compensatory change after spinal cord injury to attenuate microglia/macrophage pyroptosis.Indeed,knockdown of circ0000381 expression exacerbated microglia/macrophage pyroptosis.Collectively,our findings provide novel evidence for the upregulation of circ0000381,which may serve as a neuroprotective mechanism to attenuate microglia/macrophage pyroptosis after spinal cord injury.Accordingly,circ0000381 may be a novel therapeutic target for the treatment of spinal cord injury.

Extended finite element-based cohesive zone method for modeling simultaneous hydraulic fracture height growth in layered reservoirs

In this study,a fully coupled hydromechanical model within the extended finite element method(XFEM)-based cohesive zone method(CZM)is employed to investigate the simultaneous height growth behavior of multi-cluster hydraulic fractures in layered porous reservoirs with modulus contrast.The coupled hydromechanical model is first verified against an analytical solution and a laboratory experiment.Then,the fracture geometry(e.g.height,aperture,and area)and fluid pressure evolutions of multiple hydraulic fractures placed in a porous reservoir interbedded with alternating stiff and soft layers are investigated using the model.The stress and pore pressure distributions within the layered reservoir during fluid injection are also presented.The simulation results reveal that stress umbrellas are easily to form among multiple hydraulic fractures’tips when propagating in soft layers,which impedes the simultaneous height growth.It is also observed that the impediment effect of soft layer is much more significant in the fractures suppressed by the preferential growth of adjoining fractures.After that,the combined effect of in situ stress ratio and fracturing spacing on the multi-fracture height growth is presented,and the results elucidate the influence of in situ stress ratio on the height growth behavior depending on the fracture spacing.Finally,it is found that the inclusion of soft layers changes the aperture distribution of outmost and interior hydraulic fractures.The results obtained from this study may provide some insights on the understanding of hydraulic fracture height containment observed in filed.

Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain

Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment.However,it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain.In this study,we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2(PGE2)concentration in response to mechanical loading.Bone PGE2 levels are in proportion to their weight bearing.When weight bearing changes in the tail-suspension mice,the PGE2 concentrations in bones change in line with their weight bearing changes.Deletion of cyclooxygenase-2(COX2)in the osteoblast lineage cells or knockout of receptor 4(EP4)in sensory nerve blunts bone formation in response to mechanical loading.Moreover,knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation.Moreover,mechanical loading induces cAMP-response element binding protein(CREB)phosphorylation in the hypothalamic arcuate nucleus(ARC)to inhibit sympathetic tyrosine hydroxylase(TH)expression in the paraventricular nucleus(PVN)for osteogenesis.Finally,we show that elevated PGE2 is associated with ankle osteoarthritis(AOA)and pain.Together,our data demonstrate that in response to mechanical loading,skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis,while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.

Anatomical Retrofitting:Pi(脾)as Spleen and the Persistence of Ontological Ambivalence

Over the past decade,medical researchers in China have debated whether the Pi(脾)corresponds to the biomedical spleen or pancreas.This debate exemplifies a broader phenomenon of“anatomical retrofitting”,or the anachronistic imposition of contemporary categories onto living historical objects.“Anatomical retrofitting”as a means of rectifying cases of mistranslation further positions the biomedical spleen and pancreas as representing ahistorical,universal truths.This framework gives rise to a conceptual binary:while the biomedical spleen is universalized as what philosophers may describe as“logical”ontology,the Pi connects to a different nature of reality,or“metaphysical”ontology.Far from being an object of imprecision,the Pi was a dynamic vessel that also shared characteristics with the humoral spleen.Given that scholars in China have already subjected Pi to historical scrutiny,this paper urges scholars to do the same with biomedical anatomy.For instance,historically situating the humoral spleen demonstrates that it became less known and less articulated as it transformed into the biomedical spleen.Meanwhile,the pancreas remained an unstable epistemic object that took on the dynamic functions of the humoral spleen in nineteenth-century organotherapy.Through primary source analysis and literature review,this paper contends that the apparent ontological incommensurability between Pi and spleen is neither mutually exclusive nor irreconcilable.Instead,the dynamic nature of internal viscera,their many functions,and their participation in epistemic practices contribute to an ongoing ontological ambivalence that persists despite the forced certainty of anatomical retrofitting.

Origins of perturbations in dayside equatorial ground magnetograms

To determine the cause(s)of perturbations seen in dayside equatorial ground magnetograms,we conducted a systematic survey of simultaneous ground-based and geosynchronous satellite-based observations during the 90-day period from December 1,2020 to February 28,2021.We examined Huancayo ground magnetometer observations from 14:00:00 to 20:00:00 UT each day,during which Huancayo passed through local noon.From those data we chose perturbation events selected on the basis of large(>20 nT)event amplitude and classified the selected events as responding primarily to solar wind pressure,or to variations in the north/south component of the interplanetary magnetic field(IMF Bz),or perhaps in part to both.The results show that an equivalent number of events were identified for each model during this 90-day period.Variations in the lagged solar wind dynamic pressure routinely correspond to nearly simultaneous sudden impulses recorded at both geosynchronous orbit and on the ground.Variations in IMF Bz produce erosion signatures at geosynchronous orbit and can correspond to ground events if lag times for reconnection to enhance convection in the magnetosphere are taken into account.

Using choroidal thickness to detect myopic macular degeneration

AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.

Estimating the subsolar magnetopause position from soft X-ray images using a low-pass image filter

The Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)missions will image the Earth’s dayside magneto pause and cusps in soft X-rays after their respective launches in the near future,to specify glo bal magnetic reconnection modes for varying solar wind conditions.To suppo rt the success of these scientific missions,it is critical to develop techniques that extract the magnetopause locations from the observed soft X-ray images.In this research,we introduce a new geometric equation that calculates the subsolar magnetopause position(RS)from a satellite position,the look direction of the instrument,and the angle at which the X-ray emission is maximized.Two assumptions are used in this method:(1)The look direction where soft X-ray emissions are maximized lies tangent to the magnetopause,and(2)the magnetopause surface near the subsolar point is almost spherical and thus RSis nea rly equal to the radius of the magneto pause curvature.We create synthetic soft X-ray images by using the Open Geospace General Circulation Model(OpenGGCM)global magnetohydrodynamic model,the galactic background,the instrument point spread function,and Poisson noise.We then apply the fast Fourier transform and Gaussian low-pass filte rs to the synthetic images to re move noise and obtain accurate look angles for the soft X-ray pea ks.From the filte red images,we calculate RS and its accuracy for different LEXI locations,look directions,and solar wind densities by using the OpenGGCM subsolar magnetopause location as ground truth.Our method estimates RS with an accuracy of<0.3 RE when the solar wind density exceeds>10 cm-3.The accuracy improves for greater solar wind densities and during southward interplanetary magnetic fields.The method ca ptures the magnetopause motion during southwa rd interplaneta ry magnetic field turnings.Consequently,the technique will enable quantitative analysis of the magnetopause motion and help reveal the dayside reconnection modes for dynamic solar wind conditions.This technique will suppo rt the LEXI and SMILE missions in achieving their scientific o bjectives.

Pregnancy stressors and postpartum symptoms of depression and anxiety:the moderating role of a cognitivebehavioural therapy(CBT)intervention

Background Little is known about the association between stressors(especially positive stressors)during pregnancy and postpartum depression and anxiety.Aims We investigated the association between positive and negative stress events during different stages of pregnancy and postpartum mental health outcomes among low-income pregnant women with symptoms of anxiety in Pakistan and evaluated whether an intervention based on cognitive behavioural therapy(CBT)had a regulatory effect.Methods Participants were 621 pregnant Pakistani women with mild anxiety.Using the Pregnancy Experience Scale-Brief Version,six scores were created to assess positive and negative stressors.We performed a multivariate linear regression to examine whether these six scores,measured both at baseline and in the third trimester,were associated with postpartum anxiety and depressive symptoms.The effect of the intervention on this relationship was examined by adding an interaction term to the regression model.Results Hassles frequency measured in the third trimester was positively associated with depression(B=0.22,95%confidence interval(Cl):0.09 to 0.36)and anxiety(B=0.19,95%Cl:0.08to 0.30).At the same timepoint,uplifts intensity was negatively associated with symptoms of depression(B=-0.82,95%Cl:1.46 to-0.18)and anxiety(B=-0.70,95%Cl:-1.25 to-0.15),whereas hassles intensity was positively related to symptoms of depression(B=1.02,95%Cl:0.36 to 1.67)and anxiety(B=0.90,95%Cl:0.34 to 1.47).The intensity ratio of hassles to uplifts reported in the third trimester was positively related to both depression(B=1.40,95%Cl:0.59 to 2.20)and anxiety(B=1.26,95%Cl:0.57 to 1.96).The intervention strengthened the overall positive effects of uplfts and the negative effects of hassles.Pregnancy experiences at baseline during early pregnancy to mid-pregnancy were not associated with mental health outcomes.Conclusions Stressors in the third trimester but not earlier in pregnancy were associated with postpartum symptoms of anxiety and depression.The CBT intervention modified the association between pregnancy stressors and postpartum mental health outcomes.Programmes that promote positive experiences and reduce negative experiences,especially in late pregnancy,may mitigate postpartum mental health consequences.

The Soft X-ray Imager(SXI)on the SMILE Mission

The Soft X-ray Imager(SXI)is part of the scientific payload of the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission.SMILE is a joint science mission between the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)and is due for launch in 2025.SXI is a compact X-ray telescope with a wide field-of-view(FOV)capable of encompassing large portions of Earth’s magnetosphere from the vantage point of the SMILE orbit.SXI is sensitive to the soft X-rays produced by the Solar Wind Charge eXchange(SWCX)process produced when heavy ions of solar wind origin interact with neutral particles in Earth’s exosphere.SWCX provides a mechanism for boundary detection within the magnetosphere,such as the position of Earth’s magnetopause,because the solar wind heavy ions have a very low density in regions of closed magnetic field lines.The sensitivity of the SXI is such that it can potentially track movements of the magnetopause on timescales of a few minutes and the orbit of SMILE will enable such movements to be tracked for segments lasting many hours.SXI is led by the University of Leicester in the United Kingdom(UK)with collaborating organisations on hardware,software and science support within the UK,Europe,China and the United States.

The magnetosheath at high spectral resolution

While we eagerly anticipate SMILE’s(Solar wind Magnetosphere Ionosphere Link Explorer)unprecedented X-ray observations of the Earth’s magnetosheath and the initiation of a new era of magnetospheric research,it seems appropriate to look ahead to the abilities of the next generation of astrophysics missions.Of these,the Line Emission Mapper(LEM),a large aperture micro-calorimeter based mission,is currently planned to be able to observe the magnetosheath at high spectral resolution(~2 eV).With a field of view of~30′,LEM will allow higher spatial resolution and higher cadence measurement of the motion of a very small portion of the magnetopause over relatively short periods of time(multiple hours),complementing SMILE’s global mapping.LEM’s strength is its spectral resolution.It will be able to measure the abundance of a broad range of elements and ionization states,many of which are inaccessible to current in situ instruments,and will be able to separate the emission from the magnetosheath from the emission from the cosmic X-ray background using the difference in their relative velocities.

Ground-based and additional science support for SMILE

The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere.Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission.Here,we describe current community efforts to prepare for SMILE,and the benefits and context various experiments that have explicitly expressed support for SMILE can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these efforts.Preparations include constructing an online SMILE Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft conjunctions.We anticipate growing interest and community engagement with the SMILE mission,and we welcome novel ideas and insights from the solar-terrestrial community.

Machine learning-guided accelerated discovery of structure-property correlations in lean magnesium alloys for biomedical applications

Magnesium alloys are emerging as promising alternatives to traditional orthopedic implant materials thanks to their biodegradability,biocompatibility,and impressive mechanical characteristics.However,their rapid in-vivo degradation presents challenges,notably in upholding mechanical integrity over time.This study investigates the impact of high-temperature thermal processing on the mechanical and degradation attributes of a lean Mg-Zn-Ca-Mn alloy,ZX10.Utilizing rapid,cost-efficient characterization methods like X-ray diffraction and optical microscopy,we swiftly examine microstructural changes post-thermal treatment.Employing Pearson correlation coefficient analysis,we unveil the relationship between microstructural properties and critical targets(properties):hardness and corrosion resistance.Additionally,leveraging the least absolute shrinkage and selection operator(LASSO),we pinpoint the dominant microstructural factors among closely correlated variables.Our findings underscore the significant role of grain size refinement in strengthening and the predominance of the ternary Ca_(2)Mg_(6)Zn_(3)phase in corrosion behavior.This suggests that achieving an optimal blend of strength and corrosion resistance is attainable through fine grains and reduced concentration of ternary phases.This thorough investigation furnishes valuable insights into the intricate interplay of processing,structure,and properties in magnesium alloys,thereby advancing the development of superior biodegradable implant materials.

Tetramethylpyrazine and paeoniflorin combination(TMP-PF)alleviates atherosclerosis progress by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway

Atherosclerosis remains a great threat to human health worldwide.Previous studies found that tetramethylpyrazine(TMP)and paeonifl orin(PF)combination(TMP-PF)exerts anti-atherosclerotic effects in vitro.However,whether TMP-PF improves atherosclerosis in vivo needs further exploration.The present study aims to assess the anti-atherosclerotic properties of TMP-PF in ApoE^(-/-)mice and explore the related molecule mechanisms.Results showed that TMP and high-dose TMP-PF decreased serum triglyceride and low-density lipoprotein cholesterol levels,suppressed vascular endothelial growth factor receptor 2(VEGFR2)and nuclear receptor subfamily 4 group A member 1(NR4A1)expression in aortic tissues,inhibited plaque angiogenesis,reduced plaque areas,and alleviated atherosclerosis in ApoE^(-/-)mice.Also,TMP-PF exhibited a better modulation effect than TMP or PF alone.However,NR4A1 agonist abolished the anti-atherosclerotic effects of TMP-PF.In conclusion,TMP-PF was first found to alleviate atherosclerosis progression by reducing hyperlipemia and inhibiting plaque angiogenesis via the NR4A1/VEGFR2 pathway,indicating that TMP-PF had a positive effect on reducing hyperlipemia and attenuating atherosclerosis development.

Lecanemab Unveiled:Exploring Alzheimer’s Treatment Advancements,Assessing Strengths,Limitations,and Its Therapeutic Landscape Position

In the ever-evolving landscape of Alzheimer’s treatment,lecanemab(Leqembi)has emerged as a promising drug.Unlike conventional therapies that merely alleviate symptoms,lecanemab is a humanized monoclonal antibody with a distinct focus.It targets protofibrils,insoluble fibrils,amyloid oligomers,and soluble amyloid-beta protofibrils,which are known to be especially damaging to neurons,with high accuracy.