Trends in Cancer and Heart Failure related mortality in adult US population: A CDC WONDER database analysis from 1999 to 2020.

BACKGROUND: With the advent of novel chemotherapy, survival of patients with cancer has improved. However, people with cancer have an increased risk of heart failure (HF). Conversely, HF-related mortality may undermine survival among people with cancer. We aim to analyze the trends of mortality in people with HF and cancer in the adult US population. METHODS: We conducted an examination of death certificates sourced from the CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) database, from the years 1999 to 2020. Mortality in adults with HF and cancer was assessed. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change were reported. RESULTS: Between 1999 and 2020, 621,783 deaths occurred from HF in people with cancer. The AAMR declined from 16.4 in 1999 to 11.9 in 2017, after which an increase to 14.5 was observed in 2020. Men had consistently higher overall AAMR as compared to women (men = 18.1 vs women = 9.9). Similar AAMR was observed between non-Hispanic (NH) Blacks/African Americans (13.9) and NH Whites (13.3), with lower in American Indian/Alaska Native (9.6) and Hispanics (7.4). Asian/Pacific Islanders reported the lowest AAMR (5.7). The Midwestern region reported the highest AAMR (14.8). We observed the highest AAMR amongst the older population (61.4). CONCLUSION: The mortality rates of people with HF and cancer are increasing in the adult U.S. POPULATION: This underscores the need for increased screening, aggressive management, and subsequent surveillance of people at risk or with manifested HF in people with cancer.

Molecular Dynamics Simulations Show That Short Peptides Can Drive Synthetic Cell Division by Binding to the Inner Membrane Leaflet.

An important functionality of lifelike "synthetic cells" is to mimic cell division. Currently, specialized proteins that induce membrane fission in living cells are the primary candidates for dividing synthetic cells. However, interactions between lipid membranes and proteins that are not found in living cells may also be suitable. Here, we discuss the potential of short membrane-anchored peptides to induce cell division. Specifically, we used the coarse-grained MARTINI model to investigate the interaction between short membrane-anchored peptides and a lipid bilayer patch. The simulation revealed that the anchored peptide induces significant spontaneous curvature and suggests that the lipid-peptide complex can be considered as a conically shaped "bulky headgroup" lipid. By systematically increasing the electrostatic charge of the peptide, we find that membrane-anchored peptides may generate sufficiently large constriction forces even at dilute coverages. Finally, we show that when the peptide has an opposite charge to the membrane, the peptide may induce division by binding the inner membrane leaflet of a synthetic cell, that is, cell division from within.

Multiple-dose pharmacokinetics of cenerimod and the effect of charcoal on its elimination.

Cenerimod is a sphingosine-1-phosphate receptor 1 modulator that reduces tissue availability of circulating lymphocytes. The compound is in Phase 3 development for the treatment of systemic lupus erythematosus. Its pharmacokinetic properties are characterized by slow absorption and multiphasic elimination with a long terminal half-life (t½), potentially caused by enterohepatic circulation (EHC). In this trial in healthy participants, oral cenerimod 0.5 and 4 mg once daily was administered for 50 days, followed by oral administration of activated charcoal (ie, 50 mg every 12 h for 11 days, starting 24 h after the last cenerimod dose), to investigate the potential EHC of cenerimod and assess whether elimination of cenerimod can be accelerated. The multiple-dose pharmacokinetics, pharmacodynamics, safety, and tolerability of cenerimod were also evaluated. For both doses, peak plasma concentrations were reached 6 and 7 h after dosing. Cenerimod accumulated approximately eightfold and (near) steady-state conditions were reached after 50 doses, resembling clinically meaningful exposure to cenerimod. The t½ following 0.5 and 4 mg of cenerimod was 767 and 799 h (ie, 32 and 33 days) and 720 and 780 h (ie, 30 and 33 days) with or without administration of charcoal, respectively, indicating no statistically significant difference. Therefore, charcoal did not accelerate cenerimod elimination suggesting that there is no EHC of cenerimod. A reversible, dose-dependent decrease in total lymphocyte count was observed. No safety concerns were identified; administration of charcoal was well tolerated.

Homocysteine contributes to atherogenic transformation of the aorta in rabbits in the absence of hypercholesterolemia.

Atherosclerosis, the leading cause of cardiovascular disease, cannot be sufficiently explained by established risk factors, including cholesterol. Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis and is closely linked to cardiovascular mortality. However, its role in atherosclerosis has not been fully clarified yet. We have previously shown that rabbits fed a diet deficient in B vitamins and choline (VCDD), which are required for Hcy degradation, exhibit an accumulation of macrophages and lipids in the aorta, aortic stiffening and disorganization of aortic collagen in the absence of hypercholesterolemia, and an aggravation of atherosclerosis in its presence. In the current study, plasma Hcy levels were increased by intravenous injections of Hcy into balloon-injured rabbits fed VCDD (VCDD+Hcy) in the absence of hypercholesterolemia. While this treatment did not lead to thickening of aortic wall, intravenous injections of Hcy into rabbits fed VCDD led to massive accumulation of VLDL-triglycerides as well as significant impairment of vascular reactivity of the aorta compared to VCDD alone. In the aorta intravenous Hcy injections into VCDD-fed rabbits led to fragmentation of aortic elastin, accumulation of elastin-specific electron-dense inclusions, collagen disorganization, lipid degradation, and autophagolysosome formation. Furthermore, rabbits from the VCDD+Hcy group exhibited a massive decrease of total protein methylated arginine in blood cells and decreased creatine in blood cells, serum and liver compared to rabbits from the VCDD group. Altogether, we conclude that Hcy contributes to atherogenic transformation of the aorta not only in the presence but also in the absence of hypercholesterolemia.

CCAR1 promotes DNA repair via alternative splicing.

DNA repair is directly performed by hundreds of core factors and indirectly regulated by thousands of others. We massively expanded a CRISPR inhibition and Cas9-editing screening system to discover factors indirectly modulating homology-directed repair (HDR) in the context of ∼18,000 individual gene knockdowns. We focused on CCAR1, a poorly understood gene that we found the depletion of reduced both HDR and interstrand crosslink repair, phenocopying the loss of the Fanconi anemia pathway. CCAR1 loss abrogated FANCA protein without substantial reduction in the level of its mRNA or that of other FA genes. We instead found that CCAR1 prevents inclusion of a poison exon in FANCA. Transcriptomic analysis revealed that the CCAR1 splicing modulatory activity is not limited to FANCA, and it instead regulates widespread changes in alternative splicing that would damage coding sequences in mouse and human cells. CCAR1 therefore has an unanticipated function as a splicing fidelity factor.

International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016.

OBJECTIVE: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DESIGN: A retrospective, cross-sectional survey of 3,103 assisted reproductive technology clinics in 74 countries in 2015 and 3,249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SETTING: Seventy-nine countries and >3,000 assisted reproductive technology clinics. PATIENT(S): Patients undergoing assisted reproductive technology procedures. INTERVENTION(S): Assisted reproductive technology. MAIN OUTCOME MEASURE(S): Outcomes on country, regional, and global levels. RESULT(S): Reported for 2015: 2,358,239 cycles with 548,652 infants born; for 2016: 2,807,963 cycles with 647,188 infants born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 infants; in 2016, ≥3,100,448 cycles resulted in ≥723,026 infants. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous treatment cycles were aged ≥40 years. Frozen-thawed embryo transfer (ET) cycles accounted for 47.0% and 51.9%, respectively, of all ETs in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all ETs in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed ET was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single ETs in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single ETs in frozen-thawed ET autologous treatment cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. CONCLUSION(S): Utilization of assisted reproductive technology treatment and births per cycle increased from 2015 to 2016, although multiple births were reduced. An increasing proportion of frozen-thawed ET cycles, continuing wide variation in use of intracytoplasmic sperm injection, and an increase in single ET rates are reported.

A multi-faceted exploration of unmet needs in the continuing improvement and development of fertility care amidst a pandemic.

PURPOSE: The continuous improvement and development of fertility care, internationally, requires ongoing monitoring of current delivery processes and outcomes in clinical practice. This descriptive and exploratory mixed-methods study was conducted in eight countries (Brazil, China, France, Germany, Italy, Mexico, Spain and the United Kingdom) to assess the unmet needs of fertility patients (male and female), and existing challenges, barriers and educational gaps of physicians and laboratory specialists involved in human fertility care during the COVID-19 pandemic. MATERIALS AND METHODS: The study was deployed sequentially in two phases: 1) in-depth 45-minute semi-structured interviews (n=76), transcribed, coded and thematically analysed using an inductive reasoning approach, 2) an online survey (n=303) informed by the findings of the qualitative interviews, face validated by experts in reproductive medicine, and analysed using descriptive and inferential statistical methods. RESULTS: The integrated results of both phases indicated numerous areas of challenges, including: 1) investigating male-related infertility; 2) deciding appropriate treatment for men and selective use of assisted reproductive technology; and 3) maintaining access to high-quality fertility care during a pandemic. CONCLUSIONS: The paper presents a reflective piece on knowledge and skills that warrant ongoing monitoring and improvement amongst reproductive medicine healthcare professionals amidst future pandemics and unanticipated health system disruptions. Moreover, these findings suggest that there is an additional need to better understand the required changes in policies and organizational processes that would facilitate access to andrology services for male infertility and specialized care, as needed.

Rotational femoral osteotomies and cam resection improve hip function and internal rotation for patients with anterior hip impingement and decreased femoral version.

Femoroacetabular impingement (FAI) patients with reduced femoral version (FV) are poorly understood. The aim of this study is to assess (i) hip pain and range of motion, (ii) subjective satisfaction and (iii) subsequent surgeries of symptomatic patients who underwent rotational femoral osteotomies. A retrospective case series involving 18 patients (23 hips, 2014-2018) with anterior hip pain that underwent rotational femoral osteotomies for treatment of decreased FV was performed. The mean preoperative age was 25 ± 6 years (57% male), and all patients had decreased FV < 10° and minimum 1-year follow-up (mean follow-up 2 ± 1 years). Surgical indication was the positive anterior impingement test, limited internal rotation (IR) in 90° of flexion (mean 10 ± 8°) and IR in extension (mean 24 ± 11°), anterosuperior chondrolabral damage in Magnet resonance (MR) arthrography, CT-based measurement of decreased FV (mean 5 ± 3°, Murphy method) and no osteoarthritis (Tönnis Grade 0). Most patients had intra- and extra-articular subspine FAI (patient-specific 3D impingement simulation). Subtrochanteric rotational femoral osteotomies to increase FV (correction 20 ± 4°) were combined with cam resection (78%) and surgical hip dislocation (91%). (i) The positive anterior impingement test decreased significantly (P < 0.001) from pre- to postoperatively (100% to 9%). IR in 90° of flexion increased significantly (P < 0.001, 10 ± 8° to 31 ± 10°). (ii) Subjective satisfaction increased significantly (P < 0.001) from pre- to postoperatively (33% 77%). The mean Merle d'Aubigné and Postel score increased significantly (P < 0.001) from 14 ± 2 (8-15) points to 17 ± 1 (13-18, P < 0.001) points. Most patients (85%) reported at follow-up that they would undergo surgery again. (iii) At follow-up, all 23 hips were preserved (no conversion to total hip arthroplasty). One hip (4%) underwent revision osteosynthesis. Proximal rotational femoral osteotomies combined with cam resection improve hip pain and IR in most FAI patients with decreased FV at short-term follow-up. Rotational femoral osteotomies to increase FV are safe and effective.

A corpus of GA4GH Phenopackets: case-level phenotyping for genomic diagnostics and discovery.

The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present phenopacket-store. Version 0.1.12 of phenopacket-store includes 4916 phenopackets representing 277 Mendelian and chromosomal diseases associated with 236 genes, and 2872 unique pathogenic alleles curated from 605 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

Intraocular pressure before and after capsulorhexis using two viscoelastic substances and two surgical approaches in enucleated porcine eyes.

AIM: To investigate the influence of ophthalmic viscoelastic devices (OVDs) and different surgical approaches on the intraocular pressure (IOP) before and after creation of the curvilinear circular capsulorhexis (CCC) as a measure for anterior chamber stability during this maneuver. METHODS: Prospective experimental WetLab study carried out on enucleated porcine eyes. IOP was measured before and after CCC with the iCare Rebound tonometer (iCare ic200; iCare Finland Oy, Vantaa, Finland). The OVDs used were a cohesive one [Z-Hyalin, Carl Zeiss Meditec AG, Germany; hyaluronic acid (HA)] and a dispersive [Z-Celcoat, Carl Zeiss Meditec AG, Germany; hydroxy propylmethylcellulosis (HPMC)]. The CCC was created using Utrata forceps or 23 g microforceps in different combinations with the OVDs. RESULTS: Using the Utrata forceps the IOP dropped from 63.65±6.44 to 11.25±3.63 mm Hg during the CCC. The use of different OVDs made no difference. Using the 23 g microforceps the IOP dropped from 65.35±8.15 to 36.55±6.09 mm Hg. The difference between IOP drop using either Utrata forceps or 23 g microforceps was highly significant regardless of the OVD used. CONCLUSION: Using the sideport for the creation of the capsulorhexis leads to a lesser drop in IOP during this maneuver compared to the main incision in enucleated porcine eyes. The use of different OVD has no significant influence on IOP drop.

Evaluating Polarizable Biomembrane Simulations against Experiments.

Owing to the increase of available computational capabilities and the potential for providing a more accurate description, polarizable molecular dynamics force fields are gaining popularity in modeling biomolecular systems. It is, however, crucial to evaluate how much precision is truly gained with increasing cost and complexity of the simulation. Here, we leverage the NMRlipids open collaboration and Databank to assess the performance of available polarizable lipid models─the CHARMM-Drude and the AMOEBA-based parameters─against high-fidelity experimental data and compare them to the top-performing nonpolarizable models. While some improvement in the description of ion binding to membranes is observed in the most recent CHARMM-Drude parameters, and the conformational dynamics of AMOEBA-based parameters are excellent, the best nonpolarizable models tend to outperform their polarizable counterparts for each property we explored. The identified shortcomings range from inaccuracies in describing the conformational space of lipids to excessively slow conformational dynamics. Our results provide valuable insights for the further refinement of polarizable lipid force fields and for selecting the best simulation parameters for specific applications.

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography.

Background: Cardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. Methods: The study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. Results: Detectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45-1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39-1.90) for the first tertile to 2.02 (95 % CI 1.74-2.35) for the third tertile. Conclusions: Detectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

A roadmap for therapeutic discovery in pulmonary hypertension associated with left heart failure. A scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Working Group on Pulmonary Circulation & Right Ventricular Function.

Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF.

Functional in vitro diversity of an intrinsically disordered plant protein during freeze-thawing is encoded by its structural plasticity.

Intrinsically disordered late embryogenesis abundant (LEA) proteins play a central role in the tolerance of plants and other organisms to dehydration brought upon, for example, by freezing temperatures, high salt concentration, drought or desiccation, and many LEA proteins have been found to stabilize dehydration-sensitive cellular structures. Their conformational ensembles are highly sensitive to the environment, allowing them to undergo conformational changes and adopt ordered secondary and quaternary structures and to participate in formation of membraneless organelles. In an interdisciplinary approach, we discovered how the functional diversity of the Arabidopsis thaliana LEA protein COR15A found in vitro is encoded in its structural repertoire, with the stabilization of membranes being achieved at the level of secondary structure and the stabilization of enzymes accomplished by the formation of oligomeric complexes. We provide molecular details on intra- and inter-monomeric helix-helix interactions, demonstrate how oligomerization is driven by an α-helical molecular recognition feature (α-MoRF) and provide a rationale that the formation of noncanonical, loosely packed, right-handed coiled-coils might be a recurring theme for homo- and hetero-oligomerization of LEA proteins.

Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer.

BACKGROUND: Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. OBJECTIVES: We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. METHODS: We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 50-61, > 61 g/m2; men, < 60, 60-74, > 74 g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24 kg/m2 and weight loss ≥ 5% in the prior 12 months). Repeat echocardiograms were obtained usually within 3-6 months for 85 patients. RESULTS: Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.9-4.2), 0.8 (0.2-2.2), 0.5 (0.3-1.6) ng/mL, p = 0.029; men, 2.1 (0.8-3.2), 0.6 (0.1-1.7), 0.7 (0.2-1.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48-116), 72 (48-95), 49 (35-76) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r = - 0.591, p < 0.001; men, r = - 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r = - 0.318, p = 0.003). CONCLUSION: In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associated with a decrease in relative LVmass during follow-up.

Long-Term Intake of Proton-Pump Inhibitors Could Be Associated with an Increased Incidence of Liver Cancer in Women.

BACKGROUND: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. METHODS: A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. RESULTS: Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06-1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09-1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09-1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21-3.26). CONCLUSIONS: Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication.

Ultrafast Kapitza-Dirac effect.

Similar to the optical diffraction of light passing through a material grating, the Kapitza-Dirac effect occurs when an electron is diffracted by a standing light wave. In its original description, the effect is time independent. Here, we extended the Kapitza-Dirac effect to the time domain. By tracking the spatiotemporal evolution of a pulsed electron wave packet diffracted by a 60-femtosecond (where one femtosecond = 10-15 seconds) standing wave pulse in a pump-probe scheme, we observed time-dependent diffraction patterns. The fringe spacing in the observed pattern differs from that generated by the conventional Kapitza-Dirac effect. By exploiting this time-resolved diffraction scheme, we can access the time evolution of the phase properties of a free electron and potentially image ionic potentials and electronic decoherences.