N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.

N4 acetylcytidine (ac4C) modification mainly occurs on tRNA, rRNA, and mRNA, playing an important role in the expression of genetic information. However, it is still unclear whether microRNAs have undergone ac4C modification and their potential physiological and pathological functions. In this study, we identified that NAT10/THUMPD1 acetylates primary microRNAs (pri-miRNAs) with ac4C modification. Knockdown of NAT10 suppresses and augments the expression levels of mature miRNAs and pri-miRNAs, respectively. Molecular mechanism studies found that pri-miRNA ac4C promotes the processing of pri-miRNA into precursor miRNA (pre-miRNA) by enhancing the interaction of pri-miRNA and DGCR8, thereby increasing the biogenesis of mature miRNA. Knockdown of NAT10 attenuates the oncogenic characters of lung cancer cells by regulating miRNA production in cancers. Moreover, NAT10 is highly expressed in various clinical cancers and negatively correlated with poor prognosis. Thus, our results reveal that NAT10 plays a crucial role in cancer initiation and progression by modulating pri-miRNA ac4C to affect miRNA production, which would provide an attractive therapeutic strategy for cancers.

Actin-binding protein filamin B regulates the cell-surface retention of endothelial sphingosine 1-phosphate receptor 1.

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor essential for vascular development and postnatal vascular homeostasis. When exposed to sphingosine 1-phosphate (S1P) in the blood of ∼1 µM, S1PR1 in endothelial cells retains cell-surface localization, while lymphocyte S1PR1 shows almost complete internalization, suggesting the cell-surface retention of S1PR1 is endothelial cell specific. To identify regulating factors that function to retain S1PR1 on the endothelial cell surface, here we utilized an enzyme-catalyzed proximity labeling technique followed by proteomic analyses. We identified Filamin B (FLNB), an actin-binding protein involved in F-actin cross-linking, as a candidate regulating protein. We show FLNB knockdown by RNA interference induced massive internalization of S1PR1 into early endosomes, which was partially ligand dependent and required receptor phosphorylation. Further investigation showed FLNB was also important for the recycling of internalized S1PR1 back to the cell surface. FLNB knockdown did not affect the localization of S1PR3, another S1P receptor subtype expressed in endothelial cells, nor did it affect localization of ectopically expressed ß2-adrenergic receptor. Functionally, we show FLNB knockdown in endothelial cells impaired S1P-induced intracellular phosphorylation events and directed cell migration and enhancement of the vascular barrier. Taken together, our results demonstrate that FLNB is a novel regulator critical for S1PR1 cell-surface localization and thereby proper endothelial cell function.

Highly Enantioselective Decarboxylative Difluoromethylation.

Organofluorine molecules that contain difluoromethyl groups (CF2H) at stereogenic centers have gained importance in pharmaceuticals due to the unique ability of CF2H groups to act as lipophilic hydrogen bond donors. Despite their potential, the enantioselective installation of CF2H groups into readily available starting materials remains a challenging and underdeveloped area. In this study, we report a nickel-catalyzed decarboxylative difluoromethylation reaction that converts alkyl carboxylic acids into difluoromethylated products with exceptional enantioselectivity. This Ni-catalyzed protocol exhibits broad functional group tolerance and is applicable for synthesizing fluorinated bioisosteres of biologically relevant molecules.

High-efficiency single-frequency DBR fiber laser at 1091 nm utilizing a Yb:YAG crystal-derived silica fiber.

A single-frequency distributed Bragg Reflector (DBR) fiber laser operating at 1091 nm was demonstrated by using a Yb:YAG crystal-derived silica fiber (YDSF). The YDSF was prepared via the molten core (MC) method, with a Yb2O3 doping concentration of 5.60 wt.% in the core, resulting in a gain coefficient of 1.45 dB/cm at 1091 nm. Employing 0.8 cm of the YDSF, we attained a single-frequency laser with a maximum output power of 145 mW and a slope efficiency of 31.8%. The laser exhibited an optical signal-to-noise ratio (OSNR) exceeding 71 dB, a linewidth of ∼34 kHz, and a stabilized relative intensity noise (RIN) at -132 dB/Hz for frequencies over 4.5 MHz. The fiber laser could serve as an outstanding seed source for high-power, narrow-linewidth fiber amplifiers operating at 1091 nm.

Continuous-wave and SESAM mode-locked operation of a Yb:YSr3(PO4)3 laser.

We report on the continuous-wave (CW) and, for what we believe to be the first time, passively mode-locked (ML) laser operation of an Yb3+-doped YSr3(PO4)3 crystal. Utilizing a 976-nm spatially single-mode, fiber-coupled laser diode as pump source, the Yb:YSr3(PO4)3 laser delivers a maximum CW output power of 333 mW at 1045.8 nm with an optical efficiency of 55.7% and a slope efficiency of 60.9%. Employing a quartz-based Lyot filter, an impressive wavelength tuning range of 97 nm at the zero level was achieved in the CW regime, spanning from 1007 nm to 1104 nm. In the ML regime, incorporating a commercially available semiconductor saturable absorber mirror (SESAM) to initiate and maintain soliton-like pulse shaping, the Yb:YSr3(PO4)3 laser generated pulses as short as 61 fs at 1062.7 nm, with an average output power of 38 mW at a repetition rate of ∼66.7 MHz.

Efficient single-frequency Tm:YAG crystal-derived silica fiber laser at 1.7†µm.

A single-frequency distributed Bragg reflector (DBR) fiber laser operating at 1720 nm has been demonstrated for the first time using a Tm:YAG crystal-derived silica fiber (TCDSF), to the best of our knowledge. A single-frequency laser with an over 220 mW output power was achieved from a 1.5-cm-long TCDSF when being in-band pumped by a homemade 1610 nm fiber laser. The slope efficiency reached 25.30% for the absorbed pump power. The optical signal-to-noise ratio (OSNR) of the laser was ∼69.78 dB, and the laser linewidth was ∼84.5 kHz. Additionally, the measured relative intensity noise (RIN) remained at -130 dB/Hz at frequencies above 9 MHz. The experimental results indicate that the TCDSF is a promising gain medium for single-frequency lasers at 1.7 µm.

CT-guided radiofrequency ablation of facial and mandibular nerves in the treatment of compound Meige's syndrome.

This retrospective study examined the clinical outcomes and complications in 6 cases of compound Meige's syndrome, presenting with blepharospasm and masticatory muscle spasm, following treatment with CT-guided radiofrequency ablation targeting bilateral facial nerves and mandibular branches of the trigeminal nerve. After the operation, the symptoms of eyelid spasm and masticatory muscle spasm resolved, but mild facial paralysis and numbness of mandibular nerve innervation persisted. Follow-up for 4-28 months showed that the symptoms of facial paralysis resolved within 2-5 (3.17 ± 0.94) months after the operation, whereas the numbness in the mandibular region persisted, accompanied by a decrease in masticatory function. During the follow-up period, none of the 6 patients experienced a recurrence of Meige's syndrome. These findings suggest that CT-guided radiofrequency ablation of the bilateral facial nerve and mandibular branches of the trigeminal nerve may offer a promising approach to treating compound Meige's syndrome.

Improving the multi-functionality of optical tweezers with FPGA integration.

The development of optical tweezers aims to extend their operating function and pattern. However, excessive programming can lead to a decrease in the system's operating speed and introduce bugs or data transmission delays. In this study, we present a time-shared optical tweezers system that allows for parallel operation of multiple functions. To enable efficient data transmission, we employ a queue structure and a buffer. To assess the system's performance, we utilize a biological sample in conjunction with the optical tweezers system and scanning imaging technique. We quantify the trapping parameter while concurrently running power stabilization programs. As a result, the standard deviation of the measured stiffness is reduced by 60% in the x and y directions and 30% in the z direction, indicating a significant improvement in calibration precision. Throughout the program execution, the system maintains an operating rate of 110 kHz, and the data are continuously updated in real time on the host. The system's performance demonstrates its potential for quantification and morphological reconstruction of biological samples.

Failure risk management: adaptive performance control and mission abort decisions.

The failure behavior of safety-critical systems typically depends on the system performance level, which offers opportunities to control system failure risk through dynamic performance adjustment. Moreover, mission abort serves as an intuitive way to mitigate safety hazards during mission execution. Our study focuses on systems that execute successive missions with random durations. To balance mission completion probability and system failure risk, we examine two decision problems: when to abort missions and how to select the performance level prior to mission abort. Our objective is to maximize the expected revenue through dynamic performance control and mission abort (PCMA) decisions. We consider condition-based PCMA decisions and formulate the joint optimization problem into a Markov decision process. We establish the monotonicity and concavity of the value function. Based on this insight, we show that optimizing the mission abort policy requires a series of control limits. In addition, we provide conditions under which the performance control policies are monotone. For comparative purposes, we analytically evaluate the performances of some heuristic policies. Finally, we present a case study involving unmanned aerial vehicles executing power line inspections. The results indicate the superiority of our proposed risk control policies in enhancing operational performance for safety-critical systems. Dynamic performance adjustment and mission abort decisions provide opportunities to reduce the failure risk and increase operational rewards of safety-critical systems.

The developmental trajectory of prosocial behavior in economically disadvantaged children: General tendencies and heterogeneity.

INTRODUCTION: This study explored the general tendencies and heterogeneous developmental trajectory of prosocial behavior and predictors. METHOD: The present study conducted latent growth model and growth mixture model analyses in a sample of 814 students (Mage = 13.79 years old at baseline; 57% girls) from economically disadvantaged families, classified as being below the local income threshold in China, with four follow-up surveys administered during the following 2 years. RESULTS: The general tendency in the developmental trajectory of prosocial behavior showed a linear decrease. A gender difference in initial levels was observed, with girls showing a higher initial level of prosocial behavior than boys. Family functioning, subjective support, and support utilization significantly affected the intercept, but objective support significantly negatively affected the slope. Heterogeneity in the development of prosocial behavior was best classified with a 3-class solution, including C1 (Rapid-decrease, 10.6%), C2 (Medium-stable, 42.5%), and C3 (High-increase, 46.9%). The patterns of prosocial behavior development in economically disadvantaged children with higher family functioning were more likely to be in the High-increase Class than in the Rapid-decrease Class. CONCLUSION: The present study revealed an average decline in the trajectories of prosocial behavior development in economically disadvantaged children. However, it also captured heterogeneous developmental trajectories. Furthermore, the study revealed that family functioning, subjective support, and support utilization all served as protective factors for prosocial behavior among economically disadvantaged children.

Complications of Fat Grafting and Repositioning for Correction of Lower Eyelid Pouch With Tear Trough Deformity or Lid-Cheek Junction: A Systematic Review.

BACKGROUND: Fat grafting and repositioning may serve as a convenient, economical, and effective surgical method for correcting lower eyelid pouch with a tear trough deformity or lid-cheek junction. However, comprehensive systematic reviews and meta-analyses investigating the complications associated with this technique are lacking. OBJECTIVE: This study aimed to summarize and gather data on complications related to fat grafting and repositioning for the correction of tear trough deformity or lid-cheek junction in lower eyelid blepharoplasty. METHODS: A thorough search was performed across multiple databases including PubMed, Cochrane, Embase, ProQuest, Ovid, Scopus, and Web of Science. Specific inclusion and exclusion criteria were applied to screen the articles. The occurrence of complications was analyzed using a random-effects model. RESULTS: A total of 33 studies involving 4671 patients met the criteria for systematic evaluation and were included in this meta-analysis. The overall complication rates were 0.112 (95% confidence interval [CI]: 0.060-0.177) for total complications, 0.062 (95% CI: 0.003-0.172) for unsatisfactory correction or contour irregularity, 0.062 (95% CI: 0.009-0.151) for hematoma, swelling (not specified as bulbar conjunctiva), ecchymosis, or oozing of blood, and 0.024 (95% CI: 0.013-0.038) for reoperation. CONCLUSIONS: Fat grafting and repositioning for correcting a lower eyelid pouch with tear trough deformity or lid-cheek junction was associated with high rates of complications. Therefore, it is crucial to closely monitor the rates of unsatisfactory correction or contour irregularity, hematoma, swelling (not specified as bulbar conjunctiva), ecchymosis, or oozing of blood, and reoperation. In addition, effective communication with patients should be prioritized.

A Comparison of Telesimulation Using the Virtual Resus Room and In Situ Simulation in Pediatric Emergency Medicine.

OBJECTIVES: During the COVID-19 pandemic, there was a marked shift toward telesimulation in medical education. Limited studies exist comparing the effectiveness of online and offline simulation education. The goals of this study are to evaluate active learners' perceived effectiveness of telesimulation versus in situ simulation and to identify potential shortcomings of existing online teaching platforms. METHODS: Through participant evaluations after a simulation, we compared telesimulation using the Virtual Resus Room (VRR) to in situ simulation in the domains of (1) self-efficacy, (2) fidelity, (3) educational value, and (4) teaching quality. Study subjects included medical and pharmacy residents and medical students completing their pediatric emergency medicine rotation at two children's hospitals as well as nurses, nurse practitioners, and physician assistants who were recently hired and orienting to their new roles in the emergency department. Learners used a modified Michigan Standard Simulation Experience Scale to evaluate either a telesimulation or in situ simulation case. Survey responses were compared using Wilcoxon rank sum tests with Bonferroni correction for multiple comparisons. RESULTS: In overall assessment, in situ simulation was rated higher than telesimulation. There were significant differences noted related to perceived realism, utility in training device-related skills, and utility in training team-building skills. All P values were less than 0.0036. There were no significant differences between simulation types in perception of physical examination fidelity, instructor adequacy, or self-efficacy. CONCLUSIONS: Telesimulation using the VRR is comparable to in situ simulation in learners' perception of improvement in self-efficacy and of teaching quality for pediatric emergency medicine topics. However, participants felt less able to practice tactile and communication skills virtually. Further innovation is needed to improve learners' experience with fidelity and educational value.

Asymmetric Divergent Synthesis of ent-Kaurane-, ent-Atisane-, ent-Beyerane-, ent-Trachylobane-, and ent-Gibberellane-type Diterpenoids.

A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi-candol A, atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed based on late-stage transformations of common synthons having ent-kaurane and ent-trachylobane cores. The expeditious assembly of crucial advanced ent-kaurane- and ent-trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6-exo-trig cyclization of the alkene/enone and 3-exo-trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with πC═C and πC═O systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, and ent-gibberellane-type), nine C8-ethano-bridged diterpenoids A1-A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2, in which enantioselective total syntheses of candol A (A1, 8 steps), powerol (A2, 9 steps), sicanadiol (A3, 10 steps), epi-candol A (A4, 8 steps), ent-atisan-16α-ol (A6, 11 steps), and trachinol (A8, 10 steps) are achieved for the first time.

Enantioselective Divergent Syntheses of Cephalotaxus Alkaloids: (-)-Cephalotaxine, (-)-Cephalotine B, and (-)-Fortuneicyclidins A and B.

A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (-)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (-)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (-)-cephalotine B with an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin B with an unprecedented C3-C10 bond (14 steps), and its 2-epimer (-)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.

Single-frequency fiber laser of 315†mW at 1940†nm based on a Tm : YAG/Ho : YAG-co-derived silica fiber.

A 1940 nm single-frequency distributed Bragg reflector (DBR) fiber laser was demonstrated based on a Tm : YAG/Ho : YAG-co-derived silica fiber (THCDSF). The THCDSF, which had a core dopant concentration of 8.02 wt.% Tm2O3 and 1.18 wt.% Ho2O3, was prepared via the melt-in-tube (MIT) method using a Tm : YAG and a Ho : YAG as the precursor core and a silica tube as the cladding. Employing 1.8 cm of the THCDSF, we achieved a maximum single-frequency output power of 315 mW at 1940 nm when pumped by a 1610 nm fiber laser. The slope efficiency of the laser was 29.68% for the absorbed pump power. The laser linewidth was less than 23.65 kHz, and the relative intensity noise (RIN) stabilized at -145 dB/Hz after exceeding 4.8 MHz. To the best of our knowledge, this is the first demonstration of a single-frequency DBR laser with a Tm3+/Ho3+ fiber as the gain medium.

Proinflammatory activation of microglia in the cerebellum hyperexcites Purkinje cells to trigger ataxia.

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.

Ferroelectric and strain-tuned MoSe2/Bi2O2Se van der Waals heterostructure with band alignment evolution.

The vertically stacked two-dimensional van der Waals heterostructure (2D vdWH) provides a unique platform for integrating distinctive properties of various 2D materials by functionalizing the interfacial interaction and regulating its band alignment. Herein, we theoretically propose a new MoSe2/Bi2O2Se vdWH material, in which a zigzag-zipper structure of the Bi2O2Se monolayer is constructed to model its ferroelectric polarization and maintain a small interlayer mismatch with MoSe2. The results show a typical unipolar barrier structure with a large band offset in the conduction band and nearly zero offset in the valence band of MoSe2/Bi2O2Se when the ferroelectric polarization of Bi2O2Se is back to MoSe2, in which the electron migration is blocked and holes can migrate unimpeded. It is also found that the band alignment lies between the type-I and type-II heterostructures and band offsets can be flexibly modulated under the joint action of ferroelectric polarization of Bi2O2Se and in-plane biaxial tensile and compressive strains. This work would facilitate the development of multifunctional devices based on the MoSe2/Bi2O2Se heterostructure material.

Downregulation of NUP93 aggravates hypoxia-induced death of cardiomyocytes in vitro through abnormal regulation of gene transcription.

Nuclear pore complex in the nuclear envelope plays an important role in controlling the transportation of RNAs, proteins and other macromolecules between the nucleus and cytoplasm. The relationship between abnormal expression of nucleoporins and cardiovascular diseases is unclear. In this study we investigated how myocardial infarction affected the expression and function of nucleoporins in cardiomyocytes. We separately knocked down 27 nucleoporins in rat primary myocardial cells. Among 27 nucleoporins, knockdown of Nup93, Nup210 and Nup214 markedly increased the expression of ANP and BNP, two molecular markers of cardiomyocyte function. We showed that Nup93 was significantly downregulated in hypoxic cardiomyocytes. Knockdown of Nup93 aggravated hypoxia-induced injury and cell death of cardiomyocytes, whereas overexpression of Nup93 led to the opposite effects. RNA-seq and bioinformatics analysis revealed that knockdown of Nup93 did not affect the overall transportation of mRNAs from the nucleus to the cytoplasm, but regulated the transcription of a large number of mRNAs in cardiomyocytes, which are mainly involved in oxidative phosphorylation and ribosome subunits. Most of the down-regulated genes by Nup93 knockdown overlapped with the genes whose promoters could be directly bound by Nup93. Among these genes, we demonstrated that Nup93 knockdown significantly down-regulated the expression of YAP1. Overexpression of YAP1 partially rescued the function of Nup93 knockdown and attenuated the effects of hypoxia on cell injury and cardiomyocyte death. We conclude that down-regulation of Nup93, at least partially, contributes to hypoxia-induced injury and cardiomyocyte death through abnormal interaction with the genome to dynamically regulate the transcription of YAP1 and other genes. These results reveal a new mechanism of Nup93 and might provide new therapeutic targets for the treatment of ischemia-induced heart failure.

SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs.

N 6-Methyladenosine (m6A) is the most abundant modification within diverse RNAs including mRNAs and lncRNAs and is regulated by a reversible process with important biological functions. Human YTH domain family 2 (YTHDF2) selectively recognized m6A-RNAs to regulate degradation. However, the possible regulation of YTHDF2 by protein post-translational modification remains unknown. Here, we show that YTHDF2 is SUMOylated in vivo and in vitro at the major site of K571, which can be induced by hypoxia while reduced by oxidative stress and SUMOylation inhibitors. SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression. Moreover, Disease-free survival analysis of patients with lung adenocarcinoma derived from TCGA dataset reveals that higher expression of YTHDF2 together with higher expression of SUMO1 predicts poor prognosis. Our works uncover a new regulatory mechanism for YTHDF2 recognition of m6A-RNAs and highlight the importance of YTHDF2 SUMOylation in post-transcriptional gene expression regulation and cancer progression.

Asynchronous Learning Module for Pediatric Emergency Medicine Physicians on How to Manage Vaginal Birth and Neonatal Resuscitation in the Emergency Department.

OBJECTIVES: Newborn deliveries and neonatal resuscitation events are rare but essential skills for pediatric emergency medicine (PEM) physicians. We sought to evaluate the effect of an online module on PEM physicians' knowledge and confidence in managing newborn deliveries and neonatal resuscitation. METHODS: A team of experts in PEM, obstetrics, neonatology, and medical education developed a self-directed, 1-hour online module on managing newborn deliveries with neonatal resuscitation. The module was designed to address the learning needs of the targeted group. The module was piloted before dissemination to PEM faculty. A 10-question multiple choice test was given to assess knowledge of the material covered. A 10-point Likert scale questions survey was used to evaluate confidence. Measures were administered before initiation, after module completion, and 6 months after completion. Paired t tests were used to compare mean knowledge scores, and rank sum tests were used to compare median confidence levels. RESULTS: Most (n = 47, 89%) of the PEM faculty members completed the module. The majority (n = 43, 91%) thought the information was relevant to their practice. After completing the module, physicians' overall knowledge scores improved by 18% (mean [SD]: 74% [14.7] vs 92% [8.0], P < 0.01). Self-assessed confidence improved after the module in terms of managing uncomplicated vaginal deliveries (median 5 vs 7, P < 0.01), care of patients with complicated vaginal deliveries (2 vs 5, P < 0.01), and managing neonatal resuscitation (7 vs 8, P < 0.01). During the 6-month follow-up, there was sustained improvement in physicians' overall knowledge score (82% [16.9], P = 0.007) and self-assessed confidence in managing complicated vaginal deliveries (median 2 vs 4, P = 0.0012); however, other measures were not statistically significant. CONCLUSIONS: An online module is an appropriate method for training PEM providers about rarely used but essential skills such as managing vaginal deliveries and neonatal resuscitation.