Current Landscape of Children's Surgery in Africa: A Multicenter Analysis of 16,000 Cases.

Background: Although prior studies have estimated the burden of pediatric surgical disease in low- and middle-income countries (LMICs) through statistical modeling and hospital- or household-based surveys, few large-scale descriptions of procedures and outcomes have been published. We aimed to describe the epidemiology and outcomes of children's surgical care at multiple centers across Africa.

Methods: Perioperative clinical data were collected prospectively from 2018 to 2023 at 17 hospitals in 11 African countries using a preexisting tool.

Spirituality and Surgical Education: Beliefs and Practices Among General Surgery Program Directors.

Objective: Characterize the perception of religious beliefs and spirituality among program directors in general surgery training.

Design: Anonymous, voluntary, self-administered 33-question web-based survey examining general surgery program director demographics and perceptions of religious beliefs and spirituality in general surgery residency training.

Participants: All US general surgery program directors were invited to participate through direct email or through email to their program administrators.

Overcoming Political Upheaval to Deliver Pediatric Surgical Care in Afghanistan: Prospective Analysis of the First 1,000 Procedures.

Background: Pediatric surgical care is limited in Afghanistan. Few details are known about the state of pediatric surgery in Afghanistan. We explore the impact of a newly installed pediatric operating room by a children's charity on the provision of pediatric surgery in Afghanistan.

When the first try fails: re-implementation of SIMPL in a general surgery residency.

Background: Workplace-based assessment (WBA) can facilitate evaluation of operative performance; however, implementation of WBA is sometimes unsuccessful. The American Board of Surgery Entrustable Professional Activities WBA project was launched in July 2023. Some programs will face the challenge of re-implementation of a WBA following previous failures.

Epitranscriptomic reader YTHDF2 regulates SEK1()-JNK-cJUN inflammatory signaling in astrocytes during neurotoxic stress.

As the most abundant glial cells in the central nervous system (CNS), astrocytes dynamically respond to neurotoxic stress, however, the key molecular regulators controlling the inflammatory status of these sentinels during neurotoxic stress are many and complex. Herein, we demonstrate that the m6A epitranscriptomic mRNA modification tightly regulates the pro-inflammatory functions of astrocytes. Specifically, the astrocytic neurotoxic stressor, manganese (Mn), downregulated the m6A reader YTHDF2 in human and mouse astrocyte cultures and in the mouse brain.

Implementation science in humanitarian assistance: applying a novel approach for humanitarian care optimization.

Humanitarian assistance is hindered by a lack of strategies to optimize care delivery through research and organized networks. Distinct from global health, humanitarian assistance struggles to address its multifaceted challenges, including duplicative resources, uncoordinated communication, unregulated staff expertise and safety, financial waste, and poor-quality metrics and care delivery. Implementation science provides an exciting and underutilized approach that can be applied to address these challenges, by studying how to effectively design, implement, optimize, and scale evidence-based interventions.

Epitranscriptomic Reader YTHDF2 Regulates SEK1( )-JNK-cJUN Inflammatory Signaling in Astrocytes during Neurotoxic Stress.

As the most abundant glial cells in the CNS, astrocytes dynamically respond to neurotoxic stress, however, the key molecular regulators controlling the inflammatory status of these sentinels during neurotoxic stress have remained elusive. Herein, we demonstrate that the m6A epitranscriptomic mRNA modification tightly regulates the pro-inflammatory functions of astrocytes. Specifically, the astrocytic neurotoxic stresser, manganese (Mn), downregulated the m6A reader YTHDF2 in human and mouse astrocyte cultures and in the mouse brain.

Understanding pediatric surgical needs in North Korea: a modeling analysis.

Background: Sixty-five percent of children worldwide lack access to surgical care, the majority of whom live in low-income and middle-income countries (LMICs). Developing surgical infrastructure requires information on surgical need; however, this information is often limited in LMICs. North Korea (Democratic People's Republic of Korea, DPRK) has a low amount of publicly available data.

Evidence for a case-based module in the low-resource setting to teach ectopic pregnancy management.

Introduction: Case-based learning (CBL) utilizes authentic clinical cases that connect theory to practice. CBL has been shown to result in deeper learning and high engagement of adult learners. An open-source, web-based CBL module was created to help learners develop the cognitive foundation of ectopic pregnancy management in the low-resource setting.

Out-of-pocket costs and catastrophic healthcare expenditure for families of children requiring surgery in sub-Saharan Africa.

Background: Out-of-pocket healthcare costs leading to catastrophic healthcare expenditure pose a financial threat for families of children undergoing surgery in Sub-Saharan African countries, where universal healthcare coverage is often insufficient.

Methods: A prospective clinical and socioeconomic data collection tool was used in African hospitals with dedicated pediatric operating rooms installed philanthropically. Clinical data were collected via chart review and socioeconomic data from families.

Surgeon behaviors related to engaging patients in smoking cessation at the time of elective surgery.

Background: Despite the abundance of evidence supporting smoking cessation before elective surgery, there is wide variation in surgeon adherence to these best practices.

Methods: This qualitative study used convenience sampling to recruit General Surgery trained surgeons. Surgeons participated in semi-structured interviews based on domains from the Theoretical Domains Framework (TDF).

Bile leak incidence, risk factors and associated outcomes in patients undergoing hepatectomy: a contemporary NSQIP propensity matched analysis.

Background: Despite advances in surgical technique, bile leak remains a common complication following hepatectomy. We sought to identify incidence of, risk factors for, and outcomes associated with biliary leak.

Study Design: This is an ACS-NSQIP study.

Utility of Perioperative Measurement of Cell-Free DNA and Circulating Tumor DNA in Informing the Prognosis of GI Cancers: A Systematic Review.

Purpose: Current surveillance imaging and tumor markers lack sensitivity for the early detection of recurrence in GI cancers. This study critically evaluates the current literature on the role of sequential measurement of circulating tumor DNA (ctDNA) before and after curative resection in informing recurrence.

Methods: A systematic search using a predefined, registered protocol was conducted for studies published between January 2010 and May 2020.

Robotic Distal Pancreatectomy and Splenectomy for an Intrapancreatic Hepatocellular Carcinoma: A Case Report and Review of the Literature.

Liver parenchyma that resides outside of the normal hepatic confines is defined as accessory liver if in communication with the native biliary tree, or ectopic liver (EL) if it is not. EL can develop in a variety of tissues, including but not limited to the gallbladder, the hepatic ligaments, the pancreas, and retroperitoneum. EL has an increased propensity for malignant degeneration resulting in hepatocellular carcinoma (HCC).

Novel response to neoadjuvant anti-PD1 therapy for a patient with retrocaval melanotic schwannoma.

Melanotic schwannoma is a rare nerve sheath tumor composed of melanin-producing Schwann cells with the potential for metastasis. These tumors can be associated with familial tumor syndromes and can cause significant symptoms related to nerve compression and mass effect. Due to the rarity of these lesions, they can be initially misidentified as melanocytomas, pigmented dermatofibrosarcoma protuberans, neurofibromas or malignant melanomas.

N-Adenosine Methylation of Socs1 mRNA Is Required to Sustain the Negative Feedback Control of Macrophage Activation.

Bacterial infection triggers a cytokine storm that needs to be resolved to maintain the host's wellbeing. Here, we report that ablation of mA methyltransferase subunit METTL14 in myeloid cells exacerbates macrophage responses to acute bacterial infection in mice, leading to high mortality due to sustained production of pro-inflammatory cytokines. METTL14 depletion blunts Socs1 mA methylation and reduces YTHDF1 binding to the mA sites, which diminishes SOCS1 induction leading to the overactivation of TLR4/NF-κB signaling.

Functional role of Tet-mediated RNA hydroxymethylcytosine in mouse ES cells and during differentiation.

Tet-enzyme-mediated 5-hydroxymethylation of cytosines in DNA plays a crucial role in mouse embryonic stem cells (ESCs). In RNA also, 5-hydroxymethylcytosine (5hmC) has recently been evidenced, but its physiological roles are still largely unknown. Here we show the contribution and function of this mark in mouse ESCs and differentiating embryoid bodies.

Control of Early B Cell Development by the RNA N-Methyladenosine Methylation.

The RNA N-methyladenosine (mA) methylation is installed by the METTL3-METTL14 methyltransferase complex. This modification has critical regulatory roles in various biological processes. Here, we report that deletion of Mettl14 dramatically reduces mRNA mA methylation in developing B cells and severely blocks B cell development in mice.

Molecular biology of oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a heterogeneous and complex disease that arises due to dysfunction of multiple molecular signaling pathways. Recent advances in high-throughput genetic sequencing technologies coupled with innovative analytical techniques have begun to characterize the molecular determinants driving OCSCC. An understanding of the key molecular signaling networks underlying the initiation and progression of is essential for informing treatment of the disease.

The RNA-binding protein FMRP facilitates the nuclear export of -methyladenosine-containing mRNAs.

-Methyladenosine (mA) is the most abundant post-transcriptional mRNA modification in eukaryotes and exerts many of its effects on gene expression through reader proteins that bind specifically to mA-containing transcripts. Fragile X mental retardation protein (FMRP), an RNA-binding protein, has previously been shown to affect the translation of target mRNAs and trafficking of mRNA granules. Loss of function of FMRP causes fragile X syndrome, the most common form of inherited intellectual disability in humans.

High-Resolution Mapping of N -Methyladenosine Using mA Crosslinking Immunoprecipitation Sequencing (mA-CLIP-Seq).

N -Methyladenosine, an abundant chemical modification in mRNA, plays crucial roles in regulating gene expression and biological processes. Research on mA and its functions has progressed rapidly in the past few years, aided substantially by advances in high-throughput sequencing-based methods to profile mA along the transcriptome. We present here a protocol for mA crosslinking immunoprecipitation sequencing (mA-CLIP-seq), which profiles mA on mRNA at high resolution from as little as 1 μg of poly(A)-selected mRNA.

Single base resolution mapping of 2'-O-methylation sites in human mRNA and in 3' terminal ends of small RNAs.

The post-transcriptional modification 2'-O-Methyl (2'OMe) could be present on the ribose of all four ribonucleosides, and is highly prevalent in a wide variety of RNA species, including the 5' RNA cap of viruses and higher eukaryotes, as well as internally in transfer RNA and ribosomal RNA. Recent studies have suggested that 2'OMe is also located internally in low-abundance RNA species such as viral RNA and mRNA. To profile 2'OMe on different RNA species, we have developed Nm-seq, which could identify 2'OMe sites at single base resolution.

Dynamic transcriptomic mA decoration: writers, erasers, readers and functions in RNA metabolism.

N-methyladenosine (mA) is a chemical modification present in multiple RNA species, being most abundant in mRNAs. Studies on enzymes or factors that catalyze, recognize, and remove mA have revealed its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. This review describes the current understanding of the mA modification, particularly the functions of its writers, erasers, readers in RNA metabolism, with an emphasis on its role in regulating the isoform dosage of mRNAs.

Identifying the mA Methylome by Affinity Purification and Sequencing.

N -methyladenosine (mA) is the most abundant internal modification in eukaryotic mRNA, and is newly emerging as a key posttranscriptional mRNA regulator. Recent research has uncovered insight into the location and function of mA sites on a large scale, in part due to the transcriptome-wide identification of mA sites by high-throughput sequencing (mA-seq). Here, we present a protocol for mA-seq, which maps the mA methylome by affinity purification and sequencing.

Making Changes: N-Methyladenosine-Mediated Decay Drives the Endothelial-to-Hematopoietic Transition.

Zhang et al. (2017) report critical functions of mA during the endothelial-to-haematopoietic transition in zebrafish embryogenesis. mA affects Notch signaling, likely though mA-dependent and YTHDF2-mediated mRNA decay.