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Supplementary Data

ARACNe-AP transcriptional network from gene expression profiles

High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator proteins that were conserved across independent cohorts. A 10-protein transcriptional module—centered around a TEAD4–MYCN positive feedback loop—emerged as the regulatory driver of the high-risk subtype associated with MYCN amplification. Silencing of either gene collapsed MYCN-amplified (MYCNAmp) neuroblastoma transcriptional hallmarks and abrogated viability in vitro and in vivo. Consistently, TEAD4 emerged as a robust prognostic marker of poor survival, with activity independent of the canonical Hippo pathway transcriptional coactivators YAP and TAZ. These results suggest novel therapeutic strategies for the large subset of MYCN-deregulated neuroblastomas.Significance: Despite progress in understanding of neuroblastoma genetics, little progress has been made toward personalized treatment. Here, we present a framework to determine the downstream effectors of the genetic alterations sustaining neuroblastoma subtypes, which can be easily extended to other tumor types. We show the critical effect of disrupting a 10-protein module centered around a YAP/TAZ-independent TEAD4–MYCN positive feedback loop in MYCNAmp neuroblastomas, nominating TEAD4 as a novel candidate for therapeutic intervention. Cancer Discov; 8(5); 582–99. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 517

Supplementary Experimental Procedures; Supplementary Figures S1-S10; Supplementary Table Legends S1-S9; Supplementary Tables S8-S9; Additional References

Background Morphoea can have a significant disease burden. Aetiopathogenesis remains poorly understood, with very limited existing genetic studies. Linear morphoea (LM) may follow Blascho’s lines of epidermal development, providing potential pathogenic clues. Objective The first objective of this study was to identify the presence of primary somatic epidermal mosaicism in LM. The second objective was tTo explore differential gene expression in morphoea epidermis and dermis to identify potential pathogenic molecular pathways and tissue layer cross-talk. Methodology Skin biopsies from paired affected and contralateral unaffected skin were taken from 16 patients with LM. Epidermis and dermis were isolated using a 2-step chemical-physical separation protocol. Whole Genome Sequencing (WGS; n = 4 epidermal) and RNA-seq (n = 5-epidermal, n = 5-dermal) with gene expression analysis via GSEA-MSigDBv6.3 and PANTHER-v14.1 pathway analyses, were performed. RTqPCR and immunohistochemistry were used to replicate key results. Results Sixteen participants (93.8% female, mean age 27.7 yrs disease-onset) were included. Epidermal WGS identified no single affected gene or SNV. However, many potential disease-relevant pathogenic variants were present, including ADAMTSL1 and ADAMTS16. A highly proliferative, inflammatory and profibrotic epidermis was seen, with significantly-overexpressed TNFα-via-NFkB, TGFβ, IL6/JAKSTAT and IFN-signaling, apoptosis, p53 and KRAS-responses. Upregulated IFI27 and downregulated LAMA4 potentially represent initiating epidermal ‘damage’ signals and enhanced epidermal-dermal communication. Morphoea dermis exhibited significant profibrotic, B-cell and IFN-signatures, and upregulated morphogenic patterning pathways such as Wnt. Conclusion This study supports the absence of somatic epidermal mosaicism in LM, and identifies potential disease-driving epidermal mechanisms, epidermal-dermal interactions and disease-specific dermal differential-gene-expression in morphoea. We propose a potential molecular narrative for morphoea aetiopathogenesis which could help guide future targeted studies and therapies.

Ecological restoration is critical for climate and biodiversity resilience over the coming century. Today, there is strong evidence that wildlife can significantly influence the distribution and stoichiometry of elements across landscapes, with subsequent impacts on the composition and functioning of ecosystems. Consequently, any anthropogenic activity that modifies this important aspect of zoogeochemistry, such as changes to animal community composition, diet, or movement patterns, may support or hinder restoration goals. It is therefore imperative that the zoogeochemical effects of such anthropogenic modifications are quantified and mapped at high spatiotemporal resolutions to help inform restoration strategies. Here, we first discuss pathways through which human activities shape wildlife-mediated elemental landscapes and outline why current frameworks are inadequate to characterize these processes. We then suggest improvements required to comprehensively model, validate, and monitor element recycling and redistribution by wildlife under differing wildlife management scenarios and discuss how this might be implemented in practice through a specific example in the southern Kalahari Desert. With robust ecological forecasting, zoogeochemical impacts of wildlife can thus be used to support ecological restoration and nature-based solutions to climate change. If ignored in the restoration process, the effects of wildlife on elemental landscapes may delay, or even prevent, restoration success.

The authors examined whether there were positive spillovers in opioid use disorder medication prescribing to Medicare Part D beneficiaries in Medicaid expansion states. Although prior studies have shown several positive benefits of Medicaid expansion for Americans with opioid use disorder, research has not examined potential spillovers to Medicare beneficiaries who have been hit hard by the opioid crisis.Prescribing data were taken from the Medicare Part D Prescription Public Use File (2010-2017). A difference-in-differences linear regression framework was used to identify spillovers in prescribing of buprenorphine and injectable naltrexone to Medicare Part D beneficiaries in Medicaid expansion states. Three sets of dependent variables measured medication prescribing at the county-year level (N=24,850). All models included county and year fixed effects, with standard errors clustered at the state level to address within-state serial correlation.Medicaid expansion was associated with an increase in the probability of a county having an injectable naltrexone provider (p0.01). After expansion, the number of buprenorphine providers in expansion states increased by 5.6% (p0.05), and the number of injectable naltrexone providers increased by 3.3% (p0.01), relative to nonexpansion states. Expansion was associated with a 23.1% (p0.01) increase in the number of daily doses of injectable naltrexone, relative to nonexpansion states.Medicaid expansion states may be better equipped to address the opioid crisis because of direct benefits to Medicaid beneficiaries and availability of opioid use disorder medications for Medicare Part D beneficiaries. However, additional efforts are likely needed to close the opioid use disorder treatment gap for Medicare beneficiaries.

Designing clinical trials on hemorrhage control requires carefully balancing the need for high enrollment numbers with the need of focusing on the sickest patients. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial enrolled patients within 2 hours of arrival to the emergency department for a trial of injured patients at risk for massive transfusion. We conducted a secondary analysis to determine how time-to-randomization affected patient outcomes and the balance between enrollment and mortality.Patients from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were compared based on 30-minute time to randomization intervals. Outcomes included 24-hour and 30-day mortality, time to hemostasis, adverse events, and operative procedures. Additional analyses were conducted based on treatment arm allocation, mechanism of injury, and variation in start time (arrival vs. randomization).Randomization within 30 minutes of arrival was associated with higher injury severity (median Injury Severity Score, 29 vs. 26 overall; p0.01), lower systolic blood pressure (median, 91 vs. 102 mm Hg overall; p0.01), and increased penetrating mechanism (50% vs. 47% overall; p0.01). Faster time-to-randomization was associated with increased 24-hour (20% for 0- to 30 minute entry, 9% for 31-minute to 60-minute entry, 10% for 61-minute to 90-minute entry, 0% for 91-minute to 120-minute entry; p0.01) and 30-day mortality (p0.01). There were no significant associations between time-to-randomization and adverse event occurrence, operative interventions, or time to hemostasis.Increasing time to randomization in this large multicenter randomized trial was associated with increased survival. Fastest randomization (within 0-30 minutes) was associated with highest 24-hour and 30-day mortality, but only 57% of patients were enrolled within this timeframe. Only 3% of patients were enrolled within the last 30-minute window (91-120 minutes), with none of them dying within the first 24 hours. For a more optimal balance between enrollment and mortality, investigators should consider shortening the time to randomization when planning future clinical trials of hemorrhage control interventions.Prognostic and Epidemiologic; Level II.

The timing of stroke onset among patients with blunt cerebrovascular injury (BCVI) is not well understood. All blunt trauma patients at our institution undergo a screening computed tomographic angiography (CTA) of the neck. Most patients with CTA evidence of BCVI are treated with aspirin, and all patients with clinical evidence of stroke are treated with aspirin and undergo magnetic resonance imaging (MRI) of the brain. We conducted a retrospective review to determine the incidence of stroke upon admission and following admission.All neck CTAs and head MRIs obtained in blunt trauma patients were reviewed from August 2017 to August 2019. All CTAs that were interpreted as showing BCVI were individually reviewed to confirm the diagnosis of BCVI. Stroke was defined as brain MRI evidence of new ischemic lesions, and each MRI was reviewed to identify the brain territory affected. We extracted the time to aspirin administration and the timing of stroke onset from patients' electronic health records.Of the 6,849 blunt trauma patients, 479 (7.0%) had BCVIs. Twenty-four patients (5.0%) with BCVI had a stroke on admission. Twelve (2.6%) of the remaining 455 patients subsequently had a stroke during their hospitalization. The incidence of stroke among patients with BCVI was 7.5%; 2.6% were potentially preventable. Only 5 of the 12 patients received aspirin before the onset of stroke symptoms. All 36 patients with BCVI and stroke had thromboembolic lesions in the territory supplied by an injured vessel.With universal screening, CTA evidence of BCVI is common among blunt trauma patients. Although acute stroke is also relatively common in this population, two thirds of strokes are already evident on admission. One third of BCVI-related strokes occur after admission and often relatively early, necessitating rapid commencement of preventative treatment. Further studies are required to demonstrate the value of antithrombotic administration in preventing stroke in BCVI patients.Prognostic and Epidemiologic; Level IV.

The influence of carbon concentration variations on pearlite formation (20 h at 600 °C) in a case-carburized steel is investigated. The resultant microstructure shows three distinct regions: carburized case, a transition region, and the original core. The microstructural transition from the case to the core regions is observed to be relatively sharp. The investigated region of the carburized case (0.9 wt.% C) contains two types of pearlite: ferrite + cementite and ferrite + M23C6, where the pearlitic aggregate with M23C6 shows faster formation kinetics. The kinetics of pearlite formation in the transition region (0.3 wt.% C) is very slow and is observed with only M23C6 carbide. Only around 40% austenite decomposes into pearlite in the transition region, which, in comparison to the carburized case region of 0.9 wt.% C is a fraction that is lower by a factor of two. Pearlite is absent in the investigated core region (0.16 wt.% C). The microstructure in this region is predominantly martensite and pro-eutectoid ferrite, with a fraction of ferrite well below the equilibrium fraction. Ferrite formation in this region is limited by the redistribution of mainly Ni, Mn, and Cr, and their resulting solute drag effect on the austenite/ferrite interface. A thermodynamic and kinetic argumentation of these observations is provided with the help of thermodynamic data, precipitation simulations, and a general mixed-mode Gibbs energy balance model.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC. We simultaneously constructed an accompanying online database of BGCs, which has since been widely used by the community as a reference dataset for BGCs and was expanded to 2021 entries in 2019 (MIBiG 2.0). Here, we describe MIBiG 3.0, a database update comprising large-scale validation and re-annotation of existing entries and 661 new entries. Particular attention was paid to the annotation of compound structures and biological activities, as well as protein domain selectivities. Together, these new features keep the database up-to-date, and will provide new opportunities for the scientific community to use its freely available data, e.g. for the training of new machine learning models to predict sequence-structure-function relationships for diverse natural products. MIBiG 3.0 is accessible online at https://mibig.secondarymetabolites.org/.

The computational study of structures with chemical relevance is preceded by its modeling in such manner that no calculations can be submitted without the knowledge of their spatial atomic arrangement. In this regard, the use of an object-oriented language can be helpful both to generate the Cartesian coordinates (.xyz file format) and to obtain a ray-traced image. The modeling of chemical structures based on programming has some advantages with respect to other known strategies. The more important advantage is the generation of Cartesian coordinates that can be visualized easily by using free of charge software. Our approach facilitates the spatial vision of complex structures and make tangible the chemistry concepts delivered in the classroom. In this article an undergraduate project is described in which students generate the Cartesian coordinates of 13 Archimedean solids based on a geometrical/programming approach. Students were guided along the project and meetings were held to integrate their ideas in a few lines of programmed codes. They improved their decision-making process and their organization and collecting information capabilities, as much as their reasoning and spatial depth. The final products of this project are the coded algorithms and those made tangible the grade of learning/understanding derived of this activity.

This study aimed to determine the phenolic compounds profile, antioxidant potential and cytotoxicity of extracts and fractions of Caesalpinia palmeri. Methanolic extracts were generated from C. palmeri berries, stems and flowers. The latter was subjected to liquid-liquid partition, obtaining hexane, ethyl acetate and residues fractions. Results showed that the flower extract and ethyl acetate fraction had a larger concentration of phenolic compounds (148.9 and 307.9 mg GAE/g, respectively), being ellagic acid (6233.57 and 19550.08 μg/g, respectively), quercetin-3-β-glycoside (3023.85 and 8952.55 μg/g, respectively) and gallic acid (2212.98 and 8422.34 μg/g, respectively) the most abundant compounds. Flower extract and ethyl acetate fraction also presented the highest antioxidant capacity on all tested methods (DPPH, ABTS, ORAC and FRAP) and low cytotoxicity against ARPE-19 cells (IC

OBJECTIVE Although numerous studies have examined the geographic availability of medications for opioid use disorder, none have measured the availability of medications for alcohol use disorder (MAUD) in the United States. We examined county-level trends in MAUD offerings in the specialty substance use disorder treatment system and compared MAUD availability with local geographic characteristics and alcohol use disorder treatment need. METHOD We constructed annual county-level measures of MAUD availability for 2016-2019 using the National Directory of Drug and Alcohol Abuse Treatment Facilities, determining the number of outpatient facilities offering MAUD in each county (n = 12,568). Two-part, multivariable regression models estimated the association between MAUD availability and temporal trends, census region, urbanicity, and prevalence of excessive drinking. RESULTS Availability of MAUD increased significantly over the study period. By 2019, 38% of U.S. facilities offered at least one MAUD, 40% of counties had at least one specialty treatment facility offering MAUD, and counties with at least one facility had an average of 3.36 MAUD facilities. Availability was significantly higher in urban counties and in the Northeast (both p < .01), but not in counties with higher prevalence of excessive drinking. CONCLUSIONS We observed large increases in the availability of MAUD in the U.S. specialty treatment system from 2016 to 2019. Although these results are encouraging, a majority (60%) of U.S. counties did not have a specialty outpatient treatment facility that offered MAUD in 2019. Additional efforts are needed to improve availability of MAUD, especially in rural counties and in the southern and midwestern United States.

Traumatic injuries remain one of the leading causes of death in the United States. Patients who survive traumatic injuries but return to the emergency department with repeat injuries are said to suffer from injury recidivism. Numerous studies have described trends in injury recidivism using trauma registry and survey data. To our knowledge, no prior study has leveraged electronic medical record (EMR) data to characterize injury recidivism. The EMR is potentially more comprehensive as it contains details of patients who visited the emergency department after injury but did not meet the criteria for inclusion in the trauma registry. Such injuries could be predictive of future recidivism. We therefore aimed to describe patterns of injury recidivism seen at a Level 1 trauma center using the EMR.A retrospective review was conducted of all injury-related encounters between January 2016 and December 2019. Manual review was conducted of all recidivistic encounters with11 months between encounters to ensure the recidivistic encounter was not a sequela of the index visit. A general estimating equation logistic regression adjusted for age, race, sex, and insurance payor, estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between injury mechanism and odds of recidivistic encounter.A total of 20,566 index encounters was included during the study period. Of the 20,566 encounters, 7.6% (n = 1570) had a recidivistic encounter during the study period, half of which (n = 781) occurred within the first year of the index encounter. An over two-fold increased odds of recidivism was observed for blunt assault encounters (OR 2.53, 95% CI 2.03-3.15) and unintentional falls (OR 2.10, 95% CI 1.76-2.52). For both mechanisms, this increase was observed across the three years following the index encounter.Our study found that patients with assault injuries have the highest odds of injury recidivism and assault-related recidivistic encounters. These results demonstrate the feasibility and utility of incorporating EMR data, and suggest that the development of targeted interventions focused on mitigating assault injuries, such as hospital-based violence intervention programs, should be considered in our region.

Objective: Laryngomalacia (LM) is the most common congenital anomaly of the larynx. The cause of LM is still largely unknown, but a neurological mechanism has gained the most acceptance. There have not been any studies examining the prevalence of LM in infants with Neonatal Abstinence Syndrome (NAS). The aim of our study is to determine if infants with NAS are more likely to be diagnosed with LM. Methods: This study was a population-based inpatient registry analysis. We examined nationwide neonatal discharges in 2016 using the Kids’ Inpatient Database (KID). Only patients listed as neonates were included. The International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) codes for neonatal withdrawal symptoms from maternal use of drugs of addiction (P96.1) and diagnoses denoting LM were used. To quantify associations between the LM and NAS groups, prevalence rates and odds ratios (ORs) were used. Results: There were 3 970 065 weighted neonatal discharges in the 2016 KID. Among patients included in our dataset, 0.809% (32 128) had NAS and 0.075% (2974) had LM. There was an increased odds ratio for neonates with NAS and LM (OR of 2.85, 95% CI = 2.24-3.63) compared to infants without NAS. Multiple logistic regression accounting for possible confounders produced an adjusted OR of 1.68 (95% CI = 1.29-2.19). Conclusion: Our study found an association between NAS and LM. This suggests that prenatal exposure to opioids or possibly the sequelae of withdrawal symptoms may be risk factors for the development of LM.

Curcumin (CUR) is a phenolic compound that is safe for human consumption. It exhibits chemopreventive, antiproliferative, antiangiogenic, and antimetastatic effects. However, these benefits can be hampered due to the lipophilic nature, rapid metabolism, low bioavailability, and fast elimination of the molecule. Considering this, the present work reviews the use of CUR-based nanosystems as anticancer agents, including conventional nanosystems (i.e., liposomes, nanoemulsions, nanocrystals, nanosuspensions, polymeric nanoparticles) and nanosystems that respond to external stimuli (i.e., magnetic nanoparticles and photodynamic therapy). Previous studies showed that the effects of CUR were improved when loaded into nanosystems as compared to the free compound, as well as synergist effects when it is co-administrated alongside with other molecules. In order to maximize the beneficial health effects of CUR, critical factors need to be strictly controlled, such as particle size, morphology, and interaction between the encapsulating material and CUR. In addition, there is an area of study to be explored in the development of CUR-based smart materials for nanomedical applications. Imaging-guided drug delivery of CUR-based nanosystems may also directly target specific cells, thereby increasing the therapeutic and chemopreventive efficacy of this versatile compound.

In nutrient-poor wildlife reserves it has become common-place to provide supplemental mineral resources for wildlife. Yet, the impacts of anthropogenic mineral supplementation on community-wide wildlife nutrition, behaviour and subsequent impact on ecosystem processes remain poorly understood. Here, we examine the contribution of anthropogenic mineral lick provision to wildlife nutrient intake across a community of large mammals (>10kg) in the southern Kalahari Desert. Based on predicted daily nutrient requirements and a faecal nutrient assessment, large herbivores appear deficient in phosphorus (P), sodium (Na) and zinc (Zn). For these nutrients, anthropogenic salt and mineral licks constitute an important (>10%) source of nutrient intake helping to reduce or overcome requirement deficits. Larger-bodied species disproportionately consumed licks (p

Anaplastic large cell lymphoma (ALCL) is an aggressive, CD30+ T-cell lymphoma of children and adults. ALK fusion transcripts or mutations in the JAK-STAT pathway are observed in most ALCL tumors, but the mechanisms underlying tumorigenesis are not fully understood. Here we show that dysregulated STAT3, together with a core transcriptional regulatory circuit consisting of BATF3–IRF4– IKZF1, co-occupies gene enhancers to establish an oncogenic transcription program and maintain the malignant state of ALCL. Critical downstream targets of this network in ALCL cells include the proto-oncogene MYC, which requires active STAT3 to facilitate high levels of MYC transcription. The activity of this auto-regulatory transcription loop is reinforced by MYC binding to the enhancer regions associated with STAT3 and each of the core regulatory transcription factors. These findings provide new insights for understanding how dysregulated signaling pathways hijack cell-type-specific transcriptional machinery to drive tumorigenesis and create therapeutic vulnerabilities in genetically defined tumors.

Avocado cv. ‘Hass’ paste is the main byproduct derived from industrial avocado processing, and contains various bioactive compounds (BCs). Consumption of these compounds from different sources has been associated with positive health effects, although studies of avocado byproducts remain minimal. Avocado paste was analyzed, regarding its physicochemical properties, proximate composition, main BCs, antioxidant capacity, in vitro digestion and in silico interactions of its three main phenolics with cholesterol. Avocado paste contained 14.2% of lipids and 13.8% of protein. Total phenolic compounds were 2.1 mg GAE/g dw, with a phenolic profile that contained phenolic acids (ferulic, protocatechuic and p-coumaric acids) as its main compounds. Carotenoids (mainly β-carotene), tocopherols (mainly α-tocopherol), fatty acids (mainly oleic acid) and other BCs were also identified and quantified. Release of its phenolic compounds and antioxidant capacity were highest in the gastric phase of an in vitro digestion. In silico analyses showed that ferulic acid had the strongest interaction with cholesterol, suggesting a possible mechanism to inhibit its intestinal absorption. According to its composition and characteristics, it is possible to suggest avocado paste may be used as an unconventional source of BCs, with possible effects on cholesterol digestion.

Whale sharks are known to feed primarily on zooplankton all over the world; however, recent findings suggest that they also prey on fish using behaviors that have not been fully described. Here, we provide detailed evidence of whale sharks interacting with schools of anchovy on four occasions in Bahia de Los Angeles, Baja California, Mexico. Three of these were predatory interactions in multi-species feeding frenzies, and one was a non-predatory interaction. In predatory interactions, whale sharks exhibited two types of feeding behaviors: (1) stationary suction-feeding, a previously described behavior for whale sharks, and (2) lunge-feeding, which has not been previously described in whale sharks, but has been observed among other large filter feeders, such as rorqual whales. The whale sharks moved simultaneously around the school of anchovy, lunging simultaneously or one after another into the school, with 66% (N = 17) of these lunges occurring in the same direction. In the non-predatory interaction, whale sharks exhibited “sit-and-wait" behavior. The evidence presented here, along with previous observations, suggests that whale sharks may change their feeding strategy from suction to lunge-feeding when other predators corner schooling fish.

Background The superior parietal lobule (SPL) is involved in somatosensory and visuospatial integration with additional roles in attention, written language, and working memory. A detailed understanding of the exact location and nature of associated white matter tracts could improve surgical decisions and subsequent postoperative morbidity related to surgery in and around this gyrus. Objective To characterize the fiber tracts of the SPL based on relationships to other well-known neuroanatomic structures through diffusion spectrum imaging (DSI)-based fiber tracking validated by gross anatomical dissection as ground truth. Methods Neuroimaging data of 10 healthy, adult control subjects was obtained from a publicly accessible database published in Human Connectome Project for subsequent tractographic analyses. White matter tracts were mapped between both cerebral hemispheres, and a lateralization index was calculated based on resultant tract volumes. Post-mortem dissections of 10 cadavers identified the location of major tracts and validated our tractography results based on qualitative visual agreement. Results We identified 9 major connections of the SPL: U-fiber, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, middle longitudinal fasciculus, extreme capsule, vertical occipital fasciculus, cingulum, and corpus callosum. There was no significant fiber lateralization detected. Conclusion The SPL is an important region implicated in a variety of tasks involving visuomotor and visuospatial integration. Improved understanding of the fiber bundle anatomy elucidated in this study can provide invaluable information for surgical treatment decisions related to this region.

Background The middle frontal gyrus (MFG) is involved in attention, working memory, and language-related processing. A detailed understanding of the subcortical white matter tracts connected within the MFG can facilitate improved navigation of white matter lesions in and around this gyrus and explain the postoperative morbidity after surgery. We aimed to characterize the fiber tracts within the MFG according to their connection to neuroanatomic structures through the use of diffusion spectrum imaging-based fiber tractography and validate the findings by gross anatomic dissection for qualitative visual agreement. Methods Tractography analysis was completed using diffusion imaging data from 10 healthy, adult subjects enrolled in the Human Connectome Project. We assessed the MFG as a whole component according to its fiber connectivity with other neural regions. Mapping was completed on all tracts within both hemispheres, with the resultant tract volumes used to calculate a lateralization index. A modified Klingler technique was used on 10 postmortem dissections to demonstrate the location and orientation of the major tracts. Results Two major connections of the MFG were identified: the superior longitudinal fasciculus, which connects the MFG to parts of the inferior parietal lobule, posterior temporal lobe, and lateral occipital cortex; and the inferior fronto-occipital fasciculus, which connected the MFG to the lingual gyrus and cuneus. Intra- and intergyral short association, U-shaped fibers were also identified. Conclusions Subcortical white matter pathways integrated within the MFG include the superior longitudinal fasciculus and inferior fronto-occipital fasciculus. The MFG is implicated in a variety of tasks involving attention and memory, making it an important cortical region. The postoperative neurologic outcomes related to surgery in and around the MFG could be clarified in the context of the anatomy of the fiber bundles highlighted in the present study.