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The lymphatic system plays an integral role in the development and progression of a range of disease conditions, which has impelled medical researchers and clinicians to design, develop and utilize advanced lymphatic drug delivery systems. Following interstitial administration, most therapeutics and molecules are cleared from tissues via the draining blood capillaries. Macromolecules and delivery systems >20 kDa in size or 10–100 nm in diameter are, however, transported from the interstitium via draining lymphatic vessels as they are too large to cross the blood capillary endothelium. Lymphatic uptake of small molecules can be promoted by two general approaches: administration in association with synthetic macromolecular constructs, or through hitchhiking on endogenous cells or macromolecular carriers that are transported from tissues via the lymphatics. In this paper we review the latter approach where molecules are targeted to lymph by hitchhiking on endogenous albumin transport pathways after subcutaneous, intramuscular or intradermal injection. We describe the properties of the lymphatic system and albumin that are relevant to lymphatic targeting, the characteristics of drugs and delivery systems designed to hitchhike on albumin trafficking pathways and how to further optimise these properties, and finally the current applications and potential future directions for albumin-hitchhiking approaches to target the lymphatics.

Background Late-onset Tay-Sachs disease (LOTS) is an autosomal-recessive lysosomal storage disease caused by deficient β-hexosaminidase A activity. LOTS is rare in the Ashkenazi Jews, but even rarer in the non-Jewish population. Cases We report an Irish family expanding the LOTS phenotype (ataxia, diffuse muscle wasting, dystonia, chorea, belly dancer's dyskinesia, and neuropsychiatric features) associated with the known HEXA variant 1073 + 1G > A and a novel variant c.459 + 24G > C. Conclusions LOTS should be considered in patients with similar symptoms and cerebellar atrophy on brain imaging.

Objective To evaluate differences in physical function at 6 weeks after vaginal surgery among women positioned in candy cane and boot stirrups. Methods We conducted a single-masked, randomized controlled trial of women undergoing vaginal surgery with either candy cane or boot stirrup use. The primary outcome was a change in the PROMIS (Patient-Reported Outcomes Measurement Information System) physical function short form-20a from baseline to 6 weeks after surgery. To achieve 80% power to detect a moderate Cohen effect (d=0.5), we required 64 participants in each group. Results From March 2018 to October 2019, 141 women were randomized, and 138 women (72 in the candy cane group and 66 in the boot stirrup group) were included in the final analysis. There were no baseline differences in participant characteristics including age, body mass index, comorbidities, or preoperative history of joint replacements. There were no between-group differences in surgery type, duration of surgery, estimated blood loss, or adverse events at 6 weeks postoperation. Participants in the candy cane group demonstrated worse physical function at 6 weeks compares with the improvement seen in those in the boot stirrup group; this was significantly different between groups (-1.9±7.9 candy cane vs 1.9±7.0 boot, P Conclusion Women undergoing vaginal surgery positioned in boot stirrups have significantly better physical function at 6 weeks after surgery when compared with women positioned in candy cane stirrups. Clinical trial registration ClinicalTrials.gov, NCT03446950.

Graphene-based biosensors can be produced in a scalable manner at reasonable cost, and they show significant promise for sensitive detection of small molecules and biomarkers such as proteins, single strand nucleic acids, and drug targets. Here, we describe an approach that enables a limit of detection of ~1 aM for a ssDNA target without amplification. We also show that a sensor based on a short (20mer) probe complementary to a portion of a longer (100mer) target provides enhanced sensitivity and saturation signal level. Finally, we show that graphene-based DNA biosensors can be repeatedly recycled with consistent sensor responses by melting off bound target strands. These results show the potential utility of this technology in nucleic acid detection for disease diagnostics.

For the first time, a series of novel 1′-homo-N-2′-deoxy-α-nucleosides containing natural nucleobases as well as 5-fluoro and 5-iodopyrimidine analogs have been synthesized in an efficient manner. Additionally, a high yield protocol for the assembly of a dimeric scaffold containing two sugar moieties linked to the N-1 and N-3 positions of a single pyrimidine base has been accomplished. The structures of the novel homonucleosides were established by a single crystal X-ray structure of 1′-homo-N-2′-deoxy-α-adenosine and NMR studies. The biological activity of these 1′-homo-N-2′-deoxy-α-nucleosides as antiviral (HIV-1 and HBV) and cytotoxic studies was measured in multiple cell systems. The unique structure and easy accessibility of these compounds may allow their use in the design of new nucleoside analogs with potential biological activity and as a scaffold for combinatorial chemistry.

Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scalesin vivoremains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.

INTRODUCTION AND OBJECTIVE:Disparities in nephrolithiasis care based on gender, ethnicity and age have been well described. Fewer studies have examined the influence of insurance status in nephroli...

RESEARCH OBJECTIVE: As clinicians are increasingly called to recognize and act on social needs contributing to their patients' health, health professional schools are incorporating discussions of social factors and health equity into required curricula to help physicians navigate the intersections of society and medicine. This study aims to evaluate perceptions and attitudes of physicians and medical students as they interact with these topics in the setting of medical education. In addition, this study aims to explore how physicians and medical students interpret, engage with, and use ‘structural competency’ in the clinic. STUDY DESIGN: This longitudinal qualitative study consisted of semi‐structured interviews about the use of a ‘structural competency’ framework during a preclinical medical education course called Introduction to Medicine and Society. ‘Structural competency,’ an emerging educational framework for addressing patient's social needs, reframes clinical issues and disease as the downstream result of upstream social, political, and economic decisions (Metzl and Hansen, 2014). Interviews were conducted at three time points during the course: before participation in a structural competency based module, after participation in the module, and after the full course was completed. POPULATION STUDIED: We conducted 53 interviews with 12 first‐year medical students, 15 upper‐level student course facilitators, and 8 physician facilitators who participated in the course. PRINCIPAL FINDINGS: This paper focuses on three interrelated findings: (1) how medical students and faculty describe complex concepts like ‘structure’ and what developing a ‘competency’ of structures means; (2) what the barriers and facilitators are to developing and using structural competency in education and clinical practice; and (3) how participants understand their actions in the clinic as potential opportunities to enact structural competency or intervene on the structural factors that impact patients' health. CONCLUSIONS: Because structural competency gives an expansive lens for physicians to recognize the connection between health and society, it also highlights the ways in which physicians are constrained by the structure of health care itself, hindering their abilities to fully engage with the social aspects of their patients' well‐beings or meaningfully promote health equity. This further impacts physician efficacy and well‐being, contributing to feelings of frustration and hopelessness. IMPLICATIONS FOR POLICY OR PRACTICE: These findings have practical implications for how clinicians are trained to conceptualize and act on social factors to not only address patients' needs within the clinical encounter, but also to respond to their own professional and emotional experiences within the broader social world of US healthcare. This study also has conceptual implications for refining how existing frameworks and curricula conceive of the intersection between healthcare and broader social processes by better incorporating the lived experiences of clinicians who are practicing at these intersections everyday.

Vaginal surgery often presents challenges of access. To gain adequate visualization of relevant structures, surgical assistants often assume awkward positioning with inadequate stability of handheld retractors. Additionally, the lead surgeon is typically the only member of the surgical team who can adequately visualize the procedure being performed. To that end, devices have been manufactured with aims of optimizing both visualization and workspace while reducing the need of handheld retractors during vaginal surgery. This video presents one of those retractors: a reusable, self-retaining, vaginal Magrina-Bookwalter, with details to help achieve the optimal visualization and workspace with its use. A narrated video provides a brief history, components and proper assembly of the retractor with stepwise application of components demonstrated during a vaginal hysterectomy. The self-retaining, vaginal Magrina-Bookwalter retractor is a helpful tool to optimize the visualization and workspace while reducing the need for handheld retractors during vaginal procedures deeper into the pelvis.

Iatrogenic ureteral injuries can occur during any surgery but are more likely to occur during urologic and gynecologic procedures. The middle and distal ureter are especially at risk of injury during these surgeries. The objective of this surgical educational video was to demonstrate how to repair middle to distal ureteral injuries with the following techniques: direct ureteroureterostomy, ureteroneocystotomy, vesico-psoas hitch, and Boari-Ockerblad bladder flap. A female cadaver was used to show how to surgically repair injuries to the middle and distal ureter. Middle to distal ureteral injuries occurring during urologic and gynecologic surgeries can be repaired by the techniques demonstrated in this video manuscript.

INTRODUCTION During the coronavirus disease 2019 (COVID-19) pandemic, decreased presentations for various emergent conditions have been observed. Our objective was to compare the volume of patients with urologic emergencies presenting to emergency departments (EDs) within a single health system before and after the onset of the COVID-19 pandemic.A retrospective chart review was performed for 3 EDs within a single health system in the United States to identify all ED consults to urology from January 1, 2019 to May 31, 2020. For emergent consults, covariates were extracted, including demographic information, insurance status, Charlson Comorbidity Index (CCI) score, travel distance from home to the ED, and whether the patient had seen a provider in the hospital system before. Data were compared between COVID-19 months (March-May 2020) and corresponding months in 2019.The study period encompassed 1,179 consults and 373 urologic emergencies. We observed not only a 22% decrease in urologic presentations to the ED compared to corresponding months in 2019, but also a 54% decrease in the proportion of urologic presentations that were truly emergent. For patients with emergent diagnoses, April 2020 saw an increase in Medicare/Medicaid coverage and a decrease in private insurance, May 2020 saw a decreased travel distance from home to the ED, and March and May 2020 saw an increase in patients who had previously seen a health system provider outside of the ED. No changes were seen in demographic characteristics or CCI.During the early COVID-19 pandemic, urologic emergencies within a single health system decreased by 54% compared to the corresponding months pre-pandemic. Those who do present for care may be influenced by both locality and provider familiarity.

A number of conceptual frameworks have emerged with the goal of helping clinicians understand and navigate the intersections of the health system and broader political, economic, and cultural processes when they care for patients. In this study, we analyze the impact that one emerging framework, “structural competency,” had on medical students' and physicians' understanding of societal problems affecting patient health and the practices of health systems. In this sub-analysis of a longitudinal qualitative study conducted between August and December 2020, we analyzed 19 semi-structured interviews with 7 first-year medical students, 7 upper-level medical students, and 5 physician course facilitators who participated in a course called Introduction to Medicine and Society at an medical school in the United States affiliated with a large urban academic medical center. This paper focuses on three main findings: how medical students and faculty describe “structures” and their effects on patients and patient care; how they use or imagine using structural competency to improve patient-physician communication and work interprofessionally to address social needs; and the emotional and personal reactions that confronting societal challenges provokes. We conclude that structural competency enhances existing efforts to improve patient-physician communication and to address patients' social needs. However, we highlight how structural competency efforts might fall short of their goal to shift physicians’ perspectives “upstream” to the determinants of health due to both critical ambiguities in the concept and inattention to the emotional and personal impacts of addressing societal problems in the clinic. These findings have practical implications for how clinicians are trained to act on societal issues from within the health system and conceptual implications for refining how existing frameworks and curricula conceive of the intersection between healthcare and broader processes.

Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution., Driscoll, Rosch et al. design transparent graphene-based surface probes to achieve simultaneous electrophysiological recording and calcium imaging of epileptic seizures in mice. This method could be used to investigate circuit dynamics during seizure onset and evolution with high temporal and spatial resolution.

This work introduces a method for co-localized multi-modal imaging of sub-μm features in an additively manufactured (AM) titanium alloy. Ti-6Al-4V parts manufactured by electron beam melting powder bed fusion were subjected to hot isostatic pressing to seal internal porosity and machined to remove contour–hatch interfaces. Electron microscopy and atomic force microscopy-based techniques (electron backscatter diffraction and scanning Kelvin probe force microscopy) were used to measure and categorize the effects of crystallographic texture, misorientation, and phase content on the relative differences in the Volta potential of α-Ti and β-Ti phases. Given the tunability of additive manufacturing processes, recommendations for texture and phase control are discussed. In particular, our findings indicate that the potential for micro-galvanic corrosion initiation can be regulated in AM Ti-6Al-4V parts by minimizing both the total area of {111} prior-β grains and the number of contact points between {111} β grains and α laths that originate from {001} prior-β grains.

Recent publications show an association between exposure to anticholinergic medications and the risk of developing dementia. We hypothesized that urogynecology providers have changed their overactive bladder syndrome treatment as a result of this literature.This was an anonymous, cross-sectional, web-based survey of American Urogynecologic Society members. Survey questions queried awareness of the referenced literature, prescribing practices, the impact of insurance on treatment plans, and demographics. Our primary outcome measured the change in prescribing practice in response to literature linking anticholinergic medications with the risk of dementia. Descriptive statistics were used.A total of 222 urogynecology providers completed the survey. Nearly all respondents (99.1%) were aware of the recent literature, and, as a result, 90.5% reported changing their practice. Prior to the publication of recent literature, a "non-CNS-sparing" anticholinergic (e.g., oxybutynin) was most commonly prescribed (64.4%), whereas after the literature was published, this shifted to ßThe recent literature associating anticholinergic medications with the development of dementia has changed practice patterns among survey respondents, with a shift away from anticholinergic medications and toward ß

To evaluate the utility of adding triamcinolone acetonide to a standard bladder instillation solution for treatment of interstitial cystitis-bladder pain syndrome.This was a single-center, randomized, double-blind trial that compared symptom response in women with interstitial cystitis-bladder pain syndrome who underwent six bladder instillations with triamcinolone acetonide or six instillations without. All instillation solutions contained heparin, viscous lidocaine, sodium bicarbonate, and bupivacaine. The primary outcome was the change in interstitial cystitis-bladder pain syndrome symptoms from the first to sixth bladder instillation between groups based on the total OLS (O'Leary-Sant Questionnaire) score. Assuming a 4.03-point or larger difference in the mean total OLS score from the first to sixth bladder instillation as compared between the groups, 64 participants were needed to show a significant difference with 80% power at the 0.05 significance level.From January 2019 to October 2020, 90 women were enrolled-45 per group; 71 (79%) completed all six bladder instillations. Randomization resulted in groups with similar characteristics. There was no difference between groups in the primary outcome (bladder instillation with triamcinolone acetonide: mean OLS change -6.7 points, 95% CI 4.6-8.8 and bladder instillation without triamcinolone acetonide: mean OLS change -5.8 points, 95% CI 3.4-8.1; P=.31). Women in both groups had improvement in their interstitial cystitis-bladder pain syndrome symptoms as indicated by a decrease in the total OLS score from the first to sixth bladder instillation.The addition of triamcinolone acetonide to a standard bladder instillation solution does not improve symptoms associated with interstitial cystitis-bladder pain syndrome.ClinicalTrials.gov, NCT03463915.

OBJECTIVES This study aimed to determine if there are differences in (1) surgical procedures performed for pelvic organ prolapse (POP) and (2) rates of adverse events between racial groups. METHODS We conducted a retrospective cohort study of women 18 years and older who underwent POP surgery using the 2005-2015 American College of Surgeons National Surgical Quality Improvement Program database. Race was categorized as Black, White, Hispanic, and other minority. Pelvic organ prolapse procedures were organized into 4 groups: (1) hysterectomy without concurrent POP procedures, (2) vaginal wall repair(s) only without apical suspension, (3) apical suspension with or without vaginal wall repair(s), and (4) obliterative procedures. Patient characteristics and rates of adverse events were noted. A multivariable logistic regression model was used to assess the association between patient race and surgical procedures performed for POP. RESULTS We identified 48,005 women who met the inclusion criteria. Most women who underwent POP surgery were White (79.6% [n = 38,191]). Although only contributing to 4.7% (2,299) of the cohort, Black women experienced higher complication rates compared with White women (10.7% [246] for Black vs 8.9% [3,417] for White women, P < 0.01). Hispanic and other minority women were less likely to undergo an apical suspension than White women (adjusted odds ratios [aORs], 0.79 [0.75-0.84] for Hispanic women and 0.78 [0.71-0.86] for other minority women; P < 0.001 for both). Obliterative procedures were more likely to be performed in Black, in Hispanic, and especially in other minority women (aORs, 1.53 [1.20-1.92] for Black, 1.33 [1.12-1.58] for Hispanic, and 3.67 [3.04-4.42] for other minority women; P < 0.001 for all). CONCLUSIONS Racial differences exist among women who undergo POP surgery.

Idiopathic overactive bladder (OAB) is a chronic condition that negatively affects quality of life, and oral medications are an important component of the OAB treatment algorithm. Recent literature has shown that anticholinergics, the most commonly prescribed oral medication for the treatment of OAB, are associated with cognitive side effects including dementia. β3-adrenoceptor agonists, the only alternative oral treatment for OAB, are similar in efficacy to anticholinergics with a more favorable side effect profile without the same cognitive effects. However, there are marked cost variations and barriers to access for OAB medications, resulting in expensive copays and medication trial requirements that ultimately limit access to β3-adrenoceptor agonists and more advanced procedural therapies. This contributes to and perpetuates health care inequality by burdening the patients with the least resources with a greater risk of dementia. When prescribing these medications, health care professionals are caught in a delicate balancing act between cost and patient safety. Through multilevel collaboration, we can help disrupt health care inequalities and provide better care for patients with OAB.

Alterations in glycogen synthase kinase-3β (GSK-3β) activity have been implicated in disorders of cognitive impairment, including Alzheimer's disease and schizophrenia. Cognitive dysfunction is also characterized by the dysregulation of neuronal oscillatory activity, macroscopic electrical rhythms in brain that are critical to systems communication. A direct functional relationship between GSK-3β and neuronal oscillations has not been elucidated. Therefore, in the present study, using an adeno-associated viral vector containing a persistently active mutant form of GSK-3β, GSK-3β(S9A), the impact of elevated kinase activity in prefrontal cortex (PFC) or ventral hippocampus (vHIP) of rats on neuronal oscillatory activity was evaluated. GSK-3β(S9A)-induced changes in learning and memory were also assessed and the phosphorylation status of tau protein, a substrate of GSK-3β, examined. It was demonstrated that increasing GSK-3β(S9A) activity in either the PFC or vHIP had similar effects on neuronal oscillatory activity, enhancing theta and/or gamma spectral power in one or both regions. Increasing PFC GSK-3β(S9A) activity additionally suppressed high gamma PFC-vHIP coherence. These changes were accompanied by deficits in recognition memory, spatial learning, and/or reversal learning. Elevated pathogenic tau phosphorylation was also evident in regions where GSK-3β(S9A) activity was upregulated. The neurophysiological and learning and memory deficits induced by GSK-3β(S9A) suggest that aberrant GSK-3β signalling may not only play an early role in cognitive decline in Alzheimer's disease but may also have a more central involvement in disorders of cognitive dysfunction through the regulation of neurophysiological network function.

Objectives To design, implement, and evaluate learner attitudes of a virtual urologic surgery clinical rotation for medical students Methods Ten senior medical students at the Perelman School of Medicine at the University of Pennsylvania were enrolled. Students were administered a pre-course test on their perceived confidence of their urologic knowledge, confidence in identifying urologic conditions, comfort with performing urologic evaluations, and confidence placing consults for urologic issues. Students participated in a two-week curriculum that included both asynchronous and synchronous content. Asynchronous content included pre-recorded lectures, self-paced problem-based learning (PBL) modules, directed reading and video content, and an online discussion board. Synchronous content included real-time videoconferences covering case discussions, simulated patient presentations, and critical literature reviews. At the conclusion of the course, students were administered the post-course survey evaluating changes in their ability to identify and understand urologic conditions. Results The post-course survey demonstrated this course significantly increases students’ scores in: self-perceived urologic knowledge, confidence in naming urologic conditions, comfort with performing urologic evaluations, and confidence placing consults for urologic conditions (p

Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

Ketamine is a promising therapeutic for treatment-resistant depression (TRD) but is associated with an array of short-term psychomimetic side-effects. These disparate drug effects may be elicited through the modulation of neural circuit activity. The purpose of this study was to therefore delineate dose- and time-dependent changes in ketamine-induced neural oscillatory patterns in regions of the brain implicated in depression. Wistar-Kyoto rats were used as a model system to study these aspects of TRD neuropathology whereas Wistar rats were used as a control strain. Animals received a low (10 mg/kg) or high (30 mg/kg) dose of ketamine and temporal changes in neural oscillatory activity recorded from the prefrontal cortex (PFC), cingulate cortex (Cg), and nucleus accumbens (NAc) for ninety minutes. Effects of each dose of ketamine on immobility in the forced swim test were also evaluated. High dose ketamine induced a transient increase in theta power in the PFC and Cg, as well as a dose-dependent increase in gamma power in these regions 10-min, but not 90-min, post-administration. In contrast, only low dose ketamine normalized innate deficits in fast gamma coherence between the NAc-Cg and PFC-Cg, an effect that persisted at 90-min post-injection. These low dose ketamine-induced oscillatory alterations were accompanied by a reduction in immobility time in the forced swim test. These results show that ketamine induces time-dependent effects on neural oscillations at specific frequencies. These drug-induced changes may differentially contribute to the psychomimetic and therapeutic effects of the drug.

Introduction Familial hemiplegic migraine (FHM) is a genetic disease with a variable clinical phenotype. The imaging and electroencephalogram (EEG) correlates of FHM are not well described. Case series We describe a case series of five young women aged 12 to 32 years. Each case presented with headache, encephalopathy, and hemiparesis of varying severity. One patient developed seizures. All patients improved spontaneously. Investigations Asymmetric slow-wave activity was seen on electroencephalogram in each case. One patient developed marked unilateral cortical edema on MR imaging. Cerebro-spinal fluid (CSF) studies were normal for all patients. Genetic testing in each case showed a mutation of the ATP1A2 gene. One of the mutations identified is a novel mutation. Discussion Genetic mutation of the ATP1A2 gene results in a channelopathy which is thought to predispose to spreading depolarization, the probable physiologic correlate of migraine aura. We hypothesize that widespread prolonged depolarization accounts for the characteristic electroencephalogram findings in these cases. Familial hemiplegic migraine should be considered in the differential diagnosis of an asymmetric encephalopathy, particularly when CSF and imaging studies are normal.

Understanding soil organic matter (OM) biogeochemistry at the molecular-level is essential for assessing potential impacts from management practices and climate change on shifts in soil carbon storage. Biomarker analyses and nuclear magnetic resonance (NMR) spectroscopy were used in an ongoing detrital input and removal treatment experiment in a temperate deciduous forest in Pennsylvania, USA, to examine how above- and below-ground plant inputs control soil OM quantity and quality at the molecular-level. From plant material to surface soils, the free acyclic lipids and cutin, suberin, and lignin biomarkers were preferentially retained over free sugars and free cyclic lipids. After 20 years of above-ground litter addition (Double Litter) or exclusion (No Litter) treatments, soil OM composition was relatively more degraded, as revealed by solid-state 13C NMR spectroscopy. Under Doubled Litter inputs, soil carbon and phospholipid fatty acid (PLFA) concentrations were unchanged, suggesting that the current OM degradation status is a reflection of microbial-mediated degradation that occurred prior to the 20-year sampling campaign. Soil OM degradation was higher in the No Litter treatments, likely due to the decline in fresh, above-ground litter inputs over time. Furthermore, root and root and litter exclusion treatments (No Roots and No Inputs, respectively) both significantly reduced free sugars and PLFAs and increased preservation of suberin-derived compounds. PLFA stress ratios and the low N-acetyl resonances from diffusion edited 1H NMR also indicate substrate limitations and reduced microbial biomass with these treatments. Overall, we highlight that storage of soil carbon and its biochemical composition do not linearly increase with plant inputs because the microbial processing of soil OM is also likely altered in the studied forest.