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Abstract Background The purpose of this study was to determine the prevalence and characteristics of ligamentous knee injuries and to compare patient demographics, associated injuries and hospital stay to pedestrians who did not sustain a ligamentous knee injury. Methods A retrospective review of all adult patients presenting as pedestrians struck by a motor vehicle to a level 1 trauma center over a three-year period was performed. Demographics, length of stay, orthopedic and non-orthopedic traumatic injuries were recorded. Magnetic resonance imaging was reviewed for ligamentous, bony and chondral injuries. Results Five hundred thirty-nine patients were included. Sixty-seven (12.4%) patients sustained a total of 84 ligamentous knee injuries. OF these knee injuries that had MRI (55/84), the majority (96%) were multi-ligamentous in nature. Patients with ligamentous knee injury were more likely to also be affected by traumatic brain injury, solid organ injury, cervical and lumbar spine injury, pelvic ring injuries, distal femur fractures, patella fractures, knee dislocations, tibial plateau fractures, tibial pilon fractures, and deep vein thrombosis when compared to patients who did not sustain ligamentous knee injury. Patients who sustained ligamentous knee injury were more likely to require hospital and intensive care admission and had a longer overall hospital stay. Conclusion Given the high prevalence of ligamentous knee injuries in this patient population, these patients should be thoroughly evaluated for a ligamentous knee injury. If ligamentous knee injury is suspected, MRI should be considered as a majority of these injuries involved multiple structures. Patients with ligamentous knee injuries often had multi-system injuries with resulting longer hospital stay when compared to those without ligamentous knee injuries.

Abstract Background There is increasing evidence demonstrating the value of partial extracorporeal CO2 removal (ECCO2R) for the treatment of hypercapnia in patients with acute exacerbations of chronic obstructive pulmonary disease and acute respiratory distress syndrome. Mechanical ventilation has traditionally been used to treat hypercapnia in these patients, however, it has been well-established that aggressive ventilator settings can lead to ventilator-induced lung injury. ECCO2R removes CO2 independently of the lungs and has been used to permit lung protective ventilation to prevent ventilator-induced lung injury, prevent intubation, and aid in ventilator weaning. The Low-Flow Pittsburgh Ambulatory Lung (LF-PAL) is a low-flow ECCO2R device that integrates the fiber bundle (0.65 m2) and centrifugal pump into a compact unit to permit patient ambulation. Methods A blood analog was used to evaluate the performance of the pump at various impeller rotation rates. In vitro CO2 removal tested under normocapnic conditions and 6-h hemolysis testing were completed using bovine blood. Computational fluid dynamics and a mass-transfer model were also used to evaluate the performance of the LF-PAL. Results The integrated pump was able to generate flows up to 700 mL/min against the Hemolung 15.5 Fr dual lumen catheter. The maximum vCO2 of 105 mL/min was achieved at a blood flow rate of 700 mL/min. The therapeutic index of hemolysis was 0.080 g/(100 min). The normalized index of hemolysis was 0.158 g/(100 L). Conclusions The LF-PAL met pumping, CO2 removal, and hemolysis design targets and has the potential to enable ambulation while on ECCO2R.

Abstract Background Extracorporeal carbon dioxide removal (ECCO2R) systems have gained clinical appeal as supplemental therapy in the treatment of acute and chronic respiratory injuries with low tidal volume or non-invasive ventilation. We have developed an ultra-low-flow ECCO2R device (ULFED) capable of operating at blood flows comparable to renal hemodialysis (250 mL/min). Comparable operating conditions allow use of minimally invasive dialysis cannulation strategies with potential for direct integration to existing dialysis circuitry. Methods A carbon dioxide (CO2) removal device was fabricated with rotating impellers inside an annular hollow fiber membrane bundle to disrupt blood flow patterns and enhance gas exchange. In vitro gas exchange and hemolysis testing was conducted at hemodialysis blood flows (250 mL/min). Results In vitro carbon dioxide removal rates up to 75 mL/min were achieved in blood at normocapnia (pCO2 = 45 mmHg). In vitro hemolysis (including cannula and blood pump) was comparable to a Medtronic Minimax oxygenator control loop using a time-of-therapy normalized index of hemolysis (0.19 ± 0.04 g/100 min versus 0.12 ± 0.01 g/100 min, p = 0.169). Conclusions In vitro performance suggests a new ultra-low-flow extracorporeal CO2 removal device could be utilized for safe and effective CO2 removal at hemodialysis flow rates using simplified and minimally invasive connection strategies.

Background: Marital status has been shown to have protective effects for married patients with various cancers. We sought to determine effects of marital status on perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 709 consecutive patients who underwent RAPL between 2010 and 2022 by one surgeon. Patients were stratified by marital status at time of surgery. The Married group included married, domestically partnered, and co-habitating patients (N = 473). The Unmarried group included never married, divorced, and widowed individuals (N = 236). Demographics, preoperative comorbidities, intraoperative and postoperative complications, estimated blood loss (EBL), chest tube duration, hospital length of stay (LOS), tumor characteristics, and survival data were analyzed utilizing Student's t-test, Wilcoxon rank-sum test, Chi-square, or Fisher's exact test as appropriate, with significance at p≤0.05. Results: Unmarried patients were more likely to be female, while married patients were more likely to experience robotic-associated intraoperative complications and greater intraoperative estimated blood loss. Kaplan-Meier survival analysis revealed no difference in 5-year overall survival based on marital status. Other perioperative outcomes, intraoperative complications (except robotic-associated), postoperative complications, demographic history (except gender), and preoperative comorbidities did not significantly differ between the two groups. Conclusion: This study challenges the existing reports in the literature that marriage confers cancer treatment outcomes advantage and prolonged survival among cancer patients. Social support, in terms of a spouse or domestic partner, may be less protective in early-stage lung cancer and after minimally invasive pulmonary lobectomy compared to other cancer populations.

Abstract Background Research priorities are best defined through engagement with communities who will be impacted by the research and have lived experience of the topics to be studied. We aimed to establish a pediatric rare disease community stakeholder group and empower them in (1) eliciting perspectives from affected families in the wider region and (2) synthesizing collective ideas into a research agenda focused on shared ethical, legal, and social implications (ELSI) across rare disease. Methods This two-year project utilized a community-centered approach to engage rare disease community members as equal partners in developing a research agenda for ELSI in rare disease. We established “Rare Voices” (RV), a 22-member stakeholder group of patients, parents, clinicians and researchers. Following capacity-building trainings, RV designed and conducted listening sessions with teen patients and parents of children with rare diseases to explore challenges, positive experiences, and ethical concerns. Listening session findings were synthesized and contextualized into research topics, which RV members further refined and prioritized. We used established measures to assess RV member engagement and satisfaction. Results From 14 listening sessions with parents (n = 52) and teen patients (n = 13), RV identified eight core research topics as most important for future rare disease research: coordinating care, communication, accessing resources and care, impact on family unit, community and support in society, mental health and identity, ethical aspects of care, and uncertainty. RV members were highly engaged throughout the two-year project and reported high levels of satisfaction with the experience and research agenda. Conclusions Through capacity-building and authentic engagement, this project resulted in a community-led rare disease research agenda to guide future rare disease ELSI research that aligns with patients’ and families’ priorities. An environment of equal partnership and respect created a space for mutual learning where community members were empowered to shape the research agenda based on their collective experiences. The agenda recognizes the shared psychosocial and healthcare experiences of rare disease and offers practical areas of research to address patient and family needs.

Abstract The type VII protein secretion system (T7SS) is found in many Gram-positive bacteria and in pathogenic mycobacteria. All T7SS substrate proteins described to date share a common helical domain architecture at the N-terminus that typically interacts with other helical partner proteins, forming a composite signal sequence for targeting to the T7SS. The C-terminal domains are functionally diverse and in Gram-positive bacteria such as Staphylococcus aureus often specify toxic anti-bacterial activity. Here we describe the first example of a class of T7 substrate, TslA, that has a reverse domain organisation. TslA is widely found across Bacillota including Staphylococcus, Enterococcus and Listeria. We show that the S. aureus TslA N-terminal domain is a phospholipase A with anti-staphylococcal activity that is neutralised by the immunity lipoprotein TilA. Two small helical partner proteins, TlaA1 and TlaA2 are essential for T7-dependent secretion of TslA and at least one of these interacts with the TslA C-terminal domain to form a helical stack. Cryo-EM analysis of purified TslA complexes indicate that they share structural similarity with canonical T7 substrates. Our findings suggest that the T7SS has the capacity to recognise a secretion signal present at either end of a substrate.

Morus sp. (mulberry) has a long tradition of use as a medicinal treatment, including for cardiovascular disease and type 2 diabetes, being shown to have antioxidant properties and to promote wound healing. Extracellular vesicles (EVs) are sub-micron, membrane-enclosed particles that were first identified in mammalian bodily fluids. EV-like particles have been described in plants (PDVs) and shown to have similar characteristics to mammalian EVs. We hypothesised that some of the health benefits previously attributed to the fruit of Morus sp. could be due to the release of PDVs. We isolated PDVs from Morus nigra and Morus alba via ultracentrifugation and incubated THP-1 monocytes, differentiated THP-1 macrophages, or HMEC-1 endothelial cells with pro-oxidant compounds DMNQ (THP-1) and glucose oxidase (HMEC-1) or lipopolysaccharide (LPS) in the presence of different fractions of mulberry EVs. Mulberry EVs augmented ROS production with DMNQ in THP-1 and caused the downregulation of ROS in HMEC-1. Mulberry EVs increased LPS-induced IL-1β secretion but reduced CCL2 and TGF-β secretion in THP-1 macrophages. In scratch wound assays, mulberry EVs inhibited HMEC-1 migration but increased proliferation in both low and high serum conditions, suggesting that they have opposing effects in these two important aspects of wound healing. One of the limitations of plant-derived therapeutics has been overcoming the low bioavailability of isolated compounds. We propose that PDVs could provide the link between physiological dose and therapeutic benefit by protecting plant active compounds in the GIT as well as potentially delivering genetic material or proteins that contribute to previously observed health benefits.

ABSTRACT: Background: Outcomes of lung cancer patients traveling greater distances for surgical oncology care are not well-described. We investigated the effects of increased travel burden after robotic-assisted pulmonary lobectomy (RAPL) for lung cancer. Methods: Clinical characteristics and surgical outcomes of 711 consecutive patients who underwent RAPL from September 2010 to March 2022 were compared, stratified by primary residential ZIP code

Abstract Environmental (e)DNA has rapidly become a powerful biomonitoring tool, particularly in aquatic ecosystems. This approach has not been as widely adopted in terrestrial communities where the methods of vertebrate eDNA collection have varied from the use of secondary collectors such as blood feeding parasites and spider webs, to washing surfaces of leaves and soil sampling. Recent studies have demonstrated the potential of direct collection of eDNA from air sampling, but none have tested how effective airborne eDNA sampling might be in a biodiverse environment. We used three prototype samplers to actively sample a mixed neotropical bat community in a partially controlled environment. We assess whether airborne eDNA can accurately characterize a high diversity community with skewed abundances and to determine if filter design impacts DNA collection and taxonomic recovery. Our study provides evidence for the accuracy of airborne eDNA as a detection tool and highlights its potential for monitoring high density, diverse assemblages such as bat roosts. Analysis of air samples recovered >91% of the species present and some limited relationship between species abundance and read count. Our data suggests this method can accurately depict a diverse mixed‐mammal community, particularly when the location is contained (e.g., a roost, den or burrow) but also highlights the potential for secondary transfer of eDNA material on clothing and equipment. Our results also demonstrate that simple, inexpensive, battery‐operated homemade air samplers can collect an abundance of eDNA from the air, opening the opportunity for sampling in remote environments.

Abstract Analysis of environmental DNA (eDNA) from passively collected airborne dust has demonstrated broad success for sensitive and robust detection of plants. Recent experiments at small spatial scales have suggested that animals can also be detected using airborne eDNA. However, airborne eDNA analysis has never been used for a long‐term whole‐community assessment of a natural terrestrial community or with passive dust collectors. We conducted a metabarcoding survey targeting vertebrate eDNA from dust carried in the air on an approximately 130‐acre shortgrass prairie passively collected over the course of a year. Our survey detected a wide variety of animal forms including an amphibian species, several bird species, and both small and large mammals. We found that airborne eDNA signals changed with known patterns of animal activity, wind speed, and rainfall. Overall, we demonstrate that passively collected airborne dust carries eDNA from terrestrial animals and could be used to detect a wide variety of terrestrial vertebrate species in a natural environment with minimal effort. To develop this as a valuable monitoring tool, research needs to focus on the ecology of eDNA carried in the air, which includes the origin, state, transport, dispersal, and fate of eDNA in the environment.

Summary: Zebrafish embryos use their yolk sac reserve as the sole nutrient source during embryogenesis. The two main forms of energy fuel can be found in the form of glucose or fat. Zebrafish embryos were exposed to glucose or injected with free fatty acid/Triacylglycerol (FFA/TAG) into the yolk sac at 24 hpf. At 72 hpf, glucose exposed or FFA/TAG injected had differential effects on gene expression in embryos, with fat activating lipolysis and β-oxidation and glucose activating the insulin pathway. Bulk RNA-seq revealed that more gene expression was affected by glucose exposure compared to FFA/TAGs injection. Appetite-controlling genes were also differently affected by glucose exposure or FFA/TAG injections. Because the embryo did not yet feed itself at the time of our analysis, gene expression changes occurred in absence of actual hunger and revealed how the embryo manages its nutrient intake before active feeding.

Background: The COVID-19 pandemic presented patients with barriers to receiving healthcare. We sought to determine whether changes in healthcare access and practice during the pandemic affected perioperative outcomes after robotic-assisted pulmonary lobectomy (RAPL). Methods: We retrospectively analyzed 721 consecutive patients who underwent RAPL. With March 1st, 2020, defining the start of the COVID-19 pandemic, we grouped 638 patients as “PreCOVID-19” and 83 patients as “COVID-19-Era” based on surgical date. Demographics, comorbidities, tumor characteristics, intraoperative complications, morbidity, and mortality were analyzed. Variables were compared utilizing Student's t-test, Wilcoxon rank-sum test, and Chi-square (or Fisher's exact) test, with significance at p≤0.05. Multivariable generalized linear regression was used to investigate predictors of postoperative complication. Results: COVID-19-Era patients had significantly higher preoperative FEV1%, lower cumulative smoking history and higher incidences of preoperative atrial fibrillation, peripheral vascular disease (PVD), and bleeding disorders compared to PreCOVID-19 patients. COVID-19-Era patients had lower intraoperative estimated blood loss (EBL), reduced incidence of new-onset postoperative atrial fibrillation (POAF), but higher incidence of effusion or empyema postoperatively. Overall postoperative complication rates between the groups were similar. Older age, increased EBL, lower preoperative FEV1%, and preoperative COPD are all predictive of an increased risk for postoperative complication. Conclusions: COVID-19-Era patients having lower EBL and less new-onset POAF, despite greater incidences of multiple preoperative comorbidities, demonstrates that RAPL is safe during the COVID-19 era. Risk factors for development of postoperative effusion should be determined to minimize risk of empyema in COVID-19-Era patients. Age, preoperative FEV1%, COPD, and EBL should all be considered when planning for complication risk.

Understanding roosting behaviour is essential to bat conservation and biomonitoring, often providing the most accurate methods of assessing bat population size and health. However, roosts can be challenging to survey, e.g., physically impossible to access or presenting risks for researchers. Disturbance during monitoring can also disrupt natural bat behaviour and present material risks to the population such as disrupting hibernation cycles. One solution to this is the use of non-invasive monitoring approaches. Environmental (e)DNA has proven especially effective at detecting rare and elusive species particularly in hard-to-reach locations. It has recently been demonstrated that eDNA from vertebrates is carried in air. When collected in semi-confined spaces, this airborne eDNA can provide remarkably accurate profiles of biodiversity, even in complex tropical communities. In this study, we deploy novel airborne eDNA collection for the first time in a natural setting and use this approach to survey difficult to access potential roosts in the neotropics. Using airborne eDNA, we confirmed the presence of bats in nine out of 12 roosts. The identified species matched previous records of roost use obtained from photographic and live capture methods, thus demonstrating the utility of this approach. We also detected the presence of the white-winged vampire bat (Diaemus youngi) which had never been confirmed in the area but was long suspected based on range maps. In addition to the bats, we detected several non-bat vertebrates, including the big-eared climbing rat (Ototylomys phyllotis), which has previously been observed in and around bat roosts in our study area. We also detected eDNA from other local species known to be in the vicinity. Using airborne eDNA to detect new roosts and monitor known populations, particularly when species turnover is rapid, could maximize efficiency for surveyors while minimizing disturbance to the animals. This study presents the first applied use of airborne eDNA collection for ecological analysis moving beyond proof of concept to demonstrate a clear utility for this technology in the wild.

Background: Atrial fibrillation is a common arrhythmia previously linked to systemic inflammation, which has been correlated with leukocyte and prealbumin levels. We sought to identify predictors of postoperative atrial fibrillation (POAF) following robotic-assisted pulmonary lobectomy. Methods: This retrospective cohort study included 709 consecutive patients who underwent robotic-assisted lobectomy by one surgeon over 10.7 years. We compared demographics, preoperative comorbidities, perioperative leukocyte, prealbumin levels, complications, chest tube (CT) duration, and hospital length of stay (LOS) using Student's t-test, Chi-square (or Fisher's exact) test, or Wilcoxon rank sums test, with significance at p ≤ 0.05. Multivariable analysis investigated predictors of POAF, CT duration, hospital LOS, and overall survival (OS). Kaplan-Meier analysis estimated OS with 95% confidence intervals. Results: Preoperative atrial fibrillation or chronic steroid or immunosuppressant use excluded 131 patients, and 578 remaining patients were classified as POAF (n=76) or No POAF (n=502). Patients with new-onset POAF were older and had higher incidences of preoperative hypertension and hyperlipidemia, intraoperative complications, and postoperative anemia. The lowest postoperative prealbumin levels were reduced, and peak postoperative leukocyte counts were elevated in POAF patients. Multivariable analysis identified that patients with POAF had longer hospital LOS and lower postoperative prealbumin as factors that independently predict both POAF and increased hospital LOS. Conclusions: New-onset POAF patients had a substantial perioperative inflammatory burden characterized by preoperative hypertension, postoperative leukocytosis, and decreased prealbumin and had prolonged hospital LOS compared with patients without POAF. Postoperative leukocyte and prealbumin levels should be monitored, as these pro-inflammatory markers may forecast POAF.

Abstract The historical rise of intensive agricultural practices is hypothesized to be related to declines of grassland and aerial insectivorous birds. Drivers of declines may also influence the overall abundance and spatial distribution of insects within agricultural landscapes. Subsequently, the food provisioning rate of birds breeding within more agro‐intensive landscapes may be impacted. Lower provisioning rates in agro‐intensive landscapes may lead not only to reduced growth rate, body condition, or fledging success of nestlings but also to diminished body condition of food provisioning adults. Results from a previous study supported this hypothesis as the fledging success and proxies of nestling body condition were lowest for an aerial insectivore breeding in more agro‐intensive landscapes. Of the multiple hypotheses put forward to explain these correlations, one mechanism may act through variation in food provisioning rates. In this study, we expounded on this hypothesis using data derived from the aforementioned study system and assessed if provisioning rates to nestlings and food provisioning behavior of adults varied across a gradient of agricultural intensification in a declining aerial insectivore, the Tree Swallow (Tachycineta bicolor). We found that the hourly provisioning rate was lower in agro‐intensive landscapes, and yet travel distances were longest within less agro‐intensive landscapes. Our results highlight that, in order to maximize long‐term average gain rates, Tree Swallows breeding within agro‐intensive landscapes must forage with greater intensity, perhaps at a cost to themselves, or else costs will transfer to growing broods. Our work provides further evidence that agricultural intensification on the breeding grounds can contribute to the declines of aerial insectivores in part through a trophic pathway.

Objectives: The investigators conducted a psychosocial needs assessment of mesothelioma patients through self-report measures of quality of life (QOL), coping, depression, and social support. Methods: Patients with malignant pleural mesothelioma (MPM) (N  = 67) completed a battery of assessments at a single timepoint after being approached during routine medical oncology clinic appointments or by letter. Results: Participants were predominately male (70.0%; n  = 47) and ranged in age from 35 to 83 years old (M  = 65.61, SD = 9.71). Most participants were white (88.0%; n  = 59), and 10.0% (n  = 7) were identified as Hispanic. The majority were married or living with a partner (93.0%; n  = 62) and had some college or more education (64.0%; n  = 43). Fourteen percent of participants (n  = 11) endorsed significantly elevated depression symptoms. No significant demographic or clinical differences in depressed compared to nondepressed participants were observed, with a trend toward those identifying as Hispanic and those who were divorced as being more likely to be depressed. For the total sample, the most frequently endorsed coping strategies were active coping, emotional support, and acceptance. Significance of results: The present study did not identify any clear correlates of depression or QOL among patients with MPM. This research contributes to the small literature on psychosocial functioning in patients with MPM and provides putative directions for future larger studies and the development of interventions to provide appropriate support to diverse patients with MPM. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objective: To present a rare case of parathyromatosis. Methods: We present the clinical, laboratory, and imaging findings, along with a review of the literature. Results: A 33-year-old man with a history of right upper parathyroid adenoma removal 5 years prior due to hyperparathyroidism was admitted for severe hypercalcemia (15.6 mg/dL; normal, 8.5 to 10.5 mg/dL) with elevated plasma parathyroid hormone (PTH) (882 pg/mL; normal, 15 to 65 pg/mL). Ultrasound, computed tomography (CT), sestamibi, and positron emission tomography scans were unremarkable; however, a four-dimensional CT (4DCT) of the neck showed an area of increased signal enhancement and hypervascularity without discrete nodule in the posterior right thyroid region. The patient underwent parathyroid surgical exploration with right hemithyroidectomy and compartment neck dissection to remove the affected tissue. PTH levels dropped to 208 pg/mL postoperatively; calcium decreased but remained elevated at 12.7 mg/dL. Pathology revealed the presence of several small nodular foci of atypical hyperplastic parathyroid tissue in the right thyroid and soft tissue in the left central neck compartment consistent with parathyromatosis. Conclusion: This case report represents the first-time use of 4DCT to localize parathyromatosis. Parathyromatosis is a rare but problematic cause of recurrent hyperparathyroidism. Ultrasound and 4DCT may represent the best imaging modalities for identification and perioperative management to remove all affected tissue without reseeding.

Purpose: Epidemiologic data from several populations suggest that metformin may decrease cancer risk and mortality in patients with colorectal cancer (CRC) and type II diabetes mellitus (DM). Although type II DM and CRC are major health problems in the Middle East, no investigations have been performed to test the effect metformin has on the outcome of patients with type II DM and CRC who are also treated with metformin. Materials and Methods: We retrospectively reviewed the medical records of 1,902 patients diagnosed with CRC at King Hussein Cancer Center between January 2004 and December 2012, and identified 349 patients (18%) with type II DM; we censored the data of 28 patients because their antidiabetic medications were unknown. We then categorized these 321 patients into two groups: 192 patients treated with metformin (group A) and 129 patients treated with other antidiabetic medications (group B). Results: Group A patients had significantly longer overall survival (89 months; 95% CI, 66 to 112 months) and progression-free survival (47 months; 95% CI, 15 to 79 months) than group B patients (overall survival: 36 months; 95% CI, 24 to 48 months; P ≤ .001; progression-free survival: 21 months; 95% CI, 13 to 29 months; P = .016). After adjustment for age, sex, body mass index, aspirin use, anticholesterol treatment, and CRC stage, group A patients had a 40% reduction in mortality (hazard ratio, 0.58; 95% CI, 0.4% to 0.85%; P = .005). Conclusion: Our results support findings from other populations that patients with diabetes and CRC who are also treated with metformin have better outcomes than those treated with other antidiabetic medications.

Governing land use to achieve sustainable outcomes is challenging, because land systems manifest complex land use spillovers—i.e. processes by which land use changes or direct interventions in land use (e.g. policy, program, new technologies) in one place have impacts on land use in another place. The ERL issue ‘Focus on Leakage: informing Land-Use Governance in a Tele-coupled World’ builds on discussions in an international expert workshop conducted in Berlin in November 2017 to explore innovative ways to improve our understanding of how governance interventions, new technologies and other factors can affect land-use change both directly and indirectly through spillovers. This editorial starts by clarifying the definitions and relationships between land-use spillover , indirect land use change —a form of spillover where land use change in one place is caused by land use change in another place— leakage —a form of land use spillover, which is caused by an environmental policy (e.g. a conservation or restoration intervention), and the spillover reduces the overall benefits and effectiveness of this intervention—, and land use displacement processes. We then use this terminology to summarize the individual contributions of this special issue and conclude with lessons learned as well as directions for future research.

Long-term structural plasticity of dendritic spines plays a key role in synaptic plasticity, the cellular basis for learning and memory. The biochemical step is mediated by a complex network of signaling proteins in spines. Two-photon imaging techniques combined with two-photon glutamate uncaging allows researchers to induce and quantify structural plasticity in single dendritic spines. However, this method is laborious and slow, making it unsuitable for high throughput screening of factors necessary for structural plasticity. Here we introduce a MATLAB-based module built for Scanimage to automatically track, image, and stimulate multiple dendritic spines. We implemented an electrically tunable lens in combination with a drift correction algorithm to rapidly and continuously track targeted spines and correct sample movements. With a straightforward user interface to design custom multi-position experiments, we were able to adequately image and produce targeted plasticity in multiple dendritic spines using glutamate uncaging. Our methods are inexpensive, open source, and provides up to a five-fold increase in throughput for quantifying structural plasticity of dendritic spines.

Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy.