Oncogenic Signaling Pathways in The Cancer Genome Atlas.

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFß signaling, p53 and ß-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these pathways, and 57% percent of tumors had at least one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy.

Use of Spinal Anesthesia during Thoracic Endovascular Aortic Repair.

BACKGROUND: The purpose of this study was to assess outcomes after spinal anesthesia (SA) versus general anesthesia (GA) in patients undergoing thoracic endograft placement and to evaluate the adjunctive use of cerebrospinal fluid drainage (CSFD) placement. METHODS: A single-center retrospective review of patients that underwent thoracic endograft placement from 2001 to 2019 was performed. Patients were stratified based on the type of anesthesia they received: GA, SA or epidural, GA with CSFD, and SA with CSFD. Primary outcomes included 30-day mortality and length of stay (LOS). Baseline characteristics were analyzed with Student's t-test and Pearson's chi-squared test. Multivariate logistic regression analysis was performed to identify risk factors for 30-day mortality and longer LOS. RESULTS: A total of 333 patients underwent thoracic endograft placement; 104 patients received SA, 180 patients received GA, 30 patients received GA and CSFD, and 19 patients received SA and CSFD. Of the total patients, 16.2% underwent thoracic endograft placement for type B aortic dissection, 3.3% for type A aortic dissection, and 12.3% for penetrating ulcer. The mean age of the study population was 68.7 years old. Patients undergoing SA were older with a mean age of 73.4 years versus 64.7 years for patients undergoing GA (P < 0.001). Spinal anesthesia (SA) was preferred in patients at high risk for GA (>75 years old: 52.9% vs. 33.3%, P < 0.001; renal comorbidities: 20.6% vs. 10.6%, P = 0.03, and current smokers: 26.7% vs. 9.6%, P < 0.001). Length of stay (LOS) was decreased in the SA group (4.29 days vs. 9.70 days, P < 0.001). There was a lower incidence of spinal cord ischemia in the SA group (1.0% vs. 2.2%, P = 0.44), as well as significantly decreased 30-day mortality (0% vs. 5.6%, P = 0.01), reintervention (19.2% vs. 26.8%, P = 0.02), and return to the operating room (6.8% vs. 12.7%, P = 0.02). Of the 19 patients that had SA + CSFD, there were no signs and symptoms of spinal cord ischemia and decreased incidence of perioperative complications (0% vs. 33.3%, P = 0.01). There was no difference in the risk for intraoperative complications, neurologic complications, or 30-day mortality between GA + CSFD patients versus SA + CSFD patients. Age >75 (P = 0.002), intraoperative complications (P < 0.001), and perioperative complications (P = 0.02) were associated with increased mortality after thoracic endograft placement per multivariate logistic regression analysis. CONCLUSIONS: Spinal anesthesia (SA) in select high-risk patients was associated with reduced 30-day mortality, neurologic complications, and LOS compared to GA. The concurrent use of spinal drainage and SA had satisfactory results compared to spinal drainage and GA.

Mid-term outcomes following reverse total shoulder arthroplasty.

PURPOSE: The utilization of reverse total shoulder arthroplasty now exceeds the incidence of anatomic shoulder arthroplasty. Previous mid-to-long-term studies on rTSA have reported a decrease in shoulder function as follow-up increased. The purpose of this study was to provide data on mid-term outcomes and implant survival in a series focusing on reverse total shoulder arthroplasty. MATERIALS AND METHODS: Demographic information such as age at surgery, revision surgery status, BMI, and smoking status were recorded. The clinical endpoints measured in this study were range of motion scores (forward elevation, external rotation, internal rotation) and patient reported outcomes (VAS, ASES, SST). Radiographic variables captured included preoperative glenoid morphology, humeral lucency, and glenoid loosening. RESULTS: Fifty-six shoulders were included in this study. The overall mean age at surgery was 72.5 ± 7.2 years with an average follow-up time of 6.8 ± 3.5 years. The mean BMI was 28.1 ± 5.5. All measurements of range of motion saw significant and sustained improvements. Overall, forward elevation improved from 82° preoperatively to 133° postoperatively (p < 0.01). External rotation improved from 23° preoperatively to 36° (p < 0.01), while internal rotation improved from L3 to L1 (p = 0.05). ASES scores improved from 31 preoperatively to 70 postoperatively (p < 0.01). SST scores improved from 2 preoperatively to 7 (p < 0.01). VAS pain index scores improved from 6 to 2 following surgery (p < 0.01). Postoperative scapular notching was seen in 18 patients at final follow-up. Glenoid loosening was seen in 3 shoulders. Humeral loosening was seen in 18 shoulders. Tuberosity resorption was seen in 8 shoulders. The 5 year survival estimate was 98%, and the 10 year survival estimate was 83%. CONCLUSION: In this series, we found that rTSA provides mid-term improvements in range of motion in patients while reducing pain levels. When considered together, this demonstrates that most patients undergoing rTSA can have excellent use of their shoulder from age at surgery to end-of-life.

A Convergent Total Synthesis of (+)-Ineleganolide.

We report the total synthesis of the furanobutenolide-derived diterpenoid (+)-ineleganolide. The synthetic approach relies on a convergent strategy based on the coupling of two enantioenriched fragments, which are derived from (-)-linalool and (+)-norcarvone, respectively. A high-yielding, one-step Michael addition and aldol cascade furnishes a pentacyclic framework as a single diastereomer, thereby overcoming previous challenges in controlling stereochemistry. The endgame features an O2-facilitated C-H oxidation and a samarium diiodide-induced semipinacol rearrangement to furnish the highly rigid central seven-membered ring.

Does body mass index influence long-term outcomes after anatomic total shoulder arthroplasty?

BACKGROUND: As of 2018, upwards of 42% of the US adult population was considered obese based on body mass index (BMI) scales. With the annual number of total joint replacements increasing, this study aimed to evaluate the impact BMI has on anatomic total shoulder arthroplasty (aTSA) outcomes. METHODS: This was a retrospective analysis of 128 shoulders requiring primary aTSA. Patients were stratified into 3 cohorts based on their BMI at surgery: underweight/normal weight (U/NW; BMI ≤25.0), overweight (25.0 < BMI ≤ 30.0), and obese (BMI >30.0). BMI was separately analyzed as a continuous variable. Clinical endpoints were range of motion scores, including forward elevation, external rotation, and internal rotation, and patient-reported outcomes, including visual analog scale (VAS) scores, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores, and the Simple Shoulder Test (SST). Survivorship curves were calculated using Kaplan-Meier analysis. RESULTS: Forty-four, 50, and 34 patient shoulders were in the U/NW, overweight, and obese cohorts, respectively. The mean follow-up time was 11.4 years. The U/NW cohort had more females (73%) compared with the overweight (34%; P = .0030) and obese (35%; P = .0015) groups; no differences were seen in revision rates. BMI was negatively correlated with age at surgery (r = -0.19, P = .014); it was not correlated with any of the 6 postoperative clinical endpoints. All 3 cohorts saw significant improvements in forward elevation, external rotation, internal rotation and VAS, ASES, and SST scores when compared preoperatively to postoperatively (P < .001). There were no significant differences between the 3 cohorts with respect to postoperative range of motion. Postoperative ASES scores were higher for the overweight cohort (82.6 ± 18.6) compared with both the U/NW (63.0 ± 25.1) and obese cohorts (70.5 ± 26.8) (P < .001). The overweight cohort also had higher SST (P = .0012) postoperative scores compared with the U/NW and obese cohorts; VAS scores were comparable between groups (P = .12). The nonobese (BMI <30) group (n = 94) showed 5-, 10-, and 15-year implant survival of 98.9%, 94.9%, and 83.9%, respectively compared to 97.1%, 93.7%, and 87.0% in the obese (BMI ≥30) group (n = 34). The log rank test revealed no significant difference in survival curves (P = .82). CONCLUSION: To our knowledge, this is the longest follow-up study analyzing clinical endpoints stratified by BMI for aTSA. We saw that patients with a higher BMI required shoulder replacement at a significantly younger age. However, we also report that regardless of BMI, all patients saw significant improvements in patient-reported outcomes and range of motion scores postoperatively.

Clusters of comorbidities in fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is a type of interstitial lung disease (ILD) with a variable disease course and prognosis ranging from inflammatory and self-limiting to irreversible and progressive pulmonary fibrosis. Comorbidities are common in HP and may have an impact on prognosis. Due to the heterogeneity of HP presentation and progression, the identification of specific phenotypes in relationship to disease course and outcome is essential. The aim of this study was to identify clusters of comorbidities which could represent phenotypes in fibrotic HP and examine their impact on prognosis. METHODS: Patients diagnosed with fibrotic HP at a tertiary referral center for ILD were included. Comorbidities were systematically registered and clusters of comorbidities were identified using cluster analyses. Disease progression and survival was estimated for each cluster. RESULTS: The cohort comprised 211 patients with 53.6% males, mean age 63.0, baseline FVC 72.7%, DLCO 44.1%. Median follow-up time was 1.8 years (IQR 0.7-3.9). Three clusters with distinct comorbidity profiles and clinical characteristics were identified. One cluster dominated by elder male patients with predominantly cardiovascular diseases was associated with more respiratory hospitalizations and a worse prognosis. Differences in pulmonary function or exercise capacity trajectories between clusters were not observed. CONCLUSIONS: Three clusters with distinct comorbidities were identified and could represent phenotypes in fibrotic HP not previously recognized. The worst prognosis was observed in a cluster dominated by elder males with cardiovascular diseases. Increased focus on prevention and treatment of comorbidities could potentially improve the prognosis of patients with fibrotic HP.

Surgery for pouch inflow limb-related complications: Crohn's disease or something else?

PURPOSE: A total proctocolectomy with subsequent creation of an ileal-pouch, such as a J-pouch or a Kock pouch, has been the most common surgery performed for ulcerative colitis (UC). A small portion of these patients will develop complications with the inflow limb into the pouch requiring operative intervention. The objective was to establish a better understanding as to the pathological mechanism by which these pouch inflow limb problems develop. METHODS: This was a retrospective cohort study conducted at a single tertiary care inflammatory bowel disease (IBD) center. A database was created of all the patients who underwent pouch-related procedures, following completion of their original pouch, between 2006 and 2018. The patients requiring operative resection for inflow limb complications were identified among this cohort. Operative and pathological data were collected. RESULTS: One hundred seventy-eight UC patients underwent surgeries on their pouches between 2006 and 2018. Sixteen patients required operative resection for inflow limb problems. Reoperations for inflow limb problems included inflow limb resection with pouch excision (n = 4) and inflow limb resection with pouch revision (n = 12). The pathology findings of the inflow limb were consistent with Crohn's disease in 9 patients (56%). Two other patients (total 69%) were eventually diagnosed with Crohn's disease due to other pathological specimens or perianal pathology. The remaining patients had chronic, non-specific enteritis/serositis. CONCLUSIONS: A small proportion of pouch patients will eventually require surgery for inflow limb complications. Among these, there was a high rate of Crohn's disease of the inflow limb and overall change in diagnosis to Crohn's disease (Plietz et al. in Official Journal of the American College of Gastroenterology | ACG 114:S453, 2019).

Pathway Commons 2019 Update: integration, analysis and exploration of pathway data.

Pathway Commons (https://www.pathwaycommons.org) is an integrated resource of publicly available information about biological pathways including biochemical reactions, assembly of biomolecular complexes, transport and catalysis events and physical interactions involving proteins, DNA, RNA, and small molecules (e.g. metabolites and drug compounds). Data is collected from multiple providers in standard formats, including the Biological Pathway Exchange (BioPAX) language and the Proteomics Standards Initiative Molecular Interactions format, and then integrated. Pathway Commons provides biologists with (i) tools to search this comprehensive resource, (ii) a download site offering integrated bulk sets of pathway data (e.g. tables of interactions and gene sets), (iii) reusable software libraries for working with pathway information in several programming languages (Java, R, Python and Javascript) and (iv) a web service for programmatically querying the entire dataset. Visualization of pathways is supported using the Systems Biological Graphical Notation (SBGN). Pathway Commons currently contains data from 22 databases with 4794 detailed human biochemical processes (i.e. pathways) and ∼2.3 million interactions. To enhance the usability of this large resource for end-users, we develop and maintain interactive web applications and training materials that enable pathway exploration and advanced analysis.

Identifying modifiable and nonmodifiable cost drivers of ambulatory rotator cuff repair: a machine learning analysis.

INTRODUCTION: Implementing novel tools that identify contributors to the cost of orthopedic procedures can help hospitals maximize efficiency, minimize waste, improve surgical decision-making, and practice value-based care. The purpose of this study was to develop and internally validate a machine learning algorithm to identify key drivers of total charges after ambulatory arthroscopic rotator cuff repair and compare its performance with a state-of-the-art statistical learning model. METHODS: A retrospective review of the New York State Ambulatory Surgery and Services Database was performed to identify patients who underwent elective outpatient rotator cuff repair (RCR) from 2015 to 2016. Initial models were constructed using patient characteristics (age, gender, insurance status, patient income, Elixhauser Comorbidity Index) as well as intraoperative variables (concomitant procedures and services, operative time). These were subsequently entered into 5 separate machine learning algorithms and a generalized additive model using natural splines. Global variable importance and partial dependence curves were constructed to identify the greatest contributors to cost. RESULTS: A total of 33,976 patients undergoing ambulatory RCR were included. Median total charges after ambulatory RCR were $16,017 (interquartile range: $11,009-$22,510). The ensemble model outperformed the generalized additive model and demonstrated the best performance on internal validation (root mean squared error: $7112, 95% confidence interval: 7036-7188; logarithmic root mean squared error: 0.354, 95% confidence interval: 0.336-0.373, R2: 0.53), and identified major drivers of total charges after RCR as increasing operating room time, patient income level, number of anchors used, use of local infiltration anesthesia/peripheral nerve blocks, non-White race/ethnicity, and concurrent distal clavicle excision. The model was integrated into a web-based open-access application capable of providing individual predictions and explanations on a case-by-case basis. CONCLUSION: This study developed an ensemble supervised machine learning algorithm that outperformed a sophisticated statistical learning model in predicting total charges after ambulatory RCR. Important contributors to total charges included operating room time, duration of care, number of anchors used, type of anesthesia, concomitant distal clavicle excision, community characteristics, and patient demographic factors. Generation of a patient-specific payment schedule based on the Agency for Healthcare Research and Quality risk of mortality highlighted the financial risk assumed by physicians in flat episodic reimbursement schedules given variable patient comorbidities and the importance of an accurate prediction algorithm to appropriately reward high-value care at low costs.

Research in the Time of COVID: Virtual Fellowships at the Linda Hall Library.

When COVID-19 prevented scholars from traveling to libraries, archives, and museums, staff at those institutions devised creative strategies for providing remote access to their holdings. This article examines one such initiative launched by the Linda Hall Library of Science, Engineering, and Technology in Kansas City, Missouri. The Library's prioritization of print over archival materials, experience fulfilling document delivery requests, and investments in digitization infrastructure facilitated the transition to a completely virtual fellowship program during the 2021-22 academic year. Although virtual fellowships could not replicate every aspect of in-person residencies, they nonetheless supplied scholars with much-needed funding, research materials, and membership in a scholarly community. Based on the program's initial success, the Library plans to continue offering virtual fellowships to scholars otherwise unable to conduct research on site.

Stereocontrolled Radical Bicyclizations of Oxygenated Precursors Enable Short Syntheses of Oxidized Abietane Diterpenoids.

The power of cation-initiated cyclizations of polyenes for the synthesis of polycyclic terpenoids cannot be overstated. However, a major limitation is the intolerance of many relevant reaction conditions toward the inclusion in the substrate of polar functionality, particularly in unprotected form. Radical polycyclizations are important alternatives to bioinspired cationic variants, in part owing to the range of possible initiation strategies, and in part for the functional group tolerance of radical reactions. In this article, we demonstrate that Co-catalyzed MHAT-initiated radical bicyclizations are not only tolerant of oxidation at virtually every position in the substrate, oftentimes in unprotected form, but these functional groups can also contribute to high levels of stereochemical control in these complexity-generating transformations. Specifically, we show the effects of protected or unprotected hydroxy groups at six different positions and their impact on stereoselectivity. Further, we show how multiply oxidized substrates perform in these reactions, and finally, we document the utility of these reactions in the synthesis of three aromatic abietane diterpenoids.

Comorbidities and survival in patients with chronic hypersensitivity pneumonitis.

INTRODUCTION: Chronic Hypersensitivity Pneumonitis (cHP) is a fibrotic interstitial lung disease (ILD) resulting from repeated exposure to an offending antigen. Prognostication in cHP remains challenging, and the relationship between comorbidities and survival has yet to be characterized. The aim of this study was to describe the relationship between comorbid conditions and survival in patients with cHP. METHODS: The prospective database from a tertiary referral centre for ILD was reviewed for patient-reported comorbidities, their frequency, and relationship with survival in cHP patients. Comorbidities were assessed by direct questioning of the patient at the baseline visit and by a standardized questionnaire for the diagnosis of interstitial lung diseases. During the follow-up examinations, patients were asked about newly diagnosed comorbidities. RESULTS: Two hundred eleven patients with cHP were identified (mean age 63 years, 53% male, mean FVC 73%), with mean follow-up of 32 months. The mean number of comorbidities was 3 (10% had 0, 59% 1-3 and 31% ≥4 comorbidities). Most frequent comorbidities groups were cardiovascular (65%) and respiratory (26%), most common comorbidities were hypertension (56%), gastro-esophageal reflux disease (GERD) (24%), diabetes (20%) and coronary heart disease (18%). In general, deceased patients had more comorbidities than survivors (p = 0.005), yet there was no association between the absolute number of comorbidities and survival. Pulmonary hypertension (30.8% versus 5.7%, p = 0.001;), diastolic dysfunction (26.9% versus 6.4%, p = 0.004) and cerebrovascular disease were more frequent in non-survivors (23.1% versus 7.6%, p = 0.026). Lung cancer was not observed, and neither GERD nor antacid drugs were associated with outcome (p = 0.357 and p = 0.961, respectively). CONCLUSIONS: Comorbidities are common in cHP are associated with survival. Further work should determine whether interventions for these specific comorbidities can positively affect survival.

Hartmann's reversal: factors affecting complications and outcomes.

AIM: Hartmann's procedure is commonly performed emergently for infectious, inflammatory, or malignant processes. Most patients historically do not undergo reversal, and those who do have been found to suffer significant morbidity. The aim of this study was to study factors associated with complications after Hartmann's reversal and to provide information and guidance to surgeons. METHOD: A retrospective review of patients undergoing Hartmann's reversal between May 2002 and October 2017 was conducted at a tertiary medical center. Data included patient characteristics at the time of surgery and intra- and postoperative complications. Chi-square test was used for categorical variables. The Wilcoxon signed rank or t test where appropriate was used for multivariate analysis. RESULTS: Two hundred forty-nine patients were included. Mean age at reversal was 58.8 years, and 114 (58%) were male. Sixty-two (31.8%) patients experienced a major complication following reversal. Eight (4%) patients had an anastomotic leak. Thirteen (6.67%) patients had an intra-abdominal abscess which required either IR or operative drainage. Patients who experienced a major complication were more likely to have an ASA 4 at time of reversal (14.3% vs. 4.24%, p = 0.019), liver disease (6.6% vs. 0.8%, p = 0.021), and BMI < 30 (35% vs. 17.3%, p = 0.020). CONCLUSIONS: Nearly one-third of patients who had reversal surgery experienced a major complication. Four percent of patients undergoing reversal had an anastomotic leak, comparable to previously reported rates. Patients with ASA 4, liver disease, and BMI < 30 were at higher risk of a major complication following reversal. Patients who underwent laparoscopic reversal had no significant difference in outcomes. AIM: What does this paper add to the literature? The decision of whether to reverse a colostomy after Hartmann's procedure. Our study aims to identify risk factors associated with complications after Hartmann's reversal to better guide surgeon's facing the dilemma of whether or not to reverse the stoma.

Comparison of Subacromial Injection and Interscalene Block for Immediate Pain Management After Arthroscopic Rotator Cuff Repair.

PURPOSE: To compare the efficacy of a subacromial injection (SAI) with a single-shot interscalene block (ISB) for immediate postoperative pain relief after outpatient arthroscopic rotator cuff repair (ARCR). METHODS: We performed a retrospective chart review of consecutive patients who underwent ARCR. Patients received either an ISB before the procedure or an SAI after the procedure. Preoperative baseline patient characteristics were collected and compared. Visual analog scale (VAS) pain scores were recorded preoperatively, at 15-minute intervals over a 120-minute period in the postanesthesia care unit (PACU), and at discharge. Differences in VAS scores between groups were compared with known values of the minimal clinically important difference, and the percentage of patients with VAS scores below the patient acceptable symptom state was tabulated. Differences between preoperative characteristics were assessed using the Mann-Whitney U, Fisher exact, or χ2 test. The Mann-Whitney U test was also used to evaluate VAS scores and total time spent in the PACU between groups. RESULTS: The median VAS score was significantly lower in the ISB group at PACU admission, at all intervals throughout the PACU stay, and at discharge (P < .0001). The median total time in the PACU was 107 minutes (25th percentile-75th percentile, 90-120 minutes) and 210 minutes (25th percentile-75th percentile, 175-274 minutes) in the ISB and SAI groups, respectively (P < .0001). Between-group differences in VAS scores were greater than the values of the minimal clinically important difference at each measured interval. A total of 98% and 67% of patients in the ISB and SAI groups, respectively, were discharged with VAS scores below the patient acceptable symptom state of 3. CONCLUSIONS: Patients receiving an ISB experience significantly less pain than those receiving an SAI. In addition, they are discharged home from the PACU in half the time as patients receiving an SAI. On the basis of the comparative efficacy, an SAI cannot replace an ISB after ARCR. The ISB should therefore remain the standard of care as an adjunct to postoperative analgesia for patients who undergo outpatient ARCR. LEVEL OF EVIDENCE: Level III, retrospective, comparative therapeutic trial.

Stereospecific and Chemoselective Copper-Catalyzed Deaminative Silylation of Benzylic Ammonium Triflates.

A method for the synthesis of benzylsilanes starting from the corresponding ammonium triflates is reported. Silyl boronic esters are employed as silicon pronucleophiles, and the reaction is catalyzed by copper(I) salts. Enantioenriched benzylic ammonium salts react stereospecifically through an SN 2-type displacement of the ammonium group to afford α-chiral silanes with inversion of the configuration. A cyclopropyl-substituted substrate does not undergo ring opening, thus suggesting an ionic reaction mechanism with no benzyl radical intermediate.

Transbronchial Cryobiopsies for Diagnosing Interstitial Lung Disease: Real-Life Experience from a Tertiary Referral Center for Interstitial Lung Disease.

BACKGROUND: Transbronchial cryobiopsy (cTBB) may offer an alternative to surgical lung biopsy (SLB) for histopathological diagnosis of interstitial lung diseases (ILDs). However, real-life experience is limited, although case series are increasingly reported. OBJECTIVES: We aimed to evaluate the value of cTBB performed under real-life conditions in a tertiary care center for ILDs. METHODS: Data on all patients undergoing a cTBB for evaluation of suspected ILD between October 2015 and January 2017 were included in this retrospective case series. Procedure details, complication rates, histopathological results, and diagnostic consensus reached by a multidisciplinary team (MDT) discussion were collated and evaluated. RESULTS: A total of 109 patients (mean age 64 years, range 19-85; 66% male, 38% never smokers) referred to our center with features suggestive of ILD underwent cTBB. The mean FVC% predicted was 77% (range 41-131), with a mean DLCO of 51% (range 20-86), and a 6-min walking test (6MWT) of 402 m (range 100-642). On average, 4 samples were taken from each patient (range 1-8), with a mean biopsy diameter of 5 mm (range 2-12). Complications included pneumothorax (11.9%), all treated with chest drain. Moderate bleeding occurred in 28.4% (all resolved without active measures). No acute disease exacerbations and no deaths occurred. A histopathological pattern diagnosis was possible in 80 cases (73.4%), and 26.6% of cases were considered nonspecific. An MDT consensus diagnosis was reached in 83.5% of cases. Subsequent SLB was proposed in 13 cases and performed in 8 cases. CONCLUSIONS: In the real-world setting, cTBB has a meaningful diagnostic value in the context of a MDT approach and may enable histopathological assessment even in patients with more advanced disease unsuitable for SLB.

Community Partners Join Forces: Battling Obesity and Diabetes Together.

Our objectives was to create an initiative to change the culture of a small community to improve quality of life as it relates to health for the residents through the use of health-related educational sessions, a coordinated fitness and nutrition program, and the construction of community fitness trails. We compared the use of a health-focused community driven program to the status quo in seeking opportunities to improve perception and understanding of one's health and overall quality of life for participants. Among the various techniques identified to improve a community's health outcomes, dissemination of information through the use of educational sessions empowered citizens to take control of their health status, and ultimately, their quality of life. This came with zero negative impacts for those providing the education, as well as those participating in the sessions. Although the application of these methods depends on local resources, leadership, and partnerships, programs similar to those presented here can help to improve quality of life for citizens in communities across the country facing the challenges secondary to a sedentary lifestyle.

Using biological pathway data with paxtools.

A rapidly growing corpus of formal, computable pathway information can be used to answer important biological questions including finding non-trivial connections between cellular processes, identifying significantly altered portions of the cellular network in a disease state and building predictive models that can be used for precision medicine. Due to its complexity and fragmented nature, however, working with pathway data is still difficult. We present Paxtools, a Java library that contains algorithms, software components and converters for biological pathways represented in the standard BioPAX language. Paxtools allows scientists to focus on their scientific problem by removing technical barriers to access and analyse pathway information. Paxtools can run on any platform that has a Java Runtime Environment and was tested on most modern operating systems. Paxtools is open source and is available under the Lesser GNU public license (LGPL), which allows users to freely use the code in their software systems with a requirement for attribution. Source code for the current release (4.2.0) can be found in Software S1. A detailed manual for obtaining and using Paxtools can be found in Protocol S1. The latest sources and release bundles can be obtained from biopax.org/paxtools.

Most cited articles involving lacrosse since 1990 primarily focus on concussion and traumatic brain injury.

OBJECTIVES: The purpose of this study was to identify the 50 most-cited publications relating to lacrosse since 1990 and conduct a bibliometric analysis of the identified studies. METHODS: Clarivate Analytics Web of Science database was queried to identify all publication titles, abstracts, and keywords for the term 'lacrosse' on 9 June 2023. The resulting articles were sorted by total number of citations. Titles and abstracts were included based on their relevance to lacrosse. Once the 50 most cited articles were identified, each article was further analyzed to obtain author name, publication year, country of origin, journal name, article type, research topic, competition level, total number of citations, and the level of evidence. Citation density (total number of citations/years since publication) was calculated and recorded for each of the most-cited studies. RESULTS: The 50 most-cited articles were cited 4237 of times with an average of 84 citations per article. The most cited article was cited 637 (15.0%) times. The articles came from 2 different countries, with the United States and Australia comprising 49 and 1 articles, respectively. All articles were published in English. The American Journal of Sports Medicine published the most articles (n = 21, 42.0%). The most studied topic was concussion/traumatic brain injury (n = 18) followed by studies assessing all injuries (n = 7). Collegiate-level lacrosse was the most studied level of competition (n = 22), while high school-level followed (n = 12). CONCLUSIONS: The majority of the 50 most-cited articles related to lacrosse since 1990 focus on the prevalence, diagnosis and identification of concussion/traumatic brain injury in high school and collegiate-level athletes. These articles are predominantly epidemiological or cohort studies with Level III or IV evidence that almost unanimously originate from the United States.