bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between childhood maltreatment and the prevalence and complexity of multimorbidity: A cross-sectional analysis of 157,357 UK Biobank participants
Authors: Hanlon Peter , McCallum Marianne , Jani Bhautesh Dinesh , McQueenie Ross , Lee Duncan , Mair Frances S 
Published: July 2020

Background: Child maltreatment is associated with long-term conditions (LTCs) in adulthood. Its relationship to multimorbidity (≥2 LTCs) is less clear. We explore the relationship between child maltreatment, multimorbidity and factors complicating management. Methods: Cross-sectional analysis of 157,357 UK Biobank participants. Experience of four maltreatment types (physical/sexual/emotional/neglect) was identified. We explored the relationship between type, number and frequency of maltreatment and LTC count (0, 1, 2, 3, ≥4) using multinomial logistic regression. Binary logistic regression assessed the relationship between maltreatment and self-rated health, loneliness, social isolation, frailty and widespread pain in those with multimorbidity, adjusting for sociodemographics and lifestyle factors. Results: 52,675 participants (33%) experienced ≥1 type of maltreatment; 983 (0.6%) experienced all four. Type, frequency and number of types of maltreatment were associated with higher LTC count. People experiencing four types of maltreatment were 5 times as likely to have a LTC count of ≥4 as those experiencing none (odds ratio (OR): 5.16; 99% confidence interval (CI): 3.77-7.07). Greater number of types of maltreatment was associated with higher prevalence of combined physical/mental health LTCs (OR: 2.99; 99% CI: 2.54–3.51 for four types of maltreatment). Compared to people who reported no maltreatment, people experiencing all four types of maltreatment were more likely to have poor self-rated health (OR: 3.56; 99% CI: 2.58–4.90), loneliness (OR: 3.16; 99% CI: 2.17–4.60), social isolation (OR: 1.45; 99% CI: 1.03–2.05), widespread pain (OR: 3.19; 99% CI: 1.87–5.44) and frailty (OR: 3.21; 99% CI: 2.04–5.05). Conclusion: Peoplewith a history of maltreatment have higher LTC counts and potentially more complicated management needs reinforcing calls for early intervention.
Vitamin D level in the rotator cuff muscle and serum correlates with postoperative muscle performance at 1 year after rotator cuff repair
Authors: Rhee Sung-Min , Jeong Hyeon Jang , Oh Joo Han 
Published: July 2020

Objectives: Previously, we reported that tissue vitamin D (tVD) in the rotator cuff muscle had strong correlation with pre-operative serum vitamin D (sVD). Furthermore, tVD reflected more on the preoperative muscle power. This study was a follow-up study to evaluate correlations of tVD, vitamin D receptor (VDR), and postoperative sVD with rotator cuff muscle performance, fatty degeneration, healing failure, and functional outcomes at 1 year after rotator cuff repair (RCR). Methods: Between March and October in 2017, 36 patients who underwent RCR were prospectively enrolled and 26 patients were followed at 1 year postoperatively and analyzed. tVD was assessed using liquid chromatography, and the VDR was measured by western blotting. sVD was checked preoperatively, 6 months, and 1 year post-operatively. At 1 year after surgery, isokinetic muscle performance test (IMPT), ASES score and Constant score were evaluated, and MRI was used to analyze fatty degeneration and the healing failure. Results: The mean level of sVD at 1 year post-operatively was 20.5 ± 9.2 ng/ml. Only six patients had normal level of sVD (> 20 ng/ml, 23.1%), while 19 patients had insufficiency (10 - 20 ng/ml, 73.0%), and one patient had defi-ciency (< 10 ng/ml, 3.8%). Lower sVD at pre-operatively had lower sVD at 6 months and 1 year post-operatively (all p < 0.05). Higher pre-operative and 1 year post-operative sVD had less deficiency of IMPT in abduction (pre-operative, post-operative; CC; Abduction, -0.324, -0.395, p = 0.047, 0.041, respectively) How-ever, no correlation was found in deficiency of IMPT in ER, IR (pre-operative, post-operative; CC; ER, IR; 0.025, -0.042; p = 0.926, 0.874, respectively; post-operative; CC; ER, IR; -0.250, -0.157; p = 0.333, 0.548, re-spectively). Although, there was no correlation was found between torque of muscle power at 1 year post-operatively with pre- and post-operative sVD (all p > 0.05), higher tVD had higher torque of abduction (CC: 0.440, p = 0.043), and showed tendency of higher torque of external rotation (ER) (CC: 0.335, p = 0.077). There was no correlation of tVD and sVD with functional outcomes, fatty degeneration and re-tear rate (all p > 0.05). VDR showed no correlation with any variables (all p > 0.05). Conclusions: tVD and sVD showed positive correlation with rotator cuff muscle performance at 1 year after RCR. Regarding lower sVD at pre-operatively had lower sVD at 1 year post-operatively, and considering lower sVD had higher deficiency of muscle power, supplementation of vitamin D to these patients with low sVD would enhance rota-tor cuff muscle performance postoperatively.
Shoulder Instability, Performance and Return to Play in National Hockey League Athletes
Authors: McCormick Kyle , Tedesco Liana , Herndon Carl , Ahmad Christopher , Levine William , Popkin Charles , Swindell Hasani 
Published: July 2020

Objectives: Hockey players are at risk for various injury due to the aggressive nature of gameplay with the rate of shoulder injuries ranges from 8.6% to 21.9%. Although performance and return to play outcomes following shoulder instability events have been analyzed in other contact sports, there is a paucity of information on the effects amongst professional hockey players. Our study investigates the incidence of shoulder instability events in the National Hockey League (NHL) and the subsequent effect on return-to-play (RTP) and player performance. We hypothesized that NHL players sustaining a shoulder instability event returned to play at a high rate without significant changes in player performance after injury. Methods: A total of 67 confirmed in-season shoulder instability events were identified in the NHL between 2003 - 2017. Demographic characteristics and performance statistics one year prior to injury and one year following injury were collected and analyzed. Overall RTP was determined and differences in performance following injury were compared to experience-matched, era-matched, position-matched and age-matched controls. A separate analysis was performed comparing differences in performance as a function of operative and nonoperative treatment. Results: An average of 4.19 shoulder dislocations occurred per season in the NHL with an overall incidence rate of 0.020 instability events per 1000 game exposures (CI 0.017-0.027) with no significant differences between forwards and defensemen (p = 0.871). Overall, 33.8% of players suffered season ending injuries but 98.5% of all players were able to return to play with an average of 26.3±20.8 regular season games missed. Compared to controls, players suffering a shoulder instability event experienced an increase in both average time on ice and shooting percentage upon returning to gameplay (p = 0.002, p <0.001, respectively) yet there were no significant differences in seasons played, goals, assists and points per game; offensive, defensive and overall point shares compared to controls. In terms of treatment, 47.8% of all players were treated operatively with half of these players treated with surgery after suffering season-ending injuries. Compared to operative treatment, conservatively managed players experienced a significant decrease in points per game after injury (p = 0.034), however there were no significant differences in number of seasons played, goals per game, assists per game, offensive, defensive and overall point shares between treatment groups. Conclusion: Regardless of treatment, professional hockey players experience a high rate of return to play with acceptable performance outcomes following in-game shoulder instability events. Surgical management can be beneficial as an increase in points per game was seen in those treated operatively compared to players managed nonoperatively.
Superior Labral Anterior Posterior Repair and Biceps Tenodesis Surgery: Trends of the American Board of Orthopaedic Surgery Database
Authors: Frantz Travis , Gowd Anirudh , Erickson Brandon , Romeo Anthony , Cvetanovich Gregory 
Published: July 2020

Objectives: Recent evidence has specified indications for performing Superior Labrum Anterior and Posterior (SLAP) repair and biceps tenodesis (BT) for the treatment of bicipital-labral lesions in the shoulder. Trends in performance of these procedures are expected to reflect the growing body of research regarding this topic. The purpose of this study was to report practice trends for the surgical treatment of SLAP lesions, particularly in older patients, as the management of isolated SLAP lesions remains controversial. Methods: The American Board of Orthopaedic Surgery (ABOS) database was retrospectively queried between 2012-2017 by Current Procedural Terminology for SLAP repair (29807), open BT (23430), and arthroscopic BT (29828). The patient population was excluded if any concomitant open shoulder procedure was performed. Trends over time were evaluated with respect to case volume, patient age, surgeon subspecialty. Separate trends were evaluated with and without concomitant arthroscopic rotator cuff repair (RCR, CPT: 29827). Results: A total of 9,908 cases met inclusion/exclusion criteria: 4,632 performed with RCR and 5,276 performed without. Mean age of patients without RCR was 40.8 +/- 13.8, while those receiving RCR was 55.0 +/- 9.9 years . In patients without RCR, there was a significant decline in rate of SLAP repairs performed over this period (p < 0.001). No significant change was noted in mean age of patients receiving arthroscopic BT, open BT, SLAP repair, and BT + SLAP. A significantly greater proportion of patients receiving open and arthroscopic BT were over 35 years old, compared to those receiving SLAP repair (p < 0.001). Within the RCR cohort, there was also a significant decline in concomitant SLAP repairs performed (p < 0.001) over the study period. With respect to biceps tenodesis, in the RCR cohort, open was performed in 52.2% of cases while arthroscopic was performed in 47.8%, while in the cohort without RCR open was performed in 74.9% and arthroscopic was performed in 25.9%. Conclusion: The ABOS database reveals significantly reduced rates of SLAP repairs being performed. Trends with age remain consistent over time, in that SLAP repairs were predominantly performed in younger patients. Arthroscopic biceps tenodesis was performed much more frequently with RCR than without.
One-Year MRI Outcomes of Osteochondral Allograft Transplantation of the Knee for Large Chondral Defects: Comparison of Elliptical, Stacked, and Single Allografts
Authors: Wang Dean , Ode Gabriella , Elbuluk Ameer , Burge Alissa , Jones Kristofer , Williams Riley , Coxe Francesca 
Published: July 2020

Objectives: Osteochondral allograft transplantation (OCA) is a proven cartilage restoration procedure for patients with large chondral defects. However, elongated condylar lesions pose a challenge for dowel OCA in restoring articular surface congruity. Recently, instrumentation to harvest a single, elliptical allograft has been developed for treating ovoid lesions without requiring an adjacent-plug (stacked or snowman) technique. The purpose of this study was to compare 1-year MRI outcomes of patients treated with elliptical, stacked, or single OCA using the Osteochondral Allograft MRI Scoring System (OCAMRISS) and percent osseous integration. Methods: A retrospective review on patients treated from 2000 to 2018 with OCA for condylar defects of the knee was conducted. Inclusion criteria included those followed prospectively with a MRI at ˜1 year after surgery. OCAMRISS and osseous integration scores (0-25%; 26-50%; 51-75%; 76%-100%) were graded by a musculoskeletal radiologist blinded to the outcomes. Comparisons of demographics and MRI scores were performed with the ANOVA. Results: A total of 57 knees (mean age, 35.8 years; 70% male) met the inclusion criteria and were treated with either elliptical (n=19), stacked (n=19), or single (n=19) OCA. Mean time to post-operative MRI was 10.7, 11.1, and 12.4 months, respectively (p=0.17). There were no significant differences in demographics or number of prior ipsilateral knee surgeries among groups. Defect characteristics were significantly different between groups, where single plugs treated a higher percentage of LFC defects (58%) compared to elliptical and stacked (26%, each) (p=0.02). Total chondral defect area was greatest in the stacked group (5.4 ± 1.3) compared to elliptical (4.6 ± 1.2) and single (4.6 ± 1.4) (p=0.12). Bone, cartilage, ancillary, and total OCAMRISS scores were not significantly different between groups. A trend towards a higher percentage of osseous integration (single>stacked>elliptical) was noted which correlated with less transplanted allograft bone, however, these differences were not significant (p=0.15). Conclusion: One-year OCAMRISS and osseous integration scores did not differ among patients treated with elliptical, stacked, or single OCA. Further investigation is needed to explore potential differences in clinical outcomes and long-term osseous integration between elliptical and stacked OCA for the treatment of elongated condylar defects of the knee. [Table: see text]
Increased Costs and Health Care Utilization Associated with Delay in Diagnosis of ACL Injuries
Authors: Cook Sara , Byrnes Thomas , Hagen Mia , Gee Albert , Kweon Christopher , Slattery Casey 
Published: July 2020

Objectives: Anterior cruciate ligament (ACL) injuries can be difficult to diagnose, especially among providers with limited musculoskeletal training. Early and accurate diagnosis of ACL injuries is important for initiating proper treatment and limiting inefficient or costly healthcare utilization. We hypothesized that a delayed diagnosis in patients sustaining ACL injuries would result in treatment that is more costly and utilizes more healthcare resource compared to patients diagnosed without delay. Methods: A large national private insurance database (Truven MarketScan) was utilized to identify all patients aged 10-63 years-old diagnosed with an ACL tear from 2011 through 2015. Patients with a possible delay in diagnosis were determined via a database search for the most commonly assigned alternative knee-related diagnosis codes found in patients who were later diagnosed with an ACL tear. Patients were stratified into three groups according to time from non-specific knee diagnosis code to ACL diagnosis: 1) no delay (0 days), short delay (1-30 days) and long delay (>30 days). Subsequent cost and healthcare utilization data including physical therapy, medication use, and number of clinic visits were collected for a period of one-year after initial presentation with an ACL tear or knee-related diagnosis. Results: A search from 2011 through 2015 identified 87,435 patients meeting inclusion criteria that were diagnosed with an ACL injury. There were 24.1% of patients diagnosed at initial presentation whereas 43.5% were diagnosed between one day and 30 days. There were 38.2% of patients that were treated without surgery and had the lowest total cost regardless of delay in diagnosis (Table 1). ACL reconstruction combined with other knee procedures had the highest total cost, particularly with a longer delay in diagnosis. Each day of delay in diagnosis was three times more costly in the non-surgical (additional $27.06 cost per day of delay) versus the surgical groups ($8.09 cost per day of delay). Conclusions: A timely diagnosis of ACL injuries is associated with a lower cost of treatment and less visits to healthcare providers. Non-operative injuries may benefit the most from a timely diagnosis given the high additional cost per day of diagnosis delay. In order to further decrease the burden on the healthcare system, future studies should assess methods than can decrease delays in diagnosis while measuring cost and utilization differences as well as outcomes after ACL tears.
SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells
Authors: Okamoto Yusuke , Abe Masako , Mu Anfeng , Tempaku Yasuko , Rogers Colette B. , Mochizuki Ayako L. , Katsuki Yoko , Kanemaki Masato T. , Takaori-Kondo Akifumi , Sobeck Alexandra , Bielinsky Anja-Katrin , Takata Minoru 
Published: July 2020

Abstract
Fanconi anemia (FA) is a hereditary disorder caused by mutations in any 1 of 22 FA genes. The disease is characterized by hypersensitivity to interstrand crosslink (ICL) inducers such as mitomycin C (MMC). In addition to promoting ICL repair, FA proteins such as RAD51, BRCA2, or FANCD2 protect stalled replication forks from nucleolytic degradation during replication stress, which may have a profound impact on FA pathophysiology. Recent studies showed that expression of the putative DNA/RNA helicase SLFN11 in cancer cells correlates with cell death on chemotherapeutic treatment. However, the underlying mechanisms of SLFN11-mediated DNA damage sensitivity remain unclear. Because SLFN11 expression is high in hematopoietic stem cells, we hypothesized that SLFN11 depletion might ameliorate the phenotypes of FA cells. Here we report that SLFN11 knockdown in the FA patient-derived FANCD2-deficient PD20 cell line improved cell survival on treatment with ICL inducers. FANCD2−/−SLFN11−/− HAP1 cells also displayed phenotypic rescue, including reduced levels of MMC-induced chromosome breakage compared with FANCD2−/− cells. Importantly, we found that SLFN11 promotes extensive fork degradation in FANCD2−/− cells. The degradation process is mediated by the nucleases MRE11 or DNA2 and depends on the SLFN11 ATPase activity. This observation was accompanied by an increased RAD51 binding at stalled forks, consistent with the role of RAD51 antagonizing nuclease recruitment and subsequent fork degradation. Suppression of SLFN11 protects nascent DNA tracts even in wild-type cells. We conclude that SLFN11 destabilizes stalled replication forks, and this function may contribute to the attrition of hematopoietic stem cells in FA.
What is the future of immunotherapy in multiple myeloma?
Authors: Rasche Leo , Hudecek Michael , Einsele Hermann 
Published: July 2020

Abstract
The treatment of multiple myeloma (MM) is currently being redefined by humoral and cellular immunotherapies. For decades, there was limited belief in immune-based anti-MM therapy as a result of the moderate graft-versus-myeloma effect of allogeneic stem cell transplantation. Today, monoclonal antibodies comprise the new backbone of anti-MM therapy, and T-cell therapies targeting BCMA are emerging as the most potent single agents for MM treatment. Herein, we present our assessment of and vision for MM immunotherapy in the short and midterm.
The integrin-linked kinase is required for chemokine-triggered high-affinity conformation of the neutrophil β2-integrin LFA-1
Authors: Margraf Andreas , Germena Giulia , Drexler Hannes C. A. , Rossaint Jan , Ludwig Nadine , Prystaj Barbara , Mersmann Sina , Thomas Katharina , Block Helena , Gottschlich Wiebke , Liu Chang , Krenn Peter W. , Haller Hermann , Heitplatz Barbara , Meyer zu Brickwedde Marika , Moser Markus , Vestweber Dietmar , Zarbock Alexander 
Published: July 2020

Abstract
Neutrophil adhesion and extravasation into tissue at sites of injury or infection depend on binding of the integrin lymphocyte function–associated antigen 1 (LFA-1) to ICAM-1 expressed on activated endothelial cells. The activation-dependent conformational change of LFA-1 to the high-affinity conformation (H+) requires kindlin-3 binding to the β2-integrin cytoplasmic domain. Here we show that genetic deletion of the known kindlin interactor integrin-linked kinase (ILK) impaired neutrophil adhesion and extravasation in the cremaster muscle and in a clinically relevant model of renal ischemia reperfusion injury. Using in vitro microfluidic adhesion chambers and conformation-specific antibodies, we show that knockdown of ILK in HL-60 cells reduced the conformational change of β2-integrins to the H+ conformation. Mechanistically, we found that ILK was required for protein kinase C (PKC) membrane targeting and chemokine-induced upregulation of its kinase activity. Moreover, PKC-α deficiency also resulted in impaired leukocyte adhesion in bone marrow chimeric mice. Mass spectrometric and western blot analyses revealed stimulation- and ILK-dependent phosphorylation of kindlin-3 upon activation. In summary, our data indicate an important role of ILK in kindlin-3–dependent conformational activation of LFA-1.
Tissue factor pathway inhibitor is required for cerebrovascular development in mice
Authors: Maroney Susan A. , Westrick Randal J. , Cleuren Audrey C. , Martinez Nicholas D. , Siebert Amy E. , Zogg Mark , Ginsburg David , Weiler Hartmut , Mast Alan E. 
Published: July 2020

Abstract
Tissue factor pathway inhibitor (TFPI) inhibits proteases in the blood coagulation cascade that lead to the production of thrombin, including prothrombinase (factor Xa [FXa]/FVa), the catalytic complex that directly generates thrombin. Thus, TFPI and FV are directly linked in regulating the procoagulant response. Studies using knockout mice indicate that TFPI and FV are necessary for embryogenesis, but their contributions to vascular development are unclear. We performed extensive histological analyses of Tfpi−/− and Tfpi−/−F5−/− mouse embryos to investigate the importance of the interplay between TFPI and FV in regulating hemostasis and vascular development during embryogenesis. We observed normal tissue development throughout Tfpi−/− embryos, except in the central nervous system (CNS). The CNS displayed stunted brain growth, delayed development of the meninges, and severe vascular pathology characterized by the formation of glomeruloid bodies surrounding areas of cellular death, fibrin deposition, and hemorrhage. Removing FV from Tfpi−/− embryos completely ameliorated their brain pathology, suggesting that TFPI dampens FV-dependent procoagulant activity in a manner that modulates cerebrovascular development. Thus, we have identified a previously unrecognized role for TFPI activity within the CNS. This TFPI activity likely diminishes an effect of excess thrombin activity on signaling pathways that control cerebral vascular development.