bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombotic Thrombocytopenic Purpura associated with Pembrolizumab
Authors: Nelson Derrick , Kodsi Marina , Cockrell Dillon , Morgan Jennifer , Key Nigel 
Published: January 2022

Introduction Thrombotic thrombocytopenic purpura (TTP) is a life threatening type of thrombotic microangiopathy (TMA) caused by a deficiency in ADAMTS13. Here, we describe a case of TTP in association with pembrolizumab treatment for metastatic urothelial carcinoma. Case report Our patient was a 68-year-old male who received three cycles of pembrolizumab. Shortly after he developed an acute onset of numbness of the right side of his arm and face, slurred speech, generalized weakness, loss of appetite and shortness of breath. Initial laboratory changes in emergency department revealed hyponatremia, elevation in blood urea nitrogen (BUN) and serum creatinine, decreased hemoglobin, significant thrombocytopenia and leukocytosis. His thrombocytopenia continued to worsen, reaching low levels of 19,000 × 10 9 /L. Given the presence of schistocytes, a PLASMIC score was calculated (5). ADAMTS13 activity and inhibitor returned 8% (ref. >80%) and 3% (ref. <0.4%), respectively. The patient passed away. Management & outcome He received two 500 mL normal saline boluses and 1 unit of packed red blood cells (pRBC) as well as an extensive imaging workup. On admission, his renal function and platelet counts continued to decline. Given multiple comorbitidies his family opted out of further treatment and the patient ultimately passed away. Discussion Pembrolizumab could possibly induce TMA. In this case the abnormal ADAMTS13 activity level makes TTP more likely, though through an unknown mechanism. Although immunotherapies play an important role in the field of oncology, the effects are not entirely cell specific and unwarranted treatment related complications should be considered.
Veliparib for the treatment of solid malignancies
Authors: George Rony R , Thomas Rimisha , Davice Anna , Mathew Meby S 
Published: January 2022

Objective Veliparib is a poly adenosine diphosphate ribose polymerase (PARP) −1 and −2 inhibitor with chemo-sensitizing and anticancer activities that has shown promising results in early-phase trials. The aim of this comprehensive review is to summarise the profile of veliparib and to provide an overview of its early clinical investigations. Data Sources Details of all the completed trials evaluating the profile of veliparib were identified from ClinicalTrials.gov with the relevant keywords. Furthermore, databases such as Google Scholar and PubMed were searched using the National Clinical Trial (NCT) number to retrieve publications of results not listed in the trial registry. Data Summary A total of 25 completed clinical trials indicating the use of veliparib in solid malignancies were identified. The results showed that veliparib is well tolerated, both as a single agent and in combination with standard chemotherapy doses. Being a broad-spectrum potentiator of DNA-damaging agents and radiation, it has shown to improve the clinical outcomes, particularly in solid tumors like ovarian cancer, breast cancer and lung cancer. Conclusions The results from clinical trials indicate that veliparib can be an excellent therapeutic strategy for BRCA mutation associated cancers and tumors bearing deficiencies in the HR pathway as well. Further studies establishing the dosing, sequence of therapy, extended use and compatibility with various anti-cancer drugs are warranted to define its exact role in cancer therapy.
Potential negative pharmacodynamic interaction of spironolactone and abiraterone in two prostate cancer patients
Authors: Vicente-Valor Juan , Escudero-Vilaplana Vicente , Collado-Borrell Roberto , López-López Cristina , Villanueva-Bueno Cristina , Revuelta-Herrero José Luis , Ruiz-Briones Paula , Somoza-Fernández Beatriz , Herranz Ana , Sanjurjo María 
Published: January 2022

Introduction Spironolactone when combined with abiraterone in metastatic castration-resistant prostate cancer (mCRPC) may theoretically exert androgenic properties, thereby compromising the therapeutic effectiveness of abiraterone. Case report Two patients with a medical history of cardiovascular disease and mCRPC combined spironolactone within the course of abiraterone regimen. The abiraterone-spironolactone interaction was identified using the Lexicomp® interaction tool (classified as risk C). Management & outcome Spironolactone treatment was maintained as it was considered beneficial due to the cardiac condition. The prostate-specific antigen (PSA) levels started to rise when these two drugs were used together. Eventually, tumour progression was observed. Discussion There is increasing evidence that spironolactone behaves as a selective androgen receptor modulator. Strategies to overcome abiraterone-spironolactone interaction could involve the use of eplerenone, although this drug is also controversial. The best strategy should imply a multidisciplinary evaluation by cardiologists and oncologists.
A multicenter retrospective study on 4480 implanted PICC-ports: A GAVeCeLT project
Authors: Bertoglio Sergio , Annetta Maria Giuseppina , Brescia Fabrizio , Emoli Alessandro , Fabiani Fabio , Fino Maria , Merlicco Domenico , Musaro Andrea , Orlandi Marina , Parisella Laura , Pinelli Fulvio , Reina Simona , Selmi Valentina , Solari Nicola , Tricarico Fausto , Pittiruti Mauro 
Published: January 2022

Background: PICC-ports may be defined as totally implantable central venous devices inserted in the upper limb using the current state-of-the-art techniques of PICC insertion (ultrasound-guided venipuncture of deep veins of the arm, micro-puncture kits, proper location of the tip preferably by intracavitary ECG), with placement of the reservoir at the middle third of the arm. A previous report on breast cancer patients demonstrated the safety and efficacy of these devices, with a very low failure rate. Methods: This retrospective multicenter cohort study—developed by GAVeCeLT (the Italian Group of Long-Term Venous Access Devices)—investigated the outcomes of PICC-ports in a large cohort of unselected patients. The study included 4480 adult patients who underwent PICC-port insertion in five Italian centers, during a period of 60 months. The primary outcome was device failure, defined as any serious adverse event (SAE) requiring removal. The secondary outcome was the incidence of temporary adverse events (TAE) not requiring removal. Results: The median follow-up was 15.5 months. Device failure occurred in 52 cases (1.2%), the main causes being local infection ( n = 7; 0.16%) and CRBSI ( n = 19; 0.42%). Symptomatic catheter-related thrombosis occurred in 93 cases (2.1%), but removal was required only in one case (0.02%). Early/immediate and late TAE occurred in 904 cases (20.2%) and in 176 cases (3.9%), respectively. Conclusions: PICC-ports are safe venous access devices that should be considered as an alternative option to traditional arm-ports and chest-ports when planning chemotherapy or other long-term intermittent intravenous treatments.
Exploring the Use of Player Load in Elite Soccer Players
Authors: Oliva-Lozano José M. , Conte Daniele , Fortes Víctor , Muyor José M. 
Published: January 2022

Background: The aims of this study were to (1) analyze the distribution of the player load (PLTOTAL) in 3 axes of movement (PLAP, anterior-posterior; PLML, medial-lateral; PLV, vertical) during elite soccer matches, (2) investigate the effect of playing position on PL-related variables, and (3) explore the association between PLTOTAL and distance covered by the players. Hypothesis: Despite different load distribution between axes of movement, PLTOTAL might be used as a body load indicator for all playing positions. Study Design: Longitudinal study. Level of Evidence: Level 3. Methods: Data were collected from elite soccer players using WIMU Pro tracking systems, which included inertial sensors. Results: The axis of movement had a significant effect on the distribution of the load ( P < 0.001; conditional R2 = 0.91), with the greatest contribution from the PLV ( P < 0.001; d = 5.41-5.86). Moreover, no effect of playing position on PLTOTAL, PLV, PLML, or PLAP was observed ( P > 0.05). Finally, a large correlation was found between PLTOTAL and distance covered, and the linear mixed model showed that distance may be predicted by the PLTOTAL (conditional R2 = 0.81; P < 0.001). Conclusion: Differences in load distribution were based on the axis of movement, although playing position had no effect on any variable. The selection of either distance covered, which is representative of a 2-dimensional analysis, or PLTOTAL, which is representative of a 3-dimensional analysis, may be adequate for monitoring locomotor demands or accelerometer-derived load. Clinical Relevance: Training strategies that focus on the vertical component of match play should be adopted. In addition, given that PLTOTAL is an accelerometry-based metric, which combines the accelerations in anterior-posterior, medial-lateral, and vertical planes, strength and conditioning coaches may use this parameter as a measure of total body load.
Amelioration of DMH-induced colon cancer by eupafolin through the reprogramming of apoptosis-associated p53/Bcl2/Bax signaling in rats
Authors: Wang Congcong , Qiao Xiao , Wang Jingwen , Yang Jia , Yang Chen , Qiao Yi , Guan Yue , Wen Aidong , Jiang Liuqin 
Published: January 2022

Introduction: Colorectal cancer is the third most common malignancy and the second most deadly cancer worldwide. In this present study, the effects of eupafolin on DMH-induced colon cancer in rats were assessed. Methods: The acute and sub-acute oral toxicity study in the balb/c mice was performed to evaluate the LD50 dose and the chemotherapeutic doses of eupafolin. The colon cancer was induced in the animals through a single intraperitoneal injection (i.p) of 30 mg/kg of dimethylhydrazine followed by 2% DSS for 7 days in the drinking water in male Wistar rats. The rats were treated with eupafolin (50, 100, and 200 mg/kg) through oral route for 18 weeks. The animals were sacrificed and colon tissues were subsequently investigated for aberrant crypt foci (ACF), in vivo antioxidant studies, histology and immunohistochemical analysis, and apoptosis by TUNNEL technique after 18 weeks of eupafolin therapy. Results: The acute oral toxicity data represented the LD50 dose of eupafolin which was found to be 500 mg/kg body weight. Along with that, the sub-acute toxicity study suggested the chemotherapeutic doses of eupafolin, that is, 50, 100, and 200 mg/kg body weight. Eupafolin therapy inhibits ACF development in rat colon mucosa efficiently. Additionally, eupafolin has improved the colonic lesions and the structural integrity of the colonic mucosa. Eupafolin therapy causes anti-oxidant enzymes such as superoxide dismutase, catalase, and glutathione to increase as well. Increased levels of P53, BAX, and PCNA and a simultaneous decrease in Bcl2 and IL-6 expressions show eupafolin therapy successfully regulated these biological markers in colorectal cancer. Eupafolin also induced apoptosis efficiently in the rat colon mucous membrane. Conclusion: These results show that eupafolin can improve colon cancer by modulating the p53, Bcl2, BAX, and IL-6 pathways in rats.
Epidemiology of Pediatric Basketball Injuries Presenting to Emergency Departments: Sex- and Age-Based Patterns
Authors: Zynda Aaron J. , Wagner K. John , Liu Jie , Chung Jane S. , Miller Shane M. , Wilson Philip L. , Ellis Henry B. 
Published: January 2022

Background: There is limited epidemiologic data on pediatric basketball injuries and the comparison of these injuries before and after adolescence and between male and female athletes. Purpose: To assess common sex- and age-based injury patterns in pediatric basketball players. Study Design: Descriptive epidemiology study. Methods: Injury data from the National Electronic Injury Surveillance System (NEISS) and participation data from the National Sporting Goods Association were used to complete this study. Data on pediatric basketball injuries between January 2012 and December 2018 in patients aged 7 to 11 years (childhood) and 12 to 17 years (adolescence) were extracted and used to calculate national injury incidence rates with 95% CIs. Sex and age group patterns were examined utilizing Pearson chi-square tests. Z tests were conducted for the comparison of injury rates between female and male athletes in each age group and overall injury rate across age groups. Results: An average of 9582 basketball injuries were reported annually in the NEISS, which calculated to an annual national estimate of 294,920 injuries. The most common diagnoses were ankle strain/sprain (17.7%), finger strain/sprain/fracture (12.1%), concussion/head injury (9.4%), knee strain/sprain (4.5%), and facial laceration (3.3%). There was a significant increase in injury prevalence in adolescents (12- to 17-year-old category: 238,678 injuries per year) when compared with childhood (7- to 11-year-old category: 56,242 injuries per year) ( P < .0001). Concussions/head injuries occurred at a high rate in childhood, second only to finger strain/sprain/fracture, and at a similar rate in females and males (injuries per 100,000 athlete-days: 4.9 [95% CI, 3.1-6.7] vs. 5.9 [4.3-7.5], respectively; P = .41). From childhood to adolescence, injury prevalence increased for all areas and across both sexes, except for female finger strain/sprain/fracture; however, the rate of increase for concussion/head injuries and knee injuries was significantly higher in female compared with male athletes ( P < .0001 for both). In adolescents, ankle injuries were the most common injury overall. Conclusion: Ankle injuries continue to be the most predominant pediatric basketball injury. However, disproportionate rates of both knee and concussion/head injuries in female athletes during adolescent basketball are of concern and have implications for injury prevention.
Perioperative Pain Management Practices Vary Across Time and Setting for Pediatric ACL Reconstruction: Trends From a National Database in the United States
Authors: Markiewitz Nathan D. , Swarup Ishaan , Talwar Divya , Muhly Wallis T. , Wells Lawrence , Williams Brendan A. 
Published: January 2022

Background: Surgical and anesthetic techniques have enabled a shift to the ambulatory setting for the majority of patients with anterior cruciate ligament (ACL) tears. While this change likely reflects improvements in acute pain management, little is known about national trends in pediatric perioperative pain management after ACL reconstruction (ACLR). Purpose: To describe recent trends in the United States in perioperative pain management for pediatric ACLR. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Pediatric patients (age, ≤18 years) who underwent ACLR with peripheral nerve blocks between January 2008 and December 2017 were identified in the Pediatric Health Information System database. We modeled the use of oral and intravenous analgesic medications over time using Bayesian logistic mixed models. Models were adjusted for patient age, sex, race, primary payer, and treatment setting (ambulatory, observation, or inpatient). Results: The study criteria produced a sample of 18,605 patients. Older children were more likely to receive intravenous acetaminophen, intravenous ketorolac, and oral and intravenous opioids. Younger children were more likely to receive ibuprofen. In our adjusted logistic model, treatment setting was found to be an independent predictor of the utilization of all medications. We found an increase in the overall utilization of oral acetaminophen (adjusted odds ratio [adj OR], 1.14 [95% CI, 1.04-1.23]), intravenous acetaminophen (adj OR, 1.42 [95% CI, 1.22-1.65]), and oral opioids (adj OR, 1.16 [95% CI, 1.06-1.28]) over the study period at a typical hospital. We found significant heterogeneity in medication use across hospitals, with the most heterogeneity in intravenous acetaminophen. Other studied descriptive variables did not appear to predict practices. Conclusion: After adjusting for patient characteristics and treatment settings, pain management strategies varied among hospitals and over time. Patient age and treatment setting predicted practices. Regional anesthesia, opioid medications, and intravenous ketorolac remained the mainstays of treatment, while intravenous acetaminophen emerged in use over the course of the study period. The variability in the pain management of pediatric patients undergoing ACLR suggests that further study is necessary to establish the most effective means of perioperative pain management in these patients.
Social communication in fragile X syndrome: pilot examination of the Brief Observation of Social Communication Change (BOSCC)
Authors: Shaffer Rebecca , Thurman Angela John , Ronco Lucienne , Cadavid Diego , Raines Shane , Kim So Hyun 
Published: January 2022

Abstract
Background
Social communication is a key area of difficulty in fragile X syndrome (FXS) and there are not yet adequate outcome measurement tools. Appropriate outcome measures for FXS have been identified as a key area of research interest in order to evaluate future therapeutic trials. The Brief Observation of Social Communication Change-Minimally Verbal (BOSCC-MV), an outcome measure with strong psychometrics developed for autism spectrum disorder, has promise as an outcome measure to assess social communication change with FXS participants.

Methods
We examined the BOSCC-MV via central coders in this multi-site-trial to assess its appropriateness for FXS. Eighteen minimally verbal males ages 3–12 years were enrolled and assessed on two consecutive days and 7 participants completed a third visit 6 months later. We examined test-retest reliability, inter-rater reliability, and both convergent and divergent validity with standard clinical measures including the Autism Diagnostic and Observation Schedule-2, Vineland 3, Social Responsiveness Scale, and the Aberrant Behavior Checklist.

Results
The BOSCC-MV in FXS demonstrated strong inter-rater and test-retest reliability, comparable to previous trials in idiopathic ASD. Strong convergent validity was found with Autism Diagnostic Observation Schedule-2 and Vineland-3. Divergent validity was demonstrated between BOSCC-MV and unrelated measures.

Conclusions
The BOSCC-MV shows promise as a FXS social communication outcome measure, warranting further large-scale evaluation.
Molecular mechanism of mulberry response to drought stress revealed by complementary transcriptomic and iTRAQ analyses
Authors: Li Ruixue , Su Xueqiang , Zhou Rong , Zhang Yuping , Wang Taichu 
Published: January 2022

AbstractBackgroundThe use of mulberry leaves has long been limited to raising silkworms, but with the continuous improvement of mulberry (Morus alba) resource development and utilization, various mulberry leaf extension products have emerged. However, the fresh leaves of mulberry trees have a specific window of time for picking and are susceptible to adverse factors, such as drought stress. Therefore, exploring the molecular mechanism by which mulberry trees resist drought stress and clarifying the regulatory network of the mulberry drought response is the focus of the current work.ResultsIn this study, natural and drought-treated mulberry grafted seedlings were used for transcriptomic and proteomic analyses (CK vs. DS9), aiming to clarify the molecular mechanism of the mulberry drought stress response. Through transcriptome and proteome sequencing, we identified 9889 DEGs and 1893 DEPs enriched in stress-responsive GO functional categories, such as signal transducer activity, antioxidant activity, and transcription regulator activity. KEGG enrichment analysis showed that a large number of codifferentially expressed genes were enriched in flavonoid biosynthesis pathways, hormone signalling pathways, lignin metabolism and other pathways. Through subsequent cooperation analysis, we identified 818 codifferentially expressed genes in the CK vs. DS9 comparison group, including peroxidase (POD), superoxide dismutase (SOD), aldehyde dehydrogenase (ALDHs), glutathione s-transferase (GST) and other genes closely related to the stress response. In addition, we determined that the mulberry geneMaWRKYIII8(XP_010104968.1) underwent drought- and abscisic acid (ABA)-induced expression, indicating that it may play an important role in the mulberry response to drought stress.ConclusionsOur research shows that mulberry can activate proline and ABA biosynthesis pathways and produce a large amount of proline and ABA, which improves the drought resistance of mulberry.MaWRKYIII8was up-regulated and induced by drought and exogenous ABA, indicating thatMaWRKYIII8may be involved in the mulberry response to drought stress. These studies will help us to analyse the molecular mechanism underlying mulberry drought tolerance and provide important gene information and a theoretical basis for improving mulberry drought tolerance through molecular breeding in the future.
Safe birth in cultural safety in southern Mexico: a pragmatic non-inferiority cluster-randomised controlled trial
Authors: Sarmiento Iván , Paredes-Solís Sergio , de Jesús García Abraham , Maciel Paulino Nadia , Serrano de los Santos Felipe René , Legorreta-Soberanis José , Zuluaga Germán , Cockcroft Anne , Andersson Neil 
Published: January 2022

AbstractBackgroundAvailable research on the contribution of traditional midwifery to safe motherhood focuses on retraining and redefining traditional midwives, assuming cultural prominence of Western ways. Our objective was to test if supporting traditional midwives on their own terms increases cultural safety (respect of Indigenous traditions) without worsening maternal health outcomes.MethodsPragmatic parallel-group cluster-randomised controlled non-inferiority trial in four municipalities in Guerrero State, southern Mexico, withNahua,Na savi,Me’phaaandNancue ñomndaaIndigenous groups. The study included all pregnant women in 80 communities and 30 traditional midwives in 40 intervention communities. Between July 2015 and April 2017, traditional midwives and their apprentices received a monthly stipend and support from a trained intercultural broker, and local official health personnel attended a workshop for improving attitudes towards traditional midwifery. Forty communities in two control municipalities continued with usual health services. Trained Indigenous female interviewers administered a baseline and follow-up household survey, interviewing all women who reported pregnancy or childbirth in all involved municipalities since January 2016. Primary outcomes included childbirth and neonatal complications, perinatal deaths, and postnatal complications, and secondary outcomes were traditional childbirth (at home, in vertical position, with traditional midwife and family), access and experience in Western healthcare, food intake, reduction of heavy work, and cost of health care.ResultsAmong 872 completed pregnancies, women in intervention communities had lower rates of primary outcomes (perinatal deaths or childbirth or neonatal complications) (RD -0.06 95%CI − 0.09 to − 0.02) and reported more traditional childbirths (RD 0.10 95%CI 0.02 to 0.18). Among institutional childbirths, women from intervention communities reported more traditional management of placenta (RD 0.34 95%CI 0.21 to 0.48) but also more non-traditional cold-water baths (RD 0.10 95%CI 0.02 to 0.19). Among home-based childbirths, women from intervention communities had fewer postpartum complications (RD -0.12 95%CI − 0.27 to 0.01).ConclusionsSupporting traditional midwifery increased culturally safe childbirth without worsening health outcomes. The fixed population size restricted our confidence for inference of non-inferiority for mortality outcomes. Traditional midwifery could contribute to safer birth among Indigenous communities if, instead of attempting to replace traditional practices, health authorities promoted intercultural dialogue.Trial registrationRetrospectively registeredISRCTN12397283. Trial status: concluded.