bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association analysis of variants rs35934224 in TXNRD2 and rs6478746 in LMX1B in primary angle-closure and pseudoexfoliation glaucoma
Authors: Kondkar Altaf A , Sultan Tahira , Alobaidan Abdullah S , Azad Taif A , Osman Essam A , Almobarak Faisal A , Lobo Glenn P , Al-Obeidan Saleh A 
Published: August 2021

Objective: Previous genome-wide studies have demonstrated significant pathogenic association between variants rs35934224 within TXNRD2 and rs6478746 near LMX1B in primary open-angle glaucoma. We investigated the association between these variants in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG) patients of Saudi origin. Methods: In a case-control study, DNA samples from 249 controls (135 men and 114 women), 100 PACG cases (44 men and 56 women), and 95 PXG cases (61 men and 34 women) were genotyped by TaqMan® based real-time PCR. Statistical tests were performed to evaluate genetic association with glaucoma types and related clinical indices. Results: The allele frequencies of rs35934224 and rs6478746 did not show significant variation in PACG and PXG than controls, except that the rs35934224[T] allele was found to be significantly low among PXG women (0.10) as compared to controls (0.21) (odds ratio = 0.38, 95% confidence interval = 0.16–0.94, p = 0.024). Rs35934224 genotypes showed a nominal-to-borderline protective association with PACG and PXG among women in different genetic models. However, except for the over-dominant model in PACG ( p = 0.0095), none of the effects survived Bonferroni’s correction ( p < 0.01). Rs6478746 showed no significant genotype or allelic association with PACG and PXG. Regression analysis showed no influence on disease outcome, and neither showed any correlation with intraocular pressure and cup/disk ratio in both PACG and PXG. Conclusions: Variants rs35934224 in TXNRD2 and rs6478746 near LMX1B are not associated with PACG and PXG in the Saudi cohort, but rs35934224 may confer modest protection among women. Further population-based studies are needed to validate these results.
Psychiatrists’ motives for compulsory care of patients with borderline personality disorder – a questionnaire study
Authors: Lundahl Antoinette , Hellqvist Johan , Helgesson Gert , Juth Niklas 
Published: August 2021

IntroductionBorderline personality disorder patients are often subjected to inpatient compulsory care due to suicidal behaviour. However, inpatient care is usually advised against as it can have detrimental effects, including increased suicidality.AimTo investigate what motives psychiatrists have for treating borderline personality disorder patients under compulsory care.Materials and MethodsA questionnaire survey was distributed to all psychiatrists and registrars in psychiatry working at mental health emergency units or inpatient wards in Sweden. The questionnaire contained questions with fixed response alternatives, with room for comments, about the respondents’ motives for practising compulsory care of borderline personality disorder patients. The responses were analysed quantitatively with descriptive statistics, and comments were analysed with qualitative descriptive content analysis.ResultsThe psychiatrists’ views were divided on when it was justified to treat borderline personality disorder patients under compulsory care, as were their views on borderline personality disorder patients’ decision competence. When there was an assessed risk of harm, 53% were positive to compulsory care of decision-competent borderline personality disorder patients and another 31% because they considered the patients to be decision incompetent in such situations. Adding the risk of harm caused many respondents to alter their assessment of the patient from decision competent to decision incompetent.ConclusionThe large variations in doctors’ opinions indicate that the care of borderline personality disorder patients is arbitrary. Further, the assessed risk of harm increases the use of compulsory care, even though such care is advised against in clinical guidelines, has questionable legal support, and could lead to an increased suicide risk over time.
Drug Release and Pharmacokinetic Evaluation of Novel Implantable Mometasone Furoate Matrices in Rabbit Maxillary Sinuses
Authors: You Changcheng , Tseng Ling-Fang , Pappas Alexander , Concagh Danny , Kuang Yina 
Published: August 2021

Background Intranasal corticosteroid sprays (INCSs) used to treat chronic rhinosinusitis are suboptimal due to limited penetration into the middle meatus, rapid clearance, and poor patient compliance. A bioresorbable drug matrix, developed with the XTreoTM drug delivery platform, may overcome the limitations of INCS by providing continuous dosing over several months. Objective To evaluate the in vitro drug release and in vivo pharmacokinetics of novel mometasone furoate (MF) matrices in a rabbit dorsal maxillary osteotomy model. Methods XTreoTM matrices were formulated to consistently elute MF for up to 6 months. Matrices were surgically placed bilaterally into the maxillary sinuses of New Zealand White (NZW) rabbits. Tissue and plasma MF concentrations were measured to assess the in vivo drug delivery. The in vivo and in vitro drug release kinetics of the matrices were quantified and compared to those of rabbits receiving daily Nasonex® MF nasal sprays. Results XTreoTM matrices self-expanded upon deployment to conform to the irregular geometry of the maxillary sinus cavities in the NZW rabbits. Sustained release of MF was demonstrated in vitro and in vivo for 2 MF matrices of distinct release durations and an in vitro–in vivo correlation was established. Therapeutic levels of MF in local tissues were measured throughout the intended dosing durations. In contrast to the variable peaks and troughs of daily nasal sprays, sustained dosing via a single administration of MF matrices was confirmed by quantifiable plasma MF concentrations over the intended dosing duration. Conclusion The XTreoTM MF matrices provided targeted and efficient dosing to local sinus tissues that was superior to INCS. Sustained drug release was confirmed both in vitro and in vivo. The novel XTreoTM technology may provide precisely tuned, long-lasting drug delivery to sinus tissues with a single treatment.
Effect of spironolactone use in pulmonary arterial hypertension – analysis from pivotal trial databases
Authors: Safdar Zeenat , Cho Eunah 
Published: August 2021

Spironolactone, a common diuretic used in the treatment of pulmonary arterial hypertension (PAH), improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type‐B receptor function within pulmonary endothelial cells. Spironolactone has demonstrated vascular remodeling properties and reduced all‐cause mortality in patients with severe heart failure. Despite widespread use, however, its effect on morbidity and mortality in PAH has not been fully explored. A large cohort of PAH patients from a harmonized dataset from four pivotal trials were analyzed to characterize the patient population and outcomes associated with spironolactone treatment. Of 1229 evaluable patients, 74% were female, mean age of 47 ± 15 years, baseline six‐minute walk distance (6MWD) 345 ± 74 m and 75% were World health Organization (WHO) functional class (FC) III/IV. Of the patients receiving spironolactone, 43% were on subcutaneous treprostinil, compared to 29.9% of those patients who were not receiving spironolactone. Long‐term spironolactone‐treated PAH patients were older (p = 0.01), had lower baseline 6MWD (p = 0.01) and cardiac index (p < 0.01), higher baseline Borg dyspnea score (p = 0.01), WHO functional class, and right arterial pressure (p < 0.01). Additionally, spironolactone‐treated patients tended to have higher hazard of clinical worsening (p < 0.01). A propensity analysis was performed and when controlled for disease severity, revealed that spironolactone‐treated patients did not demonstrate improved outcomes in terms of survival and clinical worsening. Across studies, the current analysis has demonstrated that the actions of spironolactone within the context of the PAH disease process may differ from its action in CHF patients. Despite reported outcomes of spironolactone use in patients with left heart disease, these findings may not translate to right heart failure and pulmonary vascular pathology, as similar outcomes have not necessarily been recognized in the PAH patient population. Future studies are needed to explore these findings further.
Effect of dose, dosing intervals, and hypoxic stress on the reversal of pulmonary hypertension by mesenchymal stem cell extracellular vesicles
Authors: Klinger James R , Pereira Mandy , Del Tatto Michael , Dooner Mark S , Wen Sicheng , Quesenberry Peter J , Liang Olin D 
Published: August 2021

RationaleMesenchymal stem cell extracellular vesicles (MSC EVs) reverse pulmonary hypertension, but little information is available regarding what dose is effective and how often it needs to be given. This study examined the effects of dose reduction and use of longer dosing intervals and the effect of hypoxic stress of MSC prior to EV collection.MethodsAdult male rats with pulmonary hypertension induced by Sugen 5416 and three weeks of hypoxia (SuHx‐pulmonary hypertension) were injected with MSC EV or phosphate buffered saline the day of removal from hypoxia using one of the following protocols: (1) Once daily for three days at doses of 0.2, 1, 5, 20, and 100 µg/kg, (2) Once weekly (100 µg/kg) for five weeks, (3) Once every other week (100 µg/kg) for 10 weeks, (4) Once daily (20 µg/kg) for three days using EV obtained from MSC exposed to 48 h of hypoxia (HxEV) or MSC kept in normoxic conditions (NxEV).Main resultsMSC EV reversed increases in right ventricular systolic pressure (RVSP), right ventricular to left ventricle + septum weight (RV/LV+S), and muscularization index of pulmonary vessels ≤50 µm when given at doses of 20 or 100 μg/kg. RVSP, RV/LV+S, and muscularization index were significantly higher in SuHx‐pulmonary hypertension rats treated once weekly with phosphate buffered saline for five weeks or every other week for 10 weeks than in normoxic controls, but not significantly increased in SuHx‐pulmonary hypertension rats given MSC EV. Both NxEV and HxEV significantly reduced RVSP, RV/LV+S, and muscularization index, but no differences were seen between treatment groups.ConclusionsMSC EV are effective at reversing SuHx‐pulmonary hypertension when given at lower doses and longer dosing intervals than previously reported. Hypoxic stress does not enhance the efficacy of MSC EV at reversing pulmonary hypertension. These findings support the feasibility of MSC EV as a long‐term treatment for pulmonary hypertension.
The association between unmet need for contraception and unintended pregnancy among reproductive-age women in Ethiopia
Authors: Wondie Awoke Giletew 
Published: August 2021

Objectives: An unintended pregnancy and unmet need for contraception remains a serious public health issues both in developed and developing countries. This study aimed to investigate the relation between unmet needs for contraception and unintended pregnancy, and identify other factors contributing for unintended pregnancy in Ethiopia. Methods: Data were obtained from the 2016 Ethiopian Demographic and Health Survey. A total of 7590 mothers were included. The planning status of the last pregnancy was the main outcome variable, and the unmet need for contraception was the primary explanatory variable. Bivariate and multiple logistic regressions were carried out. SPSS version 20.0 was used for data analysis. Statistical significance was declared at p < 0.05. Results: More than one-fourth of mothers (26.6%) gave either mistimed or unwanted birth. The rate of unmet need for contraception was 26.5%. Women with unmet need for contraception had (adjusted odds ratio (AOR) = 10.29, 95% confidence interval (CI) = 8.70–12.10) higher odds of experiencing unintended pregnancy than those who met their contraception need. Age, history of pregnancy termination, parity, women’s autonomy, and fertility preference were factors associated with unintended pregnancy. Conclusion: An unintended pregnancy and the unmet need for contraception remain a major public health issue in Ethiopia. A strong positive association between the unmet need for contraception and unintended pregnancy suggests that interventions targeting the unmet need for contraception could reduce unintended pregnancy. Furthermore, empowering women, promoting a clear fertility goal, and improving men’s involvement would reduce unintended pregnancy.
Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia
Authors: Morales Carolina E. , Stieglitz Elliot , Kogan Scott C. , Loh Mignon L. , Braun Benjamin S. 
Published: August 2021

Abstract
Juvenile myelomonocytic leukemia (JMML) is initiated in early childhood by somatic mutations that activate Ras signaling. Although some patients have only a single identifiable oncogenic mutation, others have 1 or more additional alterations. Such secondary mutations, as a group, are associated with an increased risk of relapse after hematopoietic stem cell transplantation or transformation to acute myeloid leukemia. These clinical observations suggest a cooperative effect between initiating and secondary mutations. However, the roles of specific genes in the prognosis or clinical presentation of JMML have not been described. In this study, we investigate the impact of secondary SH2B3 mutations in JMML. We find that patients with SH2B3 mutations have adverse outcomes, as well as higher white blood cell counts and hemoglobin F levels in the peripheral blood. We further demonstrate this interaction in genetically engineered mice. Deletion of Sh2b3 cooperates with conditional Nf1 deletion in a dose-dependent fashion. These studies illustrate that haploinsufficiency for Sh2b3 contributes to the severity of myeloproliferative disease and provide an experimental system for testing treatments for a high-risk cohort of JMML patients.
Stuttering priapism in a patient with sickle cell trait treated with automated red cell exchange transfusion
Authors: Ebraheem Mohammad S. , Verhovsek Madeleine 
Published: August 2021

Abstract
Sickle cell trait (SCT) is typically an asymptomatic carrier state, but sickling complications can occur under extreme conditions. Priapism is known to be associated with sickle cell disease (SCD); The link with SCT is less well established. We report the case of a 19-year-old man with SCT presenting with prolonged priapism and a refractory, stuttering course requiring multiple invasive procedures over a 5-day period with no clear alternative triggers. In light of ongoing, stuttering priapism, he underwent red blood cell (RBC) exchange transfusion with decrease of hemoglobin S from 45.8% to 11.7%. This was followed by immediate and sustained cessation of stuttering priapism, with no further episodes at 5 months. Multiple cases of priapism associated with SCT have been reported in the literature. In most cases invasive interventions were required but RBC exchange was not attempted. RBC exchange has been reported in 2 people with exertional rhabdomyolysis in the context of SCT, with improvement in 1 case. In patients with SCT and priapism, conservative measures are used to treat brief episodes, but invasive management is required for persistent or prolonged episodes. RBC exchange transfusion may be considered for treatment of refractory, stuttering priapism in individuals with SCT.
A phase 1/2 study of thiotepa-based immunochemotherapy in relapsed/refractory primary CNS lymphoma: the TIER trial
Authors: Fox Christopher P. , Ali Ayesha S. , McIlroy Graham , Thust Steffi , Martinez-Calle Nicolás , Jackson Aimee E. , Hopkins Louise M. , Thomas Catherine M. , Kassam Shireen , Wright Josh , Chaganti Sridhar , Smith Jeffery , Chau Ian , Culligan Dominic , Linton Kim M. , Collins Graham P. , Ferreri Andrés J. M. , Lewis David , Davies Andrew J. , Johnson Rod , Auer Dorothee P. , Cwynarski Kate 
Published: August 2021

Abstract
Relapsed or refractory primary central nervous system lymphoma (rrPCNSL) confers a poor prognosis with no accepted standard of care. Very few prospective studies have been conducted in this patient group. This study was a multicenter phase 1/2 study that investigated thiotepa in combination with ifosfamide, etoposide, and rituximab (TIER) for the treatment of PCNSL relapsed or refractory to high-dose methotrexate-based chemotherapy. A 3 + 3 design investigated the recommended phase 2 dose of thiotepa for a single-stage phase 2 cohort by assessing the activity of 2 cycles of TIER against rrPCNSL. The primary outcome was overall response rate. The dose-finding study demonstrated that 50 mg/m2 of thiotepa could be safely delivered within the TIER regimen. No dose-limiting toxicities were encountered in phase 1, and TIER was well-tolerated by the 27 patients treated in phase 2. The most common grade 3 to 4 toxicities were neutropenia (56% of patients) and thrombocytopenia (39%). An overall response was confirmed in 14 patients (52%), which met the prespecified threshold for clinically relevant activity. The median progression-free survival was 3 months (95% confidence interval [CI], 2 to 6 months) and overall survival 5 months (95% CI, 3 to 9 months). Exploratory analyses suggest a greater benefit for thiotepa-naïve patients. Six patients successfully completed autologous stem cell transplantation (ASCT) consolidation, with 4 experiencing durable remissions after a median follow-up of 50 months. The TIER regimen can be delivered safely and is active against rrPCNSL. When it is followed by ASCT, it can provide durable remission and long-term survival. However, for the majority of patients, prognosis remains poor, and novel treatment strategies are urgently needed. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/search as EudraCT 2014-000227-24 and ISRCTN 12857473.
Unusual intramuscular locations as a first presentation of hydatid cyst disease in children: a report of two cases
Authors: Khasawneh Ruba A. , Mohaidat Ziyad M. , Khasawneh Rawand A. , Zoghoul Sohaib B. , Henawi Yousef M. 
Published: August 2021

Abstract
Background
Hydatid disease is an endemic disease in many countries of the world including the Middle East. It mainly affects the liver and lungs. Intramuscular hydatid disease is rarely reported in children. Such uncommon localization of hydatid cyst may pose difficulties in the clinical and radiological diagnosis; hence affecting patient’s management and outcome even in endemic areas.

Case presentation
We herein describe intramuscular hydatid cysts in 2 different children. The first case is a 5-year-old boy who presented with a painless palpable lump over the right lumbar paraspinal region. His history was remarkable for sheep contact. His laboratory results revealed a mild increase in white blood cell (WBC) count and C-reactive protein. The lesion showed typical features of a hydatid cyst on ultrasound. Further imaging including ultrasound of the abdomen and CT of the chest, abdomen, and pelvis showed infestation of the liver and lung as well. The lesions were resected surgically without complications. The patient received Albendazole preoperatively and after surgery for 3 months. No evidence of recurrence was seen during follow-up.
The second case is a 6-year-old girl who presented with an incidental palpable lump in her left thigh during her hospital admission for recurrent meningitis. Ultrasound and MRI imaging were performed demonstrating a unilocular cystic lesion in the left proximal rectus femoris muscle. A provisional diagnosis of hematoma vs. myxoma was given. Biopsy was performed and yielded blood products only. The lesion was resected surgically with a postoperative diagnosis of hydatid cyst. Blood tests performed afterward showed a positive titer for Echinococcus. The patient received Albendazole for 3 months. No evidence of recurrence was seen during follow-up.

Conclusions
Despite its rarity; skeletal muscle hydatid cyst should always be considered in the differential diagnosis of cystic muscle lesions in children in endemic areas even if imaging studies did not show any of the typical signs. This will improve patient outcome by preventing unnecessary cystic puncture which might lead to serious complications, such as anaphylaxis and local dissemination.
Retear rates after rotator cuff surgery: a systematic review and meta-analysis
Authors: Longo Umile Giuseppe , Carnevale Arianna , Piergentili Ilaria , Berton Alessandra , Candela Vincenzo , Schena Emiliano , Denaro Vincenzo 
Published: August 2021

AbstractBackgroundRotator cuff retear (RCR) is one of the main postoperative drawbacks. RCR can be considered a multifactorial issue, which causes are related either to biological than biomechanical factors. The aim of this study was to define the incidence of RCR after surgical treatment at different time points and to identify the main factors influencing the postoperative rotator cuff (RC) healing.MethodsA systematic review and meta-analysis were performed following the PRISMA guidelines. A comprehensive search of the literature was carried out in July 2020, using PubMed and Cochrane Library databases. Only level 1 and 2 clinical evidence studies were included. Studies were included if patients with preoperative repairable full-thickness RC tears were treated surgically, and if studies reported postoperative RCR confirmed by imaging diagnostic. The association between timing of retear and follow-up time points were investigated using an inverse-variance method of pooling data. A subgroup meta-analysis was performed using the DerSimonian and Laird method for the estimation of the between-study variance, i.e., τ2. The association between retear rate after surgery and patients’ age, preoperative tear size, fatty infiltration, postoperative rehabilitation protocol, surgical techniques, and RC repairs was determined by expressing the effect measure in terms of odds ratio (OR) with 95% confidence interval (CI). The Mantel-Haenszel method with 95% CIs was used.ResultsThirty-one articles were included in this study. The percentage of RCR after surgery was 15% at 3 months follow-up, 21% at 3–6 months follow-up, 16% at 6–12 months follow-up, 21% at 12–24 months follow-up, 16% at follow-up longer than 24 months. The main factors influencing RC healing are both patient-related (i.e., age, larger tear size, fatty infiltration) and not patient-related (i.e., postoperative rehabilitation protocol, surgical techniques, and procedures).ConclusionsPostoperative RC healing is influenced by patient-related and non-patient-related factors. Further high-level clinical studies are needed to provide highly relevant clinical results.