bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sitagliptin on carotid intima-media thickness in type 2 diabetes and hyperuricemia patients: a subgroup analysis of the PROLOGUE study
Authors: Zhao Yipin , Wang Huawei , Ke Dazhi , Deng Wei , Ji Yingying , Yang Jiaojiao , Lin Zebin , Li Guoxing , Xiao Li , Tang Jianmin , Chen Qingwei 
Published: June 2021

Background and Aims: Studies have shown that dipeptidyl peptidase-4 (DDP-4) inhibitors have anti-atherosclerotic effects. However, in the PROLOGUE study, sitagliptin failed to slow the progression of carotid intima-media thickness (CIMT) relative to conventional therapy. We conducted a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in CIMT in subgroups with or without hyperuricemia. Methods: The PROLOGUE study was a randomized controlled trial of 442 patients with type 2 diabetes mellitus (T2DM). Patients were randomized to receive sitagliptin added therapy or conventional therapy. Based on the serum uric acid levels of all study populations in the PROLOGUE study, we divided them into hyperuricemia subgroup ( n = 104) and non-hyperuricemia subgroup ( n = 331). The primary outcome was changed in carotid intima-media thickness (CIMT) parameters compared with baseline during the 24 months treatment period. Results: In the hyperuricemia subgroup, compared with the conventional therapy group, the changes in the mean internal carotid artery (ICA)-IMT and max ICA-IMT at 24 months were significantly lower in the sitagliptin group [−0.233 mm, 95% confidence interval (CI) (−0.419 to 0.046), p = 0.015 and −0.325 mm, 95% CI (−0.583 to −0.068), p = 0.014], although there was no significant difference in the common carotid artery CIMT. Conclusion: The results of our analysis indicated that sitagliptin attenuated the progression of CIMT than conventional therapy in T2DM and hyperuricemia patients.
Clozapine re-challenge and initiation following neutropenia: a review and case series of 14 patients in a high-secure forensic hospital
Authors: Silva Edward , Higgins Melanie , Hammer Barbara , Stephenson Paul 
Published: June 2021

Objective: Clozapine remains the most effective intervention for treatment resistant schizophrenia; however, its use is prohibited following neutropenias. We review neutrophil biology as applied to clozapine and describe the strategies to initiate clozapine following neutropenia used in a case series of 14 consecutive patients rechallenged in a United Kingdom (UK) high-secure psychiatric hospital. We examine outcomes including the use of seclusion and transfer. Methods: A case series of 14 male patients with treatment resistant schizophrenia treated with clozapine despite previous episodes of neutropenia between 2006 and 2015 is presented. Data were collected during 2015 and 2019. Using this routinely collected clinical data, we describe the patient characteristics, causes of neutropenia, the strategies used for rechallenging with clozapine and clinical outcomes. Results: Previous neutropenias were the result of benign ethnic neutropenia, clozapine, other medications and autoimmune-related. Our risk mitigation strategies included: granulocyte-colony stimulating factor (G-CSF), lithium and watch-and-wait. There were no serious adverse events; at follow up half of the patient’s had improved sufficiently to transfer them to conditions of lesser security. There were dramatic reductions in the use of seclusion. Conclusion: Even in this extreme group, clozapine can be safely and effectively re/initiated following neutropenias, resulting in marked benefits for patients. This requires careful planning based on an understanding of neutrophil biology and the aetiology of the specific episode of neutropenia.
Anatomic Total Shoulder Arthroplasty With a Stemless Humeral Component
Authors: Walters Jordan D. , Brockmeier Stephen F. 
Published: June 2021

Background: This technique video reviews anatomic total shoulder arthroplasty (TSA) with a stemless humeral component using a representative case example. Indications: Stemless TSA is indicated for patients with symptomatic glenohumeral arthritis typically younger than 65 years of age. Stemless TSA may be used for other glenohumeral degenerative conditions such as avascular necrosis or posttraumatic arthropathy, provided acceptable humeral bone quality is confirmed intraoperatively using a thumb-press test. Poor bone quality is the primary contraindication. Technique Description: Preoperatively, computed tomography is typically used for planning, and intraoperative navigation through magnetic resonance imaging is also useful. The procedure’s critical elements include beach chair positioning, standard deltopectoral approach with lesser tuberosity osteotomy (LTO), freehand proximal humeral osteotomy, perpendicular proximal humeral exposure and subsequent preparation over a central guidewire, stemless implant and humeral head sizing, perpendicular glenoid exposure and implant placement, and final humeral implantation with LTO repair/fixation. A phased rehabilitation protocol includes 6-week sling immobilization to protect the subscapularis/LTO repair and return to normal activities between 3 and 6 months postoperatively. Discussion/Conclusion: Stemless TSA shows promising early and mid-term outcomes with complication rates, including humeral loosening rates, similar to standard stemmed components. Potential complications include neurovascular injury, infection, glenoid or humeral component loosening, and rotator cuff failure.
Defining the limits of caesarean scar niche repair: new anatomical landmarks
Authors: Rao Tanushree , Lambert Neera , Ghosh Bhaswati , Chang Timothy 
Published: June 2021

Abstract
Background
Caesarean scar niche is increasingly being seen due to the rise in the number of caesarean sections worldwide. Indications and the ideal route for niche repair are still being researched. If the residual myometrium is less than 3 mm thick and potential fertility is needed, laparoscopy is the ideal surgical method for caesarean scar niche repair. The aim of this video presentation is to demonstrate techniques of identifying new anatomical landmarks during laparoscopic uterine niche repair.

Results
As seen in the video, Caesarean scar niche repair can be done in a step-by-step manner, with lateral bands serving as anatomical landmarks.

Conclusions
Lateral bands are a consistent anatomical landmark which identify the level and width of the uterine niche and thus simplify the laparoscopic repair making this a reproducible technique.
Radiological survey on radon entry path in an underground mine and implementation of an optimized mitigation system
Authors: Shahrokhi Amin , Kovacs Tibor 
Published: June 2021

Abstract
Background
The European Union council has introduced the basic safety standards (EU-BSS) for protection against the dangers arising from exposure to ionizing radiation by laying down a new radon reference level at workplaces. In this regard, all European state members must establish a national reference level based on all pre-defined requirements. After implanting the directive 2013/59/Euratom by European state members, new challenges have been revealed to mitigate radon appropriately in underground workplaces due to the exciting limitations (e.g., ventilation system, dust dispersion, air injection, etc.). Therefore, a conceptual design of an environmental radiological survey was defined and implemented by examining the hypothesis to find practical solutions following EU-BSS. The main objectives of this study were to identify the potential radon entry paths, utilize an optimized ventilation system, and carry on long-term radon monitoring in an operational underground manganese mine.

Results
The mullock rocks (the geological structure of the mine walls) contained a small amount of Ra-226 (2–4 Bq kg−1). On the other hand, the mine ore (black shale, underlayer black shale, and carbonate ore) has shown the highest concentration of Ra-226 (12–16 Bq kg−1) and the highest radon exhalation (1.2–1.6 mBq s−1 m−2). The surface radon exhalation from the mine walls was in the range of 0.7 ± 0.1 and 1.5 ± 0.2 mBq m−2 s−1. It was found that shortly after mining activity was undertaken, radon concentration increased dramatically with an average of about 5900 ± 420 Bq m−3 near the freshly broken walls. The optimized mobile mitigation system reduced radon concentration to 250 ± 41 Bq m−3 on average.

Conclusion
Apart from the fact that aged walls were involved in the radon accumulation, considering the mine ventilation performance and the total active surface area, the exhaled radon from the aged walls could not be the primary potential source of high radon concentration when mining activity was undertaken. According to the obtained results, the ores, recently fragmented during the course of mining operations, were the primary path. Therefore, after successfully identifying the radon entry path, radon concentration could be reduced to meet the EU-BSS requirement by implementing the developed mitigation system.
The legacy of Eastern Mediterranean mountain uplifts: rapid disparity of phylogenetic niche conservatism and divergence in mountain vipers
Authors: Ahmadi Mohsen , Hemami Mahmoud-Reza , Kaboli Mohammad , Nazarizadeh Masoud , Malekian Mansoureh , Behrooz Roozbeh , Geniez Philippe , Alroy John , Zimmermann Niklaus E. 
Published: June 2021

Abstract
Background
The orogeny of the eastern Mediterranean region has substantially affected ecological speciation patterns, particularly of mountain-dwelling species. Mountain vipers of the genus Montivipera are among the paramount examples of Mediterranean neo-endemism, with restricted ranges in the mountains of Anatolia, the Levant, Caucasus, Alborz, and Zagros. Here we explore the phylogenetic and ecological diversification of Montivipera to reconstruct its ecological niche evolution and biogeographic history. Using 177 sequences of three mitochondrial genes, a dated molecular phylogeny of mountain vipers was reconstructed. Based on 320 occurrence points within the entire range of the genus and six climatic variables, ecological niches were modelled and used to infer ancestral niche occupancy. In addition, the biogeographic history and ancestral states of the species were reconstructed across climate gradients.

Results
Dated phylogenetic reconstruction revealed that the ancestor of mountain vipers split into two major clades at around 12.18 Mya followed by multiple vicariance events due to rapid orogeny. Montivipera colonised coastal regions from a mountain-dwelling ancestor. We detected a highly complex ecological niche evolution of mountain vipers to temperature seasonality, a variable that also showed a strong phylogenetic signal and high contribution in niche occupation.

Conclusion
Raising mountain belts in the Eastern Mediterranean region and subsequent remarkable changes in temperature seasonality have led to the formation of important centres of diversification and endemism in this biodiversity hotspot. High rates of niche conservatism, low genetic diversity, and segregation of ranges into the endemic distribution negatively influenced the adaptive capacity of mountain vipers. We suggest that these species should be considered as evolutionary significant units and priority species for conservation in Mediterranean mountain ecosystems.
Sativex® (nabiximols) cannabinoid oromucosal spray in patients with resistant multiple sclerosis spasticity: the Belgian experience
Authors: D’hooghe Marie , Willekens Barbara , Delvaux Valerie , D’haeseleer Miguel , Guillaume Daniel , Laureys Guy , Nagels Guy , Vanderdonckt Patrick , Van Pesch Vincent , Popescu Veronica 
Published: June 2021

Abstract
Background
This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications.

Methods
Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months.

Results
Mean 0–10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks’ range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile.

Conclusions
More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.
Anxiety among Lebanese adolescents: scale validation and correlates
Authors: Merhy Georges , Azzi Vanessa , Salameh Pascale , Obeid Sahar , Hallit Souheil 
Published: June 2021

Abstract
Background
The Lebanese population has undergone several conflicts and were the most afflicted by shelling and chaos during the civil war from 1975 to 1990, or even by displacement, bereavement, emigration, family separations, not to mention the economic crises that have hit the country since 2019 under which young adults are still succumbing. Our study aims to validate the Lebanese Anxiety Scale and assess correlates of anxiety among Lebanese adolescents.

Methods
A cross-sectional study was carried between January and May 2019, using a proportionate random sampling of schools from all five Lebanese governorates, among which 1810 adolescents aged 14 to 17 years.

Results
All LAS items remained in the model and formed one factor solution that explained 61.38% of the total variance (KMO = 0.873; pBartlett test < 0.001), with an excellent Cronbach’s alpha of 0.93. Higher neglect (B = 0.38), insomnia (B = 0.21) and child psychological abuse (B = 0.08) were significantly associated with more anxiety. Those results were considered adjusted overall sociodemographic variables since the latter had no statistically significant association with anxiety.

Conclusion
The study confirmed the association between anxiety and some variables such as psychological child abuse, neglect, and insomnia and emphasized the correlation between anxiety and these factors. Further, the LAS appears to be a short, valid and efficient tool for assessing anxiety among Lebanese adolescents. Further studies need to be carried to evaluate whether the LAS-10 gives a similar diagnosis to psychiatrists.
Transdiagnostic efficacy of a group exercise intervention for outpatients with heterogenous psychiatric disorders: a randomized controlled trial
Authors: Zeibig Johanna-Marie , Seiffer Britta , Sudeck Gorden , Rösel Inka , Hautzinger Martin , Wolf Sebastian 
Published: June 2021

Abstract
Background
Exercise efficaciously reduces disorder-specific symptoms of psychiatric disorders. The current study aimed to examine the efficacy of a group exercise intervention on global symptom severity and disorder-specific symptoms among a mixed outpatient sample.

Methods
Groups of inactive outpatients, waiting for psychotherapy, with depressive disorders, anxiety disorders, insomnia, and attention-deficit/hyperactivity disorders were randomized to a manualized 12-week exercise intervention, combining moderate to vigorous aerobic exercise with techniques for sustainable exercise behaviour change (n = 38, female = 71.1% (n = 27), Mage = 36.66), or a passive control group (n = 36, female = 75.0% (n = 27), Mage = 34.33). Primary outcomes were global symptom severity and disorder-specific symptoms, measured with the Symptom Checklist-90-Revised and Pittsburgh Sleep Quality Index pre- and post-treatment. Secondary outcome was the self-reported amount of exercise (Physical Activity, Exercise, and Sport Questionnaire), measured pre-treatment, intermediate-, and post-treatment. Intention-to-treat analyses were conducted using linear mixed models. Linear regressions were conducted to examine the effect of the change of exercise behaviour on the change of symptoms.

Results
The intervention significantly improved global symptom severity (d = 0.77, p = .007), depression (d = 0.68, p = .015), anxiety (d = 0.87, p = .002), sleep quality (d = 0.88, p = .001), and increased the amount of exercise (d = 0.82, p < .001), compared to the control group. Post-treatment differences between groups were significant for depression (d = 0.63, p = .031), sleep quality (d = 0.61, p = .035) and the amount of exercise (d = 1.45, p < .001). Across both groups, the reduction of global symptom severity was significantly predicted by an increase of exercise (b = .35, p = .012).

Conclusions
The exercise intervention showed transdiagnostic efficacy among a heterogeneous clinical sample in a realistic outpatient setting and led to sustained exercise behaviour change. Exercise may serve as an efficacious and feasible transdiagnostic treatment option improving the existing treatment gap within outpatient mental health care settings.

Trial registration
The study was registered on ClinicalTrials.gov (ID: NCT03542396, 25/04/2018).
Trends in mortality and life expectancy in Fiji over 20 years
Authors: Dearie Catherine , Linhart Christine , Rafai Eric , Nand Devina , Morrell Stephen , Taylor Richard 
Published: June 2021

AbstractBackgroundFiji, a Pacific Island nation of 884,887 (2017 census), has experienced a prolonged epidemiological transition. This study examines trends in mortality and life expectancy (LE) in Fiji by sex and ethnicity over 1996–2017, with comparisons to published estimates.MethodsTrends in infant mortality rates (IMR), under-5 mortality (U5M), adult mortality (probability of dying), LE (at birth) and directly age-standardised death rates (DASRs) by sex and ethnicity, are calculated (with 95% confidence limits) using unit death records from the Fiji Ministry of Health and Medical Services. The LE gap between populations, or within populations over time, is examined using decomposition by age. Period trends are assessed for statistical significance using linear regression.ResultsOver 1996–98 to 2014–17: IMR and U5M for i-Taukei and Fijians of Indian descent declined; U5M decline for i-Taukei (24.6 to 20.1/1000 live births) was significant (p = 0.016). Mortality (15–59 years) for i-Taukei males was unchanged at 27% but declined for Indians 33 to 30% (p = 0.101). Mortality for i-Taukei females increased 22 to 24% (p = 0.011) but declined for Indians 20 to 18% (p = 0.240). DASRs 1996–2017 were lower for i-Taukei (9.3 to 8.2/1000 population) than Indian males (10.6 to 9.8/1000). DASRs declined for i-Taukei (both sexes,p < 0.05), and for Indians (both sexes,p > 0.05). Over 22 years, LE at birth increased by 1 year or less (p = 0.030 in male i-Taukei). In 2014–17, LE (years) for males was: i-Taukei 64.9, Indians 63.5; and females: i-Taukei 67.0 and Indians 68.2. Mortality changes in most 5-year age groups increased or decreased the LE gap less than 10 weeks over 22 years. Compared to international agency reports, 2014–17 empirical LE estimates (males 64.7, females 67.8) were lower, as was IMR.ConclusionsBased on empirical data, LE in Fiji has minimally improved over 1996–2017, and is lower than some international agencies report. Adult mortality was higher in Indian than i-Taukei men, and higher in i-Taukei than Indian women. Exclusion of stillbirths resulted in IMRs lower than previously reported. Differing mortality trends in subgroups highlight the need to collect census and health data by ethnicity and sex, to monitor health outcomes and inform resource allocation.
Frequent POLE-driven hypermutation in ovarian endometrioid cancer revealed by mutational signatures in RNA sequencing
Authors: Davila Jaime I. , Chanana Pritha , Sarangi Vivekananda , Fogarty Zachary C. , Weroha S. John , Guo Ruifeng , Goode Ellen L. , Huang Yajue , Wang Chen 
Published: June 2021

Abstract
Background
DNA polymerase epsilon (POLE) is encoded by the POLE gene, and POLE-driven tumors are characterized by high mutational rates. POLE-driven tumors are relatively common in endometrial and colorectal cancer, and their presence is increasingly recognized in ovarian cancer (OC) of endometrioid type. POLE-driven cases possess an abundance of TCT > TAT and TCG > TTG somatic mutations characterized by mutational signature 10 from the Catalog of Somatic Mutations in Cancer (COSMIC). By quantifying the contribution of COSMIC mutational signature 10 in RNA sequencing (RNA-seq) we set out to identify POLE-driven tumors in a set of unselected Mayo Clinic OC.

Methods
Mutational profiles were calculated using expressed single-nucleotide variants (eSNV) in the Mayo Clinic OC tumors (n = 195), The Cancer Genome Atlas (TCGA) OC tumors (n = 419), and the Genotype-Tissue Expression (GTEx) normal ovarian tissues (n = 84). Non-negative Matrix Factorization (NMF) of the mutational profiles inferred the contribution per sample of four distinct mutational signatures, one of which corresponds to COSMIC mutational signature 10.

Results
In the Mayo Clinic OC cohort we identified six tumors with a predicted contribution from COSMIC mutational signature 10 of over five mutations per megabase. These six cases harbored known POLE hotspot mutations (P286R, S297F, V411L, and A456P) and were of endometrioid histotype (P = 5e−04). These six tumors had an early onset (average age of patients at onset, 48.33 years) when compared to non-POLE endometrioid OC cohort (average age at onset, 60.13 years; P = .008). Samples from TCGA and GTEx had a low COSMIC signature 10 contribution (median 0.16 mutations per megabase; maximum 1.78 mutations per megabase) and carried no POLE hotspot mutations.

Conclusions
From the largest cohort of RNA-seq from endometrioid OC to date (n = 53), we identified six hypermutated samples likely driven by POLE (frequency, 11%). Our result suggests the clinical need to screen for POLE driver mutations in endometrioid OC, which can guide enrollment in immunotherapy clinical trials.