bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of TAC-302 for patients with detrusor underactivity and overactive bladder: a randomized, double-blind, placebo-controlled phase 2 study
Authors: Yoshida Masaki , Gotoh Momokazu , Yokoyama Osamu , Kakizaki Hidehiro , Yamanishi Tomonori , Yamaguchi Osamu 
Published: October 2022

Abstract
Purpose
This multicenter, randomized, double-blind, placebo-controlled phase 2 study evaluated the efficacy and safety of TAC-302, a novel drug that restores neurite outgrowth, in patients with detrusor underactivity (DU) and overactive bladder (OAB).

Methods
After 2–4 weeks of observation, patients were randomized 2:1 to receive oral TAC-302 200 mg or placebo twice daily for 12 weeks. The primary endpoint was detrusor contraction strength, estimated by bladder contractility index (BCI) for males and projected isovolumetric pressure 1 (PIP1) for females. Secondary endpoints included changes in bladder voiding efficiency (BVE) and safety.

Results
Seventy-six patients were included (TAC-302, n = 52; placebo, n = 24). The mean (standard deviation [SD]) BCI for males was 64.6 (16.6) at baseline and 75.2 (21.1) at week 12 (p < 0.001) with TAC-302 (n = 27), and 61.3 (16.6) and 60.5 (16.7) (p = 0.82) with placebo (n = 11). The respective mean (SD) PIP1 for females was 18.8 (6.6) and 29.4 (9.4) (p < 0.001) with TAC-302 (n = 15), and 20.6 (7.5) and 25.5 (9.6) (p = 0.14) with placebo (n = 7). TAC-302 significantly increased BCI in males and BVE in both sexes. TAC-302 efficacy on OAB was not clearly shown. The incidences of adverse events (AEs), serious AEs, and AEs leading to dose interruption were similar between groups; no adverse drug reactions occurred.

Conclusion
Considering the significant effects on BCI in males and BVE in both sexes, TAC-302 may benefit patients with DU.

Registration
ClinicalTrials.gov Identifier NCT03175029 registered 6/5/2017.
Akzeptanz psychosozialer Überbrückungsmaßnahmen im Rahmen demenzieller Erkrankungen
Authors: Buschert V. , Leicher B. , Rogl C. , Hoffmann J. , Blum A.-L. , Scherbaum N. , Benninghoff J. 
Published: October 2022

Zusammenfassung
Hintergrund
Bei COVID-19 bedingtem Ausfall eines ambulanten Behandlungsprogramms im Rahmen demenzieller Erkrankungen wurden Patient:innen und deren Angehörigen Überbrückungsmaßnahmen auf Distanz angeboten. Ziel war es zu untersuchen, in welchem Maß die Teilnehmer:innen (TN) belastet waren, und wie die Angebote angenommen und bewertet wurden.

Material und Methoden
Allen TN (n = 63) wurden über den Zeitraum von 8 Wochen regelmäßige Telefonkontakte in unterschiedlicher Frequenz (wöchentlich, 14-tägig) sowie die Zusendung kognitiver und körperlicher Trainingsaufgaben im Abstand von 2 Wochen angeboten. Um die Akzeptanz der Maßnahmen sowie das Belastungserleben der TN zu erfassen, wurden aus der klinischen Routine erhobene Daten sowie retrospektiv eine schriftliche Befragung der TN in eine Behandlungsbeobachtung einbezogen.

Ergebnisse
Von 63 kontaktierten TN wurden die Daten von 45 TN eingeschlossen. Die Überbrückungsmaßnahmen wurden durchwegs positiv bewertet, wobei eine tendenziell höhere Zustimmung vonseiten der Angehörigen zu ermitteln war. Bei allen TN blieb das Belastungserleben stabil auf geringem Niveau; Angehörige waren signifikant stärker belastet.

Diskussion
Die Ergebnisse der vorliegenden Behandlungsbeobachtung sprechen für eine gut durchführbare und ortsunabhängige psychosoziale Behandlungsform im Rahmen demenzieller Erkrankungen. Diese kann sowohl als Überbrückungsmaßnahme für zukünftige pandemiebedingte Behandlungsausfälle als auch für die Routineversorgung (z. B. für mobilitätseingeschränkte oder im ländlichen Raum ohne direkte Klinikanbindung lebende Betroffene) geeignet sein. Daneben zeigt die Studie, wie notwendig es ist, für Angehörige ebenfalls Maßnahmen zu prüfen, um die Belastung zu reduzieren.
Association of sugar intake from different sources with incident depression in the prospective cohort of UK Biobank participants
Authors: Kaiser Anna , Schaefer Sylva M. , Behrendt Inken , Eichner Gerrit , Fasshauer Mathias 
Published: October 2022

Abstract
Purpose
To elucidate the association of different sources of free sugars (FS) and intrinsic sugars with depression risk in the prospective population-based UK Biobank cohort.

Methods
Sugar consumption was assessed in 188,426 participants (age range: 39–72 years, 54.4% female) with at least one web-based dietary questionnaire (Oxford WebQ). The hazard ratios (HR) for incident depression were assessed with Cox proportional hazard regression models including sugar intake from different sources as penalized cubic splines to allow non-linear predictor effects. Over a mean follow-up of 12.3 (standard deviation 1.8) years, 5410 incident depression cases occurred.

Results
FS intake was significantly associated with depression risk in an ascending approximately linear way with the lowest HR observed at 9% total energy (%E). In contrast, consumption of intrinsic sugars was not significantly related with incident depression. FS in beverages were significantly associated with depression risk in an ascending approximately linear way with the lowest HR at 4%E whereas no association was found for FS in solids. Concerning beverage types, FS in soda/fruit drinks, milk-based drinks, and tea/coffee were significantly and positively related to depression risk whereas the association was U-shaped for juice. Major findings were robust in sensitivity analyses.

Conclusion
Only some sources of FS are positively associated with incident depression. Public health initiatives targeting FS subtypes might be most effective concerning depression risk if focused on the reduction of sugary beverages and more specifically soda/fruit drinks, milk-based drinks, and tea/coffee.
Concentrations of escitalopram in blood of patients treated in a naturalistic setting: focus on patients with alcohol and benzodiazepine use disorder
Authors: Hart X. M. , Heesen S. , Schmitz C. N. , Dörfler S. , Wedekind D. , Gründer G. , Hiemke C. , Havemann-Reinecke U. 
Published: October 2022

AbstractThe selective serotonin reuptake inhibitor escitalopram (ESC) is indicated for the treatment of major depressive disorder (MDD) and of generalized anxiety disorder (GAD). Monitoring of blood levels (BLs) is strongly indicated due to ESC’s high interindividual pharmacokinetic variability. The aim of this study was to analyse clinical efficacy and pharmacokinetic influences on ESC BLs, in patients with depressive disorder alone and with comorbid alcohol or benzodiazepine use disorder. Data were collected from patients treated under naturalistic conditions for whom Therapeutic Drug Monitoring (TDM) was requested to guide antidepressant drug therapy and analysed retrospectively. Particular emphasis was given to patients with alcohol or benzodiazepine use disorder. Responders according to the clinical global impression (CGI) scale were compared with nonresponders for their ESC blood level (BL). The patient sample included 344 patients from 16 psychiatric hospitals in Germany. Influencing factors that could explain 22% of ESC BLs were dose, sex and age. Variability was high between individuals, and doses up to 40 mg were common in real-world settings. Patients treated with ESC monotherapy who responded showed a trend towards higher BLs compared to nonresponders with a concentration of 15 ng/mL separating both groups. Pathological changes in liver function (indicated by elevated GGT in combination with an AST/ALT ratio ≥ 1) resulted in higher dose-corrected ESC concentrations. Influencing factors that could explain 22% of ESC blood levels were dose, sex, and age. Our findings confirm the currently recommended lower threshold level and support the need for standard TDM analyses in everyday clinical practice. The ICD 10 diagnosis alcohol dependence alone does not lead to pharmacokinetic changes in the metabolism of ESC, but altered liver function does.
Machine learning and discriminant function analysis in the formulation of generic models for sex prediction using patella measurements
Authors: Bidmos Mubarak A. , Olateju Oladiran I. , Latiff Sabiha , Rahman Tawsifur , Chowdhury Muhammad E. H. 
Published: October 2022

Abstract
Sex prediction from bone measurements that display sexual dimorphism is one of the most important aspects of forensic anthropology. Some bones like the skull and pelvis display distinct morphological traits that are based on shape. These morphological traits which are sexually dimorphic across different population groups have been shown to provide an acceptably high degree of accuracy in the prediction of sex. A sample of 100 patella of Mixed Ancestry South Africans (MASA) was collected from the Dart collection. Six parameters: maximum height (maxh), maximum breadth (maxw), maximum thickness (maxt), the height of articular facet (haf), lateral articular facet breadth (lafb), and medial articular facet breath (mafb) were used in this study. Stepwise and direct discriminant function analyses were performed for measurements that exhibited significant differences between male and female mean measurements, and the “leave-one-out” approach was used for validation. Moreover, we have used eight classical machine learning techniques along with feature ranking techniques to identify the best feature combinations for sex prediction. A stacking machine learning technique was trained and validated to classify the sex of the subject. Here, we have used the top performing three ML classifiers as base learners and the predictions of these models were used as inputs to different machine learning classifiers as meta learners to make the final decision. The measurements of the patella of South Africans are sexually dimorphic and this observation is consistent with previous studies on the patella of different countries. The range of average accuracies obtained for pooled multivariate discriminant function equations is 81.9–84.2%, while the stacking ML technique provides 90.8% accuracy which compares well with those presented for previous studies in other parts of the world. In conclusion, the models proposed in this study from measurements of the patella of different population groups in South Africa are useful resent with reasonably high average accuracies.
Long-term follow-up of chronic central serous chorioretinopathy patients after primary treatment of oral eplerenone or half-dose photodynamic therapy and crossover treatment: SPECTRA trial report No. 3
Authors: Feenstra Helena M. A. , van Dijk Elon H. C. , van Rijssen Thomas J. , Tsonaka Roula , Diederen Roselie M. H. , Hoyng Carel B. , Schlingemann Reinier O. , Boon Camiel J. F. 
Published: October 2022

Abstract

Purpose
Comparing anatomic and functional efficacy and safety of primary treatment with either half-dose photodynamic therapy (PDT) or oral eplerenone, or crossover treatment in chronic central serous chorioretinopathy patients.

Methods
After the SPECTRA trial baseline visit, patients were randomized to either half-dose PDT or eplerenone and received crossover treatment if persistent subretinal fluid (SRF) on optical coherence tomography (OCT) was present at first follow-up (at 3 months). Presence of SRF and best-corrected visual acuity (BCVA) was evaluated at 12 months.

Results
Out of the 90 patients evaluated at 12 months, complete SRF resolution was present on OCT in 43/48 (89.6%) of patients who were primarily randomized to half-dose PDT and in 37/42 (88.1%) who were primarily randomized to eplerenone. Out of the 42 patients that were primarily randomized to eplerenone, 35 received crossover treatment with half-dose PDT. The BCVA improved significantly more at 12 months in patients who had received primary half-dose PDT as compared to the primary eplerenone group (p = 0.030).

Conclusions
Twelve months after baseline visit, most patients treated with half-dose PDT (either primary or crossover treatment) still had complete SRF resolution. The long-term BCVA in patients who receive primary half-dose PDT is better than in patients in whom PDT is delayed due to initial eplerenone treatment with persistent SRF.
The physiological, perceptual and neuromuscular responses of team sport athletes to a running and cycling high intensity interval training session
Authors: Twist Craig , Bott Richard , Highton Jamie 
Published: October 2022

Abstract
Purpose
The acute physiological, perceptual and neuromuscular responses to volume-matched running and cycling high intensity interval training (HIIT) were studied in team sport athletes.

Methods
In a randomized cross-over design, 11 male team sport players completed 3 × 6 min (with 5 min between sets) repeated efforts of 15 s exercising at 120% speed (s$$\dot{\text{V}}$$

V
˙

O2max) or power (p$$\dot{\text{V}}$$

V
˙

O2max) at $$\dot{\text{V}}$$

V
˙

O2max followed by 15 s passive recovery on a treadmill or cycle ergometer, respectively.

Results
Absolute mean $$\dot{\text{V}}$$

V
˙

O2 (ES [95% CI] = 1.46 [0.47–2.34], p < 0.001) and heart rate (ES [95% CI] = 1.53 [0.53–2.41], p = 0.001) were higher in running than cycling HIIT. Total time at > 90% $$\dot{\text{V}}$$

V
˙

O2max during the HIIT was higher for running compared to cycling (ES [95% CI] = 1.21 [0.26–2.07], p = 0.015). Overall differential RPE (dRPE) (ES [95% CI] = 0.55 [− 0.32–1.38], p = 0.094) and legs dRPE (ES [95% CI] = − 0.65 [− 1.48–0.23], p = 0.111) were similar, whereas breathing dRPE (ES [95% CI] = 1.01 [0.08–1.85], p = 0.012) was higher for running. Maximal isometric knee extension force was unchanged after running (ES [95% CI] = − 0.04 [− 0.80–0.8], p = 0.726) compared to a moderate reduction after cycling (ES [95% CI] = − 1.17 [− 2.02–0.22], p = 0.001).

Conclusion
Cycling HIIT in team sport athletes is unlikely to meet the requirements for improving run-specific metabolic adaptation but might offer a greater lower limb neuromuscular load.
Pharmacological inhibitors of the cystic fibrosis transmembrane conductance regulator exert off-target effects on epithelial cation channels
Authors: Lin JinHeng , Gettings Sean M. , Talbi Khaoula , Schreiber Rainer , Taggart Michael J. , Preller Matthias , Kunzelmann Karl , Althaus Mike , Gray Michael A. 
Published: October 2022

AbstractThe cystic fibrosis transmembrane conductance regulator (CFTR) anion channel and the epithelial Na+ channel (ENaC) play essential roles in transepithelial ion and fluid transport in numerous epithelial tissues. Inhibitors of both channels have been important tools for defining their physiological role in vitro. However, two commonly used CFTR inhibitors, CFTRinh-172 and GlyH-101, also inhibit non-CFTR anion channels, indicating they are not CFTR specific. However, the potential off-target effects of these inhibitors on epithelial cation channels has to date not been addressed. Here, we show that both CFTR blockers, at concentrations routinely employed by many researchers, caused a significant inhibition of store-operated calcium entry (SOCE) that was time-dependent, poorly reversible and independent of CFTR. Patch clamp experiments showed that both CFTRinh-172 and GlyH-101 caused a significant block of Orai1-mediated whole cell currents, establishing that they likely reduce SOCE via modulation of this Ca2+ release-activated Ca2+ (CRAC) channel. In addition to off-target effects on calcium channels, both inhibitors significantly reduced human αβγ-ENaC-mediated currents after heterologous expression in Xenopus oocytes, but had differential effects on δβγ-ENaC function. Molecular docking identified two putative binding sites in the extracellular domain of ENaC for both CFTR blockers. Together, our results indicate that caution is needed when using these two CFTR inhibitors to dissect the role of CFTR, and potentially ENaC, in physiological processes.
Single-centre review of the management of intra-thoracic oesophageal perforation in a tertiary oesophageal unit: paradigm shift, short- and long-term outcomes over 15 years
Authors: Charalampakis Vasileios , Cardoso Victor Roth , Sharples Alistair , Khalid Maha , Dickerson Luke , Wiggins Tom , Gkoutos Georgios V. , Tucker Olga , Super Paul , Richardson Martin , Nijjar Rajwinder , Singhal Rishi 
Published: October 2022

Abstract
Background
Oesophageal perforation is an uncommon surgical emergency associated with high morbidity and mortality. The timing and type of intervention is crucial and there has been a major paradigm shift towards minimal invasive management over the last 15 years. Herein, we review our management of spontaneous and iatrogenic oesophageal perforations and assess the short- and long-term outcomes.

Methods
We performed a retrospective review of consecutive patients presenting with intra-thoracic oesophageal perforation between January 2004 and Dec 2020 in a single tertiary hospital.

Results
Seventy-four patients were identified with oesophageal perforations: 58.1% were male; mean age of 68.28 ± 13.67 years. Aetiology was spontaneous in 42 (56.76%), iatrogenic in 29 (39.2%) and foreign body ingestion/related to trauma in 3 (4.1%). The diagnosis was delayed in 29 (39.2%) cases for longer than 24 h. There was change in the primary diagnostic modality over the period of this study with CT being used for diagnosis for 19 of 20 patients (95%). Initial management of the oesophageal perforation included a surgical intervention in 34 [45.9%; primary closure in 28 (37.8%), resection in 6 (8.1%)], endoscopic stenting in 18 (24.3%) and conservative management in 22 (29.7%) patients. On multivariate analysis, there was an effect of pathology (malignant vs. benign; p = 0.003) and surgical treatment as first line (p = 0.048) on 90-day mortality. However, at 1-year and overall follow-up, time to presentation (≤ 24 h vs. > 24 h) remained the only significant variable (p = 0.017 & p = 0.02, respectively).

Conclusion
Oesophageal perforation remains a condition with high mortality. The paradigm shift in our tertiary unit suggests the more liberal use of CT to establish an earlier diagnosis and a higher rate of oesophageal stenting as a primary management option for iatrogenic perforations. Time to diagnosis and management continues to be the most critical variable in the overall outcome.
Alkaline rocks of the Bobaomby volcanic field point to a petrogenetic link between Comoros and northern Madagascar lithosphere
Authors: Cucciniello Ciro , Grifa Celestino , de’Gennaro Roberto , Franciosi Luigi , Rocco Ivana , Morra Vincenzo , Melluso Leone 
Published: October 2022

AbstractThe Bobaomby volcanic field (10–11 Ma) is the northernmost volcanic area of Madagascar, and is a monogenetic volcanic field comprising outcrops of lava flows, dykes, scoria cones, tuff rings and plugs, widely scattered over an area of roughly 500 km2. The volcanic rocks range in composition from nephelinite, basanite and tephrite, through tephritic phonolite, to F- and Cl-rich peralkaline phonolite (MgO from 13 to 0.01 wt%), and the serial affinity varies from sodic to potassic. A few mica-amphibole-rich lamprophyric dykes have tephritic composition and ultrapotassic affinity. The mafic lavas host intrusive xenoliths with evident cumulate features (wehrlites, composite olivine gabbros s.l., amphibole clinopyroxenites and “kaersutitites”), as well as various types of mantle-derived xenoliths and xenocrysts in the most primitive rocks. The very wide compositional variations of the observed phases (olivine, clinopyroxene, amphibole, oxides, feldspars, feldspathoids, apatite, titanite, aenigmatite and other accessories) in lavas, dykes and cognate xenoliths are fully consistent with the variable degree of differentiation of the host lavas/dykes, and pointing out to limited open-system or polybaric crystallization. The mafic lavas have marked enrichment in incompatible elements and light rare-earth element (LREE) (e.g., Lan/Ybn = 19–27), whereas concave REE patterns are found in the peralkaline phonolites, as a result of removal of accessory titanite starting from tephritic phonolite magmas. The gabbroic/ultramafic xenoliths are interpreted as crustal cumulates of basanitic and tephritic magmas. Several liquid lines of descent in the basanites and tephrites are evident from the trace-element distribution, and from the differing geochemistry of the evolved rocks. The isotopic compositions reach extreme values (e.g., 206Pb/204Pb = 20.065 in the ultrapotassic lamprophyre) when compared to the rest of the Cenozoic/Recent Madagascan volcanic rocks, but similar to those of the Comoros archipelago, suggesting analogies of mantle sources and enrichment processes in the lithosphere of this volcanic archipelago. The origin of the Bobaomby mafic rocks is compatible from a derivation from low degree partial melting of an incompatible element-enriched peridotite source (possibly located in the lowermost lithospheric mantle) rich in volatile-rich phases (pargasite, locally also phlogopite and possibly carbonates), matching the sources of other Cenozoic volcanic areas throughout Madagascar, and perhaps Comoros.
Favorable long-term outcome in young adults undergoing surgery for lumbar disc herniation
Authors: Roiha Miika , Marjamaa Johan , Siironen Jari , Koski-Palkén Anniina 
Published: October 2022

Abstract

Purpose
The purpose of the study was to evaluate the long-term outcome after surgery for lumbar disc herniation in a young adult population.

Methods
A total of 526 consecutive patients between 18 and 40 years of age who underwent surgery for lumbar disc between 1990 and 2005 were included in the study. The primary outcomes were the need for new lumbar spine surgery during the follow-up and secondary outcomes were short-term subjective outcome, the Oswestry Disability Index (ODI) score, and the ability to carry out employment at the end of the long-term follow-up.

Results
A total of 96% of the patients had a reduction in their symptoms at the clinical follow-up (median of 50 days post-surgery). Twenty-one patients (4.0%) had a reoperation within 28 days. Excluding these early reoperations, 136 patients (26%) had additional lumbar spine surgery and 18 patients (3.4%) underwent lumbar fusion during the follow-up of median 18 years. The annual risk for new surgery was 1.4%. In total, 316 patients (60%) returned the ODI questionnaire, and their mean score was 8.1. Patients with a higher number of additional lumbar spine surgeries (p < 0.001) reported deteriorating ODI scores.

Conclusion
Patients showed excellent short-term recovery from their symptoms. In the long term, the mean ODI score for the patients was comparable to the normative population. However, a notable proportion of the patients required additional lumbar surgery during the follow-up period, and a higher number of lumbar surgeries was associated with poor ODI scores.