bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant Chemotherapy in the Treatment of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Systematic Review and Meta‐Analysis
Authors: Chong Eric , Ratnayake Bathiya , Dasari Bobby V. M. , Loveday Benjamin P. T. , Siriwardena Ajith K. , Pandanaboyana Sanjay
Published: September 2021

Background

The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy.

Method

A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy.

Results

Eleven studies and 3393 patients with IIPMNs were included in the meta‐analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38–0.87,p = 0.009) and node‐positive patients (HR 0.29, 95% CI 0.13–0.64,p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node‐positive patients was 11.6 months (95% CI 3.83–19.38,p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node‐negative patients (HR 0.53, 95% CI 0.20–1.43,p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node‐positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion.

Conclusion

Adjuvant chemotherapy was associated with improved OS in node‐positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.
Anatomical study between the correlation of the arcuate eminence and the superior semicircular canal
Authors: García-Barrios A. , Cisneros A. I. , Obon J. , Crovetto R. , Benito J. , Whyte J.
Published: September 2021

Objective

To study the anatomical correlation between the arcuate eminence and the superior semicircular canal.

Material and methods

A study of the height of the arcuate eminence was carried out in 295 temporal bones. In addition, 30 temporals with different heights of the arcuate eminence (10 flat, 10 prominent and 10 very prominent) were randomly selected and radiological tests were performed by computed tomography (Pöschl projection) and subsequent dissection by milling until the apex of the superior semicircular canal was found, establishing, with both methods, the anatomical relationship with the arcuate eminence.

Results

The arcuate eminence was classified as: smooth, when there was no relief (1.7%); flat, measured less than 1 mm (20.3%), prominent, measured between 1 and 2 mm, in (62%), and very prominent, measured above 2 mm (12.6%). The tomographic study (CT) and its subsequent dissection by bone milling showed a direct relationship between the arcuate eminence and the semicircular canal only when it was flat, while the rest of the types corresponded to the presence of pneumatized peri-labyrinthine cells and/or cancellous bone without a direct anatomical relationship with the apex of the superior semicircular canal.

Conclusion

The correlation between the arcuate eminence and the superior semicircular canal is direct only when it is flat (1 mm), being related to peri-labyrinthine cells and/or cancellous bone when the arcuate eminence is prominent or very prominent.
Psychische Gesundheit von Contergan-geschädigten Menschen
Authors: Niecke Alexander
Published: September 2021

Hintergrund

Sechs Jahrzehnte nach der pränatalen pharmakogenen Schädigung durch Thalidomid prägen vielfältige biopsychosoziale Folgeschädigungen das klinische Bild von Menschen mit Contergan-Behinderungen.

Fragestellung

Wie lässt sich das erst in der zweiten Lebenshälfte sichtbar gewordene hohe Ausmaß psychischer Störungen näher verstehen?

Material und Methode

Literaturüberblick zum aktuellen Stand der empirischen Forschung mit Diskussion weiterführender Fragen.

Ergebnisse

Menschen mit thalidomidinduzierten Schwerstbehinderungen zeigten jahrzehntelang bemerkenswerte Kompensationsleistungen. Ein sehr hoher Bildungsstatus sowie eine gute berufliche und soziale Integration wurden über viele Jahre erreicht. In der jüngeren Vergangenheit ist es jedoch zur zunehmenden sozialen Desintegration gekommen. Erstmals wurde eine hohe Rate psychischer Störungen, bei gleichzeitig bestehenden Barrieren im Zugang zur psychotherapeutischen Versorgung, beschrieben.

Schlussfolgerung

Das große Vorkommen psychischer Störungen im Alter kann einerseits als durch multidimensionale, teilweise bereits pränatal erworbene Traumatisierungen verursacht, andererseits als eine lange Zeit zugunsten einer Monostigmatisierung bestehende selektive Nichtwahrnehmung des Psychischen verstanden werden. Nicht nur für die Betroffenen ist es wichtig, dass der Fall Contergan im kollektiven Gedächtnis erinnert wird.
Lower and upper bound estimates of inequality of opportunity for emerging economies
Authors: Hufe Paul , Peichl Andreas , Weishaar Daniel
Published: September 2021

Equality of opportunity is an important normative ideal of distributive justice. In spite of its wide acceptance and economic relevance, standard estimation approaches suffer from data limitations that can lead to both downward and upward biased estimates of inequality of opportunity. These shortcomings may be particularly pronounced for emerging economies in which comprehensive household survey data of sufficient sample size is often unavailable. In this paper, we assess the extent of upward and downward bias in inequality of opportunity estimates for a set of twelve emerging economies. Our findings suggest strongly downward biased estimates of inequality of opportunity in these countries. To the contrary, there is little scope for upward bias. By bounding inequality of opportunity from above, we address recent critiques that worry about the prevalence of downward biased estimates and the ensuing possibility to downplay the normative significance of inequality.
Methotrexat-Versorgung vor dem Einsatz von Biologika bei rheumatoider Arthritis
Authors: Pardey Nicolas , Zeidler Jan , Nellenschulte Tim Fritz , Stahmeyer Jona T. , Hoeper Kirsten , Witte Torsten
Published: September 2021

Hintergrund

Seit vielen Jahren erweitern Biologika die Therapieoptionen bei rheumatoider Arthritis (RA). Der Einsatz dieser biologischen „disease-modifying antirheumatic drugs“ (bDMARDs) ist gemäß deutscher und europäischer Behandlungsleitlinien jedoch erst bei Ausschöpfung der Methotrexat (MTX)-Erstlinientherapie von mindestens 20 mg/Woche indiziert. Ziel der Studie ist es, die Leitliniengerechtigkeit der MTX-Verordnung im ambulanten Sektor vor der Biologikatherapie zu überprüfen.

Methodik

Es wurden Routinedaten der AOK-Niedersachsen der Jahre 2013 bis 2016 für alle Versicherten zur Verfügung gestellt, die im Studienzeitraum eine RA-Diagnose sowie eine bDMARD-Verordnung aufweisen. Innerhalb eines patientenindividuellen Beobachtungszeitraums von 180 Tagen vor der ersten bDMARD-Verordnung wurde die maximal verordnete MTX-Dosierung untersucht.

Ergebnisse

Die Studienpopulation umfasst 405 Patienten (90 inzident, 315 prävalent). Bei 60,0 % der inzidenten Patienten und 67,0 % der prävalenten Patienten wurde eine maximale MTX-Verordnung von < 20 mg/Woche beobachtet. Männer weisen im Mittel mit 17,1 ± 4,8 mg eine höhere MTX-Maximaldosierung als Frauen auf (14,9 ± 5,0 mg; p < 0,0001); 29,6 % der Studienpopulation erhielten im Beobachtungszeitraum ausschließlich orale Verordnungen. Umstellungen auf eine parenterale Applikationsform wurden bei 12,4 % der Patienten festgestellt.

Diskussion

Ein gezielter Einsatz des gesamten vorgesehenen Therapiespektrums vor der Initiierung einer bDMARD-Therapie kann zu einer kosteneffizienten Versorgung der RA beitragen. Die Studie zeigt Indizien für mögliche Defizite in der ambulanten MTX-Verordnungspraxis auf und kann für eine effiziente Therapie sensibilisieren.
Stellenwert von Mycophenolat-Mofetil zur Behandlung der interstitiellen Lungenerkrankung bei systemischer Sklerose
Authors: Schneider Udo , Siegert Elise , Gläser Sven , Krüger Klaus ,   die Kommission Pharmakotherapie der DGRh, Krause Andreas
Published: September 2021

Die interstitielle Lungenbeteiligung bei systemischer Sklerose (SSc-ILD) ist eine häufige Organkomplikation mit erheblicher Mortalität. Therapeutisch kommen in erster Linie Immunsuppressiva zum Einsatz, insbesondere Cyclophosphamid (CYC) und Mycophenolat-Mofetil (MMF). Neuere Daten zeigen zudem eine Wirksamkeit der Biologika Rituximab und Tocilizumab. Die therapeutischen Optionen wurden zuletzt durch die Zulassung des Antifibrotikums Nintedanib erweitert, dessen Stellenwert insbesondere bei den trotz Immunsuppression progredient fibrosierenden Verläufen der ILD liegt. Die in dieser Übersicht zusammengestellten Daten aus kontrollierten Studien zur Wirksamkeit und Sicherheit von CYC und MMF sprechen für einen bevorzugten Einsatz von MMF. Dem entgegen steht die noch immer fehlende Zulassung von MMF für diese Indikation. Diese wird für eine verbesserte und vereinfachte Versorgung von Patienten mit SSc-ILD dringend benötigt.
Biallelic variants in YRDC cause a developmental disorder with progeroid features
Authors: Schmidt Julia , Goergens Jonas , Pochechueva Tatiana , Kotter Annika , Schwenzer Niko , Sitte Maren , Werner Gesa , Altmüller Janine , Thiele Holger , Nürnberg Peter , Isensee Jörg , Li Yun , Müller Christian , Leube Barbara , Reinhardt H. Christian , Hucho Tim , Salinas Gabriela , Helm Mark , Jachimowicz Ron D. , Wieczorek Dagmar , Kohl Tobias , Lehnart Stephan E. , Yigit Gökhan , Wollnik Bernd
Published: September 2021

The highly conserved YrdC domain-containing protein (YRDC) interacts with the well-described KEOPS complex, regulating specific tRNA modifications to ensure accurate protein synthesis. Previous studies have linked the KEOPS complex to a role in promoting telomere maintenance and controlling genome integrity. Here, we report on a newborn with a severe neonatal progeroid phenotype including generalized loss of subcutaneous fat, microcephaly, growth retardation, wrinkled skin, renal failure, and premature death at the age of 12 days. By trio whole-exome sequencing, we identified a novel homozygous missense mutation, c.662T > C, in YRDC affecting an evolutionary highly conserved amino acid (p.Ile221Thr). Functional characterization of patient-derived dermal fibroblasts revealed that this mutation impairs YRDC function and consequently results in reduced t6A modifications of tRNAs. Furthermore, we established and performed a novel and highly sensitive 3-D Q-FISH analysis based on single-telomere detection to investigate the impact of YRDC on telomere maintenance. This analysis revealed significant telomere shortening in YRDC-mutant cells. Moreover, single-cell RNA sequencing analysis of YRDC-mutant fibroblasts revealed significant transcriptome-wide changes in gene expression, specifically enriched for genes associated with processes involved in DNA repair. We next examined the DNA damage response of patient’s dermal fibroblasts and detected an increased susceptibility to genotoxic agents and a global DNA double-strand break repair defect. Thus, our data suggest that YRDC may affect the maintenance of genomic stability. Together, our findings indicate that biallelic variants in YRDC result in a developmental disorder with progeroid features and might be linked to increased genomic instability and telomere shortening.
Transsphenoidal pituitary adenoma resection: do early post-operative cortisol levels predict permanent long-term hypocortisolism?
Authors: Butenschoen Vicki M. , von Werder Alexander , Bette Stefanie , Schmette Veronika , Schwendinger Nina , Meyer Bernhard , Gempt Jens
Published: September 2021

Transsphenoidal surgery provides a minimal invasive treatment for pituitary adenoma. Our aim is to evaluate the endocrinological outcomes after adenoma resection focusing on the corticotroph function, and to identify prognostic factors for an impaired hypothalamic–pituitary–adrenal-axis function (HPA) and the reliability of postoperative early morning serum cortisol measurements. We performed a retrospective analysis of all patients treated for pituitary adenoma from April 2006 to January 2019 in our neurosurgical department. Pituitary function was assessed pre- and postoperatively as well as at 6 weeks to 12 weeks and at 1-year follow-up. Two hundred eleven patients were included. Nine percent of the patients recovered from a preoperative adrenal insufficiency, 10.4% developed a new need for hormone substitution, and a long-term deficiency of the hypothalamic–pituitary–adrenal-axis was observed in 30.9%. Cortisol measurements 5 days after surgery had a lower area under the curve (AUC) than cortisol levels detected after 6 to 12 weeks (AUC 0.740 vs. AUC 0.808) in predicting an intact corticotrope function. The cut-off value determined for cortisol measured after 6 weeks was 6.95 µg/dl (sensitivity of 94%, specificity of 68%). Postoperative early morning cortisol levels seem to be less sensitive and specific in predicting long-term corticotroph function than measurements after 6 weeks and 1 year, emphasizing the importance of endocrine follow-up testing.
Ethanol inactivation of orthonairoviruses in ixodid ticks
Authors: Schulz A. , Methling K. , Lalk M. , Eisenbarth A. , Keller M. , Groschup M. H.
Published: September 2021

Ixodid ticks represent vectors and reservoirs for a broad range of zoonotic pathogens. Collected ticks from field studies are therefore usually stored in ethanol, which in higher concentrations effectively inactivates most of the known tick-borne pathogens. Although commonly practiced as gold standard for inactivation, hardly any scientific data demonstrate that ethanol sufficiently penetrates the comparatively thick cuticula of ticks. Therefore, Amblyomma hebraeum tick pools were stored for 21 days in ethanol (96%). Afterwards, the ethanol was removed and the ticks were homogenized. Quantitative 1H-NMR spectroscopic analysis was applied to determine the residual concentration of ethanol inside the ticks. 1H-NMR spectroscopic analysis revealed that ethanol constituted 28.3–42.6 mg of the total weight of three ticks in the pools (89.9–121.5 mg). In addition, the low-pathogenic Hazara orthonairovirus (HAZV) was used as a cell culture model for this study. The virus was exposed to ethanol concentrations between 0 and 60% and incubated under various temperature conditions for four time periods. Afterwards, the residual virus infectivity was determined by titration. Following ethanol exposure, HAZV did not grow in cells after 9 h of exposure to an ethanol concentration of 25%. These results demonstrate an extremely low ethanol resistance of the virus, which was generally in line with previously reported ethanol inactivation data for Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV). After prolonged storage and impregnation, comparable ethanol concentrations are achieved in the ticks, indicating the suitability of this inactivation method also for Bunyaviruses in ticks. At the very least, a massive virus inactivation can be assumed. Definitive proof of virus inactivation would require a bioassay of ethanol-treated infected ticks under appropriate biosafety conditions.
Self-supervised representation learning for surgical activity recognition
Authors: Paysan Daniel , Haug Luis , Bajka Michael , Oelhafen Markus , Buhmann Joachim M.
Published: September 2021

Purpose: Virtual reality-based simulators have the potential to become an essential part of surgical education. To make full use of this potential, they must be able to automatically recognize activities performed by users and assess those. Since annotations of trajectories by human experts are expensive, there is a need for methods that can learn to recognize surgical activities in a data-efficient way. Methods: We use self-supervised training of deep encoder–decoder architectures to learn representations of surgical trajectories from video data. These representations allow for semi-automatic extraction of features that capture information about semantically important events in the trajectories. Such features are processed as inputs of an unsupervised surgical activity recognition pipeline. Results: Our experiments document that the performance of hidden semi-Markov models used for recognizing activities in a simulated myomectomy scenario benefits from using features extracted from representations learned while training a deep encoder–decoder network on the task of predicting the remaining surgery progress. Conclusion: Our work is an important first step in the direction of making efficient use of features obtained from deep representation learning for surgical activity recognition in settings where only a small fraction of the existing data is annotated by human domain experts and where those annotations are potentially incomplete.
Consumer attitudes towards the mountain product label: Implications for mountain development
Authors: Bassi Ivana , Carzedda Matteo , Grassetti Luca , Iseppi Luca , Nassivera Federico
Published: September 2021

To protect and promote the originality and authenticity of mountain foodstuffs, the European Union set Regulation No 1151/2012 to create the optional quality term “mountain product”. Our research aimed at exploring the attractiveness of the mountain product label for consumers, considering both attitude towards the label itself and purchase intentions. We propose a model to investigate relationships between four latent constructs — mountain attractiveness, mountain food attractiveness, attitude towards the mountain product label, and purchase intention — which have been tested, thus confirming the statistical relevance of the relationships. All 47 items selected for describing the latent constructs are suitable for this purpose. Ridge and LASSO results also show that 17 items of the first three constructs are relevant in explaining purchase intentions. Some contextual variables, such as age, income, geographical origin of consumers, and knowledge of mountain products and mountains for tourism purposes, can positively influence consumers’ behavior. These findings could support the design of mountain development strategies, in particular marketing actions for both the product and the territory.
Tourism management in national parks: Šumava and Bayerischer Wald (Bavarian Forest) in the Czech-German borderland
Authors: Kołodziejczyk Krzysztof
Published: September 2021

Along the Czech-German border there are four national parks, two Czech and two German, arranged in cross-border ‘pairs’. This article focuses on the southern ‘pair’ formed by the parks of Šumava and Bayerischer Wald (Bavarian Forest). The aim is to evaluate and compare tourism organization in their areas, taking into account selected aspects of management: the network of hiking trails with its related infrastructure, transport accessibility, a typology of tourist centers, as well as directions and destinations of tourist movements. Based on the results, it can be concluded that the availability of geographical space for tourists is much greater in the German than in the Czech national park, and the tourism infrastructure is clearly more extensive there, including the network of tourist trails. This is mainly due to the longer and fairly uninterrupted development of tourism in this area. Šumava National Park can be identified as a model in terms of how to adjust the directions of tourist movements and the layout of the tourist trail network to the needs of natural environment. On the basis of observations in both national parks, it is possible to indicate various solutions that, after appropriate adaptation, may bring benefits to other protected areas.
Early results after aortic annuloplasty with a complete external Dacron band
Authors: Kvitting John-Peder Escobar , Beitnes Jan Otto , Lundblad Runar
Published: September 2021

Objective

This study evaluates the early results of our initial experience with aortic annuloplasty using a complete external Dacron band in the setting of type Ic or type II aortic regurgitation (AR).

Methods

From May 2017 to August 2019, 16 patients (88% bicuspid aortic valves, no patients with connective tissue disorders) underwent aortic annuloplasty with an external complete Dacron band. Clinical and echocardiographic follow-up was 100% complete. Clinical and echocardiographic follow-up averaged 24.4 ± 9.3 and  15.1 ±  8.3 months, respectively.

Results

Mean cardiopulmonary and cross-clamp times were 105 ± 15 (72–127) and 86 ± 15 (51–113) min, respectively. Early and late mortality was 0%, with no incidents of endocarditis or cerebrovascular events during the follow-up. Two patients were re-operated during the follow-up, one due recurrent aortic regurgitation (12 months after the first operation) yielding a freedom from reoperation due to AR at 1 year and 3 years of 100% ± 0% and 93.3% ± 5.7%, respectively. Based on the latest echocardiogram, five patients had either none or trivial AR, six had mild AR, and three had mild-to-moderate AR.

Conclusions

The early clinical and echocardiographic results after using a complete external Dacron band are promising; however, more data and longer follow-up are needed to determine its role in annular management during aortic valve repair.
Degree sum conditions for hamiltonian index
Authors: Liu Ze-meng , Xiong Li-ming
Published: September 2021

In this note, we show a sharp lower bound of $$\min \left\{{\sum\nolimits_{i = 1}^k {{d_G}({u_i}):{u_1}{u_2} \ldots {u_k}}} \right.$$

min

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i
=
1

k

d
G

(

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i

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:

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1

u
2

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is a path of (2-)connected G on its order such that (k-1)-iterated line graphs Lk−1(G) are hamiltonian.
Weak optimal inverse problems of interval linear programming based on KKT conditions
Authors: Liu Xiao , Jiang Tao , Li Hao-hao
Published: September 2021

In this paper, weak optimal inverse problems of interval linear programming (IvLP) are studied based on KKT conditions. Firstly, the problem is precisely defined. Specifically, by adjusting the minimum change of the current cost coefficient, a given weak solution can become optimal. Then, an equivalent characterization of weak optimal inverse IvLP problems is obtained. Finally, the problem is simplified without adjusting the cost coefficient of null variable.
Forsterite-hydroxyapatite composite scaffolds with photothermal antibacterial activity for bone repair
Authors: Liu Weiye , Zuo Rongtai , Zhu Tanglong , Zhu Min , Zhao Shichang , Zhu Yufang
Published: September 2021

Bone engineering scaffolds with antibacterial activity satisfy the repair of bacterial infected bone defects, which is an expected issue in clinical. In this work, 3D-printed polymer-derived forsterite scaffolds were proposed to be deposited with hydroxyapatite (HA) coating via a hydrothermal treatment, achieving the functions of photothermal-induced antibacterial ability and bioactivity. The results showed that polymer-derived forsterite scaffolds possessed the photothermal antibacterial ability to inhibit Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro, owing to the photothermal effect of free carbon embedded in the scaffolds. The morphology of HA coating on forsterite scaffolds could be controlled through changing the hydrothermal temperature and the pH value of the reaction solution during hydrothermal treatment. Furthermore, HA coating did not influence the mechanical strength and photothermal effect of the scaffolds, but facilitated the proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs) on scaffolds. Hence, the HA-deposited forsterite scaffolds would be greatly promising for repairing bacterial infected bone defects.
Self and parent‐reported sleep problems of adolescents with childhood conduct problems and comorbid psychological problems
Authors: Tomasiello Melina , Temcheff Caroline Elizabeth , Martin‐Storey Alexa , Bégin Vincent , Poirier Martine , Déry Michèle
Published: September 2021

Introduction

Childhood conduct problems (CP) are characterized by maladaptive externalizing behaviors and are linked with poor sleep. CP are highly comorbid with other psychological problems, including attention deficit/hyperactivity disorder and depression, which are also associated with disturbed sleep. The present study examined if childhood CP and comorbid depressive and/or attentional‐hyperactivity problems were prospectively associated with parent and self‐reported sleep difficulties in adolescence.

Methods

Participants (N= 744; 53% boys) from an ongoing longitudinal study in Québec, Canada were assessed for CP and comorbidities when they were between 6 and 9 years old. Participants were classified aswithout CP,CP only,CP and depressive symptoms,CP and attention‐hyperactivity problems,orCP, depressive symptoms, and attention‐hyperactivity problems.Regressions were conducted to examine the associations between comorbidity groups, parent, and self‐reported sleep problems 7 years later (Medianage = 15.33 years), controlling for sex, age, family income, primary caregiver education and medication.

Results

Adolescents in all CP groups had higher self and parent‐reported sleep problems compared to adolescents without histories of CP. Adolescents with histories of CP, depressive symptoms and attention‐hyperactivity problems had more sleep problems than all other groups according to self‐reports, but not parent‐reports.

Conclusion

Childhood CP was prospectively linked to sleep problems in adolescence, and comorbid conditions exacerbated these problems, according to youth but not parents.
Microablative Erbium: YAG Laser Therapy for Vulvodynia – A Report on Efficacy, Safety, and Treatment Satisfaction
Authors: Trutnovsky Gerda , Bliem Brigitte , Greimel Elfriede , Tamussino Karl , Gold Daniela
Published: September 2021

Introduction

Treatment for vulvodynia is challenging and a multidisciplinary approach is recommended.

Aim

To examine the effectiveness, safety and treatment satisfaction of vulvovaginal microablative laser treatment for vulvodynia.

Methods

Case study of women who received laser treatment as part of a multidisciplinary treatment program for vulvodynia. Subjective improvement was compared to a retrospective cohort of women treated for vulvodynia without LASER therapy. LASER treatment was offered to women with vulvodynia presenting to a gynecologic pain clinic of a tertiary university hospital. LASER treatments were performed with a microablative 2,940 nm Er:YAG LASER and potentially repeated after 1 month.

Main outcome measures

Change in local vulvar pain was assessed with cotton-swab tests and rated on a numeric rating scale (NRS). Treatment discomfort and short-term adverse events were recorded. The Freiburg Index of Patient Satisfaction was used to assess treatment satisfaction. Subjective symptom improvement was assessed with the Patient Global Impression of Improvement questionnaire.

Results

35 women received at least 1 laser treatment, with overall mild treatment adverse effects (mean pain NRS 2.4 ± 1.9) and good treatment satisfaction (mean total score of 27.6 ±5.1; potential range 8–32). One month after last LASER treatment the pain NRS on vulvar cotton swab test improved from 6.1 ± 2.6 at baseline to 3.1 ± 2.6 (P < .001), and 74% of women (n = 26) reported symptom improvement. At 9–12 months follow-up 66% reported ongoing symptom improvement, with no significant difference to the control group of 32 women.

Conclusion

Microablative Er:YAG vulvovaginal LASER therapy appears safe and well accepted among vulvodynia patients, but there was no significant difference in symptom improvement compared to a control group.
Predictors and Management of Relapse to Axicabtagene Ciloleucel in Patients with Aggressive B-cell Lymphoma ☆
Authors: Forero-Forero Jose Vicente , Lengerke-Diaz Paula A. , Moreno-Cortes Eider , Melody Megan , Rahman Zaid Abdel , Rosenthal Allison C. , Kharfan-Dabaja Mohamed A. , Castro Januario E.
Published: September 2021

Objective/background:

Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal.

Methods:

We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy.

Results:

Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALCLeuk) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR] 4.6–14.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed/refractory patients to axi-cel was 3 months (IQR 1.3–5.1).

Conclusion:

The grade of CRS and ALCLeuk correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.
The Anatomical Relationships in the Space of Retzius for Penile Implants: An MRI Analysis
Authors: Punjani Nahid , Monteiro Leonardo , Sullivan John F. , Flores Jose , Ortega Yanira , Matsushita Kazuhito , Choi Judy M. , Elterman Dean , Akin Oguz , Nelson Christian J. , Sandhu Jaspreet S. , Mulhall John P.
Published: September 2021

Background

The 3-piece inflatable penile prosthesis includes an easy-to-use pump and fluid filled reservoir which is placed in either the space of Retzius (SOR) or in an alternative ectopic location. Reservoir placement in the SOR is a blind procedure despite the SOR being surrounded by many critical structures. To date only a handful of cadaveric studies have described the relevant anatomy.

Aim

To use magnetic resonance imaging (MRI) as an in-vivo model to study relevant retropubic anatomy critical for SOR reservoir placement.

Methods

The study population included men with elevated prostate specific antigen or biopsy proven prostate cancer who (i) underwent pelvic MRI, (ii) without prior pelvic or inguinal surgery, and (iii) without pelvic radiation therapy. All MRIs were completed with a 3-Tesla scanner and endorectal coil. Both T1 and T2 weighted images were captured in both axial and sagittal planes. All images were reviewed by 2 independent reviewers under the supervision of a dedicated body MRI radiologist. Bladder volume was calculated using an ellipsoid formula.

Outcomes

Relevant measurements included (i) the distance between the external inguinal ring (EIR) at the level of the pubic tubercle to the external iliac vein (EIV), (ii) the distance from the EIR at the pubic tubercle to the bladder (accounting for bladder volume) and (iii) the distance from the midline pubic symphysis to the bladder (accounting for bladder volume). Pearson correlation was used to determine correlated measurements.

RESULTS

A total of 24 patients were included. Median participant age was 63 years (interquartile range, 59-66). The mean EIR-EIV distance was 3.0 ± 0.4 cm, the mean EIR-bladder distance was 1.8 ± 1.0 cm and the mean distance from the superior pubic symphysis to bladder was 0.9 ± 0.3 cm. There was a weak correlation between bladder volume and distance between the EIR and bladder (r = -0.30, P = .16).

Clinical Implications

The use of MRI as an in-vivo model is a high-fidelity tool to study real time unaltered anatomy and allows for surgical preparation, diagnosis of anatomic variants and acts as a valuable teaching tool.

Strengths & Limitations

This is the first in-vivo model to report relevant retropubic anatomy in penile implant surgery. Our study is limited by sample size and inclusion of participants with no history of prior pelvic intervention.

CONCLUSION

We demonstrate the utility of MRI as an in-vivo model, as opposed to cadaveric models, for the understanding of relevant retropubic anatomy for implant surgeons.
Fostering interdisciplinary collaboration: A longitudinal social network analysis of the NIH mHealth Training Institutes
Authors: Ho Eric , Jeon Minjeong , Lee Minho , Luo Jinwen , Pfammatter Angela F , Shetty Vivek , Spring Bonnie
Published: September 2021

Background/Objective:

Growing recognition that collaboration among scientists from diverse disciplines fosters the emergence of solutions to complex scientific problems has spurred initiatives to train researchers to collaborate in interdisciplinary teams. Evaluations of collaboration patterns in these initiatives have tended to be cross-sectional, rather than clarifying temporal changes in collaborative dynamics. Mobile health (mHealth), the science of using mobile, wireless devices to improve health outcomes, is a field whose advancement needs interdisciplinary collaboration. The NIH-supported annual mHealth Training Institute (mHTI) was developed to meet that need and provides a unique testbed.

Methods:

In this study, we applied a longitudinal social network analysis technique to evaluate how well the program fostered communication among the disciplinarily diverse scholars participating in the 2017−2019 mHTIs. By applying separable temporal exponential random graph models, we investigated the formation and persistence of project-based and fun conversations during the mHTIs.

Results:

We found that conversations between scholars of different disciplines were just as likely as conversations within disciplines to form or persist in the 2018 and 2019 mHTI, suggesting that the mHTI achieved its goal of fostering interdisciplinary conversations and could be a model for other team science initiatives; this finding is also true for scholars from different career stages. The presence of team and gender homophily effects in certain years suggested that scholars tended to communicate within the same team or gender.

Conclusion:

Our results demonstrate the usefulness of longitudinal network models in evaluating team science initiatives while clarifying the processes driving interdisciplinary communications during the mHTIs.
Laboratory studies of the role of bandwidth in surface transport and energy dissipation of deep-water breaking waves
Authors: Sinnis James T. , Grare Laurent , Lenain Luc , Pizzo Nick
Published: September 2021

This paper presents laboratory measurements of surface transport due to non-breaking and breaking deep-water focusing surface wave packets and examines the dependence of the transport on the wave packet bandwidth,

$\varDelta$

. This extends the work of Deike et al. (J. Fluid Mech., vol. 829, 2017, pp. 364–391) and Lenain et al. (J. Fluid Mech., vol. 876, 2019, p. R1), where similar numerical and laboratory experiments were conducted, but the bandwidth was held constant. In this paper, it is shown that the transport is strongly affected by the bandwidth. A model for the horizontal length scale of the breaking region is proposed that incorporates the bandwidth, central frequency, the linear prediction of the slope at focusing and the breaking threshold slope of the wave packet. This is then evaluated with data from archived and new laboratory experiments, and agreement is found. Furthermore, the horizontal length scale of the breaking region implies modifications to the model of the energy dissipation rate from Drazen et al. (J. Fluid Mech., vol. 611, 2008, pp. 307–332). This modification accounts for differing trends in the dissipation rate caused by the bandwidth in the available laboratory data.
Camel milk consumption is associated with less childhood stunting and underweight than bovine milk in rural pastoral districts of Somali, Ethiopia: a cross-sectional study
Authors: Muleta Anbissa , Hailu Dejene , Stoecker Barbara J. , Belachew Tefera
Published: September 2021

Undernutrition is a major global health problem. Various types of animal milk are used for feeding children at early ages; however, associations of camel milk (CaM) and bovine milk (BM) with the nutritional status of children have not been explored. A comparative community-based cross-sectional study was conducted among pre-schoolers in rural pastoral districts of Somali, Ethiopia. Children were selected from households with lactating camels or cows. Anthropometric measurements followed standard procedures for height-for-age, weight-for-age and weight-for-height scores. Independent sample t-tests identified significant differences in anthropometric indices based on the type of milk consumed. Multivariable logistic regression was used to examine associations between milk consumption and other predictors of growth failures. The prevalence of stunting was 24⋅1 % [95 % confidence interval (CI) 20⋅5, 28⋅3] of pre-schoolers, 34⋅8 % (95 % CI 29⋅9, 39⋅6) were wasted and 34⋅7 % (95 % CI 30⋅1, 39⋅9) were underweight. Higher proportions of BM-fed children were severely stunted, wasted and underweight compared with CaM consumers. Using logistic regression models, children who consumed BM [adjusted odds ratio (AOR): 2⋅10; 95 % CI 1⋅22, 3⋅61] and who were anaemic (AOR: 4⋅22; 95 % CI 2⋅23, 7⋅98) were more likely to be stunted than their counterparts, while girls were less likely to be stunted than boys (AOR: 0⋅57; 95 % CI 0⋅34, 0⋅94). Similarly, children who consumed BM (AOR: 1⋅97; 95 % CI 1⋅20, 3⋅24), who were anaemic (AOR: 2⋅27; 95 % CI 1⋅38, 3⋅72) and who drank unsafe water (AOR: 1⋅91; 95 % CI 1⋅19, 3⋅07) were more likely to be underweight than their counterparts. In conclusion, CaM consumption was associated with lower prevalence of stunting and underweight than BM. Promoting CaM in pastoralist areas may help to curb the high level of undernutrition.
Dynamic association of the first identifiable symptom with rapidity of progression to first-episode psychosis
Authors: Paquin Vincent , Cupo Lani , Malla Ashok K. , Iyer Srividya N. , Joober Ridha , Shah Jai L.
Published: September 2021

Background

Rapid progression from the first identifiable symptom to the onset of first-episode psychosis (FEP) allows less time for early intervention. The aim of this study was to examine the association between the first identifiable symptom and the subsequent speed of illness progression.

Methods

Data were available for 390 patients attending a catchment-based early intervention service for FEP. Exposure to non-psychotic and subthreshold psychotic symptoms was retrospectively recorded using semi-structured interviews. Outcomes following the onset of the first identifiable symptom were (1) time to onset of FEP and (2) symptom incidence rate (i.e. number of symptoms emerging per person-year until FEP onset). These outcomes were respectively analyzed with Cox proportional hazards and negative binomial regressions.

Results

After Bonferroni correction, having a subthreshold psychotic (v. non-psychotic) symptom as the first symptom was not associated with time to FEP onset [hazard ratio (HR) = 1.39; 95% CI 0.94–2.04] but was associated with higher symptom incidence [incidence rate ratio (IRR) = 1.92; 95% CI 1.10–3.48]. A first symptom of suspiciousness was associated with shorter time to FEP onset (HR = 2.37; 95% CI 1.38–4.08) and higher symptom incidence rate (IRR = 3.20; 95% CI 1.55–7.28) compared to other first symptoms. In contrast, a first symptom of self-harm was associated with lower symptom incidence rate (IRR = 0.06; 95% CI 0.01–0.73) compared to other first symptoms. Several associations between symptoms and illness progression were moderated by the age at symptom onset.

Conclusions

Appreciating the content and timing of early symptoms can identify windows and treatment targets for early interventions in psychosis.
An interpretation of dependent type theory in a model category of locally cartesian closed categories
Authors: Bidlingmaier Martin E.
Published: September 2021

Locally cartesian closed (lcc) categories are natural categorical models of extensional dependent type theory. This paper introduces the “gros” semantics in the category of lcc categories: Instead of constructing an interpretation in a given individual lcc category, we show that also the category of all lcc categories can be endowed with the structure of a model of dependent type theory. The original interpretation in an individual lcc category can then be recovered by slicing. As in the original interpretation, we face the issue of coherence: Categorical structure is usually preserved by functors only up to isomorphism, whereas syntactic substitution commutes strictly with all type-theoretic structures. Our solution involves a suitable presentation of the higher category of lcc categories as model category. To that end, we construct a model category of lcc sketches, from which we obtain by the formalism of algebraically (co)fibrant objects model categories of strict lcc categories and then algebraically cofibrant strict lcc categories. The latter is our model of dependent type theory.
Support with extracorporeal membrane oxygenation for over 1 year duration as a bridge to cardiac transplantation: a case report and review of the literature
Authors: Shanefield Seth C. , Knewitz Daniel , Philip Joseph , Fricker F. Jay , Sullivan Kevin , Laucerica Circe , Jacobs Jeffrey P. , Peek Giles J. , Bleiweis Mark S.
Published: September 2021

We present the case of a 13-year-old male with a complex congenital cardiac history who was supported with extracorporeal membrane oxygenation for 394 days while awaiting cardiac transplantation. The patient underwent successful cardiac transplantation after 394 days of support with veno-arterial extracorporeal membrane oxygenation and is currently alive 2 years after cardiac transplantation. We believe that this case represents the longest period of time that a patient has been supported with extracorporeal membrane oxygenation as a bridge to cardiac transplantation.

We also review the literature associated with prolonged support with extracorporeal membrane oxygenation. This case report documents many of the challenges associated with prolonged support with extracorporeal membrane oxygenation, including polymicrobial bacterial and fungal infections, as well as renal dysfunction. It is possible to successfully bridge a patient to cardiac transplantation with prolonged support with extracorporeal membrane oxygenation of over 1 year; however, multidisciplinary collaboration is critical.
Urban cloverleaves: origin, aesthetics, and contradictions of the Slussen, Stockholm
Authors: Clua Uceda Álvaro
Published: September 2021

On 11 October 1935, the inauguration of the Slussen urban cloverleaf took place in front of the excited citizens of Stockholm. It had the attributes of a pure traffic machine taken from the most advanced traffic engineering publications, and it expressed the optimistic cultural modernism that five years ago the Stockholm International Exhibition had promoted.1 This urban cloverleaf was made of translucent glass, reinforced concrete, metallic handrails, and reflective tiles and was meant to solve, in one single gesture, the complex urban link between the Lake Mälaren and the Baltic Sea, between Gamla Stan – the historic city centre – and Södermalm – the southern district built on top of the 35-metre-high plateau [1]. The solution made difficult urban compromises between the foothills of the Brunkeberg topography, the smooth water surfaces of the Stockholm archipelago, the architecture of the historic urban tissue, and the demands of a complex articulated mobility. Boats, goods, suburban trains, subways, trams – later buses – pedestrians, cyclists, and automobiles finally converged on this place at different levels, completing the intricacies of a threedimensional geometry which, for the first time in history, was inserted into a compact city.
Anglican Church of Southern Africa: Safe and Inclusive Church Commission
Authors: Manning Rosalie , Saldanha Colette , Phelps Claire , Ahrends Chris , Lee Peter
Published: September 2021

The process of creating a Safe and Inclusive Church (SIC) Commission within the Anglican Church of the Province of SouthernAfrica (ACSA) is not unique in the Communion. This article seeks to explore ACSA’s specific journey to date, with a view to engaging the Communion in a learning partnership. While some of the process of establishing this ministry may be unique, there are places of commonality as we jointly grapple with the call of our Lord Jesus to continue to build the Kingdom of God in contemporary times. Most specifically, this process has highlighted a need for renewal of the Church in both our theological understanding and how we organize to best serve our call to preach the Good News. These theological and structural dimensions of ‘doing church’ speak deeply into our ‘being church’ and are at the heart of why dialogue is needed as a Communion. We offer this article as an invitation to continue discerning together how best to follow and serve our Lord and Saviour Jesus Christ by being His Body to a broken and wounded world.
Higher intakes of dietary caffeine are associated with 25-hydroxyvitamin D deficiency
Authors: Chen Qiwei , Kord-Varkaneh Hamed , Santos Heitor O. , Genario Rafael , Dang Minyan
Published: September 2021

Abstract. Low serum 25-hydroxyvitamin D [25(OH)D] levels remain a challenge worldwide. While some in vitro studies show a caffeine-induced decrease in vitamin D receptor expression, there is a paucity of research to define the extent of caffeine intake and effects on 25(OH)D levels. Therefore, we aimed to associate dietary caffeine intake with 25(OH)D deficiency through a recognized dataset. Using data collected from the 2005–2006 National Health and Nutrition Examination Survey (NHANES), 25(OH)D levels and dietary caffeine intake were extracted from 13134 individuals (30–47 years, interquartile range). We used one-way ANOVA and chi-square tests for quantitative and qualitative variables, respectively, and performed multivariate logistic regression for four models to assess the odds ratio (OR) of 25(OH)D deficiency (<20 ng/ml or <50 nmol/L) based on quartiles of dietary caffeine intake. Both crude and multivariable models detected higher OR for 25(OH)D deficiency according to the highest intakes of caffeine (15.8±9.5, 51.9±11.9, and 177±156 mg/d) when compared to the reference category (2.19±1.04 mg/d), in which the OR in the highest category of caffeine intake was 1.24 (95% CI: 1.12 to 1.37) and 1.48 (95% CI: 1.16 to 1.78) for the crude model and the most complete multivariable analysis (adjustment for age, sex, race, body mass index, smoking, physical activity, occupation, energy intake, protein intake, and fat intake), respectively. In conclusion, higher dietary intakes of caffeine were associated with 25(OH)D deficiency in a representative sample of the American population, but further investigation is warranted to determine causation.