bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico drug repurposing for filarial infection predicts nilotinib and paritaprevir as potential inhibitors of the Wolbachia 5′-aminolevulinic acid synthase
Authors: Kwarteng Alexander , Asiedu Ebenezer , Sylverken Augustina , Larbi Amma , Mubarik Yusif , Apprey Charles 
Published: April 2021

AbstractFilarial infections affect millions of individuals and are responsible for some notorious disabilities. Current treatment options involve repeated mass drug administrations, which have been met with several challenges despite some successes. Administration of doxycycline, an anti-Wolbachia agent, has shown clinical effectiveness but has several limitations, including long treatment durations and contraindications. We describe the use of an in silico drug repurposing approach to screening a library of over 3200 FDA-approved medications against the filarial endosymbiont,Wolbachia. We target the enzyme which catalyzes the first step of heme biosynthesis in theWolbachia. This presents an opportunity to inhibit heme synthesis, which leads to depriving the filarial worm of heme, resulting in a subsequent macrofilaricidal effect. High throughput virtual screening, molecular docking and molecular simulations with binding energy calculations led to the identification of paritaprevir and nilotinib as potential anti-Wolbachia agents. Having higher binding affinities to the catalytic pocket than the natural substrate, these drugs have the structural potential to bind and engage active site residues of thewolbachia5′-Aminolevulinic Acid Synthase. We hereby propose paritaprevir and nilotinib for experimental validations as anti-Wolbachia agents.
Amplification-free RNA detection with CRISPR–Cas13
Authors: Shinoda Hajime , Taguchi Yuya , Nakagawa Ryoya , Makino Asami , Okazaki Sae , Nakano Masahiro , Muramoto Yukiko , Takahashi Chiharu , Takahashi Ikuko , Ando Jun , Noda Takeshi , Nureki Osamu , Nishimasu Hiroshi , Watanabe Rikiya 
Published: April 2021

AbstractCRISPR-based nucleic-acid detection is an emerging technology for molecular diagnostics. However, these methods generally require several hours and could cause amplification errors, due to the pre-amplification of target nucleic acids to enhance the detection sensitivity. Here, we developed a platform that allows “CRISPR-based amplification-free digital RNA detection (SATORI)”, by combining CRISPR-Cas13-based RNA detection and microchamber-array technologies. SATORI detected single-stranded RNA targets with maximal sensitivity of ~10 fM in <5 min, with high specificity. Furthermore, the simultaneous use of multiple different guide RNAs enhanced the sensitivity, thereby enabling the detection of the SARS-CoV-2 N-gene RNA at ~5 fM levels. Therefore, we hope SATORI will serve as a powerful class of accurate and rapid diagnostics.
Arrb2 causes hepatic lipid metabolism disorder via AMPK pathway based on metabolomics in alcoholic fatty liver
Authors: Sun Ying-Yin , Wu Dong-Qing , Yin Na-Na , Yang Lei , Chen Xin , Li Hai-Di , Li Xiao-Feng , Huang Cheng , Meng Xiao-Ming , Wang Hua , Li Jun 
Published: April 2021

Abstract
Background and aims: Alcoholic fatty liver (AFL) is an early form of alcoholic liver disease (ALD) that usually manifests as lipid synthesis abnormalities in hepatocytes. β-arrestin2 (Arrb2) is involved in multiple biological processes. The present study aimed to explore the role of Arrb2 in the regulation of lipid metabolism in AFL and the underlying mechanism and identify potential targets for the treatment of AFL. Methods: The expression of Arrb2 was detected in liver tissues obtained from AFL patients and Gao-binge AFL model mice. In addition, we specifically knocked down Arrb2 in AFL mouse liver in vivo and used Arrb2-siRNA or pEX3-Arrb2 to silence or overexpress Arrb2 in AML-12 cells in vitro to explore the functional role and underlying regulatory mechanism of Arrb2 in AFL. Finally, we investigated whether Arrb2 could cause changes in hepatic lipid metabolites, thereby leading to dysregulation of lipid metabolism based on liquid chromatography-mass spectrometry (LC-MS) analysis. Results: Arrb2 was up-regulated in the livers of AFL patients and AFL mice. The in vivo and in vitro results confirmed that Arrb2 could induce lipid accumulation and metabolism disorders. Mechanistically, Arrb2 induced hepatic metabolism disorder via AMP-activated protein kinase (AMPK) pathway. The results of LC-MS analysis revealed that hepatic lipid metabolites with the most significant differences were primary bile acids. Conclusions: Arrb2 induces hepatic lipid metabolism disorders via AMPK pathway in AFL. On one hand, Arrb2 increases fatty acid synthesis. On the other hand, Arrb2 could increase the cholesterol synthesis, thereby leading to the up-regulation of primary bile acid levels.
A Cognitive Psychometric Investigation of Word Production and Phonological Error Rates in Logopenic Progressive Aphasia
Authors: Petroi Diana , Walker Grant M. , Duffy Joseph R. , Hickok Gregory S. , Josephs Keith A. 
Published: April 2021

Purpose
This study investigated the relationship between word production rates (WPRs) and phonological error rates (PERs) in generative and responsive tasks in logopenic progressive aphasia (lvPPA). We examined whether a portion of the reduced WPR during generative tasks related directly to phonological impairments affecting PER on all tasks, irrespective of other task differences that contributed to WPR.

Method
Two cognitive psychometric models were hypothesized and fit to the total number of words produced and the number of phonological errors produced by 22 participants on 10 tasks. Bayesian inference was used to construct posterior distributions of participant ability and task difficulty parameters. Model fit statistics were compared. Association strengths for average generative WPR and average responsive PER were also evaluated with linear least-squares regression.

Results

Average generative WPR and average responsive PER were significantly associated (
r
= −.77,
p
= .00002). A cognitive psychometric model that assumed reduced WPR on generative tasks reflects a portion of general phonological impairment yielded better fit than a model that ignored performance differences between generative and responsive tasks. Generative fluency tasks that elicited few phonological errors still reflected phonological impairment, via suppression. Individual participants were estimated to suppress between 62% and 93% of phonological errors on generative tasks that would have emerged on responsive tasks.

Conclusions
Suppression of phonological errors may present as decreased WPR on generative tasks in lvPPA. Failure to account for this suppression tendency may lead to overestimation of phonological ability. The findings indicate the need to account for task demands in assessing lvPPA.
Metadeglutition? Rate of Aspiration-Related Events in Healthy Females Using a Novel Data Collection App
Authors: Evitts Paul M. , Fields Kyanne , Lande Benjamin 
Published: April 2021

Purpose
Recently, there has been increased emphasis in the dysphagia literature on what constitutes the “normal” swallow, including rates of aspiration and penetration in healthy persons across the age ranges. Since a majority of the normed-based studies utilized videofluoroscopy and were conducted in a tightly controlled environment, there is a need to increase the ecological validity of this body of research and investigate the swallow during functional, day-to-day activities. The aim of this study is to track the incidence of swallowing difficulty in young, healthy adults over an extended period to determine the frequency of aspiration-related events and under what environmental circumstances these events occurred.

Method
Sixty-nine young, healthy women (aged 18–39 years) participated in the study and recorded data for 95 consecutive days. Participants installed a web-based application on their cell phones and were asked to access the app and answer three simple questions immediately following any adverse swallowing events. These data were used to determine the frequency of aspiration-related events and their relationship to environmental circumstance.

Results
Fifty-three of the 69 participants (76.8%) reported coughing or choking, 43 (62.3%) reported clearing their throat, 19 (27.5%) reported a globus sensation, and 14 (20.2%) reported difficulty initiating a swallow. The environmental circumstances most commonly associated with aspiration-related events were talking, being distracted, and using an electronic device.

Conclusion
Results suggest that young, healthy adults experience aspiration-related events at a high frequency and that these events typically occur during activities that require dual attention.
Crosslinking und Keratokonus
Authors: Lang Stefan J. , Maier Philip , Reinhard Thomas 
Published: April 2021

ZusammenfassungEin Keratokonus führt zu einer progressiven Vorwölbung und Verdünnung der
Hornhaut. Um dies aufzuhalten, kann ein Crosslinking durchgeführt werden. Dabei
ist eine Behandlung nach dem „Dresdener Protokoll“ eine effektive und sichere
Behandlungsmöglichkeit, aber auch zahlreiche neue Anwendungsprotokolle
(akzeleriertes Crosslinking, transepitheliales Crosslinking) und sogar weitere
Indikationen (refraktive Eingriffe, infektiöse Keratitis) wurden in den letzten
Jahren veröffentlicht.
Soziale Ungleichheiten im Zugang und in der Inanspruchnahme von medizinischen Rehabilitationsmaßnahmen
Authors: Fach Eva-Maria , Markert Jenny , Spanier Katja , Bethge Matthias , Schlumbohm Anna , Richter Matthias 
Published: April 2021

Zusammenfassung
Ziel der Studie Der Einfluss des sozialen Status auf die Gesundheit ist gut belegt. Für den Bereich der Rehabilitation geben wenige Studien erste Hinweise auf sozial ungleiche Versorgung. Die Studie untersucht anhand einer Risikokohorte der Deutschen Rentenversicherung Bund die Rolle sozialer Ungleichheiten beim Zugang und in der Inanspruchnahme von Leistungen zur medizinischen Rehabilitation.
Methodik Die Datengrundlage bilden Fragebogendaten der ersten beiden Wellen des Dritten Sozialmedizinischen Panels für Erwerbspersonen (SPE III) sowie administrative Daten der Teilnehmenden (2013–2016). Diese Risikokohorte umfasst 40- bis 54-jährige Erwerbspersonen mit Krankengeldbezug im Jahr 2012. Mittels logistischer Regressionsmodelle wurden Antragstellung, Bewilligung und Ablehnung, Bewilligung nach Widerspruch und Inanspruchnahme von Rehabilitationsleistungen analysiert. Der soziale Status wurde sowohl als sozioökonomischer Status (Index) als auch in der Einzeldimension Bildung als Prädiktor herangezogen. Die Analysen erfolgten getrennt nach Geschlecht. Alter, Erwerbsstatus sowie der subjektive Gesundheitszustand wurden als Kontrollvariablen berücksichtigt.
Ergebnisse Insgesamt wurden 2376 Versicherte, davon 1284 Frauen, in die Analysen eingeschlossen. 639 (26,9%) stellten mindestens einen Antrag auf Leistungen zur medizinischen Rehabilitation. Die Chance auf Antragstellung war bei Männern mit niedrigem sozioökonomischen Status (OR=1,8; 95%-KI=1,3–2,5) bzw. niedriger (OR=1,9; 95%-KI=1,3–2,8) und mittlerer Bildung (OR=1,5; 95%-KI=1,1–2,2) im Vergleich zur hohen Status- bzw. Bildungsgruppe erhöht. Bei den Frauen zeigte sich bei der Antragstellung ein signifikanter Unterschied zugunsten niedriger Bildung (OR=1,6; 95%-KI=1,1–2,5). Nach Adjustierung des Gesundheitszustandes und der aktuellen Erwerbstätigkeit verschwanden die Unterschiede. Hinsichtlich Bewilligung und Inanspruchnahme zeigten sich keine signifikanten Unterschiede nach sozialem Status, jedoch erfolgte bei Frauen mit mittlerer Bildung signifikant häufiger eine Bewilligung auf Grundlage eines Widerspruchverfahrens (OR=3,0; 95%-KI=1,1–8,2) als bei Frauen mit hoher Bildung.
Schlussfolgerung Die Analysen gaben keine Hinweise auf einen sozial ungleichen Zugang oder eine sozial ungleiche Inanspruchnahme von Leistungen zur medizinischen Rehabilitation. Allerdings beantragten Versicherte mit niedrigem sozialen Status insbesondere aufgrund einer schlechteren subjektiven Gesundheit häufiger Leistungen zur medizinischen Rehabilitation. Weitere Untersuchungen sind nötig, um zu überprüfen, ob dies dem objektiven Bedarf dieser Statusgruppe gerecht wird.
39-jährige Frau mit schwerer COVID-19-Pneumonie: Erfolgreiches Weaning nach septischem Schock und Vorfußamputation wegen mikrovaskulärer Komplikationen
Authors: Pinzon D. , Baumgarten D. , Galetke W. 
Published: April 2021

ZusammenfassungWir präsentieren den Fall einer leicht adipösen 39-jährigen Patientin mit dem schweren Verlauf einer COVID-19-Pneumonie. Die Patientin wurde aus einem Krankenhaus der Regelversorgung mit Verdacht auf eine COVID-19-Pneumonie zugewiesen. Initial bestand die klinische Symptomatik aus Dysurie und Fieber. Im Röntgen-Thorax zeigte sich ein bilaterales Infiltrat. Im CT-Thorax fanden sich beidseits fortgeschrittene COVID-19-typische Veränderungen. Bestätigt wurde die COVID-19-Infektion durch eine positive SARS-CoV-2-PCR aus dem Nasen-Rachen-Abstrich. Bei progredientem ARDS mit respiratorischer Erschöpfung wurde die Patientin intubiert und invasiv beatmet. Unter einem Verdacht auf eine bakterielle Superinfektion leiteten wir eine empirische antibiotische Therapie ein. Es wurde mit Dexamethason begonnen zu behandeln. Zusätzlich wurde ASS und gewichtsadaptiertes halbtherapeutisches niedermolekulares Heparin in die Therapie mit aufgenommen. Im Rahmen der intensivmedizinischen Behandlung entwickelte die Patientin einen fulminanten septischen Schock mit konsekutiver schwerer Thrombozytopenie. Es erfolgte eine dilatative Tracheotomie. Der Weaning-Progress blieb durch rezidivierende septische Schübe erschwert. Als ursächlich für die septischen Schübe konnte eine Nekrose im Bereich des rechten Fußes ausgemacht werden. Bei fehlendem alternativen Fokus erfolgte die chirurgische Sanierung mit Teilamputation. Anschließend blieb die Patientin infektfrei und konnte vom Respirator entwöhnt werden.
Distally Based Peroneus Brevis Muscle Flap for Lower Extremity Defect Reconstruction in Severely Ill Multimorbid Patients
Authors: Schubert Cornelius Dieter , von Freyhold-Hünecken Jochen , Bittrich Thomas , Onken Marie Luise , Tomala Laura , Montenegro Vladan , Elsner Jörg 
Published: April 2021

Abstract
Background Reconstruction of lower extremity soft tissue defects is an exceptional surgical challenge, especially in multimorbid, elderly and severely ill patients with their thin and tense local soft-tissue conditions and increased perioperative risk. The distally based peroneus brevis muscle flap (DPBM), a local flap based on the muscular branches of the fibular artery, could pose a pragmatic solution. The objective of this study was to evaluate and quantify DPBM defect reconstruction in the lower leg, especially in elderly, multimorbid and severely ill patients.
Material and Methods The DPBM as a surgical option in defect reconstruction in multimorbid, elderly, severely ill patients (inclusion criteria: at least 3 pre-existing comorbidities, patient age: at least 55 years, ASA status: at least III) was evaluated in a retrospective single-centre study from 01 April 2014 to 31 December 2019. The electronic SAP health records (EHR) were analysed according to 18 criteria, including patient details, extent of multimorbidity, defect characteristics, clinical outcome, and complications.
Outcome Ten patients with a mean age of 72.6 years, a mean number of 8.5 pre-existing comorbidities and a mean ASA status of 3.1 met the inclusion criteria. The leading causes of defects, each with exposed tendons, bones, joint capsule, or joint, were chronic ulcers (n = 5) and soft tissue defects resulting from fractures (n = 3). In case of DMPB the success rate was 100% (no partial or total loss) with a short operating time (mean: 103 min) and a brief postoperative length of stay (mean: 11 d). In 2 patients (20%), DPBM surgery had to be discontinued intraoperatively and an alternative technique of defect reconstruction had to be adopted. The reasons included impaired muscle perfusion and fatty degeneration of the peroneus brevis muscle.
Conclusion The DPBM flap allows straightforward, fast and safe defect reconstruction in the lower extremity, particularly in elderly, multimorbid and severely ill patients at risk. In patients with inadequate peroneal brevis muscle, however, DMPB surgery should be discontinued intraoperatively and the defect reconstructed using alternative techniques.
Identification of Potential High-Risk Patients on the Basis of PROMs in a Certified Centre for Joint Replacement (EndoProthetikZentrum) Using the Example of Hip Arthroplasty
Authors: Osmanski-Zenk Katrin , Klinder Annett , Ellenrieder Martin , Darowski Martin , Goosmann Martin , Mittelmeier Wolfram 
Published: April 2021

Abstract
Background In addition to clinical parameters, the subjective assessment by the patient to evaluate the operative outcome of an arthroplasty is becoming increasingly important. Questionnaires are used to identify patients who have not achieved the treatment goal at an early stage so that further interventions can be indicated.
Material and Methods A questionnaire consisting of different PROMs was completed pre- and 3 months postoperatively by patients who had been treated with a hip arthroplasty. A standardised follow-up examination of these patients was carried out 12 to 16 weeks postoperatively, after which it was determined whether further therapy was necessary to achieve the treatment goal. Different consequences were defined for this.
Results Significant differences were found between the groups of consequences of follow-up examinations over both time points, but also when postoperative scores were considered exclusively. Furthermore, the correlations for the postoperative scores and some consequences of the clinical follow-up for the Oxford Hip Score (OHS), the OHS functional score and the Euroquol-5D show moderate effects. Thus, the collection of these postoperative scores is sufficient to identify potential high risk patients. Based on a receiver operating characteristic (ROC) analysis, threshold values could be determined for these scores, for which a follow-up examination is recommended.
Conclusion Patients who could not achieve functional improvement, pain reduction and improvement in quality of life after implantation of a total hip replacement must be identified at an early stage. The results of our study show that with the help of the Oxford Hip Score and Euroquol-5D, which are answered by the patients three months postoperatively, such high risk patients can be identified. This finding is an added value for the further development of the EndoCert certification system and holistic quality assurance in arthroplasties, while the personnel and time effort remain manageable.
Injuries after Forklift Trucks Accidents – Injury Patterns, Therapy and Outcome in the Context of the Statutory Accident Insurance
Authors: Ull Christopher , Ehlers Hans , Yilmaz Emre , Lotzien Sebastian , Schildhauer Thomas A. , Reinke Charlotte , Kruppa Christiane 
Published: April 2021

Abstract
Introduction The use of forklift trucks during work has a high accident potential. The aim of this study is to describe injury patterns, treatment and outcome after forklift truck accidents in the context of the employersʼ liability insurance association.
Methods Retrospective data collection of all cases between 2004 and 2019. Excluded were patients < 18 years, without follow-up or with definitive external treatment. Trauma mechanism, injury patterns and distribution, treatment, complications, time of incapacity for work, return to work and impairment of earning capacity were recorded.
Results Of 109 patients with 110 injuries, 52.7% showed isolated injuries and 47.3% combined injuries, which affected the lower extremity in 95 cases. There were fractures in 85.5%, including 32.7% in open form. The mean length of stay was 29.1 days (range 1 – 129); an indication for surgery was seen in 80.9%. Surgical treatment required an average of 3 interventions, with significantly more operations for soft tissue closure than for the fractures (p ≤ 0.023). Amputations were necessary in 8 cases; complications occurred in 29.1%. Return to work was possible in 90%, after a mean period of incapacity for work of 33.6 weeks. A total of 40% showed a pensionable impairment of earning capacity.
Conclusion Accidents with forklift trucks result in complex lower extremities injuries with the need of multi-stage treatment and show relatively high complication rates. A return to work is often possible after a long period of convalescence, and a pensionable impairment of earning capacity often persists.
Histopathology of Microvascular Anastomosis—Comparison of Patent and Nonpatent Anastomosis: An Experimental Study
Authors: Gohil Dhaval , Mohammed Nasser , Mahadevan Anita , Pruthi Nupur 
Published: April 2021

Abstract
Objective To compare the histopathology of patent and nonpatent microvascular anastomosis using rat femoral artery end-to-end anastomosis model.
Materials and Methods In 15 Sprague–Dawley rats, end-to-end anastomosis was performed on the right femoral artery. The classical method was used in four cases and one-way up method in 11 cases. The animals were sacrificed after 2 weeks and the anastomosis was subjected to histopathology. The pathological changes in patent and nonpatent cases were compared.
Results The immediate patency rate and delayed patency (after 2 weeks) rate was 86.7% and 66.7%, respectively. The mean follow-up was 3 months. At sacrifice, 5/15 anastomosis were not patent. Marked subintimal thickening was noted in ⅘ (80%) of the nonpatent group, which was absent in the patent group. Severe loss or fibrosis of tunica media and marked adventitial inflammation were noted in all nonpatent cases (5/5, 100%). As much as ⅘ of the nonpatent cases had poor or indeterminate apposition; in contrast, good apposition was seen in 6/10 (60%) of the patent group. The mean clamp time and mean suturing time were significantly longer in the nonpatent group (69.2 minutes and 53.8 minutes, respectively) as compared with the patent group (48.8 minutes and 31.8 minutes, respectively). A single case that was initially nonpatent was found to have recanalized at 6 months.
Conclusion Minimal intimal injury and reaction, minimal thinning of tunica media, mild-to-moderate adventitial changes, good apposition, and equidistant sutures were associated with a successful microvascular anastomosis. Short duration of vessel clamping time and suturing comes with experience and dedicated practice in a skills laboratory.