bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic genetic variants from highly connected cancer susceptibility genes confer the loss of structural stability
Authors: Reza Mahjerin Nasrin , Ferdous Nadim , Emon Md. Tabassum Hossain , Islam Md. Shariful , Mohiuddin A. K. M. , Hossain Mohammad Uzzal 
Published: September 2021

AbstractGenetic polymorphisms in DNA damage repair and tumor suppressor genes have been associated with increasing the risk of several types of cancer. Analyses of putative functional single nucleotide polymorphisms (SNP) in such genes can greatly improve human health by guiding choice of therapeutics. In this study, we selected nine genes responsible for various cancer types for gene enrichment analysis and found that BRCA1, ATM, and TP53 were more enriched in connectivity. Therefore, we used different computational algorithms to classify the nonsynonymous SNPs which are deleterious to the structure and/or function of these three proteins. The present study showed that the major pathogenic variants (V1687G and V1736G of BRCA1, I2865T and V2906A of ATM, V216G and L194H of TP53) might have a greater impact on the destabilization of the proteins. To stabilize the high-risk SNPs, we performed mutation site-specific molecular docking analysis and validated using molecular dynamics (MD) simulation and molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) studies. Additionally, SNPs of untranslated regions of these genes affecting miRNA binding were characterized. Hence, this study will assist in developing precision medicines for cancer types related to these polymorphisms.
Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis
Authors: Imani Seyedeh Zahra Hosseini , Hojati Zohreh , Khalilian Sheyda , Dehghanian Fariba , Kheirollahi Majid , Khorrami Mehdi , Shaygannejad Vahid , Mirmosayyeb Omid 
Published: September 2021

AbstractMultiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.
Genetic disruption of Plasmodium falciparum Merozoite surface antigen 180 (PfMSA180) suggests an essential role during parasite egress from erythrocytes
Authors: Bahl Vanndita , Chaddha Kritika , Mian Syed Yusuf , Holder Anthony A. , Knuepfer Ellen , Gaur Deepak 
Published: September 2021

AbstractPlasmodium falciparum, the parasite responsible for severe malaria, develops within erythrocytes. Merozoite invasion and subsequent egress of intraerythrocytic parasites are essential for this erythrocytic cycle, parasite survival and pathogenesis. In the present study, we report the essential role of a novel protein, P. falciparum Merozoite Surface Antigen 180 (PfMSA180), which is conserved across Plasmodium species and recently shown to be associated with the P. vivax merozoite surface. Here, we studied MSA180 expression, processing, localization and function in P. falciparum blood stages. Initially we examined its role in invasion, a process mediated by multiple ligand-receptor interactions and an attractive step for targeting with inhibitory antibodies through the development of a malaria vaccine. Using antibodies specific for different regions of PfMSA180, together with a parasite containing a conditional pfmsa180-gene knockout generated using CRISPR/Cas9 and DiCre recombinase technology, we demonstrate that this protein is unlikely to play a crucial role in erythrocyte invasion. However, deletion of the pfmsa180 gene resulted in a severe egress defect, preventing schizont rupture and blocking the erythrocytic cycle. Our study highlights an essential role of PfMSA180 in parasite egress, which could be targeted through the development of a novel malaria intervention strategy.
Anal human papillomavirus infection and its relationship with abnormal anal cytology among MSM with or without HIV infection in Japan
Authors: Shiojiri Daisuke , Mizushima Daisuke , Takano Misao , Watanabe Koji , Ando Naokatsu , Uemura Haruka , Yanagawa Yasuaki , Aoki Takahiro , Tanuma Junko , Tsukada Kunihisa , Teruya Katsuji , Kikuchi Yoshimi , Gatanaga Hiroyuki , Oka Shinichi 
Published: September 2021

AbstractAnal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7–62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p < .001. Among hr-HPV-infected participants, 82.8% (312/377) were infected with at least one of 9 valent vaccine-covered hr-HPV genotypes. From regression analysis, detection of abnormal cytology correlated positively with HIV infection (OR 2.17 [95% CI 1.51–3.13]), number of hr-HPV genotypes infected (OR 1.83 [1.59–2.10]), history of STI (OR 1.58 [1.14–2.22]) and No. of lifetime sexual partners (OR 1.56 [1.10–2.21]), albeit multivariate analysis identified the number of detected hr-HPV genotypes (adjusted OR 1.78 [1.54–2.06]) as the independent risk factor for abnormal cytology. High rates of anal hr-HPV infection, especially 9-valent HPV vaccine-preventable hr-HPV were detected among our MSM participants in Japan. HPV vaccination should also be encouraged for MSM in Japan.
Analysis of longitudinal coupling dynamic characteristics of deep sea mining vessel and stepped lifting pipe
Authors: Song QingHui , Jiang HaiYan , Song QingJun , Xiao LinJing , Wang Yu 
Published: September 2021

AbstractIn deep-sea mining, the coupling dynamic response between the mining vessel and the lifting pipe is a significant problem, which directly affects the structural design of the lifting system and the safety of field operation. The characteristics of coupled motion model have not been fully considered in the existing research. Therefore, this paper uses time-domain coupled numerical model as the research object, considering ocean current, surface wave, pipe dynamics and vessel-pipe contact mechanics, to study the dynamic behavior of the lifting pipe and mining vessel during the process of deep-sea mining using AQWA and OrcaFlex softwares. The response amplitude operator (RAO) is used to compare the measured and simulations dynamic response of the mining vessel. There is a very good agreement in RAO between the experiments and simulations. The coupling simulation results show that the coupling effect has a significant effect on the time domain dynamic response of the lifting pipe, but has little effect on the average effective tension and longitudinal amplitude along the pipe length. The research results of this paper are of great significance to the safety design of deep-sea mining lifting system and the planning of deep-sea operation activities.
Robust behavioural effects in response to acute, but not repeated, terpene administration in Zebrafish (Danio rerio)
Authors: Szaszkiewicz Joshua , Leigh Shannon , Hamilton Trevor J. 
Published: September 2021

AbstractTerpenes are fragrant aromatic compounds produced by a variety of plants, most notably cannabis and hops. With increasing legalization of cannabis there is a need to better understand the behavioural effects of terpenes and ultimately their therapeutic value. Our study investigated the dose-dependent impact of three terpenes (limonene 0.25, 0.5, 0.75%; β-myrcene 0.001, 0.01, 0.1%; and 0.0001, 0.001, 0.00125% linalool) on zebrafish (Danio rerio) behaviour when exposed both acutely and repeatedly over a 7-day period. Anxiety-like behaviour, boldness, and locomotion were assessed using the open field test and the novel object approach test. In the acute dosing experiment, limonene and β-myrcene exposed groups demonstrated a significant decrease in locomotion, a decrease in anxiety-like behaviour, and an increase in boldness, while linalool treatment groups demonstrated only minor alterations in locomotion. Moreover, repeated exposure to limonene (0.39%) or β-myrcene (0.0083%) for a seven day period did not result in any significant behavioural effects. In conclusion, our study provides support for an anxiolytic and sedative effect in zebrafish in response to acute limonene and β-myrcene exposure that is no longer present after one week of repeated exposure.
Common and disorder-specific upregulation of the inflammatory markers TRAIL and CCL20 in depression and schizophrenia
Authors: Klaus Federica , Guetter Karoline , Schlegel Rebecca , Spiller Tobias R. , Seifritz Erich , Cathomas Flurin , Kaiser Stefan 
Published: September 2021

AbstractSchizophrenia (SZ) and major depressive disorder (MDD) are severe mental disorders, which have been associated with alterations of the peripheral inflammatory network. However, studies for both disorders have not been fully consistent and have focused on few canonical markers with high relevance to the innate immune system, while the role of the adaptive immune system is studied less. Furthermore, it is unclear to what extent inflammatory abnormalities are diagnosis-specific or transdiagnostic. The purpose of this study was to investigate 75 peripheral inflammatory markers including the acute phase protein high-sensitivity C-reactive protein (hsCRP) in patients with MDD (n = 37), SZ (n = 42) and healthy controls (HC) (n = 17), while considering possible confounders and correcting rigorously for multiple testing in group comparisons. We identified C–C chemokine ligand 20 (CCL20) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as the inflammatory markers with significant group differences after controlling for multiple comparisons and adjusting for BMI, sex and smoking as confounders. TRAIL was elevated in both MDD and SZ compared to HC. CCL20 was specifically increased in SZ compared to MDD and HC. There were no significant group differences in hsCRP after correcting for multiple testing. Finally, we observed no significant correlations among CCL20, TRAIL and CRP. TRAIL is a transdiagnostic marker for SZ and MDD, with both markers being independent from CRP and body mass index (BMI). CCL20 may be a novel and specific biomarker of schizophrenia, but an influence of antipsychotic medication cannot be excluded. Identifying novel markers in mental disease bears the potential for future research towards novel treatment strategies by modifying inflammation-related processes.
Genome-wide autosomal, mtDNA, and Y chromosome analysis of King Bela III of the Hungarian Arpad dynasty
Authors: Wang Chuan-Chao , Posth Cosimo , Furtwängler Anja , Sümegi Katalin , Bánfai Zsolt , Kásler Miklós , Krause Johannes , Melegh Béla 
Published: September 2021

AbstractThe ancient Hungarians, “Madzsars”, established their control of the Carpathian Basin in the late ninth century and founded the Hungarian Kingdom around 1000AD. The origin of the Magyars as a tribal federation has been much debated in the past. From the time of the conquest to the early fourteenth century they were ruled by descendants of the Arpad family. In order to learn more about the genetic origin of this family, we here analyzed the genome of Bela III one of the most prominent members of the early Hungarian dynasty that ruled the Hungarian Kingdom from 1172 to 1196. The Y-Chromosome of Bela III belongs to haplogroup R1a-Z2123 that is today found in highest frequency in Central Asia, supporting a Central Asian origin for the ruling lineage of the Hungarian kingdom. The autosomal DNA profile of Bela III, however, falls within the genetic variation of present-day east European populations. This is further supported through his mtDNA genome that belongs to haplogroup H, the most common European maternal lineage, but also found in Central Asia. However, we didn’t find an exact haplotype match for Bela III. The typical autosomal and maternal Central Eastern European ancestry among Bela III autosomes might be best explained by consecutive intermarriage with local European ruling families.
Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database
Authors: Qi Guangzhao , Zhang Jingmin , Han Chao , Zhou Yubing , Li Duolu , Ma Pengfei 
Published: September 2021

AbstractInter-individual differences of drug responses could be attributed to genetic variants of pharmacogenes such as cytochrome P450 (CYP), phase 2 enzymes, and transporters. In contrast to extensive studies on the genetic polymorphisms of CYP gene, genetic mutation spectrum of other pharmacogenes was under-representative in the pharmacogenetics investigations. Here we studied the genetic variations of 125 pharmacogenes including drug transporters, non-CYP phase 1 enzymes, phase 2 enzymes, nuclear receptors and others in Chinese from the Chinese Millionome Database (CMDB), of which 38,188 variants were identified. Computational analyses of the 2554 exonic variants found 617 deleterious missense variants, 91.1% of which were rare, and of the 54 loss-of-function (splice acceptor, splice donor, start lost, and stop gained) variants, 53 (98.1%) were rare. These results suggested an enrichment of rare variants in functional ones for pharmacogenes. Certain common functional variants including NUDT15 13:48611934 G/A (rs186364861), UGT1A1 2:234676872 C/T (rs34946978), and ALDH2 12:112241766 G/A (rs671) were population-specific for CMDB Chinese because they were absent (with a zero of variant allele frequency) or very rare in other gnomAD populations. These findings might be useful for the further pharmacogenomics research and clinical application in Chinese.
Temporäre Endgelenkstransfixation bei subkutanen Strecksehnenabrissen der Zone 1 am Fingerendglied
Authors: Suffa Nadine , Merkel Pauline , Horch Raymund E. , Arkudas Andreas , Ludolph Ingo , Stumpfe Maximilian Christoph 
Published: September 2021

Zusammenfassung
Ziel Diese retrospektive, unizentrische Kohortenstudie untersucht die klinischen und subjektiven Ergebnisse nach temporärer K-Drahttransfixation in leichter Überstreckung des distalen Interphalangealgelenkes bei Strecksehnenabrissen.
Patienten und Methoden Die demografischen Daten der Patienten, der Bewegungsumfang des Endgelenkes, der Quick-DASH-Score sowie die Patientenzufriedenheit (0 = unzufrieden, 10 = sehr zufrieden), fortbestehende Schmerzen (ja/nein) und postoperative Komplikationen wurden anhand eines eigens entworfenen Fragebogens und einer zur Bestimmung des Bewegungsausmaßes des Fingerendgelenkes durch die Patienten selbst entwickelten Schablone ermittelt. Fragebogen und Schablone wurden 132 Patienten zugesandt, bei denen im Zeitraum von Januar 2009 bis Dezember 2019 ein Strecksehnenabriss am Fingerendgelenk mittels temporärer K-Drahttransfixation behandelt wurde. 65 Patienten (49,2 %) – 40 Männer und 25 Frauen mit einem durchschnittlichen Alter von 53,3 Jahren – sandten Fragebogen und Schablone vollständig ausgefüllt zurück. 40-mal lag eine akute, 25-mal eine chronische Verletzung vor. 35-mal (54 %) war der Mittel-, 19-mal (29 %) der Klein-, 10-mal (15 %) der Ring- und nur einmal (2 %) der Zeigefinger betroffen. Das Gesamtergebnis wurde unter Berücksichtigung des Streckdefizits entsprechend der Crawford-Klassifikation und dem Vorhandensein von persistierenden Schmerzen bewertet.
Ergebnisse Entsprechend der modifizierten Crawford-Klassifikation fanden sich 75 % exzellente, 14 % gute und 11 % befriedigende Ergebnisse. Die Patienten waren subjektiv im Durchschnitt mit 7,9 von 10 Punkten sehr zufrieden. 15 Patienten berichteten über Komplikationen, 6 davon beklagten anhaltend Schmerzen. Der Quick-DASH-Score lag durchschnittlich bei 5,4 Punkten.
Schlussfolgerung Die temporäre Transfixation des distalen Interphalangealgelenkes in Hyperextensionsstellung stellt ein effektives Verfahren zur Behandlung subkutaner Strecksehnenabrisse mit hoher Patientenzufriedenheit dar.
Distal interphalangeal Joint Arthrodesis using only Kirschner Wires in small distal Phalanges
Authors: Lee Jun-Ku , Lee Soonchul , Choi SeongJu , Han Dong Hun , Oh Jongbeom , Kil Minkyu , Han Soo-Hong 
Published: September 2021

Abstract
Purpose To report the clinical and radiographic results of arthrodesis of relatively small-sized distal interphalangeal joints (DIPJs) using only K-wire fixation.
Patients and methods Between January 2000 and December 2018 28 arthrodesis in 21 patients (9 males and 12 females with an average age of 52.1 years) with relatively small-sized DIPJs were performed using only K-wires. Data on patient’s characteristics, such as age, sex, affected finger, and the number and size of the used k-wires were collected from the medical database. The narrowest diameter of the cortex and medulla of the distal phalanx was measured on preoperative plain radiographs. The time to union and the arthrodesis angle was determined using serial X-ray radiography follow-up. Preoperatively and at the latest follow-up examination, pain using the visual analogue scale (VAS) and the quick DASH score was registered. In addition, complications were investigated.
Results Average follow-up period was 11.4 months. The small finger was mostly affected (n = 12; 42.9 %). The narrowest diameters of the distal phalanx cortex and the medulla measured on preoperative X-ray images were 2.8 mm (SD 0.5) and 1.2 mm (SD 0.4), respectively. Seven fusions were done with use of 1 K-wire, 20 with 2 (71.4 %), and 1 with 3 K-wires. The most common K-wire sizes were 1.1-inch (24 K-wires = 48 %), and 0.9 inch (21 K-wires = 42 %) The preoperative VAS score and quick DASH score improved from 6.1 (range: 0–9) and 25.8 (range: 2–38) to 0.4 (range: 0–2) and 3.4 (range: 0–10.2), respectively. 25 (89.3 %) out of 28 fingers achieved bony union in an average of 96.1 days (range: 58–114) with three non-union.
Conclusion Arthrodesis of small DIPJs with K-wire fixation has a high success rate. Therefore, we suggest K-wire fixation as an acceptable alternative for patients with a small phalanx which may be at risk of mismatch with bigger implants. However, concerns remain in terms of fusion delay with K-wire only fixation.
Der Gelenkersatz mit einem Silikonimplantat bei der Primärversorgung offener Defektverletzungen eines Fingergelenkes
Authors: Besmens Inga Swantje , Giesen Thomas , Guidi Marco , Calcagni Maurizio 
Published: September 2021

ZusammenfassungFingergelenksarthroplastiken mit Silikonimplantaten zur Behandlung einer degenerativen, rheumatischen oder posttraumatischen Gelenksdestruktion werden seit Jahren mit gutem Erfolg durchgeführt. Bei akut schwer traumatisierten Händen erfolgt der Einsatz von Silikonimplantaten selten. Wir berichten über 5 konsekutive Patienten, bei denen bei einer Defektverletzung eines Fingergelenkes bei der Primärversorgung das defekte Gelenk durch ein Silikonimplantat komplikationslos ersetzt wurde. Die Nachbeobachtungszeit betrug mindestens 8 Monate. Bei allen Patienten verlief die Heilung ereignislos ohne Infektionen und mit einem funktionellen Bewegungsumfang. Kein Patient klagte über Instabilität. Bei richtiger Patientenselektion ist der Gelenkersatz mit Silikonimplantaten auch in der akuten Unfallsituation eine sinnvolle Alternative zur Arthrodese von zerstörten Fingergelenken.
The Effect of early active Movement following Repair of Extensor Tendons in Zone IV using three different suture Techniques – A cadaveric Study
Authors: Zeynalov Samir Ilgaroglu , Ismailoglu Abdulveli , Verimli Ural , Alakbarov Anar , Cansü Eren 
Published: September 2021

AbstractPurpose The aim of this study was to investigate the effects of early active movement on the area repaired with three different suture techniques used in extensor tendon injuries in zone IV.Materials and Methods A total of nine cadaver’s 35 extensor tendons from 9 intact upper extremities were used in this study. The proximal and distal borders of the extensor tendons in zone IV were marked. The distance between the proximal and distal border was measured with a 0.5 mm precision tape measure and the mid-point was marked. Intertendinous connections were dissected and loop sutures were prepared for each extensor digitorum. Afterwards, force was applied to each digit along the tendon axis from the loops inserted into the extensor tendons, to measure the extensor forces required to extend the MCP joints to 0˚ with a hand scale. The flexor tendons of the digits were dissected at zone III, and loop sutures were prepared individually for the tendons to enable independent flexion for each digit. The force required to fully flex the digits was measured with a hand scale. The extensor tendons were incised transversely and repaired at the mid-point in zone IV with three different suture techniques (double Kessler, double figure of eight, running interlocking horizontal mattress (RIHM)). The extenxor tendon lengths in zone IV were re-measured for all digits after suturing. The predetermined forces required for full flexion and extension of the digits were applied to the repaired digits. After force was applied 20 times to each tendon, the gap formation was checked. Totally 200 flexion and 200 extension movements were applied to each finger with the help of a hand-held scale. Formation of 2-mm gap was failure criteria. At the end of the movements the extent of the gaps was recorded. In the absence of insufficiency at the repair site, 50 additional flexion and extension movements with double the previously recorded forces were applied to the tendons.Results There was a significant shortening of the extensor tendons after repair independent from the used suture technique. No significant gap formation was detected in all three suture techniques.Conclusion All three suturing techniques are reliable for early active movements following the zone IV extensor tendon repairs. Therefore, surgeons can choose one of those three suture techniques to repair extensor tendon injuries in zone IV.