bluuebunny/crossref_metadata_2025 huggingface dataset:
Activating transcription factor 3 inhibits NF‑κB p65 signaling pathway and mediates apoptosis and cell cycle arrest in cervical cancer cells
Authors: Akbarpour Arsanjani Amirhossein , Abuei Haniyeh , Behzad-Behbahani Abbas , Bagheri Zahra , Arabsolghar Rita , Farhadi Ali
Published: December 2022

Background

As a novel tumor suppressor mediator, activating transcription factor 3 (ATF3) has recently aroused an interest in its possible therapeutic applications in various cancers. In this study, we evaluated the effect of ATF3 overexpression on the cellular level of nuclear factor kappa B (NF-κB) in human papillomavirus (HPV)-infected Ca Ski cells. Further, we examined whether ATF3 could mediate cell cycle arrest and alter the apoptosis level of Ca Ski cells.

Methods

The biological behavior of Ca Ski cells was evaluated prior and subsequent to the overexpression of ATF3 by MTT assay, fluorescence microscopy, cell cycle and annexin V/PI flow cytometric analysis. The effect of ectopic ATF3 expression on the cellular level of NF-κB in HPV-positive cells was evaluated by western blotting assay.

Results

The overexpression of ATF3 in Ca Ski cells led to significant apoptosis and cell cycle arrest in the G1 phase. Western blotting assay revealed a discernible reduction of NF-κB p65 level in cervical cancer cells.

Conclusion

ATF3 acts as a tumor suppressor factor in HPV16-infected Ca Ski cells and exerts anti-cancer effects on HPV16-related cervical cancer cells potentially by hindering cell growth and inducing cell cycle arrest through the down-regulation of NF-κB. Our results suggest that ATF3 induction or NF-κB suppression may be useful targets for HPV16-related cervical cancer prevention and treatment.
Comparison of the neuromuscular effects of two infusion rates of rocuronium in anesthetized pigs
Authors: Pedersen Kamilla , Kruhøffer Linda Loisa , Lykkesfeldt Jens , Kousholt Birgitte Saima
Published: December 2022

Background:

Neuromuscular blocking agents are frequently administered to pigs used for research. In humans, administration of the drugs is not without risk and may result in accidental awareness under general anaesthesia and postoperative residual neuromuscular blockade that can lead to serious respiratory complications. Despite the extensive administration, the pharmacodynamics of neuromuscular blocking agents are not thoroughly studied in pigs. Therefore, this study investigates the neuromuscular response of two infusion rates of rocuronium, a commonly used non-depolarizing neuromuscular blocking agent. A group of 14 female Danish Landrace-Yorkshire-Duroc pigs used for supervised surgical training, weighing 40.3 ± 2.1 kg (mean ± SD), were included in the study. They received a loading dose of 0.85 mg/kg rocuronium intravenously followed by infusion of either 2.5 mg/kg/hour (L, low dose) or 5 mg/kg/hour (H, high dose) rocuronium for 30 min. Neuromuscular monitoring was performed with acceleromyography using train-of-four (TOF) stimulation. Onset time, time to reappearance of T1, T4, TOF ratio 90% and 100% were recorded.

Results:

All pigs in group H experienced loss of T1 throughout rocuronium infusion, whereas six out of seven pigs in group L had reappearance of T1 during rocuronium infusion, with additional reappearance of T4 in three of these pigs. The time to recovery of TOF ratio 90% was 14.0 ± 5.4 (L) and 21.7 ± 6.1 (H) minutes and recovery to TOF ratio 100% was 18.7 ± 6.5 (L) and 27.9 ± 9.2 min (H) (mean ± SD). Substantial inter-animal variation in neuromuscular recovery time was observed.

Conclusion

The large inter-animal variation in pharmacodynamic profiles emphasizes that individual neuromuscular monitoring and titration to effect should be used routinely in research protocols that include rocuronium. In addition to other important measures, these actions are key in order to avoid overdosing and limit the risk of residual neuromuscular blockade.
IGF2BP2-induced circRUNX1 facilitates the growth and metastasis of esophageal squamous cell carcinoma through miR-449b-5p/FOXP3 axis
Authors: Wang Chang , Zhou Mingxia , Zhu Peiyu , Ju Chenxi , Sheng Jinxiu , Du Dan , Wan Junhu , Yin Huiqing , Xing Yurong , Li Hongle , He Jing , He Fucheng
Published: December 2022

Background

Esophageal squamous cell carcinoma (ESCC) is one of the most common digestive malignancies with relatively high morbidity and mortality. Emerging evidence suggests circular RNAs (circRNAs) play critical roles in tumor cell malignancy. However, the biological function and clinical significance of many circRNAs in ESCC remain elusive.

Methods

The expression level and clinical implication of circRUNX1 in ESCC tissues were evaluated using qRT-PCR. In vitro and in vivo functional studies were conducted to investigate the underlying biological effects of circRUNX1 on ESCC cell growth and metastasis. Moreover, bioinformatics analysis, RNA sequencing (RNA-seq), RNA immunoprecipitation (RIP) assays, dual-luciferase reporter assays, and rescue experiments were performed to explore the relationships between circRUNX1, miR-449b-5p, Forkhead box protein P3 (FOXP3), and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2).

Results

CircRUNX1 was found to be significantly up-regulated in ESCC tissues and associated with TNM stage and differentiation grade. Functionally, circRUNX1 promoted ESCC cell proliferation and metastasis in vitro and in vivo. CircRUNX1 enhanced FOXP3 expression by competitively sponging miR-449b-5p. Notably, both miR-449b-5p mimics and FOXP3 knockdown restored the effects of circRUNX1 overexpression on cell proliferation and metastasis. Furthermore, IGF2BP2 binding to circRUNX1 prevented its degradation.

Conclusions

IGF2BP2 mediated circRUNX1 functions as an oncogenic factor to facilitate ESCC progression through the miR-449b-5p/FOXP3 axis, implying that circRUNX1 has the potential to be a promising diagnostic marker and therapeutic target for ESCC patients.
Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies
Authors: Mendogni Paolo , Affatato Roberta , Cabri Enrico , Chiappa Michela , Ndembe Gloriana , Tosi Davide , Del Gobbo Alessandro , Fratelli Maddalena , Pardini Eleonora , Petrini Iacopo , Rosso Lorenzo , Broggini Massimo , Marabese Mirko
Published: December 2022

Background

Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies.

Main body

Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin.

Short conclusion

The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.
The traditional chinese medicine monomer Ailanthone improves the therapeutic efficacy of anti-PD-L1 in melanoma cells by targeting c-Jun
Authors: Yu Pian , Wei Hui , Li Kaixuan , Zhu Shiguo , Li Jie , Chen Chao , Zhang Detian , Li Yayun , Zhu Lei , Yi Xiaoqing , Liu Nian , Liu Panpan , Zhao Shuang , Chen Xiang , Peng Cong
Published: December 2022

Background

C-Jun, a critical component of AP-1, exerts essential functions in various tumors, including melanoma, and is believed to be a druggable target for cancer therapy. Unfortunately, no effective c-Jun inhibitors are currently approved for clinical use. The advent of immune checkpoint inhibitor (ICI) has brought a paradigm shift in melanoma therapy, but more than half of patients fail to exhibit clinical responses. The exploration of new combination therapies has become the current pursuit of melanoma treatment strategy. This study aims to screen out Chinese herbal monomers that can target c-Jun, explore the combined effect of c–Jun inhibitor and ICI, and further clarify the related molecular mechanism. 

Methods

We adopted a combinatorial screening strategy, including molecular docking, ligand-based online approaches and consensus quantitative structure-activity relationship (QSAR) model, to filter out c-Jun inhibitors from a traditional Chinese medicine (TCM) library. A mouse melanoma model was used to evaluate the therapeutic efficacy of monotherapy and combination therapy. Multicolor flow cytometry was employed to assess the tumor microenvironment (TME). Multiple in vitro assays were performed to verify down-streaming signaling pathway. CD4 + T-cell differentiation assay was applied to investigate Treg differentiation in vitro.

Results

Ailanthone (AIL) was screened out as a c-Jun inhibitor, and inhibited melanoma cell growth by directly targeting c-Jun and promoting its degradation. Surprisingly, AIL also facilitated the therapeutic efficacy of anti-programmed death ligand-1 (PD-L1) in melanoma cells by reducing the infiltration of Tregs in TME. Additionally, AIL treatment inhibited c-Jun-induced PD-L1 expression and secretion. As a consequence, Treg differentiation was attenuated after treatment with AIL through the c-Jun/PD-L1 axis.

Conclusion

Our findings identified AIL as a novel c-Jun inhibitor, and revealed its previously unrecognized anti-melanoma effects and the vital role in regulating TME by Treg suppression, which provides a novel combination therapeutic strategy of c-Jun inhibition by AIL with ICI.

Graphical Abstract

AIL down-regulates c-Jun by reducing its stability, and inhibits the function of Tregs via AIL-c-Jun-PD-L1 pathway, ultimately suppressing melanoma progression and enhancing the efficacy of anti-PD-L1.
Aedes aegypti Malpighian tubules are immunologically activated following systemic Toll activation
Authors: Sneed Sarah D. , Dwivedi Sutopa B. , DiGate Cameron , Denecke Shane , Povelones Michael
Published: December 2022

Background

Canine heartworm is a widespread and potentially fatal mosquito-borne disease caused by infections with the parasitic nematode, Dirofilaria immitis. We have previously shown that systemic activation of the Toll immune pathway via silencing of the negative regulator Cactus in Aedes aegypti blocks parasite development in the Malpighian tubules (MT), the mosquito renal organ. However, it was not established whether the MT were directly responding to Toll activation or were alternatively responding to upregulated proteins or other changes to the hemolymph driven by other tissues. Distinguishing these possibilities is crucial for developing more precise strategies to block D. immitis while potentially avoiding the fitness cost to the mosquito associated with Cactus silencing.

Methods

This study defines the transcriptional response of the MT and changes to the hemolymph proteome of Ae. aegypti after systemic Toll activation via intra-thoracic injection of double-stranded Cactus (dsCactus) RNA.

Results

Malpighian tubules significantly increased expression of the Toll pathway target genes that significantly overlapped expression changes occurring in whole mosquitoes. A significant overlap between the transcriptional response of the MT and proteins upregulated in the hemolymph was also observed.

Conclusions

Our data show that MT are capable of RNA interference-mediated gene silencing and directly respond to dsCactus treatment by upregulating targets of the canonical Toll pathway. Although not definitive, the strong correspondence between the MT transcriptional response and the hemolymph proteomic responses provides evidence that the MT may contribute to mosquito humoral immunity.

Graphical Abstract
Lifestyle characteristics in adolescent female football players: data from the Karolinska football Injury Cohort
Authors: Fältström Anne , Skillgate Eva , Weiss Nathan , Källberg Henrik , Lyberg Victor , Waldén Markus , Hägglund Martin , Asker Martin , Tranaeus Ulrika
Published: December 2022

Background

Normative values of lifestyle characteristics in adolescent female football players may be used by clinicians and coaches to take actions because the potential important for well-being, performance on the pitch, and risk of injury. The aim was to report descriptive characteristics of lifestyle factors in adolescent female football players and potential changes over 1 year.

Methods

We included 419 adolescent competitive female football players from 12 clubs and 27 teams (age 14 ± 1 years, range 12–17 years) and 286 were followed over 1 year. The players completed an extensive questionnaire regarding demographics, football-related factors, and lifestyle factors including tobacco consumption, alcohol use, medicine intake, eating and sleeping habits, well-being, stress, coping, and passion. Baseline data are presented for the total cohort and separately for 4 age groups (12, 13, 14, and 15–17 years).

Results

12% skipped breakfast, 8% skipped lunch and 11% used protein supplements several days per week. 16% slept less than 8 h/night, 8% had impaired sleep with daytime consequences, and 22% stated that they were tired in daily activities several days per week. 32% experienced stress some or most days/week and 24% were classified as having psychological distress. Medicine intake (23% vs. 34%), skipping breakfast or lunch several days per week (10% vs. 47% and 20 vs. 33%), tiredness (20% vs. 27%), stress (26% vs. 40%), and psychological distress (27% vs. 37%) increased significantly (P = 0.031 to < 0.001) at the 1-year follow-up.

Conclusion

Many adolescent female football players skip breakfast and lunch, have insufficient sleep, experience stress and are classified as having psychological distress. These factors increased over 1 year.
Spontaneous cholecystocutaneous fistula secondary to xanthogranulomatous cholecystitis: a case report
Authors: Almayouf Abdullah A. , Ahmed Hassan M. , Alzahrani Adel A. , Alashkar Abdulrahman H.
Published: December 2022

Background

Xanthogranulomatous cholecystitis, a rare variant of cholecystitis, may infrequently be complicated by spontaneous cholecystocutaneous fistula.

Case presentation

We report the case of a 75-year-old Saudi Arabian man who presented with “a painful area of redness” (cellulitis) over his right upper abdomen. Abdominal computed tomography revealed multiple collections, which were drained surgically. A discharging sinus was identified, and a fistulogram revealed cholecystocutaneous fistula during his follow-up visit. The patient underwent laparoscopic management and recovered uneventfully. Final histopathological evaluation confirmed acute-on-chronic xanthogranulomatous cholecystitis .

Conclusions

Although rare, surgeons should consider cholecystocutaneous fistula in the differential diagnosis of anterior abdominal wall abscesses, particularly in patients with concurrent or background symptoms of gallbladder disease. We report the first case of laparoscopic management for cholecystocutaneous fistula in Saudi Arabia.
Threatening the 5G core via PFCP DoS attacks: the case of blocking UAV communications
Authors: Amponis George , Radoglou-Grammatikis Panagiotis , Lagkas Thomas , Mallouli Wissam , Cavalli Ana , Klonidis Dimitris , Markakis Evangelos , Sarigiannidis Panagiotis
Published: December 2022

The modern communications landscape requires reliable, high-speed, high-throughput and secure links and sessions between user equipment instances and the data network. The 5G core implements the newly defined 3GPP network architecture enabling faster connectivity, low latency, higher bit rates and network reliability. The full potential of this set of networks will support a set of critical Internet of things (IoT) and industrial use cases. Nevertheless, several components and interfaces of the next-generation radio access network (NG-RAN) have proven to be vulnerable to attacks that can potentially obstruct the network’s capability to provide reliable end-to-end communication services. Various inherent security flaws and protocol-specific weaknesses have also been identified within the 5G core itself. However, little to no research has gone into testing and exposing said core-related weaknesses, contrary to those concerning the NG-RAN. In this paper, we investigate, describe, develop, implement and finally test a set of attacks on the Packet Forwarding Control Protocol (PFCP) inside the 5G core. We find that, by transmitting unauthorised session control packets, we were able to disrupt established 5G tunnels without disrupting subscribers’ connectivity to the NG-RAN, thus hindering the detection of said attacks. We evaluate the identified PFCP attacks in a drone-based scenario involving 5G tunnelling between two swarms.
Analysis of a stochastic predator–prey system with fear effect and Lévy noise
Authors: Xue Renxiu , Shao Yuanfu , Cui Minjuan
Published: December 2022

This paper studies a stochastic predator–prey model with Beddington–DeAngelis functional response, fear effect, and Lévy noise, where the fear is of prey induced by predator. First, we use Itô’s formula to prove the existence and uniqueness of a global positive solution and its moment boundedness. Next, sufficient conditions for the persistence and extinction of both species are given. We further investigate the stability in distribution of our system. Finally, we verify our analytical results by exhaustive numerical simulations.
3D printing of molds for the creation of facsimiles and volumetric reintegrations in wax anatomical sculptures
Authors: Sterp Moga Emanuel , Sánchez-Ortiz Alicia , Hernández-Muñoz Óscar
Published: December 2022

In recent years, 3D printing technologies have had a considerable impact on the field of conservation and restoration of cultural heritage. Professionals in this sector have been provided with exploratory tools for documenting, analyzing, intervening, and preserving objects and works of art that make up our history. This research focuses on finding the most suitable material along with the ideal printing position that could provide molds for the production of anatomical wax facsimiles that guarantee maximum quality and fidelity when compared to its original. These replicas and fragments allow conservator-restorers to volumetrically reintegrate while testing different options before applying direct treatment to the works. The results obtained from testing on different types of printing materials as well as the positives achieved from them are presented.
Εffect of cleansers on the composition and mechanical properties of orthodontic aligners in vitro
Authors: Iliadi Anna , Enzler Vera , Polychronis Georgios , Peltomaki Timo , Zinelis Spiros , Eliades Theodore
Published: December 2022

Background

The aim of the study was to investigate the effect of three aligner cleaners on the composition and mechanical properties of two types of orthodontic aligners.

Materials and methods

The cleaners tested were two alkaline peroxide solutions (Retainer Brite—RB; Retainer Cleaner—RC) and one peroxide-free (Steraligner—ST) and the aligners Clear Aligner (C, polyester) and Invisalign (I, polyester–urethane). The aligners were immersed in the cleaner solutions as instructed every day (15 min for RB, RC; 5 min for ST) for a two-week period. The acidity of the solutions was tested with a pH meter. The changes in the chemical composition of the aligners were studied by attenuated total-reflection Fourier transform infrared spectrometry (ATR-FTIR), while Instrumented Indentation Testing (IIT) was used for assessment of changes in Martens Hardness (HM), modulus (EIT), elastic index (nIT) and relaxation (RIT).

Results

RB and RC were weakly acidic (pH = 6.3), whereas ST was mildly acidic (pH = 4.8). The ATR-FTIR analysis demonstrated evidence of acidic hydrolysis of C in ST and I in RB. The IIT-derived properties of I were not affected by the cleaners. However, for C a significant change was found in HM (all cleaners), nIT (all cleaners) and RIT (RB, ST). Although the chemical changes support a hydrolytic material deterioration, the results of mechanical properties may interfere with the material residual stresses during fabrication.

Conclusions

Caution should be exerted in the selection of aligner cleaners. The mild acidic cleanser was more aggressive to the polyester, whereas an alkaline peroxide to the polyester–urethane aligner.
Effects of cerebellar transcranial direct current stimulation on upper limb motor function after stroke: study protocol for the pilot of a randomized controlled trial
Authors: Yuasa Akiko , Uehara Shintaro , Ushizawa Kazuki , Toyama Takamichi , Gomez-Tames Jose , Hirata Akimasa , Otaka Yohei
Published: December 2022

Background

Transcranial direct current stimulation (tDCS) is a technique that can noninvasively modulate neural states in a targeted brain region. As cerebellar activity levels are associated with upper limb motor improvement after stroke, the cerebellum is a plausible target of tDCS. However, the effect of tDCS remains unclear. Here, we designed a pilot study to assess: (1) the feasibility of a study that aims to examine the effects of cerebellar tDCS combined with an intensive rehabilitation approach based on the concept of constraint-induced movement therapy (CIMT) and (2) the preliminary outcome of the combined approach on upper limb motor function in patients with stroke in the chronic stage.

Methods

This pilot study has a double-blind randomized controlled design. Twenty-four chronic stroke patients with mild to moderate levels of upper limb motor impairment will be randomly assigned to an active or sham tDCS group. The participants will receive 20 min of active or sham tDCS to the contralesional cerebellum at the commencement of 4 h of daily intensive training, repeatedly for 5 days per week for 2 weeks. The primary outcomes are recruitment, enrollment, protocol adherence, and retention rates and measures to evaluate the feasibility of the study. The secondary outcome is upper limb motor function which will be evaluated using the Action Research Arm Test, Fugl-Meyer Assessment, for the upper extremity and the Motor Activity Log. Additionally, neurophysiological and neuroanatomical assessments of the cerebellum will be performed using transcranial magnetic stimulation and magnetic resonance imaging. These assessments will be conducted before, at the middle, and after the 2-week intervention, and finally, 1 month after the intervention. Any adverse events that occur during the study will be recorded.

Discussion

Cerebellar tDCS combined with intensive upper limb training may increase the gains of motor improvement when compared to the sham condition. The present study should provide valuable evidence regarding the feasibility of the design and the efficacy of cerebellar tDCS for upper limb motor function in patients with stroke before a future large trial is conducted.

Trial registration

This study has been registered at the Japan Registry of Clinical Trials (jRCTs042200078). Registered 17 December 2020
Influences of early diagnostic suggestions on clinical reasoning
Authors: Kourtidis Ploutarchos , Nurek Martine , Delaney Brendan , Kostopoulou Olga
Published: December 2022

Previous research has highlighted the importance of physicians’ early hypotheses for their subsequent diagnostic decisions. It has also been shown that diagnostic accuracy improves when physicians are presented with a list of diagnostic suggestions to consider at the start of the clinical encounter. The psychological mechanisms underlying this improvement in accuracy are hypothesised. It is possible that the provision of diagnostic suggestions disrupts physicians’ intuitive thinking and reduces their certainty in their initial diagnostic hypotheses. This may encourage them to seek more information before reaching a diagnostic conclusion, evaluate this information more objectively, and be more open to changing their initial hypotheses. Three online experiments explored the effects of early diagnostic suggestions, provided by a hypothetical decision aid, on different aspects of the diagnostic reasoning process. Family physicians assessed up to two patient scenarios with and without suggestions. We measured effects on certainty about the initial diagnosis, information search and evaluation, and frequency of diagnostic changes. We did not find a clear and consistent effect of suggestions and detected mainly non-significant trends, some in the expected direction. We also detected a potential biasing effect: when the most likely diagnosis was included in the list of suggestions (vs. not included), physicians who gave that diagnosis initially, tended to request less information, evaluate it as more supportive of their diagnosis, become more certain about it, and change it less frequently when encountering new but ambiguous information; in other words, they seemed to validate rather than question their initial hypothesis. We conclude that further research using different methodologies and more realistic experimental situations is required to uncover both the beneficial and biasing effects of early diagnostic suggestions.
COVID19-induced immunosuppression and aggressive progression of primary cranial vault lymphoma presenting as a management challenge, a case report, and a literature review
Authors: Jha Vikas Chandra , Alam Mohammad Shahnawaz
Published: December 2022

Background

We needs to study Primary Large cell Non-Hodgkin’s Lymphoma of the cranial vault, which is rare, and its association with COVID19 has not been reported, which may have an immunosuppressive effect to aggravate its progression.

Patient details

Our patient, a 53-year-old male, noticed fast growth of posterior cranial vault lesion from 2 to 10 cm size in last 6 months after COVID 19 affliction. MRI brain with contrast revealed lesions suggesting meningioma. The whole-body PET scan was normal. Following Subtotal excision of the mass, histopathology revealed large B-cell Non-Hodgkin’s lymphoma (DLBCL). Immunohistochemistry showed positive results for CD10, CD20, CD45 (LCA), ALK, and BCL-VE with a Ki-67 index of 90–95%. Following radiotherapy and chemotherapy patient is disease-free on imaging and doing well at 5 months of follow-up.

Conclusions

Early intervention with excisional biopsy and timely chemo and radiotherapy in favorable immunostaining may add survival benefits even in malignant features induced by immunosuppressing diseases such as COVID19 in diffuse large B-cell lymphoma (DLBCL) of the scalp.
ALSFRS-R-SE: an adapted, annotated, and self-explanatory version of the revised amyotrophic lateral sclerosis functional rating scale
Authors: Maier André , Boentert Matthias , Reilich Peter , Witzel Simon , Petri Susanne , Großkreutz Julian , Metelmann Moritz , Lingor Paul , Cordts Isabell , Dorst Johannes , Zeller Daniel , Günther René , Hagenacker Tim , Grehl Torsten , Spittel Susanne , Schuster Joachim , Ludolph Albert , Meyer Thomas ,   for the MND-NET consensus group
Published: December 2022

Background

The ALS Functional Rating Scale in its revised version (ALSFRS-R) is a disease-specific severity score that reflects motor impairment and functional deterioration in people with amyotrophic lateral sclerosis (ALS). It has been widely applied in both clinical practice and ALS research. However, in Germany, several variants of the scale, each differing slightly from the others, have developed over time and are currently in circulation. This lack of uniformity potentially hampers data interpretation and may decrease item validity. Furthermore, shortcomings within the standard ALSFRS-R questions and answer options can limit the quality and conclusiveness of collected data.

Methods

In a multistage consensus-building process, 18 clinical ALS experts from the German ALS/MND network analyzed the ALSFRS-R in its current form and created an adapted, annotated, and revised scale that closely adheres to the well-established standardized English version.

Results

Ten German-language variants of the ALSFRS-R were collected, three of which contained instructions for self-assessment. All of these variants were compiled and a comprehensive linguistic revision was undertaken. A short introduction was added to the resulting scale, comprising general instructions for use and explanations for each of the five reply options per item. This adapted version of the scale, named ALSFRS-R-SE (with the “SE” referring to “self-explanatory”), was carefully reviewed for language and comprehensibility, in both German and English.

Conclusion

An adapted and annotated version of the ALSFRS-R scale was developed through a multistage consensus process. The decision to include brief explanations of specific scale items and reply options was intended to facilitate ALSFRS-R-SE assessments by both healthcare professionals and patients. Further studies are required to investigate the accuracy and utility of the ALSFRS-R-SE in controlled trials and clinical real-world settings.
Genotype by environment interaction analysis for Fusarium head blight response and yield performance of bread wheat (Triticum aestivum L.) in southern Ethiopia
Authors: Mengesha Getachew Gudero , Abebe Shiferaw Mekonnen , Tsakamo Yisahak Tsegaye , Issa Bilal Temmam , Lera Zerhun Tomas , Shertore Misgana Mitku , Fedilu Kedir Bamud , Tadesse Yosef Berihun , Mekonnen Asaminew Amare , Esho Abate Gebremikael , Dojamo Tariku Simion , Halengo Muluneh Mekiso , Mena Gedyon Tamru , Adamo Wondimu Adila , Cheleko Dizgo Chencha , Woldesilassie Agdew Bekele
Published: December 2022

Fusarium head blight (FHB) is one of the major biotic constraints to wheat due to its direct detrimental effects on yield quality and quantity. To manage the disease, the deployment of resistant genotypes is ideal in terms of effectiveness, eco-friendliness, and sustainability of production. The study was conducted to determine the responses of different wheat genotypes to FHB, and to identify suitable and stable wheat genotype(s) regarding the FHB resistance and yield performance. A field study was carried out using eleven bread wheat genotypes in seven locations in southern Ethiopia during the 2019 main cropping season. A randomized complete block design with three-time replicates was applied in this study. The results showed that the lowest mean FHB severity (11.33%) and highest mean yield (4.54 t/ha) were recorded at Bonke. Conversely, the highest mean FHB severity (83.38%) and the lowest mean yield (0.94 t/ha) were observed at North Ari. It was also showed that maximum mean FHB severity (49.25%) and minimum mean yield (2.95 t/ha) were recorded on the genotype Hidase under crosswise assessment. Across locations, a minimum mean FHB severity (17.54, 18.83, and 21.31%) and maximum mean yield (3.92, 3.96, and 3.93 t/ha) were noted from the Shorima, Bondena, and Wane genotypes, respectively. GGE biplot analysis and various comparison tests for FHB severity revealed a higher percentage of variation concerning FHB resistance reactions due to the environment (47% as an interactive element), followed by genotype by environment interaction (21%). AMMI analysis revealed genotype, environment, and genotype by environment interaction had a total variation of 7.10, 58.20, and 17.90% for yield performance, respectively. The inconsistency between genotype responses to FHB and yield performance demonstrated that the environmental component was responsible for significant variability in FHB reaction, yield performance, and the dominance of cross-over interaction. However, the greatest level of resistance to FHB was comparatively found in the genotypes Shorima, Bondena, Wane, and Huluka across locations. Considering both FHB resistance response and yield stability, in most environments, Shorima, Bondena, Wane, and Huluka genotypes were suggested for consideration of cultivation where they are well-performed under the pressure of FHB. North Ari and Hulbareg were acknowledged as more discriminating environments than the others for test genotypes against FHB. Bonke and Chencha were considered ideal environments for selecting superior genotypes with good yield performance.
Evidence of orthohantavirus and leptospira infections in small mammals in an endemic area of Gampaha district in Sri Lanka
Authors: Sunil-Chandra N. P. , Fahlman Åsa , Waidyarathna Shantha , Näslund Jonas , Jayasundara M. V. M. L. , Wesula Lwande Olivia , Bucht Göran
Published: December 2022

Background

Orthohantaviruses and leptospira are emerging zoonotic pathogens of high public health significance. The epidemiology of orthohantavirus infections and leptospirosis is similar and presents related clinical pictures in humans. However, a paucity of data on actual reservoir hosts for orthohantaviruses and leptospira exists. Therefore, this study aimed at determining the occurrence of orthohantaviruses and leptospira in small mammals captured in an endemic region of Sri Lanka.

Methods

Rodents and shrews were morphologically and/or genetically identified using morphological keys and DNA barcoding techniques targeting the cytochrome oxidase b subunit gene (Cytb). Lung tissues and sera were subsequently analyzed for the presence of orthohantavirus RNA using qRT-PCR. Sera of rats were tested for IgG antibodies against orthohantaviruses and leptospira.

Results

Forty-three (43) small mammals representing: Rattus (R.) rattus (black rat) or R. tanezumi (Asian rat), Suncus murinus (Asian house shrew), R. norvegicus (brown rat) and Mus musculus (house mouse) were investigated. No orthohantavirus RNA was detected from the lung tissue or serum samples of these animals. Elevated levels of IgG antibodies against Puumala orthohantavirus (PUUV) and/or Seoul orthohantavirus (SEOV) antigens were detected in sera of 28 (72%) out of the 39 rats analysed. Interestingly, 36 (92%) of the 39 rats also showed presence of anti leptospira-IgG antibodies in their serum, representing dual infection or dual exposure in 26/39 (66.7%) of examined rats.

Conclusions

This project targets important public health questions concerning the occupational risk of orthohantavirus infections and/or leptospirosis in an endemic region of Sri Lanka. Most rats (72%) in our study displayed antibodies reacting to orthohantavirus NP antigens, related to PUUV and/or SEOV. No correlation between the orthohantavirus and leptospira IgG antibody levels were noticed. Finally, a combination of both morphological and DNA barcoding approaches revealed that several species of rats may play a role in the maintenance and transmission of orthohantavirus and leptospira in Sri Lanka.
Characterization of the gut microbiome and resistome of Galapagos marine iguanas (Amblyrhynchus cristatus) from uninhabited islands
Authors: Vasco Karla , Guevara Nataly , Mosquera Juan , Zapata Sonia , Zhang Lixin
Published: December 2022

Background

Understanding the natural microbiome and resistome of wildlife from remote places is necessary to monitor the human footprint on the environment including antimicrobial use (AU). Marine iguanas are endemic species from the Galapagos Islands where they are highly affected by anthropogenic factors that can alter their microbiota as well as their abundance and diversity of antimicrobial-resistant genes (ARGs). Thus, this study aims to apply culture-independent approaches to characterize the marine iguana’s gut metagenomic composition of samples collected from the uninhabited islands Rabida (n = 8) and Fernandina (Cabo Douglas, n = 30; Punta Espinoza, n = 30). Fresh feces from marine iguanas were analyzed through SmartChip RT-PCR, 16S rRNA, and metagenomic next-generation sequencing (mNGS) to identify their microbiome, microbial-metabolic pathways, resistome, mobilome, and virulome.

Results

The marine iguana’s gut microbiome composition was highly conserved despite differences in ecological niches, where 86% of taxa were shared in the three locations. However, site-specific differences were mainly identified in resistome, mobilome, virulorome, and metabolic pathway composition, highlighting the existence of factors that induce microbial adaptations in each location. Functional gut microbiome analyses revealed its role in the biosynthesis and degradation of vitamins, cofactors, proteinogenic amino acids, carbohydrates, nucleosides and nucleotides, fatty acids, lipids, and other compounds necessary for the marine iguanas. The overall bacterial ARG abundance was relatively low (0.006%); nevertheless, the presence of genes encoding resistance to 22 drug classes was identified in the iguana’s gut metagenome. ARG-carrying contig and co-occurrence network analyses revealed that commensal bacteria are the main hosts of ARGs. Taxa of public health interest such as Salmonella, Vibrio, and Klebsiella also carried multidrug-resistance genes associated with MGEs which can influence the dissemination of ARGs through horizontal gene transfer.

Conclusion

Marine iguanas depend on the gut microbiome for the biosynthesis and degradation of several compounds through a symbiotic relationship. Niche-specific adaptations were evidenced in the pool of microbial accessory genes (i.e., ARGs, MGEs, and virulence) and metabolic pathways, but not in the microbiome composition. Culture-independent approaches outlined the presence of a diverse resistome composition in the Galapagos marine iguanas from remote islands. The presence of AR pathogens in marine iguanas raises concerns about the dispersion of microbial-resistant threats in pristine areas, highlighting wildlife as sentinel species to identify the impact of AU.
Posterior-stabilized total knee arthroplasty kinematics and joint laxity: A hybrid biomechanical study
Authors: Sekeitto Allan R. , McGale Jance G. , Montgomery Liam A. , Vasarhelyi Edward M. , Willing Ryan , Lanting Brent A.
Published: December 2022

Background

Posterior-stabilized (PS)-total knee arthroplasty (TKA) arose as an alternative to cruciate-retaining (CR)-TKA in the 1970s. Since then, it has become a popularly utilized TKA design with outcomes comparable to CR-TKA. The post-cam mechanism is unique to PS-TKA as it substitutes the function of the posterior cruciate ligament (PCL). The study aimed to understand the kinematic and laxity changes in PS-TKA with under- and overstuffing of the tibiofemoral joint space with the polyethylene (PE) insert.

Methods

This study employed a hybrid computational-experimental joint motion simulation on a VIVO 6 degrees of freedom (6-DoF) joint motion simulator (AMTI, Watertown, MA, USA). Physical prototypes of a virtually-performed TKA in mechanical alignment (MA) and kinematic alignment (KA) based on cadaveric CT scans and a virtual ligament model were utilized. The reference, understuffed (down 2 mm) and overstuffed (up 2 mm) joint spaces were simulated, neutral flexion and laxity testing loads and motions were performed for each configuration.

Results

The PE insert thickness influenced post-cam engagement, which occurred after 60º in the overstuffed configurations, after 60º–75º in the reference configurations and after 75º in the understuffed configurations. The understuffed configurations, compared to the reference configurations, resulted in a mean 2.0º (28%) and 2.0º (31%) increase in the coronal laxity in MA and KA respectively. The overstuffed configurations, compared to the reference configuration, resulted in an increase in the mean joint compressive forces (JCFs) by 73 N (61%) and 77 N (62%) in MA and KA models, respectively.

Conclusions

The under- and overstuffing in PS-TKA alter the kinematics with variable effects. Understuffing decreases the stability, JCFs and inverse with overstuffing. Subtle changes in the PE insert thickness alter the post-cam mechanics.
A case of SAPHO syndrome: a DISH of radiological features to be considered
Authors: Sabooniha Fakhreddin
Published: December 2022

Background

The acronym SAPHO stands for synovitis, acne, pustulosis, hyperostosis, and osteitis. It is a rare heterogenous disease with unknown etiology and a chronic relapsing and remitting course1. Its skin and osteoarticular manifestations including palmoplantar pustulosis (PPP) and synovitis may be transient which further complicate the diagnosis. So, awareness about all features of the syndrome throughout the time seems mandatory for correct diagnosis and avoidance of unnecessary procedures.

Case presentation.

A case of SAPHO syndrome being reported in a middle-aged man who presented with bilateral PPP and exacerbation of back pain which developed shortly after covid-19 vaccine injection with a history of more than 20 years of inflammatory thoracic back pain and psoriasis vulgaris who initially had been worked up for metastatic bony lesions based on radiologic studies, irrespective of his skin lesions. The patient had good response to alendronate 70 mg weekly and celecoxib 200 mg BID without aggravation of existing skin lesions or new psoriatic lesions.

Conclusion

This case report aims to inform rheumatologists and radiologists about various radiologic and dermatologic manifestations of SAPHO syndrome with emphasizing on taking into consideration of past and present skin lesions in the interpretation of the radiologic signs in order to prevent irrelevant procedures or hazardous imaging and to urge rheumatology societies to set up a SAPHO registry for future randomized controlled trials. Suggestion of PPP responsiveness to NSAIDs as a new potential diagnostic tool for SAPHO diagnosis is another goal. It also aims to point out the possible coexistence of SAPHO and SpA or DISH syndrome.
The role of Hedgehog and Notch signaling pathway in cancer
Authors: Xia Ruolan , Xu Maosen , Yang Jing , Ma Xuelei
Published: December 2022

Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.
Immunotherapy and Biomarker Testing in Recurrent and Metastatic Head and Neck Cancers: ASCO Guideline
Authors: Yilmaz Emrullah , Ismaila Nofisat , Bauman Julie E. , Dabney Raetasha , Gan Gregory , Jordan Richard , Kaufman Marnie , Kirtane Kedar , McBride Sean Matthew , Old Matthew O. , Rooper Lisa , Saba Nabil F. , Sheth Siddharth , Subramaniam Rathan M. , Wise-Draper Trisha Michel , Wong Deborah , Mell Loren K.
Published: December 2022

PURPOSE

To provide evidence-based recommendations for practicing physicians and other health care providers on immunotherapy and biomarker testing for head and neck cancers.

METHODS

ASCO convened an Expert Panel of medical oncology, surgical oncology, radiation oncology, radiology, pathology, and patient advocacy experts to conduct a literature search, including systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2022. Outcomes of interest included survival, overall response, and locoregional control. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

RESULTS

The literature search identified 28 relevant studies to inform the evidence base for this guideline.

RECOMMENDATIONS

When possible, evidence-based recommendations were developed to address biomarker testing, first-line treatment regimens based on programmed death ligand-1 scores, immunotherapy in platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma, immunotherapy in nasopharyngeal carcinoma, and radiation therapy in combination with immunotherapy for treatment of local recurrence. Additional information is available at www.asco.org/head-neck-cancer-guidelines .
Reorienting Visual Reading
Authors: Mor Liron
Published: December 2022

This essay explores visual reading and its colonial aspects by analyzing the novel Ze ʿim ha-panim elenu (The One Facing Us, 1995), by Ronit Matalon, an Israeli Jewish author of Egyptian descent. In this novel Matalon displaces the dramas of Mizrahi Jews (Jews originating from the Arab and Muslim world) to Cameroon, thus stressing her protagonists’ uneasy positioning within the colonizer-colonized, West-East divides and connecting Zionist racialization to broader, global processes of colonial capitalism. By exploring her elaborate readings of photographs in the novel, the essay reveals two rival traditions of reading the visual: the first involves what might be described, following Matalon, as a certain “intending toward” the photograph—a colonial reading practice through which a subject converts her absence from the photographic moment into a visionary, intentional presence. In this Barthesian tradition, the image is an empty land to be colonized, and Oriental subjects are racialized by being fetishistically associated with both authentic matter and theological aura. The second tradition, typified in the novel by the protagonist’s Egyptian mother, is a laborious collective practice of reading photographs that is attentive to subtext, nonverbal communication, and social codes. The essay argues that this reading practice has nothing to do with postcolonial or Levantine hybridity or with a “migratory state of mind”—concepts that govern scholarship on Matalon—and that its subsistence requires in fact a solid, counterdiasporic sense of home.
Πρότυπα γυναικών στα σύγχρονα παιδικά βιβλία γνώσεων. Καταρρίπτοντας την έμφυλη ιδεολογική διχοτομία στον χώρο των Επιστημών
Authors: Αγγελάκη Ρόζη-Τριανταφυλλιά
Published: December 2022

Τα πραγματογνωστικά παιδικά βιβλία γνώσεων είναι έργα πολυτροπικά με μορφωτικό χαρακτήρα, που σκοπό έχουν να πληροφορήσουν παιδιά προσχολικής ή πρωτοσχολικής ηλικίας για οτιδήποτε τους περιβάλλει, μέσα από απλές και τεκμηριωμένες περιγραφές. Τα τελευταία χρόνια παρατηρείται η τάση των τέτοιων έργων να περιπλέκουν ηθελημένα το μυθοπλαστικό στοιχείο στις ιστορίες τους. Συχνά, η μορφή των σύγχρονων κειμένων είναι ιδιάζουσα, καθώς φέρουν χαρακτηριστικά της μυθιστορηματικής βιογραφίας, της αυτοβιογραφίας και των παιδικών εικονοβιβλίων, επιβεβαιώνοντας την υβριδικότητα του είδους. Εν προκειμένω, θα εξετάσουμε το έργο της Στέλλας Κάσδαγλη 30 γυναίκες που άλλαξαν τον κόσμο και πως μπορείς να τον αλλάξεις κι εσύ (2020), και τον Άτλαντα σπουδαίων προσωπικοτήτων. 101 προσωπικότητες της Ιστορίας που άλλαξαν τον κόσμο (2019) της Μιράλντα Κολόμπο. Θα μας απασχολήσει πώς οι συγγραφείς επιχείρησαν να πληροφορήσουν τα παιδιά για την ενασχόληση των γυναικών με τις Επιστήμες, με σκοπό να τα καταστήσουν επιστημονικά γραμματισμένα και να συμβάλλουν στη διακοπή της αναπαραγωγής διακρίσεων και ανισοτήτων, ιδιαίτερα όσον αφορά στην ενασχόληση των γυναικών με τις Επιστήμες και την Τεχνολογία.