bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear B-spline finite element method for the generalized diffusion equation with delay
Authors: Lubo Gemeda Tolessa , Duressa Gemechis File
Published: June 2022

Objectives

The main aim of this paper is to develop a linear B-spline finite element method for solving generalized diffusion equations with delay. The linear B-spline basis function is used to discretize the space variable. The time discretization process is based on Crank-Nicolson. The benefit of the scheme is that the numerical solution is obtained as a smooth piecewise continuous function which empowers one to find an approximate solution at any desired position in the domain.

Result

Sufficient and necessary conditions for the numerical method to be asymptotically stable are derived. The convergence of the numerical method is studied. Some numerical experiments are performed to verify the applicability of the numerical method.
Hyperthermia increases HSP production in human PDMCs by stimulating ROS formation, p38 MAPK and Akt signaling, and increasing HSF1 activity
Authors: Liu Ju-Fang , Chen Po-Chun , Ling Thai-Yen , Hou Chun-Han
Published: June 2022

Background

Human placenta-derived multipotent cells (hPDMCs) are isolated from a source uncomplicated by ethical issues and are ideal for therapeutic applications because of their capacity for multilineage differentiation and proven immunosuppressive properties. It is known that heat shock preconditioning induces the upregulation of heat shock proteins (HSPs), which enhance survival and engraftment of embryonic stem cells (ESCs) during transplantation in live animal models, although whether heat shock preconditioning has the same effects in hPDMCs is unclear.

Methods

The hPDMCs were isolated from placenta of healthy donors. The cells were treated with heat shock (43 °C, 15 min), followed by evaluation of cell viability. Furthermore, the HSPs expression was assessed by Western blot, qPCR. The reactive oxygen species (ROS) production and signal pathway activation were determined by flow cytometry and Western blot, respectively. The regulatory pathways involved in HSPs expression were examined by pretreatment with chemical inhibitors, and siRNAs of MAPK, Akt, and heat shock factor 1 (HSF1), followed by determination of HSPs expression.

Results

This study demonstrates that heat shock treatment induced ROS generation and HPSs expression in hPDMCs. Heat shock stimulation also increased p38 MAPK and Akt phosphorylation. These effects were reduced by inhibitors of ROS, p38 MAPK and Akt. Moreover, we found that heat shock treatment enhanced nuclear translocation of the HSF1 in hPDMCs, representing activation of HSF1. Pretreatment of hPDMCs with ROS scavengers, SB203580 and Akt inhibitors also reduced the translocation of HSF1 induced by heat shock.

Conclusions

Our data indicate that heat shock acts via ROS to activate p38 MAPK and Akt signaling, which subsequently activates HSF1, leading to HSP activation and contributing to the protective role of hPDMCs.
Human umbilical cord-derived mesenchymal stromal cells ameliorate aging-associated skeletal muscle atrophy and dysfunction by modulating apoptosis and mitochondrial damage in SAMP10 mice
Authors: Piao Limei , Huang Zhe , Inoue Aiko , Kuzuya Masafumi , Cheng Xian Wu
Published: June 2022

Background

Skeletal muscle mass and function losses in aging individuals are associated with quality of life deterioration and disability. Mesenchymal stromal cells exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in aging-related degenerative disease.

Methods and results

We investigated the efficacy of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) on sarcopenia-related skeletal muscle atrophy and dysfunction in senescence-accelerated mouse prone 10 (SAMP10) mice. We randomly assigned 24-week-old male SAMP10 mice to a UC-MSC treatment group and control group. At 12 weeks post-injection, the UC-MSC treatment had ameliorated sarcopenia-related muscle changes in performance, morphological structures, and mitochondria biogenesis, and it enhanced the amounts of proteins or mRNAs for myosin heavy chain, phospho-AMP-activated protein kinase, phospho-mammalian target of rapamycin, phospho-extracellular signal-regulated kinase1/2, peroxisome proliferator-activated receptor-γ coactivator, GLUT-4, COX-IV, and hepatocyte growth factor in both gastrocnemius and soleus muscles, and it reduced the levels of proteins or mRNAs for cathepsin K, cleaved caspase-3/-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and gp91phox mRNAs. The UC-MSC treatment retarded mitochondria damage, cell apoptosis, and macrophage infiltrations, and it enhanced desmin/laminin expression and proliferating and CD34+/Integrin α7+ cells in both types of skeletal muscle of the SAMP10 mice. In vitro, we observed increased levels of HGF, PAX-7, and MoyD mRNAs at the 4th passage of UC-MSCs.

Conclusions

Our results suggest that UC-MSCs can improve sarcopenia-related skeletal muscle atrophy and dysfunction via anti-apoptosis, anti-inflammatory, and mitochondrial biogenesis mechanisms that might be mediated by an AMPK-PGC1-α axis, indicating that UC-MSCs may provide a promising treatment for sarcopenia/muscle diseases.
Clearance of senescent cells with ABT-263 improves biological functions of synovial mesenchymal stem cells from osteoarthritis patients
Authors: Miura Yugo , Endo Kentaro , Komori Keiichiro , Sekiya Ichiro
Published: June 2022

Background

Osteoarthritis (OA) is an age-related joint disease characterized by progressive cartilage loss. Synovial mesenchymal stem cells (MSCs) are anticipated as a cell source for OA treatment; however, synovial MSC preparations isolated from OA patients contain many senescent cells that inhibit cartilage regeneration through their senescence-associated secretory phenotype (SASP) and poor chondrogenic capacity. The aim of this study was to improve the biological function of OA synovial MSCs by removing senescent cells using the senolytic drug ABT-263.

Methods

We pretreated synovial MSCs derived from 5 OA patients with ABT-263 for 24 h and then evaluated senescence-associated beta-galactosidase (SA-β-gal) activity, B cell lymphoma 2 (BCL-2) activity, apoptosis, surface antigen expression, colony formation ability, and multipotency.

Results

The ABT-263 pretreatment significantly decreased the percentage of SA-β-gal-positive cells and BCL-2 expression and induced early- and late-stage apoptosis. Cleaved caspase-3 was expressed in SA-β-gal-positive cells. The pretreated MSCs formed greater numbers of colonies with larger diameters. The expression rate of CD34 was decreased in the pretreated cells. Differentiation assays revealed that ABT-263 pretreatment enhanced the adipogenic and chondrogenic capabilities of OA synovial MSCs. In chondrogenesis, the pretreated cells produced greater amounts of glycosaminoglycan and type II collagen and showed lower expression of senescence markers (p16 and p21) and SASP factors (MMP-13 and IL-6) and smaller amounts of type I collagen.

Conclusion

Pretreatment of synovial MSCs from OA patients with ABT-263 can improve the function of the cells by selectively eliminating senescent cells. These findings indicate that ABT-263 could hold promise for the development of effective cell-based OA therapy.
Expansion of FGFR3-positive nucleus pulposus cells plays important roles in postnatal nucleus pulposus growth and regeneration
Authors: Xu Meng , Huang Junlan , Jin Min , Jiang Wanling , Luo Fengtao , Tan Qiaoyan , Zhang Ruobin , Luo Xiaoqing , Kuang Liang , Zhang Dali , Liang Sen , Qi Huabing , Chen Hangang , Ni Zhenhong , Su Nan , Yang Jing , Du Xiaolan , Chen Bo , Deng Chuxia , Xie Yangli , Chen Lin
Published: June 2022

Background

Intervertebral disc degeneration (IVDD) can cause low back pain, a major public health concern. IVDD is characterized with loss of cells especially those in nucleus pulposus (NP), due to the limited proliferative potential and regenerative ability. Few studies, however, have been carried out to investigate the in vivo proliferation events of NP cells and the cellular contribution of a specific subpopulation of NP during postnatal growth or regeneration.

Methods

We generatedFGFR3-3*Flag-IRES-GFPmice and crossedFGFR3-CreERT2mice withRosa26-mTmG, Rosa26-DTAandRosa26-Confettimice, respectively, to perform inducible genetic tracing studies.

Results

Expression of FGFR3 was found in the outer region of NP with co-localized expressions of proliferating markers. By fate mapping studies, FGFR3-positive (FGFR3+) NP cells were found proliferate from outer region to inner region of NP during postnatal growth. Clonal lineage tracing byConfettimice and ablation of FGFR3·+NP cells byDTAmice further revealed that the expansion of the FGFR3+cells was required for the morphogenesis and homeostasis of postnatal NP. Moreover, in degeneration and regeneration model of mouse intervertebral disc, FGFR3+NP cells underwent extensive expansion during the recovery stage.

Conclusion

Our present work demonstrates that FGFR3+NP cells are novel subpopulation of postnatal NP with long-existing proliferative capacity shaping the adult NP structure and participating in the homeostasis maintenance and intrinsic repair of NP. These findings may facilitate the development of new therapeutic approaches for IVD regeneration.
Adolescents’ lived experience of panic disorder: an interpretative phenomenological analysis
Authors: Baker Holly J. , Hollywood Amelia , Waite Polly
Published: June 2022

Background

Panic disorder is a debilitating anxiety disorder that has a serious impact on adolescents’ social and academic functioning and general wellbeing. Panic disorder is experienced by around 1 to 3% of the adolescent population. The aim of this study was to examine adolescents’ experiences of having panic disorder.

Methods

Semi-structured interviews were conducted with eight adolescents with a primary diagnosis of panic disorder. Interpretative Phenomenological Analysis was used to gain an understanding of adolescents’ lived experience of panic disorder.

Results

Two superordinate themes were identified: (1) Drowning in sensations, and (2) An unacceptable self. The findings show that adolescents experience panic disorder as extremely overwhelming and unpleasant, with debilitating feelings of drowning in sensations. Adolescents’ experiences largely fit with the cognitive model of panic, in which catastrophic misinterpretation of bodily sensations is associated with anxiety, avoidance, and safety behaviours, creating a vicious cycle. Attempts to avoid or prevent the attacks appear to inadvertently make them worse. Social worries, feeling broadly misunderstood, and unhelpful responses from others, contributed to feelings of being different or abnormal and were connected to a negative self-concept. Negative social interactions with teachers and peers in the school environment were particularly damaging.

Conclusions

These findings offer new insight into these adolescents’ lived experience of panic disorder and highlight the need for adolescents to access timely, evidence-based treatment, as well as the need for increased awareness and understanding of panic disorder in schools.
2D materials: increscent quantum flatland with immense potential for applications
Authors: Ranjan Pranay , Gaur Snehraj , Yadav Himanshu , Urgunde Ajay B. , Singh Vikas , Patel Avit , Vishwakarma Kusum , Kalirawana Deepak , Gupta Ritu , Kumar Prashant
Published: June 2022

Quantum flatland i.e., the family of two dimensional (2D) quantum materials has become increscent and has already encompassed elemental atomic sheets (Xenes), 2D transition metal dichalcogenides (TMDCs), 2D metal nitrides/carbides/carbonitrides (MXenes), 2D metal oxides, 2D metal phosphides, 2D metal halides, 2D mixed oxides, etc. and still new members are being explored. Owing to the occurrence of various structural phases of each 2D material and each exhibiting a unique electronic structure; bestows distinct physical and chemical properties. In the early years, world record electronic mobility and fractional quantum Hall effect of graphene attracted attention. Thanks to excellent electronic mobility, and extreme sensitivity of their electronic structures towards the adjacent environment, 2D materials have been employed as various ultrafast precision sensors such as gas/fire/light/strain sensors and in trace-level molecular detectors and disease diagnosis. 2D materials, their doped versions, and their hetero layers and hybrids have been successfully employed in electronic/photonic/optoelectronic/spintronic and straintronic chips. In recent times, quantum behavior such as the existence of a superconducting phase in moiré hetero layers, the feasibility of hyperbolic photonic metamaterials, mechanical metamaterials with negative Poisson ratio, and potential usage in second/third harmonic generation and electromagnetic shields, etc. have raised the expectations further. High surface area, excellent young’s moduli, and anchoring/coupling capability bolster hopes for their usage as nanofillers in polymers, glass, and soft metals. Even though lab-scale demonstrations have been showcased, large-scale applications such as solar cells, LEDs, flat panel displays, hybrid energy storage, catalysis (including water splitting and CO2 reduction), etc. will catch up. While new members of the flatland family will be invented, new methods of large-scale synthesis of defect-free crystals will be explored and novel applications will emerge, it is expected. Achieving a high level of in-plane doping in 2D materials without adding defects is a challenge to work on. Development of understanding of inter-layer coupling and its effects on electron injection/excited state electron transfer at the 2D-2D interfaces will lead to future generation heterolayer devices and sensors.
Pain detect questionnaire and pain catastrophizing scale affect gait pattern in patients with knee osteoarthritis
Authors: Harato Kengo , Iwama Yu , Kaneda Kazuya , Kobayashi Shu , Niki Yasuo , Nagura Takeo
Published: June 2022

Purpose

Although pain phenotype affects clinical score in patients with knee osteoarthritis (OA), little information has been available on the relationship between pain phenotype and gait analysis. The purpose was to investigate the relationship between pain phenotype and gait parameters. 

Methods

A total of 34 patients (24 females and 10 males) with end-stage medial compartmental knee OA participated. All the patients were evaluated based on pain detect questionnaire (PD-Q) and pain catastrophizing scale (PCS). They were divided into two categories: Group Low (PD-Q score ≤ 12) and Group High (PD-Q score > 12), PCS + (PCS ≥ 23) and PCS- (PCS < 23). Gait analysis was performed using three-dimensional motion analysis system. Statistical analysis was done to compare gait parameters between groups for each allocation of PD-Q or PCS, separately. 

Results

Peak vertical ground reaction forces in Group Low and High were 0.99 ± 0.054 and 0.82 ± 0.17, respectively (P = 0.015). Peak knee adduction moments in Group Low and High were 0.70 ± 0.19 and 0.39 ± 0.14, respectively (P = 0.0022). For PCS allocation, knee extension limitation during mid-stance during gait were significantly larger in PCS- (P = 0.038).

Conclusions

Patients with high PD-Q score had atypical gait pattern with smaller peak vertical ground reaction force and knee adduction moment, compared to patients with low PD-Q score. Moreover, patient with low PCS had different gait pattern in extension limitation, compared to those with high PCS. PD-Q and PCS would affect gait pattern in patients with knee OA. Level of evidence: III.
Molecular imaging phenotyping for selecting and monitoring radioligand therapy of neuroendocrine neoplasms
Authors: Iravani Amir , Parihar Ashwin Singh , Akhurst Timothy , Hicks Rodney J.
Published: June 2022

Neuroendocrine neoplasia (NEN) is an umbrella term that includes a widely heterogeneous disease group including well-differentiated neuroendocrine tumours (NETs), and aggressive neuroendocrine carcinomas (NECs). The site of origin of the NENs is linked to the intrinsic tumour biology and is predictive of the disease course. It is understood that NENs demonstrate significant biologic heterogeneity which ultimately translates to widely varying clinical presentations, disease course and prognosis. Thus, significant emphasis is laid on the pre-therapy evaluation of markers that can help predict tumour behavior and dynamically monitors the response during and after treatment. Most well-differentiated NENs express somatostatin receptors (SSTRs) which make them appropriate for peptide receptor radionuclide therapy (PRRT). However, the treatment outcomes of PRRT depend heavily on the adequacy of patient selection by molecular imaging phenotyping not only utilizing pre-treatment SSTR PET but 18F-Fluorodeoxyglucose (18F-FDG) PET to provide insights into the intra- or inter-tumoural heterogeneity of the metastatic disease. Molecular imaging phenotyping may go beyond patient selection and provide useful information during and post-treatment for monitoring of temporal heterogeneity of the disease and dynamically risk-stratify patients. In addition, advances in the understanding of genomic-phenotypic classifications of pheochromocytomas and paragangliomas led to an archetypical example in precision medicine by utilizing molecular imaging phenotyping to guide radioligand therapy. Novel non-SSTR based peptide receptors have also been explored diagnostically and therapeutically to overcome the tumour heterogeneity. In this paper, we review the current molecular imaging modalities that are being utilized for the characterization of the NENs with special emphasis on their role in patient selection for radioligand therapy.
Protection from contamination by 211At, an enigmatic but promising alpha-particle-emitting radionuclide
Authors: Ohnuki Kazunobu , Yoshimoto Mitsuyoshi , Haba Hiromitsu , Manabe Shino , Takashima Hiroki , Yasunaga Masahiro , Takenaka Yasumasa , Fujii Hirofumi
Published: June 2022

Purpose

211At, a promising alpha-particle-emitting radionuclide, can easily volatilize and contaminate the environment. To safely manage this unique alpha-particle-emitting radionuclide, we investigated the permeability of four types of plastic films and two types of rubber gloves against 211At and identified suitable materials that prevent contamination by 211At.

Methods

Four types of plastic films, polyethylene, polyvinylidene chloride, polyvinyl chloride, and a laminated film, and two types of rubber gloves, latex and nitrile, were examined. Small pieces of filter paper were covered with these materials, and a drop containing 100 kBq of 211At was placed on them. The radioactivity of the pieces of filter paper under the materials was evaluated by measuring counts using a gamma counter and obtaining autoradiograms 3.5 h later. These experiments were also performed using 225Ac, 125I, 111In, 201Tl, and 99mTc.

Results

211At solution easily penetrated polyethylene, polyvinyl chloride, and latex rubber. Similar results were obtained for 125I, while other radionuclides did not penetrate films or gloves. These results suggest that halogenic radionuclides under anionic conditions are likely to penetrate plastic films and rubber gloves.

Conclusion

Our evaluation revealed that, when 211At solution is used, the protection by polyvinylidene chloride, a laminated film, or nitrile rubber would be more effective than that by polyethylene, polyvinyl chloride, or latex rubber.
Huge esophageal gastrointestinal stromal tumor successfully resected under mediastino-laparoscopic transhiatal esophagectomy: a case report
Authors: Mishima Keisuke , Matsutani Takeshi , Yamagiwa Ryo , Hanawa Hidetsugu , Kurihara Yuji , Motoda Norio , Taniai Nobuhiko , Yoshida Hiroshi
Published: June 2022

Background

Esophageal gastrointestinal stromal tumors (E-GISTs) are often diagnosed early due to complaints such as dysphagia and are rarely found to be huge in size. Here, we report the treatment of a case of huge E-GIST successfully resected by minimally invasive surgery after neoadjuvant imatinib therapy.

Case presentation

An 86-year-old male patient with a 3-month history of dysphagia was referred to our hospital because of a suspected mediastinal tumor on chest X-ray. The chest computed tomography scan revealed a huge solid tumor, of about 100 mm in diameter, protruding into the left thoracic cavity. Histopathological examination results of fine-needle aspiration biopsy under endoscopic ultrasonography revealed a c-kit and CD34-positive esophageal gastrointestinal stromal tumor. The patient received neoadjuvant therapy with imatinib (400 mg/day) to reduce the size of the tumor and prevent rupture during resection. After 28 days of oral administration of imatinib, the tumor size decreased. However, the patient refused to continue treatment with imatinib and therefore underwent mediastino-laparoscopic transhiatal esophagectomy. We successfully resected the tumor completely with mediastino-laparoscopic surgical techniques. Esophageal reconstruction was performed using a gastric tube in the posterior sternal route. After an uneventful postoperative course, the patient was discharged postoperative day 14. Immunohistochemical findings of the resected specimen showed that the tumor cells were positive for c-kit, DOG-1 and CD34 and negative for smooth muscle actin and S100.

Conclusions

Hybrid surgical procedure utilizing mediastino-laparoscopy might be useful for high-risk patient with esophageal tumors.
Towards elimination of Lymphatic Filariasis in Kenya: improving advocacy, communication and social mobilization activities for mass drug administration, a qualitative study
Authors: Kibe Lydiah W. , Kimani Bridget W. , Okoyo Collins , Omondi Wyckliff P. , Sultani Hadley M. , Njomo Doris W.
Published: June 2022

Introduction

The Kenya Breaking Transmission Strategy for Neglected Tropical Diseases (NTD) from 2019 to 2023 intensifies advocacy, coordination, and partnerships. The purpose of this study was to explore views and experiences of stakeholders and health workers on ways of improving the Advocacy, Communication and Social Mobilization (ACSM) activities of Mass Drug Administration (MDA) for Lymphatic Filariasis (LF) programs through participatory approaches in Kilifi County, Kenya.

Methods

Two wards were purposely selected in the Kaloleni sub-county, Kilifi County, where there was an average treatment coverage of 56% in 2015, 50.5% in 2016. Qualitative data collection methods were employed, which included participatory meetings with county stakeholders to understand their views, experiences, and suggestions on how ACSM strategies can be improved in MDA for LF. Twelve In-Depth Interviews (IDIs) were conducted (six with opinion leaders and six with Community Health Extension Workers (CHEWs) and two semi-structured interviews (SSIs) were held with county and sub-county coordinators involved in MDA administration. The aim was to better to understand their perceptions of the NTD program about ACSM, challenges to ACSM strategies, and ways to improve the strategies for ACSM in MDA for LF. The Data was organized and classified into codes and themes using QSR NVIVO version 12.

Results

The study observed the low participation of stakeholders in the ACSM activities of MDA for LF and identified potential areas for stakeholders’ involvement to strengthen the activities. Challenges hindering effective implementation of ACSM activities include late delivery of Information, Educational and Communication (IEC) and few IEC materials, insufficient funding, inadequate time allocated to reach the assigned households with messages, messaging, and packaging of information for dissemination due to the vastness of the area. The stakeholders recommended innovative strategies and techniques to improve ACSM activities.

Discussion and conclusion

The results of this study show key challenges to ACSM implementation of MDA for LF. Implementers need to pay attention to these challenges to enhance the effectiveness of MDA per the Kenya NTD Breaking Transmission Strategy. ACSM efforts in MDA for LF control and elimination should be linked with overarching efforts to mainstream partnerships and coordination in control and elimination.
Diagnostic value of presepsin in odontogenic infection: a retrospective study
Authors: Kang Eun-Sung , Lee Jae-Hoon
Published: June 2022

Background

Most head and neck infections originate from odontogenic causes; therefore, it is important to determine the severity of odontogenic infections. Since severe infection can cause sepsis, a systemic examination should be performed when evaluating a patient with odontogenic infection. C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT), and presepsin (PSEP) can be used to evaluate the severity of inflammatory status and sepsis in patients in the early stages of visiting the emergency room. Moreover, sepsis can be diagnosed based on the systemic inflammatory response syndrome (SIRS) classification. In relation to PSEP, significant study results on sepsis have been reported in other organ infections. However, there has been no progress in odontogenic infection; therefore, this study aimed to determine the diagnostic value of sepsis derived from odontogenic infection.

Methods

This study was conducted from March 2021 to October 2021 on 43 patients admitted to the Department of Oral and Maxillofacial Surgery, Dankook University Hospital, in the emergency room for odontogenic infection. All patients underwent vital sign assessment and diagnostic tests (CRP, WBC, PCT, PSEP) in the emergency room. Sepsis was classified according to the SIRS criteria, and CRP, WBC, PCT, and PSEP levels were measured. The Statistical Package for the Social Sciences was used for statistical analyses.

Results

The results of this study showed a moderately positive correlation between CRP and PCT, CRP and PSEP, and CT and PSEP levels. In addition, PCT and PSEP levels showed a positive correlation with sepsis. The odds ratios of sepsis and PCT and sepsis and PSEP were statistically significant. The optimal cut-off values obtained through the receiver operating characteristic curve were 0.24 and 671.5 for PCT and PSEP, respectively. Finally, there were positive correlations between CRP level and length of stay, WBC and Flynn scores, PCT level and Flynn scores, PCT level and length of stay, and PSEP level and length of stay.

Conclusion

WBC and CRP and PCT levels have been used in the past to determine the severity of infection and sepsis in patients with odontogenic infection, but PSEP was also found to have diagnostic value in this study. According to this study, a PSEP level of 671.5 pg/ml or higher for odontogenic infection can be considered an abnormal level.
Consulting properly rather than acting: advocating for real patient involvement in summative OSCEs
Authors: Kearney Grainne P. , Johnston Jennifer L. , Hart Nigel D. , Cullen Kathy M. , Gormley Gerard J.
Published: June 2022

Background

In this “Advancing simulation practice” article, we offer an expose of the involvement of real patients in Objective Structured Clinical Examinations (OSCEs), inviting educators who traditionally involve solely SPs in their summative OSCEs to consider the practice. The need for standardisation in summative assessments can make educators understandably wary to try this, even if the rhetoric to involve real patients is accepted. We offer this as an instance of the tussle between standardisation and validity experienced throughout health professions education.

Main text

We offer our experience and empirical evidence of this simulation practice, based on an institutional ethnographic examination of the involvement of real patients in summative OSCEs from an undergraduate medical school in the UK. Our critique demonstrates the merits of this approach as an assessment environment closer to the real clinical environments where these soon-to-be doctors interact in a more authentic way with real patients and their illness experiences. We balance this against the extra work required for all involved and suggest the biggest challenge is in the reorientation work required for both Faculty and students who are institutionalised to expect standardisation above all in assessment.

Conclusion

We advocate for involving real patients in summative OSCEs and hope that readers may feel compelled and empowered to foster this shift in mindset required to introduce this practice into their assessments.
Marine-derived microbes and molecules for drug discovery
Authors: Tanaka Yoshimasa , Nishikawa Megumi , Kamisaki Kaho , Hachiya Saki , Nakamura Moeka , Kuwazuru Takahiro , Tanimura Susumu , Soyano Kiyoshi , Takeda Kohsuke
Published: June 2022

Increasing attention has been paid to marine-derived biomolecules as sources of therapeutics for autoimmune diseases. Nagasaki Prefecture has many islands and is surrounded by seas, straits, gulfs, bays, and coves, giving it the second longest coastline in Japan after Hokkaido. We have collected more than 20,000 marine microbes and have been preparing an original marine microbial extract library, which contains small and mid-size biomolecules that may penetrate cell membranes and interfere with the intracellular protein–protein interaction involved in the development of autoinflammatory diseases such as familial Mediterranean fever. In addition, we have been developing an indoor shark farming system to prepare shark nanobodies that could be developed as potential therapeutic agents for autoimmune diseases. Sharks produce heavy-chain antibodies, called immunoglobulin new antigen receptors (IgNARs), consisting of one variable domain (VNAR) and five constant domains (CNAR); of these, VNAR can recognize a variety of foreign antigens. A VNAR single domain fragment, called a nanobody, can be expressed in Escherichia coli and has the properties of an ideal therapeutic candidate for autoimmune diseases. Shark nanobodies contain complementarity-determining regions that are formed through the somatic rearrangement of variable, diversity, and joining segments, with the segment end trimming and the N- and P-additions, as found in the variable domains of mammalian antibodies. The affinity and diversity of shark nanobodies are thus expected to be comparable to those of mammalian antibodies. In addition, shark nanobodies are physically robust and can be prepared inexpensively; as such, they may lead to the development of highly specific, stable, effective, and inexpensive biotherapeutics in the future. In this review, we first summarize the history of the development of conventional small molecule drugs and monoclonal antibody therapeutics for autoimmune diseases, and then introduce our drug discovery system at Nagasaki University, including the preparation of an original marine microbial extract library and the development of shark nanobodies.
Quality of life and its predictors among patients with migraine in Qassim region, Saudi Arabia: a cross-sectional study
Authors: Almosaiteer Sarah Abdulrahman , Rabbani Unaib , Alharbi Basil Abdulrahman , Aldukhayel Abdulrhman
Published: June 2022

Background

Migraine attacks can last for hours to days with severe pain which can affect the daily activities. Literature on quality of life of migraineurs is Saudi Arabia is scarce. This study aimed to assess the quality of life and its predictors among patients with migraine in Qassim region, Saudi Arabia.

Methods

A cross-sectional study was conducted among patients with migraines in Qassim, Saudi Arabia. A self-administered questionnaire was distributed online among migraine patients that included; socio-demographic characteristics and an Arabic version of validated migraine-specific quality of life questionnaire (MSQ), version 2.1. Data analyses were performed in SPSS version 26.

Results

A total of 320 patients with migraines participated in the study. The most common age group was 18–25 years (36.6%) with females were dominant (60.9%). According to the results of MSQ version 2.1, the mean ± SD scores of Role Restrictive (RR), Role Preventive (RP), and Emotion Function (EF) were 67.7 ± 19.7, 68.5 ± 20.6, and 70.6 ± 22.1, respectively. Statistical tests revealed that patients who reported less frequent migraine attacks, had better scores in RR, RP, and EF, while the use of paracetamol and painkillers for the treatment of headache were associated with lower scores in RR, RP, and EF.

Conclusions

The quality of life among patients with migraines was generally moderate. Males demonstrated better QOL than females. Furthermore, patients who had less frequent migraine attacks exhibited better QOL than the others but working patients were likely to demonstrate poor QOL.
Clinical outcomes and survivorship of cementless triathlon total knee arthroplasties: a systematic review
Authors: Carlson Brian J. , Gerry Adam S. , Hassebrock Jeffrey D. , Christopher Zachary K. , Spangehl Mark J. , Bingham Joshua S.
Published: June 2022

Background

Over the last decade, cementless total knee arthroplasty has demonstrated improved outcomes and survivorship due to advances in technologies of implant design, manufacturing capabilities, and biomaterials. Due to increasing interest in cementless implant design for TKA, our aim was to perform a systematic review of the literature to evaluate the clinical outcomes and revision rates of the Triathlon Total Knee system over the past decade.

Methods

A systematic review of the literature was conducted following PRISMA guidelines for patients who underwent total knee arthroplasty with cementless Triathalon Total Knee System implants. Patients had a minimum of two-year follow-up and data included clinical outcome scores and survivorship data.

Results

Twenty studies were included in the final analysis. The survivability of the Stryker Triathlon TKA due to all causes was 98.7%, with an aseptic survivability of 99.2%. The overall revision incidence per 1,000 person-years was 3.4. Re-revision incidence per 1,000 person-years was 2.2 for infection, and 1.3 for aseptic loosening. The average KSS for pain was 92.2 and the average KSS for function was 82.7.

Conclusions

This systematic review demonstrated excellent clinical outcomes and survivorship at a mean time of 3.8 years. Additional research is necessary to examine the long-term success of the Stryker Triathlon TKA and the use of cementless TKAs in obese and younger populations.

Level of evidence

III.
The role of radiogenomics in the diagnosis of breast cancer: a systematic review
Authors: Darvish Leili , Bahreyni-Toossi Mohammad-Taghi , Roozbeh Nasibeh , Azimian Hosein
Published: June 2022

Background

One of the most common cancers diagnosed worldwide is breast cancer (BC), which is the leading cause of cancer death among women. The radiogenomics method is more accurate for managing and inhibiting this disease, which takes individual diagnosis on genes, environments, and lifestyles of each person. The present study aims to highlight the current state-of-the-art, the current role and limitations, and future directions of radiogenomics in breast cancer.

Method

This systematic review article was searched from databases such as Embase, PubMed, Web of Science, Google Scholar, Scopus, and Cochrane Library without any date or language limitations of databases. Searches were performed using Boolean OR and AND operators between the main terms and keywords of particular topic of the subject under investigation. All retrospective, prospective, cohort, and pilot studies were included, which were provided with more details about the topic. Articles such as letter to the editor, review, and short communications were excluded because of lack of information, discussions, or use of radiogenomics method on other cancers. For quality assessment of articles, STROBE checklist was used.

Result

For the systematic review, 18 articles were approved after assessing the full text of selected articles. In this review, 3614 patients with BC of selected articles were evaluated, and all radiogenomics were associated with more power in classification, differential diagnosis, and prognosis of BC. Among the various modalities to predict genomic indicators and molecular subtypes, DCE-MRI has the higher performance and finally the highest amount of AUC value (0.956) belonged to PI3K gene.

Conclusion

This review shows that radiogenomics can help with the diagnosis and treatment of breast cancer in patients. It has shown that recognizing and specifying radiogenomic phenotypes in the genomic signatures can be helpful in treatment and diagnosis of disease. The molecular methods used in these articles are limited to miRNAs expression, gene expression, Ki67 proliferation index, next-generation RNA sequencing, whole RNA sequencing, and molecular histopathology that can be completed in future studies by other methods such as exosomal miRNAs, specific proteins expression, DNA repair capacity, and other biomarkers that have prognostic and predictive value for cancer treatment response. Studies with control group and large sample size for evaluation of radiogenomics in diagnosis and treatment recommended.
Potential roles of claudin-3 and claudin-4 in ovarian cancer management
Authors: Uthayanan Leshanth , El-Bahrawy Mona
Published: June 2022

Background

Ovarian cancer has the highest mortality amongst all gynaecological malignancies, with around two-thirds of patients diagnosed with advanced disease due to late presentation. Furthermore, around 90% of patients develop recurrence and eventually become chemoresistant. Therefore, there is a high demand to identify biomarkers specific to this disease for screening for early detection, as well as new therapeutic targets. Tight junctions (TJs) regulate paracellular permeability and are vital in establishing epithelial cell polarity. One hallmark of tumorigenesis is the loss of TJs, with loss of cell-to-cell adhesion. Claudins are integral TJ membrane proteins, which have been found to play a critical role in maintaining the TJ’s barrier function. Furthermore, claudin-3 (CLDN3) and claudin-4 (CLDN4) are overexpressed in ovarian cancer. This article aims to explore the biological role of CLDN3 and CLDN4 and their potential in different aspects of the management of ovarian cancer.

Main body

CLDN3 and CLDN4 have been shown to be effective markers for the early detection of ovarian cancer. Whilst there is difficulty in screening for both claudins in serum, their assessment by gene expression analysis and immunohistochemical methods shows promising potential as diagnostic and prognostic biomarkers for ovarian cancer. The localisation and overexpression of claudins, such as CLDN3, have been shown to correlate with poorer survival outcomes. The added value of combining claudins with other markers such as CA125 for diagnosis has also been highlighted. Therapeutically, CLDN3 and more so CLDN4 have been shown to be effective targets of Clostridium perfringens enterotoxin (CPE). Interestingly, CPE has also been shown to resensitise chemoresistant tumours to therapy.

Conclusions

This review presents the diagnostic and prognostic potential of CLDN3 and CLDN4 and their emerging role as therapeutic targets in ovarian cancer. Clinical trials are required to validate the promising results of the in vitro and in vivo studies for CLDN3 and CLDN4, possibly adding onto current ovarian cancer management.
Malignancy risk stratification of thyroid nodules smaller than 10 mm with ACR-TIRADS, K-TIRADS, and ATA-2015 guidelines: a prospective study
Authors: Nabahati Mehrdad , Moazezi Zoleika
Published: June 2022

Background

Small thyroid nodules (≤ 10 mm) are common findings in thyroid ultrasonography. The first purpose of this study was to compare the performance of three guidelines in the diagnosis of malignancy for small thyroid nodules. The second aim was to find the ultrasonographic characteristics potentially associated with the risk of malignancy. This prospective cross-sectional study was performed on the patients with a diagnosis of small thyroid nodules (≤ 10 mm), who were rereferred to the radiologists for sonography and FNA. Sonographic features were recorded and scored according to the American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS), American Thyroid Association (ATA-2015), and Korean-TIRADS (K-TIRADS). Finally, FNA was conducted and cytological findings were reported.

Results

In total, 287 thyroid nodules from 256 subjects (64 men and 192 women) were finally included in the study. The accuracy of ACR-TIRADS categories TR5 and TR4/5 was 88.9% and 72.1%, respectively. This rate for ATA-2015 classes high suspicion and intermediate suspicion/high suspicion was 88.9% and 82.6%, respectively. For K-TIRADS classes 5 and 4/5, the diagnostic accuracy was 89.6% and 82.9%, respectively. Significant direct associations were found between malignancy and punctate echogenic foci (odds ratio [OR] = 6.46), hypoechogenicity (OR = 6.39), ill-defined margin (OR = 4.38), and irregular margin (OR = 7.33).

Conclusion

The differences in the strength of the three guidelines in the prediction of the malignancy should be considered by clinicians and radiologists in the management of thyroid nodules smaller than 10 mm.
Impact of breeder seed multiplication and certified quality seed distribution on rice production in India
Authors: Prasad Gogineni S. V. , Rao Chilukuri S. , Suneetha Kota , Muralidharan Kalambur , Siddiq E. A.
Published: June 2022

Background

The All India Coordinated Rice Improvement Project (AICRIP) organizes multi-location tests (METs) with new genotypes from breeding programs. The best performing genotypes in METs for 3–4 years are identified and notified as commercial cultivars by the Government of India (GOI) to authorize breeder seed (BS) production.

Methods

We created a database and analyzed data on BS production for 24 years (1995–96 to 2018–19) in 475 inbred and 22 F1 hybrid cultivars. Estimates were made to rank cultivars on the proportional contribution of a cultivar, quantity produced and a new BS index. Correlation and regression analyses were used to find the relationships between BS, certified quality seed distributed (CQSD), and milled rice production. We compared cultivars in BS production chain with those grown in farmers’ fields across the country as identified in the production-oriented surveys.

Results

The top ten inbred cultivars identified are Jaya (notified by GOI in 1969), Swarna, Kranthi, IR 36, Sarjoo 52, Samba Mahsuri and Pusa Basmati 1 (notified in 1980–1989), and IR 64, Vijetha and Cottondora Sannalu (notified in 1991–2000). BS production in hybrid F1 was insignificant. We detected a Pearson correlation (r = 0.806, P < 0.01) between the BS production and CQSD, and a linear relationship between the annual rice production in India and the CQSD (R2 = 0.850, P < 0.01). The rice area coverage in 2018–19 with CQSD estimated was 41%. A total of 1877 cultivars (528 notified and 1349 not notified) were found at farms in rice growing districts in India.

Conclusions

From 1995–2019, BS and CQSD together increased the annual milled rice production in step with increases in population. Diverse rice genotypes have enabled rice to endure crop constraints in fragmented landholdings spread over 43 m ha. AICRIP’s efforts have sustained availability of > 73 kg rice per capita per year (~ 40% of food grains). The process of notification, receipt of indent for BS from states, allotment and BS production, and de-notification of a cultivar by GOI need a review to ensure profits to farmers. As the 1000-seed weight varies in cultivars, it must be notified by GOI to adjust seed rate and maintain the recommended plant population at the farms. There is scope to increase the priceless BS production in cultivars to raise the country’s production further, facilitate export and ensure profits to all stakeholders.
The temporal relationships between defeat, entrapment and suicidal ideation: ecological momentary assessment study
Authors: van Ballegooijen Wouter , Littlewood Donna L. , Nielsen Emma , Kapur Nav , Gooding Patricia
Published: June 2022

Background

Psychological models of suicidal experiences are largely based on cross-sectional or long-term prospective data with follow-up intervals typically greater than 1 year. Recent time-series analyses suggest that these models may not account for fluctuations in suicidal thinking that occur within a period of hours and/or days.

Aims

We explored whether previously posited causal relationships between defeat, entrapment and suicidal ideation accounted for temporal associations between these experiences at small time intervals from 3 to 12 h.

Method

Participants (N = 51) completed an ecological momentary assessment (EMA) study, comprising repeated assessments at semi-random time points up to six times per day for 1 week, resulting in 1852 completed questionnaires. Multilevel vector autoregression was used to calculate temporal associations between variables at different time intervals (i.e. 3 to 12 h between measurements).

Results

The results showed that entrapment severity was temporally associated with current and later suicidal ideation, consistently over these time intervals. Furthermore, entrapment had two-way temporal associations with defeat and suicidal ideation at time intervals of approximately 3 h. The residual and contemporaneous network revealed significant associations between all variables, of which the association between entrapment and defeat was the strongest.

Conclusions

Although entrapment is key in the pathways leading to suicidal ideation over time periods of months, our results suggest that entrapment may also account for the emergence of suicidal thoughts across time periods spanning a few hours.
Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study
Authors: Asherson Philip J. , Johansson Lena , Holland Rachel , Bedding Megan , Forrester Andrew , Giannulli Laura , Ginsberg Ylva , Howitt Sheila , Kretzschmar Imogen , Lawrie Stephen M. , Marsh Craig , Kelly Caroline , Mansfield Megan , McCafferty Clare , Khan Khuram , Müller-Sedgwick Ulrich , Strang John , Williamson Grace , Wilson Lauren , Young Susan , Landau Sabine , Thomson Lindsay D. G.
Published: June 2022

Background

Research has shown that 20–30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.

Aims

To estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.

Method

We conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16–25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.

Results

In the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI −2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.

Conclusions

ADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.