bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative reimbursement models for health providers in high performance sport: stakeholder experiences and perceptions
Authors: Carter Hannah Elizabeth , Allen Michelle , Toohey Liam A. , McPhail Steven M. , Drew Michael K.
Published: March 2023

Background
Value-based healthcare provider reimbursement models have been proposed as an alternative to traditional fee-for-service arrangements that can align financial reimbursement more closely to the outcomes of value to patients and society. This study aimed to investigate stakeholder perceptions and experiences of different reimbursement systems for healthcare providers in high performance sport, with a focus on fee-for-service versus salaried provider models.
Results
Three in-depth semi-structured focus group discussions and one individual interview were conducted with key stakeholders across the Australian high performance sport system. Participants included healthcare providers, health managers, sports managers and executive personnel. An interview guide was developed using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, with key themes deductively mapped to the innovation, inner context and outer context domains. A total of 16 stakeholders participated in a focus group discussion or interview. Participants identified several key advantages of salaried provider models over fee-for-service arrangements, including: the potential for more proactive and preventive models of care; enhanced inter-disciplinary collaboration; and the ability for providers to have a deeper understanding of context and how their role aligns with a broader set of priorities for an athlete and the organisation. Noted challenges of salaried provider models included the potential for providers to revert to reactive care delivery when not afforded adequate capacity to provide services, and difficulties for providers in demonstrating and quantifying the value of their work.
Conclusions
Our findings suggest that high performance sporting organisations seeking to improve primary prevention and multidisciplinary care should consider salaried provider arrangements. Further research to confirm these findings using prospective, experimental study designs remains a priority.
Mental health during COVID-19: an evaluation of an academic university’s contribution to existing research
Authors: Tawil Samah , Salameh Pascale
Published: March 2023

Background:Increases in mental health problems have been observed during COVID-19 pandemic. Therefore, this topic of research became a priority, especially at the academic level. The objectives of this review were to summarize an institutional contribution to mental health research during the era of COVID-19.
Methods: A scoping review of studies conducted at a local university and examining alterations in mental health during the pandemic during the last three years was conducted.
Results: Fifty-five studies were included. These focused on different mental health changes that occurred in the era of COVID-19 such as changes in work habits or existing psychological conditions, COVID-19-related fear depression, anxiety and stress. Most of the included studies were observational (76.7%). The majority of the publications were published in Scimago Journal Rank Q1 journals (57.1%). The average number of citations per publication was 15.3±30.13 [0-125]. The number of citations was higher in papers with international collaboration of authors (p=0.031). Publications with COVID-19 as a main objective were more cited than papers not directly related to this subject (25.9±39.45 vs. 4.14±3.2; p=0.044).
Conclusion: Mental health problems are a common response to the COVID-19 pandemic. The contribution of a local university to different mental health research studies that took place during COVID-19 outbreak have underlined this reality. However, more representative research from other institutional settings will be needed, particularly in vulnerable populations.
Network analysis using cytoscape
Authors: Verma Srishti , Mangla Lakshay
Published: March 2023

In the following research, we have made cytoscape an easy and compact tool for network analysis. We study the relation between the data sets. Creating edge list and node list for determining relations between the columns and rows hence forming a csv table for the same. Here we have used Cytoscape and Open refine software. Open refine to create the csv file and cytoscape to study the networks.
The Role of Basement Faults in the Miocene Formations of Fars and Bandar Abbas Hinterland, Southern Iran
Authors: Moshkelgosha Maryam
Published: March 2023

The Zagros fold and Thrust Belt (ZFB) is located in southwestern Iran. The geological structure of this region consists of a set of northwest–southeast trending compact anticlines and synclines with upright axial planes. This indicates that (ZFB) the marginal and mobile section of the Arabian platform. In the last stages of sedimentation in this vast basin, the folds are inclined to the southwest due to progressive change in the fold axial planes. For the first time, the tectono- stratigraphy of the Miocen Formations of Fars and Bandar Abbas Hinterland, Southern Iran has been studied in this article. For this purpose, the stratigraphic section of Miosen Formationin five different location namely, Bastak, Taghdis-e- Bahar, Dasht-eArzhan, Saedi mountain, and Yasuj have been collected and analyzed. To the Isopach map prepared for the region, the thicknesses of the Miocene Formations vary in all of these locations. In the Arjan plain the sedimentary facies of the evaporitic sedimentary rocks of Gachsaran Formation changes to the marine sedimentary rocks of the Rzak Formation and the calcareous rocks of Asmari Formation along a northwest – southwest border. This facies change could be related to the activity of basement fault zone such as, Kareh – Bas, Sabzpooshan, Sarvestan, and Kazerun. Tectonic- stratigraphic studies in this paper indicate that changes in sedimentary basin depth and facies changes of the sedimentary rock were affected by several basement faults that followed the Arabian trend. while others basement faults controlling the sedimentary basin in the region in Miocene are in line with the Zagros trend.
Frequency of serological results of antibodies related to autoimmune hepatitis in patients with non-viral hepatitis referring to an inpatient clinic in 2019
Authors: Basir Hamid Reza Ghasemi , Khalilian Alireza , Eslami-Ghayour Anahita , Ghobakhlou Mehdi
Published: March 2023

Background
Autoimmune hepatitis as a chronic inflammatory disease of the liver can occur when the body's immune system is stimulated against liver cells, but its exact cause is unknown. Autoimmune hepatitis, if left untreated, leads to liver damage or cirrhosis over time, which can eventually cause liver failure.
Objective
This descriptive-analytical study was done to assess the frequency of serological results of autoimmune hepatitis-related antibodies in patients with non-viral hepatitis referring to an inpatient clinic in 2019 and provide basic information for future studies and assistance in localization of external guidelines performed to diagnose autoimmune hepatitis.
Methods
All patients were evaluated for age and sex, ANA, ASMA, and LKM antibodies, and immunoglobulin by preparing 5 cc of blood samples using laboratory techniques and electrophoresis. The collected data were recorded in the checklist created by the researcher.
Results
The total number of 209 patients with non-viral hepatitis, with a mean age of 37.98 years participated in this study. In patients with non-viral hepatitis, 50.2% of patients had polyclonal hypergammaglobulinemia, in 17.2% ANA was positive, in 16.3% ASMA was positive, and 1.9% LKM was positive.
Conclusion
hypergammaglobulinemia, ANA, and ASMA are suitable antibodies for autoimmune hepatitis. Moreover, laboratory results of ANA and ASMA in patients with autoimmune hepatitis indicate low levels of these antibodies in Iran and their deficiency in other countries. Conventional diagnostic methods can provide a definitive diagnosis. Therefore, it shows the need for further examination of laboratory instruments and wider use of other diagnostic methods, including biopsy and further assessments.
Comparison of Infliximab with Adalimumab for the treatment of non- infectious uveitis: a systematic review and meta-analysis
Authors: Liu Weishai , Bai Dan , Kou Lieling
Published: March 2023

Purpose: To compare Infliximab and Adalimumab on the efficacy and safety for the treatment of non-infectious uveitis (NIU).
Methods: We searched for relevant studies in the PubMed, Embase, ClinicalTrials.gov, Cochrane Library databases, with language restricted in English, China National Knowledge Infrastructure (CNKI), and Wan Fang databases up to September 2022. The incidences of complete inflammation remission, overall inflammation remission, adverse events and corticosteroid-sparing effects were evaluated.
Results: Eleven clinical trials covering 1459 NIU patients were included. Complete inflammation remission after therapy was achieved in 161 (37.5%) patients in Infliximab group and 151 (39.6%) patients in Adalimumab group. These two groups had no significant difference (P = 0.37). Overall inflammation remission of anti-TNF drugs involved 449 patients, with 241/272 (88.6%) being treated with Infliximab and 153/177 (86.4%) being treated with Adalimumab. No signiﬁcant difference was observed with regard to the overall inflammation remission between the two cohorts (P = 0.86). There were no significant differences between Infliximab and Adalimumab as far as corticosteroid-sparing effects (P = 0.58). Pooled effect size (P = 0.001) showed a statistically significant difference, with incidence of adverse events being 17.91% in Infliximab and 12.12% in Adalimumab.
Conclusion: Our systematic review and meta-analysis of 11 studies suggests that Infliximab and Adalimumab offer similar therapeutic efficacy and corticosteroid-sparing effects for patients with NIU. But Adalimumab has a marginal advantage over Infliximab in terms of adverse events. Large-scale RCTs with a longer follow-up are required to further evaluate these two anti-TNF-α agents for NIU patients.
Lymphoproliferative disorder during temozolomide therapy; a representative case of a formidable complication and management challenges
Authors: Sato Daisuke , Takami Hirokazu , Shunsaku Takayanagi , Taoka Kazuki , Tanaka Mariko , Matsuura Reiko , Tanaka Shota , Saito Nobuhito
Published: March 2023

Background: Lymphoproliferative disorder represents a heterogeneous clinicopathological spectrum characterized by uncontrolled proliferation of lymphocytes. Immunodeficiency is a major trigger of its development. While induction of immunodeficiency is a well-known adverse effect of temozolomide therapy, development of lymphoproliferative disorder following temozolomide therapy has not previously been described.
Case presentation: A patient with brainstem glioma developed constitutional symptoms, pancytopenia, splenomegaly and generalized lymphadenopathy during the 2nd cycle of maintenance therapy following induction therapy with temozolomide. Epstein-Barr virus-infected lymphocytes were observed histopathologically and “other iatrogenic immunodeficiency-associated lymphoproliferative disorder” (OIIA-LPD) was diagnosed. Although discontinuation of temozolomide led to rapid remission, relapse was observed 4 months later. CHOP chemotherapy was induced, resulting in secondary remission. Vigilant follow-up for another 14 months showed radiologically stable brainstem glioma and no further recurrence of OIIA-LPD.
Conclusions: This is the first report documenting OIIA-LPD during temozolomide administration. Timely diagnosis of the disease and discontinuation of the causative agent were considered to be the management of choice. Close monitoring for relapse should be continued. Finding a balance between glioma management and controlling the remission of OIIA-LPD remains to be clarified.
Inflammatory memory restrains intestinal stem cell regeneration
Authors: Reddy Pavan , Zhao Dongchang , Ravikumar Visweswaran , Lauder Emma , Li Lu , Sun Yaping , Oravecz-Wilson Katherine , Brooks Michael , Keller Evan , Chen Fengju , Maneix Laure , Santibanez Ana , Creighton Chad , Rao Arvind
Published: March 2023

Intestinal stem cells (ISC) encounter inflammatory insults in immune mediated gastro-intestinal (GI) diseases. It remains unknown whether, and how, they adapt, and if the adaptation leaves scars on the ISCs that affects their subsequent regeneration capacity. We investigated the consequences of inflammation on Lgr5+ISCs in well-defined clinically relevant models of gastro-intestinal acute graft-versus-host disease (GI GVHD). Utilizing single cell transcriptomics, organoid, metabolic, epigenomic and in vivo models we found that Lgr5+ISCs undergo metabolic changes that lead to accumulation of succinate, which reprograms its epigenome. These changes reduced the ability of ISCs to differentiate and regenerate ex vivo in serial organoid cultures demonstrating the persistence of the maladaptive impact of an in vivo inflammatory encounter by the ISCs. Thus, inflammation from GI GVHD leaves a memory of its effects on ISCs that persist and are likely to affect their sensitivity to adapt to future stress or challenges.
Parametric Resonance Climate Model
Authors: Caccamo Maria Teresa , Magazù Salvatore
Published: March 2023

The variations in the distribution of solar radiation due to the ∼105 years Milankovitch cycle alone cannot explain the sharp drop in temperature of approximately 10 K that marks the transition from the interglacial to the glacial age registered in the last ∼5.5 106 years temperature variation behavior. More specifically, only a temperature variation of 0.2÷0.3 K can be attributed to this ∼105 years cycle connected to the Earth eccentricity variation and, therefore, positive feedback effects should be taken into account to explain the registered effect. In the present work, a parametric resonance model for climate that justifies the temperature variation from the interglacial to the glacial age is postulated. According to this model, the system energization is due to periodic variations in the internal solar system parameters. In particular, it is put into evidence that the model works when only a weak oscillation is present in the system and that even small oscillations increase over time proportionally to the system energy itself, i.e., exponentially, and hence, a series of connected resonances is able to energize the system.
Aftershocks following the 2011 Tohoku-Oki earthquake driven by both stress transfer and afterslip
Authors: Ueda Taku , Kato Aitaro
Published: March 2023

Aftershocks are a fundamental characteristic of seismicity, and their generation mechanism is mainly characterized by two physical models, stress transfer from large earthquakes and afterslip-induced stress loading. However, the contribution of each mechanism to aftershock generation remains unclear. Here we investigate the spatiotemporal variations in aftershock activity following the 2011 Tohoku-Oki earthquake by applying the Hierarchical Space-Time Epidemic-Type Aftershock Sequence (HIST-ETAS) model to the decade of recorded seismicity since the mainshock. Using the estimated HIST-ETAS model, we categorize the aftershocks into background earthquakes (which are caused by aseismic phenomena) and triggered earthquakes (which are caused by earthquake-to-earthquake interactions). Most of the earthquakes that occurred updip of the large coseismic slip zone along the Japan Trench are triggered earthquakes, consistent with the lack of afterslip in this area. Conversely, background earthquakes are the predominant earthquake type in the long-term downdip of the large coseismic slip zone, and they positively correlate with the afterslip evolution. Our results suggest the importance of combining these two end-member aftershock generation models to explain aftershock activity and thus provide new insights into the relationship between afterslip and spatiotemporal aftershock distribution. Our classifications may also contribute to the monitoring of afterslip in a given region that hosts a large earthquake, particularly where geodetic observation networks are too sparse to evaluate afterslip evolution.
Diminished Function of Maintaining Cerebral Perfusion during Systemic Hypotension in Elderly Humans
Authors: Abdali Kulsum , Chen Xiaoan , Zhao Jinfeng , Ross Sarah , Davis Sandra , Zhou Zhengyang , Shi Xiangrong
Published: March 2023

Background
The study sought to test the hypothesis that the function of maintaining cerebral perfusion is diminished in elderly adults due to compromised cerebral autoregulation (CA) and cardiovascular function with aging.
Methods
Healthy elderly (n = 13, 68 ± 1 year) and young (n = 13, 26 ± 1 year) adults underwent a systemic-hypotension induced by rapid-deflation of bilateral thigh-cuffs after 3-min supra-systolic occlusion. The responses of heart rate (HR), mean arterial pressure (MAP), and blood flow velocity of the middle cerebral artery (VMCA) were determined. Cerebral vascular conductance (CVC) was estimated from mean VMCA/MAP. Duration and rate of the recovery from the nadir of MAP and VMCA were compared between the groups.
Results
Thigh-cuff occlusion-deflation elicited a similar hypotension (ΔMAP) and hypoperfusion to the brain (ΔVMCA) in the elderly and young groups. However, the time elapsed from the cuff-deflation to the nadir of MAP and VMCA (TΔ), and the recovery time from the nadir to reaching the respective baseline levels (TR) were significantly longer in the elderly subjects. There were significant differences between the groups in the response rates of HR, MAP and CVC following the cuff-deflation. Overall TR-VMCA was significantly explained by the response rates of the cardiac-factor, vasomotor-factor, and CVC-factor. However, the TR-VMCA/vasomotor-factor slope (-3.0 ± 0.9) was steeper (P = 0.046) than the TR-VMCA/cardiac-factor slope (-1.1 ± 0.4). The TR-VMCA/CVC-factor slope (-2.4 ± 0.6) was greater (P = 0.072) than the TR-VMCA/cardiac-factor slope; but it did not differ from the TR-VMCA/vasomotor-factor slope (P = 0.52).
Conclusions
Both CA and systemic mechanisms contributed to cerebral perfusion recovery elicited by systemic hypotension; and the vasomotor factor was dominant over the cardiac factor. Recovery from cerebral hypoperfusion is slower in the elderly adults because of the age-diminished rates of the CVC response and cardiovascular reflex regulation. Vasomotor-response mediated perfusion pressure seems more significant in maintaining cerebral perfusion during systemic hypotension.
Management and Surgical Treatment of Parathyroid Carcinoma: a 6-years’ experience of single centre of Endocrine Surgery Unit
Authors: Laforgia Rita , Tomasicchio Giovanni , Cavalera Federica , Sblendorio Maria , Spadone Annamaria , Panebianco Annunziata , Pezzolla Angela
Published: March 2023

Parathyroid carcinoma (PC) affects 0.1–0.3% of the general population1 and represents the rarest malignant neoplasms among endocrinological disease, representing less than 1%. Differential diagnostic from malignant to benign disease is challenging and the best therapeutic treatment and management are still debated in literature14. The aim of this study is the evaluation of management and surgical treatment of Parathyroid Carcinoma after 6 years enrollment from the Endocrine Surgery Unit of the University Hospital of Bari. A retrospective observational study was carried out using a prospectively maintained database of patients affected by primary hyperparathyroidism underwent surgery in the Endocrine Surgery Unit between January 2017 and September 2022. Nine patients were included with hystological diagnosis of PC and the evidence of pre operative high levels of serum PTH and calcium. No mortality was recorded while the incidence of recurrence was 22.2% with a disease-free survival of 8 and 10 months respectively. PC represents a great challenge in terms of pre-operative diagnostic, management and treatment. Surgical approach represents the first best option for PC in referral endocrine surgery units. The early identification of risky patients should be dominant to plan an appropriate therapy and to perform an adequate en bloc surgery.
The Science of Startups: The Impact of Founder Personalities on Company Success
Authors: Braesemann Fabian , McCarthy Paul , Gong Xian , Stephany Fabian , Rizoiu Marian-Andrei , Kern Margaret
Published: March 2023

Startup companies solve many of today’s most complex and challenging scientific, technical and social problems, such as the decarbonisation of the economy, air pollution, and the development of novel life-saving vaccines. Startups are a vital source of social, scientific and economic innovation, yet the most innovative are also the least likely to survive. The probability of success of startups has been shown to relate to several firm-level factors such as industry, location and the economy of the day. Still, attention has increasingly considered internal factors relating to the firm’s founding team, including their previous experiences and failures, their centrality in a global network of other founders and investors as well as the team’s size. The effects of founders’ personalities on the success of new ventures are mainly unknown. Here we show that founder personality traits are a significant feature of a firm’s ultimate success. We draw upon detailed data about the success of a large-scale global sample of startups (n=26,781). We found that the Big 5 personality traits of startup founders across 30 dimensions significantly differed from that of the population at large. We can train a classifier to distinguish founders from employees with 82.5% accuracy. Key personality facets that distinguish successful entrepreneurs include a preference for variety, novelty and starting new things (openness to adventure), like being the centre of attention (lower levels of modesty) and being exuberant (higher activity levels). However, we do not find one “Founder-type” personality; instead, six different personality types appear, with startups founded by a “Hipster, Hacker and Hustler” being twice as likely to succeed. Our results also demonstrate the benefits of larger, personality-diverse teams in startups, which has the potential to be extended through further research into other team settings within business, government and research.
A Multi-Material 3D Printing-Assisted Micropatterning
Authors: Jambhulkar Sayli , Ravichandran Dharneedar , Thippanna Varunkumar , Patil Dhanush , Song Kenan
Published: March 2023

Micropatterned structures have applications in microchips, circuit board designs, microfluidics, evaporator/condenser coils, microelectronics, metasurfaces, and other functional devices. Conventional microfabrication techniques include lithography, vapor deposition, and laser writing. However, these methods have slow processing rates, complex requirements, or costly procedures. As a result, it is challenging to fabricate micropatterned structures onto large-scale surfaces with high production rates and resolution features. Thus, this study focuses on a non-conventional, mask-free micropatterning technique that combines bottom-up 3D printing capable of processing multiple materials and top-down wet etching for selective elimination of sacrificial material. The unique 3D printing, Multiphase Direct Ink Writing (MDIW), utilizes various polymer and nanoparticle systems as feedstocks for depositing lamellar structures containing sublayers of varying compositions (i.e., wet etchable sacrificial ink and ultraviolet-curable patterning ink). The rapid phase transformation of photosensitive ink into solidified features enables "micro-confinement" of the sacrificial ink. Subsequently, wet etching can locally and selectively dissolve sacrificial polymers by solvent diffusion and polymer dissolution at the polymer-solvent interface. The parameter control (i.e., ink rheology, polymer-polymer interdiffusion, layer multiplication, phase transformation, and solvent-polymer interactions) can precisely tune the lamellar-groove transition, thus forming desirable surfaces or internal microstructures. Our MDIW 3D printing and its facilitation in surface micropatterning demonstrate the massive potential of distributing nanoparticles for dissipating thermal energies. With production scalability, operation simplicity, and multi-material compatibility, our 3D-printed micropatterning shows broader applications in nanoparticle assembly, drug delivery, optical lenses, intelligent microbots, and morphing objects.
Diagnosis and Treatment Outcomes of Urethritis-like Symptoms in Young Males: A Retrospective Cohort Study
Authors: Hsu Yi-Ting , Chuang Tzu-Yu , Hsiao Jui Chang , Cheng Weiming
Published: March 2023

Background
Urethritis in young males is most commonly caused by sexually transmitted pathogens, although other non-infectious diseases can cause similar symptoms. The study evaluated the prevalence of gonorrhoea and chlamydia infections in sexually active young males with urethritis-like symptoms and their treatment outcomes.
Methods
Data of 20–50-year-old males who visited our clinic with urethritis symptoms between March 2019 and April 2022 were retrospectively collected. All patients underwent urinalysis, urine culture, and urinary polymerase chain reaction (PCR) testing for gonorrhoea and chlamydia at the first visit. Student’s t-test and Pearson’s chi-square test were used to compare the differences between participants with at least one positive test result and those with negative results in all three tests. Regression analyses were used to evaluate the predictive factors for positive PCR results for gonorrhoea or chlamydia in patients with negative urinalysis and urine culture results.
Results
Of the 365 participants with urethritis symptoms, those with negative results (39%) in all tests were significantly older and showed less frequent urethral discharge than those with at least one positive result. Among the 202 patients with negative urinalysis and urine culture results, 29.7% were diagnosed with gonorrhoea or chlamydia using PCR. The presence of discharge was an independent predictor of positive PCR results for gonorrhoea or chlamydia. For patients showing negative results in all tests, the most common tentative diagnosis was balanitis. Patients with negative results for all three tests have good prognosis.
Conclusion
The present study outlined the high frequency of negative urinalysis and urine culture results in young male patients with gonorrhoea- and chlamydia-related urethritis and indicated the importance of a history of urethral discharge as an indicator for antibiotic treatment of gonorrhoea and chlamydia in these patients. The findings of this study will be valuable for urologists treating young males with urethritis symptoms, and the insights provided here will facilitate appropriate management and patient satisfaction in such cases.
A Qualitative Analysis of the Botswana Schistosomiasis Control Policy and Plan Using Policy Triangle Framework
Authors: Gabaake Kebabonye Priscillah , Lucero-Prisno Don Eliseo , Thakadu Olekae Tsompi , Phaladze Nthabiseng A
Published: March 2023

Background: The present goal of the World Health Organization (WHO) 2021-2030 roadmap for Neglected Tropical Diseases (NTDs) is to eliminate schistosomiasis as a public health problem, and reduce its prevalence of heavy infections to less than 1%. Given the evolution and impact of schistosomiasis in the Ngamiland district of Botswana, this study reviewed the control policies for the district.
Aim: The purpose of the study was to analyze the Botswana schistosomiasis control policies using the Policy Triangle Framework (PTF).
Methods: The study used qualitative approaches of a review of policy documents and interviews with twelve (12) informants purposively selected. Although the informants were recruited from all levels of the NTD sector, the analysis of the program responses were predominantly from the Ngamiland district. Data were analyzed using Braun and Clarke`s approach to content analysis.
Results: The study highlights the presence of clear, objectives and targets for the Ngamiland control policy. Another theme was a success in morbidity control, which was realized primarily through cycles of MDA in schools. The contextual background for the policy was high morbidity and lack of programming data. The implementation process of the policy was centralized at the Ministry of Health (MOH) and WHO, and there was minimal involvement of the community and other stakeholders. The policy implementation process was impeded by lack of domestic resources and lack of comprehensive policy content on snail control and none expansion of the policy content beyond SAC. The actors were predominately MOH headquarters and WHO, with little representation of the district, local level settings, NGOs and private sectors. Conclusions: The lack of resources and content in the control of environmental determinants and inclusion of other at risk groups in the policy impeded sustained elimination of the disease. There is a need to guide the treatment of pre-school-aged children and develop national guidelines on treating foci of intense transmission. Moreover, the dynamic of the environmental transmissions and reorientation of the schistosomiasis policy to respond to the burden of schistosomiasis morbidity, local context, and health system context are required.
Rapid Short-Pulses of Focused Ultrasound and Microbubbles Deliver a Range of Agent Sizes to the Brain
Authors: Chang William Lim Kee , Chan Tiffany G. , Raguseo Federica , Mishra Aishwarya , Chattenton Dani , de Rosales Rafael T. M. , Long Nicholas J. , Morse Sophie V
Published: March 2023

Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood-brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood-brain barrier closing within 10 minutes. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.
D2 receptor sensitization: Neurobiological basis of increase sensitivity of stress on stimulant induced impaired behavioural sensetization
Authors: Alam Nausheen , Abbasi shagufta , Naeem Sadaf
Published: March 2023

Stress is associated with high risk of psychological disorders and cognitive impairment. Psychostimulants are also known to potentiate cognition & ameliorate depression, but their long-term use causes behavioural sensitization. The locomotor response to psychostimulant potentiated after repeated exposure to stressful stimulus & dopamine is thought to play a major role in sensitization-like phenomena. The present study is conducted to visualize responsiveness of dopamine D2 receptors by challenge dose of haloperidol following long term psychostimulant administration in restrained & unrestrained rats. Behavioural Effects of oral repeated administration of methylphenidate (10mg/kg/day 2 times daily) & modafinil (75mg/kg/day once daily) in restrained (exposed to immobilization stress for 2 hours daily) and unrestrained rats were monitored to observe locomotor sensitization, by using familiar environment of home cage (performed after every two days) and novel environment of open field (weekly) however, exploratory activity in Head Dip Test and cognitive activity in passive avoidance test (PAT) were carried out weekly for 35 days (till the behavioral sensitization produced). Effects of haloperidol challenge dose (1 mg/kg i.p.) were monitored after 35 days of treatment using Home Cage, Open Field, Head Dip and PAT, 30-, 60-, 90- & 120-minutes post injection. The result shows increase in locomotor activity in drug treated rats potentiated by restrained stress and sensitization effect was significant in 3rd week of psychostimulant administration and was more pronounced in modafinil treated rats. Exploratory activity in Head dip test reduced by restrained stress whereas potentiated by MOD & MPH in unrestrained rats. In restrained rats only MOD prevents stress-induced effect on exploratory behaviour. Restrained stress produced cognitive deficits but MOD and MPH improved cognitive performance in PAT. Challenge dose of haloperidol ameliorated motor activity in familiar and novel environment, impaired cognition in PAT and decreased activity in head dip test, effect was more pronounced in psychostimulant treated restrained mice. This study will be beneficial for the understanding of neurobiological basis of the effect of psychostimulants on stress induced motor and cognitive deficits so helpful to investigate drugs that could prevent psychostimulant induced behavioural sensitization in stressful environment
Sterilization characteristics inside narrow tube using nitrogen oxides generated by atmospheric pressure air plasma
Authors: Muto Reona , Hayashi Nobuya
Published: March 2023

The sterilization characteristics of the inner surface of silicon tube were investigated using active species generated by atmospheric dielectric barrier discharge (DBD) plasma using air and oxygen gas. A DBD torch-type device installed at one end of the tube and generated long-lifetime active species flowing into the tube. The strip-type BI (Biological indicator) with 105 spore-forming bacteria placed at the position opposite to the DBD device in a 60 cm tube was sterilized within 30 min by active particles generated from air plasma. Major factors for the sterilization using air plasma were HNO3 and N2O5. When the organic materials (keratin, aspartic acid and dipicolinic acid) comprising spores were treated same as sterilization, the treatment hardly changed the composition of dipicolinic acid. Keratin was oxidized by ozone and NOx generated from oxygen plasma and air plasma. The result of aspartic acid showed little change in composition by ozone generated from oxygen plasma, whereas nitro (NO2), nitroso (NO) and aldehyde (CHO) groups were formed by ozone and NOx generated from air plasma.
Knockdown of mechanosensitive adaptor Hic-5 ameliorates post-traumatic osteoarthritis in rats through repression of MMP-13
Authors: Miyauchi Aya , Noguchi Masahito , Lei Xiao-Feng , Sakaki Masashi , Kobayashi-Tanabe Momoko , Haraguchi Shogo , Miyazaki Akira , Kim-Kaneyama Joori
Published: March 2023

Osteoarthritis (OA) is the most common joint disease associated with articular cartilage destruction. Matrix metalloproteinase-13 (MMP-13) has an essential role in OA pathogenesis by degradation of collagen II, a major component of articular cartilage. Hydrogen peroxide-inducible clone-5 (Hic-5; TGFB1I1), a transforming growth factor-β-inducible mechanosensor, has previously been reported to promote OA pathogenesis by upregulating MMP-13 expression in mouse osteoarthritic lesions. In our current study, immunohistochemical analysis showed that Hic-5 protein expression was increased in human OA cartilage compared with normal cartilage. Functional experiments demonstrated that Hic-5 and MMP-13 expression was increased by mechanical stress, and mechanical stress-induced MMP-13 expression was suppressed by Hic-5 siRNA in human chondrocytes. Moreover, intracellular localization of Hic-5 shifted to the nucleus from focal adhesions in human chondrocytes subjected to mechanical stress, and nuclear Hic-5 increased MMP-13 gene expression. In vivo, intra-articular injection of Hic-5 siRNA decreased the Osteoarthritis Research Society International score and MMP-13 protein expression in articular cartilage of OA rats. Our findings suggest that Hic-5 regulates transcription of MMP-13 in human chondrocytes, and Hic-5 may be a novel therapeutic target for OA because OA progression was suppressed by intra-articular injection of Hic-5 siRNA in rats.
Biomechanical Test of the Stability of a Cervical Interfacet Self-Locking Cage
Authors: Sun Maji , Li Zhongwei , Wang Qiu'an , Chu Fuchao , Yuan Feng
Published: March 2023

Purpose To compare the biomechanical properties of a novel 3D-printed cervical interfacet self-locking cage (CISC) using medical titanium alloy (Ti-6Al-4V) material with the lateral mass screw–rod system.
Methods CT scans were performed on seven preserved human cervical spine specimens (C2–T1) to exclude deformities, infections, tumors, fractures and other lesions, and titanium CISCs were 3D-printed based on the CT scan data. A moment of 1.5 Nm was applied to the specimen using a biomechanics machine. The range of motion (ROM) in bending, extension, lateral bending and rotation directions of each specimen in the different groups was measured, including an intact group (group A), a C5–C6 posterior ligamentous complex (PLC) resection group (group B), a C5–C6 lateral mass screw–rod system fixation group (group C), and a C5–C6 novel CISC fixation group (group D).
Results Groups C and D had smaller ROM than groups A and B in flexion–extension, lateral bending and rotation directions, and the difference was statistically significant (P < 0.05). Group D had significantly greater ROM than group C in the forward flexion and posterior extension directions (P < 0.05).
Conclusions Injury to the posterior ligament complex of the lower cervical spine can cause flexion and extension, lateral bending, and instability in the direction of axial rotation. CISC fixation is equivalent to the fixation effect of the lateral mass screw-rod system, and can be used as a simple fixation or supplementary fixation for the posterior cervical spine.
Sequential vs Myeloablative vs Reduced Intensity Conditioning for Patients with Myelodysplastic Syndromes with an excess of blasts at time of allogeneic haematopoietic cell transplantation: A Retrospective Study by the Chronic Malignancies Working Party of the EBMT
Authors: Potter Victoria , Gras Luuk , Biezen Anja van , Kroeger Nicolaus , Sockel Katja , Ganser Arnold , Finke Jürgen , labussiere helene , de Latour Regis Peffault , Koc Yener , Friis Lone , Salmenniemi Urpu , Jindra Pavel , Schroeder Thomas , Tischer Johanna , Arat Mutlu , Pascual María , de Wreede Liesbeth , Hayden Patrick , Raj Kavita , Drozd-solowska Joanna , Scheid Christof , McLornan Donal , Robin Marie , Yakoub-Agha Ibrahim
Published: March 2023

The optimal conditioning for patients with higher risk MDS receiving potentially curative allogeneic haematopoietic stem cell transplant(allo-HCT) remains to be defined. This is particularly the case for patients with excess of blasts at time of allo-HCT. Sequential(Seq) conditioning, whereby chemotherapy is followed rapidly by transplant conditioning, offers an opportunity to decrease disease burden, potentially improving outcomes allo-HCT outcomes. Herein we present the only analysis comparing Seq to myeloablative(MAC) and reduced intensity conditioning(RIC) specifically focussed on MDS patients with excess of blasts at allo-HCT. 303 patients were identified in the EBMT registry, receiving RIC(n=158,) Seq(n=105,), and MAC(n=40, ). Median follow-up was 67.2 months and median age at allo-HCT was 59.5 years(IQR 53.5 - 65.6). For the entire cohort, 3yr overall survival(OS) was 50%(95% CI45-56%) and relapse free survival(RFS) 45%(95%CI 40-51%). No differences in outcomes were observed per protocol with respect to OS and RFS. On multivariable analysis, lower performance status, worse IPSS-R cytogenetics, sibling donor (compared to 8/8 MUD) and >20% blasts at allo-HCT were associated with worse outcomes. In conclusion, the Seq protocol did little to influence the outcome in this high-risk group of patients, with outcomes mostly determined by baseline disease risk and patient characteristics such as performance status.
Clinical features and treatment outcomes of a patient with retinitis pigmentosa secondary to adult coats' disease
Authors: Fu Wenzhong , Xu Hongxia , Ma Yujun , Jiang Huaiyan
Published: March 2023

Retinitis pigmentosa(RP) is a set of hereditary retinal diseases. We describe a patient who suffered retinitis pigmentosa secondary to adult coats' disease. The patient had undergone pars plana vitrectomy(PPV),intravitreal injection of anti-VEGF drugs as well as steroids. Eventually, the patient had a good anatomical result postoperatively.
Accuracy of Fit for Cobalt-Chromium Bar Over Two Implants Fabricted with Different Manufacturing Techniques‑An in Vitro Study.
Authors: Nassar Hossam I , Fateen Ayman
Published: March 2023

Objective
The purpose of the invitro research was to compare the fit of Cobalt Chromium customized bar fabricated with different manufacturing processes cast metal bar, milled bar and 3D printed bar using scanning electron microscope.
Material and Methods
Clear epoxy resin molds were prepared. In each mold two parallel implants with a 14 mm distance from each other were embedded. Thirty Co-Cr custom bars were constructed and were divided equally into three groups: Group (I) (Co-Cr conv), group (II) milled bar (Co-Cr milled), and group (III) printed bar (Co-Cr print). The marginal fit at implant-abutment interface was scanned using scanning electron microscope (SEM)
Results
There was a significant difference between the three studied groups regarding marginal misfit the between implant and fabricated bars with p-value < 0.001. The highest value of micro-gap distance was found in Co-Cr conventional group (7.95 ± 2.21µm) followed by Co-Cr 3D printed group (4.98 ± 1.73) and the lower value were found in Co-Cr milled (3.22 ± 0.75).
Conclusion
The marginal fit of milled, 3D printed and conventional cast for Co-Cr alloy were within the clinically acceptable range of misfit. CAD/CAM milled Co-Cr bar revealed a superior internal fit at the implant-abutment interface. This was followed by selective laser melting (SLM) 3D printed bar and the least fit was shown for customized bar with the conventional lost wax technique.
Technology Based Supportive Care for Metastatic Breast Cancer Patients
Authors: Schmitz Kathryn H. , Kanski Beth , Gordon Brett , Caru Maxime , Vasakar Monali , Truica Cristina I. , Wang Ming , Doerksen Shawna , Lorenzo Abby , Winkels Renata , Qui Ling , Abdhullah Saeed
Published: March 2023

PurposeMetastatic breast cancer (MBC) patients are living longer. However, symptom burden remains a significant issue. Technology-based interventions may be a solution. The purpose of this study was to test a virtual assistant for addressing symptoms in MBC using the Amazon Echo Show with Alexa.MethodsIn this partial crossover randomized trial, the immediate treatment group was exposed to the intervention, called Nurse AMIE (Addressing Metastatic Individuals Everyday) for six months. The comparison group was unexposed for the first 3 months, then exposed for 3 months. The randomized controlled trial (RCT) during the first 3 months allowed for evaluation of intervention effects on symptoms and function. The partial crossover maximized exposure to the intervention for evaluation of feasibility, usability, and satisfaction. RCT outcome data were collected at baseline and 3 months. Feasibility, usability, and satisfaction data were collected throughout the first 3 months of intervention exposure.ResultsForty-two MBC patients were randomized (1:1). Participants were 53±11 years old and 4±7 years from diagnosis with metastatic disease. No significant effects on psychosocial distress, pain, sleep disturbance, fatigue (vitality), quality of life, or chair stands were noted, despite high levels of acceptability (51%), feasibility (65%), and satisfaction (70%).ConclusionA high level of participant acceptability, feasibility, usability, and satisfaction all suggest further research on this platform is warranted. The lack of statistically significant effects on symptoms, quality of life, and function may be the result of small sample size. Clinical Trials.gov Registration number: NCT04673019; Registration date: December 17, 2020
Unravelling the effects of active site densities and energetics on the water oxidation activity of iridium oxides
Authors: Liang Caiwu , Rao Reshma , Svane Karine , Hadden Joseph , Moss Benjamin , Scott Soren , Sachs Michael , Murawski James , Frandsen Adrian , Riley Jason , Ryan Mary , Durrant James , Rossmeisl Jan , Stephens Ifan
Published: March 2023

Understanding what controls the reaction rate on iridium-based catalysts is central to designing more active and stable electrocatalysts for the water oxidation reaction in proton exchange membrane (PEM) electrolysers. Here, we quantify the densities of redox active centres and probe their binding strengths on amorphous IrOx and rutile IrO2 using a combination of operando time-resolved optical spectroscopy, X-ray absorption spectroscopy (XAS) and time of flight secondary ion mass spectrometry (TOF-SIMs). Firstly, our results show that although IrOx exhibits an order of magnitude higher geometry current density compared to IrO2, the intrinsic rates of reaction per active state, on IrOx and IrO2 are comparable at a given potential. Secondly, we establish a quantitative experimental correlation between the intrinsic rate of water oxidation and the energetics of the active states. We use density functional theory (DFT) based models to provide a molecular scale interpretation of our data. We find that the *O species formed at water oxidation potentials have repulsive adsorbate-adsorbate interactions, and thus increasing their coverage weakens their binding and promotes the rate-determining O-O bond formation. Finally, we provide insights into how the intrinsic water oxidation kinetics can be increased by optimising both the binding energy and the interaction strength of the catalytically active states.