bluuebunny/crossref_metadata_2025 huggingface dataset:
Inequality in health opportunities in Indonesia: long-term influence of early-life circumstances on health
Authors: Aizawa Toshiaki
Published: July 2022

Background

This study explores inequality of opportunity in terms of the health of adult Indonesian people, associated with household and parental circumstances in childhood and adolescence.

Methods

Exploiting the longitudinal nature of the Indonesian Family Life Survey, this study measures inequalities relating to being underweight, overweight, hypertensive and diabetic across adult Indonesians aged between 20 and 35 through the dissimilarity index. This study explores their determinants by decomposing the observed inequality levels into contributing factors. Moreover, this study sheds light on the underlying mechanisms through which early-life circumstances influence the health of grown-up respondents, by estimating the intermediate effects of early-life circumstances on current lifestyles.

Results

For all health conditions, health risks are unequally distributed (all p<0.01). Demographic factors and parental health are major contributors to inequalities relating to being underweight, overweight and hypertensive. Family structure and parental occupation are major contributors to inequality in diabetes. The greater part of this inequality is explained by the indirect pathways through which early-life circumstances mediate current diet and exercise habits.

Conclusions

The results suggest that such interventions that compensate for disadvantaged early-life circumstances would be essential in reducing future health risks and mitigating health inequality.
Safety and feasibility of the transoral endoscopic thyroidectomy vestibular approach with neuroprotection techniques for papillary thyroid carcinoma
Authors: Chen Zhen-Xin , Song Ya-Min , Chen Jing-Bao , Zhang Xiao-Bo , Pang Feng-Shun , Lin Zhan-Hong , Yang Li-Ming , Cai Bei-Yuan , Qin You
Published: July 2022

Background

This study aimed to evaluate the feasibility and safety of the trans-oral endoscopic thyroidectomy vestibular approach (TOETVA) with neuroprotection techniques for the surgical management of papillary thyroid carcinoma (PTC).

Methods

Patients with PTC who underwent TOETVA between December 2016 and July 2020 were included in this study, and their relevant clinical characteristics, operational details, and surgical outcomes were reviewed and extracted from their medical records for further analysis.

Results

A total of 75 patients successfully underwent TOETVA with zero conversions. Unilateral lobectomy with isthmectomy and total thyroidectomy were completed for 58 and 17 patients, respectively, all using our unique neuroprotective procedure and ipsilateral central neck dissection (CND). The mean number of retrieved lymph nodes versus positive lymph nodes was 6.8 ± 3.7 vs. 1.5 ± 2.3. Postoperative complications included three cases of transient superior laryngeal nerve (SLN) palsy (4.0%), five cases of transient recurrent laryngeal nerve (RLN) palsy (6.7%), 14 cases of transient hypoparathyroidism (18.7%), two cases of numb chin (2.7%) and two cases of flap perforation (2.7%). The follow-up period for patients with PTC lasted for 15.6 ± 10.9 months, during which no other complications or tumor recurrence were observed.

Conclusion

TOETVA can be safely performed for patients with PTC with satisfactory results during the short-term follow-up period. Our neuroprotection techniques can be integrated into TOETVA, which is worth recommending for PTC patients who desire better cosmetic surgical outcomes.
Reasonable requests: echocardiography referral forms as a measure of coherent clinical communication
Authors: Kotzé C. , Parrish A.
Published: July 2022

Background

Well performed clinical communication is a cornerstone of collaborative care in medicine but may be confounded by inconsistent intentions of the messenger and biased interpretation by the recipient. A comparison of the findings of electronic echocardiography reports with clinician-completed standardised request forms provided an opportunity to assess communication quality.

Aim

The study aimed to determine clinician aptitude to complete written echocardiography referral forms by assessing the completeness, appropriateness, accuracy, and coherency of the reported clinical findings, conclusions and requests made on the referral forms. The study explored factors that may influence the quality of communication through this referral medium.

Methods

A retrospective cohort study was conducted on patients who underwent trans-thoracic echocardiography imaging at Cecilia Makiwane Hospital in East London over 26 months. Paper echocardiography request forms that recorded the requesting clinician’s findings on examination, the provisional clinical diagnosis, and the specific echocardiographic information sought, were compared with the actual findings on echocardiography.

Results

Of 613 request forms reviewed, 97 cases were excluded due to illegibility or because they lacked analysable information or requester details, leaving 516 forms suitable for study. No pathology was found on echocardiography in 31%. Of the murmurs expected from the echocardiography findings, only half were recorded on the request form (sensitivity and positive predictive value both 52%.). Only 35% of request forms that mentioned a mitral systolic murmur gave a working diagnosis of mitral regurgitation and only 38% of request forms that mentioned an aortic systolic murmur considered aortic stenosis. Clinically suspected cardiomyopathy (CMO) had a PPV of 43% and echocardiographic CMO was missed clinically in 41%. Apex beat displacement reported clinically was not associated with echocardiographic LV dilatation in 65% of cases. One-third (34%) of forms reporting murmurs did not request valve function assessment and 17% considering cardiomyopathy did not request left ventricular function assessment.

Conclusion

Echocardiography request forms highlight vulnerabilities in clinical communication. Specifically, important clinical features were missing and more concerningly, included when unlikely to be present. There was a lack of concordance between recorded clinical findings and postulated diagnoses. Clinicians sometimes appeared unclear about the value or appropriateness of the requested assistance. Greater emphasis on teaching examination and communication skills may foster safer and more efficient use of scarce resources.
Cost-minimisation analysis of plasma exchange versus IVIg in the treatment of autoimmune neurological conditions
Authors: Klemencic Kozul Tara , Yudina Anna , Donovan Carley , Pinto Ashwin , Osman Chinar
Published: July 2022

Background

Plasma exchange (PLEX) is an effective treatment for antibody-mediated neurological disorders and has been shown to be equally efficacious to intravenous immunoglobulin (IVIg) with comparable adverse event profiles. IVIg has traditionally been the preferred treatment option due to its ease of use. However, advancing technology has allowed PLEX to be performed with a centrifugal system via peripheral access as opposed to central access via a membrane filter.

Methods

We prospectively collected data from a cohort of patients who underwent PLEX at the Wessex Neurological Centre, UK, to perform a cost-minimisation analysis comparing PLEX to IVIg, the standard of care, between May 2019 and May 2020. Data obtained included indication, admission type (inpatient, daycase or intensive care), access (peripheral or central), number of PLEX cycles, exchange volume, patient weight, complications and clinical outcomes. The cost of PLEX delivered in an outpatient setting for an average 80kg person was calculated and compared to the equivalent cost of delivering IVIg by means of a cost-minimization model.

Results

The provision of PLEX was roughly half as costly when compared to what it would have been for IVIg (£886 per exchange vs £1778 per infusion or £4432 per cycle of 5 exchanges vs £8890 per cycle of 5 infusions). Our cohort included a total of 44 patients who received a total of 357 PLEX exchanges during the 12-month period (the majority of which were in a daycase setting). We calculated an annual cost saving for PLEX over IVIg of £318,589. The robustness of this result was confirmed by a one-way deterministic sensitivity analysis, showing the cost-effectiveness of PLEX.

Conclusion

Our findings demonstrate that PLEX is more cost-effective than IVIg in this setting. Our study supports the economic case for development of plasma exchange centres in regional neurology units, a case made all the more relevant in the context of constrained supplies of IVIg.
Family caregivers’ preparedness to support the physical activity of patients at risk for hospital readmission in rural communities: an interpretive descriptive study
Authors: Fox Mary T. , Butler Jeffrey I. , Sidani Souraya , Nguyen An
Published: July 2022

Background

Physical activity in the post-discharge period is important to maximize patient recovery and prevent hospital readmission. Healthcare providers have identified family caregivers as potential facilitators of patients’ engagement in physical activity. Yet, there is very little research on family caregivers’ perspectives on their preparedness to support the physical activity of patients, particularly those at risk for hospital readmission in rural communities. Accordingly, this study explored the challenges related to family caregivers’ preparedness to support the physical activity of a recently discharged, rural-dwelling relative at risk for hospital readmission.

Methods

In this interpretive descriptive study, semi-structured interviews were conducted by telephone with 16 family caregivers. Interview transcripts were analyzed using thematic analysis.

Results

Participants were predominantly women (n = 14; 87.5%) with an average age of 49 years (range 26–67) who were the primary caregivers of a relative who had been hospitalized for a medical illness (n = 12; 75%) and was at high risk for hospital readmission. Four themes were identified: 1) family caregivers generally felt unprepared to support their relative’s physical activity, 2) some family caregivers believed that rest was more important than physical activity to their relative’s recovery, 3) insufficient physical activity preparation led to family caregiver-relative conflicts, and 4) to defuse these conflicts, some family caregivers wanted healthcare providers to be responsible for promoting physical activity.

Conclusions

Despite assertions that family caregivers are a potential source of support for patient physical activity, our findings indicate that family caregivers are largely unprepared to assume that role and that more work needs to be done to ensure they can do so effectively. We suggest that healthcare providers be conscious of the potential for family caregiver-patient conflict surrounding physical activity, assess family caregivers’ ability and willingness to support physical activity, educate them on the hazards of inactivity, and provide physical activity instructions to family caregivers and patients conjointly. Preparing family caregivers to support their relative’s physical activity is particularly important given the current emphasis on early discharge in many jurisdictions, and the limited formal healthcare services available in rural communities.
The testis-specific E3 ubiquitin ligase RNF133 is required for fecundity in mice
Authors: Nozawa Kaori , Fujihara Yoshitaka , Devlin Darius J. , Deras Ricardo E. , Kent Katarzyna , Larina Irina V. , Umezu Kohei , Yu Zhifeng , Sutton Courtney M. , Ye Qiuji , Dean Laura K. , Emori Chihiro , Ikawa Masahito , Garcia Thomas X. , Matzuk Martin M.
Published: July 2022

Background

Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin–proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids fromUbe2j1KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated E3 ubiquitin-protein ligases that function during spermatogenesis remain unknown.

Results

We identified four evolutionarily conserved testis-specific E3 ubiquitin-protein ligases [RING finger protein 133 (Rnf133); RING finger protein 148 (Rnf148); RING finger protein 151 (Rnf151); and Zinc finger SWIM-type containing 2 (Zswim2)]. Using the CRISPR/Cas9 system, we generated and analyzed the fertility of mutant mice with null alleles for each of these E3-encoding genes, as well as double and triple knockout (KO) mice. Male fertility, male reproductive organ, and sperm-associated parameters were analyzed in detail. Fecundity remained largely unaffected inRnf148,Rnf151, andZswim2KO males; however,Rnf133KO males displayed severe subfertility. Additionally,Rnf133KO sperm exhibited abnormal morphology and reduced motility. Ultrastructural analysis demonstrated that cytoplasmic droplets were retained inRnf133KO spermatozoa. AlthoughRnf133andRnf148encode paralogous genes that are chromosomally linked and encode putative ER transmembrane E3 ubiquitin-protein ligases based on their protein structures, there was limited functional redundancy of these proteins. In addition, we identified UBE2J1 as an E2 ubiquitin-conjugating protein that interacts with RNF133.

Conclusions

Our studies reveal that RNF133 is a testis-expressed E3 ubiquitin-protein ligase that plays a critical role for sperm function during spermiogenesis. Based on the presence of a transmembrane domain in RNF133 and its interaction with the ER containing E2 protein UBE2J1, we hypothesize that these ubiquitin-regulatory proteins function together in ER quality control during spermatogenesis.
Perioperative oxygen therapy: a protocol for an overview of systematic reviews and meta-analyses
Authors: Elfeky Adel , Chen Yen-Fu , Grove Amy , Hooper Amy , Wilson Anna , Couper Keith , Thompson Marion , Uthman Olalekan , Court Rachel , Tomassini Sara , Yeung Joyce
Published: July 2022

Background

Oxygen is routinely given to patients during and after surgery. Perioperative oxygen administration has been proposed as a potential strategy to prevent and treat hypoxaemia and reduce complications, such as surgical site infections, pulmonary complications and mortality. However, uncertainty exists as to which strategies in terms of amount, delivery devices and timing are clinically effective. The aim of this overview of systematic reviews and meta-analyses is to answer the research question, ‘For which types of surgery, at which stages of care, in which sub-groups of patients and delivered under what conditions are different types of perioperative oxygen therapy clinically effective?’.

Methods

We will search key electronic databases (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CENTRAL, Epistemonikos, PROSPERO, the INAHTA International HTA Database and DARE archives) for systematic reviews and randomised controlled trials comparing perioperative oxygen strategies.

Each review will be mapped according to type of surgery, surgical pathway timepoints and clinical comparison. The highest quality reviews with the most comprehensive and up-to-date coverage of relevant literature will be chosen as anchoring reviews. Standardised data will be extracted from each chosen review, including definition of oxygen therapy, summaries of interventions and comparators, patient population, surgical characteristics and assessment of overall certainty of evidence. For clinical outcomes and adverse events, the overall pooled findings and results of subgroup and sensitivity analyses (where available) will be extracted. Trial-level data will be extracted for surgical site infections, mortality, and potential trial-level effect modifiers such as risk of bias, outcome definition and type of surgery to facilitate quantitative data analysis. This analysis will adopt a multiple indication review approach with panoramic meta-analysis using review-level data and meta-regression using trial-level data. An evidence map will be produced to summarise our findings and highlight any research gaps.

Discussion

There is a need to provide a panoramic overview of systematic reviews and meta-analyses describing peri-operative oxygen practice to both inform clinical practice and identify areas of ongoing uncertainty, where further research may be required.

Systematic review registration

PROSPERO CRD42021272361
Analysis of stochastic neutral fractional functional differential equations
Authors: Siva Ranjani Alagesan , Suvinthra Murugan , Balachandran Krishnan , Ma Yong-Ki
Published: July 2022

This work deals with the large deviation principle which studies the decay of probabilities of certain kind of extremely rare events. We consider stochastic neutral fractional functional differential equation with multiplicative noise and show large deviation principle for its solution processes in a suitable Polish space. The existence and uniqueness results are presented using the Picard iterative method, which is indeed essential for further analysis. The establishment of Freidlin–Wentzell type large deviation principle is solely based on the variational representation developed by Budhiraja and Dupuis in which the weak convergence technique is used to show the sufficient condition. Examples are provided to emphasize the theory.
Existence of positive solutions for a singular third-order two-point boundary value problem on the half-line
Authors: Bao Yongdong , Wang Libo , Pei Minghe
Published: July 2022

In this paper, we consider the following singular third-order two-point boundary value problem on the half-line of the form$$ \textstyle\begin{cases} x'''+\phi (t)f(t,x,x',x'')=0, \quad 0< t< +\infty , \\ x(0)=0, \qquad x'(0)=a_{1},\qquad x'(+\infty )=b_{1}, \end{cases} $${x‴+ϕ(t)f(t,x,x′,x″)=0,0<t<+∞,x(0)=0,x′(0)=a1,x′(+∞)=b1,where$\phi \in C[0,+\infty )$ϕ∈C[0,+∞),$f\in C([0,+\infty )\times (0,+\infty )\times \mathbb{R}^{{2}},\mathbb{R})$f∈C([0,+∞)×(0,+∞)×R2,R)may be singular at$x=0$x=0, and$a_{1}$a1,$b_{1}$b1are positive constants. Using the Leray–Schauder nonlinear alternative and the diagonalization method together with the truncation function technique, we obtain the existence and qualitative properties of positive solutions for the problem. As applications, an example is given to illustrate our result.
A sumoylation program is essential for maintaining the mitotic fidelity in proliferating mantle cell lymphoma cells
Authors: Hanel Walter , Lata Pushpa , Youssef Youssef , Tran Ha , Tsyba Liudmyla , Sehgal Lalit , Blaser Bradley W. , Huszar Dennis , Helmig-Mason JoBeth , Zhang Liwen , Schrock Morgan S. , Summers Matthew K. , Chan Wing Keung , Prouty Alexander , Mundy-Bosse Bethany L. , Chen-Kiang Selina , Danilov Alexey V. , Maddocks Kami , Baiocchi Robert A. , Alinari Lapo
Published: July 2022

Background

Mantle cell lymphoma (MCL) is a rare, highly heterogeneous type of B-cell non-Hodgkin’s lymphoma. The sumoylation pathway is known to be upregulated in many cancers including lymphoid malignancies. However, little is known about its oncogenic role in MCL.

Methods

Levels of sumoylation enzymes and sumoylated proteins were quantified in MCL cell lines and primary MCL patient samples by scRNA sequencing and immunoblotting. The sumoylation enzyme SAE2 was genetically and pharmacologically targeted with shRNA and TAK-981 (subasumstat). The effects of SAE2 inhibition on MCL proliferation and cell cycle were evaluated using confocal microscopy, live-cell microscopy, and flow cytometry. Immunoprecipitation and orbitrap mass spectrometry were used to identify proteins targeted by sumoylation in MCL cells.

Results

MCL cells have significant upregulation of the sumoylation pathway at the level of the enzymes SAE1 and SAE2 which correlated with poor prognosis and induction of mitosis associated genes. Selective inhibition of SAE2 with TAK-981 results in significant MCL cell death in vitro and in vivo with mitotic dysregulation being an important mechanism of action. We uncovered a sumoylation program in mitotic MCL cells comprised of multiple pathways which could be directly targeted with TAK-981. Centromeric localization of topoisomerase 2A, a gene highly upregulated in SAE1 and SAE2 overexpressing MCL cells, was lost with TAK-981 treatment likely contributing to the mitotic dysregulation seen in MCL cells.

Conclusions

This study not only validates SAE2 as a therapeutic target in MCL but also opens the door to further mechanistic work to uncover how to best use desumoylation therapy to treat MCL and other lymphoid malignancies.
The developing airway and gut microbiota in early life is influenced by age of older siblings
Authors: Christensen Emil Dalgaard , Hjelmsø Mathis Hjort , Thorsen Jonathan , Shah Shiraz , Redgwell Tamsin , Poulsen Christina Egeø , Trivedi Urvish , Russel Jakob , Gupta Shashank , Chawes Bo L. , Bønnelykke Klaus , Sørensen Søren Johannes , Rasmussen Morten Arendt , Bisgaard Hans , Stokholm Jakob
Published: July 2022

Background

Growing up with siblings has been linked to numerous health outcomes and is also an important determinant for the developing microbiota. Nonetheless, research into the role of having siblings on the developing microbiota has mainly been incidental.

Results

Here, we investigate the specific effects of having siblings on the developing airway and gut microbiota using a total of 4497 hypopharyngeal and fecal samples taken from 686 children in the COPSAC2010cohort, starting at 1 week of age and continuing until 6 years of age. Sibship was evaluated longitudinally and used for stratification. Microbiota composition was assessed using 16S rRNA gene amplicon sequencing of the variable V4 region.

We found siblings in the home to be one of the most important determinants of the developing microbiota in both the airway and gut, with significant differences in alpha diversity, beta diversity, and relative abundances of the most abundant taxa, with the specific associations being particularly apparent during the first year of life. The age gap to the closest older sibling was more important than the number of older siblings. The signature of having siblings in the gut microbiota at 1 year was associated with protection against asthma at 6 years of age, while no associations were found for allergy.

Conclusions

Having siblings is one of the most important factors influencing a child’s developing microbiota, and the specific effects may explain previously established associations between siblings and asthma and infectious diseases. As such, siblings should be considered in all studies involving the developing microbiota, with emphasis on the age gap to the closest older sibling rather than the number of siblings.
Numerical modeling of the propagation process of landslide surge using physics-informed deep learning
Authors: Wu Yinghan , Shao Kaixuan , Piccialli Francesco , Mei Gang
Published: July 2022

The landslide surge is a common secondary disaster of reservoir bank landslides, which can cause more serious damage than the landslide itself in many cases. With the development of large-scale scientific and engineering computing, many new techniques have been applied to the study of hydrodynamic problems to make up for the shortcomings of traditional methods. In this paper, we use the physics-informed neural network (PINN) to simulate the propagation process of surges caused by landslides. We study different characteristics of landslide surges by changing water depth and particle density. We find that: (1) the landslide surge propagation process simulation method based on the physics-informed neural network has good applicability, and the stages of landslide surge propagation can be well presented; (2) the depth of water influences the landslide surge propagation as the amplitude of the surge increases with deeper water; (3) the particle density of water influences the landslide surge propagation as the fluctuation of the surge is more obvious with larger particle density. Our study is helpful to understand the propagation process of landslide surges more clearly and provides new ideas for the follow-up study of this kind of complex fluid–structure interaction problem.
Exploring the experience of young people receiving treatment for an eating disorder: family therapy for anorexia nervosa and multi-family therapy in an inpatient setting
Authors: Coopey Emily , Johnson George
Published: July 2022

Background

Research indicates that family therapy for anorexia nervosa (FT-AN) and multi-family therapy (MFT) are effective treatments for adolescents experiencing anorexia nervosa (AN). However, less is known about young people’s experiences of these two treatments, as there is limited qualitative research, and to date no qualitative research within an inpatient setting. It is argued that the lack of such insight limits the development of services for young people experiencing AN.

Method

Five young people were recruited to the study from a specialist inpatient unit who were receiving treatment on the AN pathway which included both FT-AN and MFT. Semi structured interviews were undertaken and analysed using Interpretative Phenomenological Analysis.

Results

Four superordinate themes and ten subthemes were developed from the data. The four superordinate themes were: ‘Process of Understanding’, ‘Reviving Connection’, ‘Emerging from the Eating Disorder and ‘Development of I’.

Conclusions

There appeared to be two overarching concepts: the role of the individual and the role of others, that helpfully framed the results. The superordinate themes: ‘Emerging from the Eating Disorder’ and ‘Development of I’ focused on the development of the individual. Conversely, the superordinate themes: ‘The Process of Understanding’ and ‘Reviving Connection’ were centred on the relationships existing within the family system. The results could help inform future service developments regarding inpatient provision and service design.

Plain English Summary

The most widely used and recognised treatment for anorexia nervosa in young people is family therapy for anorexia nervosa (FT-AN). An alternative treatment is multi-family therapy (MFT). Both treatments are deemed to be effective and usually happen in the community. However, some hospitals provide these treatments while the young people are in-patients. There is no research exploring young people’s experiences of these two treatments while in an in-patient unit.

Young people who had received both FT-AN and MFT in an inpatient setting were asked to share their experiences of these two treatments. Their stories were analysed by a researcher. The analysis identified four themes: ‘Process of Understanding’, ‘Reviving Connection’, ‘Emerging from the Eating Disorder and ‘Development of I’.

The results highlighted that the young people appeared to place more value on the role of others and perhaps others changing enabled them to change. The research highlighted the benefit in others’ understanding and therefore how improving societal understanding more broadly would be helpful. The young people reflected that both they and their parents benefited from FT-AN and MFT in an in-patient setting and it is proposed that this could help inform future service developments regarding inpatient provision.
Discontinuities in vocational education and training: the influence of early-risk factors and personality constructs on premature training termination and subsequent trajectories
Authors: Michaelis Christian , Richter Maria
Published: July 2022

Background

For adolescents, preventing a premature training termination (PTT) and withdrawal from education and training after a PTT is an important societal task. While studies reveal that early-risk factors such as a low educational background or selected personality constructs are relevant for predicting PTT, less is known about subsequent trajectories after a PTT and the factors that determine them.

Methods

Using data from the German National Educational Panel Study, we examine the influence of early-risk factors and personality constructs on the first PTT (n = 4892) in the training course using a binomial logistic regression model. In a second step, by using a sequence and cluster analysis we explore subsequent trajectory patterns within 24 months after PTT (n = 944) and analyze the influence of early-risk factors and personality constructs on subsequent trajectory clusters after PTT.

Results

We identify 7 different trajectory clusters, of which three clusters show risk-related trajectories (37.0%) with tendencies to withdraw from education and training. Furthermore, our analysis confirms the relevance of early-risk factors for predicting PTT as well as trajectories after PTT: a low educational qualification, graduation after more than the typical number of years, and low parental education increase the probability of discontinuities in adolescents’ educational and training paths. Additionally, it is important to consider the influence of personality traits on the subsequent trajectories: adolescents with strong openness tend to have continued school attendance after PTT, indicating a constructive career adaptation process, while adolescents with strong self-efficacy seem to assess their chances in the labor market as positive even without a vocational qualification.

Conclusions

The longitudinal perspective on the consequences of a first termination of a VET program revealed that educational trajectories after a PTT are highly heterogeneous indicating the need for different types of policy measures to minimize the incidence of PTT and withdrawing from education and training.
Electromagnetic conjugacy of ionospheric disturbances after the 2022 Hunga Tonga-Hunga Ha’apai volcanic eruption as seen in GNSS-TEC and SuperDARN Hokkaido pair of radars observations
Authors: Shinbori Atsuki , Otsuka Yuichi , Sori Takuya , Nishioka Michi , Perwitasari Septi , Tsuda Takuo , Nishitani Nozomu
Published: July 2022

To elucidate the characteristics of electromagnetic conjugacy of traveling ionospheric disturbances just after the 15 January 2022 Hunga Tonga-Hunga Ha’apai volcanic eruption, we analyze Global Navigation Satellite System-total electron content data and ionospheric plasma velocity data obtained from the Super Dual Auroral Radar Network Hokkaido pair of radars. Further, we use thermal infrared grid data with high spatial resolution observed by the Himawari 8 satellite to identify lower atmospheric disturbances associated with surface air pressure waves propagating as a Lamb mode. After 07:30 UT on 15 January, two distinct traveling ionospheric disturbances propagating in the westward direction appeared in the Japanese sector with the same structure as those at magnetically conjugate points in the Southern Hemisphere. Corresponding to these traveling ionospheric disturbances with their large amplitude of 0.5 – 1.1 × 1016 el/m2 observed in the Southern Hemisphere, the plasma flow direction in the F region changed from southward to northward. At this time, the magnetically conjugate points in the Southern Hemisphere were located in the sunlit region at a height of 105 km. The amplitude and period of the plasma flow variation are ~ 100–110 m/s and ~ 36–38 min, respectively. From the plasma flow perturbation, a zonal electric field is estimated as ~ 2.8–3.1 mV/m. Further, there is a phase difference of ~ 10–12 min between the total electron content and plasma flow perturbations. This result suggests that the external electric field variation generates the traveling ionospheric disturbances observed in both Southern and Northern Hemispheres. The origin of the external electric field is an E-region dynamo driven by the neutral wind oscillation associated with atmospheric acoustic waves and gravity waves. Finally, the electric field propagates to the F region and magnetically conjugate ionosphere along magnetic field lines with the local Alfven speed, which is much faster than that of Lamb mode waves. From these observational facts, it can be concluded that the E-region dynamo electric field produced in the sunlit Southern Hemisphere is a main cause of the two distinct traveling ionospheric disturbances appearing over Japan before the arrival of the air pressure disturbances.

Graphical Abstract
The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer
Authors: Sirhan Zaid , Thyagarajan Anita , Sahu Ravi P.
Published: July 2022

Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15–20% of breast cancer cases. HER2 is a member of the epidermal growth factor receptor (EGFR) family with tyrosinase kinase activity, and its overexpression is linked to poor prognosis and shorter progression-free survival (PFS) and overall survival (OS). Among various treatment options, HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors (TKIs) have mostly been applied in recent decades to treat HER2-positive (HER2+) breast cancer patients. Although positive clinical outcomes were documented in both advanced disease and neoadjuvant settings, the development of resistance mechanisms to such approaches has been one of the major challenges with the continuous usage of these drugs. In addition, patients who experience disease progression after treatment with multiple HER2-targeted therapies often have limited treatment options. The Food and Drug Administration (FDA) has recently approved a new TKI (i.e., tucatinib) for use in combination with immunotherapy and/or chemotherapeutic agents for the treatment of advanced-stage/metastatic HER2+ breast cancer. This review highlights recent updates on the efficacy of tucatinib-based therapeutic approaches in experimental models as well as in the clinical settings of HER2+ breast cancer.
Methanol leaf extracts of Chrysophyllum albidum and Irvingia gabonensis protected against dyslipidaemia and oxidative stress induced by high-fat diet in Wistar rats
Authors: Ibukun Osebhahiemen , Omoregie Ehimwenma S.
Published: July 2022

Background

High-fat diet (HFD) has been linked to oxidative stress, dyslipidaemia, obesity and cardiovascular diseases. Studies have shown that medicinal plants have antioxidant properties and may have protective effects against oxidative stress and dyslipidaemia induced by high-fat diet. Chrysophyllum albidum (white star apple) and Irvingia gabonensis (African bush mango) are very useful medicinal plants common in the tropical and subtropical regions of the world. This study was aimed at investigating the protective effect of methanol leaf extracts of Chrysophyllum albidum and Irvingia gabonensis against dyslipidaemia and oxidative stress in Wistar rats promoted by the consumption of HFD as well as characterize active compounds in the extracts. Thirty-six male Wistar rats were assigned into six groups of six animals each and respective groups received normal fat diet (NFD), HFD, HFD + Chrysophyllum albidum (250 mg/kg/ 500 mg/kg), HFD + Irvingia gabonensis (250 mg/kg/ 500 mg/kg) for fifty six days. Dietary intake, body weight, lipid profile and indicators of oxidative stress were measured.

Results

Administration of plant extracts did not change the pattern of food intake of the animals. There was a significant inhibition (p < 0.05) of increase in the body weight of rats treated with plant extracts in comparison with those rats that consumed HFD only. There was significant increase (p ˂ 0.05) in total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and malondialdehyde concentrations in rats fed with HFD only when compared with NFD control and extract treated groups. However, HFD control produced significantly lower (p < 0.05) high-density lipoprotein cholesterol, reduced glutathione and glutathione peroxidase than normal control and extract treated groups. Gas chromatography flame ionization detector analysis of these extracts revealed the abundance of kaempferol, quercetin, luteolin, myricetin and naringenin and tannic acid.

Conclusions

The observed antioxidant and anti-dyslipidaemic properties of leaves of Chrysophyllum albidum and Irvingia gabonensis may be attributed to the presence of flavonoids and tannic acid.
Wall thickness image construction in wellbore casings using data-driven inversion of magnetic flux leakage
Authors: Assous Said , Dolmatova Anastasiya V. , Goldobin Denis S. , Elkington Peter , Bacciarelli Mark
Published: July 2022

We describe the response of magnetic flux leakage measurements obtained in wellbore casings and detail an analytical approach for inverting the data to construct a 3D image of metal loss for the general case in which the magnetic permeability of the casing is unknown. This approach contrasts with current practice which assumes a defect shape and attempts to deduce metal loss from one or more response metrics matched to a library of defects generated under laboratory conditions for that shape. The traditional approach breaks down where defects do not conform to the assumed shape and when the properties of the laboratory casing are not the same as the properties of the installed casing. Moreover, there is no direct way to know whether magnetic flux in the casing is at saturation level; thus, the measurement could be operating in a nonlinear part of the magnetization curve whose shape also is unknown. The new method makes no assumptions about defect shape and approximates the relevant part of the magnetization curve within an inversion process that transforms the flux scan into a metal loss scan showing the shape and depth of metal loss. The approach is validated using data from simulations, laboratory tests, and field operations. Unlike images of flux distribution, thickness profiles reconstructed from the results of the inversion reflect the actual distribution of metal loss to a useful level of accuracy and thereby enable the casing’s mechanical integrity to be assessed with greater confidence.
A retrospective analysis of patients administered neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin with oral metronomic chemotherapy (OMCT) in locally advanced borderline resectable/technically unresectable head and neck cancers.
Authors: Pathak Shruti , Peelay Zoya , Patil Vijay Maruti , Noronha Vanita , Menon Nandini Sharrel , Chaturvedi Pankaj , Prabhash Kumar
Published: July 2022

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Background: Neoadjuvant chemotherapy with TPF though the standard is seldom used in India due to its adverse events rate. Two drug regimen of Paclitaxel and Carboplatin (PC) though favoured has inferior outcomes. Hence, we did an analysis to estimate the efficacy and adverse event rate of addition of 3 drug metronomic schedule to PC. Methods: Patients of locally advanced head and neck cancer referred from multidisciplinary board for neoadjuvant chemotherapy and unsuitable for TPF were selected for this analysis. These patients had received 2 drug regimen of intravenous PC with 3 drug regimen of weekly methotrexate 9 mg per m2, Celecoxib 200 mg twice daily, erlotinib 150 mg once daily all administered orally. All patients underwent a response assessment at 5-7 weeks post start of therapy and we're discussed in MDT for further treatment. Adverse events were recorded in accordance with CTCAE version 4.03 and response in accordance with RECIST version 1.1. PFS and OS were estimated with Kaplan Meier method. Results: 72 patients were identified with the median age being 45 (27-80) and M:F ratio (67:5). The indication for NACT were borderline resectability in all patients.. The response rate was 61.1% and grade 3 and above adverse event rate was 33.5%. A total number of 34 among 40 borderline resectable patients underwent surgery. The overall estimated PFS and OS were 18.5 (95%CI = 14.4-22.7) months and 18.05 (95%CI = 14.2-21.8) months respectively. The three most adverse events observed were grade 3 thrombocytopenia in 2 patients (2.8%), grade 3 aspartate aminotransferase (AST) derangement in 4 patients (5.6%) and grade 3 alanine aminotransferase (ALT) in 4 patients (5.6%). Conclusions: The 5 drug combination regimen is safe, tolerable and seems to have similar efficacy as a three drug TPF regimen.
Trends in Medically Integrated Dispensing Among Oncology Practices
Authors: Kanter Genevieve P. , Parikh Ravi B. , Fisch Michael J. , Debono David , Bekelman Justin , Xu Yao , Schauder Stephanie , Sylwestrzak Gosia , Barron John J. , Cobb Rebecca , Qato Dima M. , Jacobson Mireille
Published: July 2022

PURPOSE:

The integration of pharmacies with oncology practices—known as medically integrated dispensing or in-office dispensing—could improve care coordination but may incentivize overprescribing or inappropriate prescribing. Because little is known about this emerging phenomenon, we analyzed historical trends in medically integrated dispensing.

METHODS:

Annual IQVIA data on oncologists were linked to 2010-2019 National Council for Prescription Drug Programs pharmacy data; data on commercially insured patients diagnosed with any of six common cancer types; and summary data on providers' Medicare billing. We calculated the national prevalence of medically integrated dispensing among community and hospital-based oncologists. We also analyzed the characteristics of the oncologists and patients affected by this care model.

RESULTS:

Between 2010 and 2019, the percentage of oncologists in practices with medically integrated dispensing increased from 12.8% to 32.1%. The share of community oncologists in dispensing practices increased from 7.6% to 28.3%, whereas the share of hospital-based oncologists in dispensing practices increased from 18.3% to 33.4%. Rates of medically integrated dispensing varied considerably across states. Oncologists who dispensed had higher patient volumes ( P < .001) and a smaller share of Medicare beneficiaries ( P < .001) than physicians who did not dispense. Patients treated by dispensing oncologists had higher risk and comorbidity scores ( P < .001) and lived in areas with a higher % Black population ( P < .001) than patients treated by nondispensing oncologists.

CONCLUSION:

Medically integrated dispensing has increased significantly among oncology practices over the past 10 years. The reach, clinical impact, and economic implications of medically integrated dispensing should be evaluated on an ongoing basis.
Real-Time Ultrasound-Guided Spinal Injection Using a Transverse In-Plane Dependent Technique: A Case Series
Authors: Sivakumar Ranjith Kumar , Areeruk Pornpatra , Mok Louis Y. H. , Samy Winnie , Karmakar Manoj Kumar
Published: July 2022

Ultrasound-guided (USG) spinal injection is generally performed using a paramedian sagittal oblique scan, with the patient in the lateral decubitus position, and the spinal needle inserted in-plane from the nondependent side. This report evaluated the feasibility of performing USG spinal injection, using an alternative transverse interspinous scan with in-plane needle insertion, a transverse in-plane dependent (TIPD) technique, in 30 adult patients undergoing elective surgery under spinal anesthesia. Dural puncture was successfully achieved in 29 of 30 (96.6%) patients with 2 (1–3) attempts in 5 (4–8) minutes using the TIPD technique. Multiple interspinous osteophytes accounted for technical failure in 1 patient.
Development of Environmentally Friendly Dehydrogenative Oxidation Reactions Using Multifunctional Heterogeneous Catalysts
Authors: Yamaguchi Kazuya , Jin Xiongjie , Yatabe Takafumi , Suzuki Kosuke
Published: July 2022

Our design strategies for multifunctional heterogeneous catalysts based on nanosized metal oxides and metal nanoparticles as well as the development of several novel dehydrogenative oxidation reactions unique to these heterogeneous catalysts are summarized in this review article. We established a methodology for the precise design of nanosized crystalline oxides in organic solvents and developed new reactions that can be realized only with heterogeneous catalysts designed by this method; for example, we realized oxidative amidation of primary alcohols and other substrates using O2 and NH3 by using nanocrystalline manganese oxides. We discovered the particular dehydrogenation abilities of Au, Pd, and their binary nanoparticles, and successfully developed several new reactions that effectively utilize them. Using designed supported Au nanoparticle catalysts, we have successfully developed various environmentally benign reactions involving dehydrogenation, such as formal amine oxygenation, cross dehydrogenative coupling, and flavonoid synthesis. Furthermore, dehydrogenative aromatization reactions with H2 production were realized using a Pd nanoparticle-based catalyst design. We believe that the reactions we have developed are environmentally benign and that the results of our research will have substantial practical implications in addition to academic ones, such as providing new methodologies for catalyst design and pioneering new reactions.
Overarching policies to address the pandemic crisis in Europe
Authors: Papadonikolaki Jenny , Souliotis Kyriakos
Published: July 2022

COVID-19 pandemic has had a devastating impact on our world, affecting societies, economies, and healthcare systems across the globe, while changing many social, economic, and healthcare determinants. Europe is facing one of the most critical crises in its recent history, not only because of the economic challenges that the COVID-19 pandemic has created but also because of its significant political dimension. The aim of this paper is to provide a descriptive analysis of the different strategies European member states developed to monitor and contain the outbreak during the first wave, and the policy response of the European Union (EU) altogether. Despite the different approaches and time response in tackling the pandemic at its very beginning, EU quickly demonstrated a successful policy response that helped maintain the structure of the economy and sustain societies in the face of this exogenous shock.
"Acute Kidney Injury predictive models: advanced yet far from application in resource-constrained settings."
Authors: Mrara Busisiwe , Paruk Fathima , Oladimeji Olanrewaju
Published: July 2022

Acute kidney injury (AKI) remains a significant cause of morbidity and mortality in hospitalized patients, particularly critically ill patients. It poses a public health challenge in resource-constrained settings due to high administrative costs. AKI is commonly misdiagnosed due to its painless onset and late disruption of serum creatinine, which is the gold standard biomarker for AKI diagnosis. There is increasing research into the use of early biomarkers and the development of predictive models for early AKI diagnosis using clinical, laboratory, and imaging data. This field note provides insight into the challenges of using available AKI prediction models in resource-constrained environments, as well as perspectives that practitioners in these settings may find useful
SURROGATE MOTHERHOOD IN UKRAINE AND AROUND THE WORLD: LEGAL REGULATION & MANAGEMENT PRACTICE
Authors: Dzholos Sergii , Koshulko Oksana
Published: July 2022

This paper presents the results of theoretical and practical studies of surrogate motherhood in Ukraine and worldwide, its legal regulation, management practice, and prospects of development. It deals with a critical analysis of Ukrainian legislation concerning this subject. The methodology of the research consisted of primary and secondary sources of information. The authors collected primary data from semi-structured interviews with Ukrainians living in Poland, Ukraine, the United States, and several other countries. The interviews aimed to investigate the reasons for the growth of commercial surrogacy in Ukraine. The authors also scrutinized the attitudes of Ukrainians towards the flourishing of this phenomenon in their country. Secondary information the author took from sources such as the International Labour Organization (ILO), the United Nations (UN), and others. The paper also considers surrogacy maternity as a legal fiction and one of the rights of the fourth generation and discusses the links between surrogate pregnancy, exploitation, and human trafficking.