bluuebunny/crossref_metadata_2025 huggingface dataset:
Swedish trial on embolization of middle meningeal artery versus surgical evacuation in chronic subdural hematoma (SWEMMA)—a national 12-month multi-center randomized controlled superiority trial with parallel group assignment, open treatment allocation and blinded clinical outcome assessment
Authors: Drake Mattias , Ullberg Teresa , Nittby Henrietta , Marklund Niklas , Wassélius Johan
Published: November 2022

Background

Chronic subdural hematoma (cSDH) is one of the most common neurosurgical disorders and the incidence is rising. The routine treatment is neurosurgical hematoma evacuation, which is associated with recurrence rates up to 10–25%. In recent years, endovascular embolization of the middle meningeal artery (eMMA) has garnered much attention due to recurrence rates as low as < 5%. Several randomized controlled trials are planned or ongoing. In most of these trials, conventional neurosurgical treatment with or without adjunctive endovascular embolization is compared. The proposed trial aims to conduct a head-to-head comparison between neurosurgical and endovascular treatment as stand-alone treatments.

Methods

The trial is academically driven and funded within existing public healthcare systems and infrastructure. Patients with uni- or bilateral cSDH, presenting with mild-to moderate symptoms, and admitted to neurosurgery on clinical grounds will be offered participation. Subjects are randomized 1:1 between conventional neurosurgical treatment (control) and endovascular embolization of the middle meningeal artery (intervention). Primary endpoint is reoperation due to clinically and/or radiologically significant recurrence within 3 months. Secondary endpoints include safety, technical success rate, neurological disability, and quality of life.

Discussion

There are mounting retrospective data suggesting eMMA, as sole treatment or as an adjunctive to neurosurgery for cSDH, is safe and effective with a reoperation rate lower than neurosurgical hematoma evacuation alone. If randomized controlled trials confirm these findings, there is a potential for a paradigm shift in the treatment of cSDH where a minimally invasive procedure can replace open surgery in a large and oftentimes old and fragile patient cohort.

Trial registration

ClinicalTrials.gov, ClinicalTrials.gov IdentifierNCT05267184. Registered March 4, 2022.
Inclusion of progression criteria in external randomised pilot trials: a cross-sectional study of funding applications submitted to the NIHR Research for Patient Benefit Programme
Authors: Mellor Katie , Harwood James , Hejdenberg Jennie , Morgan Ben , Dutton Susan J. , Hopewell Sally
Published: November 2022

Background

External randomised pilot trials aim to assess whether a future definitive randomised controlled trial (RCT) is feasible. Pre-specified progression criteria help guide the interpretation of pilot trial findings to decide whether, and how, a definitive trial should be conducted. We aimed to examine how researchers report and plan to assess progression criteria in external pilot trial funding applications submitted to the NIHR Research for Patient Benefit Programme.

Methods

We conducted a cross-sectional study of progression criteria inclusion in Stage 1 (outline) and corresponding Stage 2 (full) funding applications for external randomised external pilot trials submitted to NIHR RfPB between July 2017 and July 2019.

Results

Of the 100 Stage 1 outline applications assessed, 95 were eligible for inclusion (of these, 52 were invited to Stage 2 full application; 43 were rejected) and 49/52 were eligible for inclusion at Stage 2 full application (of these, 35 were awarded funding; 14 were rejected). Over half of applications assessed at Stage 1 (48/95, 51%), and 73% of those assessed at Stage 2 (36/49) included progression criteria in their research plans. Progression criteria were most often reported in a stop-go format, often with additional specified factors that should be considered when determining feasibility (Stage 1 33/48, 69%; Stage 2 21/36, 58%). Recruitment and retention were the most frequent indicators of feasibility to inform progression criteria. One-third of applications provided some justification or rationale for their targets (Stage 1 16/48, 33%; Stage 2 12/36, 33%). Funding committee feedback mentioned progression criteria in over 20% of applications (Stage 1 22/95, 23%; Stage 2 11/49, 22%) to either request the addition of progression criteria or provide justification for the criteria stipulated.

Conclusions

Our findings indicate that researchers do not always include progression criteria in external randomised pilot trial applications submitted to research funders. This can result in a lack of transparency in the assessment of randomised pilot trial feasibility.

Trial registration

Open Science Framework osf.io/89ap7, registered 29th June 2021.
Vector-borne and other pathogens of potential relevance disseminated by relocated cats
Authors: Maggi Ricardo Guillermo , Halls Vicky , Krämer Friederike , Lappin Michael , Pennisi Maria Grazia , Peregrine Andrew S. , Roura Xavier , Schunack Bettina , Scorza Valeria , Tasker Séverine , Baneth Gad , Bourdeau Patrick , Bowman Dwight D. , Breitschwerdt Edward B. , Capelli Gioia , Cardoso Luís , Dantas-Torres Filipe , Dobler Gerhard , Ferrer Lluís , Gradoni Luigi , Irwin Peter , Jongejan Frans , Kempf Volkhard A. J. , Kohn Barbara , Little Susan , Madder Maxime , Maia Carla , Marcondes Mary , Miró Guadalupe , Naucke Torsten , Oliva Gaetano , Otranto Domenico , Penzhorn Barend L. , Pfeffer Martin , Sainz Ángel , Shin SungShik , Solano-Gallego Laia , Straubinger Reinhard K. , Traub Rebecca , Wright Ian
Published: November 2022

Large populations of unowned cats constitute an animal welfare, ecological, societal and public health issue worldwide. Their relocation and homing are currently carried out in many parts of the world with the intention of relieving suffering and social problems, while contributing to ethical and humane population control in these cat populations. An understanding of an individual cat’s lifestyle and disease status by veterinary team professionals and those working with cat charities can help to prevent severe cat stress and the spread of feline pathogens, especially vector-borne pathogens, which can be overlooked in cats. In this article, we discuss the issue of relocation and homing of unowned cats from a global perspective. We also review zoonotic and non-zoonotic infectious agents of cats and give a list of practical recommendations for veterinary team professionals dealing with homing cats. Finally, we present a consensus statement consolidated at the 15th Symposium of the Companion Vector-Borne Diseases (CVBD) World Forum in 2020, ultimately to help veterinary team professionals understand the problem and the role they have in helping to prevent and manage vector-borne and other pathogens in relocated cats.

Graphical Abstract
Association between rheumatoid factor and metabolic syndrome in general population
Authors: Li Lan , Feng Donglai , Zeng Jing , Ye Peng , Chen Yao , Wei Dong
Published: November 2022

Background

Rheumatoid arthritis, metabolic syndrome (MS) and cardiovascular disease (CVD) are mutually connected. We aim to investigate the association between rheumatoid factor (RF) and MS in general population, explore the potential value of RF for assessment of metabolic status, and further provide a reference to the establishment of CVD primary prevention for this population.

Methods

We assessed the health check-up subjects, accordance with the inclusive criteria, from 1 January 2015 to 31 October 2021 in a large refereed general hospital, in this retrospective study. Subjects were categorized into four groups according to their levels of RF. Multivariate logistic regression models along with the Odds ratio (OR) and Confidence interval (CI) values were used to measure the association between RF and MS.

Results

A total of 13,690 subjects were analyzed. Prevalence of MS increased with RF level (P for trend < 0.001). Logistic regression analysis showed that, after adjusting for multiple covariates, RF level was significantly associated with MS prevalence (highest RF quartile: OR, 1.420; 95% CI 1.275,1.581, according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria; OR, 2.355; 95% CI 2.085,2.660, according to the International Diabetes Federation criteria) (both P for trends < 0.001). Among the MS components, there were evidence of increasing trends for overweight/obesity (highest RF quartile: OR, 3.165; 95% CI 2.827,3.543) and hypertension (highest RF quartile: OR, 1.722; 95% CI 1.549,1.914) (both P for trends < 0.001), but decreasing trend for low high-density lipoprotein-cholesterol (highest RF quartile: OR, 0.245; 95% CI 0.214,0.281) (P for trend < 0.001), with increasing RF quartiles.

Conclusions

RF level is associated with MS prevalence in general population. RF might be a valuable biomarker for assessment of metabolic status in this population. We should be aware of the cardiovascular risk for the higher-RF subjects.
Gaps in sexually transmitted infection screening among youth living with HIV in Alabama
Authors: Budhwani Henna , Hao Jiaying , Maragh-Bass Allysha C. , Hill Samantha V. , Long Dustin M. , Simpson Tina
Published: November 2022

Objective:

Gaps in sexually transmitted infection (STI) testing can lead to poor health outcomes due to untreated illness among youth living with HIV (YLHIV). Thus, the objective of this study is to examine STI testing behavior and outcomes among a sample of YLHIV in the southern United States. Clinical records of 139 YLHIV who received HIV care in Alabama (2017–2020) were evaluated for receipt of STI testing (gonorrhea, chlamydia, syphilis), prevalence of positive test results, and factors associated with testing outcomes (933 clinical visits).

Results:

Nearly 80% of our sample identified as African American, most were 20–24 years, and about 60% reported detectable viral load at first visit during the study period. Just under 60% of cisgender male and transgender female clients reported receipt of at least one STI test, compared to less than 40% of cisgender females. Identifying as a cisgender male and having been diagnosed with HIV related to sex with men were associated with greater likelihood receiving STI testing. Cisgender males reported higher rates of positive syphilis test results than cisgender females; the highest rates of positive STI tests were among transgender females. Results underscore need for providers to promote routine STI testing to YLHIV.
Severe abacavir hypersensitivity reaction in a patient with human immunodeficiency virus infection: a case report
Authors: Koech Mathew K. , Ali Shamim M. , Karoney Mercy J. , Kigen Gabriel
Published: November 2022

Background

Abacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done.

Case report

We report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well.

Conclusions

Clinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.
Development of machine learning classifiers to predict compound activity on prostate cancer cell lines
Authors: Bonanni Davide , Pinzi Luca , Rastelli Giulio
Published: November 2022

Prostate cancer is the most common type of cancer in men. The disease presents good survival rates if treated at the early stages. However, the evolution of the disease in its most aggressive variant remains without effective therapeutic answers. Therefore, the identification of novel effective therapeutics is urgently needed. On these premises, we developed a series of machine learning models, based on compounds with reported highly homogeneous cell-based antiproliferative assay data, able to predict the activity of ligands towards the PC-3 and DU-145 prostate cancer cell lines. The data employed in the development of the computational models was finely-tuned according to a series of thresholds for the classification of active/inactive compounds, to the number of features to be implemented, and by using 10 different machine learning algorithms. Models’ evaluation allowed us to identify the best combination of activity thresholds and ML algorithms for the classification of active compounds, achieving prediction performances with MCC values above 0.60 for PC-3 and DU-145 cells. Moreover, in silico models based on the combination of PC-3 and DU-145 data were also developed, demonstrating excellent precision performances. Finally, an analysis of the activity annotations reported for the ligands in the curated datasets were conducted, suggesting associations between cellular activity and biological targets that might be explored in the future for the design of more effective prostate cancer antiproliferative agents.
Nontrivial solutions for Klein–Gordon–Maxwell systems with sign-changing potentials
Authors: Zhang Xian , Huang Chen
Published: November 2022

This paper is concerned with the nonlinear Klein–Gordon–Maxwell systems. Unlike all known results in the literature, the Schrödinger operator $-\Delta +V$
−
Δ
+
V
is allowed to be indefinite and the weaker superlinear conditions are imposed instead of the common 4-superlinear conditions on f. By combining a local linking argument and Morse theory, we obtain that the system admits a nontrivial solution.
Effects and related mechanism of alpha-adrenergic receptor inhibitor phentolamine in a rabbit model of acute pulmonary embolism combined with shock
Authors: Wang Yuting , Qiu Li , Yu Delong , Yu Yijun , Hu Liqun , Gu Ye
Published: November 2022

Background

To observe the effect and mechanism of alpha-adrenergic receptor inhibitor phentolamine (PTL) in a rabbit model of acute pulmonary embolism (APE) combined with shock.

Methods

Twenty-four New Zealand rabbits were randomly divided into sham operation group (S group, n = 8), model group (M group, n = 8) and PTL group (n = 8), the model of APE combined with shock was established. Mean pulmonary arterial pressure (MPAP), peripheral mean arterial pressure (MAP) and pulmonary circulation time were evaluated. The expression levels of α1 receptor, α2 receptor and their downstream molecules in pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions lung tissues were detected and compared, respectively.

Results

In M group, α receptor-related signaling pathways were significantly activated in both PE and non-PE areas as expressed by up-regulated α1, α2 receptor and phospholipase C (PLC); the expression level of phosphorylated protein kinase A (p-PKA) was significantly down-regulated; myosin light chain kinase (MLCK) and α-smooth muscle actin (α-SMA) levels were up-regulated. PTL treatment significantly improved pulmonary as well as systemic circulation failure: decreased MPAP, restored blood flow in non-PE area, shortened pulmonary circulation time, increased MAP, and restored the circulation failure. PTL induced significantly down-regulated expression of α1 receptor and its downstream molecule PLC in both PE and non-PE area, the expression level of α2 receptor was also down-regulated, the expression level of p-PKA was significantly up-regulated. PTL treatment can inhibit both α1 and α2 receptor-related signaling pathways in whole lung tissues, and inhibit Ca2+ signaling pathways. The expression level of MLCK and α-SMA were significantly down-regulated. Compared with PE area, the changes of expression levels of α receptor and its downstream molecules were more significant in the non-PE region.

Conclusion

In this model of APE combined with shock, the sympathetic nerve activity was enhanced in the whole lung, α1 and α2 receptor and their downstream signaling activation might mediate blood flow failure in the whole lung. PTL treatment can effectively restore pulmonary blood flow in non-PE area and improve pulmonary as well as systemic circulation failure possibly through down-regulating α1 and α2 receptor and their downstream signaling pathways.
Plant-based nano-fertilizer prepared from Paulownia Tomentosa: fabrication, characterization, and application on Ocimum basilicum
Authors: Sohrabi Yousef , Sharifi Kalyani Firouzeh , Heydari Moslem , Yazdani Majed , Omer Khalid M. , Yousefi Ali Reza
Published: November 2022

Background

The use of hazardous and toxic chemical material has become limited by the green synthesis of nano-particles (NPs) from plants and other living organisms. In the current study, a new nano-fertilizer was green synthesized from Paulownia tomentosa leaves and then its effectiveness in alleviation of drought stress in Ocimum basilicum was investigated. Five concentrations of nano-fertilizer (0, 50, 70, 90 and 110 ppm) at three irrigation regimes including 100% of field capacity (IRF100), 75% of field capacity (IRF75), and 50% of field capacity (IRF50) were evaluated. Nano-fertilizers were prepared using the green hydrothermal method.

Results

Based on TEM analyses nanoparticles sizes were 5–8 nm. The results of FTIR appearance indicated the main distinctive peaks of the Paulownia-based nano-fertilizer (NFPs) in the spectrum. In addition, the nitrogen peaks in the XPS spectra indicate that the prepared carbon dots NFPs are nitrogen-doped. Moreover, there are functional groups, such as COOH or OH groups on the surface of Paulownia-based nano-fertilizer (NFPs). The results illustrated that drought stress increased proline (73%), alcohol-soluble carbohydrates (78%), and malondialdehyde (41%) in comparison with normal irrigation; in contrast, soluble proteins (73%), Chlorophyll a (46%), Chlorophyll b (39%), Chlorophyll total (42%), and carotenoid (77%) were reduced in the same condition. The O. basilicum biological yield was reduced in moderate (12.40%) and severe (24.42%) drought stress in comparison with full irrigation conditions (IRF100). Paulownia-based nano-fertilizer (NFPs) caused an increase in soluble proteins and photosynthetic pigments. Application of NFP-90 reduced the production of proline and malondialdehyde, respectively, 51.8% and 30.8% compared to non-application under severe stress conditions, which indicates alleviated the adverse effect of drought stress. The highest biological yield of basil was obtained at a 110 ppm concentration of NFPs.

Conclusion

Overall, results showed that using NPs biosynthesized from Paulownia leaves could be an economically and environmentally friendly method as a nano-fertilizer.

Graphical Abstract
Phase separation and formation of sodium caseinate/pectin complex coacervates: effects of pH on the complexation
Authors: Ardestani Faezeh , Haghighi Asl Ali , Rafe Ali
Published: November 2022

Background

The electrostatic interactions between polysaccharides and proteins are an interesting field in the complex coacervation. PH and mixing ratio have major effect on the complexation and the coacervates structure. Hence, it is necessary to find the optimum pH and mixing ratio of the coacervates as well as understanding the thermal, mechanical, and structural characterization of the coacervates. Thus, structural changes of the complexes of sodium caseinate (NaCas) and high methoxyl pectin as a function of pH (2.00–7.00), biopolymer ratios (1:1, 2:1, 4:1, and 8:1), and total biopolymer concentration (0.1, 0.2, and 0.4% w/v) were evaluated by light scattering and ζ-potential measurements. The phase separation behavior of the NaCas/HMP coacervate and its kinetics turbidity were also investigated via monitoring the turbidity profiles. Moreover, the thermal, rheological and structural behavior of the coacervates was evaluated at the selected pH values.

Results

The highest turbidity, particle size, and viscosity were achieved at pHmax = 3.30 and formation or dissociation around the pHmax was confirmed by particle size and FTIR. The optimum condition for the coacervation of NaCas and HMP was obtained at ratio 4:1 and 0.4% w/v. Thermal and mechanical stability of the NaCas/HMP coacervates was improved at pH 3.30. By increasing the total concentration of biopolymers, the NaCas/pectin ratio shifted to higher pH values. Furthermore, the maximum coacervate yield was achieved at 39.8% w/w at a ratio of 4:1 of NaCas/HMP and a total biopolymer concentration of 0.4% w/v.

Conclusion

Phase separation behavior of the coacervates exhibited the optimum pH in coacervation between NaCas and HMP. Furthermore, the rheological, thermal and structural stability of the coacervates were improved in comparison with the single biopolymers.

Graphical Abstract
Dislocation of a middle lobe torsion-preventing bridging structure with an absorptive sheet and fibrin glue: a case report
Authors: Matsumiya Hiroki , Kuroda Koji , Mori Masataka , Kanayama Masatoshi , Taira Akihiro , Shinohara Shinji , Takenaka Masaru , Tanaka Fumihiro
Published: November 2022

Background

Middle lobe torsion is a rare complication of right upper lobectomy. Middle lobe torsion can be critical; thus, various preventive measures are used.

Case presentation

A 77-year-old man underwent thoracoscopic right upper lobectomy with partial middle resection and S6 segmentectomy for right upper lobe lung cancer located at the confluence of the three lobes and lower lobe lung cancer. Inversion of the middle lobe was observed during lung expansion before chest closure. A bridging structure with an absorptive sheet and fibrin glue was placed in the basal section of the middle lobe under lung expansion to prevent torsion. On postoperative day 1, the patient was tachycardic and was found to have decreased lung field permeability. The patient underwent emergency surgery for suspected middle lobe torsion. Dislocation of the bridging structure between the basal segments of the middle lobe was confirmed, and the middle lobe was deviated cephalad. In addition, pulmonary congestion in S4 due to pressure stenosis of V4 caused by the deviation of the middle lobe was observed, and middle lobe resection was performed. The postoperative course was uneventful.

Conclusions

This case suggested that the reinforcement method with an absorptive sheet and fibrin glue lacked sufficient strength to prevent middle lobe torsion. Stronger fixation should be considered if the middle lobe rotation is thought to be sufficiently strong when the lung is reinflated before chest closure.
Dietary diversity and micronutrient adequacy among women of reproductive age: a cross-sectional study in Southern Thailand
Authors: Puwanant Maneerat , Boonrusmee Sasivara , Jaruratanasirikul Somchit , Chimrung Kanjana , Sriplung Hutcha
Published: November 2022

Introduction

Adequate nutritional intake of both macronutrients and micronutrients is essential for maintaining good health throughout life, particularly for women of reproductive age (WRA). The Minimum Dietary Diversity for WRA (MDD-W), or the sum of dietary diversity, is recommended as a simple indicator to identify at-risk WRA populations. However, there are no studies on the MDD-W among WRA in Thailand.

Objectives

To determine food group diversity, MDD-W, and micronutrient intake of WRA in Southern Thailand.

Participants

From December 2020 to November 2021, 120 healthy, young WRA (average age 33.2 ± 4.5 years) were enrolled.

Methods

A 24-h food record was used to quantitatively and qualitatively assess the food consumed. Dietary diversity was classified into ten food groups. The macronutrients and 15 micronutrients were calculated using the software program INMUCAL, which is the standard program for calculating nutrients in Thai food. The calculated intake of each micronutrient was transformed to the probability of adequacy (PA).

Results

The most common foods consumed were rice, followed by meat, eggs, fruits, and vegetables. Fewer than 40% of the participants consumed beans, dairy products, vitamin A-rich fruits and vegetables, dark green vegetables, and pulses. The average MDD-W score was 5 (range 2–8). The mean caloric intake (1,865 cal/day) was adequate for non-lactating WRA but was approximately 300 kcal/day lower than the recommendation for lactating WRA. Most WRA consumed lower amounts of micronutrients than those recommended. The mean PA (MPA) of the 15 micronutrients was 0.33 (range 0.0–0.9).

Conclusions

Non-pregnant WRA in Songkhla consumed adequate macronutrients but inadequate micronutrients. A nutritional education program regarding the importance of micronutrients should be provided to the public, with special attention to WRA.
Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy
Authors: Lusa Amanda , Alvarez Carolina , Saxena Beem Shruti , Schwartz Todd A. , Ishizawar Rumey
Published: November 2022

Introduction

Immune checkpoint inhibitors (ICIs) enhance the immune system’s ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.

Methods

We performed a retrospective chart review of patients with a pre-existing rheumatologic diagnosis receiving ICIs at the University of North Carolina from 2014 to 2019. Risk differences (RD) and asymptotic 95% confidence intervals (95% CIs) using a continuity correction along with odds ratios (OR) and exact 95% CIs were produced between pre-specified risk factors and flares of the underlying rheumatologic disease and/or irAEs. Kaplan–Meier survival estimates for time to unfavorable cancer response between subsets of patients were compared using the log-rank test.

Results

We identified 45 patients receiving an ICI with an underlying rheumatologic diagnosis, including 22 with rheumatoid arthritis (RA). Overall, 13 patients (29%) had a flare of their autoimmune disease, 20 patients (44%) had a new-onset irAE, and 27 (60%) had either a flare or new-onset irAE. Patients with RA had higher risk of flares compared to those with other rheumatologic disorders (45% vs 13%, RD 32%, 95% CI 2.0–56.8); all RA flares were ≤ grade 2 and treated in the outpatient setting. Concurrent treatment of the rheumatologic disease at the start of ICI therapy was not associated with a reduced risk of flare (OR 0.86, 95% CI 0.19–3.76) or new onset irAE (OR 3.21, 95% CI 0.83–13.6) compared to those not on anti-rheumatic medications. Anti-rheumatic therapy did not impact time to unfavorable malignancy outcome (p = 0.52).

Conclusion

The majority of our study cohort experienced a flare or new onset irAE with ICI treatment. Treatment with anti-rheumatic therapy did not prevent disease flares or new onset irAEs, but did not negatively impact malignancy outcomes. Research is needed to determine safe anti-rheumatic therapy options to prevent flares and irAEs that do not interfere with malignancy outcomes.
Phase II study of trastuzumab-pkrb and docetaxel anhydrous combination therapy in recurrent or metastatic salivary ductal carcinomas (KCSG HN18-08/KM11).
Authors: Lee Jiyun , Park Sehhoon , Jung Hyun Ae , Lee Se-Hoon , Seo Seyoung , Kim Sung-Bae , Kim Ji-Won , Lee Keun Wook , Kang Eun Joo , Kim Ju Won , Choi Yoon Ji , Shim Byoung Yong , An Ho Jung , Park Lee Chun , Shin SeongHoon , Kim Jae-Joon , Oh So Yeon , Kim Min Kyoung , Ahn Myung-Ju
Published: November 2022

6018

Background: Salivary gland cancers (SGCs) are relatively rare, accounting for 1-6% of all neoplasms of the head and neck, have diverse disease course with respect to origin and pathology. Salivary duct carcinoma (SDC) is the most aggressive tumor subtype of primary SGC, showing high rates of local recurrence and distant metastases. In regard to previous studies which reported a high prevalence of HER2 positivity in SDCs, we conducted a single-arm, phase II study to evaluate the antitumor activity and safety of Herzuma (a trastuzumab biosimilar which demonstrated an equivalent efficacy to reference trastuzumab) in combination with docetaxel anhydrous (Nanoxel) in patients with HER2-positive advanced SDCs. Methods: Eligible patients had histologically confirmed HER2-positive (defined as IHC≥2+ and/or FISH HER2/CEN17 ratio ≥2.0) recurrent/metastatic SDC, or subtypes of SGC that were pathologically similar to SDC (excluding ACCs). They received Herzuma (8mg/kg i.v. loading dose, followed by 6mg/kg i.v.) and Nanoxel (75mg/m2 i.v.) every 3 weeks. The primary endpoint was the investigator-assessed objective response rate (ORR) according to RECIST v1.1. Secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. The calculated sample size was 43 patients for H1 of ORR ≥40%. Safety was evaluated by CTCAE v4.0. Results: A total of 43 patients were enrolled. Patient characteristics included: median age 60 (range 35–81); 86% male; 84% ECOG1; 84% SDC, 9% adenocarcinoma, 2% high grade mucoepidermoid carcinoma, and 5% other subtypes. Confirmed ORR was seen in 67% (95% CI, 52–81). No patient had a complete response as their BOR, 29 (67%) had a partial response, 11 (26%) had stable disease, 1 (2%) had progressive disease, and 2 (5%) were unevaluable. The DCR was 93% (95% CI, 81–99). The median PFS and OS were 8.2 months (95% CI, 6.7–9.7) and 23.3 months (95% CI, 19.9–26.7), respectively. Thirty-eight (88%) patients experienced a treatment-related AE (TRAE), with 15 (35%) patients experiencing ≥grade 3 TRAE including: neutropenia (10), febrile neutropenia (4), anemia (1), sepsis (1), anaphylaxis (1), decreased LVEF (1). There were no treatment-related deaths. Conclusions: The study met the primary endpoint of ORR. Herzuma and Nanoxel combination therapy demonstrated a promising treatment outcome in patients with HER2-positive recurrent/metastatic SDC. Clinical trial information: NCT03614364.
Active percolation in pusher-type microswimmers
Authors: Schwarzendahl Fabian Jan , Mazza Marco G.
Published: November 2022

The aggregation of microorganisms in colonies and biofilms underpins a myriad of biological processes, and has crucial implications in ecology and biomedical sciences. While much of our knowledge of microbial motion is based on single-cell mechanisms or cell-cell interactions, the origin of cooperativity in microbial communities is not yet fully understood. Here, we reveal the existence of a continuum percolation transition in two model suspensions of pusher-type microswimmers: an asymmetric dumbbell and a squirmer model. Clusters of swimmers held together by hydrodynamic forces dynamically aggregate and separate. Using simulations with explicit hydrodynamics and theory, we find that as the microswimmers' filling fraction increases, the cluster size distribution approaches a scale-free form and system-spanning clusters emerge.
A State of Natriuretic Peptide Deficiency
Authors: Nyberg Michael , Terzic Dijana , Ludvigsen Trine P , Mark Peter D , Michaelsen Natasha B , Abildstrøm Steen Z , Engelmann Mads , Richards A Mark , Goetze Jens P
Published: November 2022

Measurement of natriuretic peptides (NPs) has proven its clinical value as biomarker, especially in the context of heart failure (HF). In contrast, a state of partial NP deficiency appears integral to several conditions in which lower NP concentrations in plasma presage overt cardiometabolic disease. Here, obesity and type 2 diabetes have attracted considerable attention. Other factors—including age, sex, race, genetics, and diurnal regulation—affect the NP “armory” and may leave some individuals more prone to development of cardiovascular disease. The molecular maturation of NPs has also proven complex, with highly variable O-glycosylation within the biosynthetic precursors. The relevance of this regulatory step in post-translational propeptide maturation has recently become recognized in biomarker measurement/interpretation and cardiovascular pathophysiology. An important proportion of people appear to have reduced effective net NP bioactivity in terms of receptor activation and physiological effects. The state of NP deficiency both entails a potential for further biomarker development and could also offer novel pharmacological possibilities. Alleviating the state of NP deficiency before development of overt cardiometabolic disease in selected patients could be a future path for improving precision medicine.
Mechanism of Formate Dehydrogenase Catalyzed CO2 Reduction with the Cation Radical of a 2,2′-Bipyridinium Salt Based on a Theoretical Approach
Authors: Miyaji Akimitsu , Amao Yutaka
Published: November 2022

The visible-light driven redox system of an electron donor, a photosensitizer, an electron mediator and formate dehydrogenase from Candida boidinii (CbFDH; EC.1.2.1.2) as a catalyst has received much attention for CO2 reduction to formate. In this system, elucidation of the electron transfer process between the electron mediator and CbFDH is important for improving efficiency of CO2 reduction to formate. 2,2′-Bipyridinium salt (2,2′-BP2+) is a remarkable electron mediator for CbFDH-catalyzed CO2 reduction. Especially, the direct interaction between cation radicals of 2,2′-BPs (2,2′-BP+•s) and CbFDH is a significant factor for the CO2 reduction. By using 1,1′-ethylene-2,2′-bipyridinium salt (DB2+), 1,1′-trimethylene-2,2′-bipyridinium salt (TB2+), 1,1′-tetramethylene-2,2′-bipyridinium salt (QB2+) and 1,1′-dimethyl-2,2′-bipyridinium salt (DM2+), 2,2′-BP+• with a small dihedral angle between the two pyridine rings (DB or TB) accelerates the CbFDH-catalyzed CO2 reduction. This work illuminated the direct interaction of the cation radicals of DB, TB, QB and DM in the substrate-binding site of CbFDH on the basis of a docking-simulated prediction. Moreover, the electron transfer process from the cation radicals of DB, TB, QB and DM to CO2 in the CbFDH was investigated based on the energy of the molecular orbital calculated by density functional theory (DFT). From these results, it can be predicted that efficient CO2 reduction to formate can be achieved by suppressing the three-dimensional structural change between the 2,2′-BP dication and the cation radical in the substrate-binding pocket of CbFDH as much as possible.
Moment Analysis of Solute Permeation Kinetics at an Interface of Mixed Micelles of Anionic and Nonionic Surfactants
Authors: Miyabe Kanji , Aoki Kayoko
Published: November 2022

Solubilization phenomena of neutral solutes into mixed micelles of anionic and nonionic surfactants were studied by means of micellar electrokinetic chromatography (MEKC). MEKC experiments were conducted by using mixed micelles consisting of sodium dodecylsulfate (SDS) and polyoxyethylene sorbitan monolaurate (Tween 20) or monostearate (Tween 60) as pseudo-stationary phases while changing the concentration of SDS-Tween mixed micelles and the molar fraction of Tween 20 or 60 in mixed micelles. Elution peak profiles measured by MEKC were analyzed on the basis of the moment theory to determine the solute partition equilibrium constant (Kp) and the rate constants of solute permeation at the interface of mixed micelles (kin and kout). It seems that the values of Kp, kin, and kout are increased by adding Tween 20 or 60 and that the influence of the addition of Tween 60 on their values is more remarkable than that of Tween 20. It was demonstrated that moment analysis of MEKC data is effective for studying solubilization phenomena of surfactant micelles under the conditions that both immobilization and chemical modification (i.e., fluorescence labeling) of solute and micelles are not required.
Landscape science in Ukraine: The current state and trends
Authors: Grodzynskyi Mykhailo
Published: November 2022

The state of landscape science in Ukraine has been considered since the early 2000s, when, moving away from the Soviet canons of this science, it acquired its own face and its leaders. From that time until now, two general trends in the development of Ukrainian landscape science have been set: expansion in the field of landscape research and strengthening the theoretical foundations of its concept. Currently, in Ukraine the landscape is studied in three academic areas—landscape science, landscape ecology and transdisciplinary geoecology. There are different points of view on their essence and correlation among Ukrainian scientists, and they are discussed in the article. There is also no consensus on understanding the concept of the landscape, because there are at least three interpretations of it: the landscape as a general metascientific category, the landscape as a real object, and the landscape as a representation or an image of reality. The article discusses the current state, gaps and prospects for the development of landscape science in Ukraine regarding the main problem areas of ​​this science, namely landscape theory, landscape mapping, dynamics of landscapes, their anthropization, humanitarian dimensions of the landscape, landscape planning, landscape modeling, physical-geographical regionalization.
Shell colouration and different introductions of the land snail Cepaea hortensis (Gastropoda: Helicidae) into Western Ukraine
Authors: Gural-Sverlova Nina , Gural Roman
Published: November 2022

The primary introduction of C. hortensis into Western Ukraine, most likely in the second half of the 20th century, led to the formation of many populations characterised not only by a reduced phenotypic composition, but also by a peculiar phenotypic marker (absence of banded shells with a non-white ground colour). White banded shells, common in Western Ukraine, are also found in different parts of the present species range, but less frequently than yellow banded ones. When studying the shell colour and banding polymorphism in C. hortensis, white shells are often combined into one group with yellow ones. Therefore, the findings of these two phenotypes as well as white unbanded shells in Europe were mapped based on the analysis of more than 7 thousand photographs from citizen science database iNaturalist. The results of later introductions of C. hortensis to Western Ukraine, which may occur through different garden centres, are easily distinguished by the presence of yellow banded and/or pink shells. And the presence of a dark lip in all pink shells can be a phenotypic marker of snails, whose ancestors were introduced to the west of Ukraine through the garden centre “Club of Plants” near Lviv. Only near this garden centre were also found three brown-shelled snails not known for other introduced Eastern European populations of C. hortensis.
EVALUATION OF THE STATE PROGRAM FOR THE DEVELOPMENT OF SCIENCE AND EDUCATION IN THE REPUBLIC OF TATARSTAN
Authors: Valiev Ayrat , Ziganshin Bulat , Klychova Guzaliya , Zakirova Alsu , Zakirov Ayaz
Published: November 2022

One of the driving forces for increasing the economic efficiency and competitiveness of business structures in the context of the development of an innovative economy is human capital. When forming state programs for the development of science and education, it is necessary to resolve issues related to its assessment. The study was carried out in order to assess the current state program in the Republic of Tatarstan aimed at the development of education (professional, postgraduate) and science, to identify significant shortcomings and use the results obtained in the process of developing new regulations. As a result of a phased analysis, recommendations were formulated for making changes to the text part of the subprogram. One of its defects is the insufficient structuring of the resource support for the implementation of the subprogram. This makes it very difficult to assess the nature of distribution and analyze the effectiveness of the use of financial resources within specific activities. In addition, specific stages of the implementation of the subprogram have not been identified. To eliminate this shortcoming, it is proposed to detail the sources of funding. Based on the results of the SWOT analysis, strong (all activities are broken down into specific tasks, indicators for evaluating the final results are broken down by activities, a detailed description of each activity is given, performers, deadlines and stages of implementation are indicated) and weak (tasks are formulated concisely, most of the indicators for evaluating the end results are indicated in relative terms, and there is no detail of financing by activities) of the wording and structure of the subprogram. Its implementation in its current form can lead to the emergence of certain threats. As a result of the Outcome analysis, both positive and negative qualitative and socio-economic effects were noted that followed or may follow in the implementation of various tasks and activities of the subprogram. Based on the results obtained in the course of the analysis, it is possible to correct measures aimed at the development of professional and postgraduate education.
RESEARCH ON APPROACHES TO EVALUATION OF DIGITAL TRANSFORMATION FACTORS OF AGRICULTURE
Authors: Sanzhina O. , Itygilova E. , Vanchikova Elena , Imeskenova Erzhena , Vanzatova Elena
Published: November 2022

The article considers the problems of digital transformation of agriculture in terms of achieving the objectives set by the state to form the digital maturity of agriculture in the region. The study is based on the hypothesis that in the regions, where there are no large agricultural holdings which determine the realization of advanced technologies and which form the perception of digital innovations, it is difficult to launch the processes of digital transformation. But it is possible only with a certain level of digital readiness of the population, high digital literacy of agricultural producers and their investment opportunities. Given the mandatory fulfillment of the indicators of digital maturity of agriculture, regional leaders need to understand the level of existing digital readiness of small businesses in order to implement digital technologies and readiness of rural areas population to use digital services and technologies in everyday life. The study was conducted in one of the districts of the Republic of Buryatia. That is region where there are no agricultural holdings, and the main producers of agricultural products are peasant farms and personal subsidiary farms. To assess the digital readiness of the population of the study area, the method of random survey through social networks was chosen. The analysis of that results made it possible to assess the level of digital literacy and digital trust of the rural population of the study area. These results can be reasonably extrapolated to the republic as a whole. In order to manage the process of digital transformation it is proposed to make the study of these indicators the subject of continuous monitoring and further use the data for training the neural network. The practical value of the study is determined by the fact that in our country small farming enterprises produce 42.3% of agricultural products in value terms therefor the digital readiness of the rural population of such regions is the main factor determining the success of the digital transformation.
SUBSTANTIATION AND DETERMINATION OF FURROWER PARAMETERS OF POTATO PLANTER
Authors: Kalimullin Marat , Haliullin Damir , Gayfullin Ilnur , Hamitov Radik
Published: November 2022

Furrow formation is one of the most labor-intensive operations in potato cultivation technology. The article discusses the justification and determination of furrower parameters of the potato planter. Analytical dependences of the height of the junction point of the disks and the width of the furrow bottom are obtained, taking into account the technological parameters, its design features and the physical and mechanical properties of the soil. Potatoes are planted in the usual way. The main row spacing in our country is 70 cm. However, in areas of high humidity and in irrigated areas, wide-row planting with a row spacing of 90 cm is used. In some areas of the European part, in arid areas, potatoes are planted with a row spacing of 60 cm. By the time of harvesting, the potato field has a ridged appearance, obtained as a result of hilling, where the height of the ridges is 11…20 cm. The angle of the row seed drills is that the vanishing point of the coulter rises above the bottom of the furrow by 6.3 cm. With an increase in the angle of entry of the coulter into the soil from 2° to 11°, the depth of the coulter travel increases. At angle values from 3° to 8°, the stroke depth approaches the optimum (12…18 cm).
Digital dementia and its impact on human cognitive and emotional functioning
Authors: Horoszkiewicz Bartosz
Published: November 2022

Digital dementia is a term coined by Spitzer and associated with a decline in mental abilities in memory, attention, and thinking by people who overuse new technologies. The aim of the study was to analyse the scientific literature in the field of new technology on digital dementia and its impact on human cognitive and emotional functioning. The study was based on a content analysis of current articles on Google Scholar on the topic of digital dementia. The negative phenomena associated with digital dementia and their impact on human cognitive and emotional functioning were presented. It is shown that inappropriate use of social media can be a risk factor and a source of mental health problems. A more important contemporary problem is not escaping from modern technology, but rather the rational ability to use it.
En el ‘ojo’ de la diabetes
Authors: Amador-Munoz Diana Patricia , Hernández Stefany
Published: November 2022

La diabetes mellitus es considerada como una de las enfermedades crónicas más alarmantes del siglo XXI. De no ser tratada correctamente, los pacientes pueden presentar daños en distintos órganos, entre ellos, los ojos. Un reciente estudio de la Universidad del Rosario encontró que la córnea, además de la retina, también se deteriora en los casos de diabetes, y en los pacientes con el Tipo 1 se lesiona más rápido que en los pacientes con el Tipo 2.