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Abstract Background Plant biostimulants constitute a promising environmentally friendly alternative for increasing crop yield and tolerance to unfavorable conditions. Among various types of such formulations, botanical extracts are gaining more recognition as products supporting plant performance. Moreover, novel tools such as cold-plasma or low-pressure microwave plasma discharge are being proposed as techniques that might improve their efficacy. Elucidation of the biostimulant’s mode of action requires complex research at a molecular level. Transcriptional changes occurring after biostimulant spraying might be investigated using RT-qPCR. However, this technique requires data normalization against stable endogenous controls. Results Here, we tested the expression stability of ten candidate genes in soybean plants exposed to various biostimulants treatment. Selection of the best-performing reference genes was conducted using four algorithms (geNorm, NormFinder, BestKeeper, and ΔCt method). According to the obtained results, Bic-C2 (RNA-binding protein Bicaudal-C) and CYP (cyclophilin type peptidyl-prolyl cis–trans isomerase) showed highest expression stability, while expression of EF1B (elongation factor 1-beta) fluctuated the most among a tested set of candidate genes. Conclusions Overall, we recommend using Bic-C2 together with CYP for the RT-qPCR data normalization in soybean biostimulation experiments. To our best knowledge, this is the first comprehensive study of reference genes stability in plants subjected to biostimulant treatment. The results of this study will aid in further biostimulant research in crop plants, facilitating analyses performed on the transcriptional level. Graphical Abstract

Abstract Introduction Treatment of multiple myeloma (MM) has been transformed by novel therapies, including CD38 monoclonal antibodies (mAbs), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), resulting in increasing numbers of patients who are triple-class exposed (TCE; exposed to ≥ 1 drug in each class). Many patients are penta-exposed (PE; ≥ 2 IMiDs, ≥ 2 PIs, and a CD38 mAb), some are triple-class refractory (TCR), and some are PE and TCR (PE-TCR). Data on real-world outcomes in elderly patients with MM across this spectrum of exposure are limited. Methods Data from the Medicare Chronic Conditions Warehouse Database from November 2006–December 2020 were used to examine cohorts of TCE, TCR, PE, and PE-TCR patients. Outcomes were assessed from the start of the index line of therapy (LOT), defined as the first LOT after becoming TCE or PE. Results A total of 2830 TCE, 1371 TCR, 1121 PE, and 774 PE-TCR patients were identified. Pomalidomide was the most frequently used medication for the index LOT in all cohorts (32.6% [PE-TCR] to 43.3% [TCR]). The most frequently used regimens for the index LOT were pomalidomide plus daratumumab for TCE (17.2%) and PE (7.0%), pomalidomide plus carfilzomib for TCR (10.3%), and pomalidomide plus elotuzumab for PE-TCR (7.4%). Median time to discontinuation (TTD) ranged from 4.2 (PE-TCR) to 6.9 (TCE) months, and overall survival (OS) ranged from 13.0 (TCR) to 15.9 (PE) months. Healthcare resource utilization (HRU) was lowest for TCE and highest for PE-TCR patients. Mean monthly healthcare costs (HCC) ranged from $23,091 (TCE) to $24,412 (PE-TCR). MM medications represented 66.2% (PE-TCR) to 72.8% (TCE) of costs. Conclusions In this study across a spectrum of Medicare TCE patients, there was heterogeneity in treatment regimens, suggesting no standard of care. TTD and OS were short, and HRU and HCC were high. These results underscore the potential for new therapies in this population.

Abstract Background The Collaborative Care Model (CoCM) increases access to mental health treatment and improves outcomes among patients with mild to moderate psychopathology; however, it is unclear how effective CoCM is for patients with elevated suicide risk. Methods We examined data from the Penn Integrated Care program, a CoCM program including an intake and referral management center plus traditional CoCM services implemented in primary care clinics within a large, diverse academic medical system. In this community setting, we examined: (1) characteristics of patients with and without suicidal ideation who initiated CoCM, (2) changes in suicidal ideation (Patient Health Questionnaire-9 [PHQ-9] item 9), depression (PHQ-9 total scores), and anxiety (Generalized Anxiety Disorder Scale-7 scores) from the first to last CoCM visit overall and across demographic subgroups, and (3) the relationship between amount of CoCM services provided and degree of symptom reduction. Results From 2018 to 2022, 3,487 patients were referred to CoCM, initiated treatment for at least 15 days, and had completed symptom measures at the first and last visit. Patients were 74% female, 45% Black/African American, and 45% White. The percentage of patients reporting suicidal ideation declined 11%-7% from the first to last visit. Suicidal ideation severity typically improved, and very rarely worsened, during CoCM. Depression and anxiety declined significantly among patients with and without suicidal ideation and across demographic subgroups; however, the magnitude of these declines differed across race, ethnicity, and age. Patients with suicidal ideation at the start of CoCM had higher depression scores than patients without suicidal ideation at the start and end of treatment. Longer CoCM episodes were associated with greater reductions in depression severity. Conclusions Suicidal ideation, depression, and anxiety declined following CoCM among individuals with suicidal ideation in a community setting. Findings are consistent with emerging evidence from clinical trials suggesting CoCM’s potential for increasing access to mental healthcare and improving outcomes among patients at risk for suicide.

Cel artykułu. Nastąpił wzrost liczby transakcji finansowych za pośrednictwem dokumentów finansowych z międzynarodowymi elementami. W szczególności artykuł odnosi się do umów kredytowych sporządzonych zgodnie ze standardami LMA, podlegających angielskiemu prawu, oraz do potencjalnych dostawców zabezpieczeń kredytowych działających w wielu jurysdykcjach, np. "spółek zależnych" pełniących rolę poręczycieli lub dodatkowych dłużników, a czasem także kredytobiorców. Wielość jurysdykcji stawia przed doradcami kredytowymi oraz głównym dłużnikiem wyzwanie dotyczące wyboru instrumentów zabezpieczenia w każdej jurysdykcji, w zależności od lokalizacji przedmiotu zabezpieczenia. Artykuł ma na celu przedstawienie przeglądu najczęściej stosowanych rodzajów zabezpieczeń w polskim prawie, służących zabezpieczeniu umów kredytowych w jurysdykcjach innych niż polska. Autor dokonał również oceny, która może być pomocna dla praktyków spoza Polski w doborze odpowiedniego zabezpieczenia dla długu. Głównym celem jest zapoznanie osób nieobeznanych z polskim prawem ze standardami prawa polskiego dotyczącego zabezpieczeń kredytowych, a główna hipoteza zakłada, że polskie zabezpieczenia zapewniają pewność instytucjom zagranicznym udzielającym kredytów, w których uczestniczy polski podmiot jako dostawca zabezpieczenia. Metoda badawcza. Artykuł stanowi kompleksową recenzję literatury dotyczącej polskiego zabezpieczenia prawnego dla należności z umów kredytowych udzielonych na mocy prawa obcego (włączając w to akty prawne). Zastosowane metody obejmują metodę hermeneutyczną, metodę porównawczą oraz metodę analizy i syntezy. Wyniki badań. Na podstawie przeprowadzonych badań stwierdzono, że polskie dokumenty zabezpieczenia są wystarczające do zabezpieczenia należności wynikających z umów kredytowych regulowanych przez prawo obce. Główna hipoteza wydaje się, że została udowodniona. Ponadto na podstawie badań udowodniono, że polskie dokumenty zabezpieczenia, ze względu na ich znaczenie prawne, powinny stanowić zachętę dla zagranicznych instytucji finansowych do działania na terenie Polski. Wnioskiem jest, że polskie prawo zabezpieczeń jest bogate w narzędzia pozwalające na pewność obrotu międzynarodowego instytucji.

Rice and wheat provide nearly 40% of human calorie and protein requirements. They share a common ancestor and belong to the Poaceae (grass) family. Characterizing their genetic homology is crucial for developing new cultivars with enhanced traits. Several wheat genes and gene families have been characterized based on their rice orthologs. Rice–wheat orthology can identify genetic regions that regulate similar traits in both crops. Rice–wheat comparative genomics can identify candidate wheat genes in a genomic region identified by association or QTL mapping, deduce their putative functions and biochemical pathways, and develop molecular markers for marker-assisted breeding. A knowledge of gene homology facilitates the transfer between crops of genes or genomic regions associated with desirable traits by genetic engineering, gene editing, or wide crossing.

Abstract Background Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy. Methods Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage. Results Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity. Conclusions Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.

Like many other Mediterranean countries, Albania faces unique challenges and opportunities to achieve an efficient and fully decarbonized household sector by applying real energy efficiency measures and numbers toward nearly zero-energy buildings. The study findings showed that nZEB in 2030 can be achieved by combining active and passive energy efficiency measures. Behind the study's state-of-the-art stands a multivariable regression analysis of both electricity consumption and electricity generation executed for three validated consecutive years, 2021, 2022, and 2023, including demand side (electricity bills) and supply side generation provided from a nearby existing onsite PV with an installed capacity of 5.5 kWp. A good mathematical correlation is carried out using Durbin – Watson criteria on statistics using RETScreen software to correlate electricity consumption and generation as a function of weather parameters for the tested household and selected region. The goals to meet the nZEB concept require the insulation of the existing exterior wall and window replacements in compliance with the Energy Performance Methodology on Building and installing rooftop Solar Water Heating (SWH) panels of 3.73 m2 as expostulated in scenario 7. The simulation results show that integrating a rooftop PV system with an installed capacity of 5.5 kWp would provide enough electricity to convert residential buildings into Positive Energy Buildings in 2050 based on the selected dwelling and location (Mediterranean region). At the national level, the proposed model would reduce the national annual electricity import level by 1.64 %, saving annually around €31,021,162 and reducing at least 0.068 MtCO2 per year. Subsidizing passive energy efficiency measures at a rate of 3 % per year coupled with onsite renewable energy sources schemes and other incentivization pathways from the government and other interested parties at a rate of 80 % in the roadmap towards nZEB and PEB is mandatory.

Composite dowels opened new possibilities for engineers designing composite structures. The fundamental and most important characteristic of composite dowels is the shape of the cutting pattern (called line). It is important to understand why only one particular shape of the cutting line, the modified clothoidal (MCL) shape, is being used in bridge engineering, while so many different shapes have been investigated by many researchers. The essential part of the process of developing composite dowels – the development of shape of the cutting line – is presented in this paper. The investigation, development, and evolution of the MCL shape, which is the final form of composite dowels for bridges and has been widely introduced in bridge engineering, are presented. The results of comparative tests of different shapes under cyclic loads are discussed. The background for the design formulas for the steel part and the fabrication aspects are highlighted.

Abstract In this work, the properties of biochar produced from green macroalga Ulva intestinalis by pyrolysis were studied at temperatures of 300, 500, and 700 °C. This biochar was characterized in terms of multielemental composition, BET surface area, total pore volume, and biosorption properties toward phosphate ions. Biochar produced at 700 °C–25 m2/g had the highest surface area. The kinetics and isotherms of sorption processes of phosphate ions as sorbate by these sorbents were investigated. Modified biochar was able to remove 84.3% of phosphate ions from wastewater, whereas non-modified biochar—only 40.6%. Hence, biochar enriched with phosphate ions can serve as a valuable soil amendment. Pot experiments performed on winter wheat (Triticum aestivum) with a 3% addition of dry Ulva intestinalis, pristine biochar, and Mg-modified biochar enriched with phosphate ions showed that these amendments stimulated plant growth (length and fresh weight of plants) as well as enlarging the chlorophyll content in leaves. Our results indicate that the production of biochar (pristine and Mg-impregnated) is a sustainable option to valorize the biomass of seaweeds, and to recycle phosphorus from wastewater. Graphical Abstract

Objective To synthesise qualitative evidence on clinicians’ views and experiences of defensive practice.Design Systematic review of qualitative data.Data sources MEDLINE, Embase, PsycINFO, AMED, Maternity and Infant Care, CINAHL, ASSIA, Sociological Abstracts, Proquest Dissertations & Theses and PROSPERO were searched from 2000 to October 2023.Eligibility criteria We included English-language studies of clinicians which reported qualitative data on the impact of litigation or complaints on clinical practice.Data extraction and synthesis We coded findings data line by line using a grounded theory approach. We assessed quality using Hawker et al’s tool and synthesised data thematically.Results 17 studies were included. Participants identify a range of clinical decisions which may be defensively motivated, relating to diagnosis and documentation as well as to treatment. Defensive practice often relates to a diffuse sense of risk rather than the direct threat of litigation and may overlap with other motivations, such as perceived pressure from patients or the desire to avoid harm. Defensive practice is seen to be harmful in many ways, but again, these perceptions may gain force from broader narratives of mistrust and disempowerment, as much as from the risk of litigation.Conclusions The idea of defensive practice, as enacted, is more complex than some theoretical accounts suggest and may often function to express broader concerns about the work of clinical care. The qualitative evidence calls into question the view of defensive practice as a key mediator linking litigation risk to inappropriate treatment and excess costs.

Abstract BackgroundThe increasing demand for skin quality interventions in aesthetic medicine underscores the necessity for objective, evidence-based assessment tools that may be used to evaluate novel interventions or devices. ObjectivesTo develop and validate a 5-point photonumeric rating scale for assessing overall skin quality, including radiance, color evenness, and smoothness. MethodsThe IBSA (Institut Biochimique SA) Composite Skin Quality Scale was developed and underwent live validation with 88 real-world patients, chosen to encompass a broad spectrum of skin qualities and Fitzpatrick skin types. Scale validation was performed by board-certified plastic surgeons and dermatologists over 2 rounds, 2 weeks apart. Reliability was assessed through intrarater and interrater agreements, utilizing weighted kappa statistics and intraclass correlation coefficient (ICC). The scale’s ability to discern a clinically relevant 1-grade difference was evaluated with 72 photo pairs. ResultsCombined intrarater reliability results showed weighted kappa values of 0.812 (right side) and 0.815 (left side) and an ICC of 0.903 for both sides, indicating an almost perfect agreement. Interrater reliability ranged from substantial to almost perfect, with kappa coefficients between 0.654 and 0.853 and ICCs between 0.657 and 0.855 across all rater pairs in both rounds. The ability to detect a clinically relevant 1-point difference using the scale was established. ConclusionsIntegrating various key aspects of skin quality, the IBSA Composite Skin Quality Scale is a clinically relevant and highly reliable tool, suitable for skin assessment in clinical studies of new aesthetic technologies and products. Level of Evidence: 3

Kwestionariusz Samooceny Głosu dla Transpłciowych Kobiet (Trans Woman Voice Questionnaire – TWVQ) jest narzędziem diagnostycznym stworzonym specjalnie na potrzeby feminizującej terapii głosu. Uzupełnia on obiektywną diagnozę o subiektywne odczucia pacjentki. Terapeuta otrzymuje bezcenne informacje dotyczące jej potrzeb i oczekiwań, a sama pacjentka ma możliwość lepiej uświadomić sobie swój stosunek do własnego głosu. Kwestionariusz – zaprojektowany pierwotnie w języku angielskim – wymagał przełożenia na język polski. Proces tłumaczenia, a później adaptacji i walidacji został przeprowadzony zgodnie z rygorystycznymi wytycznymi Światowej Organizacji Zdrowia, w tym z udziałem transpłciowych pacjentek. Polska wersja TWVQ została zaakceptowana przez współautorkę oryginału i jest za darmo dostępna w internecie. Logopedzi i logopedki w Polsce otrzymali specjalistyczne narzędzie pomocne w terapii transpłciowych pacjentek.

Two new species and two new subspecies of the satyrine butterfly genus Punargentus Heimlich, P. atusparia sp. n., P. heimlichi sp. n., P. blanchardi libertas ssp. n. and P. atusparia yupania ssp. n., are described from north-central Peru (Ancash, Huánuco and La Libertad). The affinities of the new taxa are evaluated based on molecular data obtained using target enrichment and COI barcoding. Punargentus is fully supported and consists of two branches, the P. lamna clade with four species and P. blanchardi clade with three species, two of which are described here. Species in the P. blanchardi clade occur in Andean shrubland, at altitudes between 2800-3600 m, whereas those in the P. lamna clade occur in puna grassland at 3600-4600 m, with occasional overlaps. Based on their habitat preferences, none of the newly described species are in need of immediate conservation measures. The genus Etcheverrius Herrera is reinstated, with E. chiliensis (Guérin-Méneville) and E. tandilensis (Köhler), comb. n.

The use of phosphodiesterase inhibitors in the treatment of Parkinson’s disease is currently widely discussed. The study aimed to investigate the impact of acute and chronic treatment with the phosphodiesterase 5 inhibitor, sildenafil, at low and moderate doses of 2 mg/kg and 6 mg/kg, and L-DOPA (12.5 mg/kg), alone or in combination, on asymmetric behavior and dopamine (DA) and serotonin metabolism in the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Acute administration of sildenafil at both tested doses jointly with L-DOPA significantly increased the number of contralateral rotations during a 2 h measurement compared to L-DOPA alone. The effect of a lower dose of sildenafil combined with L-DOPA was much greater in the second hour of measurement. However, the acute combined administration of a higher dose of sildenafil with L-DOPA resulted in an immediate and much stronger increase in the number of contralateral rotations compared to L-DOPA alone, already visible in the first hour of measurement. Interestingly, the chronic combined administration of 2 mg/kg of sildenafil and L-DOPA significantly reduced the number of contralateral rotations, especially during the first hour of measurement, compared to the long-term treatment with L-DOPA alone. Such an effect was not observed after the long-term combined treatment of a higher dose of sildenafil and L-DOPA compared to L-DOPA alone. The concentration of DA in the ipsilateral striatum and substantia nigra after the last combined chronic dose of sildenafil (2 or 6 mg/kg) and L-DOPA (12.5 mg/kg) was significantly higher than after L-DOPA alone. In spite of much stronger increases in the DA concentration in the ipsilateral striatum and substantia nigra, the number of contralateral rotations was reduced in the group of rats treated with the combination of 2 mg/kg sildenafil and L-DOPA compared to the group receiving L-DOPA alone. Moreover, the combined treatment with a low dose of sildenafil and L-DOPA had an opposite effect on DA catabolism, as assessed by DOPAC/DA and HVA/DA indexes, and these indexes were reduced in the ipsilateral striatum but increased in the contralateral striatum and substantia nigra compared to the treatment with L-DOPA alone. The results of the present study show that the addition of a low dose of a PDE5 inhibitor to the standard L-DOPA therapy differently modulates rotational behavior, the tissue DA concentration and its catabolism in the striatum and substantia nigra.

This article presents an original methodology to determine the optimal level of reactive energy transmission to low-voltage consumers supplied from MV/LV substations that guarantees the lowest total costs of reactive energy transmission through the DSO network and its generation in receiving installations within the reactive power compensation process. The average value of the optimal factor tgφ to be maintained by customers depends on the efficiency of the network, the characteristics of the load, and the market costs of energy losses due to the transmission of reactive energy through the network that are covered by the DSO and the costs of reactive energy generation in receiving installations. The results presented for real MV/LV substations operating in the Polish distribution network demonstrate the application of annual measurements of active and reactive energy consumed and generated registered by AMI systems to calculate the optimal reactive power compensation level. They can be applied to verify the permissible levels of reactive energy compensation applied by the DSOs until now within the yearly tariffs for customers.