High Rates of Organ Preservation in Rectal Cancer with Papillon Contact X-ray Radiotherapy: Results from a Swiss Cohort.

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake.

Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these neurons has not been mapped. Here, we isolate DANs from Dat-eGFP mice to generate a GPCR atlas by unbiased qPCR array expression analysis of 377 GPCRs. Combined with data mining of scRNA-seq databases, we identify multiple receptors in DAN subpopulations with 38 of these receptors representing the majority of transcripts. We identify 41 receptors expressed in midbrain DANs but not in non-DAN midbrain cells, including the free fatty acid receptor 4 (FFAR4). Functional expression of FFAR4 is validated by ex vivo Ca2+ imaging, and in vivo experiments support that FFAR4 negatively regulates food and water intake and bodyweight. In addition to providing a critical framework for understanding metabotropic DAN regulation, our data suggest fatty acid sensing by FFAR4 as a mechanism linking high-energy intake to the dopamine-reward pathway.

Hapsolutely: a user-friendly tool integrating haplotype phasing, network construction, and haploweb calculation.

Motivation: Haplotype networks are a routine approach to visualize relationships among alleles. Such visual analysis of single-locus data is still of importance, especially in species diagnosis and delimitation, where a limited amount of sequence data usually are available and sufficient, along with other datasets in the framework of integrative taxonomy. In diploid organisms, this often requires separating (phasing) sequences with heterozygotic positions, and typically separate programs are required for phasing, reformatting of input files, and haplotype network construction. We therefore developed Hapsolutely, a user-friendly program with an ergonomic graphical user interface that integrates haplotype phasing from single-locus sequences with five approaches for network/genealogy reconstruction. Results: Among the novel options implemented, Hapsolutely integrates phasing and graphical reconstruction steps of haplotype networks, supports input of species partition data in the common SPART and SPART-XML formats, and calculates and visualizes haplowebs and fields for recombination, thus allowing graphical comparison of allele distribution and allele sharing among subsets for the purpose of species delimitation. The new tool has been specifically developed with a focus on the workflow in alpha-taxonomy, where exploring fields for recombination across alternative species partitions may help species delimitation. Availability and implementation: Hapsolutely is written in Python, and integrates code from Phase, SeqPHASE, and PopART in C++ and Haxe. Compiled stand-alone executables for MS Windows and Mac OS along with a detailed manual can be downloaded from https://www.itaxotools.org; the source code is openly available on GitHub (https://github.com/iTaxoTools/Hapsolutely).

Targeting postsynaptic glutamate receptor scaffolding proteins PSD-95 and PICK1 for obesity treatment.

Human genome-wide association studies (GWAS) suggest a functional role for central glutamate receptor signaling and plasticity in body weight regulation. Here, we use UK Biobank GWAS summary statistics of body mass index (BMI) and body fat percentage (BF%) to identify genes encoding proteins known to interact with postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors. Loci in/near discs large homolog 4 (DLG4) and protein interacting with C kinase 1 (PICK1) reached genome-wide significance (P < 5 × 10-8) for BF% and/or BMI. To further evaluate the functional role of postsynaptic density protein-95 (PSD-95; gene name: DLG4) and PICK1 in energy homeostasis, we used dimeric PSD-95/disc large/ZO-1 (PDZ) domain-targeting peptides of PSD-95 and PICK1 to demonstrate that pharmacological inhibition of PSD-95 and PICK1 induces prolonged weight-lowering effects in obese mice. Collectively, these data demonstrate that the glutamate receptor scaffolding proteins, PICK1 and PSD-95, are genetically linked to obesity and that pharmacological targeting of their PDZ domains represents a promising therapeutic avenue for sustained weight loss.

Patient-reported outcome measures (PROMs) of digital and conventional impression methods for fixed dentures.

BACKGROUND: Digital impression technique or computer-aided impression (CAI) has been recently concluded as a clinically acceptable alternative to conventional impression method (CIM) in the fabrication of crowns, short fixed partial dentures (FPDs), and implant-supported crowns. OBJECTIVE: The purpose of this study was to investigate the patients' opinion and subjective perception of two different ways of impression - digital and conventional. METHODS: A total of 45 patients were treated with CAI and CIM for the fabrication of tooth or implant-supported crowns. They fulfilled a questionnaire including 11 questions regarding the treatment time, gag reflex, discomfort related to manipulation, and other aspects of treatment. RESULTS: CAI was considered the preferential method for future treatment in 53% of patients, whereas 28.9% of the respondents preferred CIM. The preference for the impression method was influenced by the total time spent with the procedure, discomfort during manipulation with the tray or scanning head, size of the tray or scanning head, maximal opening discomfort, and (the tendency towards) gag reflex. CONCLUSION: CAI was considered a more comfortable and preferential method. Discomfort or difficulties during CAI negatively affected the patients' attitude to CAI, whereas the difficulties associated with CIM did not have any influence on the preferred method.

Classical Drift in the Arnold Web Induces Quantum Delocalization Transition.

We demonstrate that quantum dynamical localization in the Arnold web of higher-dimensional Hamiltonian systems is destroyed by an intrinsic classical drift. Thus quantum wave packets and eigenstates may explore more of the intricate Arnold web than previously expected. Such a drift typically occurs, as resonance channels widen toward a large chaotic region or toward a junction with other resonance channels. If this drift is strong enough, we find that dynamical localization is destroyed. We establish that this drift-induced delocalization transition is universal and is described by a single transition parameter. Numerical verification is given using a time-periodically kicked Hamiltonian with a four-dimensional phase space.

Low, medium, and high molecular weight hyaluronic acid effects on human dental pulp stem cells in vitro.

Hyaluronic acid (HA), an extracellular biopolymer found throughout the human body, holds promise as a biocompatible and biodegradable scaffold material. High molecular weight (HMW) HA degrades, generating low molecular weight (LMW) fragments with distinct properties. These fragments can influence the behaviour of cells, including human dental pulp stem cells (hDPSCs) incorporated into HA-containing hydrogels or scaffolds. Therefore, a comprehensive examination of the impact of a range of HA molecular weights on hDPSCs is essential before designing HA-based scaffolds for these cells. hDPSC lines were cultured with LMW HA (800 Da, 1600 Da, 15 kDa), medium molecular weight HA (237 kDa), or HMW HA (1500 kDa) over six passages. The various molecular weights had negligible effects on hDPSCs viability, morphology, adhesion, or relative telomere length. Furthermore, the expression of key surface stemness markers (CD29, CD44, CD73, CD90) remained unaltered. HA did not induce osteogenic, chondrogenic, or adipogenic differentiation. Moreover, the potential for chondrogenic and osteogenic differentiation was not adversely affected by LMW or HMW HA. Various molecular weights of HA seem safe, biocompatible and therefore suitable components for hDPSCs-containing scaffolds. These findings affirm that the hDPCSs will not be negatively affected by HA fragments resulting from scaffold degradation.

Comparison of COVID-19 epidemic among Czech dentists and the Czech general population.

Dentists are one of the professional groups most at risk for COVID-19 infection. Enhanced protective measures in dentistry have been adopted worldwide; however, it is unclear to what extent they were sufficient. To assess whether the protective measures outweighed the high infection risk, we compared COVID-19-related data between Czech dentists and the general Czech population. The data was obtained through a survey study attended by 15.8% of Czech Dental Chamber members. Data of the general population were acquired from the Czech Ministry of Health database. By the end of May 2022, COVID-19 full vaccination and 1st booster dose rates among study participants were 85.8% and 70.1%, respectively, which is significantly higher (p < 0.0001) compared to the Czech general population aged over 24 years (74.9% and 49.4%, respectively). To the same date, PCR/Antigen test verified COVID-19 prevalence among participants was 41.7%, and 49.9% among the general population (p < 0.0001). Prevalence and reinfection rates among individuals who received the 1st booster were significantly lower than among individuals without the booster or full vaccination (p < 0.0001). Persons who received the booster showed a faster return to work, shorter and different types of complications. Willingness to future vaccination was positive among 79.7% of respondents. Mandatory vaccination for healthcare workers and the general population was supported by 62.0% and 49.0%, respectively. The results showed that the high risk of COVID-19 infection associated with dentistry did not lead to higher COVID-19 prevalence among respondents compared to the general population.

Wide Antral Circumferential Re-Ablation for Recurrent Atrial Fibrillation after Prior Pulmonary Vein Isolation Guided by High-Density Mapping Increases Freedom from Atrial Arrhythmias.

Performing repeated pulmonary vein isolation (re-PVI) after recurrent atrial fibrillation (AF) following prior PVI is a standard procedure. However, no consensus exists regarding the most effective approach in redo procedures. We assessed the efficacy of re-PVI using wide antral circumferential re-ablation (WACA) supported by high-density electroanatomical mapping (HDM) as compared to conventional re-PVI. Consecutive patients with AF recurrences showing true PV reconnection (residual intra-PV and PV antral electrical potentials within the initial ablation line) or exclusive PV antral potentials (without intra-PV potentials) in the redo procedure were prospectively enrolled and received HDM-guided WACA (Re-WACA group). Conventional re-PVI patients treated using pure ostial gap ablation guided by a circular mapping catheter served as a historical control (Re-PVI group). Patients with durable PVI and no antral PV potentials were excluded. Arrhythmia recurrences ≥30 s were calculated as recurrences. In total, 114 patients were investigated (Re-WACA: n = 56, 68 ± 10 years, Re-PVI: n = 58, 65 ± 10 years). There were no significant differences in clinical characteristics including the AF type or the number of previous PVIs. In the Re-WACA group, 11% of patients showed electrical potentials only in the antrum but not inside any PV. At 402 ± 71 days of follow-up, the estimated freedom from arrhythmia was 89% in the Re-WACA group and 69% in the Re-PVI group (p = 0.01). Re-WACA independently predicted arrhythmia-free survival (HR = 0.39, 95% CI 0.16-0.93, p = 0.03), whereas two previous PVI procedures predicted recurrences (HR = 2.35, 95% CI 1.20-4.46, p = 0.01). The Re-WACA strategy guided by HDM significantly improved arrhythmia-free survival as compared to conventional ostial re-PVI. Residual PV antral potentials after prior PVI are frequent and can be easily visualized by HDM.

Contactless quasi-steady-state photoconductance (QSSPC) characterization of metal halide perovskite thin films.

We apply the contactless quasi-steady-state photoconductance (QSSPC) method to co-evaporated methyl ammonium lead iodide (MAPbI3) perovskite thin-films. Using an adapted calibration for ultralow photoconductances, we extract the injection-dependent carrier lifetime of the MAPbI3 layer. The lifetime is found to be limited by radiative recombination at the high injection densities applied during the QSSPC measurement, enabling the extraction of the electron and hole mobility sum in the MAPbI3 using the known coefficient of radiative recombination of MAPbI3. Combining the QSSPC measurement with transient photoluminescence measurements, performed at much lower injection densities, we obtain the injection-dependent lifetime curve over several orders of magnitude. From the resulting lifetime curve, we determine the achievable open-circuit voltage of the examined MAPbI3 layer.

Wake-Up Receiver for Underwater Acoustic Communication Using in Shallow Water.

A data frame transmitted over the underwater acoustic channel usually begins with a preamble. Therefore, underwater communication systems have a dedicated receiver that constantly listens to the preamble signals. A receiver that is to work effectively in shallow waters must have solutions that effectively reduce the impact of the permanently occurring multipath propagation. The article presents a solution based on complementary broadband signals. Initial tests were carried out using the Watermark simulator to determine its reliability in such a difficult propagation environment. The results of experimental tests carried out in a model pool are also included. Details of the implementation of the wake-up receiver are presented.

Composition and electronic structure of [Formula: see text]/[Formula: see text]/Al passivating carrier selective contacts on n-type silicon solar cells.

Carrier-selective and passivating SiO[Formula: see text]/TiO[Formula: see text] heterocontacts are an attractive alternative to conventional contacts due to their high efficiency potentials combined with relatively simple processing schemes. It is widely accepted that post deposition annealing is necessary to obtain high photovoltaic efficiencies, especially for full area aluminum metallized contacts. Despite some previous high-level electron microscopy studies, the picture of atomic-scale processes underlying this improvement seems to be incomplete. In this work, we apply nanoscale electron microscopy techniques to macroscopically well-characterized solar cells with SiO[Formula: see text]/TiO[Formula: see text]/Al rear contacts on n-type silicon. Macroscopically, annealed solar cells show a tremendous decrease of series resistance and improved interface passivation. Analyzing the microscopic composition and electronic structure of the contacts, we find that partial intermixing of the SiO[Formula: see text] and TiO[Formula: see text] layers occurs due to annealing, leading to an apparent thickness reduction of the passivating SiO[Formula: see text]. However, the electronic structure of the layers remains clearly distinct. Hence, we conclude that the key to obtain highly efficient SiO[Formula: see text]/TiO[Formula: see text]/Al contacts is to tailor the processing such that the excellent chemical interface passivation of a SiO[Formula: see text] layer is achieved for a layer thin enough to allow efficient tunneling through the layer. Furthermore, we discuss the impact of aluminum metallization on the above mentioned processes.

Case report: "A healthy woman with exertional dyspnea: Indication of a pacemaker or not?"

The selection of patients with chronotropic incompetence (CI) for cardiac pacing therapy remains challenging. Here, we present a case of a 40-year-old woman with severe exertional dyspnea. The exercise test revealed a blunted increase in the heart rate (HR) (maximum of 110 bpm). Her exercise capacity significantly improved under atrial stimulation at 170 bpm using a temporary pacing lead. Therefore, we implanted a rate-adaptive dual-chamber pacemaker with a blended sensor. During follow-up exercise capacity normalized, and she had no residual exertional dyspnea at 6 months. This case highlights the potential value for individual assessments of CI to identify clear indications for pacemaker implantation.

COVID-19 among Czech Dentistry Students: Higher Vaccination and Lower Prevalence Compared to General Population Counterparts.

The restrictions on medical students' clinical education during the COVID-19 pandemic has affected their professional readiness and often lengthened their training. These negative impacts are often considered a necessary price as clinical education is hypothesized to be associated with a high risk of pandemic spread. This work assesses this hypothesis based on COVID-19 epidemiological data among Czech dentistry students and their comparison to data of the Czech general population of similar age. We addressed two of the five Czech medical faculties (Charles University, Faculty of Medicine in Hradec Kralove and in Pilsen) providing dentistry study program with a survey. A total of 240 students participated, representing a 66.9% response rate. Over 75% of respondents participated in clinical education during the pandemic. The school environment was identified as a place of infection by only 9.8% of respondents who were aware of where they were infected. Overall, 100% of students used FFP2 respirators, and 75.3% used face shields or protective glasses while working with patients. By the end of May 2022, COVID-19 full vaccination and 1st booster rates among students were 93.8% and 54.6%, respectively, which is significantly higher (p < 0.0001, OR 7.3, 95% CI 4.4−12; p < 0.0001, OR 3.7, 95% CI 2.9−4.8, respectively) compared to their peers from the general population (67.1% and 24.4%, respectively). A total of 75.4% of respondents supported mandatory COVID-19 vaccination for healthcare professionals. To the same date, PCR and/or antigen test verified COVID-19 prevalence among students was 37.1%, while among peers from the general population, it was 45.1% (p = 0.015, OR 1.2, 95% CI 1.0−1.5). The combination of extensive protective measures and high vaccination against COVID-19 led to significantly lower COVID-19 prevalence among the students compared to their general population counterparts.

The Effect of Priority Access of Dentists to COVID-19 Vaccination in the Czech Republic.

The lack of vaccines in the first half of 2021 led to the need to prioritize access to vaccination. This approach has been associated with a number of issues, including ethics and effectiveness. However, analyses providing data on this topic are scarce. This work describes the effect of a priority approach to vaccination on the different development of the pandemic between Czech dentists and the Czech general population. The dentist-related data were obtained from survey studies published in 2021 and 2022, and the Czech general population data were mined from the Our World in Data online database. The analysis shows that until the beginning of vaccination, i.e., in December 2020, the prevalence of laboratory-confirmed COVID-19 infection among dentists was higher than in the general population by 22.5% (8.65% vs. 6.70%). This trend was reversed already in the first month after the start of vaccination, and the difference increased every month. Finally, in June 2021, priority vaccination statistically significantly (p < 0.0001) reduced the resulting prevalence among dentists (12.67%) compared to the general population (15.55%), which is a difference of 18.5%. This represents a prevalence shift between the populations by 40% during 6 months of priority vaccination. The results support the conclusion that the priority vaccination of healthcare workers was not only ethical but also rational and effective.

Effect of Human Platelet Lysate as Cultivation Nutrient Supplement on Human Natal Dental Pulp Stem Cell In Vitro Expansion.

Despite several scientific or ethical issues, fetal bovine serum (FBS) remains the standard nutrient supplement in the mesenchymal stem cell cultivation medium. Cell amplification plays an important role in human stem cell therapies. Increasing interest in this field has supported attempts to find suitable human alternatives to FBS for in vitro cell propagation. Human platelet lysate (hPL) has recently been determined as one of them. Our study aimed to evaluate the influence of 2% hPL in the growth medium for in vitro expansion of human natal dental pulp stem cells (hNDP-SCs). The effect was determined on proliferation rate, viability, phenotype profile, expression of several markers, relative telomere length change, and differentiation potential of four lineages of hNDP-SCs. As a control, hNDP-SCs were simultaneously cultivated in 2% FBS. hNDP-SCs cultivated in hPL showed a statistically significantly higher proliferation rate in initial passages. We did not observe a statistically significant effect on mesenchymal stem cell marker (CD29, CD44, CD73, CD90) or stromal-associated marker (CD13, CD166) expression. The cell viability, relative telomere length, or multipotency remained unaffected in hNDP-SCs cultivated in hPL-medium. In conclusion, hPL produced under controlled and standardized conditions is an efficient serum supplement for in vitro expansion of hNDP-SCs.

The Prevalence and Development of Neck and Lower Back Pain and Associated Factors in Dentistry Students-A Long-Term Prospective Study.

Musculoskeletal disorders (MSDs) represent a significant occupational burden for dentists and dentistry students. This study aimed to assess the five-year development of most common musculoskeletal complaints among dentistry students during the whole length of their studies and to analyze the impact of some potentially associated risk factors. A longitudinal questionnaire survey regarding the occurrence of MSDs was conducted among a total of 73 dentistry students between 2014 and 2021. The same students enrolled in three consecutive years were monitored throughout their entire studies. Statistical analysis was performed using methods of descriptive statistics, Chi-square test, Fisher's exact test, McNemar test, and univariate and multivariate logistic regression analyses. The most frequent areas of complaints were neck (61.6%) and lower back (49.3%). The increase in self-reported complaints between the first and the fifth year was statistically significant for neck pain (increase by 15%, p = 0.043) but not for lower back pain (by 6.8%, p = 0.44). According to our data, age, performing top-level sport, and participating in regular sporting activities had a statistically significant influence on neck and/or back pain. The results of this longitudinal prospective study showed that neck, as well as lower back pain, are significant problems for dentistry students.

Acute cardiac side effects after COVID-19 mRNA vaccination: a case series.

BACKGROUND: Vaccination against SARS-CoV-2 has been the main tool to contain the pandemic. The rush development of the 3 vaccines and their expedited approval have led to inoculation of millions of patients around the world, leading to a containment of the disease. Despite continuous viral mutations and the identification of weaker variants, the severity of the infections has been mild, with many patients being either asymptomatic or recovering at home. Currently the focus has shifted from the host of organ damage related to the infection to potential side effects of the vaccine. Myocarditis has been reported as one of the potential side effects from the mRNA vaccine, affecting young healthy individuals. Up to September 30, 2021, 1.243 cases of myocarditis after vaccination with BNT162b2 Comirnaty© were registered in young adults by the Paul-Ehrlich-Institute in Germany alone. The exact pathophysiology and the risk factors for myocarditis following vaccination remain unclear. We present a case series of eight patients with cardiac symptom shortly after SARS-CoV-2 mRNA vaccination (BNT162b6, Biontech, Comirnaty© or mRNA-1237 Moderna, Spikevax©). PATIENTS AND METHODS: Eight patients between 13 and 56 years of age, vaccinated with either BNT162b2 or mRNA-1273 mRNA vaccine between January and August 2021 developed cardiac side effects shortly after either their first or second dose of the vaccine. Clinical data were retrieved from the clinical information system and analyzed. To support diagnosis of myocarditis or pericarditis, cardiac magnetic resonance imaging (MRI) was performed shortly after the onset of symptoms, with further investigations in severe cases. Symptoms were defined as dyspnea, chest pain and cardiac arrhythmia as determined by electrocardiography. RESULTS: Eight patients (5 males and 3 females) developed cardiac symptoms compatible with myocarditis, according to the CDC criteria, shortly after SARS-CoV-2 mRNA vaccination. Three patients (2 males, 1 female) required hospitalization due to severe chest pain and elevated troponin levels. All patients recovered fully within 7 days from the symptom onset. CONCLUSIONS: Our data suggest that cardiac adverse events such as myocarditis or pericarditis shortly after SARS-CoV-2 mRNA vaccination are rare but possible and occur particularly in male patients.

Innovative Approach in the Cryogenic Freezing Medium for Mesenchymal Stem Cells.

The physical stresses during cryopreservation affect stem cell survival and further proliferation. To minimize or prevent cryoinjury, cryoprotective agents (CPAs) are indispensable. Despite the widespread use of 10% dimethyl sulfoxide (DMSO), there are concerns about its potential adverse effects. To bypass those effects, combinations of CPAs have been investigated. This study aimed to verify whether high-molecular-hyaluronic acid (HMW-HA) serves as a cryoprotectant when preserving human mesenchymal stem cells (hMSCs) to reduce the DMSO concentration in the cryopreservation medium. We studied how 0.1% or 0.2% HMW-HA combined with reduced DMSO concentrations (from 10% to 5%, and 3%) affected total cell count, viability, immunophenotype, and differentiation potential post-cryopreservation. Immediately after cell revival, the highest total cell count was observed in 10% DMSO-stored hMSC. However, two weeks after cell cultivation an increased cell count was seen in the HMW-HA-stored groups along with a continued increase in hMSCs stored using 3% DMSO and 0.1% HMW-HA. The increased total cell count corresponded to elevated expression of stemness marker CD49f. The HA-supplemented cryomedium did not affect the differential potential of hMSC. Our results will participate in producing a ready-to-use product for cryopreservation of mesenchymal stem cells.