Patient-reported outcomes of topical finasteride/minoxidil treatment for male androgenetic alopecia: A retrospective study using telemedical data.

BACKGROUND: Oral finasteride and topical minoxidil are the current standard of care for male androgenetic alopecia and a combination of the two treatments can be considered for greater efficacy. Clinical trials of topical finasteride have also yielded promising results, but routine care data are lacking. AIMS: To examine patient-reported outcomes of men with androgenetic alopecia who received topical finasteride admixed with minoxidil compared to the current standard of care (oral finasteride). METHODS: Retrospective, cross-sectional study with data from a German direct-to-consumer teledermatology platform between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided after 6 weeks on topical finasteride/minoxidil or oral finasteride treatment. RESULTS: A total of 1545 patients who received topical finasteride/minoxidil treatment were included; 238 (15.4%) participated in the follow-up questionnaire. At week six, 62.2% (148/238) reported positive changes in their hair appearance, and 44.1% (105/238) reported an improvement of self-esteem. Treatment-related adverse events were reported in 11.8% (28/238). Full treatment adherence was observed in 74.4% (177/238). Comparing the topical treatment group to those receiving oral finasteride, lower treatment adherence was reported, along with higher rates of local adverse events; no difference was found in the incidence of sexual adverse events. CONCLUSION: Based on patient-reported outcomes, topical finasteride/minoxidil seems to be effective and well tolerated, but not superior to oral finasteride. Lower treatment adherence for topical usage must be considered when considering treatment options. Additional real-world data are needed to further evaluate the efficacy and safety of topical finasteride/minoxidil.

Patient-reported treatment outcomes and safety of direct-to-consumer teledermatology for finasteride treatment in male androgenetic alopecia: A cross-sectional study.

Objective: The use of direct-to-consumer (DTC) teledermatology platforms has increased, particularly for androgenetic alopecia (AGA). However, little is known about the efficacy and safety of these platforms. This study aimed to investigate the patient-reported treatment outcomes and safety of DTC teledermatology for the finasteride treatment of male AGA. Methods: This retrospective, cross-sectional study used data from a German DTC platform for finasteride treatment between December 2021 and January 2023. Patient-reported outcomes were collected through voluntary follow-up questionnaires provided to the patients six weeks after the first prescription to assess treatment outcomes and safety. Results: Data collection included 2269 patients. Of all patients who answered the follow-up questionnaire (n = 191), 79% (150 out of 191) self-reported positive changes in hair appearance, and 59% (113 out of 191) reported an improvement in self-esteem under treatment. Patients with self-reported positive changes in hair appearance were more likely to report improved self-esteem (P < 0.0001). Treatment-related adverse events occurred in 12% (22 out of 191) of the patients. Full treatment adherence was reported in 87% (167 out of 191) of patients. Conclusion: From the patient's perspective, DTC teledermatology has the potential to improve hair appearance and self-esteem. Our results suggest that it may be an effective and safe treatment option for men with AGA, justifying low-threshold access. However, treatment-related adverse events should be closely monitored during follow-up. Further studies are required to evaluate the long-term effects of the DTC teledermatology treatment. By collecting real-world data, teledermatology platforms could be useful beyond their primary focus and could play an important role in the context of future research.

Assessment of Patient Risk Profiles by a Male Sexual Health Direct-to-Consumer Prescription Platform: A Cross-Sectional Study.

Background: Direct-to-consumer (DTC) online prescription platforms (OPP) for sexual health represent a potential paradigm shift in the diagnosis and treatment for sexual dysfunctions in the way men seek care. Knowledge of patients' risk profile using these platforms is limited. Aim: To assess risk profiles of patients reaching out to health care professionals through their DTC. Methods: Anonymized data originally collected between February 2021 to May 2022 by a DTC platform in the men's health care space were retrospectively analyzed. Data included the content of patient requests through a communication function, as well as the corresponding responses by the attending physician on staff. Each request was then assessed by two independent urologists and categorized by the level of the risk profile as well as the need to refer the patient to further medical evaluation. Results: Of 585 patient requests, 531 (90.8%) were classified as low risk. In the high-risk group, 32 patients were recommended to schedule an urgent appointment at a specialist. Only three patients (0.5%) were advised to seek emergency care. The overall referral rate for both risk groups was 52.3%. The requests of 279 patients (47.7%) were assessed as digitally treatable. Almost all patients who were digitally treatable were low risk. Side effects accounted for only 9.6% of all requests in the low-risk group, compared with 46.3% in the high-risk group. Conclusion: Overall, low-risk levels in the requests of patients using a DTC platform were reported, with almost half of them suitable to be solved digitally, whereas the other half required referral to an in-person specialist.

Online Traffic Analysis of Direct-to-Consumer Websites for Hair Loss Treatment and Characterization of Finasteride Patients on a Platform in Germany: A Potential Paradigm Shift in the Treatment of Androgenetic Alopecia.

Purpose: The number of online prescription platforms (OPPs) offering telemedical diagnosis and treatment, including finasteride, for androgenetic alopecia (AA) by using medical questionnaires (MQs) has increased. This type of care delivery differs completely from traditional forms. This study aimed to investigate a potential paradigm shift in AA treatment by measuring the extent of traffic generated by OPPs that exclusively treat AA and furthermore by characterizing sociodemographic features of men undergoing finasteride treatment from an OPP in Germany. Patients and Methods: Examination of three OPPs (Keeps, Shapiro MD, Myspring), offering finasteride treatment via MQ between Q1 2018 and Q1 2022 was performed by using SEMRush, a marketing software platform for traffic analysis. Further data regarding sociodemographic characteristics were collected from Myspring by recruiting men with AA who obtained finasteride prescriptions between March 2021 and January 2022. Results: A high number of unique quarterly visitors was recorded. The number of visitors increased on all platforms (Keeps 846%, Shapiro MD 109%, Myspring 427%). Most patients had accessed the platforms from mobile devices. Further data from Myspring included a total of 2904 men. Of all patients who answered the follow-up questionnaire (n = 177), 33.9% had been referred to the platform by television advertising. Of all respondents, 21.5% reported a monthly net income below 1000 euros. 45.2% of responding patients reported being single, while 15.3% considered themselves homosexual, and 4.5% bisexual. Convenience was the most common reason indicated for using an OPP (79.1%). Conclusion: The tremendous increase in the number of visits to OPPs for AA suggests a paradigm shift in medical care, particularly regarding MQ-based finasteride treatment. Sociodemographic data and reasons for platform use suggest that the shift away from traditional care models may increase in the future. The broad use of these digital health services warrants further investigation, particularly regarding patient safety.

Direct-to-Consumer Teledermatology in Germany: A Retrospective Analysis of 1,999 Teleconsultations Suggests Positive Impact on Patient Care.

Background: There is a high demand for dermatological care in Germany. As use of teledermatology has increased significantly, this study aimed to investigate the impact of teledermatology on patient care. Methods: This retrospective cross-sectional study used data from a direct-to-consumer teledermatology platform using store-and-forward technology available in Germany between July 2021 and April 2022. Additional patient characteristics were collected using a voluntary follow-up questionnaire, 28 days after teleconsultation. Results: Data of 1,999 enrolled patients were evaluated. Patients had a mean age of 36 years, and 61.2% (1,223/1,999) lived in a rural residence. The most common diagnoses included eczema (36.0%, 701/1,946), fungal diseases (15.4%, 299/1,946), and acne (12.5%, 243/1,946). The follow-up questionnaire was answered by 166 patients (8.3%, 166/1,999). In total, 42.8% (71/166) of patients had undergone no previous medical consultation. The most frequent reason for using teledermatology was the waiting time for a dermatology outpatient appointment (62.0%, 103/166). A total of 62.0% (103/166) participants rated the treatment success as good or very good, while 86.1% (143/166) rated the quality of telemedical care as equal or better to that of an outpatient visit. Conclusion: This study showed that patients often use teledermatology because of functional barriers (waiting times). In this cohort, the diagnoses strongly corresponded to reasons for outpatient presentation. Most patients rated the quality of teledermatology service as at least equivalent to that of outpatient physician visits and reported treatment success. Thus, teledermatology can relieve the burden of outpatient care while providing high benefits from the patient's perspective.

Tetra-aqua-dodekakis-µ2-chlorido-di-iodido-octa-hedro-hexa-niobium(12 Nb-Nb) tetra-hydro-furan octa-solvate.

The title compound, [Nb6Cl12I2(H2O)4]·8THF (THF is tetra-hydro-furan, C4H8O), comprises an uncharged niobium cluster unit surrounded by THF solvent mol-ecules. The edges of the {Nb6} octa-hedron are µ 2-coordinated by twelve chlorido ligands. Four in-plane (equatorial plane) aqua ligands and two iodido ligands coordinating above and below the plane are bound at the corners of the {Nb6} atomic octa-hedron. O-H⋯O hydrogen bonds are formed between the aqua ligands and the THF solvent mol-ecules; one THF molecule is disordered over two positions with the major component having a site occupancy of 0.64 (2).

Cluster Compounds with Oxidised, Hexanuclear [Nb6 Cli 12 Ia 6 ]n- Anions (n=2 or 3).

Four mixed-halide cluster salts with chloride-iodide-supported octahedral Nb6 metal atoms cores were prepared and investigated. The cluster anions have the formula [Nb6 Cli 12 Ia 6 ]n- with Cl occupying the inner ligand sites and I the outer one. They are one- or two-electron-oxidized (n=2 or 3) with respect to the starting material cluster. (Ph4 P)+ and (PPN)+ function as counter cations. The X-ray structures reveal a mixed occupation of the outer sites for only one compound, (PPN)3 [Nb6 Cli 12 Ia 5.047(9) Cla 0.953 ]. All four compounds are obtained in high yield. If in the chemical reactions a mixture of acetic anhydride, CH2 Cl2 , and trimethylsilyl iodide is used, the resulting acidic conditions lead to form the two-electron-oxidised species (n=2) with 14 cluster-based electrons (CBEs). If only acetic anhydride is used, the 15 CBE species (n=3) is obtained in high yield. Interesting intermolecular bonding is found in (Ph4 P)2 [Nb6 Cli 12 Ia 6 ] ⋅ 4CH2 Cl2 with I⋅⋅⋅I halogen bonding and π-π bonding interactions between the phenyl rings of the cations in (PPN)3 [Nb6 Cli 12 Ia 5.047(9) Cla 0.953 ]. The solubility of (Ph4 P)2 [Nb6 Cli 12 Ia 6 ] ⋅ 4CH2 Cl2 has been determined qualitatively in a variety of solvents, and good solubility in the aprotic solvents CH3 CN, THF and CH2 Cl2 has been found.

Self-Explaining Social Robots: An Explainable Behavior Generation Architecture for Human-Robot Interaction.

In recent years, the ability of intelligent systems to be understood by developers and users has received growing attention. This holds in particular for social robots, which are supposed to act autonomously in the vicinity of human users and are known to raise peculiar, often unrealistic attributions and expectations. However, explainable models that, on the one hand, allow a robot to generate lively and autonomous behavior and, on the other, enable it to provide human-compatible explanations for this behavior are missing. In order to develop such a self-explaining autonomous social robot, we have equipped a robot with own needs that autonomously trigger intentions and proactive behavior, and form the basis for understandable self-explanations. Previous research has shown that undesirable robot behavior is rated more positively after receiving an explanation. We thus aim to equip a social robot with the capability to automatically generate verbal explanations of its own behavior, by tracing its internal decision-making routes. The goal is to generate social robot behavior in a way that is generally interpretable, and therefore explainable on a socio-behavioral level increasing users' understanding of the robot's behavior. In this article, we present a social robot interaction architecture, designed to autonomously generate social behavior and self-explanations. We set out requirements for explainable behavior generation architectures and propose a socio-interactive framework for behavior explanations in social human-robot interactions that enables explaining and elaborating according to users' needs for explanation that emerge within an interaction. Consequently, we introduce an interactive explanation dialog flow concept that incorporates empirically validated explanation types. These concepts are realized within the interaction architecture of a social robot, and integrated with its dialog processing modules. We present the components of this interaction architecture and explain their integration to autonomously generate social behaviors as well as verbal self-explanations. Lastly, we report results from a qualitative evaluation of a working prototype in a laboratory setting, showing that (1) the robot is able to autonomously generate naturalistic social behavior, and (2) the robot is able to verbally self-explain its behavior to the user in line with users' requests.

Digital Real-world Data Suggest Patient Preference for Tadalafil over Sildenafil in Patients with Erectile Dysfunction.

BACKGROUND: Erectile dysfunction (ED) is a major care problem worldwide. Tadalafil and sildenafil are the two most common phosphodiesterase-5 inhibitors (PDE5is) used to treat ED. OBJECTIVE: This study aimed to evaluate patient data of a large online prescription platform (OPP), specifically analyzing preference for tadalafil over sildenafil. DESIGN, SETTING, AND PARTICIPANTS: Data from a prospectively collected German OPP were retrospectively analyzed. This dataset included patients with a history of taking one or both substances (n = 26 821). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ED patient baseline characteristics were derived from medical questionnaires for PDE5i prescriptions between May 2019 and May 2020. Order behavior was analyzed in patients who ordered both substances over time. We applied Kruskal-Wallis tests, χ² tests, and fisher's exact tests for statistical analysis. RESULTS AND LIMITATIONS: Baseline characteristics were comparable for both PDE5is in patients with a median age of 49 yr (sildenafil [interquartile range {IQR} 38-57]; tadalafil [IQR 39-56]), a median body mass index (BMI) of 26 kg/m² (sildenafil [IQR 24.54-29.03]; tadalafil [IQR 24.49-28.69]), ED onset time of >12 mo (sildenafil [87%]; tadalafil [88%]), and the presence of morning erections (sildenafil [62%]; tadalafil [61%]). Tadalafil prescriptions increased significantly from 30% (first order) to 80% (last order) in patients who had already tested both drugs. Patients with age ≤40 yr, BMI ≤25 kg/m², and sustained morning erections preferred tadalafil to sildenafil. CONCLUSIONS: Using database information from an OPP, preference for tadalafil was shown for patients who had tested both PDE5is. This preference was particularly pronounced in patients with age ≤40 yr, BMI ≤25 kg/m², and sustained morning erections. A well-managed OPP can be used for research on more complex health services. PATIENT SUMMARY: Analysis of large online prescription platforms provide the benefit of identifying young treatment-naïve patients with early-stage disease, which is highlighted by the fact that about two-thirds of our patients analyzed still maintained spontaneous morning erections. Patients who had tested tadalafil once developed preference for this drug.

Hexa-aqua-dodeca-µ2-iodido-octahedro-hexa-tantalum diiodide tetra-hydrate.

In the crystal structure of the cluster salt, [Ta6I12(H2O)6]I2·4H2O, the octa-hedral {Ta6} cluster core is µ2-coordinated by twelve iodido ligands (inner ligand sphere) whereas the six aqua ligands coordinate each at the six outer positions. The discrete, inversion-symmetric cluster complex is double-positively charged, and two iodide anions are present in the crystal structure as counter-ions. In addition, four water mol-ecules are co-crystallized. Hydrogen bonds between the cluster unit, the iodide anions and co-crystallized water mol-ecules stabilize the charge-assisted packing in the crystal structure.

Hexa-aquadodeca-µ2-chlorido-octa-hedro-hexa-niobium diiodide.

The title compound, [Nb6Cl12(H2O)6]I2, consists of the niobium cluster cation [Nb6Cl12(H2O)6]2+ and two non-coordinating, charge-balancing iodide ions. The edges of the Nb6 octa-hedron are bridged by chlorido ligands. Each Nb atom is further coordinated by a water ligand. The cluster cation has a charge of +2, which is balanced by that of two iodide anions.

Aclonifen targets solanesyl diphosphate synthase, representing a novel mode of action for herbicides.

BACKGROUND: Aclonifen is a unique diphenyl ether herbicide. Despite its structural similarities to known inhibitors of the protoporphyrinogen oxidase (e.g. acifluorfen, bifenox or oxadiazon), which result in leaf necrosis, aclonifen causes a different phenotype that is described as bleaching. This also is reflected by the Herbicide Resistance Action Committee (HRAC) classification that categorizes aclonifen as an inhibitor of pigment biosynthesis with an unknown target. RESULTS: A comprehensive Arabidopsis thaliana RNAseq dataset comprising 49 different inhibitor treatments and covering 40 known target pathways was used to predict the aclonifen mode of action (MoA) by a random forest classifier. The classifier predicts for aclonifen a MoA within the carotenoid biosynthesis pathway similar to the reference compound norflurazon that inhibits the phytoene desaturase. Upon aclonifen treatment, the phytoene desaturation reaction is disturbed, resulting in a characteristic phytoene accumulation in vivo. However, direct enzyme inhibition by the herbicide was excluded for known herbicidal targets such as phytoene desaturase, 4-hydroxyphenylpyruvate dioxygenase and homogentisate solanesyltransferase. Eventually, the solanesyl diphosphate synthase (SPS), providing one of the two homogentisate solanesyltransferase substrate molecules, could be identified as the molecular target of aclonifen. Inhibition was confirmed using biochemical activity assays for the A. thaliana SPSs 1 and 2. Furthermore, a Chlamydomonas reinhardtii homolog was used for co-crystallization of the enzyme-inhibitor complex, showing that one inhibitor molecule binds at the interface between two protein monomers. CONCLUSION: Solanesyl diphosphate synthase was identified as the target of aclonifen, representing a novel mode of action for herbicides. © 2020 Society of Chemical Industry.

A molecular movie of ultrafast singlet fission.

The complex dynamics of ultrafast photoinduced reactions are governed by their evolution along vibronically coupled potential energy surfaces. It is now often possible to identify such processes, but a detailed depiction of the crucial nuclear degrees of freedom involved typically remains elusive. Here, combining excited-state time-domain Raman spectroscopy and tree-tensor network state simulations, we construct the full 108-atom molecular movie of ultrafast singlet fission in a pentacene dimer, explicitly treating 252 vibrational modes on 5 electronic states. We assign the tuning and coupling modes, quantifying their relative intensities and contributions, and demonstrate how these modes coherently synchronise to drive the reaction. Our combined experimental and theoretical approach reveals the atomic-scale singlet fission mechanism and can be generalized to other ultrafast photoinduced reactions in complex systems. This will enable mechanistic insight on a detailed structural level, with the ultimate aim to rationally design molecules to maximise the efficiency of photoinduced reactions.

Non-equilibrium relaxation of hot states in organic semiconductors: Impact of mode-selective excitation on charge transfer.

The theoretical study of open quantum systems strongly coupled to a vibrational environment remains computationally challenging due to the strongly non-Markovian characteristics of the dynamics. We study this problem in the case of a molecular dimer of the organic semiconductor tetracene, the exciton states of which are strongly coupled to a few hundreds of molecular vibrations. To do so, we employ a previously developed tensor network approach, based on the formalism of matrix product states. By analyzing the entanglement structure of the system wavefunction, we can expand it in a tree tensor network state, which allows us to perform a fully quantum mechanical time evolution of the exciton-vibrational system, including the effect of 156 molecular vibrations. We simulate the dynamics of hot states, i.e., states resulting from excess energy photoexcitation, by constructing various initial bath states, and show that the exciton system indeed has a memory of those initial configurations. In particular, the specific pathway of vibrational relaxation is shown to strongly affect the quantum coherence between exciton states in time scales relevant for the ultrafast dynamics of application-relevant processes such as charge transfer. The preferential excitation of low-frequency modes leads to a limited number of relaxation pathways, thus "protecting" quantum coherence and leading to a significant increase in the charge transfer yield in the dimer structure.

Erratum: Tensor Network Simulation of Non-Markovian Dynamics in Organic Polaritons [Phys. Rev. Lett. 121, 227401 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.121.227401.

Tensor network simulation of multi-environmental open quantum dynamics via machine learning and entanglement renormalisation.

The simulation of open quantum dynamics is a critical tool for understanding how the non-classical properties of matter might be functionalised in future devices. However, unlocking the enormous potential of molecular quantum processes is highly challenging due to the very strong and non-Markovian coupling of 'environmental' molecular vibrations to the electronic 'system' degrees of freedom. Here, we present an advanced but general computational strategy that allows tensor network methods to effectively compute the non-perturbative, real-time dynamics of exponentially large vibronic wave functions of real molecules. We demonstrate how ab initio modelling, machine learning and entanglement analysis can enable simulations which provide real-time insight and direct visualisation of dissipative photophysics, and illustrate this with an example based on the ultrafast process known as singlet fission.

Tensor Network Simulation of Non-Markovian Dynamics in Organic Polaritons.

We calculate the exact many-body time dynamics of polaritonic states supported by an optical cavity filled with organic molecules. Optical, vibrational, and radiative processes are treated on an equal footing employing the time-dependent variational matrix product states algorithm. We demonstrate signatures of non-Markovian vibronic dynamics and its fingerprints in the far-field photon emission spectrum at arbitrary light-matter interaction scales, ranging from the weak to the strong coupling regimes. We analyze both the single- and many-molecule cases, showing the crucial role played by the collective motion of molecular nuclei and dark states in determining the polariton dynamics and the subsequent photon emission.

Publisher Correction: Studying light-harvesting models with superconducting circuits.

The original HTML version of this Article contained an error in the second mathematical expression in the fourth sentence of the fourth paragraph of the 'Excitation transfer with uniform white noise' section of the Results. This has been corrected in the HTML version of the Article.The original PDF version of this Article incorrectly stated that 'Correspondence and requests for materials should be addressed to A. Pcn.', instead of the correct 'Correspondence and requests for materials should be addressed to A. Potocnik'. This has been corrected in the PDF version of the Article.

Studying light-harvesting models with superconducting circuits.

The process of photosynthesis, the main source of energy in the living world, converts sunlight into chemical energy. The high efficiency of this process is believed to be enabled by an interplay between the quantum nature of molecular structures in photosynthetic complexes and their interaction with the environment. Investigating these effects in biological samples is challenging due to their complex and disordered structure. Here we experimentally demonstrate a technique for studying photosynthetic models based on superconducting quantum circuits, which complements existing experimental, theoretical, and computational approaches. We demonstrate a high degree of freedom in design and experimental control of our approach based on a simplified three-site model of a pigment protein complex with realistic parameters scaled down in energy by a factor of 105. We show that the excitation transport between quantum-coherent sites disordered in energy can be enabled through the interaction with environmental noise. We also show that the efficiency of the process is maximized for structured noise resembling intramolecular phononic environments found in photosynthetic complexes.

Novel allelic variants in ACD6 cause hybrid necrosis in local collection of Arabidopsis thaliana.

Hybrid necrosis is a common type of hybrid incompatibility in plants. This phenomenon is caused by deleterious epistatic interactions, resulting in spontaneous activation of plant defenses associated with leaf necrosis, stunted growth and reduced fertility in hybrids. Specific combinations of alleles of ACCELERATED CELL DEATH 6 (ACD6) have been shown to be a common cause of hybrid necrosis in Arabidopsis thaliana. Increased ACD6 activity confers broad-spectrum resistance against biotrophic pathogens but reduces biomass production. We generated 996 crosses among individuals derived from a single collection area around Tübingen (Germany) and screened them for hybrid necrosis. Necrotic hybrids were further investigated by genetic linkage, amiRNA silencing, genomic complementation and metabolic profiling. Restriction site associated DNA (RAD)-sequencing was used to understand genetic diversity in the collection sites containing necrosis-inducing alleles. Novel combinations of ACD6 alleles found in neighbouring stands were found to activate the A. thaliana immune system. In contrast to what we observed in controlled conditions, necrotic hybrids did not show reduced fitness in the field. Metabolic profiling revealed changes associated with the activation of the immune system in ACD6-dependent hybrid necrosis. This study expands our current understanding of the active role of ACD6 in mediating trade-offs between defense responses and growth in A.  thaliana.