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This paper introduces a modular simulation testbed developed for decision support in logistics and urban planning within the tourism sector, specifically applied to Şanlıurfa, Turkey, as part of the GeostaloVR project. The testbed integrates tourism value chains, urban development processes, and mobility flows to facilitate scenario testing and evaluation. By incorporating real-world data, the simulation framework enables the analysis of key performance indicators for sustainable urban tourism development. This approach aims to advance the application of modeling techniques to address complex challenges in urban tourism in order to provide valuable insights for stakeholders involved in urban and logistics planning.

The department of Medical Informatics of the University Hospital Münster and the Gesakon GmbH (an university offspring) initiated the cooperative development of an electronic health record (EHR) called "akteonline.de" in 2000. From 2001 onwards several clinics of the university hospital have already offered this EHR (within pilot projects) as an additional service to selected subsets of their patients. Based on the experiences of those pilot projects the system architecture and the basic data model underwent several evolutionary enhancements, e.g. implementations of electronic interfaces to other clinical systems (considering for example data interchange methods like the Clinical Document Architecture - standardized within the HL7 group - and also interfacing architectures of German GP systems, such as VCS and D2D). "akteonline.de" in its current structure supports patients as well as health care professionals and aims at providing a collaborative health information system which perfectly supports the clinical workflow even across institutional boundaries and including the patient himself. Since such an EHR needs to strictly fulfill high data security and data protection requirements, a complex authorization and access control component has been included. Furthermore the EHR data are encrypted within the database itself and during their transfer across the internet.

Conformer–rotamer sampling tool (CREST) is an open-source program for the efficient and automated exploration of molecular chemical space. Originally developed in Pracht et al. [Phys. Chem. Chem. Phys. 22, 7169 (2020)] as an automated driver for calculations at the extended tight-binding level (xTB), it offers a variety of molecular- and metadynamics simulations, geometry optimization, and molecular structure analysis capabilities. Implemented algorithms include automated procedures for conformational sampling, explicit solvation studies, the calculation of absolute molecular entropy, and the identification of molecular protonation and deprotonation sites. Calculations are set up to run concurrently, providing efficient single-node parallelization. CREST is designed to require minimal user input and comes with an implementation of the GFNn-xTB Hamiltonians and the GFN-FF force-field. Furthermore, interfaces to any quantum chemistry and force-field software can easily be created. In this article, we present recent developments in the CREST code and show a selection of applications for the most important features of the program. An important novelty is the refactored calculation backend, which provides significant speed-up for sampling of small or medium-sized drug molecules and allows for more sophisticated setups, for example, quantum mechanics/molecular mechanics and minimum energy crossing point calculations. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome coronavirus (MERSCoV) circulates in dromedary camels in the Arabian Peninsula and occasionally causes spillover infections in humans. MERS-CoV diversity is poorly understood because of the lack of sampling during the COVID-19 pandemic. We collected 558 swab samples from dromedary camels in Saudi Arabia during November 2023-January 2024. We found 39% were positive for MERS-CoV RNA by reverse transcription PCR. We sequenced 42 MERSCoVs and 7 human 229E-related coronaviruses from camel swab samples by using high-throughput sequencing. Sequences from both viruses formed monophyletic clades apical to recently available genomes. MERS-CoV sequences were most similar to B5 lineage sequences and harbored unique genetic features, including novel amino acid polymorphisms in the spike protein. Further characterization will be required to understand their effects. MERS-CoV spillover into humans poses considerable public health concerns. Our findings indicate surveillance and phenotypic studies are needed to identify and monitor MERS-CoV pandemic potential. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract. In contrast, two bat sarbecovirus S proteins drove cell entry in an ACE2-independent, trypsin-dependent fashion and several ACE2-dependent S proteins could switch to the ACE2-independent entry pathway when exposed to trypsin. Several TMPRSS2-related cellular proteases but not the insertion of a multibasic cleavage site into the S protein allowed for ACE2-independent entry in the absence of trypsin and may support viral spread in the respiratory tract. Finally, the pan-sarbecovirus antibody S2H97 enhanced cell entry driven by two S proteins and this effect was reversed by trypsin while trypsin protected entry driven by a third S protein from neutralization by S2H97. Similarly, plasma from quadruple vaccinated individuals neutralized entry driven by all S proteins studied, and availability of the ACE2-independent, trypsin-dependent pathway reduced neutralization sensitivity. In sum, our study reports a pathway for entry into human cells that is ACE2-independent, can be supported by TMPRSS2-related proteases and may be associated with antibody evasion. Author summary: Bats host a wide range of coronaviruses, including those related to SARS-CoV-1 and SARS-CoV-2 (subgenus Sarbecovirus), but their ability to infect human cells remains poorly understood. Identifying sarbecoviruses with zoonotic potential and understanding the factors controlling their entry into human cells are crucial for risk assessment and antiviral development. In this study, we examined how bat sarbecovirus spike proteins facilitate entry into human cells and identified key host factors involved. Using pseudovirus particles, we show that several bat sarbecovirus spike proteins use human and animal ACE2 receptors for entry. Additionally, we confirm that some spike proteins utilize an ACE2-independent entry pathway requiring trypsin treatment and demonstrate that this process is controlled by the spike protein receptor binding domain. Furthermore, we reveal that a subset of ACE2-using bat sarbecovirus spike proteins can switch to ACE2-independent entry following trypsin exposure and show that certain human type II transmembrane serine proteases can substitute for trypsin, enabling ACE2-independent entry. Finally, we demonstrate that repeated COVID-19 vaccination generates cross-neutralizing activity against bat sarbecoviruses, though ACE2-independent entry reduces neutralization sensitivity. [ABSTRACT FROM AUTHOR]

Many low-cost or semiempirical quantum mechanical-based electronic structure methods suffer from the use of unpolarized minimal atomic orbital (AO) basis sets. In this work, we overcome this limitation by a fully DFT variationally optimized, adaptive minimal basis set consistently available for the elements up to radon (Z = 86). The new key feature is to make the linear coefficients of the primitive Gaussians in a contracted AO dependent on the effective atomic charge of the atom in the molecule, i.e., each symmetry-unique atom obtains its "own" specifically adapted basis functions. In this way, the physically important "breathing" of the AOs in a molecule with (a) atomic charge (expansion/contraction for anionic/cationic states) and (b) the number of close-lying bonded neighbor atoms is accounted for. The required atomic charges are obtained from a specially developed extended Hückel type Hamiltonian and the coordination numbers from the molecule geometry. Proper analytical derivatives of the resulting adaptive basis functions can easily be derived. Moreover, the basis functions are electric field-dependent, thus improving the description of, e.g., dipole moments and polarizabilities. The new basis set termed q-vSZP (charge dependent valence single-ζ, polarized) is thoroughly benchmarked for atomic/molecular and thermochemical properties compared to standard minimal and double-ζ basis sets at the DFT level with the accurate ωB97X-D4 functional. It is shown that q-vSZP is clearly superior to existing minimal basis sets, often reaching double-ζ quality or even better results. We expect it to be the optimal choice in future semiempirical quantum mechanical methods. [ABSTRACT FROM AUTHOR]

Decision-making in supply chains is challenged by high complexity, a combination of continuous and discrete processes, integrated and interdependent operations, dynamics, and adaptability. The rapidly increasing data availability, computing power and intelligent algorithms unveil new potentials in adaptive data-driven decision-making. Reinforcement Learning, a class of machine learning algorithms, is one of the data-driven methods. This semi-systematic literature review explores the current state of the art of reinforcement learning in supply chain management (SCM) and proposes a classification framework. The framework classifies academic papers based on supply chain drivers, algorithms, data sources, and industrial sectors. The conducted review revealed a few critical insights. First, the classic Q-learning algorithm is still the most popular one. Second, inventory management is the most common application of reinforcement learning in supply chains, as it is a pivotal element of supply chain synchronisation. Last, most reviewed papers address toy-like SCM problems driven by artificial data. Therefore, shifting to industry-scale problems will be a crucial challenge in the next years. If this shift is successful, the vision of data-driven decision-making in real-time could become a reality. [ABSTRACT FROM AUTHOR]

Background: Brain biopsy is required for the accurate specification and further diagnosis of intracranial findings. The conventional stereotactic frames are used clinically for biopsies and offer the highest possible precision. Unfortunately, they come with some insurmountable technical and logistical limitations. The aim of the present work is to determine the clinical precision in the needle biopsy of the human brain using a new patient-specific stereotactic navigation device based on 3D printing. Methods: MRI data sets of human cadaver heads were used to plan 32 intracranial virtual biopsy targets located in different brain regions. Based on these data, 16 individualized stereotactic frames were 3D-printed. After the intraoperative application of the stereotactic device to the cadaver's head, the actual needle position was verified by postoperative CT. Results: Thirty-two brain areas were successfully biopsied. The target point accuracy was 1.05 ± 0.63 mm, which represents the difference between the planned and real target points. The largest target point deviation was in the coronal plane at 0.60 mm; the smallest was in the transverse plane (0.45 mm). Conclusions: Three-dimensional-printed, personalized stereotactic frames or platforms are an alternative to the commonly used frame-based and frameless stereotactic systems. They are particularly advantageous in terms of accuracy, reduced medical imaging, and significantly simplified intraoperative handling. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019.sup.1,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses.sup.3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung.sup.2,4; the same receptor tropism is thought to have determined the pathogenicity--but also aided in the control--of severe acute respiratory syndrome (SARS) in 2003.sup.5. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission.sup.6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 10.sup.8 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples--in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19. Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract., Author(s): Roman Wölfel [sup.1] , Victor M. Corman [sup.2] , Wolfgang Guggemos [sup.3] , Michael Seilmaier [sup.3] , Sabine Zange [sup.1] , Marcel A. Müller [sup.2] , Daniela Niemeyer [sup.2] [...]