Institut Fizik Malaysia, IFM) was formed on January 29, 1973, and celebrates its golden jubilee this year. This article briefly traces the formation of IFM against the backdrop of physics in Malaysia, highlights some of the achievements and sketches possible future directions of IFM.This year, 2023, marks a significant milestone in the history of physics in Malaysia. The Malaysian Institute of Physics . Physics was offered as a degree programme in UM from 1961. Shortly thereafter, degree programs in physics began to be offered in Institut Teknologi MARA , Universiti Sains Malaysia , Universiti Kebangsaan Malaysia , Universiti Putra Malaysia  and Universiti Teknologi Malaysia .A recent article  highlighAs the number of physicists in Malaysia grew steadily in the early 1960s, a desire arose for a body to represent the physics community. Although some physicists in local universities were members of the Institute of Physics (United Kingdom), many physicists, teachers and those in the research and service sectors were not. This shortcoming began to be rectified when the first interim committee met in Kuala Lumpur in 1971 with the objective of setting up IFM. The institute’s constitution was drafted and approved by the Registrar of Societies, which enabled the process to proceed.Written documentation preceding the formation of IFM is scarce; however, the IFM Constitution indicates the priorities that the framers had. These are (1) to promote physics and elevate the profession of physicists, (2) to educate and train those who wish to practice as physicists, and those who are interested in physics, (3) to hold meetings/conferences, workshops and to deliver lectures, and (4) to organize activities of interest to IFM members related to research, education, and outreach programs.Universiti Malaya (UM), Universiti Sains Malaysia (USM), Universiti Kebangsaan Malaysia (UKM), Agricultural College Serdang , Tunku Abdul Rahman College  and Mara Institute of Technology , there was representation from the Meteorological Department, Defence Research Centre, Radioisotope Unit of Universiti Hospital , National Institute for Scientific and Industrial Research (NISIR), and Cochrane Road School. It is noteworthy that the diversity of the meeting attendees reflected the breadth of the impact of physics in the academic realm as well as in industrial research.The inaugural general meeting of the IFM was held on January 29, 1973, at UM with 34 members. Apart from representation from The inaugural IFM Council comprised Prof. Thong Saw Pak , Prof. Chatar Singh , Dr. Neo Yee Pan , Dr. Tan Hong Siang , with the following council members: Dr. Khalijah Mohd. Salleh (UKM), Prof. Khaik Leang Lim (UM), Dr. Teh Hock Heng (UM), Dr. R. Ratnalingam (USM) and Dr. Lee Sing (UM). Altogether, there have been seven presidents: Prof. Thong Saw Pak , Prof. Chatar Singh (1976–1977), Prof. Mohd. Zawawi Ismail , Prof. Tan Beng Cheok , Prof. Chia Swee Ping , Prof. Kurunathan Ratnavelu  and Prof. Tou Teck Yong . (Note: Prof. Lee Sing served as the acting president for some months in 1990.)https://ifm.org.my/.Since its inception, IFM has operated from the Department of Physics, UM. Starting with an initial 34 members in 1973, growth was slow but began to accelerate in the 1980s. To date, IFM has approximately 1530 members, of which 550 are active. IFM has nine Honorary Fellows and 54 Fellows. The IFM webpage is Persidangan Fizik Kebangsaan (PERFIK). Due to the Covid-19 pandemic, the most recent conferences, i.e., PERFIK 2021 and PERFIK 2022, were conducted online. It has been a valuable experience to have to rely solely on internet technologies. While it has been advantageous in widening participation, a purely online conference has come at a cost of a reduction in face-to-face interaction. Nevertheless, it is likely that some form of hybrid conference, workshop and meeting may become a new norm in the future.IFM has co-organised a physics conference or symposium annually since 1975. It was initially known as the National Physics Symposium (NAPS) and is now more widely known as Periodically, international events such as the International Conference on Frontiers in Quantum Physics 1997) , the Int , the InJurnal Fizik Malaysia (JFM) since 1984, succeeding the Bulletin of the Institute of Physics, Malaysia, which was launched in 1980. Up until 2020, it appeared in print form but is now published solely online. Jurnal Fizik Malaysia is now indexed by Clarivate Analytics Emerging Sources Citation Index (ESCI). Information regarding submissions to JFM can be found at https://ifm.org.my/jurnal.IFM has also published the Universiti Kebangsaan Malaysia, and by members of the IFM Education Subgroup. Five students are shortlisted to represent the country. Throughout the years of participation, Malaysian students have received honorable mention, bronze, silver, and gold medals. The students have benefited greatly from the exposure gained from the competition. Many have continued to pursue physics degrees and other science and engineering majors, and some have become prominent scientists and researchers in their own fields.IFM has also supported the training of Malaysian high school students for the Asian and International Physics Olympiads  since the 33rd IPhO in 2002 held in Bali, Indonesia. This has enabled our top physics students to compete with the best in the world. Following a preliminary test, selected students attend several intensive camps conducted by the trainers of IFM has supported the training of young physicists in international schools via recommendations and partial financial assistance. Locally, IFM has initiated workshops and schools to train local and international physicists. Among the earliest training provided was a Workshop on Microcomputers and Applications (1981), in addition to other activities organised by IFM divisions and subgroups. IFM has two main divisions, i.e., Plasma Physics and Medical Physics. In addition to organising the Tropical College on Applied Physics  –13, the IFM is affiliated to the following organisations, as (1) a founding member of the Association of Asia Pacific Physical Societies (AAPPS), (2) a founding member of the Asia Pacific Center for Theoretical Physics (APCTP), (3) an associate council member of the Asia Oceania Forum for Synchrotron Radiation Research (AOFSRR), and (4) as a founding member of the Confederation of Scientific and Technological Associations in Malaysia (COSTAM). In addition, IFM cooperates with most other physics institutes/organizations of other countries.In its first 50 years, IFM established itself as a body supporting the interests of the local physics community through training, conferences, and the establishment of networks with the international physics communities. These can, and should, be continued. However, much remains to be done.First, the physics community in Malaysia remains rather scattered with researchers typically working independently in their respective fields with minimal collaboration between them. Working in isolation robs researchers of the rewards of synergy that would then enable more impactful work to be attempted, such as those outlined in the Sustainable Development Goals (SDGs) of the United Nations . IFM hasSecond, IFM needs to better engage with the public to increase awareness of physics. Moving beyond how physics has traditionally been presented in a classroom setting, we need to use technology creatively to bring out the beauty of physics and the excitement of discovery that lies at its heart.Third, there has been the perception that a physics degree does not appear to have a well-defined career path as opposed to, say, an engineering degree. In reality, a physics graduate is equipped with critical thinking skills and versatility so as to adapt to different career paths, whether in industry or the service sectors. IFM needs to initiate frequent engagement with industrial partners as well as more effectively organize outreach programs to schools.Finally, researchers and students interested in exciting topics in fundamental physics, for example in particle physics, black holes, and search for dark matter, have difficulty securing positions in Malaysian universities, resulting in the brain drain of these talented researchers to other countries. It remains a challenge to build up a critical mass of physicists, and IFM has a role to play to address this issue.In conclusion, the first 50 years of IFM have been eventful both for the physics community as well as for our nation. Given the increased pace of change and advances in technology, we can expect IFM to rise to these challenges and continue to support the physics community in the years ahead. Fig. .Fig. 1PaAcknowledgementsWe would like to express our thanks and appreciation to Prof. Tan Beng Cheok, Prof. Dato’ Roslan Abd. Shukor and Prof. Tou Teck Yong for their respective ideas and input in the preparation of this manuscript.Statements and declarationsThe authors declare that they have no competing interests.In conjunction with the 100th anniversary of the International Union of Pure and Applied Physics (IUPAP), members of Asia Pacific region organized a successful panel discussion at the main celebration event in Trieste on July 12, 2022. The panelists were William J. Munro , Xiaoyen Shen, Venu Gopal Achanta , Junichi Yokoyama . Below are some of the key points that emerged from the Panel discussion in Trieste.  website which is linked to the main IUPAP website. The current status is that the vendor for the development of IUPAP-AP site has been identified and approval of EC obtained for awarding contract. The partial payment to the web development company is being processed. Once that happens we would proceed with this activity.Foster close links with AAPS to better network physics community in AP region.Use the IUPAP-AP site to enable physicists in this region to organize virtual conferences with IUPAP sponsorship which obviate the need for travel which is very difficult for geopolitical and financial reasons.Encourage use of Indico to facilitate the hosting of these virtual conferences with emphasis on gender and geographical balance.Seek out the participation of eminent physicists from across the world by leveraging IUPAP sponsorship.Given the massive population and demographics the growth of physics in the AP region would be very important for the global development of physics.Therefore, the immediate recommendations are as follows:https://pcs.ibs.re.kr/ICTP_Asian_Network/ICTP_Asian_Network.html) was initially launched in 2017 and ran for the 3-year period 2017–2019. Unfortunately, due to COVID-19, the Network underwent a hiatus for 3 years from 2020 to 2022. We are now pleased to announce that, starting from 3 February, the Network is funded and relaunched to run for the 3-year period 2023–2026.The Asian Network on Condensed Matter, Complex Systems and Statistical Physics , the Asia Pacific Center for Theoretical Physics (APCTP), the Institute for Basic Science Center for Theoretical Physics of Complex Systems (PCS-IBS) and five participating Southeast Asian nodes in Vietnam, Thailand, Philippines, Indonesia, and Cambodia. Only the first three nodes were included in the first iteration of the Network and the Indonesian and Cambodian nodes were welcomed in the second expanded iteration of our Network. The ICTP and APCTP funding is provided through their various external activity programs. In principle, the ICTP funding can be extended for three more years but, ultimately, it is hoped that the Network will become self-sustaining with funding just from within Asia.Notionally, a scientific Network consists of a number of Institutes and research groups in an entire region, pursuing a common scientific project over an extended period. The network program represents an efficient approach to overcoming the problem of isolation of scientists and stimulates interaction and collaboration. The Network contributes to regional efforts to advance scientific expertise in the developing world, providing young scientists in Southeast Asia with the further training and skills they need to enjoy productive careers. In effect, the combined expertise from ICTP, APCTP, and PCS-IBS is projected into Southeast Asia.The activities of the Network include (i) scientist exchanges, (ii) an annual November School rotating between Hanoi, Nakhon Ratchasima and Manila, (iii) two annual workshops held at APCTP and PCS-IBS, and (iv) a Mini-School/Workshop to be held in Jakarta and Phnom Penh in 2024 and 2025 respectively. From 2017 through to 2019, the Network supported 12 scientist exchanges. Typically, a scientist visits more than one Institute in each supported itinerary of up to 4 weeks duration. It is expected that a similar number of scientist exchange visits will be supported between 2023 and 2026.• Boris Altshuler, Columbia University, New York, USA• Peter Fulde, Max Planck Institute, Dresden, Germany• Giuseppe Mussardo, SISSA, Trieste, Italy• Naoto Nagaosa, University of Tokyo, Tokyo, JapanOver 150 scientists and many more graduate students are participating in our Network which benefits from the guidance and input from four distinguished International Scientific Advisers:• Marcello Dalmonte, CMSP Section• Mikhail Kiselev, CMSP Section• Antonello Scardicchio, CMSP Section• Matteo Marsili, QLS SectionIn addition, valuable expertise is gained from the participation of leading ICTP scientists includingThe scientific program of this Network encompasses three disciplines with a focus on Condensed Matter Physics. Our aims are to cross-fertilize research on exciton–polariton condensates, superconducting networks, quantum dot networks, ultracold atomic gases, optical waveguide networks, topology, frustration, flatband physics, Fano resonant nanoscale devices, artificial gauge fields, dissipative quantum chaos, many body localization, quantum thermalization, quantum stochastic dynamics, targeted energy transfer, transport in nano structures, nonlinear nanophotonics, topological insulators, and more. In particular, within Condensed Matter Physics, we will focus on the following core topics of our research during the following years:• Complex condensed matter systemsNonequilibrium many-body dynamics, macroscopic degeneracies, flat bands, non-Hermitian physics, optical cavities, and machine learning, with subtopics including exciton-polariton condensates, ultracold atomic gases, photonic waveguide networks, optical microcavities, Fano resonances, spin glasses, topology, frustration, disorder, many body localization, artificial gauge fields, dissipative quantum chaos, open quantum systems, quantum many-body interactions, nonlinear dynamics, disordered systems, mesoscopic electron transport, nano-electromechanical systems.• Light-matter interaction in nanostructuresSemiconductor microcavities, exciton polaritons, quantum transport, open quantum systems, quantum coherence, dissipative solitons, quantum dots, spins in mesostructures, polariton devices .Strongly correlated electronic systems• Development of numerical algorithms to study correlated electronic systems, correlation effects in materials with strong spin–orbit coupling, computational study of spectral properties in strongly correlated systems, quantum embedding theories, dynamical mean field theory and impurity solvers.• Theoretical photonics: nonlinear optics, topological phases, non-Hermitian systems, disorder and Anderson localization, flat bands, scattering, Floquet systems, photonic lattices, solitons, and quantum optics.• Nonequilibrium quantum thermodynamicsDissipative quantum systems, quantum and classical thermodynamics, quantum thermodynamic machines, nonlinear dynamics and thermodynamic phase transitions, heat transport in molecular junctions, open Floquet systems, symmetries and metastability in open systems, and Landau-Zener open systems.• Quantum chaos in many-body systemsLate-time quantum chaos and BGS conjecture, early-time quantum chaos and operator growth, quantum batteries, many-body localization, and quantum many-body scars.• Topological and correlated quantum matterTopological and unconventional superconductivity with strong spin–orbit coupling, Moire materials and twistronics, bosonic topological phases in spin systems, nano-device applications of topological materials, aperiodic systems, and quasicrystals.• Optics of quantum fluids and nanomaterialsOptical properties of nanostructures, optical phonons in nanoparticles and Raman scattering, disorder effects on phonons in nanostructures, nonlinear aspects of lattice dynamics in nanoparticles, absorption and elastic scattering of light by nanodiamonds, quantum fluids of light, vortices and solitons dynamics, quantum turbulence, artificial photonic lattices, and effects of disorder on quantum fluid dynamics.• Superconducting hybrid quantum systemsSuperconducting hybrid nanostructures, States read-out using circuit-QED, Majorana fermions in topological superconductors, magnetic impurities in superconductors, coherent electron transport in mesoscopic systems.• Entanglement and dynamics in quantum matterFrustrated magnetism, quantum spin liquids, topological phases of matter, quantum dynamics, many-body localization, novel phases in ultra cold atoms, non-equilibrium quantum systems, quantum computing and algorithms, tensor networks, density matrix renormalization group, dynamical mean-field theory, and ab initio electronic structure computations.Although financial support from Network funds is limited to the members of the Network, all activities of the Network are open to participants from all ICTP supported (OEA) countries and all APCTP Member Countries. Lecturers that can support their own participation are particularly welcome at our Schools. Fig. .


Non-obstructive azoospermia (NOA) is considered to be the most severe form of male infertility. Before the emergence of surgical testicular sperm extraction and assisted reproductive technology, NOA patients could hardly become biological fathers of their children. However, failure of the surgery could cause physical and psychological harm to patients such as testicular damage, pain, hopeless of fertility and additional cost. Therefore, predicting the successful sperm retrieval (SSR) is so important for NOA patients to make their choice whether to do the surgery or not. Because seminal plasma is secreted by the testes and accessory gonads, it can reflect the spermatogenic environment, making it a preferential choice for SSR valuation. The purpose of this paper is to summarize the available evidence and provide the reader with a broad overview of biomarkers in seminal plasma for SSR prediction.A total of 15,390 studies were searched from PUBMED, EMBASE, CENTRAL and Web of Science, but only 6615 studies were evaluated after duplications were removed. The abstracts of 6513 articles were excluded because they were irrelevant to the topic. The full texts of 102 articles were obtained, with 21 of them being included in this review. The included studies range in quality from medium to high. In the included articles, surgical sperm extraction methods included conventional testicular sperm extraction (TESE) and microdissection testicular sperm extraction (micro-TESE). Currently, the biomarkers in seminal plasma used to predict SSR are primarily RNAs, metabolites, AMH, inhibin B, leptin, survivin, clusterin, LGALS3BP, ESX1, TEX101, TNP1, DAZ, PRM1 and PRM2.The evidence does not conclusively indicate that AMH and INHB in seminal plasma are valuable to predict the SSR. It is worth noting that RNAs, metabolites and other biomarkers in seminal plasma have shown great potential in predicting SSR. However, existing evidence is insufficient to provide clinicians with adequate decision support, and more prospective, large sample size, and multicenter trials are urgently needed. It is estimated that infertility affects 8–12% of couples globally, with a male factor being a primary or contributing cause in approximately 50% of couples –5. HistoSeminal plasma (SP) is a biological fluid made up of secretions from glands, such as testes, in the male urogenital tract. It could be a rich source of noninvasive biomarkers, including tissue-specific RNAs and proteins, where abnormal changes could directly indicate a pathological process in the testis . TherefoA search of PUBMED, EMBASE, CENTRAL and Web of Science were made for studies that compared SP biomarkers in NOA men with positive and negative surgical testicular sperm extraction Table . The seaA total of 15,390 studies were searched, but only 6615 studies were included for evaluation after duplications were removed. 6513 articles were excluded based on the abstracts irrelevant to the topic. The full texts of 102 articles were retrieved, of which 81 articles did not meet the inclusion criteria and were excluded from the review  are small noncoding RNA molecules with 18–25 nucleotides, which can regulate post translation gene expression by triggering translation inhibition or mRNA degradation. It has been confirmed that miRNAs are involved in the regulation of germ cell development and spermatogenesis , 34. Givn = 6 in each group) and fertile men (n = 6). Their results showed that high levels of hsa-miR-34b-3p and hsa-miR-34c-3p expressions were associated with successful micro-TESE. In contrast, high levels of hsa-miR-3065-3p and hsa-miR-4446-3p expressions are associated with failed micro-TESE. Furthermore, a predictive model based on these four miRNAs was developed with high predictive accuracy (AUC = 0.927). Although these SP-miRNAs need to be validated in larger cohort studies, the current results indicate that SP-miRNAs have a high potential for predicting the SSR of NOA patients.Barceló et al.  found noLong non-coding RNAs (lncRNAs) are a group of RNA transcripts with longer than 200 nucleotides and without protein-coding capacity. It was revealed that the lnc RNAs could be involved in the regulation of gene expression at the transcriptional, post-transcriptional and epigenetic levels, and chromatin remodeling. Studies have also demonstrated that lncRNAs play a critical role in spermatogenesis , 39, indCircular RNAs (circRNAs) are covalent closed-loop structures formed by front-to-tail reverse shearing of precursor mRNAs .CircRNAsP < 0.0001). Moreover, tRF-Val-AAC-010 had a higher predictive accuracy than testicular volume and serum FSH. More importantly, it was demonstrated that tRF-Val-AAC-010 can be expressed in testicular tissues of patients with NOA and participate in spermatogenesis, implying that tRF-Val-AAC-010 could be a potential SP biomarker for predicting SSR.tRNA derived small RNAs (tsRNAs), known as new regulatory small non coding RNAs, are precisely regulated by the processing of tRNA and its precursors. It has been demonstrated that tsRNAs are widely involved in large quantities of physiological and pathological processes . AccordiFollowing genomics and proteomics, metabonomics is a developed discipline that is an important part of systems biology. Gene and protein expression are closely linked, whereas metabolites can better reflect the cell environment, which is closely related to cell nutrition, the role of drugs and pollutants in the environment, and other external factors. Approximately 40,000 human metabolites have been found in the 3.0 Human Metabolome Database . At presThe Anti-Mullerian hormone (AMH), which plays an important role in the maturation and differentiation of spermatogenic cells, is expressed in Sertoli cells and it governs the regression of the Müllerian ducts of the male fetus . It is wFénichel et al.  publisheInhibin B (INHB), a glycoprotein primarily produced by Sertoli cells, has a negative correlation with gonadotropin and FSH in feedback regulation and is closely related to the degree of spermatogenesis in testicular histology . Howevern = 26). Another study [Nagata et al.  compareder study  with a lOverall, given the above contradictory results, the predictive value of SP-INHB for SSR in patients with NOA remains debatable. Randomized clinical trials with a large sample size and a multicenter design may help to clarify whether seminal plasma inhibin B contributes to SSR prediction in patients with NOA.Survivin, which can regulate apoptosis, is found in rodent testes germ cells, particularly mature spermatocytes , and a dAlthough the predictive value of SP-AMH and SP-INHB for SSR was expected, the available evidence suggests that neither SP-AMH nor SP-INHB is widely accepted as predicting SSR in men with NOA. It is worth noting that RNAs, metabolites, and other biomarkers in SP have demonstrated a high potential in predicting SSR. If the specific role of these RNAs and metabolites in spermatogenesis can be confirmed in future research and further prospective, large sample size, and multicenter trials, it will provide more powerful support for SSR prediction.


Rehabilitation is a complex intervention that takes place in a complex setting. The MeeR project (characteristics of successful rehabilitation facilities) aims to identify complex conditions of successful rehabilitation outcomes.k = 273 orthopedic rehabilitation facilities comprising n = 112,895 patients and k = 86 cardiac rehabilitation institutions comprising n = 30,299 patients based on their outcome index score by means of a league table, and (3) adjust the ranking by basic patient characteristics . In the qualitative main study, k = 6 rehabilitation facilities (orthopedic and cardiac rehabilitation centers) were recruited based on the results of the quantitative analysis: three facilities that ranked top 10% and three facilities that ranked lowest 10% of the adjusted league table. All six rehabilitation facilities were visited each for 1 week by two researchers. We conducted participant observations, expert interviews with medical and administrative leaders, group discussions with rehab team members, and group discussions with patients. Subsequently, a systematic comparison of the results of the upper and lower 10% facilities was conducted to identify those characteristics that distinguished those institutions from one another.A project with a sequential mixed-methods study design with a quantitative prestudy and a qualitative main study was applied. In the quantitative study, quality assurance data of the German Pension Insurance was used to (1) develop and compute a multifacet z-standardized outcome index based on patient-reported outcome data, (2) rank One of the three clusters of characteristics that distinguished the above and below 10% facilities related to teamwork or interdisciplinary cooperation: among others, the extent of interdisciplinary cooperation was higher in the rehabilitation facilities with a higher degree of success, the leading medical doctors were less dominant in these institutions, and there was also a more comprehensive representation of the team within team meetings, i.e., the quality and amount of interdisciplinary cooperation were higher in these institutions compared to rehabilitation facilities with a lower level of success.This project provided qualitative evidence for the role of interdisciplinary cooperation and collaborative leadership and its different facets for patient-related successful rehabilitation in orthopedic and cardiac rehabilitation. It provides valuable insights into the fabric and structure of a rehabilitation institution and a variety of target points for team development and group-leading interventions. In Germany, medical rehabilitation is mainly provided by intensive multidisciplinary complex services in rehabilitation facilities specialized in different patient groups of short-term duration  through mostly inpatient care with the option of after-care services in the community. The era of assessment and accountability  has strosuccess in a specific sense . Therefore, the question of how to explain differences among rehabilitation service organizations with regard to patient-level success remains unanswered. In preparation for our study, we have conducted a narrative review on potential relevant characteristics of rehabilitation facilities for patient success . The stcooperation and teamwork in rehabilitation clinics, which is one of the three themes identified within the larger project  and k = 80 cardiac rehabilitation facilities. Based on the results of this survey, a workshop comprising n = 23 different stakeholders of the rehabilitation field, i.e., staff members of the German Pension Insurance, CEOs of rehabilitation facilities, and representatives from quality management and research, was held to set up the theoretical perspectives for the visitation phase of our project. These included sensitizing concepts like working staff orientation and satisfaction of staff members, organization of the facility , interdisciplinary cooperation, patient orientation and satisfaction , communication and motivation, especially enhancement of motivation, philosophy of the institution and the rehabilitation concept, aspects to be considered prior and after the rehabilitation phase, and the integration and cooperation of the institution with funding bodies and regional networks. Based on quality assurance data of the German Pension Insurance , we set up case-mix-adjusted league tables ranking all rehabilitation facilities using a composite outcome index. From these league tables, we identified those clinics that belonged to the upper and lower 10% of the league table. Of 11 rehabilitation facilities contacted, we reached the respective number of k = 6 rehabilitation facilities willing to participate in the study. Research team members were blind to the results of the allocation of the clinic . (Members of the) Rehabilitation facilities were assured that their participation in the project would not be made public. They were offered a face-to-face presentation and discussion of study results relating to all six participating rehabilitation facilities.The main idea of the MeeR projectThe sampling procedure resulted in two orthopedic clinics and one cardiac rehabilitation clinic belonging to the upper 10% of the league table, and two orthopedic clinics and one cardiac rehabilitation clinic belonging to the lower 10% of the league table that were visited by two research team members for the duration of one working week. We applied a mix of qualitative research methods: a group discussion with patients, a group discussion with rehabilitation team members, an expert interview with the leading physician and the leading administrator, and participatory observations –25.post hoc based on prespecified documentation sheets. These documentation sheets consisted of a common head to label the situation, characterize time  and place , characterize people involved and their respective functions, and characterize possible specifics of the situation. This was followed by a place for open field notes related to different broad issues as defined by the sensitizing concepts (see above), e.g., communication and motivation, interdisciplinary cooperation, patient orientation and satisfaction, working staff orientation, and satisfaction of staff members. Also, a field for additional notes not fitting to the categories provided was added. Analysis of participatory observations was based on thematic analysis . In principle, there was no video or audio taping during the observations. Observations were documented analysis , 26.All group discussions and interviews were audio-taped (when possible and agreement was present) and transcribed verbatim. Group discussions with patients were conducted using a moderation guide that aimed to elicit patient-related experiences regarding different aspects of patient handling and care. Questions were focused on experiences of the initial clinical investigation, goal setting, different therapies, communication and interaction with staff members, and contacts with fellow patients. We tried to evoke self-perpetuating discussions using open questions and—possible controversial—quotations taken from prior research as points of departure. Group discussions with rehabilitation team members were set up to include all medical and therapeutic professionals and nursing and social work professionals. While we asked not to include senior physicians in the group discussions, senior physicians actually took part in every (!) staff group discussion. Questions were focused on experiences with the patients and other professionals, especially focusing on issues of interprofessional teamwork. We also used quotations from prior research as points of departure to elicit discussions among the participants. Group discussions were set up to last 90 min. Analysis of group discussions was based on thematic analysis. Also, an in-depth analysis of group discussions with rehabilitation team members was used by applying the method of documentary analysis, which is especially suitable for analyzing interactions , 23, 27.Individual expert interviews were conducted with the chief physician and the administration manager. Questions of the interview guide focused on aspects of patient orientation , philosophy of work , staff orientation , and communication and cooperation. The duration of interviews differed with regard to the time available, usually from 60 to 90 min. On one occasion, the researcher was invited to the room of the administration manager, but it turned out that he was not willing to conduct an interview, and we were not able to document the contents of our conversation. Analysis of interviews was primarily based on thematic analysis .In principle, the analysis followed an explorative approach using broader concepts to guide our questions and observations as a point of departure and, at the same time, being open to new emerging themes or topics. Analysis of the different qualitative data was conducted in four steps. First, a comprehensive thematic analysis of the data was conducted to get an overview of the different topics appearing in the data . We thenEthical approval was granted by the Ethics Committee of the Hannover Medical School.Before we move to the results relating to interdisciplinary work, we have to point out that the differences between the clinics from the upper and lower parts of the league table were not as obvious, simple, or unequivocal as might have been expected. We could not identify a single characteristic that could distinguish the different institutions. In every rehabilitation facility, we were grateful to meet staff members highly engaged in the care of their patients on a personal level. We had to delve deeper into our analysis to make the complex and sometimes subtle differences visible. They relate to three domains labeled (1) interdisciplinary cooperation; (2) rehabilitation goal setting; and (3) design of rehabilitation services in respect of patient and staff members. Within this paper, we will focus on the first domain.The involvement of team members in team meetings is more pronounced in rehabilitation facilities with higher levels of success. Team meetings are appreciated to a higher degree in these facilities.All organizations have in common that physicians represent the only professional group whose complete participation in team meetings goes without saying. Other professional groups might only be represented by means of delegates, often the leading person of the respective group. This is the case in two of the three institutions with a lower level of patient success but in none of those with an upper level of patient success. Team members who are not able to take part in the team sessions regularly criticize this type of delegation. For example, a physiotherapist from a facility with a lower level of patient success reports in a group discussion:And probably it would be good sometimes, it is, clearly, just not always possible here, I would say with eighteen therapists altogether in our team, that we can sit together within the team and take part in team meetings or case reports all together, I do favour it when those involved with the patient, when just now, when you know ahead of time in the Thursday meeting we will talk about this patient, that the respective therapist maybe could just take part in that meeting. Since it is always better to say something in person, compared to letting it done by our team leader. (B2/GDST/FC/181–191)This goes along with the perceptions of the staff members that these team sessions are not appreciated enough. An occupational therapist from another facility with a lower level of patient success states in a group discussion:But I really miss those Monday meetings, where every therapist had taken part, I shall say. (B1/GDST/FC/88–89)Observational protocols of these team meetings indicate that team meetings applying a delegate model were not used effectively. Although team members from different professions come together, in these meetings, a mutually shared ground for interdisciplinary communication was hardly accomplished.The same female physician now presents a patient (case history). The male senior physician calls this patient an interesting case, it was about a scoliosis that has been corrected late in life. The x-rays are shown, at the same time everybody is talking to each other, not together within the group, but in one-to-one conversations. (B1/OP/team meeting)The meeting starts with a salutation from the chief physician. Then the handover of the physician from the night shift takes place. He talks immensely fast and muted, a one-to-one conversation with the chief physician follows directly afterwards, in which no other person is involved. Even the eye-contact of both is restricted to their conversation. (B1/OP/early team meeting)However, these results only relate to two of the three rehabilitation facilities with a lower level of patient success. This limitation makes clear that differences in success cannot simply be reduced to a single obvious characteristic. Still, in rehabilitation facilities with an upper level of patient success, therapists and physicians are completely represented without using the respective leading managers. In one of these three clinics, they applied a partial delegate model. Here, not every team member took part in the team meeting, but the respective group sent different delegates (not only the leading manager) to these meetings. Within these institutions, participation in interdisciplinary team meetings is positively appraised and both valued by the staff members and the leading managers. A psychologist states in a group discussion:(…) I am really happy to be part of the team meetings or the early meetings, that take part every day, since from a psychological perspective it is also important to know, of course, how they [i.e. the patients] behave within the other therapies, in the occupational therapy, how do they present themselves in the teaching kitchen? (A1/GDST/FE/144–149)A leading administrator states in an interview:Yes, and this topic meeting or exchange is a very important topic in our clinic × [name of the facility] there is exchange on the different levels, but it is within a lot of meetings that take place, is always, well, interdisciplinary and not just, it does not just stick within the departments, but there are always many disciplines involved. (A3/IVLA/245–251)The degree and mode of reciprocity in interdisciplinary cooperation are more pronounced in rehabilitation facilities with an upper level of patient success. In rehabilitation facilities with a lower level of patient success, we found that communication of the different team members is concentrated toward the physicians. Therapists and nurses forwarded information mainly to the physicians.The physiotherapist recommends removing a patient from the so-called shoulder-group. Also at this point, her mode of speech appears low, cautious and hesitant. She introduces the issue, if it would not be better to exclude all patients with a “bad” cervical spine status from the shoulder group. The leading physicians, however, stand for a different approach, i.e. they hold that all patients with cervical spine syndrome should take part in the shoulder group. (…) The issue is not further elaborated on or discussed, the physicians` statement determines the further conduct. No opposition can be observed. (B3/OP/team meeting)Orders came from the physicians directed to the staff members of the other health professions.Well, when first talk to each other and for me the final word always comes from the physician. That's how I forward it to the patients, too. Even when I do have a different opinion, and I talk with doctor P [name of physician] about it, then I just make my own thoughts, well, I see it differently, but to the patient I say that the doctor has said somehow or other, and we stick to it. (B3/GDST/FG/874–879)We found this hierarchical order also expressed in the seating arrangements in team meetings.The interdisciplinary team meeting takes part in the office of the chief physician. This office is about 25 m² big and comprises a treatment bed, a sink, a sideboard, a table with about eight chairs and a big writing desk. The physicians sit at the big round table, two places are still vacant. The physiotherapist, the occupational therapist, the dietician and the social worker sit in the background on the treatment bed, which makes most of the physicians at the table to turn their back on them. (B1/OP/team meeting)There were indications that this lack of reciprocity in interdisciplinary work emanated both from the physicians themselves and from the self-conception of the team members of the other health professions. The following example results from the opportunity to observe different staff members, situations, or fields of action within our study and to relate these situations to each other. It stands for lack of or a failed interprofessional interaction.A nurse realizes that a patient is still taking a medication for gastric protection despite the fact that he had discontinued to take his painkiller. She states that tomorrow will be the ward round of the leading physician, then this could be clarified. She does not make a note in the patient records. This, so she says, is not a nursing task. She assumes that this would transcend her competencies. (B1/OP/nursing)A lack of interprofessional communication that appears to be intrinsically related to a self-appreciation of one's professional role results in futile or even harmful care.We were present at the next morning in the ward round. Nobody noticed that the patient still takes a medication for gastric protection that appears not to be necessary any more. (B1/OP/ward round)In sum, we noticed a lesser amount or even lack of cooperation in rehabilitation facilities with lower levels of patient success.On the contrary, we noticed more intense, reciprocal professional communication across the different professions in rehabilitation facilities with upper levels of patient success. For example, in these facilities, the team meetings were not merely dominated by physicians. Other professionals participated in or initiated discussions on patients without being called upon.The chief physician then asks the physiotherapists about their experiences with the patient from a physiotherapist`s perspective. A physiotherapist reports what has been done so far. She makes proposal how to proceed further, these proposals are being taken up by the physicians. The dietician then asks, without being addressed beforehand, about the nutritional state of the patient. A response is provided by the nurses. The review of the patient is concluded thereby. (A2/OP/team meeting)Therapists approach physicians with a proposal for further therapeutic actions. The following situation has been observed in a facility with upper levels of patient success within an early morning meeting of physicians.Somebody knocks at the door and a female physiotherapist enters. A seat is offered to her and she gets seated. Shortly after that, the leading physician hands over to her. She says she is here because of the stool group 2. She inquires if the physicians all are aware about the difference between stool group 1 and 2. Hereupon she explicates the meaning of this difference and asserts that there are frequent mismatches of patients in the groups. She assures herself that everybody has understood her delineation. She also asks if everybody knows how to manage the correct assignment of patients within the management system. Some nod, others do not react. The physiotherapist delivers a prepared handout to every physician that explains the correct assignment of patients into the groups. Hereupon she expresses her gratitude and leaves the room. (A3/OP/early meeting of physicians)Even patients of these facilities perceived that therapeutic decisions were not exclusively in the hands of the physicians. A patient from the same facility states during the group discussion:You do not notice some differences among physicians, nurses, therapists, I have not noticed them. I sense that, wherever I say something, if it is related to health they align themselves, every opinion counts apparently, team decisions et cetera. (A3/GDPT/FE/1289–1293)Still, even in these institutions, decisions that are important for interdisciplinary work are made by physicians, too. Staff members of different professions can contribute to these decisions in a substantial way. Decisions have to be transparent and justified in these institutions. We have observed that professional controversies were made transparent and discussed openly.(…) We do lead a lot of open discussions. Even when it is ((he clears his throat)) about strategies how to deal with patients, everybody can engage in the discussion. When I have the feeling that everybody has given a comment, then a final decision has to be taken. And this decision is taken based on best arguments that have been put forward by each individual. (…) (A3/INLP/160–166)In every rehabilitation facility we visited, we found a dominant role of the physicians within the rehabilitation team when it came to the distribution and ascription of responsibilities. Still, within the rehabilitation facilities with a lower level of patient success, we could notice a more comprehensive and pronounced dominant role of the physicians. Both aspects we have elaborated on before, i.e., the organization of the team meetings and the related reciprocity of interaction between the professions, point to a special role of physicians in this context. This dominance was reasoned to be legally based. A physician elaborates on this within a group discussion:Back to the issue of who can call upon someone etc. if somebody has a different opinion on the therapy from a mere legal position the physician is held responsible, if it is about the kind of treatment or if you look at patients` complaints or the evaluation questionnaires, we take the stick and there are critics that are really below the belt and to more than 90 percent address physicians, not therapists or nurses. Or rather we as physicians have to take the can, maybe even with legal measures. That is why it is important that there is a certain hierarchy that is indisputable especially regarding the prescriptions. (B3/GDST/HD/953–964)Still, rehabilitation facilities with an upper and a lower level of patient success differ in how they deal with this exceptional position of the physicians. One example from a facility with a lower level of patient success has been presented above, where a nurse refrained from doing something potentially helpful for a patient with explicit reference to the fact that some actions or decisions can only be taken by physicians. In another example, a nurse pinpoints the exceptional role of physicians` prescriptions for the conduct of rehabilitation processes:Therefore, it is always the communication, that is the prescription, that is very important for us, yes, that we have a prescription by a physician for everything that we have to fulfil, yes, since, as stated, we have to work according to prescriptions, yes, we need the prescriptions for the patients. (B1/GDST/FF/146–150)This way of dealing was different in the rehabilitation facilities with an upper level of patient success. Here, we have found statements pointing to the necessity of mutual trust, which should form the basis for responsible decisions.Or trust among colleagues. That is what I think, is a much better expression than flat hierarchies. Trust among colleagues, or trusting interaction, professional trusting interaction, very important, yes. (A1/GDST/HC/1211–1214)Here, we observed discussions about the useful degree of delegation. Opportunities to voice onès position and to experience a defined space for self-determined decisions were more pronounced in these institutions. For example, a leading physician elaborates in an interview on the usefulness and necessity of delegating certain tasks to other professional groups:Well, for me it is currently a very important topic. We still have very traditional role understandings here, that are not sustainable any more and will not be possible in the future. Simply because we cannot manage it by the personnel (…). You can certainly find a number of tasks of physicians that can be delegated to well-trained, non-medical assistants. By the time we do have far-reaching concepts that claim nurses or others with a good medical education could do a sort of a pre-anamnesis. Certain documents to be sorted, asking targeted questions and, in a way, to prepare an extended patient record. And this could be the basis for the physicians consultation. It could within the logistics, the planning, regarding diagnostics and processes, a lot could be withdrawn from the physician, what is currently attached to the physician`s profession. (A2/IVLP/536–555)Interestingly, in the interviews with the leading physicians in the rehabilitation facilities with an upper level of patient success, we found statements on the need to improve interdisciplinary cooperation, which included a better integration of nursing staff in the rehabilitation team .Well, the better the single professions are toothed or integrated, the better it is for the staff and the patients. Because the exchange of experiences can take place from any side, problems can be considered much faster, well, it would be also preferable if nurses could take part in our team meetings. Like that for example. We have done that before. But this is due to our low staffing. That is how one has to see that (…). If you could draw on unlimited resources, you could surely do even better than now. (A3/IVLP/601–612)need for improvement of interdisciplinary cooperation was not found in the rehabilitation facilities with a lower level of patient success.This kind of statement regarding the We found a different way of interaction between the participants of the group discussion (staff members) that could be related to different perspectives on hierarchies. In a separate step, we analyzed the group discussions of staff members more thoroughly . Staff mWe could also observe differences in how the staff members participated in the group discussion. Interestingly, in the rehabilitation facilities with a lower level of patient success, aspects of professional hierarchies were addressed by persons at the upper level of the hierarchy, while those in the lower level of the hierarchy addressed mainly issues of personal relationships or topics related to work atmosphere. In the rehabilitation facilities with an upper level of patient success, no such division of content was present; group members of different hierarchy levels contributed in different ways to this discussion. Also, the description related to situations that were relevant to hierarchies differed. For example, while in a rehabilitation facility with an upper level of patient success, participants portrayed a situation how they negotiated a disputed topic; for participants in a rehabilitation facility with a lower level of patient success, it was of main importance to reach a consensus visible to others. In sum, communication in rehabilitation facilities with an upper level of patient success appeared to be less centered around physicians. Hierarchical structures appeared to be less pronounced and more directed toward one leading manager. Also, professional discussions about ways of treating patients seemed to be given more room for discussion.In a systematic comparison of rehabilitation facilities with an upper and a lower level of patient success, we could depict a difference in the daily practices of interdisciplinary cooperation among team members. Physicians were found to play an important part in this game. Our point of departure was subtle differences in the representation of team members within team meetings, which were directly related to the perception of worth and respect toward one’s work. While the communication structure was more centered around the physicians in the rehabilitation facilities with a lower level of patient success, there was a higher level of mutual exchange on eyes’ level in the rehabilitation facilities with an upper level of patient success. This also related to perceptions of hierarchy in the rehabilitation team, which were more one-sided and physician-related in the rehabilitation facilities with a lower level of patient success. In these institutions, the physicians seemed to take a more dominant role in the team.It should be noted that the only study that related organizational-level information to members of the rehabilitation team found a positive relationship between network social capital and patient outcome . NetworkFrom a theoretical perspective, it seems appropriate to relate our results to the work of Strasser and Falconer  on team We found substantial convergence of our results with the team effectiveness model developed by Strasser and Falconer (see ). This mpotential prerequisites of patient success, while further determinants and their interactions with team-level characteristics have to be identified on the patient level.How could these results relate to success on a patient level? The team effectiveness model is not specific about how these characteristics identified on an organizational level actually translate to greater success on a patient outcome level. We have to delve much deeper into potential effective ingredients of rehabilitation care on the patient outcome level to answer this question. Presumably, we have only captured There are different limitations of our study. One point of critique may be related to our main reliance on patient-reported outcome data to appraise a rehabilitation facility as an upper or a lower level of patient success. While patient-reported outcomes are widely applied in clinical and health-related research as well as quality assurance, issues of validity have to be taken into account , especian of 6—which does not look very convincing. However, we were able to dig into important mechanisms compatible with the literature on team effectiveness. It is highly plausible to assume that our results also apply to other rehabilitation facilities not included in our study or even to other patient groups cared for in rehabilitation facilities not considered in our study. It comes as no surprise that the results of our study were thoroughly discussed with a field of care not included in our study at all: patients with addictive behaviors and their respective rehabilitation care institutions (Also, we could argue that our study design follows a mere explorative approach, which is in line with the idea of ending up with empirically founded hypotheses as a study result. We can understand our study design as a case–control study comprising an itutions . The empitutions  and is oitutions .


Augmented reality (AR) is an emerging technique usedto improvevisualization and comprehension of complex 3D materials. This approachhas been applied not only in the field of chemistry but also in realestate, physics, mechanical engineering, and many other areas. Here,we demonstrate the workflow for an app-free AR technique for visualizationof metal–organic frameworks (MOFs) and other porous materialsto investigate their crystal structures, topology, and gas adsorptionsites. We think this workflow will serve as an additional tool forcomputational and experimental scientists working in the field forboth research and educational purposes. MOFs have received considerable interest over the past 25years due to their structural diversity, high surface area, and tunableproperties making them suitable materials for a broad range of adsorptionapplications including gas storage,15 Adsorption simulation snapshots can be used to analyze energeticallyfavorable adsorption sites in porous materials, and AR can createaesthetic representations of pores along with the adsorbed molecules.AR enhances spatial understanding by enabling visualization and manipulationof complex structures under specific conditions in 3D, offering additionalinsights when studying structure–property relationships andguest–host interactions. The use of AR has been previouslyreported for molecular structures using an app,16 for polymers using an app-free technique,17 as well as published workflows that build VR models whichcan also be viewed in AR:18 these are typicallyused for educational purposes as a teaching medium.21 Here, followingthe work of Roshandel et al.,17 we developeda protocol for app-free AR models that can be used to display MOFsunder adsorption conditions or represent crystal structures in conjunctionwith their topology which can be viewed using a smartphone runningAndroid or iOS.Details regarding MOFs’ structural network, pores,surfacechemistry, and adsorption sites are critical pieces of informationwhen investigating the adsorption properties of these structurallycomplex materials, and this information is often used in conjunctionwith simulation software to predict gas adsorption properties.Before we discuss the workflow for creatingAR models of MOFs,let us demonstrate an example for AR gas adsorption visualizationin an educational setting. 222 it is possible to create these AR models usingany CIF or PDB file from other sources. A detailed guide showing step-by-stepinstructions on how to obtain and process these files can be foundin the Supporting Information , followed by the repair of broken or unusual chemicalbonds. Often, PDB outputs have certain configured bonding patterns,and the CSD software suite is ideal for fast and easy correctionsto these abnormalities. It is essential that all models are correctedin this preliminary stage so that errors are not carried forward intothe AR representations, and it is recommended to manually check allatoms in the structure even after autocorrection to ensure there areno “floating” atoms remaining or undesired solventsstill present in the pores. It is also possible to “snip-off”any over branching linkers that exceed the dimensions of the unitcell at this stage to ensure uniformity of the crystal structure.Theinitial stage of AR visualization begins by selecting a MOF, openingthe corresponding CIF/PDB file, and expanding the representation toits unit cell or supercell. In this process, we select structuresfrom CSD ConQuest and use Mercury2.224 an open-sourcefile conversion and visualization software. From Jmol, detailed instructionsin the 25  Once the OBJ file is added to Blender, the remainingstages involve the removal of the light and camera layers, followedby a check of structure face count. If the face count exceeds 750,000,the image will not render correctly into AR so the “decimate”function can be used to reduce the number of faces. For best results,keeping the number of faces as close as possible to 750,000 is recommended.The reduced file can then be manipulated so that the orientation ispresented as desired, before it is exported as an FBX file.Once all bonding information has been determined and corrected,and the structure representation has been chosen  it is possible to export the file aseither a PDB or CIF. Once the file is saved as a PDB or CIF file,it can be opened in Jmol,2.326 The FBX file can beuploaded, and the structure’s final orientation and color schemecan be selected. It is also possible to customize the online viewerto display the structure with different background colors, selectmouse/keyboard configurations for controllability, and determine thescale of AR representation. Each file is then given a unique URL whichcan be assigned a static QR code using any, freely available QR codegenerator (we used https://www.the-qrcode-generator.com/) to create a QR linkto the AR enabled structure. 27The publication stage is very simple but requires a free (or paid)subscription to p3d.in, an online 3D model hosting platform with built-inAR functionality.321 We previously introduced astep-by-step guide to use AR in the field of MOFs in 2022;28 however, this process was tedious and complexrequiring the development and publication of an app. The current approachfollows an easier, app-free, workflow. Although it would be straightforwardto produce AR representations for basic MOF structures, it is possibleto make these tools more useful. For example, the representation ofmolecular interactions between gases adsorbed in MOFs are mostly representedin 2D which can make it difficult to fully appreciate the complexinterplay between structural network, pore shapes and sizes, surfacechemistry, and preferential adsorption sites. Clearly, a 3D AR technologyto assist in the detection of adsorption sites or topological featuresof MOFs provides better understanding of the adsorption phenomenaand the pore environment.AR has seen increasing use in the field of 3D chemical and molecularstructure modeling in recent years, originating from a very limitednumber of publications to an increasingly popular and more widespreadaudience.3.1For this article,we created several interesting and diverse AR representations of MOFsunder various conditions to demonstrate the relevance and reach ofAR in the field, from basic MOF visualizations to more complex representationsof their topologies and gas adsorption. 3.229 or CrystalNets30 to generate the underlying net for a given CIF.It is essential that topological nets correctly match the dimensionsof the CIF so they can be overlaid together for AR representation.Once the topology is determined, the next stage is to convert boththe CIF and its corresponding net into separate OBJ files where theycan then be layered together in Blender for export into a single FBXfile. Topology nets are typically created as CGD or MOL2 files thatcan be imported into CSD Mercury, before being exported as PDB filesfor use in Jmol. One disadvantage of this method is that the underlyingnet representation cannot later be switched on/off in the free versionof p3d.in, but it remains an interesting tool for demonstrating theunderlying connectivity of MOFs. Another interestinguse of AR is for the comparison between the complex crystal structureof MOFs and their underlying topologies. The creation of “MOFplus topology” AR representations involves the use of softwaresuch as ToposPro3.327 for running MonteCarlo simulations of adsorption in MOFs. Once the simulation at aspecific temperature and pressure in the isotherm is equilibrated,RASPA provides CIF and PDB output files for the framework and theadsorbate molecules, and to visualize gas adsorption snapshots, thesetwo files should be merged into a single file followed by the AR developmentprocess, as explained in 2 adsorption isotherm simulated in UiO-67at room temperature. As can be seen, we can use AR to visualize gasadsorption snapshots as pressure is increased from 0.15 to 20 bar.These snapshots are all produced in RASPA forming the basis of ARmodel creation for gas adsorption visualization.Toobtain more information from AR modeling, one can run adsorption simulationsand generate “snapshots” of gas adsorption sites forvisualization in AR at desirable operating temperatures and pressures.Here, we use RASPA2 andH2O adsorption in selected MOFs. By simply scanning therelevant QR code, one can create an immersive experience, investigatinghow the pore environment and surface chemistry affect the adsorptionof CO2 or water in MOF-812, CALF-20, UiO-66, HKUST-1, andKAUST-7. In contrast to typical 2D visualization of simulation snapshots,AR can thoroughly capture the clustering of water molecules and theformation of hydrogen bonds, typically seen in hydrophilic MOFs suchas in Cu-BTC. In CALF-20, it can be seen that CO2 moleculessit tightly within the channels of the oxalic acid linkers where theystrongly interact with the metal nodes. In UiO-66, we can use thisexperience to easily visualize that CO2 molecules occupythe tetrahedral cages first at low pressure conditions.In 3.4We demonstrated some ofthe MOF AR visualizations via QR codes at the first MediterraneanPorous Materials Conference in May 2023 in Crete, Greece, and againat the sixth Annual UK Porous Materials Conference in June 2023 inSheffield, United Kingdom, receiving approximately 350 views combined.We received many positive comments regarding the quality and clarityof the modeling, and we shared a number of additional QR codes todemonstrate the flexibility of these methods with various structuresand gases. We also received constructive feedback for AR demonstrationof, e.g., bond vibrations, structural flexibility, and increasinginteractivity by implementing measuring tools.4This article showcases thecapability of AR modeling for visualizationof MOFs and other porous materials for a variety of applications.We used AR for representing MOFs crystalline structure, their underlyingtopologies and favorable gas adsorption regions without the need foradditional downloads, as the models can be viewed on an Android oriOS smartphone app-free. The technique outlined in this paper andthe


Antidepressant monotherapy is effective in achieving treatment remission in only approximately one third of patients with depression, and even switching to a second antidepressant brings the cumulative remission rate to only 50%-55%. This has led to an interest in augmentation therapy for the management of treatment-resistant depression.To assess (a) selective serotonin reuptake inhibitor/selective norepinephrine reuptake inhibitor (SSRI/SNRI) adherence when augmented with second-generation atypical antipsychotics (SGAs) or L-methylfolate using a modified application of the Healthcare Effectiveness Data and Information Set (HEDIS) acute medication management (AMM) measures at the time of augmentation, and (b) the depression-specific and total health care cost, comparing the 2 forms of augmentation therapy in the treatment of depressive disorder.Patients with a diagnosis of depression and a pharmacy claim for an SSRI/SNRI between January 1, 2006, and December 31, 2009 (index date), and receiving concomitant augmentation therapy with either an SGA or L-methylfolate (augmentation date), were identified in the MarketScan database and followed for 231 days (follow-up). Patients were excluded for having any pharmacy claim for an antidepressant or SGA 90 days pre-index; having an L-methylfolate claim 6 months pre-index; age less than  18 years on the index date; or a diagnosis of pregnancy, dementia, psychotic-related mental disorders, Alzheimer’s disease, or Parkinson’s disease in the 12-month pre-index period. Propensity score matching  was used to select the final study cohorts, using covariates of age, gender, comorbidities, index SSRI/SNRI, and index SSRI/SNRI dose. Adherence to antidepressant therapy was measured from the augmentation date and included a modified application of the HEDIS (mHEDIS) AMM acute and chronic phase measures as well as the 6-month medication possession ratio. Health care utilization and cost were measured for the 6-month postaugmentation period and included both total as well as depression-related utilization/cost. Comparisons between the closely matched SGA and L-methylfolate-augmented cohorts were made using chi-square tests for binary measures and t-tests for continuous measures.Following propensity score matching, 4,053 SGA and 1,351 L-methylfolate patients were found to have augmentation of the index SSRI/SNRI within 12 months of the index date. The comparison groups were well matched on age, gender, comorbidities, and the type and dose of the SSRI/SNRI being augmented. The most common antidepressants augmented in both groups were escitalopram, duloxetine, and venlafaxine. Mean (standard deviation [SD]) time from index to augmentation was 73.5 [96.7] days for SGA and 105.9 [108.7] days for L-methylfolate (P  less than  0.001). The most common SGAs utilized for augmentation were quetiapine, aripiprazole, and risperidone. L-methylfolate was primarily dosed at 7.5 mg/day.The mHEDIS AMM acute phase measure was met by 68.7% of the SGA cohort and 78.7% of the L-methylfolate cohort (P  less than  0.001). The mHEDIS continuation phase measure was met by 50.3% of the SGA cohort and 62.1% of the L-methylfolate cohort (P  less than  0.001) following augmentation. Medical utilization  was significantly higher for the SGA group, while total prescription utilization was significantly higher in the L-methylfolate group. Mean [SD] total 6-month postaugmentation costs for the SGA group was $8,499  and $7,371  for the L-methylfolate group (P = 0.005), and 6-month depression-related costs were $2,688  for the SGA group and $1,613  for the L-methylfolate group (P  less than  0.001).Patients who augmented SSRI/SNRI therapy with SGA or L-methylfolate achieved mHEDIS AMM acute phase and continuation phase adherence scores of 69%-79% and 50%-62%, respectively. These modified scores exceeded the 2012 national median benchmarks for unmodified HEDIS AMM measures for commercial health plans. In this study, augmentation with L-methylfolate was associated with significantly higher adherence measures compared with augmentation with SGA. In addition, health care utilization and total health care costs, as well as depression-related costs, were significantly lower in the L-methylfolate augmentation group compared with augmentation with SGA.


FMR1 premutation (PM) allele are at risk of one or more clinical conditions referred to as FX premutation-associated conditions (FXPAC). Since the FMR1 gene is on the X chromosome, the activation ratio (AR) may impact the risk, age of onset, progression, and severity of these conditions. The aim of this study was to evaluate the reliability of AR measured using different approaches and to investigate potential correlations with clinical outcomes. Molecular and clinical assessments were obtained for 30 PM female participants, and AR was assessed using both Southern blot analysis (AR-Sb) and methylation PCR (AR-mPCR). Higher ARs were associated with lower FMR1 transcript levels for any given repeat length. The higher AR-Sb was significantly associated with performance, verbal, and full-scale IQ scores, confirming previous reports. However, the AR-mPCR was not significantly associated (p > 0.05) with these measures. Similarly, the odds of depression and the number of medical conditions were correlated with higher AR-Sb but not correlated with a higher AR-mPCR. This study suggests that AR-Sb may be a more reliable measure of the AR in female carriers of PM alleles. However, further studies are warranted in a larger sample size to fully evaluate the methylation status in these participants and how it may affect the clinical phenotype.Carriers of the  FMR1) gene is located on chromosome Xq27.3 and encodes the FMR1 protein, FMRP. The 5′ untranslated region of a normal allele of the FMR1 gene contains a tandem repeat tract harboring 5–44 CGG trinucleotide repeats, while premutation (PM) alleles contain 55–200 CGG repeats. The prevalence of PM in the general population is about 1:855 in males and 1:300 in females [The Fragile X Messenger Ribonucleoprotein 1  mitochondrial dysfunction [The MR1 mRNA . The incMR1 mRNA , which ifunction , (iv) refunction ,7,8, andfunction .FMR1 FM causes Fragile X syndrome (FXS), the most common form of inherited intellectual disability (ID) and monogenic cause of autism spectrum disorder (ASD). The FM becomes epigenetically silenced, leading to a reduction or absence of FMRP [As the size of the CGG repeat tract increases, the PM allele displays increasing degrees of repeat instability within tissues and across generations ,11,12. I of FMRP . The ris of FMRP , but it  of FMRP .Furthermore, our group has demonstrated somatic instability in the blood of female carriers of PM alleles . AccordiFMR1 gene, if skewed X chromosome inactivation (XCI) occurs, resulting in more of the normal allele on the inactive X, the lack of FMRP in FM allele carriers may result in a more severe clinical phenotype. Indeed, several studies have reported how methylation status and AR significantly impact the degree of neurocognitive and physical phenotypes in females with FMR1 FM [FMR1 gene.The activation ratio (AR), which represents the fraction of the normal allele carried on the active X chromosome, has been shown to be a relevant clinical parameter in many diseases involving X-linked genes, including hemophilia B ,18, Duch FMR1 FM ,24,25. I FMR1 FM . AlthougThe Human Androgen Receptor Assay (HUMARA) is considered the gold standard for determining X inactivation status . HoweverParticipants were 30 female PM carriers whose PM status (CGG repeat size 55–200) was confirmed via both Sb and PCR approaches . The femFMR1 gene. The assessment of the FMR1 CGG repeat allele size was performed using PCR and Sb analysis as previously described [Molecular data were obtained from peripheral blood samples (3 mL), and the genomic DNA was isolated from 30 PM females using the Gentra Puregene Blood Kit  and utilized for measuring the size of CGG trinucleotide repeats (expansion), a number of the AGG interruptions, and methylation status of the escribed ,28,31. Cescribed ,33. VisuFMR1 allele on the active X chromosome (AR) was assessed using both Sb and mPCR analysis [The X-inactivation status was determined using an assay based on a short polymorphic repeat tract present in the X-linked androgen receptor (HUMARA) gene as previously described . Allele analysis ,35. AR wanalysis , and is analysis .FMR1 total mRNA was isolated from peripheral blood collected in PAX gene collection tubes  and quantified using the Agilent 2100 Bioanalyzer system. FMR1 mRNA levels were measured using qRT-PCR used Assays-On-Demand  and custom TaqMan primers and probe assays as reported in Tassone et al. (2000) [The . (2000) .An expert medical professional (RJH) evaluated the presence and severity of FXTAS and FXAND in patients with PM after conducting a thorough medical examination and reviewing the patients’ Magnetic Resonance Imaging (MRI) pictures. Occurrence of early menopause prior to 40 years of age, followed by medical examination, defined as FXPOI  was alsoThe presence of psychiatric conditions related to FXAND occurring at the same time was determined using (i) the Structured Clinical Interview for DSM Disorders (SCID-5), a semi-structured interview guide for making diagnoses of anxiety, depression, and ADHD according to the diagnostic criteria published in DSM-5 and the Symptom Checklist-90-R (SCL-90 R) ,37 and  , and theThe Behavioral Dyscontrol Scale-2 (BDS-2), a nine-item assessment, was used to measure executive functioning deficits, as prediction of functioning in daily life ,41.Clinical assessment, following under the umbrella of FXPAC, included the following: (i) presence of FXTAS, FXPOI, and FXAND; (ii) number of psychiatric conditions related to FXAND, which included depression, anxiety, ASD, and attention deficit hyperactivity disorder (ADHD), occurring at the same time; (iii) Intelligence Quotient (IQ) as measure of a cognitive assessment; (iv) presence of executive functioning deficits.FMR1 mRNA via AR (AR-Sb and AR-mPCR) and CGG, using generalized additive models (GAMs), in which the relationship between FMR1 mRNA and AR was allowed to be nonlinear, were performed.Statistical analyses were performed via R version 4.2.1 (23 June 2022) , and theParticipants in this study were 30 carrier females, and the ages of the participants in this study at the time their blood was drawn was 60.5 ± 11.7 y. . Among them, three did not have children, and 14 PM (46.7%) had a child with FXS. The average years of education in this cohort were 15.7 ± 2.6 (n = 21). Molecular measures, including CGG repeat number, number of AGG interruptions, AR, instability, and FMR1 mRNA levels are shown in The clinical presentation of this cohort is also summarized in p < 0.001) between AR-Sb1 and AR-Sb2 (repeated Southern blot measurements) ; p < 0.001 and the confidence intervals for the two correlation coefficients that do not overlap , whilst the bottom 50% were not significantly different (p = 0.65). This lends weight to the hypothesis that the mPCR assay tends to overestimate the AR in our patient cohort for samples in the higher AR range. The mPCR assay measures the difference in the yield of PCR product from the normal allele with and without HpaII digestion. Given the difficulty in the amplification of CGG-repeats, a situation that is exacerbated when the repeats are embedded in a long GC-rich DNA fragment, it is possible that the systematically higher AR as measured via the AR-mPCR assay reflects the improved efficiency of PCR amplification of PM alleles after HpaII digestion. Without HpaII digestion, the normal allele would be preferentially amplified, whilst, after HpaII digestion, this bias would be reduced. This would result in an apparent reduction in the fraction of normal alleles on the inactive X and thus a higher apparent AR.However, as shown in p = 0.03) or after adjusting for AR-mPCR (p = 0.05). As expected, participants with higher AR-Sb or higher AR-mPCR showed significantly lower FMR1 mRNA after adjusting for CGG repeats; p = 0.03 and p = 0.04, respectively. The ANOVA revealed that the length of the CGG was not significantly related to the number of AGG interruptions (F test p = 0.86).Linear regression analysis of FMR1 mRNA expression level by the number of CGG repeats and either AR-Sb or AR-mPCR showed that PM females with more CGG repeats had higher FMR1 mRNA levels after adjusting for AR-Sb  or instability . However, instability was significantly higher for PM participants with greater numbers of CGG repeats . Furthermore, the results of the linear regression analysis revealed that instability was not significantly associated with the level of FMR1 mRNA (p = 0.145).Linear regression analyses of AR-Sb and AR-mPCR showed no significant association with the number of CGG repeats (p = 0.03), while the frequency of FXPOI did not correlate with AR-mPCR. Moreover, neither FXTAS nor FXPOI frequency correlated significantly with AR-Sb . A lack of correlation between FXPOI and AR is consistent with previous reports using the HUMARA assay and Southern blotting approaches [FXTAS was seen in 40% of PM carriers and FXPOI in 46% of carriers. The frequency of FXTAS was inversely correlated with AR-mPCR values .As expected, a significant correlation was observed between CGG repeat number and  studies , while np = 0.02, p = 0.06, 335 p = 0.14). In this sub-cohort, nine  had a child with FXS, while 11  had depression but did not have a child with FXS. Furthermore, five participants without depression had children with FXS. Logistic regression showed no significant association between the occurrence of depression and parenting a child with FXS (p = 0.883). The average years of education in participants with depression (data were available for 16 participants) was 15.9 ± 2.8, and 15.2 ± 1.8 years in those without depression (data were available for 5 participants). This difference was not statistically significant .In terms of FXAND, 20 PM allele carriers (66.7%) were diagnosed with depression, with the likelihood of depression being significantly reduced for carriers of PM alleles with greater AR-Sb . In addition, 10/22 (45.5%) of carriers of PM alleles diagnosed with anxiety had a child with FXS, while only one PM carrier without anxiety had a child with FXS, suggesting that there was no significant association between the occurrence of anxiety and parenting a child with FXS (p = 0.090). The average years of education in PM females with anxiety (data were available for 17 participants) was 15.4 ± 2.7, and 17.0 ± 1.8 years in PM carriers without anxiety (data were available for 4 participants). There was not a statistically significant difference between years of education between PM carriers with and without anxiety .Anxiety, an FXAND-associated condition, was present in 22 of the 30 (73.3%) participants. However, the odds of anxiety did not differ significantly by AR-Sb or AR-mPCR . None of the participants were diagnosed with ASD.The odds of ADHD, which were presented in 6 of the 30 (20%) PM carriers, did not differ significantly by AR-Sb and AR-mPCR (p = 0.02) and showed a trend for higher AR-mPCR (p = 0.054) (p = 0.205).Furthermore, the entire number of medical disorders associated with FXAND, including anxiety, depression, ADHD, and ASD, was significantly lower for greater AR-Sb (= 0.054) . Moreovep values of 0.02, 0.02, and 0.042, respectively, as shown in Importantly, the linear regression analysis showed that carriers of PM alleles with higher AR-Sb had significantly higher PIQ and VIQ scores and FSIQ, , 0.32 (p = 0.229), and 0.43 (p = 0.107), respectively.Furthermore, the results of the linear regression analysis showed that performance IQ, verbal IQ, and FSIQ were not also significantly associated with instability . BDS-2 score was not significantly associated with instability (p = 0.43). According to the results of the logistic regression analysis, BDS-2 scores were not significantly associated with parenting a child diagnosed with FXS (p = 0.387).Finally, the results of the linear regression analysis showed that BDS-2 scores were not significantly associated with either AR-Sb or AR-mPCR (FMR1 FM [It has been reported that methylation status and AR have a significant impact on the phenotype of women with FMR1 FM ,24. HoweA systematic comparison of the AR values obtained via Sb and mPCR showed a weak correlation between the AR values, with AR-mPCR values typically being higher than those found via AR-Sb. However, we observed that while higher AR-Sb was significantly correlated with higher performance IQ, verbal IQ, and FSIQ and lower odds of depression, no correlation was seen with a higher AR-mPCR for any of these conditions. Thus, our results would be consistent with the idea that the AR-Sb is a more robust metric for assessing any potential correlation with FXAND. However, the AR-mPCR did show a negative correlation with the FXTAS stage, whilst the AR-Sb did not. The reason for this is unclear and suggests that a larger study comparing the performance of the different assays is warranted.FMR1 transcript levels for any given repeat length confirming previous findings [We also showed that AR, whether measured via AR-Sb or AR-mPCR, did not significantly correlate with either CGG repeat number or with somatic instability, but that instability was significantly associated with greater numbers of CGG repeats, in accordance with previous findings ,48,49,50findings ,52.This current study identifies the AR obtained via Sb as a relevant parameter for some fragile X-premutation-associated conditions. Specifically, our results suggest that AR-Sb would be useful in assessing the risk of specific psychiatric conditions, including depression, sleep disorders, ADHD, ASD, and anxiety symptoms, including social avoidance, interpersonal sensitivity, shyness, eye contact avoidance, social phobia, panic disorders, etc., which are common in PM carriers ,53. In aAccording to some previously conducted studies examining the effects of FMR1 mutations on executive function, female PM carriers’ general cognitive abilities were unchanged ,62. HoweIn conclusion, this work demonstrates that AR is a critical moderator of PM symptoms and that using AR-Sb to test AR in individuals who carry these alleles and see whether there may be a connection to their clinical status is a beneficial method. However, we acknowledge several limitations of this study, including the small sample size, which may have had limited statistical power for the detection of significant associations. Future studies can be improved by increasing the overall sample size. In addition, it is important to note that AR in different neuronal cell types may differ from each other and from the AR in blood. Finally, future studies are warranted to investigate FMRP expression levels and the ratio AR/FMRP, in different tissues, which could further provide relevant information about the underlying molecular mechanisms leading to PM phenotypes.