Lunar exploration offers an exciting opportunity for humanity to advance scientific knowledge and future potential economic growth and possibly allow humans to become a multi-planetary species. On April 2, 2024 the US Office of Science and Technology Policy released a memorandum outlining the current Biden-Harris Administration\'s policy on the need to establish time standards at celestial bodies other than Earth. This memorandum also introduced the need for Coordinated Lunar Time (CLT), the concept of having a reference time for the moon. The establishment of CLT would provide a multitude of benefits for astronaut health, from expedition planning, to maintaining a sense of order in an austere environment. International agreements and collaboration will be required prior to the recognition of CLT.

BACKGROUND: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented.
METHODS: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age- and sex-matched healthy control.
RESULTS: Seven patients who had severe infections in the first 6 months of life were diagnosed with T-B-NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post-transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12-45) months of follow-up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation.
CONCLUSIONS: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient\'s quality of life.

Long-lasting exposure to low gravity, such as in lunar settlements planned by the ongoing Artemis Program, elicits muscle hypotrophy, bone demineralization, cardio-respiratory and neuro-control deconditioning, against which optimal countermeasures are still to be designed. Rather than training selected muscle groups only, \'whole-body\' activities such as locomotion seem better candidates, but at Moon gravity both \'pendular\' walking and bouncing gaits like running exhibit abnormal dynamics at faster speeds. We theoretically and experimentally show that much greater self-generated artificial gravities can be experienced on the Moon by running horizontally inside a static 4.7 m radius cylinder (motorcyclists\' \'Wall of Death\' of amusement parks) at speeds preventing downward skidding. To emulate lunar gravity, 83% of body weight was unloaded by pre-tensed (36 m) bungee jumping bands. Participants unprecedentedly maintained horizontal fast running (5.4-6.5 m s-1) for a few circular laps, with intense metabolism (estimated as 54-74 mlO2 kg-1 min-1) and peak forces during foot contact, inferred by motion analysis, of 2-3 Earth body weight (corresponding to terrestrial running at 3-4 m s-1), high enough to prevent bone calcium resorption. A training regime of a few laps a day promises to be a viable countermeasure for astronauts to quickly combat whole-body deconditioning, for further missions and home return.

The aim of this study was to identify Artemis as a predictive biomarker for guiding preoperative chemoradiotherapy in locally advanced rectal cancer. The resection specimens were collected from 50 patients with rectal cancer who underwent preoperative chemoradiotherapy. Artemis expression in biopsy tissues was evaluated using immunohistochemical staining according to the percentage of positively stained cells combined with staining intensity. Among the 50 patients, 36 (72%) had a weakly positive Artemis protein expression, 10 (20%) had a moderately positive expression, and 4 (8%) showed a strongly positive expression. The criteria of magnetic resonance imaging tumor regression grade (mrTRG) and pathological rectal cancer regression grade (RCRG) were used to assess the tumor response to chemoradiotherapy. Correlation analysis shows that there is a significant negative correlation between high Artemis immunoscore and treatment response (r = -0.532, p < 0.001). The results imply that high Artemis expression was associated with poor treatment response. Our study suggested a potential role of Artemis as a predictive biomarker of the tumor response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Because it is safe and has a simple genome, recombinant adeno-associated virus (rAAV) is an extremely appealing vector for delivery in in vivo gene therapy. However, its low transduction efficiency for some cells, limits its further application in the field of gene therapy. Bleomycin is a chemotherapeutic agent approved by the FDA whose effect on rAAV transduction has not been studied. In this study, we systematically investigated the effect of Bleomycin on the second-strand synthesis and used CRISPR/CAS9 and RNAi methods to understand the effects of Bleomycin on rAAV vector transduction, particularly the effect of DNA repair enzymes. The results showed that Bleomycin could promote rAAV2 transduction both in vivo and in vitro. Increased transduction was discovered to be a direct result of decreased cytoplasmic rAAV particle degradation and increased second-strand synthesis. TDP1, PNKP, and SETMAR are required to repair the DNA damage gap caused by Bleomycin, TDP1, PNKP, and SETMAR promote rAAV second-strand synthesis. Bleomycin induced DNA-PKcs phosphorylation and phosphorylated DNA-PKcs and Artemis promoted second-strand synthesis. The current study identifies an effective method for increasing the capability and scope of in-vivo and in-vitro rAAV applications, which can amplify cell transduction at Bleomycin concentrations. It also supplies information on combining tumor gene therapy with chemotherapy.

Monitoring space radiation is of vital importance for risk reduction strategies in human space exploration. Radiation protection programs on Earth and in space rely on personal and area radiation monitoring instruments. Crew worn radiation detectors are crucial for successful crew radiation protection programs since they measure what each crewmember experiences in different shielding configurations within the space habitable volume. The Space Radiation Analysis Group at NASA Johnson Space Center investigated several compact, low power, real-time instruments for personal dosimetry. Following these feasibility studies, the Crew Active Dosimeter (CAD) has been chosen as a replacement for the legacy crew passive radiation detectors. The CAD device, based on direct ion storage technology, was developed by Mirion Dosimetry Services to meet the specified NASA design requirements for the International Space Station (ISS) and Artemis programs. After a successful Technology demonstration on ISS, the CAD has been implemented for ISS Crew operations since 2020. The current paper provides an overview of the CAD development, ISS results and comparison with the ISS Radiation Assessment Detector (RAD) and the Radiation Environment Monitor 2 (REM2) instruments.

UNASSIGNED: Hypomorphic mutations of DCLRE1C cause an atypical severe combined immunodeficiency (SCID), and Epstein-Barr virus (EBV)-related colon lymphoma is a rare complication.
UNASSIGNED: A teenage boy presented with colon EBV-related colon lymphoma, plantar warts, and a history of recurrent pneumonia. His peripheral blood lymphocyte count and serum level of immunoglobulin (Ig) G were normal, but he exhibited a T+B-NK+ immunophenotype. Genetic analysis by whole exome sequencing revealed compound heterozygous mutations of DCLRE1C (NM_001033855.3), including a novel paternal splicing donor mutation (c.109 + 2T>C) in intron 1, and a maternal c.1147C>T (p.R383X) nonsense mutation in exon 13. Based on his clinical features and genetic results, the diagnosis of atypical SCID with colon lymphoma was established. Our review shows that seven patients, including our patient, have been reported to develop lymphoma, all with hypomorphic DCLRE1C mutations. Among these cases, six had EBV-related B-cell lineage lymphoma, and one had Hodgkin lymphoma with EBV reactivation. Unfortunately, all of the patients died.
UNASSIGNED: Recognizing the radiosensitivity of the disease is critical for the prognosis. Hematopoietic stem cell transplantation before being infected with EBV is an optimal treatment.

DNA in sperm is packed with small, charged proteins termed SNBPs (sperm nuclear basic proteins), including mammalian and Drosophila protamines. During spermiogenesis, somatic-type chromatin is taken apart and replaced with sperm chromatin in a multistep process leading to an extraordinary condensation of the genome. During fertilization, the ova face a similarly challenging task of SNBP eviction and reassembly of nucleosome-based chromatin. Despite its importance for the animal life cycle, sperm chromatin metabolism, including the biochemical machinery mediating the mutual replacement of histones and SNBPs, remains poorly studied. In Drosophila, Mst77F is one of the first SNBPs loaded into the spermatid nuclei. It persists in mature spermatozoa and is essential for sperm compaction and male fertility. Here, by using in vitro biochemical assays, we identify chaperones that can mediate the eviction and loading of Mst77F on DNA, thus facilitating the interconversions of chromatin forms in the male gamete. Unlike NAP1 and TAP/p32 chaperones that disassemble Mst77F-DNA complexes, ARTEMIS and APOLLO, orthologs of mammalian importin-4 (IPO4), mediate the deposition of Mst77F on DNA or oligonucleosome templates, accompanied by the dissociation of histone-DNA complexes. In vivo, a mutation of testis-specific Apollo brings about a defect of Mst77F loading, abnormal sperm morphology, and male infertility. We identify IPO4 ortholog APOLLO as a critical component of sperm chromatin assembly apparatus in Drosophila. We discover that in addition to recognized roles in protein traffic, a nuclear transport receptor (IPO4) can function directly in chromatin remodeling as a dual, histone- and SNBP-specific, chaperone.

UNASSIGNED: Recent advances have been made in targeting the phosphoinositide 3-kinase pathway in breast cancer. Phosphatase and tensin homolog (PTEN) is a key component of that pathway.
UNASSIGNED: To understand the changes in PTEN expression over the course of the disease in patients with triple-negative breast cancer (TNBC) and whether PTEN copy number variation (CNV) by next-generation sequencing (NGS) can serve as an alternative to immunohistochemistry (IHC) to identify PTEN loss.
UNASSIGNED: We compared PTEN expression by IHC between pretreatment tumors and residual tumors in the breast and lymph nodes after neoadjuvant chemotherapy in 96 patients enrolled in a TNBC clinical trial. A correlative analysis between PTEN protein expression and PTEN CNV by NGS was also performed.
UNASSIGNED: With a stringent cutoff for PTEN IHC scoring, PTEN expression was discordant between pretreatment and posttreatment primary tumors in 5% of patients (n = 96) and between posttreatment primary tumors and lymph node metastases in 9% (n = 33). A less stringent cutoff yielded similar discordance rates. Intratumoral heterogeneity for PTEN loss was observed in 7% of the patients. Among pretreatment tumors, PTEN copy numbers by whole exome sequencing (n = 72) were significantly higher in the PTEN-positive tumors by IHC compared with the IHC PTEN-loss tumors (p < 0.0001). However, PTEN-positive and PTEN-loss tumors by IHC overlapped in copy numbers: 14 of 60 PTEN-positive samples showed decreased copy numbers in the range of those of the PTEN-loss tumors.
UNASSIGNED: Testing various specimens by IHC may generate different PTEN results in a small proportion of patients with TNBC; therefore, the decision of testing one versus multiple specimens in a clinical trial should be defined in the patient inclusion criteria. Although a distinct cutoff by which CNV differentiated PTEN-positive tumors from those with PTEN loss was not identified, higher copy number of PTEN may confer positive PTEN, whereas lower copy number of PTEN would necessitate additional testing by IHC to assess PTEN loss.
UNASSIGNED: NCT02276443.

UNASSIGNED: Colloid cysts are benign tumors usually located at the level of the foramen of Monro and account for approximately 1% of all intracranial tumors. Endoscopic surgical treatment represents the approach of choice for removal of these tumors and is usually preferred over transcortical or transcallosal microsurgical approaches. Our purpose is to demonstrate the feasibility of endoscopic removal of colloid cysts using a novel aspiration and fragmentation system, currently designed for evacuation of cerebral hematomas.
UNASSIGNED: We performed an evaluation of the results obtained in patients with symptomatic colloid cysts of the third ventricle operated on using an endoscopic neuroevacuation system (Artemis Neuro Evacuation Device, Penumbra, Alameda, California, USA) between April 2020 and April 2022. Instrumentation and surgical technique are described in detail. All patients underwent postoperative MRI to assess the extent of cyst removal.
UNASSIGNED: Five patients were included in our study. The predominant symptom at onset was headache. No intraoperative complications related to the technology in use occurred. The surgical time for the cyst removal was significantly shorter than removal via a standard endoscopic technique (80 vs. 120 min). Removal was complete, both content and capsule of the cyst, in all patients. In all cases there was a complete regression of the previously complained symptoms.
UNASSIGNED: The Artemis Neuro Evacuation Device has proved to be effective and safe in removal of colloid cysts of the third ventricle and may be proposed as a possible alternative or as a complement of the standard instruments routinely used in neuroendoscopy.