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Abstract Alzheimer’s disease (AD) is the most common form of dementia and is characterized by the accumulation of amyloid β (Aβ) and phosphorylated tau. Neuroinflammation, mainly mediated by glial activation, plays an important role in AD progression. Although there is growing evidence for the anti-neuroinflammatory and neuroprotective effects of the cannabinoid system modulation, the detailed mechanism remains unclear. To address these issues, we analyzed the expression levels of cannabinoid receptor type II (Cnr2/Cb2) in App NL-G-F/NL-G-F mice and human AD precuneus, which is vulnerable to amyloid deposition in AD, and the effects of JWH 133, a selective CB2 agonist, on neuroinflammation in primary glial cells and neuroinflammation and cognitive impairment in App NL-G-F/NL-G-F mice. The levels of Cnr2/Cb2 were upregulated in microglia isolated from the cerebral cortex of App NL-G-F/NL-G-F mice. CNR2 expression was also increased in RNAs derived from human precuneus with advanced AD pathology. Chronic oral administration of JWH 133 significantly ameliorated the cognitive impairment of App NL-G-F/NL-G-F mice without neuropsychiatric side effects. Microglia and astrocyte mRNAs were directly isolated from the mouse cerebral cortex by magnetic-activated cell sorting, and the gene expression was determined by quantitative PCR. JWH 133 administration significantly decreased reactive astrocyte markers and microglial C1q, an inducer for the reactive astrocytes in App NL-G-F/NL-G-F mice. In addition, JWH133 administration inhibited the expression of p-STAT3 (signal transducer and activator of transcription 3) in astrocytes in App NL-G-F/NL-G-F mice. Furthermore, JWH 133 administration suppressed dystrophic presynaptic terminals surrounding amyloid plaques. In conclusion, stimulation of microglial CB2 ameliorates cognitive dysfunction in App NL-G-F/NL-G-F mice by controlling astrocyte activation and inducing beneficial neuroinflammation, and our study has implications that CB2 may represent an attractive therapeutic target for the treatment of AD and perhaps other neurodegenerative diseases involving neuroinflammation.

Objective There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM. Methods We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023. Results During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%–40.7%) and 70.0% (95% CI, 55.5%–84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates. Conclusion Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.

Introduction Understanding of adverse reactions to coronavirus disease 2019 vaccines remains limited. Case presentation Case 1: A 52‐year‐old woman, post‐kidney transplantation, experienced sudden vision loss in her left eye after receiving a second dose of coronavirus disease 2019 vaccine. She was diagnosed with ischemic optic neuropathy. Case 2: A 53‐year‐old woman, post‐kidney transplantation, presented with worsening diplopia and left eye pain following the second dose of coronavirus disease 2019 vaccine. She was diagnosed with left abducens nerve palsy. Conclusion Vigilance is essential for recognizing the potential for delayed cranial neuropathy in immunocompromised individuals after coronavirus disease 2019 vaccination.

Ovarian neuroendocrine carcinoma is a rare and aggressive tumor with a poor prognosis. Ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI) are often used for diagnosis. However, no specific features exist, and preoperative diagnosis is often difficult. We present a case in which ovarian neuroendocrine carcinoma was diagnosed postoperatively, with the intention to discuss its imaging features on 18F fluoro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). A 70-year-old woman presented to a local hospital with abdominal pain. CT showed a uterine mass and multiple swollen lymph nodes. The mass expanded from the uterus into the left ovarian vessels on dynamic MRI. The SUVmax of the mass and lymph nodes on 18F-FDG PET/CT were notably elevated to 53.2 and 33.0 respectively. Considering the tumor location and high SUVmax, a malignant uterine tumor was suspected. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omental biopsy, and resection of the left ovarian vessels were performed. Histological examination confirmed that the tumor was a neuroendocrine carcinoma derived from the left ovary. To the best of our knowledge, there are only few reports on the 18F-FDG uptake in ovarian neuroendocrine carcinomas. Conversely, in other organs, the carcinomas frequently exhibit markedly elevated SUVmax on 18F-FDG PET/CT. It is possible that ovarian neuroendocrine carcinomas share similar traits, and elevated SUVmax could indicate the potential presence of this histological type.

Deep subsurface microorganisms constitute over 80 % of Earth's prokaryotic biomass and play an important role in global biogeochemical cycles. Geochemical processes driven by geothermal heating are key factors influencing their biomass and activities, yet their full breadth remains uncaptured. Here, we investigated the microbial community composition and metabolism in microbial-natural-gas-bearing aquifers at temperatures ranging from 38 to 81 °C, situated above nonmicrobial-gas- and oil-bearing sediments at temperatures exceeding 90 °C. Cultivation-based and molecular gene analyses, including radiotracer measurements, of formation water indicated variations in predominant methanogenic pathways across different temperature regimes of upper aquifers: high potential for hydrogenotrophic–methylotrophic, hydrogenotrophic, and acetoclastic methanogenesis at temperatures of 38, 51–65, and 73–81 °C, respectively. The potential for acetoclastic methanogenesis correlated with elevated acetate concentrations with increasing depth, possibly due to the decomposition of sedimentary organic matter. In addition to acetoclastic methanogenesis, in aquifers at temperatures as high as or higher than 65 °C, acetate is potentially utilized by microorganisms responsible for the dissimilatory reduction of sulfur compounds other than sulfate because of their high relative abundance at greater depths. The stable sulfur isotopic analysis of sulfur compounds in water and oil samples suggested that hydrogen sulfide, generated through the thermal decomposition of sulfur compounds in oil, migrates upward and is subsequently oxidized with iron oxides present in sediments, yielding elemental sulfur and thiosulfate. These compounds are consumed by sulfur-reducing microorganisms, possibly reflecting elevated microbial populations in aquifers at temperatures as high as or higher than 73 °C. These findings reveal previously overlooked geothermal-heat-driven geochemical and microbiological processes involved in carbon and sulfur cycling in the deep sedimentary biosphere.

Though promoting student advocacy has become an essential part of leadership education, few studies explore development of advocacy in leadership education. This article offers how distortions, an aspect of a Black feminist reframing of dissonance, is related to existing leadership education literature. It then introduces students' voices demonstrating the importance of the realization of distortions in student advocacy development and links distortions with how power communicates and upholds systemic oppression. Finally, we offer practical recommendations based on a case scenario that utilize Black feminist perspectives of dissonance in refining student advocacy leadership education. Such insight prompts more effective strategies in student advocate development.

Though advocacy and activism have been frequent topics of research, few studies explore this work across campus roles, meaning inclusive of students, faculty, and staff. A more holistic understanding of advocacy would pave the way for more effective social justice efforts. Researchers used hermeneutic phenomenology to engage with 26 advocates finding that identity influences advocacy; advocates work for, with, and to others; and advocates take risks with consequences associated with their identities. The American Counseling Association's Advocacy Competencies extended the analysis to reveal the lack of alliances in cross-campus advocacy.

Summary: Lymphatic vessels are required for the clearance of excess fluid and immune cells from inflamed tissue, making the regulation of lymphangiogenesis an important area of research. Although the positive regulatory mechanisms of lymphangiogenesis are well known, the negative regulatory mechanisms observed during inflammation remain unclear. Here, we identify tenascin-C (TNC) as a spatiotemporal negative regulator of lymphangiogenesis during inflammation. We found an inverse correlation between lymphangiogenesis and TNC expression in a mouse lymphedema model. Genetic deletion of Tnc promotes lymphangiogenesis and improves lymphatic drainage function, thereby accelerating the resolution of inflammation. Conversely, the exogenous addition of TNC suppresses lymphangiogenesis and prolongs inflammation. TNC inhibits the proliferation and promotes apoptosis of lymphatic endothelial cells. Mechanistically, TNC facilitates integrin αvβ1 heterodimer formation, leading to the activation of non-canonical (TAK1/p38MAPK/ATF-2) TGFβ signaling to suppress lymphangiogenesis. Our study highlights the importance of negative regulation of lymphangiogenesis in modulating immune responses.

ABSTRACT Background Cachexia is a poor prognostic factor in many advanced cancers. Cachexia diagnostic criteria of the European Palliative Care Research Collaboration (EPCRC) may underestimate cachexia in Asians; therefore, new criteria have been proposed by the Asian Working Group for Cachexia (AWGC). We compared both criteria to determine differences in diagnostic rates and their association with lung cancer prognosis. Patients and Methods This single‐center, retrospective cohort study considered lung cancer outpatients receiving chemotherapy. Survival was analyzed using Kaplan–Meier curves and log‐rank tests. The association between cachexia diagnosis and prognosis was examined for each set of criteria using a Cox proportional hazards model. C‐statistic analysis was performed to compare the discriminative power for prognosis. Results Among the 106 participants analyzed (median age, 75 [71–79] years; 75 males [70.8%]; 91 [85.9%] with performance status [PS] 0–1), 58 (54.7%) and 77 (72.6%) cachexia cases were diagnosed using the EPCRC and AWGC criteria, respectively. The latter encompassed all but one patient diagnosed using the EPCRC criteria. Patients with cachexia had a significantly poorer prognosis according to both criteria (EPCRC, p = 0.002; AWGC, p = 0.001). Both criteria had almost equal discriminative power for prognosis (EPCRC, C‐statistic = 0.658; AWGC, C‐statistic = 0.658). CRP in the AWGC criteria was most strongly related to prognosis. Conclusions Cachexia was an independent poor prognostic factor in lung cancer patients receiving chemotherapy under the AWGC and EPCRC criteria, both of which had similar prognostic discriminatory power. Among CRP, anorexia, and grip strength, elevated CRP may be the most prognostically relevant parameter in the AWGC criteria.

Objective This study investigated the effects of early treatment and pathophysiology on eosinophilic granulomatosis with polyangiitis neuropathy (EGPA-N).Methods Twenty-six consecutive patients with EGPA-N were diagnosed and treated within a day of admission and underwent clinical analysis. Peripheral nerve recovery rates were evaluated after early treatment by identifying the damaged peripheral nerve through detailed neurological findings.Results The eosinophil count at onset was significantly correlated with the total number of damaged nerves. There was a strong correlation between the timing of treatment and the recovery rate in patients who started treatment within 50 days, as the recovery rate did not increase after 50 days of treatment. Antineutrophil cytoplasmic antibodies (ANCA)-negative cases showed significantly higher recovery rates than ANCA-positive cases. Vasculitis was detected in 67% of ANCA-positive and 29% of ANCA-negative patients in the sural nerve and skin biopsy specimen. In addition, infiltration of eosinophils into peripheral nerve tissues was observed in 40% of ANCA-negative patients, whereas it was absent in ANCA-positive patients. Intrafascicular oedema was found in 95% of all patients.Discussion Our results suggest three pathological pathways: (1) ischaemic peripheral nerve due to vasculitis mainly in ANCA-positive cases, (2) direct infiltration and degranulation of eosinophils in ANCA-negative cases and (3) progression of axonal ischaemia due to intrafascicular oedema in both cases. The study also found that ANCA-negative cases exhibited better responsiveness to acute-phase treatment than ANCA-positive cases. It is essential to treat patients with EGPA-N as early as possible because the patients could recover time-dependently within 50 days of the onset.

Scrub typhus (tsutsugamushi disease) is an acute febrile illness caused by Orientia tsutsugamushi, often found in Asia and Oceania. The presence of an eschar, characterized by a crust, is a key diagnostic finding. Many symptoms of this disease are already known, however reactive arthritis following scrub typhus is very rare. Here, we present a case of 79-year-old man who was referred to our hospital because of continuous fever and left shoulder pain. We found 4-fold rise in Orientia tsutugamushi-specific IgG titer using paired serum samples and Orientia sp. genes by real-time PCR from a crust of right thigh. And the left shoulder joint image was consistent with aseptic arthritis; thus we diagnosed as scrub typhus with reactive arthritis. This case highlights the importance of recognizing reactive arthritis as a symptom of scrub typhus. In this report, we also review published cases of reactive arthritis associated with scrub typhus, and we suppose that this arthritis related to this infection may recover after antibiotic use and have a good prognosis. Physicians' awareness of newly appeared arthritis may contribute to facilitate early diagnosis, and may improve the course of such patients.

Background: Nutritional intake during childhood can shape health and well-being throughout life. Although excess macronutrient intake is considered the main driver of obesity development, micronutrients, i.e., minerals and vitamins, can potentiate or ameliorate pathological processes of adiposity. Hence, the micronutrient intake relationship to childhood obesity can guide precision approaches to nutritional needs, considering the dietary habits of a population. Childhood obesity is a health disparity throughout the United States–Affiliated Pacific (USAP) region. Objectives: The study examined the association between micronutrient intake with body mass index (BMI in kg/m2) and the presence of insulin resistance proxy, acanthosis nigricans (AN), in 3529 children aged 2–8 y from the USAP region in the Children’s Healthy Living study. Methods: The association of micronutrient intakes with BMI and the presence of AN was stratified by World Bank income groups. Main food sources for micronutrients were also identified from 2 d of food records. Obesity and AN were measured by standardized staff. Results: Most USAP children did not meet daily intake recommendations for micronutrients, with low intake of calcium, potassium, vitamin D, vitamin E, excess sodium, vitamin A, folate, and niacin. Obesity was directly associated with thiamin intake and inversely associated with selenium intake. AN was inversely associated with calcium, copper, iron, phosphorus, potassium, riboflavin, vitamin B6, vitamin D, and vitamin E intakes and directly associated with selenium and pantothenic acid intake. Micronutrient intake imbalances were most associated with insulin resistance and obesity in lower-middle and high-income groups in the USAP region, respectively. Conclusions: The profile of micronutrient intake in USAP children and its association with obesity and insulin resistance can be used to provide precision nutrition policy guidance according to the World Bank income group to improve micronutrient intake and curb childhood obesity.

Cold-spray processing is a promising technique for the metallization of carbon fiber-reinforced plastics (CFRPs). However, the adhesion between the cold-sprayed metal deposits and CFRP substrate needs to be improved. In this study, a novel two-step strategy was developed to significantly enhance the adhesion strength of cold-sprayed Sn/epoxy-based CFRP interfaces. The first step involved eroding the CFRP substrate at a high gas temperature (623 K) to artificially expose the carbon fibers at the surface. In the second step, Sn particles were deposited on the eroded CFRP substate at 523 K, forming a uniform coating. The exposed carbon fibers (CFs) serve as linkages and anchors at the Sn/CFRP interfaces, significantly enhancing the adhesion strength of the single-step Sn coating (∼2 MPa) to ∼ 6.25 MPa after three or more passes. A surface roughness of Sa ≈ 40 μm after the first step was optimal for enhancing the mechanical interlocking at the interfaces. These findings emphasize the importance of interfacial modification in enhancing the mechanical interlocking between the materials, which is crucial for the dominant adhesion mechanism, and suggest an effective strategy that can be applied in continuous cold-spray processing.

BackgroundEvidence of the effectiveness of physiotherapy, including muscle strength training, coordination training, aerobic exercise, cycling regimen, balance training, gait training, and activity of daily living training, in patients with degenerative cerebellar ataxia (DCA) was insufficient for clinical decision making. We aimed to explore clinical outcomes and examine the parameters associated with physical impairment and activity in people with DCA based on preregistration (PROSPERO: CRD42024493883).MethodsThe PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted. The Grading of Recommendations Assessment, Development, and Evaluation framework (GRADE) was used to assess the quality of evidence, and a meta-analysis was performed.ResultsEighteen RCTs, which included 398 participants, showed a serious risk of bias (RoB) and low certainty of evidence for this primary outcome. For meta-analysis, 315 patients assessed based on the Scale for Assessment and Rating of Ataxia (SARA) were included. Overall, physiotherapy significantly reduced SARA scores (MD = −1.41, [95% CI: −2.16, −0.66]); the subgroup analysis showed that the following interventions exerted significant effects: multi-aspect training program (5 studies, MD = −1.59, [95% CI: −5.15, −0.03]), balance training (3 studies, MD = −1.58, [95% CI: −2.55, −0.62]), and aerobic training (3 studies, MD = −1.65, [95% CI: −2.53, −0.77]). By contrast, vibration (2 studies, MD = −0.56, [95% CI: −2.05, 0.93]) and dual-task training (1 study, MD = 0.24, [95% CI: −6.4, 6.88]) exhibited no significant effects.ConclusionPhysical therapy, especially multi-aspect physical therapy such as muscle strengthening, coordination training, gait training, and ADL training, may reduce DCA symptoms. Further, balance and aerobic training can be added to the program. However, the estimated effect size may change in future studies because of the serious RoB, very low certainty of evidence, and high heterogeneity with SARA as the primary outcome. High-quality RCTs are required to establish evidence for the effectiveness of physical therapy in patients with DCA.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=493883, identifier: CRD42024493883.

Abstract This study investigates backbone engineering and evaluates the thermoelectric properties of FeCl3‐doped naphthobisthiadiazole (NTz)‐based donor–acceptor (D‐A) conjugated polymer films. The NTz acceptor unit is coupled with three distinct donor units, namely dialkylated terthiophene (3T), dialkylated quaterthiophene (4T), and dialkylated bisthienyl thienothiophene (2T‐TT) to yield copolymers designated as PNTz3T, PNTz4T, and PNTzTT. The difference in donor units leads to diverse molecule stacking and electronic properties, which can be systematically discovered via the three polymers. The linear structure of PNTz4T enables an orderly arrangement of side chains, thereby promoting dopant intercalation for enhanced carrier concentration. Additionally, this linear structure leads to an edge‐on stacking mode, thereby improving the in‐plane carrier mobility. As a result, the doped PNTz4T exhibits the highest electrical conductivity (σ) of 88.3 S cm−1 along with a Seebeck coefficient (S) of 62.2 µV K−1, thereby achieving the highest power factor (PF) of 34.2 µW m−1 K−2. These results highlight the relationship between the molecular design, microstructure, and doping effects in manipulating the thermoelectric performance of doped NTz‐based D‐A polymers.

ABSTRACT Introduction Extensive small cell lung cancer (ES‐SCLC) are currently managed using first‐line chemotherapy options, including atezolizumab (Atezo) plus etoposide and carboplatin (CE) or durvalumab (Durva) plus etoposide with either cisplatin (PE) or carboplatin (CE). However, a definitive distinction in therapeutic effects between Atezo and Durva in these regimens remains unestablished. Methods We analyzed data from 100 patients diagnosed with ES‐SCLC who received immune checkpoint inhibitors (ICIs) as first‐line chemotherapy. Among them, 70 were administered Atezo + CE, 12 received Durva + PE, and 18 received Durva + CE. We assessed the efficacy of the two ICIs across various factors. Results The progression‐free survival (PFS) and overall survival (OS) did not significantly differ between Atezo + CE and Durva + CE/PE as first‐line chemotherapy treatments for SCLC. We observed no significant differences in age, sex, performance status (PS), liver metastasis, bone metastasis, or platinum‐based agent usage between the treatment cohorts. However, a marked improvement in PFS and OS was observed in the solitary patient with brain metastasis treated with Atezo + CE. Conclusion The primary distinction between these treatments was observed in the management of patients with brain metastasis. The literature lacks comparative studies on the effects of first‐line ICI treatment on the central nervous system, rendering our findings significant in clinical practice. Despite the retrospective nature of this study and the potential for various biases, we recommend the preferential use of Atezo + CE in patients with brain metastasis to potentially enhance prognosis.

IntroductionAtopic dermatitis (AD) is a common and relapsing skin disease characterized by skin barrier dysfunction, inflammation, and chronic pruritus. Both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of the pathology of AD. Although various anti-inflammatory pharmacological agents, including cytokine inhibitors and signaling pathway blockers, have been developed recently, keeping the skin clean is of utmost importance in maintaining physiological cutaneous barrier function and avoiding an AD flare. Ultrafine bubbles (UFBs) are less than 1 μm in diameter and usually used to clean medical equipment. A UFB shower is expected to keep skin clean with attention to the temperature and strength of the shower.MethodsWe examined the effects of a UFB shower on two mouse models of AD: Dermatophagoides farinae body (Dfb)- induced AD in NC/Nga mice and interleukin (IL)-33 transgenic (tg) mice. Each model comprised three groups: UFB shower-treated, normal shower-treated, and untreated. We evaluated the mice using a dermatitis score, scratching counts, histology, and the expression of inflammatory cytokines and skin barrier-related proteins.ResultsIn the Dfb-induced AD mouse model, clinical features improved markedly in the UFB shower-treated mice compared to other groups. IL-4 and IL-13 levels decreased in the skin of normal and UFB shower-treated mice. In addition, in the skin of UFB shower-treated mice, the expression levels of skin barrier-related proteins were increased compared to normal showertreated mice. However, we found no significant differences in IL33tg mice.DiscussionThese results suggest that UFB shower can recover the skin barrier function and improve skin inflammation, especially in conditions such as extrinsic AD.

The SLC25A20 gene encodes carnitine-acylcarnitine translocase (CACT), facilitating the transport of long-chain acylcarnitine required for energy production via β-oxidation into the mitochondria. Loss-of-function mutations in this gene lead to CACT deficiency, a rare autosomal recessive disorder of fatty acid metabolism characterized by severe symptoms including cardiomyopathy, hepatic dysfunction, rhabdomyolysis, hypoketotic hypoglycemia, and hyperammonemia, often resulting in neonatal mortality. Here, we utilized CRISPR/Cas9 gene editing to isolate slc25a20 mutant zebrafish. Homozygous mutants displayed significant lethality, with the majority succumbing before reaching maturity. However, we identified a notably rare homozygous individual that survived into adulthood, prompting a histological examination. Firstly, we observed adipose tissue accumulation at various sites in the homozygous mutant. The mutant heart exhibited hypertrophy, along with degenerated myocardial and muscle cells containing numerous eosinophilic nuclei. Additionally, we found no large oil droplet vacuoles in the mutant liver; however, the hepatocytes displayed numerous small vacuoles resembling lipid droplets. Iron deposition was evident in the spleen and parts of the liver. Overall, our slc25a20 zebrafish mutant displayed tissue pathologies analogous to human CACT deficiency, suggesting its potential as a pathological model contributing to the elucidation of pathogenesis and the improvement/development of therapies for CACT deficiency.

Anticipating the onset, location and severity of radiation dermatitis before radiotherapy can aid in dermatological care. This study developed a method for creation of a prediction diagram for dermatitis and conducted a comparative verification between the prediction diagram and actual patient condition. The prediction diagram involved converting skin doses into 2 Gy fractionated equivalent doses using α/β of 10.0, defining regions of interest (ROIs) from 20-50 Gy at 10 Gy intervals. Overlaps between these ROIs at each dose level and the skin (external) was sequentially color-coded as blue, yellow, red, and purple. The study included four patients: two underwent head and neck treatment and two received neck and chest treatment. This approach involved a visual assessment comparing the prediction diagram with skin photographs captured at the end of treatment. Nurses marked skin sites corresponding to grades 1 and 2 on photographs, assessing their correlation with the predicted range. Visual assessment results were largely positive, although one patient exhibited slightly lower scores. Results revealed a correlation between grade 1 skin reactions and the 20 Gy regions. Grade 2 reactions were observed in regions near 30 and 40 Gy. Although discrepancies between prediction diagram and actual skin symptoms were observed in patients, a broad agreement was evident. The prediction diagram cannot accurately predict radiation dermatitis, as it does not account for skin symptoms unrelated to the dose. However, the diagram is significant as it provides physicians, nurses, and patients with concise and visually comprehensible information regarding the location of dermatitis.

Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in AID-prone MRL/MpJ-Faslpr/lpr mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ-Faslpr/lpr at five months and defined as moLpr and moMpJ, respectively. AID indices (spleen weight and serum autoantibody levels) and fertility status (number and size of fetuses, morphology, and comprehensive gene expression of placentas) were evaluated on gestational day 15.5. Both strains showed equivalent fertility, but moLpr showed lighter placentas and fetuses than moMpJ, and decreased fertility with AID severity. moLpr placentas had a higher number of T cells, higher expression of genes associated with T helper 2 and T follicular helper functions, and altered expression of genes (Krt15, Slc7a3, Sprr2a3) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (Ccl5, Cxcl9) was significantly increased in moLpr placentas, and CCL5 and CXCL9 were detected in moLpr placentas, particularly in T cells and placenta-component cells, respectively. Thus, AID altered placental morphofunction and fertility in mice; however, fertility was maintained at the examined time points. This study enhances our understanding of placental alterations and gestational risk due to AIDs.

Biological patterning events that occur early in development establish proper tissue morphogenesis. Identifying the mechanisms that guide these patterning events is necessary in order to understand the molecular drivers of development and disease and to build tissues in vitro. In this study, we use an in vitro model of gastrulation to study the role of tight junctions and apical/basolateral polarity in modulating bone morphogenic protein-4 (BMP4) signaling and gastrulation-associated patterning in colonies of human pluripotent stem cells (hPSCs). Disrupting tight junctions via knockdown (KD) of the scaffolding tight junction protein-1 (TJP1, also known as ZO1) allows BMP4 to robustly and ubiquitously activate pSMAD1/5 signaling over time, resulting in loss of the patterning phenotype and marked differentiation bias of pluripotent stem cells to primordial germ cell-like cells (PGCLCs). These findings give important insights into how signaling events are regulated and lead to spatial emergence of diverse cell types in vitro.

Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene are linked to Fragile X Syndrome, the most common monogenic cause of intellectual disability and autism. People affected with mutations in FMR1 have higher incidence of obesity, but the mechanisms are largely unknown. In the current study, we determined that male Fmr1 knockout mice (KO, Fmr1-/y), but not female Fmr1-/-, exhibit increased weight when compared to wild-type controls, similarly to humans with FMR1 mutations. No differences in food or water intake were found between groups; however, male Fmr1-/y display lower locomotor activity, especially during their active phase. Moreover, Fmr1-/y have olfactory dysfunction determined by buried food test, although they exhibit increased compulsive behavior, determined by marble burying test. Since olfactory brain regions communicate with hypothalamic regions that regulate food intake, including POMC neurons that also regulate locomotion, we examined POMC neuron innervation and numbers in Fmr1-/y mice. POMC neurons express Fmrp, and POMC neurons in Fmr1-/y have higher inhibitory GABAergic synaptic inputs. Consistent with increased inhibitory innervation, POMC neurons in the Fmr1-/y mice exhibit lower activity, based on cFOS expression. Notably, Fmr1-/y mice have fewer POMC neurons than controls, specifically in the rostral arcuate nucleus, which could contribute to decreased locomotion and increased body weight. These results suggest a role for Fmr1 in the regulation of POMC neuron function and the etiology of Fmr1-linked obesity.