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A field survey of indoor environmental measurements and questionnaires on thermal sensation, overall comfort, and behaviors was conducted in four office buildings in Japan by visiting each office every month over a duration of more than a year during the coronavirus disease 2019 (COVID-19) pandemic. The indoor environment was measured concurrently. We obtained 1047 votes from office workers in their 20s to 60s. The regression and Griffiths’ methods were used to calculate the indoor comfort temperature. A logistic regression analysis was used to develop the occupant behavior model. Over 70% of the occupants found the indoor environment comfortable at a mean comfort temperature of 23.2 to 25.9 °C. Gender differences were observed in thermal sensation and overall comfort, but a gender difference was observed only in the cooling mode for the indoor comfort temperature. An adaptive model was developed for the office buildings in Nagasaki city to predict the indoor comfort temperature from the outdoor air temperature. The proportions of heating, cooling, and fan usage can be predicted from the outdoor air temperature using a logistic regression analysis. The adaptive model and occupant behavior model are useful for the indoor temperature control of the existing buildings and thermal simulation of the new building design.

Thermal comfort in office buildings is instrumental in improving the productivity of employees while maintaining their health. The primary objectives of this research were to analyze the comfort temperature in Japanese office buildings and investigate its relationship with outdoor air temperature. Additionally, we examined the differences in comfort temperatures with respect to closed and opened windows to factor in the increase in the opening of windows during the COVID-19 pandemic when air-conditioning systems were operated. We investigated the environmental conditions of office buildings and the thermal comfort of the occupants through monthly visits to each office building over a year. Field data were collected from four office buildings located in Nagasaki City, with 1047 votes obtained from 143 participants. The survey indicated that the occupants were highly satisfied with the thermal environment in their offices. The correlation between indoor comfort temperature and outdoor temperature was high in the FR mode. Based on the analysis, we developed an adaptive model for office buildings in Nagasaki City and compared it with existing adaptive models used for buildings in other regions of Japan. The proposed model is useful for energy-saving designs that bring out human adaptive capacity.

Immune checkpoint inhibitors (ICIs) play a central role in various cancers. ICIs can cause immune-related adverse events (irAEs). As severe irAEs can be life-threatening, biomarkers for estimating irAE onset are crucial. The neutrophils-to-lymphocytes ratio (NLR) reflects the systemic immune condition and known as a prognostic marker in ICI treatment. Our study evaluated if the NLR corresponded with irAEs, and its feasibility as a biomarker for irAE onset. We retrospectively analyzed 275 cancer patients treated with anti-PD-1 monotherapy. We observed 166 irAEs in 121 patients. The NLR was significantly elevated during irAEs. Patients experiencing interstitial pneumonitis showed NLR elevation 4 weeks before initial symptoms and diagnosis. Analyzing receiver operating characteristics curves revealed that elevated NLR distinguished subsequent pneumonitis severity with high accuracy (AUC 0.93, sensitivity 88.9%, specificity 88.2%, cut-off 2.37, p  = 0.0004). After a severe irAE occurred, two NLR trends were observed. Patients who showed a prompt reduction in elevated NLRs had favorable progression-free survival (hazard ratio 0.32, 95% CI 0.10–1.01, p = 0.0140) and overall survival (hazard ratio 0.23, 95% CI 0.06–0.86, p  = 0.0057) compared to the patients who maintained elevated NLRs. These findings suggest that continuous monitoring of NLR trends may predict irAE onset and severity and subsequent prognosis.

Families of critically ill patients are predisposed to tremendous burdens when their relatives are admitted to the intensive care unit (ICU). Postintensive care syndrome family (PICS‐F) can be described as a devastated life, encompassing psychological, physical, and socioeconomical burdens that begin with the emotional impact experienced by the family when the patient is admitted to the ICU. PICS‐F was primarily proposed as a clinically significant psychological impairment, but it needs to be extended beyond the psychological impairment of the family to include physical and socioeconomical impairments in the future. The prevalence of physiological problems including depression, anxiety and post‐traumatic syndrome is 20–40%, and that of non‐physiological problems including fatigue is 15% at 6 months after the ICU stay. Assessment of PICS‐F was frequently conducted at 3‐ or 6‐month points, although the beginning of the evaluation was based on different assessment points among each of the studies. Families of ICU patients need to be given and understand accurate information, such as the patient's diagnosis, planned care, and prognosis. Prevention of PICS‐F requires a continuous bundle of multifaceted and/or multidisciplinary interventions including providing a family information leaflet, ICU diary, communication facilitators, supportive grief care, and follow‐up, for the patient and families from during the ICU stay to after discharge from the ICU. This is the first comprehensive review of PICS‐F to address the concept, risk factors, assessment tools, prevalence, and management to prevent PICS‐F to facilitate acute care physicians' understanding of PICS‐F. Postintensive care syndrome family (PICS‐F) is grave, which is a psychological, physical, and socioeconomic disorder of the family after the patient is admitted to the ICU that has a major impact on the quality of life of the families and the ability to support the recovery of ICU patients.

Objective Dead-time loss is reported to be non-negligible for some patients with a high tumor burden in Lu-177 radionuclide therapy, even if the administered activity is 7.4 GBq. Hence, we proposed a simple method to shorten the apparent dead time and reduce dead-time loss using a thin lead sheet in previous work. The collimator surface of the gamma camera was covered with a lead sheet in our proposed method. While allowing the detection of 208-keV gamma photons of Lu-177 that penetrate the sheet, photons with energies lower than 208 keV, which cause dead-time loss, were shielded. In this study, we evaluated the usefulness of tungsten functional paper (TFP) for the proposed method using Monte Carlo simulation. Methods The count rates in imaging of Lu-177 administered to patients were simulated with the International Commission on Radiological Protection (ICRP) 110 phantom using the GATE Monte Carlo simulation toolkit. The simulated gamma cameras with a 0.5-mm lead sheet, 1.2-mm TFP, or no filter were positioned closely on the anterior and posterior sides of the phantom. The apparent dead times and dead-time losses at 24 h after administration were calculated for an energy window of 208 keV ± 10%. Moreover, the dead-time losses at 24–120 h were analytically assessed using activity excretion data of Lu-177-DOTATATE. Results The dead-time loss without a filter was 5% even 120 h after administration in patients with a high tumor burden and slow excretion, while those with a lead sheet and TFP were 0.22 and 0.58 times less than those with no filter, respectively. The count rates with the TFP were 1.3 times higher than those with the lead sheet, and the TFP could maintain primary count rates at 91–94% of those without a filter. Conclusions Although the apparent dead time and dead-time loss with the lead sheet were shorter and less than those with TFP, those with TFP were superior to those without a filter. The advantage of TFP over the lead sheet is that the decrease in primary count rates was less.

Individuals with Down syndrome (DS) commonly show unique pathological phenotypes throughout their life span. Besides the specific effects of dosage-sensitive genes on chromosome 21, recent studies have demonstrated that the gain of a chromosome exerts an adverse impact on cell physiology, regardless of the karyotype. Although dysregulated transcription and perturbed protein homeostasis are observed in common in human fibroblasts with trisomy 21, 18, and 13, whether and how this aneuploidy-associated stress acts on other cell lineages and affects the pathophysiology are unknown. Here, we investigated cellular stress responses in human trisomy 21 and 13 neurons differentiated from patient-derived induced pluripotent stem cells. Neurons of both trisomies showed increased vulnerability to apoptotic cell death, accompanied by dysregulated protein homeostasis and upregulation of the endoplasmic reticulum stress pathway. In addition, misfolded protein aggregates, comprising various types of neurodegenerative disease-related proteins, were abnormally accumulated in trisomic neurons. Intriguingly, treatment with sodium 4-phenylbutyrate, a chemical chaperone, successfully decreased the formation of protein aggregates and prevented the progression of cell apoptosis in trisomic neurons. These results suggest that aneuploidy-associated stress might be a therapeutic target for the neurodegenerative phenotypes in DS.

Background The effect of early parenteral nutrition (EPN) therapy on brain development in extremely premature infants at a gestational age (GA) of 22–25 weeks remains unknown. Objectives This study investigated the effect of EPN therapy on GA 22 to 25 weeks of gestation using magnetic resonance imaging (MRI) global brain abnormality score (GBAS). Subjects Forty-six preterm infants born before 26 weeks of gestation were divided into the GA 22–23 weeks (GA 22–23; n = 18) and GA 24–25 weeks (GA 24–25; n = 28) group. Methods Each infant received ≥3.0 g/kg/day of amino acids from day 1 of life and ≥1.0 g/kg/day of lipid emulsion the next day. Weight change during hospitalization, GBAS at discharge, and developmental quotient (DQ) until three years old were compared between the groups. Results GA 22–23 showed long-term postnatal weight loss, but weight at 41 weeks of postmenstrual age did not differ between the groups. The GBAS score was not significantly different, but the head circumference was smaller in GA 22–23 than in GA 24–25 until 2 years old. The DQ at 1–1.5 years old was lower in GA 22–23 than that of GA 24–25; however, there was no significant difference in DQ after 2 years old between the groups. Conclusions The effect of nutritional support with EPN therapy in premature neonates born at <24 weeks of gestation may still be inadequate. GBAS is useful for assessing brain development in very preterm infants, and the importance of nutritional support during the first few weeks of life should continue to be explored.

Background The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. Methods We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1–3), important, but not critical (4–6), and critical (7–9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. Results In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. Conclusion Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

[...]in a phase 2 trial of the PD‐1 inhibitor nivolumab in ATL patients with an increased mutational load and overexpression of PD‐L1, the first 3 patients unexpectedly developed rapid progression of disease after a single dose of nivolumab. 3 Analysis of primary cells obtained from these patients revealed a tumor‐suppressive role for PD‐1 in ATL. 4 Conversely, in a Japanese phase 2 trial, 8 patients with ATL received at least 1 dose of nivolumab without such rapid acceleration of disease. 5 HTLV‐1 is a human retrovirus that causes HTLV‐1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases in addition to ATL. 6 Although the precise mechanisms of progression from the asymptomatic state to HTLV‐1–associated disease in HTLV‐1 carriers are unknown, risk factors for ATL development in such individuals are thought to include a high HTLV‐1 proviral load in peripheral blood, older age, a family history of ATL, and the presence of symptoms. 7 PD‐1 inhibitors have shown unprecedented clinical activity and have changed the standard of care for many types of cancer. 8 Although HTLV‐1 is not routinely tested for, c. 5% of cancer patients have been found to be HTLV‐1 carriers in HTLV‐1 endemic areas. 9 However, the risk for development of HTLV‐1–associated disease in asymptomatic carriers treated with PD‐1 inhibitors for cancer is not known. [...]a 75‐y‐old man with adenocarcinoma was treated with pembrolizumab for >16 mo without evidence of HTLV‐1–associated disease and without progression of lung cancer. The median follow‐up period for these 3 patients was 12 mo (range, 7‐16 mo), and none of them developed ATL or any other disease related to HTLV‐1 infection during the follow‐up period. 1 TableCharacteristics of patients with HTLV‐1 and NSCLC treated with PD‐1 inhibitors Case Age Sex ECOG PS Histology Driver mutation PD‐L1 TPS Line/drugs BOR a Duration of PD‐1 therapy Follow‐up period 1 68 M 1 Adeno None detected 85% 2/Pembro PR 16 mo, ongoing 16 mo 2 62 M 1 Sq None detected N/A 3/Nivo SD 4 mo, discontinued due to PD 7 mo 3 75 M 0 Adeno None detected N/A 5/Nivo PD 1 mo, discontinued due to PD 12 mo Abbreviations: Adeno, adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group performance status; M, male; N/A, not available; Nivo, nivolumab; PD, progression disease; PD‐L1, programmed death ligand‐1; Pembro, pembrolizumab; PR, partial response; SD, stable disease; Sq, squamous cell carcinoma; TPS, tumor proportion score. aBest overall response (BOR) as assessed by the investigator according to the Response Evaluation Criteria in Solid Tumors, version 1.1.