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The autophagy–lysosome pathway and apoptosis constitute vital determinants of cell fate and engage in a complex interplay in both physiological and pathological conditions. Central to this interplay is the archetypal autophagic cargo adaptor p62/SQSTM1/Sequestosome-1 which mediates both cell survival and endoplasmic reticulum stress-induced apoptosis via aggregation of ubiquitinated caspase-8. Here, we investigated the role of p62-mediated apoptosis in head and neck squamous cell carcinoma (HNSCC), which can be divided into two groups based on human papillomavirus (HPV) infection status. We show that increased autophagic flux and defective apoptosis are associated with radioresistance in HPV(-) HNSCC, whereas HPV(+) HNSCC fail to induce autophagic flux and readily undergo apoptotic cell death upon radiation treatments. The degree of radioresistance and tumor progression of HPV(-) HNSCC respectively correlated with autophagic activity and cytosolic levels of p62. Pharmacological activation of the p62-ZZ domain using small molecule ligands sensitized radioresistant HPV(-) HNSCC cells to ionizing radiation by facilitating p62 self-polymerization and sequestration of cargoes leading to apoptosis. The self-polymerizing activity of p62 was identified as the essential mechanism by which ubiquitinated caspase-8 is sequestered into aggresome-like structures, without which irradiation fails to induce apoptosis in HNSCC. Our results suggest that harnessing p62-dependent sequestration of ubiquitinated caspase-8 provides a novel therapeutic avenue in patients with radioresistant tumors.

Helicobacter pylori (HP) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Increased virulence in HP isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island ( cag PAI). We analyzed the microvariants in cag PAI genes with the hypothesis that they may play an important role in determining HP virulence. We tested DNAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (CG, N = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cag PAI genes from Latin American Western HP strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.

Purpose This study aimed to describe the experiences of nurses who were employed in a psychiatric hospital in Fukushima prefecture during the Great East Japan Earthquake and to explore what sustained the nurses while they worked in the damaged hospital. Design and Methods The research design was a qualitative descriptive study. The setting for the study was one of the Fukushima psychiatric hospitals where functions were disrupted by the earthquake and tsunami. Data were collected through a dialogic interview and Katarai (a form of group interview). Nine psychiatric nurses from the hospital participated. The interview and Katarai were transcribed and the narratives were analyzed using a phenomenological approach. Findings Themes identified from the transcripts were: (a) the nurses’ internalized perception of their duties, (b) responsibility toward their patients, (c) conflicts among nurses and dilemmas nurses faced during this period, and (d) what sustained the nurses to continue working. Conclusions Through the earthquake experience, the nurses in this study reconsidered their own ways of living and ways of nursing that they had not thought about before the disaster. The findings also revealed that the state of hospital management and nursing care under normal conditions are reflected during the crisis situation in a disaster. Clinical Relevance Clearly, whether it is natural disaster or conflict caused by man, healthcare infrastructures are challenged when unexpected disruptions occur. The findings of this study are applicable not only because they provide guidance about infrastructure development for disaster preparedness, but also because they provide practical methods to support nurses who are placed in strongly stressful situations and have to protect patients.

•Developmental changes in brain hemodynamics related to tactile stimulation from neonates to 10 months of chronological age were assessed.•The time to peak for oxygenated hemoglobin was not affected by age in any brain region.•Oxygenated hemoglobin amplitude was influenced by the development of broader areas, including sensorimotor-related but excluding supplementary motor area. Neural-activity-associated hemodynamic changes have been used to noninvasively measure brain function in the early developmental stages. However, the temporal changes in their hemodynamics are not always consistent with adults. Studies have not evaluated developmental changes for a long period using the same stimuli; therefore, this study examined the normalized relative changes in oxygenated hemoglobin (Δ[oxy-Hb]) in full-term infants and compared them with neonates up to 10 months of age during the administration of tactile vibration stimuli to their limbs using whole-head functional near-infrared spectroscopy. The time to peak of normalized Δ[oxy-Hb] was not affected by age. The amplitude of normalized Δ[oxy-Hb] showed an effect of age in broader areas, including sensorimotor-related but excluding supplementary motor area; the amplitude of normalized Δ[oxy-Hb] decreased the most in the 1–2-month-old group and later increased with development. We hypothesized that these results may reflect developmental changes in neural activity, vasculature, and blood oxygenation.

For the last 500 years, the Americas have been a melting pot both for genetically diverse humans and for the pathogenic and commensal organisms associated with them. One such organism is the stomach-dwelling bacterium Helicobacter pylori, which is highly prevalent in Latin America where it is a major current public health challenge because of its strong association with gastric cancer. By analyzing the genome sequence of H. pylori isolated in North, Central and South America, we found evidence for admixture between H. pylori of European and African origin throughout the Americas, without substantial input from pre-Columbian (hspAmerind) bacteria. In the US, strains of African and European origin have remained genetically distinct, while in Colombia and Nicaragua, bottlenecks and rampant genetic exchange amongst isolates have led to the formation of national gene pools. We found three outer membrane proteins with atypical levels of Asian ancestry in American strains, as well as alleles that were nearly fixed specifically in South American isolates, suggesting a role for the ethnic makeup of hosts in the colonization of incoming strains. Our results show that new H. pylori subpopulations can rapidly arise, spread and adapt during times of demographic flux, and suggest that differences in transmission ecology between high and low prevalence areas may substantially affect the composition of bacterial populations.

Compound identification is a critical step in untargeted metabolomics. Its most important procedure is to calculate the similarity between experimental mass spectra and either predicted mass spectra or mass spectra in a mass spectral library. Unlike the continuous similarity measures, there is no study to assess the performance of binary similarity measures in compound identification, even though the well-known Jaccard similarity measure has been widely used without proper evaluation. The objective of this study is thus to evaluate the performance of binary similarity measures for compound identification in untargeted metabolomics. Fifteen binary similarity measures, including the well-known Jaccard, Dice, Sokal–Sneath, Cosine, and Simpson measures, were selected to assess their performance in compound identification. using both electron ionization (EI) and electrospray ionization (ESI) mass spectra. Our theoretical evaluations show that the accuracy of the compound identification was exactly the same between the Jaccard, Dice, 3W-Jaccard, Sokal–Sneath, and Kulczynski measures, between the Cosine and Hellinger measures, and between the McConnaughey and Driver–Kroeber measures, which were practically confirmed using mass spectra libraries. From the mass spectrum-based evaluation, we observed that the best performing similarity measures were the McConnaughey and Driver–Kroeber measures for EI mass spectra and the Cosine and Hellinger measures for ESI mass spectra. The most robust similarity measure was the Fager–McGowan measure, the second-best performing similarity measure in both EI and ESI mass spectra.

(HP) infection has been linked to nearly 90 different health conditions, including gastric malignant and premalignant lesions. Recently, Mendelian randomization (MR) has gained popularity to overcome limitations in observational studies. This review aims to compile MR studies on the causal relationship between HP infection and health outcomes, systematically assess the quality of individual studies, evaluate the overall evidence in comparison with other existing data, and identify common strengths and weaknesses in order to guide future research directions on HP-associated health outcomes. Eligible studies were identified from the two major biomedical literature databases, PubMed and Embase. After removing overlaps, we found 33 unique records published by July 10, 2024. Among those, 16 were qualified for full-text review as original research papers presenting MR analysis with HP infection as the primary exposure of interest. Among the 16 studies, one was one-sample MR study and the rest 2-sample MR studies. All except one were conducted on individuals of European descent. Health outcomes studied include four metabolic conditions, four cardiovascular diseases (CVDs), five gastrointestinal conditions, and three other miscellaneous conditions. All used genome-wide association study (GWAS) data on HP serology to select instrumental variants, ranging from 1 to 84. Nine out of 16 studies concluded that HP had a causal association with the disease of their interest. However, not all papers fully examined whether MR key assumptions were met and there are inaccurate descriptions and misinterpretations in many papers. In addition, there are inconsistencies between studies, depending on the choice of exposure GWAS from which instrumental variants were chosen. Overall, published MR studies concerning HP infection and various health outcomes to date are limited in their quality/integrity. The results from HP eradication trials completed or in progress may help address the causality of some of the health outcomes with high incidence rates. In addition, MR studies in non-European populations with higher HP prevalence are warranted.

Cerebral haemodynamics during the immediate transition period in neonates may differ depending on whether delivery is vaginal or by caesarean section. However, these differences have never been confirmed by near-infrared time-resolved spectroscopy (TRS). Therefore, the purpose of this study was to compare cerebral blood volume (CBV) and cerebral haemoglobin oxygen saturation (ScO 2 ) between healthy term neonates by mode of delivery. Subjects were 31 healthy term neonates who did not require resuscitation. Thirteen neonates were delivered vaginally (VD group) and 18 were delivered by elective caesarean section (CS group). Absolute oxyhaemoglobin, deoxyhaemoglobin, and total haemoglobin concentrations were measured continuously by TRS; oxyHb × 100/totalHb (ScO 2 ) (%) and CBV (mL/100 g brain tissue) were also calculated. Measurements were started as soon as possible after birth, obtained from 1 to 2 min after birth, and continued until 15 min after birth. CBV was significantly higher in the VD group than in the CS group in the 4 min after birth but not thereafter. There were no significant between-group differences in ScO 2 and SpO 2 . These findings indicate that there is a difference in cerebral haemodynamic patterns in the first 4 min after delivery between term neonates by mode of delivery when CBV is monitored by TRS.

We previously reported the neuroprotective potential of combined hydrogen (H 2 ) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H 2 gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H 2 gas ventilation and TH with TH alone. Piglets were divided into three groups: HI insult with normothermia (NT, n = 10), HI insult with hypothermia (TH, 33.5 ± 0.5 °C, n = 8), and HI insult with hypothermia plus H 2 ventilation (TH + H 2 , 2.1–2.7%, n = 8). H 2 ventilation and TH were administered and the cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO 2 ) were recorded for 24 h after the insult. CBV was significantly higher at 24 h after the insult in the TH + H 2 group than in the other groups. ScO 2 was significantly lower throughout the 24 h after the insult in the TH + H 2 group than in the NT group. In conclusion, combined H 2 gas ventilation and TH increased CBV and decreased ScO 2 , which may reflect elevated cerebral blood flow to meet greater oxygen demand for the surviving neurons, compared with TH alone.

Purpose We described unmet information and service needs of adolescent and young adult (AYA) cancer survivors (15–39 years of age) and identified sociodemographic and health-related factors associated with these unmet needs. Methods We studied 523 AYAs recruited from seven population-based cancer registries, diagnosed with acute lymphocytic leukemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, germ cell cancer, or sarcoma in 2007–2008. Participants completed surveys a median of 11 months from diagnosis. Multivariable logistic regression analyses were used to estimate associations between unmet (information and service) needs and sociodemographic and health-related factors. Results More than half of AYAs had unmet information needs relating to their cancer returning and cancer treatments. AYAs needing services, but not receiving them, ranged from 29 % for in-home nursing to 75 % for a support group. The majority of AYAs who needed a pain management expert, physical/occupational therapist, mental health worker, or financial advice on paying for health care did not receive services. In multivariable analyses, older participants, men, participants of non-white race/ethnicity, and participants who reported less than excellent general health or fair/poor quality of care were more likely to report unmet information needs. Factors associated with both unmet service and information needs included physical health or emotional problems interfering with social activities or having ≥3 physical treatment-related symptoms. Conclusions Recently diagnosed AYA cancer survivors have substantial unmet information needs varying by demographic and health-related factors. Implications for cancer survivors We identified subgroups of AYA cancer survivors with high unmet needs that can be targeted for interventions and referrals.